Sample records for relevant patient specific

  1. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  2. Allergen specificity is relevant for immunotherapy prescription in polysensitised children

    Ciprandi Giorgio


    Full Text Available Abstract The sensitization to more allergens, such as polysenitization, is becoming a frequent characteristic of allergic patients, since the childhood. However, this phenomenon is considered an obstacle to prescribe immunotherapy by many doctors. This study investigated the relevance of polysensitization in a cohort of allergic children and evaluated the number of allergen extracts prescribed for these children. There are allergens that are frequent, but not prescribed. This issue should be matter of adequate debate for Italian paediatricians.

  3. Specificity and Engagement: Increasing ELSI's Relevance to Nano-Scientists.

    Shumpert, Barry L; Wolfe, Amy K; Bjornstad, David J; Wang, Stephanie; Campa, Maria Fernanda


    Scholars studying the ethical, legal, and social issues (ELSI) associated with emerging technologies maintain the importance of considering these issues throughout the research and development cycle, even during the earliest stages of basic research. Embedding these considerations within the scientific process requires communication between ELSI scholars and the community of physical scientists who are conducting that basic research. We posit that this communication can be effective on a broad scale only if it links societal issues directly to characteristics of the emerging technology that are relevant to the physical and natural scientists involved in research and development. In this article, we examine nano-ELSI literature from 2003 to 2010 to discern the degree to which it makes these types of explicit connections. We find that, while the literature identifies a wide range of issues of societal concern, it generally does so in a non-specific manner. It neither links societal issues to particular forms or characteristics of widely divergent nanotechnologies nor to any of the many potential uses to which those nanotechnologies may be put. We believe that these kinds of specificity are essential to those engaged in nano-scale research. We also compare the literature-based findings to observations from interviews we conducted with nanoscientists and conclude that ELSI scholars should add technical- and application-related forms of specificity to their work and their writings to enhance effectiveness and impact in communicating with one important target audience-members of the nanoscale science community.

  4. Specificity and Engagement: Increasing ELSI s Relevance to Nano Scientists

    Shumpert, Barry L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wolfe, Amy K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bjornstad, David J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Stephanie [Higher Education Research Experiences at Oak Ridge, TN (United States); Campa Ayala, Maria F. [Univ. of Tennessee, Knoxville, TN (United States)


    Scholars studying the ethical, legal, and social issues (ELSI) associated with emerging technologies maintain the importance of considering these issues throughout the research and development cycle, even during the earliest stages of basic research. Embedding these considerations within the scientific process requires communication between ELSI scholars and the community of physical scientists who are conducting that basic research. We posit that this communication can be effective on a broad scale only if it links societal issues directly to characteristics of the emerging technology that are relevant to the physical and natural scientists involved in research and development. In this article, we examine nano-ELSI literature from 2003 to 2010 to discern the degree to which it makes these types of explicit connections. We find that, while the literature identifies a wide range of issues of societal concern, it generally does so in a non-specific manner. It neither links societal issues to particular forms or characteristics of widely divergent nanotechnologies nor to any of the many potential uses to which those nanotechnologies may be put. We believe that these kinds of specificity are essential to those engaged in nano-scale research. We also compare the literature-based findings to observations from interviews we conducted with nanoscientists and conclude that ELSI scholars should add technical- and application-related forms of specificity to their work and their writings to enhance effectiveness and impact in communicating with one important target audience members of the nanoscale science community.

  5. Review: Biological relevance of disseminated tumor cells in cancer patients.

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus


    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  6. Specificity of reflex adaptation for task-relevant variability.

    Franklin, David W; Wolpert, Daniel M


    The motor system responds to perturbations with reflexes, such as the vestibulo-ocular reflex or stretch reflex, whose gains adapt in response to novel and fixed changes in the environment, such as magnifying spectacles or standing on a tilting platform. Here we demonstrate a reflex response to shifts in the hand's visual location during reaching, which occurs before the onset of voluntary reaction time, and investigate how its magnitude depends on statistical properties of the environment. We examine the change in reflex response to two different distributions of visuomotor discrepancies, both of which have zero mean and equal variance across trials. Critically one distribution is task relevant and the other task irrelevant. The task-relevant discrepancies are maintained to the end of the movement, whereas the task-irrelevant discrepancies are transient such that no discrepancy exists at the end of the movement. The reflex magnitude was assessed using identical probe trials under both distributions. We find opposite directions of adaptation of the reflex response under these two distributions, with increased reflex magnitudes for task-relevant variability and decreased reflex magnitudes for task-irrelevant variability. This demonstrates modulation of reflex magnitudes in the absence of a fixed change in the environment, and shows that reflexes are sensitive to the statistics of tasks with modulation depending on whether the variability is task relevant or task irrelevant.

  7. Patient-Specific Computational Modeling

    Peña, Estefanía


    This book addresses patient-specific modeling. It integrates computational modeling, experimental procedures, imagine clinical segmentation and mesh generation with the finite element method (FEM) to solve problems in computational biomedicine and bioengineering. Specific areas of interest include cardiovascular problems, ocular and muscular systems and soft tissue modeling. Patient-specific modeling has been the subject of serious research over the last seven years and interest in the area is continually growing and this area is expected to further develop in the near future.

  8. Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease

    Mohamed Ali Abol Hassan


    Full Text Available Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.

  9. Traditional risk factors are more relevant than HIV-specific ones for carotid intima-media thickness (cIMT in a Brazilian cohort of HIV-infected patients.

    Antonio G Pacheco

    Full Text Available Combination antiretroviral therapy (cART had a dramatic impact on the mortality profile in human immunodeficiency virus (HIV infected individuals and increased their life-expectancy. Conditions associated with the aging process have been diagnosed more frequently among HIV-infected patients, particularly, cardiovascular diseases.Patients followed in the Instituto de Pesquisa Clínica Evandro Chagas (IPEC prospective cohort in Rio de Janeiro were submitted to the general procedures from the Brazilian Longitudinal Study of Adult Health, comprising several anthropometric, laboratory and imaging data. Carotid intima-media thickness (cIMT was measured by ultrasonography, following the Mannheim protocol. Linear regression and proportional odds models were used to compare groups and covariables in respect to cIMT. The best model was chosen with the adaptive lasso procedure.A valid cIMT exam was available for 591 patients. Median cIMT was significantly larger for men than women (0.56mm vs. 0.53mm; p = 0.002; overall = 0.54mm. In univariable linear regression analysis, both traditional risk factors for cardiovascular diseases (CVD and HIV-specific characteristics were significantly associated with cIMT values, but the best multivariable model chosen included only traditional characteristics. Hypertension presented the strongest association with higher cIMT terciles (OR = 2.51; 95%CI = 1.69-3.73, followed by current smoking (OR = 1,82; 95%CI = 1.19-2.79, family history of acute myocardial infarction or stroke (OR = 1.60; 95%CI = 1.10-2.32 and age (OR per year = 1.12; 95%CI = 1.10-1.14.Our results show that traditional cardiovascular disease (CVD risk factors are the major players in determining increased cIMT among HIV infected patients in Brazil. This finding reinforces the need for thorough assessment of those risk factors in these patients to guarantee the incidence of CVD events remain under control.

  10. Translating Culture-Specific Items: From the Perspective of Relevance Theory



      This paper offers an exploratory analysis of translating culture-specific items from the angle of relevance theory in terms of semantic level, syntactic level and contextual level. It was revealed that due to the translation dilemma in the translation process, seman-tic meaning and syntactic structure are usually sacrificed for optimal relevance in contextual level.

  11. Patient-relevant needs and treatment goals in nail psoriasis

    Blome, C; Costanzo, A; Dauden, E;


    , but not with age or disease duration. Manual dexterity and social interaction were of particular importance. Goal importance and quality of life were associated, but not redundant (r = 0.612, p specific treatment goals. Goal importance...... is a construct different from disease-specific quality of life and should be assessed separately. The new questionnaire can support goal setting in clinical practice.......PURPOSE: Patient-centered health care implies that medical decisions are made jointly by physician and patient, based on patient needs. Aims were to (a) identify treatment goals for a new questionnaire on patient needs and benefits in nail psoriasis treatment; (b) analyze the importance...

  12. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    Lilla Mihályi


    Full Text Available The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus, diamino diphenyl sulfone (dapsone therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

  13. The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

    Proutski Vitali


    Full Text Available Abstract Background To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome. Methods DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information. Results The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance. Conclusions Analysis from our in vitro and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including IGF2BP2, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear

  14. The clinical relevance of orthostatic hypotension in elderly patients.

    Hartog, Laura; Kleefstra, Nanne; Luigies, Rene; de Rooij, Sophia; Bilo, Henk; van Hateren, Kornelis


    Orthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints. We aimed to explore the relation between different definitions of OH, including relative decrease of blood pressure, and orthostatic complaints and falling. A cross-sectional study was performed with 1415 participants aged ≥65 years visiting a mobile fall-prevention team. The CAREFALL Triage Instrument and data on blood pressure, orthostatic complaints and previous fall incidents were collected. Multivariate binary logistic regression analyses were performed to assess the association of different definitions of OH and orthostatic complaints or falling. Ten different definitions of OH based on different relative declines of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were defined. The 2011 consensus definition of OH was not related to orthostatic complaints (Odds Ratio (OR) 1.07 (95 % Confidence Interval (CI) 0.68-1.69)) or previous fall incidents (OR 1.08 (95%CI 0.83-1.41)). A ≥ 25 % SBP decrease was significantly related to orthostatic complaints (OR 2.81 (95%CI 1.31-6.05)) and a ≥ 25 % DBP decrease was related to previous fall incidents (OR 2.56 (95%CI 1.08-6.09)). With the exception of a decrease of ≥25 % SBP or DBP, the clinical relevance of incidental OH blood pressure measurements seems very limited with respect to orthostatic complaints or fall incidents in elderly patients. Using relative decreases may be more appropriate in clinical practice. Geriatr Gerontol Int 2016; ••: ••-••. © 2017 Japan Geriatrics Society.

  15. Intercultural doctor-patient communication in daily outpatient care: relevant communication skills.

    Paternotte, Emma; Scheele, Fedde; Seeleman, Conny M; Bank, Lindsay; Scherpbier, Albert J J A; van Dulmen, Sandra


    Intercultural communication (ICC) between doctors and patients is often associated with misunderstandings and dissatisfaction. To develop ICC-specific medical education, it is important to find out which ICC skills medical specialists currently apply in daily clinical consultations. Doctor-patient consultations of Dutch doctors with non-Dutch patients were videotaped in a multi-ethnic hospital in the Netherlands. The consultations were analyzed using the validated MAAS-Global assessment list in combination with factors influencing ICC, as described in the literature. In total, 39 videotaped consultations were analyzed. The doctors proved to be capable of practising many communication skills, such as listening and empathic communication behaviour. Other skills were not practised, such as being culturally aware and checking the patient's language ability. We showed that doctors did practice some but not all the relevant ICC skills and that the ICC style of the doctors was mainly biomedically centred. Furthermore, we discussed the possible overlap between intercultural and patient-centred communication. Implications for practice could be to implement the relevant ICC skills in the existing communication training or develop a communication training with a patient-centred approach including ICC skills.

  16. Patient-Specific Modeling in Tomorrow's Medicine


    This book reviews the frontier of research and clinical applications of Patient Specific Modeling, and provides a state-of-the-art update as well as perspectives on future directions in this exciting field. The book is useful for medical physicists, biomedical engineers and other engineers who are interested in the science and technology aspects of Patient Specific Modeling, as well as for radiologists and other medical specialists who wish to be updated about the state of implementation.

  17. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

    Lilla Mihályi; Mária Kiss; Attila Dobozy; Lajos Kemény; Sándor Husz


    The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin ...

  18. Is hyperhomocysteinemia relevant in patients with celiac disease?

    Giovanni Casella; Gabrio Bassotti; Vincenzo Villanacci; Camillo Di Bella; Fabio Pagni; Gian Luigi Corti; Giuseppe Sabatino; Mara Piatti; Vittorio Baldini


    AIM: To investigate whether this might be related to the presence of hyperhomocysteinemia. METHODS: From January 1998 to December 2008, we evaluated the presence of hyperhomocysteinemia in a series of 165 adult celiac disease (CD) patients (138 females and 27 males, mean age 43 years). RESULTS: Hyperhomocysteinemia was evident in 32 patients (19.3%), although most of them had moderate levels (mean value 25 mcg/ml; range 15-30). Only one patient had a history of myocardial infarction (heterozygosis for N5-N10-metil tetrahydrofolate reductase mutation). CONCLUSION: The systematic assessment of hyperhomocysteinemia seems, at present, unjustified in CD patients.

  19. Quantification of relevance of quality of life assessment for patients with cognitive impairment: the suitability indices.

    Baumstarck, Karine; Boucekine, Mohamed; Boyer, Laurent; Aghababian, Valérie; Parola, Nathalie; Reuter, Françoise; Loundou, Anderson; Lançon, Christophe; Pelletier, Jean; Auquier, Pascal


    The extent to which MS patients with cognitive dysfunction can accurately self-report outcomes has been a crucial issue. The aim of this study was to quantify and compare the relevance of the quality of life (QoL) assessment between two populations with a high occurrence of cognitive dysfunction, specifically in individuals with multiple sclerosis (MS) and in individuals suffering from schizophrenia (SCZ). A cross-sectional study was performed using the following inclusion criteria: MS and SCZ patients were diagnosed according to the McDonald criteria and DSM-IV criteria, respectively. Data on sociodemographic (age, gender, education level) and clinical (disease severity, disease duration) factors, QoL (disease-specific questionnaires, MusiQoL and SQoL) and cognitive performance (executive, memory, and attention functions) were collected. Non-impaired and impaired populations were defined according to the French norms. Psychometric properties were compared to those reported in reference populations, which were assessed in the respective validation studies. Suitability indices were provided used to quantitatively compare how the structures in the different populations matched with the initial structure of the questionnaires (reference populations). One hundred and twenty-four MS patients and 113 SCZ patients were enrolled. Factor analysis was performed on the impaired populations and revealed that the questionnaire structure adequately matched the initial structure of the disease-specific QoL questionnaires. All of the suitability indices of construct and external validity in the non-impaired populations ranged from 70 to 100%. Our study suggested that cognitive dysfunction did not compromise the reliability or validity of the self-reported QoL questionnaires among subjects with cognitive dysfunction, such as MS and SCZ. Thus, this report may clarify the relevance of using self-reported QoL assessments in clinical practice.

  20. Relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab

    Lumig, P.P.M. van; Driessen, R.J.B.; Roelofs-Thijssen, M.A.; Boezeman, J.B.M.; Kerkhof, P.C.M. van de; Jong, E.M.G.J. de


    BACKGROUND: Guidelines concerning biological treatment of patients with psoriasis recommend different pretreatment and monitoring laboratory panels in variable frequencies to monitor treatment. OBJECTIVES: To investigate the relevance of laboratory investigations in monitoring patients with psoriasi

  1. Predictors of patient relevant outcome after total hip replacement for osteoarthritis

    Nilsdotter, A-K; Petersson, I F; Roos, Ewa M.


    To investigate prospectively long term patient relevant outcomes after unilateral total hip replacement (THR) for osteoarthritis (OA). To identify non-responders to this intervention and patient related predictors of unsatisfactory outcome.......To investigate prospectively long term patient relevant outcomes after unilateral total hip replacement (THR) for osteoarthritis (OA). To identify non-responders to this intervention and patient related predictors of unsatisfactory outcome....

  2. Morphing patient-specific musculoskeletal models

    Rasmussen, John; Galibarov, Pavel E.; Al-Munajjed, Amir

    other conditions may require CT or MRI data. The method and its theoretical assumptions, advantages and limitations are presented, and several examples will illustrate morphing to patient-specific models. [1] Carbes S; Tørholm S; Rasmussen, J. A Detailed Twenty-six Segments Kinematic Foot model...

  3. Identifying genes relevant to specific biological conditions in time course microarray experiments.

    Singh, Nitesh Kumar; Repsilber, Dirk; Liebscher, Volkmar; Taher, Leila; Fuellen, Georg


    Microarrays have been useful in understanding various biological processes by allowing the simultaneous study of the expression of thousands of genes. However, the analysis of microarray data is a challenging task. One of the key problems in microarray analysis is the classification of unknown expression profiles. Specifically, the often large number of non-informative genes on the microarray adversely affects the performance and efficiency of classification algorithms. Furthermore, the skewed ratio of sample to variable poses a risk of overfitting. Thus, in this context, feature selection methods become crucial to select relevant genes and, hence, improve classification accuracy. In this study, we investigated feature selection methods based on gene expression profiles and protein interactions. We found that in our setup, the addition of protein interaction information did not contribute to any significant improvement of the classification results. Furthermore, we developed a novel feature selection method that relies exclusively on observed gene expression changes in microarray experiments, which we call "relative Signal-to-Noise ratio" (rSNR). More precisely, the rSNR ranks genes based on their specificity to an experimental condition, by comparing intrinsic variation, i.e. variation in gene expression within an experimental condition, with extrinsic variation, i.e. variation in gene expression across experimental conditions. Genes with low variation within an experimental condition of interest and high variation across experimental conditions are ranked higher, and help in improving classification accuracy. We compared different feature selection methods on two time-series microarray datasets and one static microarray dataset. We found that the rSNR performed generally better than the other methods.

  4. The effect of patient origin and relevance of contact on patient and caregiver satisfaction in the emergency room

    Mygind, Anna; Nørredam, Marie Louise; Nielsen, Anette S;


    AIMS: This study examined (1) whether patient and caregiver satisfaction in the emergency room (ER) varies according to patient origin, and (2) whether relevance of visit can explain any variation. METHODS: Data were obtained from a questionnaire survey of walk-in patients and their caregivers...... at four ERs in Copenhagen. The patient questionnaire was available in nine languages, and addressed patient satisfaction. The caregiver questionnaire addressed caregiver satisfaction and relevance of the patient contact in the ER. A total of 3,809 patients and 3,905 caregivers responded. The response rate...... satisfaction rates when patients were of Middle Eastern compared with Danish origin. Satisfaction of both groups was associated with the relevance of the visit as assessed by the caregiver. Visits by patients of Middle Eastern origin were less often assessed as being relevant, but caregivers were less...

  5. Clinical relevance of sirolimus drug interactions in transplant patients.

    Sádaba, B; Campanero, M A; Quetglas, E G; Azanza, J R


    Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability. Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant. The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.

  6. [Relevance of the socioeconomic and health context in patient satisfaction].

    Pérez-Romero, Shirley; Gascón-Cánovas, Juan J; Salmerón-Martínez, Diego; Parra-Hidalgo, Pedro; Monteagudo-Piqueras, Olga

    To determine which factors of the socioeconomic and health contexts influence the perception of the satisfaction of the population with the health services. The data come from the European Health Survey of 2009. In the 22,188 subjects surveyed, the relationship between the perception of satisfaction with the health services received and the individual and contextual variables was studied, applying a multilevel analysis. The factors of the socioeconomic and health contexts that influence satisfaction are: higher rates of low level of studies where the perception of excellence is less likely (odds ratio [OR]: 0.48-0.82) and dissatisfaction is more prevalent (OR: 1.46-1.63). Likewise, the proportion of unsatisfied citizens is lower when per capita expenditure on health services is very high (>1400 €) (OR: 0.49-0.87) and the ratio "primary health care physicians/inhabitants" is high (>60) (OR: 0.500.85). In addition, the prevalence of dissatisfaction describes a positive linear trend with the unemployment rate (OR: 1.12; p=0.0001) and the relative magnitude of the services sector (OR: 1.03; p=0.001). By contrast, this linear trend is negative as the Health Care Coverage Ratio increases (OR: 0.88; p=0.04). The individual factors that determine patient satisfaction are: sex, age, mental health and country of birth. In addition, there are differences in patient satisfaction among the autonomous communities according to socio-economic determinants such as GDP per capita, low-level study rates, unemployment rates or number of inhabitants/doctor's ratio. User satisfaction studies as well as being adjusted for individual variables such as sex, age or health level should also take into account characteristics of the socioeconomic environment of the geographic area where they reside. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Relevance of pharmacokinetic and pharmacodynamic modeling to clinical care of critically ill patients.

    Bulitta, Jurgen B; Landersdorfer, Cornelia B; Forrest, Alan; Brown, Silvia V; Neely, Michael N; Tsuji, Brian T; Louie, Arnold


    Efficacious therapy is of utmost importance to save lives and prevent bacterial resistance in critically ill patients. This review summarizes pharmacokinetic (PK) and pharmacodynamic (PD) modeling methods to optimize clinical care of critically ill patients in empiric and individualized therapy. While these methods apply to all therapeutic areas, we focus on antibiotics to highlight important applications, as emergence of resistance is a significant problem. Nonparametric and parametric population PK modeling, multiple-model dosage design, Monte Carlo simulations, and Bayesian adaptive feedback control are the methods of choice to optimize therapy. Population PK can estimate between patient variability and account for potentially increased clearances and large volumes of distribution in critically ill patients. Once patient- specific PK data become available, target concentration intervention and adaptive feedback control algorithms can most precisely achieve target goals such as clinical cure of an infection or resistance prevention in stable and unstable patients with rapidly changing PK parameters. Many bacterial resistance mechanisms cause PK/PD targets for resistance prevention to be usually several-fold higher than targets for near-maximal killing. In vitro infection models such as the hollow fiber and one-compartment infection models allow one to study antibiotic-induced bacterial killing and emergence of resistance of mono- and combination therapies over clinically relevant treatment durations. Mechanism-based (and empirical) PK/PD modeling can incorporate effects of the immune system and allow one to design innovative dosage regimens and prospective validation studies. Mechanism-based modeling holds great promise to optimize mono- and combination therapy of anti-infectives and drugs from other therapeutic areas for critically ill patients.

  8. A review of potential factors relevant to coping in patients with advanced cancer

    Thomsen, Thora Grothe; Hansen, Susan Rydahl; Wagner, Lis


    The aim was to identify characteristics that are considered to describe coping in patients with advanced cancer, as seen from a patient perspective. Based on the identified characteristics, the second aim was to identify potential factors that are relevant to coping in patients with advanced cancer....

  9. Toward patient-specific articular contact mechanics.

    Ateshian, Gerard A; Henak, Corinne R; Weiss, Jeffrey A


    The mechanics of contacting cartilage layers is fundamentally important to understanding the development, homeostasis and pathology of diarthrodial joints. Because of the highly nonlinear nature of both the materials and the contact problem itself, numerical methods such as the finite element method are typically incorporated to obtain solutions. Over the course of five decades, we have moved from an initial qualitative understanding of articular cartilage material behavior to the ability to perform complex, three-dimensional contact analysis, including multiphasic material representations. This history includes the development of analytical and computational contact analysis methods that now provide the ability to perform highly nonlinear analyses. Numerical implementations of contact analysis based on the finite element method are rapidly advancing and will soon enable patient-specific analysis of joint contact mechanics using models based on medical image data. In addition to contact stress on the articular surfaces, these techniques can predict variations in strain and strain through the cartilage layers, providing the basis to predict damage and failure. This opens up exciting areas for future research and application to patient-specific diagnosis and treatment planning applied to a variety of pathologies that affect joint function and cartilage homeostasis.

  10. Patient-specific simulation of tidal breathing

    Walters, M.; Wells, A. K.; Jones, I. P.; Hamill, I. S.; Veeckmans, B.; Vos, W.; Lefevre, C.; Fetitia, C.


    Patient-specific simulation of air flows in lungs is now straightforward using segmented airways trees from CT scans as the basis for Computational Fluid Dynamics (CFD) simulations. These models generally use static geometries, which do not account for the motion of the lungs and its influence on important clinical indicators, such as airway resistance. This paper is concerned with the simulation of tidal breathing, including the dynamic motion of the lungs, and the required analysis workflow. Geometries are based on CT scans obtained at the extremes of the breathing cycle, Total Lung Capacity (TLC) and Functional Residual Capacity (FRC). It describes how topologically consistent geometries are obtained at TLC and FRC, using a `skeleton' of the network of airway branches. From this a 3D computational mesh which morphs between TLC and FRC is generated. CFD results for a number of patient-specific cases, healthy and asthmatic, are presented. Finally their potential use in evaluation of the progress of the disease is discussed, focusing on an important clinical indicator, the airway resistance.

  11. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.


    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  12. The incidence of aspirin resistance and relevant influencing factors in patients on maintenance hemodialysis



    Objective To explore aspirin resistance(AR)and its relevant influencing factors in patients on maintenance hemodialysis(MHD).Methods Patients on MHD who visited Beijing Chaoyang Hospital from June 1 to 30,2011 were enrolled in this study.A total of 150 age and gender matched individuals with normal renal function were taken as control group.Anthropometric data,bio-

  13. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    Haahtela, T.; Burbach, G. J.; Bachert, C.


    BackgroundWithin a large prospective study, the Global Asthma and Allergy European Network (GA(2)LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. ObjectiveTo improve clinical interpretation of SPT results for inhalant allergens...... SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10mm depending on the allergen. ConclusionThese reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form...

  14. Exploring the potential relevance of human-specific genes to complex disease

    Cooper David N


    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database ( revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  15. Which Domains of Thyroid-Related Quality of Life Are Most Relevant? Patients and Clinicians Provide Complementary Perspectives

    Watt, Torquil; Hegedüs, Laszlo; Rasmussen, Åse Krogh;


    rating, and a combined overall patient/expert rating. The 75 most relevant issues overall and the 15 most relevant issues in each patient category were selected. Results: Based on the above, 92 issues were selected, covering a broad range of clinical and QoL domains. Across patient groups, broader Qo......L domains were most relevant, especially fatigue and emotional susceptibility. However, when focusing on individual patient groups, diagnosis-related physical symptoms were very relevant too. Patients rated issues about psychosocial problems and impact on daily life as more relevant, whereas clinicians...... focused on thyroid-characteristic issues. CONCLUSIONS: A broad range of QoL issues and physical symptoms are relevant for thyroid patients, particularly fatigue and emotional susceptibility. Patients and clinicians offer complementary perspectives on relevance...

  16. Phenylketonuria: protein content and amino acids profile of dishes for phenylketonuric patients. The relevance of phenylalanine.

    Pimentel, Filipa B; Alves, Rita C; Costa, Anabela S G; Torres, Duarte; Almeida, Manuela F; Oliveira, M Beatriz P P


    Phenylketonuria is an inborn error of metabolism, involving, in most cases, a deficient activity of phenylalanine hydroxylase. Neonatal diagnosis and a prompt special diet (low phenylalanine and natural-protein restricted diets) are essential to the treatment. The lack of data concerning phenylalanine contents of processed foodstuffs is an additional limitation for an already very restrictive diet. Our goals were to quantify protein (Kjeldahl method) and amino acid (18) content (HPLC/fluorescence) in 16 dishes specifically conceived for phenylketonuric patients, and compare the most relevant results with those of several international food composition databases. As might be expected, all the meals contained low protein levels (0.67-3.15 g/100 g) with the highest ones occurring in boiled rice and potatoes. These foods also contained the highest amounts of phenylalanine (158.51 and 62.65 mg/100 g, respectively). In contrast to the other amino acids, it was possible to predict phenylalanine content based on protein alone. Slight deviations were observed when comparing results with the different food composition databases.

  17. Clinically applied medical ethnography: relevance to cultural competence in patient care.

    Engebretson, Joan


    Medical anthropology provides an excellent resource for nursing research that is relevant to clinical nursing. By expanding the understanding of ethnographic research beyond ethnicity, nurses can conduct research that explores patient's constructions and explanatory models of health and healing and how they make meaning out of chronic conditions and negotiate daily life. These findings can have applicability to culturally competent care at both the organizational or systems level, as well as in the patient/provider encounter. Individual patient care can be improved by applying ethnographic research findings to build provider expertise and then using a cultural negotiation process for individualized patient care.

  18. Relevance of inhalant and food allergens to the etiology and management of patients with atopic dermatitis

    Platts-Mills, T.A.; Mitchell, E.B.; Rowntree, S.; Heymann, P.W.; Chapman, M.D.

    Patients with atopic dermatitis have IgE antibodies to common environmental antigens, both foods and inhalants. Such antibodies are probably relevant and exposure to the corresponding antigens can give rise to eczema. Nevertheless, the mechanisms involved and the role of other etiologies, e.g. contact reactions, remain to be elucidated. Patients with atopic dermatitis should have comprehensive evaluations to determine the role of environmental antigens.

  19. A 5 year prospective study of patient-relevant outcomes after total knee replacement

    Nilsdotter, A-K; Toksvig-Larsen, S; Roos, E M


    OBJECTIVE: To prospectively describe self-reported outcomes up to 5 years after total knee replacement (TKR) in Osteoarthritis (OA) and to study which patient-relevant factors may predict outcomes for pain and physical function (PF). METHODS: 102 consecutive patients with knee OA, 63 women and 39...... postoperatively. RESULTS: Response rate at 5 years was 86%. At 6 months significant improvement was seen in all KOOS and SF-36 scores (P

  20. Behavioral Relevance of Species-Specific Vasotocin Anatomy in Gregarious Finches

    Aubrey M Kelly


    Full Text Available Despite substantial species differences in the vasotocin/vasopressin (VT/VP circuitry of the medial bed nucleus of the stria terminalis (BSTm and lateral septum (LS; a primary projection target of BSTm VT/VP cells, functional consequences of this variation are poorly known. Previous experiments in the highly gregarious zebra finch (Estrildidae: Taeniopygia guttata demonstrate that BSTm VT neurons promote gregariousness in a male-specific manner and reduce anxiety in both sexes. However, in contrast to the zebra finch, the less gregarious Angolan blue waxbill (Estrildidae: Uraeginthus angolensis exhibits fewer VT-immunoreactive cells in the BSTm as well as differences in receptor distribution across the LS subnuclei, suggesting that knockdown of VT production in the BSTm would produce behavioral effects in Angolan blue waxbills that are distinct from zebra finches. Thus, we here quantified social contact, gregariousness (i.e. preference for the larger of two groups, and anxiety-like behavior following bilateral antisense knockdown of VT production in the BSTm of male and female Angolan blue waxbills. We find that BSTm VT neurons promote social contact, but not gregariousness (as in male zebra finches, and that antisense effects on social contact are significantly stronger in male waxbills than in females. Knockdown of BSTm VT production has no effect on anxiety-like behavior. These data provide novel evidence that species differences in the VT/VP circuitry arising in the BSTm are accompanied by species-specific effects on affiliation behaviors.

  1. Revisiting verbs of emission: an update on some relevant theoretical accounts of lexical specification and argument structure of emission verbs

    Natasa Milivojevic


    Full Text Available The paper addresses the question of what semantic properties lexicalized in verbs determine their syntactic behavior in intransitive motion events and in resultative constructions in English and Serbian. Special attention is devoted to English and Serbian verbs of emission (specifically verbs of sound emission and partly also verbs of light, smell and substance emission regarding their potential to surface as main verbs in these constructions and to combine with directional phrases within specific morphosyntactic templates (unaccusatives and unergatives. The presented research promotes a theoretical view according to which the established syntactic patterns can be applied across the whole class of verbs of emission to express a full er range of atypical verb meanings in motion events. Theoretical conclusions of the research are also relevant for a wider theoretical description of motion events and resultatives in a cross - linguistic perspective. The paper puts forth additional implica tions regarding the projectionalist approach to semantic verb classes against the theoretical framework of Beth Levin (1993. Finally, the paper considers the relevant points of structurally realized similarities via relevant constructional templates in En glish and in Serbian, as well as some important points of morphosyntactic divergence between the two languages. The conclusions presented aim at a more comprehensive contrastive language typology based on language “framing” parameters.

  2. Upper GI endoscopy in elderly patients: predictive factors of relevant endoscopic findings.

    Buri, Luigi; Zullo, Angelo; Hassan, Cesare; Bersani, Gianluca; Anti, Marcello; Bianco, Maria A; Cipolletta, Livio; Giulio, Emilio Di; Matteo, Giovanni Di; Familiari, Luigi; Ficano, Leonardo; Loriga, Piero; Morini, Sergio; Pietropaolo, Vincenzo; Zambelli, Alessandro; Grossi, Enzo; Tessari, Francesco; Intraligi, Marco; Buscema, Massimo


    Elderly patients are at increased risk for peptic ulcer and cancer. Predictive factors of relevant endoscopic findings at upper endoscopy in the elderly are unknown. This was a post hoc analysis of a nationwide, endoscopic study. A total of 3,147 elderly patients were selected. Demographic, clinical, and endoscopic data were systematically collected. Relevant findings and new diagnoses of peptic ulcer and malignancy were computed. Both univariate and multivariate analyses were performed. A total of 1,559 (49.5%), 213 (6.8%), 93 (3%) relevant findings, peptic ulcers, and malignancies were detected. Peptic ulcers and malignancies were more frequent in >85-year-old patients (OR 3.1, 95% CI = 2.0-4.7, p = 0.001). The presence of dysphagia (OR = 5.15), weight loss (OR = 4.77), persistent vomiting (OR = 3.68), anaemia (OR = 1.83), and male gender (OR = 1.9) were significantly associated with a malignancy, whilst overt bleeding (OR = 6.66), NSAIDs use (OR = 2.23), and epigastric pain (OR = 1.90) were associated with the presence of peptic ulcer. Peptic ulcer or malignancies were detected in 10% of elderly patients, supporting the use of endoscopy in this age group. Very elderly patients appear to be at higher risk of such lesions.

  3. A systematic review of quality-of-life domains and items relevant to patients with spondyloarthritis.

    Kwan, Yu Heng; Fong, Warren; Tan, Victoria Ie Ching; Lui, Nai Lee; Malhotra, Rahul; Østbye, Truls; Thumboo, Julian


    To summarize, from the literature, quality-of-life (QoL) domains and items relevant to patients with spondyloarthritis (SpA), and to determine if commonly used SpA patient-reported outcome (PRO) instruments include the identified domains. We used PRISMA statement for systematic review and searched Medline(®) , Embase(®), and PsycInfo(®) using relevant keywords. In addition, hand searches of references of the included articles were conducted. All articles were reviewed for inclusion by 2 independent reviewers. QoL domains and items relevant to patients with axial or peripheral SpA were extracted and presented using the adapted World Health Organization Quality-of-Life (WHOQOL) domain framework. SpA PROs were assessed to determine if they included the domains identified. We retrieved 14,343 articles, of which 34 articles fulfilled inclusion criteria for review. Twenty-five articles were conducted in the European population. Domains such as negative feelings and activities of daily living were found to be present in 28 and 27 articles, respectively. SpA impacted QoL in all domains of the adapted WHOQOL framework. Domains that differed between types of SpA were financial resources, general levels of independence and medication side effects. Embarrassment, self-image, and premature ageing were items that differed by geographical setting. PROs to capture domains for peripheral SpA were similar for axial SpA. We found that a wide range of domains and items of QoL were relevant to patients with SpA with minimal differences between patients with axial and peripheral SpA. Clinicians may consider using peripheral SpA PROs to measure QoL of patients with axial SpA. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Research for us! Which Topics are Relevant for Patients with Depression?

    Bernges, Tabea; Iden, Laura; Gielen, Reinhard; Scholl, Michael; Brütt, Anna Levke


    Objective To identify and prioritize research questions about treatment and care of depression which are relevant to patients, carers and clinicians. The importance of involvement of those stakeholder groups in health services research is increasingly recognized internationally. Methods Research topics were collected in an online survey using unipark software. Patients, carers and clinicians wrote down research topics, i. e. uncertainties they experienced when dealing with depression. The stated research topics were summarized by the authors to generate research questions. Patients, carers and clinicians rated the importance of the identified research questions using a 7 point likert-scale in a further online-survey. Results Respondents rated research questions with regard to accessibility and organization of care as especially relevant. A research question regarding the effectiveness of self-help and coping-strategies was rated as most important. Further relevant research questions refer to decide on and find effective therapy. Conclusion According to patients, carers and clinicians more research about self-help and access to treatment should be conducted. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Analysis of Clinically Relevant Factors for Pulmonary Hypertension in Maintenance Hemodialysis Patients

    Shen, Shen; Sun, Qianmei


    Background Pulmonary hypertension (PH) is common in patients with maintenance hemodialysis (MHD) and is associated with high mortality. This study analyzed clinically relevant factors for pulmonary hypertension in MHD patients and the effect of serum pentraxin3 (PTX3) in the pathogenesis of PH to provide the basis for early diagnosis and treatment of MHD patients with PH. Material/Methods This study included 60 MHD patients (group A) and 30 healthy controls (group B). Group A was further divided into PH and non-PH groups. Clinical characteristics, auxiliary examination results and serum PTX3 level of the PH and non-PH groups were compared. Binary logistic regression was used to assess the risk factors for PH in MHD patients. ROC curve was applied to evaluate the diagnostic value of PTX3 in PH. Results The incidence rate of PH in MHD patients was 50%, and most presented as mild to moderate. Compared with the non-PH group, patients in PH group presented significantly longer atrial diameter, right ventricular diameter and main pulmonary artery diameter (PMHD patients. AUC of PTX3 was 0.721 (95%CI: 0.590–0.851, P=0.003). Conclusions The prevalence of PH was higher in MHD patients and mostly presented as mild to moderate. Such patients often developed heart structural changes and cardiac ultrasound was highly recommended. Serum PTX3 level was significantly elevated and could be used as a marker of PH in MHD patients. PMID:26706606

  6. Promoting the use of personally relevant stimuli for investigating patients with disorders of consciousness

    Perrin, Fabien; Castro, Maïté; Tillmann, Barbara; Luauté, Jacques


    Sensory stimuli are used to evaluate and to restore cognitive functions and consciousness in patients with a disorder of consciousness (DOC) following a severe brain injury. Although sophisticated protocols can help assessing higher order cognitive functions and awareness, one major drawback is their lack of sensitivity. The aim of the present review is to show that stimulus selection is crucial for an accurate evaluation of the state of patients with disorders of consciousness as it determines the levels of processing that the patient can have with stimulation from his/her environment. The probability to observe a behavioral response or a cerebral response is increased when her/his personal history and/or her/his personal preferences are taken into account. We show that personally relevant stimuli (i.e., with emotional, autobiographical, or self-related characteristics) are associated with clearer signs of perception than are irrelevant stimuli in patients with DOC. Among personally relevant stimuli, music appears to be a promising clinical tool as it boosts perception and cognition in patients with DOC and could also serve as a prognostic tool. We suggest that the effect of music on cerebral processes in patients might reflect the music’s capacity to act both on the external and internal neural networks supporting consciousness. PMID:26284020

  7. Promoting the use of personally-relevant stimuli for investigating patients with disorders of consciousness

    Fabien ePerrin


    Full Text Available Sensory stimuli are used to evaluate and to restore cognitive functions and consciousness in patients with a disorder of consciousness (DOC following a severe brain injury. Although sophisticated protocols can help assessing higher order cognitive functions and awareness, one major drawback is their lack of sensitivity. The aim of the present review is to show that stimulus selection is crucial for an accurate evaluation of the state of patients with disorders of consciousness as it determines the levels of processing that the patient can have with stimulation from his/her environment. The probability to observe a behavioral response or a cerebral response is increased when her/his personal history and/or her/his personal preferences are taken into account. We show that personally-relevant stimuli (i.e. with emotional, autobiographical or self-related characteristics are associated with clearer signs of perception than are irrelevant stimuli in patients with DOC. Among personally-relevant stimuli, music appears to be a promising clinical tool as it boosts perception and cognition in patients with DOC and could also serve as a prognostic tool. We suggest that the effect of music on cerebral processes in patients might reflect the music’s capacity to act both on the external and internal neural networks supporting consciousness.

  8. Intercultural doctor-patient communication in daily outpatient care: relevant communication skills

    Paternotte, E.; Scheele, F.; Seeleman, C.M.; Bank, L.; Scherpbier, A.J.; Dulmen, S. van


    INTRODUCTION: Intercultural communication (ICC) between doctors and patients is often associated with misunderstandings and dissatisfaction. To develop ICC-specific medical education, it is important to find out which ICC skills medical specialists currently apply in daily clinical consultations.

  9. Skin Biopsy and Patient-Specific Stem Cell Lines

    Li, Yao; Nguyen, Huy V.; Tsang, Stephen H.


    The generation of patient-specific induced pluripotent stem (iPS) cells permits the development of next-generation patient-specific systems biology models reflecting personalized genomics profiles to better understand pathophysiology. In this chapter, we describe how to create a patient-specific iPS cell line. There are three major steps: (1) performing a skin biopsy procedure on the patient; (2) extracting human fibroblast cells from the skin biopsy tissue; and (3) reprogramming patient-specific fibroblast cells into the pluripotent stem cell stage. PMID:26141312

  10. Evidence-Based Indicators of Neuropsychological Change in the Individual Patient: Relevant Concepts and Methods

    Duff, Kevin


    Repeated assessments are a relatively common occurrence in clinical neuropsychology. The current paper will review some of the relevant concepts (e.g., reliability, practice effects, alternate forms) and methods (e.g., reliable change index, standardized based regression) that are used in repeated neuropsychological evaluations. The focus will be on the understanding and application of these concepts and methods in the evaluation of the individual patient through examples. Finally, some future directions for assessing change will be described. PMID:22382384

  11. Do whiplash patients differ from other patients with non-specific neck pain regarding pain, function or prognosis?

    Verhagen, Arianne P; Lewis, Martyn; Schellingerhout, Jasper M; Heymans, Martijn W; Dziedzic, Krysia; de Vet, Henrica C W; Koes, Bart W


    We evaluated whether patients with self-reported whiplash differed in perceived pain, functional limitation and prognosis from patients with other painful neck complaints. Data from three Dutch trials and an English trial were used all evaluating conservative treatment in neck pain patients in primary care. All patients had non-specific neck pain. Information on any trauma or injury came from self-report at baseline. We compared frequencies of baseline variables and outcome at short-term and long term for whiplash and non-trauma neck pain patients separately. The total study population consisted of 804 neck pain patients. Of these patients 133 reported (16.5%) that an injury was the cause of their neck pain. In all trials there were 17-18% more male patients in the whiplash group. At follow-up pain decreased between 12 and 28%, function 10%, and 25-50% of patients recovered in all trials. Post-treatment improvements in pain, function and recovery were comparable between whiplash and non-trauma patients. We also found no different prognostic factors between whiplash and non-trauma patients. Overall we found in a population with mild to moderate pain no clinically relevant differences between patients with self-reported whiplash and patients with other painful neck complaints. The findings suggest that whiplash patients with mild to moderate pain should not be considered a specific subgroup of patients with non-specific neck pain.

  12. EMTALA and patients with psychiatric emergencies: a review of relevant case law.

    Lindor, Rachel A; Campbell, Ronna L; Pines, Jesse M; Melin, Gabrielle J; Schipper, Agnes M; Goyal, Deepi G; Sadosty, Annie T


    Emergency department (ED) care for patients with psychiatric complaints has become increasingly challenging given recent nationwide declines in available inpatient psychiatric beds. This creates pressure to manage psychiatric patients in the ED or as outpatients and may place providers and institutions at risk for liability under the Emergency Medical Treatment and Labor Act (EMTALA). We describe the patient characteristics, disposition, and legal outcomes of EMTALA cases involving patients with psychiatric complaints. Jury verdicts, settlements, and other litigation involving alleged EMTALA violations related to psychiatric patients between the law's enactment in 1986 and the end of 2012 were collected from 3 legal databases (Westlaw, Lexis, and Bloomberg Law). Details about the patient characteristics, disposition, and reasons for litigation were independently abstracted by 2 trained reviewers onto a standardized data form. Thirty-three relevant cases were identified. Two cases were decided in favor of the plaintiffs, 4 cases were settled, 10 cases had an unknown outcome, and 17 were decided in favor of the defendant institutions. Most patients in these 33 cases were men, had past psychiatric diagnoses, were not evaluated by a psychiatrist, and eventually committed or attempted suicide. The most frequently successful defense used by institutions was to demonstrate that their providers used a standard screening examination and did not detect an emergency medical condition that required stabilization. Lawsuits involving alleged EMTALA violations in the care of ED patients with psychiatric complaints are uncommon and rarely successful. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  13. Morphing patient-specific musculoskeletal models

    Rasmussen, John; Galibarov, Pavel E.; Al-Munajjed, Amir;

    Anatomically realistic musculoskeletal models tend to be very complicated. The current full-body model of the AnyScript Model Repository comprises more than 1000 individually activated muscles and hundreds of bones and joints, and the development of these generic body parts represents an investment...... the generic model differs significantly from the patient in question. The scenario therefore entails two sets of data: (i) a generic musculoskeletal model representing a single (average) individual, and (ii) a set of 3-D medical imaging data, typically in the form of a DICOM file obtained from CT, MRI...... or surface scans. Furthermore, we assume that a set of corresponding anatomical landmarks can be identified in the medical imaging data and on the generic musculoskeletal model. A nonlinear transformation, i.e. a morphing, is created by means of radial basis functions that maps points set (i) to point set...

  14. [Sometimes We Should Maintain a Mental Distance from a Patient--Relevance to Caring for Cancer Patients in Denial].

    Akechi, Tatsuo


    In Japan, cancer has been the leading cause of death since 1981 and is the most common and representative life-threatening disease. Cancer treatment has markedly progressed, and so the development of cancer is now not necessarily a death sentence. Nevertheless, approximately half of cancer patients actually die as a result of the disease even today. Cancer causes marked suffering of patients. Patients with advanced and/or terminal cancer suffer from various physical symptoms and are forced to face a continuous decline in their physical function, and previous studies reported that psychological distress is frequently observed in cancer patients, especially in advanced and/or terminally ill patients. Several types of psychological defense mechanism, especially denial, are frequently observed in these patients. There are multiple levels of denial For example, a patient with true denial denies the presence of cancer itself, although true denial is quite rare. A patient with moderate denial is likely to deny an association between distressing symptoms and disease, while one with mild denial denies the life-threatening nature of disease. Denial is a psychological defense mechanism that often helps advanced cancer patients to manage their anxiety and depression. It allows such patients to continue living while facing the painfulness of their situation. In this situation, it is important for therapists to note the patient's denial. Simply being aware of the denial can, in itself, be supportive for the patient. However, when denial does not work adaptively, such as it prohibiting adherence to necessary treatment and not being useful for ameliorating psychological distress and improving the quality of life, medical staff may consider confronting a patient with the reality of the situation carefully. This paper discusses the relevance of acknowledging denial and caring for patients with denial from the point of view of psycho-oncology.

  15. Orbital and Maxillofacial Computer Aided Surgery: Patient-Specific Finite Element Models To Predict Surgical Outcomes

    Luboz, V; Swider, P; Payan, Y; Luboz, Vincent; Chabanas, Matthieu; Swider, Pascal; Payan, Yohan


    This paper addresses an important issue raised for the clinical relevance of Computer-Assisted Surgical applications, namely the methodology used to automatically build patient-specific Finite Element (FE) models of anatomical structures. From this perspective, a method is proposed, based on a technique called the Mesh-Matching method, followed by a process that corrects mesh irregularities. The Mesh-Matching algorithm generates patient-specific volume meshes from an existing generic model. The mesh regularization process is based on the Jacobian matrix transform related to the FE reference element and the current element. This method for generating patient-specific FE models is first applied to Computer-Assisted maxillofacial surgery, and more precisely to the FE elastic modelling of patient facial soft tissues. For each patient, the planned bone osteotomies (mandible, maxilla, chin) are used as boundary conditions to deform the FE face model, in order to predict the aesthetic outcome of the surgery. Seven F...

  16. A 2-year prospective study of patient-relevant outcomes in patients operated on for knee osteoarthritis with tibial osteotomy

    Toksvig-Larsen Sören


    Full Text Available Abstract Background Tibial osteotomy is a treatment for younger and/or physically active patients suffering from uni-compartmental knee osteoarthritis. The open wedge osteotomy by the hemicallotasis technique includes the use of external fixation. The use of external fixation has several advantages, as early mobilization and the opportunity for optimal correction. However, the hemicallotasis technique has also been described as a cumbersome procedure for the patient. The aim of this study was to prospectively evaluate patient-relevant outcomes during the first 2 post-operative years. Especially the treatment period, during which external fixation was used, was closely monitored. Methods In an uncontrolled study, fifty-eight consecutive patients, 30 men and 28 women (mean age 54 years were operated on by the hemicallotasis technique were evaluated with the patient-relevant outcome measure Knee injury and Osteoarthritis Outcome Score (KOOS preoperatively, during the treatment with external fixation, one week after removal of the external fixation, at 6 months, and at one and two years postoperatively. Results At the 2-year postoperative follow-up, all subscales of the KOOS were improved (p Conclusion Tibial osteotomy by the hemicallotasis technique yields large improvement in self-rated pain, function and quality of life, which persists over two years. Surprisingly, large improvements occurred already during the immediate post-operative period when the external fixation was still used.

  17. How pharmacist-patient communication determines pharmacy loyalty? Modeling relevant factors.

    Patrícia Antunes, Liliana; Gomes, João José; Cavaco, Afonso Miguel


    Portuguese community pharmacies provide pharmaceutical services, such as therapeutic outcomes follow-up, supplemented by relevant point-of-care testing that require continuity of provision to be effective. To identify factors of technical and communication nature that during a patient interview contribute to patients' loyalty. A cross-sectional descriptive study, with a purposive sample of community pharmacies providing pharmaceutical care, was conducted. Patient interviews were taped and transcribed verbatim. Duration, segments and utterances were identified and time stamped, using a previously validated coding scheme. To identify predictors of loyalty, logistic regression analyses were performed. From 59 interviews, participants' average age was 65.7 years and 42 (71.2%) were female; 45 (76.3%) interviews were classified as outcomes measurements and 14 (23.7%) as pharmaceutical consultations, with 33.2% of the patients booking a following appointment. The significant items to explain loyalty were associated with lifestyle and psychosocial exchange, age of the patient, and the presence of all interview segments (i.e. a complete consultation). Contrary to common professional beliefs and practice orientation it would appear that pharmacists' technical skills are not the essential factors that promote patients' loyalty needed for continuity of care, at least in the same extent as the social and lifestyle-related content of the exchange. Pharmaceutical care education should focus on relational skills as much as on medication-related competencies. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mining Specific and General Features in Both Positive and Negative Relevance Feedback. QUT E-Discovery Lab at the TREC󈧍 Relevance Feedback Track


    relevance feedback algo- rithm. Four methods, εMap [1], MapA , P10A, and StatAP [2], were used in the track to measure the performance of Phase 2 runs...εMap and StatAP were applied to the runs us- ing the testing set of only ClueWeb09 Category-B, whereas MapA and P10A were applied to those using the...whole ClueWeb09 English set. Because our experiments were based on only ClueWeb09 Category-B, measuring our per- formance by MapA and P10A might not

  19. Improved radiographic outcomes with patient-specific total knee arthroplasty.

    Ivie, Conrad B; Probst, Patrick J; Bal, Amrit K; Stannard, James T; Crist, Brett D; Sonny Bal, B


    Patient-specific guides can improve limb alignment and implant positioning in total knee arthroplasty, although not all studies have supported this benefit. We compared the radiographs of 100 consecutively-performed patient-specific total knees to a similar group that was implanted with conventional instruments instead. The patient-specific group showed more accurate reproduction of the theoretically ideal mechanical axis, with fewer outliers, but implant positioning was comparable between groups. Our odds ratio comparison showed that the patient-specific group was 1.8 times more likely to be within the desired +3° from the neutral mechanical axis when compared to the standard control group. Our data suggest that reliable reproduction of the limb mechanical axis may accrue from patient-specific guides in total knee arthroplasty when compared to standard, intramedullary instrumentation.

  20. Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates.

    Leiter, Andrea M


    This paper highlights the relevance of age-specific hazard rates in explaining the age variation in "value of statistical life" (VSL) figures. The analysis-which refers to a stated preference framework-contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual's age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.

  1. On the Relative Relevance of Subject-Specific Geometries and Degeneration-Specific Mechanical Properties for the Study of Cell Death in Human Intervertebral Disk Models

    Malandrino, Andrea; Pozo, José M.; Castro-Mateos, Isaac; Frangi, Alejandro F.; van Rijsbergen, Marc M.; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme


    Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration. PMID:25717471

  2. On the relative relevance of subject-specific geometries and degeneration-specific mechanical properties for the study of cell death in human intervertebral disk models.

    Malandrino, Andrea; Pozo, José M; Castro-Mateos, Isaac; Frangi, Alejandro F; van Rijsbergen, Marc M; Ito, Keita; Wilke, Hans-Joachim; Dao, Tien Tuan; Ho Ba Tho, Marie-Christine; Noailly, Jérôme


    Capturing patient- or condition-specific intervertebral disk (IVD) properties in finite element models is outmost important in order to explore how biomechanical and biophysical processes may interact in spine diseases. However, disk degenerative changes are often modeled through equations similar to those employed for healthy organs, which might not be valid. As for the simulated effects of degenerative changes, they likely depend on specific disk geometries. Accordingly, we explored the ability of continuum tissue models to simulate disk degenerative changes. We further used the results in order to assess the interplay between these simulated changes and particular IVD morphologies, in relation to disk cell nutrition, a potentially important factor in disk tissue regulation. A protocol to derive patient-specific computational models from clinical images was applied to different spine specimens. In vitro, IVD creep tests were used to optimize poro-hyperelastic input material parameters in these models, in function of the IVD degeneration grade. The use of condition-specific tissue model parameters in the specimen-specific geometrical models was validated against independent kinematic measurements in vitro. Then, models were coupled to a transport-cell viability model in order to assess the respective effects of tissue degeneration and disk geometry on cell viability. While classic disk poro-mechanical models failed in representing known degenerative changes, additional simulation of tissue damage allowed model validation and gave degeneration-dependent material properties related to osmotic pressure and water loss, and to increased fibrosis. Surprisingly, nutrition-induced cell death was independent of the grade-dependent material properties, but was favored by increased diffusion distances in large IVDs. Our results suggest that in situ geometrical screening of IVD morphology might help to anticipate particular mechanisms of disk degeneration.

  3. Intercultural doctor-patient communication in daily outpatient care: relevant communication skills.

    Paternotte, E.; Scheele, F.; Seeleman, C.M.; Bank, L.; Scherpbier, A.J.J.A.; Dulmen, A.M. van


    Introduction Intercultural communication (ICC) between doctors and patients is often associated with misunderstandings and dissatisfaction. To develop ICC-specific medical education, it is important to find out which ICC skills medical specialists currently apply in daily clinical

  4. Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience.

    Houmes, Robert Jan; Ten Kate, Chantal A; Wildschut, Enno D; Verdijk, Rob M; Wijnen, René M H; de Blaauw, Ivo; Tibboel, Dick; van Heijst, Arno F


    Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands. In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare. An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients. III. Diagnostic study. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients.

    Kovarik, Miroslav; Hronek, Miloslav; Zadak, Zdenek


    Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Clinically-relevant chemotherapy interactions with complementary and alternative medicines in patients with cancer.

    Yap, Kevin Yi-Lwern; See, Cheng Shang; Chan, Alexandre


    Complementary and alternative medicines (CAMs), in particular herbal medicines, are commonly used by cancer patients in conjunction with chemotherapy treatment for their anticancer properties and supportive care. However, the effects of many of these herbs are not well-documented due to limited studies done on them. Severe herb-drug interactions (HDIs) have been recorded in some cases, and failure to recognize these harmful HDIs can lead to dire consequences in cancer patients. This study discusses clinically-relevant interactions between anticancer drugs (ACDs) and herbs classified into 7 categories: cancer treatment and prevention, immune-system-related, alopecia, nausea and vomiting, peripheral neuropathy and pain, inflammation, and fatigue. Some promising patents which contain these herbs and thus may manifest these interactions are also presented in this article. Pharmacokinetic interactions involved mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoprotein, while pharmacodynamic interactions were related to increased risks of central nervous system-related effects, hepatotoxicity and bleeding, among others. Clinicians should be vigilant when treating cancer patients who take CAMs with concurrent chemotherapy since they face a high risk of HDIs. These HDIs can be minimized or avoided by selecting herb-drug pairs which are less likely to interact. Furthermore, close monitoring of pharmacological effects and plasma drug levels should be carried out to avoid toxicity and ensure adequate chemotherapeutic coverage in patients with cancer.

  7. Relevance ofEGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

    Cheng-De Wang; Xin-Rong Wang; Chao-Yang Wang; Yi-Jun Tang; Ming-Wen Hao


    Objective:To study the relevance ofEGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods: A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFRgene mutation were detected with fluorescence quantitative PCR. Relevance ofEGFR gene mutation with clinical and pathological features was analyzed, and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients, 136 (45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age, gender, smoking history, family history of cancer and clinical stage (P>0.05); there was significant relevance betweenEGFR gene mutation and blood type, pathologic types, differentiation and diameter of cancer (P<0.05). The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance (P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features, the prognosis of EGFR- mutant-patients is better than that of EGFR- wide type-patients.

  8. The Determination of Relevant Goals and Criteria Used to Select an Automated Patient Care Information System: A Delphi Approach

    Chocholik, Joan K.; Bouchard, Susan E.; Tan, Joseph K. H.; Ostrow, David N.


    Objectives: To determine the relevant weighted goals and criteria for use in the selection of an automated patient care information system (PCIS) using a modified Delphi technique to achieve consensus.

  9. Rasmussen's encephalitis: the relevance of neuropsychological assessment in patient's treatment and follow up

    Guimarães Catarina Abraão


    Full Text Available Rasmussen's encephalitis is characterized by refractory epilepsy, neurological deterioration and progressive atrophy of one cerebral hemisphere. The objective of this study is to describe the importance of neuropsychological evaluation in the treatment decision and follow-up of patients with Rasmussen´s encephalitis. Neuropsychological assessment was performed in two steps. Firstly, the clinical history was obtained and the Vineland adaptative behavior scale (VABS was applied. After this first step, the patients with social maturity level equal or higher than the inferior limit underwent a battery of neuropsychological assessment. We evaluated three patients before any specific treatment was started, and six months after the intervention (surgery or plasmapheresis. Patient 1 underwent left hemispherectomy and had global improvement on second neuropsychological assessment. This suggests that the decision of performing surgery was adequate. Patients 2 and 3 underwent plasmapheresis. They did not present cognitive decline between both evaluations which suggest that our decision of postponing surgery was adequate as well. We conclude that neuropsychological assessment is important when evaluating patients with Rasmussen´s encephalitis. That is especially true for patients in whom disease progression is slow, and surgery timing has to be carefully planned.

  10. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications

    Min-Hua Chen; Wei Yang; Kun Yan; Wen Gao; Ying Dai; Yan-Bin Wang; Xiao-Peng Zhang; Shan-Shan Yin


    AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic malignant tumor and the relevant complications.METHODS: A total of 338 patients with 763 hepatic tumors underwent ultrasound-guided RFA (565 procedures).There were 204 cases of hepatic cellular carcinoma (HCC)with 430 tumors, the mean largest diameter was 4.0 cm.Of them, 48 patients (23.5%) were in stages Ⅰ-Ⅱ (UICC Systems) and 156 (76.5%) in stages Ⅲ-Ⅳ There were 134 cases of metastatic liver carcinoma (MLC), with 333metastases in the liver, the mean diameter was 4.1 cm,the liver metastases of 96 patients (71.6%) came from gastrointestinal tract. Ninety-three percent of the 338patients were treated using the relatively standard protocol. Crucial attention must be paid to monitor the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structures injury in time. The tumors were considered as ablated completely, if no viability was found on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up for 3-57 mo.RESULTS: The ablation success rate was 93.3% (401/430tumors) for HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors),respectively. A total of 137 patients (40.5%) underwent 2-11times of repeated ablations because of tumor recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was84.6%, 66.6%, and 63.1%, respectively;the survival rate from 48 patients of Ⅰ-Ⅱ stage HCC was 93.7%, 80.4%,and 80.4%, respectively. The major complication rate in this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin burn.CONCLUSION: RFA, as a minimally invasive local treatment,has become an effective and relatively safe alternative for the patients of hepatic

  11. Knee Replacement for Women with Patient-Specific Instructions

    Full Text Available Knee Replacement for Women with Patient-Specific Instructions Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  12. Knee Replacement for Women with Patient-Specific Instructions

    Full Text Available Knee Replacement for Women with Patient-Specific Instructions Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  13. Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance

    Yunfei Zha


    Full Text Available Purpose. To investigate the reproducibility of aortic distensibility (D measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA. Methods. 54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1. and at the level of its maximal diameter (level 2. by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aortic D and anthropometric and biochemical parameters. Results. A mean distensibility of Dlevel  1.=(1.05±0.22×10-5  Pa-1 and Dlevel  2.=(0.49±0.18×10-5  Pa-1 was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2=0.68 to BMI, diastolic blood pressure, and AAA diameter. Conclusions. Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

  14. Toward patient-specific simulations of cardiac valves: state-of-the-art and future directions.

    Votta, Emiliano; Le, Trung Bao; Stevanella, Marco; Fusini, Laura; Caiani, Enrico G; Redaelli, Alberto; Sotiropoulos, Fotis


    Recent computational methods enabling patient-specific simulations of native and prosthetic heart valves are reviewed. Emphasis is placed on two critical components of such methods: (1) anatomically realistic finite element models for simulating the structural dynamics of heart valves; and (2) fluid structure interaction methods for simulating the performance of heart valves in a patient-specific beating left ventricle. It is shown that the significant progress achieved in both fronts paves the way toward clinically relevant computational models that can simulate the performance of a range of heart valves, native and prosthetic, in a patient-specific left heart environment. The significant algorithmic and model validation challenges that need to be tackled in the future to realize this goal are also discussed.

  15. Surgeon Design Interface for Patient-Specific Concentric Tube Robots.

    Morimoto, Tania K; Greer, Joseph D; Hsieh, Michael H; Okamura, Allison M


    Concentric tube robots have potential for use in a wide variety of surgical procedures due to their small size, dexterity, and ability to move in highly curved paths. Unlike most existing clinical robots, the design of these robots can be developed and manufactured on a patient- and procedure-specific basis. The design of concentric tube robots typically requires significant computation and optimization, and it remains unclear how the surgeon should be involved. We propose to use a virtual reality-based design environment for surgeons to easily and intuitively visualize and design a set of concentric tube robots for a specific patient and procedure. In this paper, we describe a novel patient-specific design process in the context of the virtual reality interface. We also show a resulting concentric tube robot design, created by a pediatric urologist to access a kidney stone in a pediatric patient.

  16. [Evaluation of relevance in concussion and damage of health by monitoring of neuron specific enolase and S-100b protein].

    Vajtr, D; Průsa, R; Kukacka, J; Houst'ava, L; Sámal, F; Pelichovská, M; Strejc, P; Toupalík, P


    Proteins released to the circulation from affected glial (neuron specific enolasis, NSE) or ganglial cells (S-100b protein) during traumatic brain injury might be used in diagnosis of traumatic brain injury in cases with negative finding on computer tomography scan (concussion) or in patients where the serious clinical status does not corresponde with mild changes on CT scan (diffuse axonal injury, DAI). Classification of DAI according Gennarelli considered the concussion as lower degree of DAI. 15 patients were divided into group I of mild conccussion (n=3) with 1-day duration of hospitalisation, group II of serious concussion (n=4) with more days duration of hospitalisation with negative findings on CT scan and group III of patients with diagnosis of DAI (n=8). Blood samples were investigated by immunoanalysis for NSE and protein S-100b (Elecsys 2010, Roche). Values of NSE (16.30 +/- 2.33 vs. 110.48 +/- 34.99 vs. 24.07 +/- 6.29 microg/l), and protein S-100b (0.207 +/- 0.03 vs. 0.945 +/- 0.69 vs. 0.736 +/- 0.36 microg/l) overdrow the reference value in cases of group I, II, and III. We discuss the biomechanics of trauma and the blood brain barrier damage in comparison with values of NSE and S-100b protein. [corrected] We proved the significantly higher values of the NSE in group of serious concussion compared to group of DAI. We demonstrated that concussions in some cases lead to serious damage of health.

  17. [The relevance of body composition in cancer patients: what is the evidence?].

    Coronha, Ana Lúcia; Camilo, Maria Ermelinda; Ravasco, Paula


    In the past few years, there has been a growing interest on body composition changes of cancer patients. Muscle mass and fat mass are pointed out as the most important compartments from a physiological point of view, as their changes are the ones with the most impact on disease. The excess of fat mass is related with increased risk of incidence and recurrence of some types of cancer, and some studies identify it as a major contributing factor for increased morbidity and mortality in cancer patients. Weight loss in cancer is frequent and is associated with symptoms, circulating pro-cachectic substances produced by the tumour, and/or hypermetabolism states, not compensated with adequate intake. Muscle mass depletion is the most worrying, and has been associated with decreased functional capacity, increased toxicity of anti-neoplastic treatments, longer length of stay and higher risk of nosocomial infections. In end stage disease, some patients may develop cancer cachexia, an irreversible condition highly associated with mortality. Of note that, lean body mass depletion may occur with excess fat mass (sarcopenic obesity), a condition that combines the health risks of obesity and those of sarcopenia. The high prevalence of malnutrition in cancer patients justifies its relevance. Many patients point it as a cause for the reduction of physical, cognitive, emotional and social functions, as well as anorexia, fatigue, dyspnoea, insomnia, gastrointestinal symptoms and worse Quality of Life. Additionally, body composition may be affected by nutrition, lifestyles and physical activity; therefore, any approach to the patient should include all these dimensions, with special emphasis on individualised nutritional intervention. Therefore, nutritional therapy should be adjuvant to any treatment, as it is essential in all stages of the disease: for its development, during the treatment(s) and in the follow-up period. The aim of nutritional intervention is to promote changes in

  18. Effects of Vessel Tortuosity on Coronary Hemodynamics: An Idealized and Patient-Specific Computational Study.

    Vorobtsova, Natalya; Chiastra, Claudio; Stremler, Mark A; Sane, David C; Migliavacca, Francesco; Vlachos, Pavlos


    Although coronary tortuosity can influence the hemodynamics of coronary arteries, the relationship between tortuosity and flow has not been thoroughly investigated partly due to the absence of a widely accepted definition of tortuosity and the lack of patient-specific studies that analyze complete coronary trees. Using a computational approach we investigated the effects of tortuosity on coronary flow parameters including pressure drop, wall shear stress, and helical flow strength as measured by helicity intensity. Our analysis considered idealized and patient-specific geometries. Overall results indicate that perfusion pressure decreases with increased tortuosity, but the patient-specific results show that more tortuous vessels have higher physiological wall shear stress values. Differences between the idealized and patient-specific results reveal that an accurate representation of coronary tortuosity must account for all relevant geometric aspects, including curvature imposed by the heart shape. The patient-specific results exhibit a strong correlation between tortuosity and helicity intensity, and the corresponding helical flow contributes directly to the observed increase in wall shear stress. Therefore, helicity intensity may prove helpful in developing a universal parameter to describe tortuosity and assess its impact on patient health. Our data suggest that increased tortuosity could have a deleterious impact via a reduction in coronary perfusion pressure, but the attendant increase in wall shear stress could afford protection against atherosclerosis.

  19. Patient-reported symptoms during radiotherapy. Clinically relevant symptom burden in patients treated with palliative and curative intent

    Koerner, Philipp [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany); Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Ehrmann, Katja [Universitaetsklinikum Wuerzburg, Medizinische Psychologie und Psychotherapie, Medizinische Soziologie und Rehabilitationswissenschaften, Wuerzburg (Germany); Hartmannsgruber, Johann [Praxis Landshut, Kinderzahnheilkunde, Landshut (Germany); Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael [Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Oorschot, Birgitt van [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany)


    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom burden

  20. Relevance of a Geriatric Assessment for Elderly Patients With Lung Cancer-A Systematic Review.

    Schulkes, Karlijn J G; Hamaker, Marije E; van den Bos, Frederiek; van Elden, Leontine J R


    Lung cancer is predominantly a disease of the elderly: one half of all newly diagnosed patients will be > 70 years old. In the Netherlands, > 12,000 new cases are diagnosed annually. We sought to assemble all available evidence on the relevance of a geriatric assessment for lung cancer patients. A systematic Medline and Embase search was performed for studies in which a geriatric assessment was used to detect health issues or that had addressed the association between a baseline geriatric assessment (composed of ≥ 2 of the following domains: cognitive function, mood/depression, nutritional status, activities of daily living, instrumental activities of daily living, polypharmacy, objectively measured physical capacity, social support and frailty) and outcome. A total of 23 publications from 18 studies were included. The median age of patients was 76 years (range, 73-81 years). Despite generally good Eastern Cooperative Oncology Group performance status, the prevalence of geriatric impairments was high, with the median ranging from 29% for cognitive impairment to 70% for instrumental activities of daily living impairment. Objective physical capacity and nutritional status, as items of the geriatric assessment, had a consistent association with mortality. The information revealed by a geriatric assessment led to changes in oncologic treatment and nononcologic interventions. The present review has demonstrated that a geriatric assessment can detect multiple health issues not reflected in the Eastern Cooperative Oncology Group performance status. Impairments in geriatric domains have predictive value for mortality and appear to be associated with treatment completion. It would be useful to develop and validate an individualized treatment algorithm that includes these geriatric domains.

  1. Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

    Hella, Jerry; Said, Khadija; Kamwela, Lujeko; Sasamalo, Mohamed; Maroa, Thomas; Chiryamkubi, Magreth; Mhalu, Grace; Schindler, Christian; Reither, Klaus; Knopp, Stefanie; Utzinger, Jürg; Gagneux, Sébastien; Fenner, Lukas


    Background Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania. Methodology Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB. Principal findings A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88–1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03–4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38–5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12–1.16, p = 0.088). Conclusions/Significance S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB

  2. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A. [Canis Lupus LLC and Department of Human Oncology, University of Wisconsin, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Departments of Human Oncology, Medical Physics, and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53792 (United States)


    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa


    D. K. Kenbaeva


    Full Text Available Cellular mechanisms are quite important immunological components of tumor surveillance, being, however, most vulnerable to influence of different adverse factors, including surgery-associated stress and ionizing radiation. Our study was aimed for assessing specific effects of immunotherapy upon indices of cellular immunity in patients with cervical cancer. Eighty-eight patients with cervical cancer (clinical stage I-IIA, Т1аN0M0-T2aN0M0, who underwent appropriate surgery (for IA stage, or a combined treatment, including surgery gamma-ray teletherapy (IB, IIA stages are under study. The patients were distributed in two groups, depending on the therapy applied. Group 1 included patients subjected to surgical treatment plus and radiation therapy, Group 2 included those patients who were treated according to this protocol, with addition of a specific immunotherapy. Contents of T cells and various CD subpopulations of T-lymphocytes were identified by immunofluorescence techniques. Among patients with cervical cancer at clinical stages IA, IB, IIA, a reliable decrease in cellular immunity indices was registered, both after surgery, and during combined treatment. Introduction of specific immunotherapy to the conventional treatment schedule was associated with increase of cellular immune indices, and, in first line, the antineoplastic mechanisms (e.g., NK’s and NKT cell contents. One should point to a relatively low efficiency of this immunotherapy in combined treatment of patients with cervical cancer at IIA stage.

  4. Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker.

    Tatjana M H Niers

    Full Text Available BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (cVEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. METHODOLOGY: We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC and 12 patients with renal cell carcinoma (RCC. In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6, non-RCC: 6.2 IU/10(6 platelets, p = 0.001. In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001, and not related to platelet VEGF concentration. CONCLUSIONS: Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in

  5. Patient-specific modeling of human cardiovascular system elements

    Kossovich, Leonid Yu.; Kirillova, Irina V.; Golyadkina, Anastasiya A.; Polienko, Asel V.; Chelnokova, Natalia O.; Ivanov, Dmitriy V.; Murylev, Vladimir V.


    Object of study: The research is aimed at development of personalized medical treatment. Algorithm was developed for patient-specific surgical interventions of the cardiovascular system pathologies. Methods: Geometrical models of the biological objects and initial and boundary conditions were realized by medical diagnostic data of the specific patient. Mechanical and histomorphological parameters were obtained with the help mechanical experiments on universal testing machine. Computer modeling of the studied processes was conducted with the help of the finite element method. Results: Results of the numerical simulation allowed evaluating the physiological processes in the studied object in normal state, in presence of different pathologies and after different types of surgical procedures.

  6. Study on hemodynamics in patient-specific thoracic aortic aneurysm


    The objective of this study is to investigate the hemodynamics in patient-specific thoracic aortic aneurysm and discuss the reason for formation of aortic plaque.A 3-Dimensional pulsatile blood flow in thoracic aorta with a fusiform aneurysm and 3 main branched vessels was studied numerically with the average Reynolds number of 1399 and the Womersley number of 19.2.Based on the clinical 2-Dimensional CT slice data,the patient-specific geometry model was constructed using medical image process software.Un...

  7. Patient-specific hip prostheses designed by surgeons

    Coigny Florian


    Full Text Available Patient-specific bone and joint replacement implants lead to better functional and aesthetic results than conventional methods [1], [2], [3]. But extracting 3D shape information from CT Data and designing individual implants is demanding and requires multiple surgeon-to-engineer interactions. For manufacturing purposes, Additive Manufacturing offers various advantages, especially for low volume manufacturing parts, such as patient specific implants. To ease these new approaches and to avoid surgeon-to-engineer interactions a new design software approach is needed which offers highly automated and user friendly planning steps.

  8. Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients.

    Maria Carmen Cenit

    Full Text Available CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis.The CD5 SNPs rs2241002 (C/T; Pro224Leu and rs2229177 (C/T; Ala471Val were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed.T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC haplotype, compared to the more recently derived Pro224-Val471 (CT. The same allelic combination was statistically associated with Lupus nephritis.The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.

  9. Current diagnostic approach to patients with adnexal masses:which tools are relevant in routine praxis?

    Milan M.Terzic; Jelena Dotlic; Ivana Likic; Nebojsa Ladjevic; Natasa Brndusic; Nebojsa Arsenovic; Sanja Maricic


    The aim of the study was to investigate which anamnestic,laboratory and ultrasound parameters used in routine practice could predict the nature of adnexal mass,thus enabling referral to relevant specialist.Methods:Study involved the women treated for adnexal tumors throughout a period of 2 years.On admission,detailed anamnestic and laboratory data were obtained,expert ultrasound scan was performed,and power Doppler index (PDI),risk of malignancy index (RMI) and body mass index (BMI) were calculated for all patients.Obtained data were related to histopathological findings,and statistically analyzed.Results:The study included 689 women (112 malignant,544 benignant,and 33 borderline tumors).Malignant and borderline tumors were more frequent in postmenopausal women (P=0.000).Women who had benignant tumors had the lowest BMI (P=0.000).There were significant (P<0.05) differences among tumor types regarding erythrocyte sedimentation rate,CA125 and carcinoembryonic antigen (CEA) levels.Among ultrasound findings,larger tumor diameter and ascites were more frequent in malignant tumors (P=0.000).Women with malignant tumors had highest values of RMI and PDI (P=0.000).Conclusions:Anamnestic data,ultrasound parameters and laboratory analyses were all found to be good discriminating factors among malignant,benignant and borderline tumors.

  10. The Genomic Scrapheap Challenge; Extracting Relevant Data from Unmapped Whole Genome Sequencing Reads, Including Strain Specific Genomic Segments, in Rats.

    van der Weide, Robin H; Simonis, Marieke; Hermsen, Roel; Toonen, Pim; Cuppen, Edwin; de Ligt, Joep


    Unmapped next-generation sequencing reads are typically ignored while they contain biologically relevant information. We systematically analyzed unmapped reads from whole genome sequencing of 33 inbred rat strains. High quality reads were selected and enriched for biologically relevant sequences; similarity-based analysis revealed clustering similar to previously reported phylogenetic trees. Our results demonstrate that on average 20% of all unmapped reads harbor sequences that can be used to improve reference genomes and generate hypotheses on potential genotype-phenotype relationships. Analysis pipelines would benefit from incorporating the described methods and reference genomes would benefit from inclusion of the genomic segments obtained through these efforts.

  11. TAVI device selection: time for a patient-specific approach.

    Lee, Marcus; Modine, Thomas; Piazza, Nicolo; Mylotte, Darren


    Individualised, patient-centred care is a central tenet of modern medicine. The variety of transcatheter heart valves currently available affords the opportunity to select the most appropriate device for each individual patient. Prosthesis selection should be based on operator experience and pre-procedural multimodal three-dimensional imaging. Herein, we outline a number of clinical scenarios where specific transcatheter heart valve technologies have the potential to optimise clinical outcome.

  12. The relevance of the high frequency audiometry in tinnitus patients with normal hearing in conventional pure-tone audiometry

    Veronika Vielsmeier; Astrid Lehner; Jürgen Strutz; Thomas Steffens; Kreuzer, Peter M; Martin Schecklmann; Michael Landgrebe; Berthold Langguth; Tobias Kleinjung


    Objective. The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz–8 kHz). Here we explored whether the results of the high frequency audiometry (>8 kHz) provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical chara...

  13. Elucidation of Relevant Neuroinflammation Mechanisms Using Gene Expression Profiling in Patients with Amyotrophic Lateral Sclerosis

    Choi, Young-Chul; Ha, Yoon; Kim, Hyongbum; Kim, Do-Young; Kim, Myung-Sun; Yu, Ji Hea; Seo, Jung Hwa; Kim, MinGi; Cho, Sung-Rae; Kang, Seong-Woong


    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by damage of motor neurons. Recent reports indicate that inflammatory responses occurring within the central nervous system contribute to the pathogenesis of ALS. We aimed to investigate disease-specific gene expression associated with neuroinflammation by conducting transcriptome analysis on fibroblasts from three patients with sporadic ALS and three normal controls. Several pathways were found to be upregulated in patients with ALS, among which the toll-like receptor (TLR) and NOD-like receptor (NLR) signaling pathways are related to the immune response. Genes—toll-interacting protein (TOLLIP), mitogen-activated protein kinase 9 (MAPK9), interleukin-1β (IL-1β), interleukin-8 (IL-8), and chemokine (C-X-C motif) ligand 1 (CXCL1)—related to these two pathways were validated using western blotting. This study validated the genes that are associated with TLR and NLR signaling pathways from different types of patient-derived cells. Not only fibroblasts but also induced pluripotent stem cells (iPSCs) and neural rosettes from the same origins showed similar expression patterns. Furthermore, expression of TOLLIP, a regulator of TLR signaling pathway, decreased with cellular aging as judged by changes in its expression through multiple passages. TOLLIP expression was downregulated in ALS cells under conditions of inflammation induced by lipopolysaccharide. Our data suggest that the TLR and NLR signaling pathways are involved in pathological innate immunity and neuroinflammation associated with ALS and that TOLLIP, MAPK9, IL-1β, IL-8, and CXCL1 play a role in ALS-specific immune responses. Moreover, changes of TOLLIP expression might be associated with progression of ALS. PMID:27812125

  14. Substance Use in Patients With First-Episode Psychosis: Is Gender Relevant?

    Arranz, Belen; Safont, Gemma; Corripio, Iluminada; Ramirez, Nicolas; Dueñas, Rosa Maria; Perez, Victor; Alvarez, Enric; San, Luis


    Only a few studies in patients with first-episode psychosis have included gender in the study hypothesis or considered this a primary study variable. The aim of this study was to explore the influence of gender in the pattern of substance use in patients with first-episode psychosis. This is a sub-analysis of a randomized open clinical trial that compared 1-year treatment retention rates of patients with first-episode psychosis randomized to haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone. Our sub-analysis included 85 men and 29 women. Substance use was relatively high among these patients and differed significantly by gender. Men were more likely to use substances overall than women (89.4% for men vs. 55.2% for women), χ(2) = 16.2, df = 1, p <.001, and were also more likely to use alcohol (χ(2) = 13, df = 1, p <.001), cannabis (χ(2) = 9.9; df = 1, p <.002), and cocaine (χ(2) = 10.3; df = 1, p <.001), compared to women. While there were no gender differences in age at first consumption of alcohol or cocaine, men were significantly younger at first consumption of cannabis (M = 16.08 years, SD = 2.1) than women (M = 18.0 years, SD = 3.8), F(1, 59) = 5, p <.02. When analyzed separately by gender, women showed no significant differences in the influence of number of substances used on age at onset of psychosis, F(3, 29) = 1.2, p =.30. However, there was a significant difference among men, with earlier onset of psychosis noted in men consuming multiple substances; F(4, 85) = 5.8, p <.0001. Regarding prediction of age at onset of psychosis, both male gender and the use of a higher number of substances significantly predicted an earlier age at onset of psychosis. Our study provides some evidence of gender differences in the pattern of substance use in patients with first-episode psychosis, suggesting the possible need for gender-specific approaches in the interventions performed in these patients. This study is registered as #12610000954022 with the

  15. Language-specific dysgraphia in Korean stroke patients.

    Yoon, Ji Hye; Suh, Mee Kyung; Kim, HyangHee


    We investigated how changes in the writing of 14 Korean stroke patients reflect the unique features of the Korean writing system. The Korean writing system, Han-geul, has both linguistic and visuospatial/constructive characteristics. In the visuospatial construction of a syllable, the component consonant(s) and vowel(s) must be arranged from top-to-bottom and/or left-to-right within the form of a square. This syllabic organization, unique to Korean writing, may distinguish dysgraphia in Korean patients from the disorder in other languages, and reveal the effects of stroke on visuospatial/constructive abilities. We compared 2 groups of patients affected by stroke, 1 group with left hemisphere (LH) lesions and the other with right hemisphere (RH) lesions. We instructed them to write from a dictation of 90 monosyllabic stimuli, each presented with a real word cue. Patients had to repeat a target syllable and a word cue, and then to write the target syllable only. Patients with LH and RH lesions produced qualitatively different error patterns. While the LH lesion group produced primarily linguistic errors, visuospatial/constructive errors predominated in the group with RH lesions. With regard to language-specific features, these Korean patients with RH lesions produced diverse visuospatial/constructive errors not commonly observed in dysgraphia of the English language. Language-specific writing errors by Korean stroke patients reflect the unique characteristics of Korean writing, which include the arrangement of strokes and graphemes within a square syllabic form by dimensional and spatial rules. These findings support the notion that the Korean writing system possesses a language-specific nature with both linguistic and visuospatial/constructive processes. Distinctive patterns of dysgraphia in the Korean language also suggest interactivity between linguistic and visuospatial/constructive levels of processing. This study is noteworthy for its systematic description of

  16. A specific nursing educational program in patients with Cushing's syndrome.

    Martínez-Momblán, M Antonia; Gómez, Carmen; Santos, Alicia; Porta, Nuria; Esteve, Julia; Úbeda, Inmaculada; Halperin, Irene; Campillo, Beatriz; Guillaumet, Montserrat; Webb, Susan M; Resmini, Eugenia


    Cushing's syndrome (CS) is a rare endocrine disease, due to cortisol hypersecretion. CS patients have comorbidities, often still present after biochemical cure. Specific nursing healthcare programs to address this disease and achieve improved health related quality of life (HRQoL) are lacking. Thus, an educational nursing intervention, through the development and promotion of specific educational tools, appears to be justified. The objective of this study is to assess the effectiveness of an educational nursing program in CS patients on HRQoL, clinical parameters, level of pain and physical activity, patterns of rest, and use of health resources. A prospective, randomized study was conducted in two reference hospitals for CS. Sixty-one patients (mean age 47 ± 12.7 years, 83.6 % females) were enrolled and divided into 2 groups: an "intervention" group where educational sessions were performed over 9 months and a "control" group, without these sessions. Specific questionnaires were used at the beginning and end of the study. After educational sessions, the intervention group had a better score in the CushingQoL questionnaire (p educational nursing program improved physical activity, healthy lifestyle, better sleep patterns, and reduced pain in CS patients, influencing HRQoL and reducing consumption of health resources. Moreover, the brief nature of the program suggests it as a good candidate to be used in CS patients.

  17. 3D-printed patient-specific applications in orthopedics

    Wong KC


    Full Text Available Kwok Chuen Wong Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Abstract: With advances in both medical imaging and computer programming, two-dimensional axial images can be processed into other reformatted views (sagittal and coronal and three-dimensional (3D virtual models that represent a patients’ own anatomy. This processed digital information can be analyzed in detail by orthopedic surgeons to perform patient-specific orthopedic procedures. The use of 3D printing is rising and has become more prevalent in medical applications over the last decade as surgeons and researchers are increasingly utilizing the technology’s flexibility in manufacturing objects. 3D printing is a type of manufacturing process in which materials such as plastic or metal are deposited in layers to create a 3D object from a digital model. This additive manufacturing method has the advantage of fabricating objects with complex freeform geometry, which is impossible using traditional subtractive manufacturing methods. Specifically in surgical applications, the 3D printing techniques can not only generate models that give a better understanding of the complex anatomy and pathology of the patients and aid in education and surgical training, but can also produce patient-specific surgical guides or even custom implants that are tailor-made to the surgical requirements. As the clinical workflow of the 3D printing technology continues to evolve, orthopedic surgeons should embrace the latest knowledge of the technology and incorporate it into their clinical practice for patient-specific orthopedic applications. This paper is written to help orthopedic surgeons stay up-to-date on the emerging 3D technology, starting from the acquisition of clinical imaging to 3D printing for patient-specific applications in orthopedics. It 1 presents the necessary steps to prepare the medical images that are

  18. Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts.

    Scholefield, Janine; Watson, Lauren; Smith, Danielle; Greenberg, Jacquie; Wood, Matthew J A


    Polyglutamine (polyQ) disorders are inherited neurodegenerative conditions defined by a common pathogenic CAG repeat expansion leading to a toxic gain-of-function of the mutant protein. Consequences of this toxicity include activation of heat-shock proteins (HSPs), impairment of the ubiquitin-proteasome pathway and transcriptional dysregulation. Several studies in animal models have shown that reducing levels of toxic protein using small RNAs would be an ideal therapeutic approach for such disorders, including spinocerebellar ataxia-7 (SCA7). However, testing such RNA interference (RNAi) effectors in genetically appropriate patient cell lines with a disease-relevant phenotype has yet to be explored. Here, we have used primary adult dermal fibroblasts from SCA7 patients and controls to assess the endogenous allele-specific silencing of ataxin-7 by two distinct siRNAs. We further identified altered expression of two disease-relevant transcripts in SCA7 patient cells: a twofold increase in levels of the HSP DNAJA1 and a twofold decrease in levels of the de-ubiquitinating enzyme, UCHL1. After siRNA treatment, the expression of both genes was restored towards normal levels. To our knowledge, this is the first time that allele-specific silencing of mutant ataxin-7, targeting a common SNP, has been demonstrated in patient cells. These findings highlight the advantage of an allele-specific RNAi-based therapeutic approach, and indicate the value of primary patient-derived cells as useful models for mechanistic studies and for measuring efficacy of RNAi effectors on a patient-to-patient basis in the polyQ diseases.

  19. Convolutional Neural Networks for patient-specific ECG classification.

    Kiranyaz, Serkan; Ince, Turker; Hamila, Ridha; Gabbouj, Moncef


    We propose a fast and accurate patient-specific electrocardiogram (ECG) classification and monitoring system using an adaptive implementation of 1D Convolutional Neural Networks (CNNs) that can fuse feature extraction and classification into a unified learner. In this way, a dedicated CNN will be trained for each patient by using relatively small common and patient-specific training data and thus it can also be used to classify long ECG records such as Holter registers in a fast and accurate manner. Alternatively, such a solution can conveniently be used for real-time ECG monitoring and early alert system on a light-weight wearable device. The experimental results demonstrate that the proposed system achieves a superior classification performance for the detection of ventricular ectopic beats (VEB) and supraventricular ectopic beats (SVEB).

  20. A combination of transcriptome and methylation analyses reveals embryologically-relevant candidate genes in MRKH patients

    Riess Olaf


    Full Text Available Abstract Background The Mayer-Rokitansky-Küster-Hauser (MRKH syndrome is present in at least 1 out of 4,500 female live births and is the second most common cause for primary amenorrhea. It is characterized by vaginal and uterine aplasia in an XX individual with normal secondary characteristics. It has long been considered a sporadic anomaly, but familial clustering occurs. Several candidate genes have been studied although no single factor has yet been identified. Cases of discordant monozygotic twins suggest that the involvement of epigenetic factors is more likely. Methods Differences in gene expression and methylation patterns of uterine tissue between eight MRKH patients and eight controls were identified using whole-genome microarray analyses. Results obtained by expression and methylation arrays were confirmed by qRT-PCR and pyrosequencing. Results We delineated 293 differentially expressed and 194 differentially methylated genes of which nine overlap in both groups. These nine genes are mainly embryologically relevant for the development of the female genital tract. Conclusion Our study used, for the first time, a combined whole-genome expression and methylation approach to reveal the etiology of the MRKH syndrome. The findings suggest that either deficient estrogen receptors or the ectopic expression of certain HOXA genes might lead to abnormal development of the female reproductive tract. In utero exposure to endocrine disruptors or abnormally high maternal hormone levels might cause ectopic expression or anterior transformation of HOXA genes. It is, however, also possible that different factors influence the anti-Mullerian hormone promoter activity during embryological development causing regression of the Müllerian ducts. Thus, our data stimulate new research directions to decipher the pathogenic basis of MRKH syndrome.

  1. Patient-specific instrumentation improves tibial component rotation in TKA.

    Silva, Alcindo; Sampaio, Ricardo; Pinto, Elisabete


    To compare the femoral and tibial components rotational alignment in total knee arthroplasty (TKA) performed either with conventional or with patient-specific instrumentation. Forty-five patients underwent primary TKA and were prospectively randomized into two groups: 22 patients into the conventional instrumentation group (group A) and 23 patients into the Signature™ patient-specific instrumentation group (group B). All patients underwent computed tomography of the operated knee in the first week after surgery to measure the components rotation. The femoral component rotation was 0.0° (-0.25, 1.0) in group A, and 0.0° (0.0, 1.0) in group B. The tibial component rotation was -16.0° (-18.5, 11.8) in group A, and -16.0° (-19.0, -14.0) in group B. There were no significant differences between the two groups in tibial and femoral components rotation. The difference between the tibial component rotation and the neutral tibial rotation was similar in both groups [2.0° (-0.5, 6.3) in group A and 2.0° (-1.0, 4.0) in group B], but the dispersion around the median was different between the two groups. The amplitude of the difference between tibial rotation and neutral position was 27° (-13, 14) in group A and 9° (-3, 6) in group B. There is a smaller chance of internal malrotation of the tibial component with the Signature™ patient-specific instrumentation system, with less dispersion and amplitude of the tibial component rotation around the neutral position. II.

  2. Relevance of quality of life assessment for multiple sclerosis patients with memory impairment.

    Karine Baumstarck

    Full Text Available BACKGROUND: Memory disturbances, in particular episodic verbal memory dysfunction, are the most frequent cognitive impairment observed in multiple sclerosis (MS patients. The use of self-reported outcomes for evaluating treatment and managing care of these subjects has been questioned. The aim of this study was to provide new evidence about the suitability of self-reported outcomes for use in this impaired population by exploring the internal structure, reliability and external validity of a specific quality of life (QoL instrument, the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL. METHODS: DESIGN: cross-sectional study. INCLUSION CRITERIA: MS patients of any disease subtype. DATA COLLECTION: sociodemographic (age, gender, marital status, education level, and occupational activity and clinical data (MS subtype, Expanded Disability Status Scale, disease duration; QoL (MusiQoL and SF36; and memory performance (Grober and Buschke test. In accordance with the French norms of the memory test, non-impaired and impaired populations were defined for short- and long-delay free composites and for short- and long-delay total composites. For the 8 populations, psychometric properties were compared to those reported from the reference population assessed in the validation study. PRINCIPAL FINDINGS: One hundred and twenty-four consecutive patients were enrolled. The analysis performed in the impaired populations showed that the questionnaire structure adequately matched the initial structure of the MusiQoL. The unidimensionality of the dimensions was preserved, and the internal/external validity indices were close to those of the reference population. CONCLUSIONS/SIGNIFICANCE: Our study suggests that memory dysfunction did not compromise the reliability or validity of the self-reported QoL questionnaires.

  3. A test of safety, violence prevention, and civility climate domain-specific relationships with relevant workplace hazards

    Gazica, Michele W; Spector, Paul E


    Safety climate, violence prevention climate, and civility climate were independently developed and linked to domain-specific workplace hazards, although all three were designed to promote the physical...

  4. Comparing non-specific physical symptoms in environmentally sensitive patients : Prevalence, duration, functional status and illness behavior

    Baliatsas, Christos; Van Kamp, Irene; Hooiveld, Mariette; Yzermans, Joris; Lebret, Erik


    Objective: Little is known about the potential clinical relevance of non-specific physical symptoms (NSPS) reported by patients with self-reported environmental sensitivities. This study aimed to assess NSPS in people with general environmental sensitivity (GES) and idiopathic environmental intolera

  5. Comparing non-specific physical symptoms in environmentally sensitive patients: prevalence, duration, functional status and illness behavior.

    Baliatsas, C.; Kamp, I. van; Hooiveld, M.; Yzermans, J.; Lebret, E.


    Objective: Little is known about the potential clinical relevance of non-specific physical symptoms (NSPS) reported by patients with self-reported environmental sensitivities. This study aimed to assess NSPS in people with general environmental sensitivity (GES) and idiopathic environmental intolera

  6. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy.

    Weidemann, Frank; Maier, Sebastian K G; Störk, Stefan; Brunner, Thomas; Liu, Dan; Hu, Kai; Seydelmann, Nora; Schneider, Andreas; Becher, Jan; Canan-Kühl, Sima; Blaschke, Daniela; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter


    Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holter electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holter ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 ± 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses ≥3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter-defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holter ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with

  7. Carbohydrate malabsorption in patients with non-specific abdominal complaints


    Non-specific abdominal complaints are a considerable problem worldwide. Many patients are affected and many differential diagnoses have to be considered.Among these, carbohydrate malabsorption seems to play an important role. However, so far, only incomplete absorption of lactose is broadly accepted, while the malabsorption of fructose and sorbitol is still underestimated, although in many parts of the world it is much more frequent. Despite the success of dietary interventions in many patients, there are still a lot of unanswered questions that make further investigations necessary.

  8. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Meng-Lu Liu


    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  9. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients.

    Liu, Meng-Lu; Zang, Tong; Zhang, Chun-Li


    Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs) exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs) with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  10. Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

    Larissa Bubnovskaya


    Full Text Available Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs in bone marrow (BM of patients with gastric cancer (GC and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1 expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P<0.024. DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (P<0.0248. Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (P<0.05. Overall survival (OS of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only (P=0.0497. Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.

  11. Introducing the Concept of the Minimally Important Difference to Determine a Clinically Relevant Change on Patient-Reported Outcome Measures in Patients with Intermittent Claudication

    A.P. Conijn (Anne P.); W. Jonkers (Wilma); E.V. Rouwet (Ellen); A. Vahl (Anco); J.A. Reekers (Jim); M.J. Koelemay


    textabstractPurpose: The minimally important difference (MID) represents the smallest change in score on patient-reported outcome measures that is relevant to patients. The aim of this study was to introduce the MID for the Vascular Quality of Life Questionnaire (VascuQol) and the walking impairment

  12. [Diagnosis of acute heart failure and relevance of biomarkers in elderly patients].

    Ruiz Ortega, Raúl Antonio; Manzano, Luis; Montero-Pérez-Barquero, Manuel


    Diagnosis of acute heart failure (HF) is difficult in elderly patients with multiple comorbidities. Risk scales and classification criteria based exclusively on clinical manifestations, such as the Framingham scales, lack sufficient specificity. In addition to clinical manifestations, diagnosis should be based on two key factors: natriuretic peptides and echocardiographic study. When there is clinical suspicion of acute HF, a normal natriuretic peptide level will rule out this process. When a consistent clinical suspicion is present, an echocardiographic study should also be performed. Diagnosis of HF with preserved ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers seems to be due to myocardial injury and the compensatory mechanisms of the body against this injury (hormone and inflammatory response and repair mechanisms). Elevation of markers of cardiac damage (troponins and natriuretic peptides) have been shown to be useful both in the diagnosis of acute HF and in prediction of outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to biomarkers with diagnostic value, other biomarkers are helpful in prognosis in the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and urea), inflammation (cytokines and CRP), and the cell regeneration marker, galectin-3. A promising idea that is under investigation is the use of panels of biomarkers, which could allow more accurate diagnosis and prognosis of acute HF.

  13. Patient-Specific Pluripotent Stem Cells in Neurological Diseases

    Serpen Durnaoglu


    Full Text Available Many human neurological diseases are not currently curable and result in devastating neurologic sequelae. The increasing availability of induced pluripotent stem cells (iPSCs derived from adult human somatic cells provides new prospects for cellreplacement strategies and disease-related basic research in a broad spectrum of human neurologic diseases. Patient-specific iPSC-based modeling of neurogenetic and neurodegenerative diseases is an emerging efficient tool for in vitro modeling to understand disease and to screen for genes and drugs that modify the disease process. With the exponential increase in iPSC research in recent years, human iPSCs have been successfully derived with different technologies and from various cell types. Although there remain a great deal to learn about patient-specific iPSC safety, the reprogramming mechanisms, better ways to direct a specific reprogramming, ideal cell source for cellular grafts, and the mechanisms by which transplanted stem cells lead to an enhanced functional recovery and structural reorganization, the discovery of the therapeutic potential of iPSCs offers new opportunities for the treatment of incurable neurologic diseases. However, iPSC-based therapeutic strategies need to be thoroughly evaluated in preclinical animal models of neurological diseases before they can be applied in a clinical setting.

  14. Using an EPID for patient-specific VMAT quality assurance

    Bakhtiari, M.; Kumaraswamy, L.; Bailey, D. W.; Boer, S. de; Malhotra, H. K.; Podgorsak, M. B. [Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 (United States); Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 and Department of Physics, State University of New York at Buffalo, Buffalo, New York 14260 (United States); Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 and Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214 (United States)


    Purpose: A patient-specific quality assurance (QA) method was developed to verify gantry-specific individual multileaf collimator (MLC) apertures (control points) in volumetric modulated arc therapy (VMAT) plans using an electronic portal imaging device (EPID). Methods: VMAT treatment plans were generated in an Eclipse treatment planning system (TPS). DICOM images from a Varian EPID (aS1000) acquired in continuous acquisition mode were used for pretreatment QA. Each cine image file contains the grayscale image of the MLC aperture related to its specific control point and the corresponding gantry angle information. The TPS MLC file of this RapidArc plan contains the leaf positions for all 177 control points (gantry angles). In-house software was developed that interpolates the measured images based on the gantry angle and overlays them with the MLC pattern for all control points. The 38% isointensity line was used to define the edge of the MLC leaves on the portal images. The software generates graphs and tables that provide analysis for the number of mismatched leaf positions for a chosen distance to agreement at each control point and the frequency in which each particular leaf mismatches for the entire arc. Results: Seven patients plans were analyzed using this method. The leaves with the highest mismatched rate were found to be treatment plan dependent. Conclusions: This in-house software can be used to automatically verify the MLC leaf positions for all control points of VMAT plans using cine images acquired by an EPID.

  15. Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy

    Campbell James J


    Full Text Available Abstract Background Circulating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors. We reasoned that a bias (either enrichment or depletion of CSF T cell expression of known organ-specific trafficking determinants might suggest that homing of T cells to the subarachnoid space could be governed by a CNS-specific adhesion molecule or chemokine receptor. Results The expression of cutaneous leukocyte antigen (CLA and CC-chemokine receptor 4 (CCR4; associated with skin-homing as well as the expression of integrin α4β7 and CCR9 (associated with gut-homing was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry. CSF contained similar proportions of CD4+ memory T cells expressing CLA, CCR4, integrin α4β7 and CCR9 as paired blood samples. Conclusion The results extend our previous findings that antigen-experienced CD4+ memory T cells traffic through the CSF in proportion to their abundance in the peripheral circulation. Furthermore, the ready access of skin- and gut-homing CD4+ memory T cells to the CNS compartment via CSF has implications for the mechanisms of action of immunotherapeutic strategies, such as oral tolerance or therapeutic immunization, where immunogens are administered using an oral or subcutaneous route.

  16. Explaining spatial patterns of sap flow: day-to-day shifts in relevance of site- and tree-specific controls

    Hassler, Sibylle K.; Weiler, Markus; Blume, Theresa


    Transpiration is a key process in the hydrological cycle and a sound understanding and quantification of transpiration is essential for management decisions and for hydrological and climatological modelling. To assess transpiration at the tree scale sap flow velocity is commonly measured. Besides atmospheric conditions and soil moisture state, tree-specific characteristics such as species, size or social status control sap flow of individual trees. Within forest stands, properties such as species composition, basal area or stem number also affect sap flow via competition or facilitation mechanisms. Finally, sap flow patterns might also be influenced by landscape-scale characteristics such as geology, slope position or aspect because they affect water and energy availability; however, so far little is known about these larger-scale controls. We studied the relative importance of various tree- and site-specific characteristics with linear statistical models for daily sap velocity observations on 38 trees at 12 locations in mixed beech and oak forests in a catchment in Luxemburg. The temporal variation of the predictors' importance for sap velocity patterns was then related to hydro-meteorological conditions. Results indicate that a combination of tree- and site-specific controls influence sap velocity patterns, namely tree species, tree diameter, stand basal area, geology and aspect. The temporal dynamics of these controls are related to hydro-meteorological conditions, with tree-specific controls dominating when the atmospheric gradient is strong, i.e. the vapour pressure deficit is large, leading to higher sap velocities, whereas landscape-scale site characteristics are more important during weak atmospheric gradients. The importance of individual predictors also varies between spring and summer, probably due to different soil moisture and atmospheric conditions of the two periods. We conclude that both tree- and site-specific characteristics control sap velocity

  17. ELN 2013 response status criteria: relevance for de novo imatinib chronic phase chronic myeloid leukemia patients?

    Etienne, Gabriel; Dulucq, Stéphanie; Lascaux, Axelle; Schmitt, Anna; Bidet, Audrey; Fort, Marie-Pierre; Lippert, Eric; Bureau, Caroline; Adiko, Didier; Hayette, Sandrine; Reiffers, Josy; Nicolini, Franck-Emmanuel; Mahon, François-Xavier


    The response definitions proposed by the European Leukemia Net (ELN) have been recently modified. We evaluated the new criteria for de novo imatinib (400 mg/d) chronic phase chronic myeloid leukemia (CP-CML) patients. Response status according to the 2009 and 2013 criteria were determined in 180 unselected patients. Outcome of the subgroups of patients were then compared. The 180 patients were classified as optimal responders (OR2009; n = 113, 62.7%), suboptimal responders (SOR2009; n = 47, 26.1%) and failures (FAIL2009; n = 20, 11.1%) according to the 2009 ELN criteria and optimal responders (OR2013; n = 77, 42.7%), warnings (WAR2013; n = 59, 32.7%), and failures (FAIL2013; n = 44, 24.4%) according to the 2013 ELN criteria. No difference in terms of outcome was observed between OR2009 patients who became WAR2013 when compared with OR2013 patients. When compared with FAIL2009 patients, SOR2009 patients who became WAR2013 had better EFS, FFS, PFS, and OS. No difference was observed in PFS or OS in SOR2009 patients who became FAIL2013. The 2013 ELN response status criteria have improved patients classification in terms of response status. However, in our patient population this improvement is related to a better definition of failure rather than that of optimal response for CP-CML patients treated with IM frontline therapy.


    Céline Nodimar


    We confirm that PD is associated with changes in BC, whether for incident or prevalent patients. The BCM®, a simple, reproducible and inexpensive technique, could be proposed in the systematic nutritional monitoring of PD patients, in order to detect early modification of nutritional status in those patients and then to adapt clinical management.

  19. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    M J Pont

    Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

  20. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Pont, M J; Honders, M W; Kremer, A N; van Kooten, C; Out, C; Hiemstra, P S; de Boer, H C; Jager, M J; Schmelzer, E; Vries, R G; Al Hinai, A S; Kroes, W G; Monajemi, R; Goeman, J J; Böhringer, S; Marijt, W A F; Falkenburg, J H F; Griffioen, M


    Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

  1. The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation.

    Haji, Shamir; Planchard, Ryan; Zubair, Adeel; Graff-Radford, Jonathan; Rydberg, Charlotte; Brown, Robert D; Flemming, Kelly D


    The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6%. At 3 years, 90.6% of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6% CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.

  2. Tract specific analysis in patients with sickle cell disease

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John


    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.


    Calleja Fernández, Alicia; Pintor de la Maza, Begoña; Vidal Casariego, Alfonso; Villar Taibo, Rocío; Urioste Fondo, Ana; Cano Rodríguez, Isidoro; Ballesteros Pomar, María D


    Dysphagia is a common problem among elderly and also in some pathological conditions such as neurodegenerative diseases or tumors. Making an adequate diet for this disease may present some difficulties. The aim of this document is to make a detailed technical report about the characteristics of the products that are available in Spain to hydrate and to feed patients with dysphagia. Food and pharmaceutical industries have developed a range of products designed to ensure homogeneous texture and a suitable viscosity to guaranty an adequate hydration. An adequate nutritional status is also achieved with these products for patients with dysphagia, without compromising their safety. The ingredients used to achieve a suitable viscosity are different types of starches, gums and other substances. It has been developed thickeners and gellified water for hydratation, and in case of food there are purees (dehydrated, lyophilized, pasteurized and sterilized), fruit purees, fruit pudding, and dehydrated cereal. Patients who do not meet their nutritional needs have also oral supplements with different viscosities. The industry offers extensive information about the technical characteristics of the products, except for viscosity. It would be recommended for the manufacturers to include in detail the technical specifications of the used methodology and the measurement and the results obtained in the analysis of viscosity that can be consulted by professionals of the Clinical Nutrition and Dietetics Units who treat these patients.

  4. Behçet's syndrome patients exhibit specific microbiome signature.

    Consolandi, Clarissa; Turroni, Silvia; Emmi, Giacomo; Severgnini, Marco; Fiori, Jessica; Peano, Clelia; Biagi, Elena; Grassi, Alessia; Rampelli, Simone; Silvestri, Elena; Centanni, Manuela; Cianchi, Fabio; Gotti, Roberto; Emmi, Lorenzo; Brigidi, Patrizia; Bizzaro, Nicola; De Bellis, Gianluca; Prisco, Domenico; Candela, Marco; D'Elios, Mario M


    Behçet syndrome is a systemic inflammatory condition characterized by muco-cutaneous and ocular manifestations, with central nervous system, vascular and/or gastro-intestinal involvement. The association of microbiota with Behçet syndrome has not been shown yet. Our work was aimed to compare the gut microbiota structure and the profiles of short-chain fatty acids production in Behçet syndrome patients and healthy control relatives. Here, we compared the fecal microbiota of 22 patients with Behçet syndrome and that of 16 healthy co-habiting controls, sharing the same diet and lifestyle by pyrosequencing of the V3-V4 hypervariable regions of the 16 rDNA gene and biochemical analyses. Our analyses showed significant differences in gut microbiota between Behçet patients and healthy cohabitants. In particular we found that Behçet's patients were significantly depleted in the genera Roseburia and Subdoligranulum. Roseburia showed a relative abundance value of 10.45±6.01% in healthy relatives and 4.97±5.09% in Behçet's patients, and Subdoligranulum, which reached a relative abundance of 3.28±2.20% in healthy controls, was only at 1.93±1.75% of abundance in Behçet's patients. Here we report, for the first time, that a peculiar dysbiosis of the gut microbiota is present in patients with Behçet syndrome and this corresponds to specific changes in microbiome profile. A significant decrease of butyrate production (P=0.0033) in Behçet's patients was demonstrated. Butyrate is able to promote differentiation of T-regulatory cells, and consequently the results obtained prompt us to speculate that a defect of butyrate production might lead to both reduced T-reg responses and activation of immuno-pathological T-effector responses. Altogether, our results indicate that both a peculiar dysbiosis of the gut microbiota and a significant decrease of butyrate production are present in patients with Behçet syndrome. Published by Elsevier B.V.

  5. A Closer Look at Seborrheic Keratoses: Patient Perspectives, Clinical Relevance, Medical Necessity, and Implications for Management.

    Del Rosso, James Q


    The author sought to discover why seborrheic keratoses that are not symptomatic or clinically suspicious are not considered therapeutically important to most clinicians. The author conducted an office-based, observational study examining how the diagnosis of asymptomatic seborrheic keratoses personally affects patients and what these patients think concerning treatment. Many patients reported being bothered by the diagnosis of seborrheic keratoses, even when told it's not cancerous, and indicated an interest in its treatment. Lack of insurance coverage for the treatment of non-symptomatic seborrheic keratoses may be the primary reason clinicians do not consider seborrheic keratoses therapeutically important, as clinicians often find the discussion of "self payment" with their patients to be awkward. Furthermore, patients may not understand the implications that "lack of medical necessity" may have on their treatment options. The author describes a clinical approach that may better serve patients and clinicians through the compartmentalization of asymptomatic seborrheic keratoses treatment as a cosmetic procedure within the clinical practice model.

  6. Relevance of immobility and importance of risk assessment management for medically ill patients.

    Hull, Russell D


    Recent or continued immobility is a significant risk factor for venous thromboembolism (VTE) in acutely ill medical patients. Patients may benefit from thromboprophylaxis; however, its optimal duration remains unclear. The Extended Clinical Prophylaxis in Acutely Ill Medical Patients (EXCLAIM) study was the first trial to systematically investigate how the degree of immobilization relates to the risk of developing VTE. EXCLAIM offers insights into the duration of VTE risk associated with reduced mobility and helps identify which patients would benefit most from extended-duration thromboprophylaxis. Further recent studies suggest that extended-duration thromboprophylaxis may be in order in certain high-risk patients to protect the patients from the risk of VTE events occurring, particularly in the posthospitalization period. Baseline d-dimer data and level of mobility could be included in risk assessment. Physicians are recommended to consider the use of extended-duration thromboprophylaxis based on individual risk assessment management (RAM) and balance of benefit and harm.

  7. Taxa-specific eco-sensitivity in relation to phytoplankton bloom stability and ecologically relevant lake state

    Napiórkowska-Krzebietke, Agnieszka; Dunalska, Julita A.; Zębek, Elżbieta


    Phytoplankton (including plant-like, animal-like algae and Cyanobacteria) blooms have recently become a serious global threat to the sustenance of ecosystems, to human and animal health and to economy. This study focused on the composition and stability of blooms as well as their taxa-specific ecological sensitivity to the main causal factors (especially phosphorus and nitrogen) in degraded urban lakes. The analyzed lakes were assessed with respect to the trophic state as well as ecological status. Total phytoplankton biomass (ranging from 1.5 to 181.3 mg dm-3) was typical of blooms of different intensity, which can appear during a whole growing season but are the most severe in early or late summer. Our results suggested that steady-state and non-steady-state bloom assemblages including mono-, bi- and multi-species or heterogeneous blooms may occur in urban lakes. The most intense blooms were formed by the genera of Cyanobacteria: Microcystis, Limnothrix, Pseudanabaena, Planktothrix, Bacillariophyta: Cyclotella and Dinophyta mainly Ceratium and Peridinium. Considering the sensitivity of phytoplankton assemblages, a new eco-sensitivity factor was proposed (E-SF), based on the concept of Phytoplankton Trophic Index composed of trophic scores of phytoplankton taxa along the eutrophication gradient. The E-SF values of 0.5, 1.3, 6.7 and 15.1 were recognized in lakes having a high, good, moderate or poor ecological status, respectively. For lake restoration, each type of bloom should be considered separately because of different sensitivities of taxa and relationships with environmental variables. Proper recognition of the taxa-specific response to abiotic (especially to N and P enrichment) and biotic factors could have significant implications for further water protection and management.

  8. Patient-Specific Bacteroides Genome Variants in Pouchitis.

    Vineis, Joseph H; Ringus, Daina L; Morrison, Hilary G; Delmont, Tom O; Dalal, Sushila; Raffals, Laura H; Antonopoulos, Dionysios A; Rubin, David T; Eren, A Murat; Chang, Eugene B; Sogin, Mitchell L


    A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch. This longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each

  9. Patient-Specific Computational Modeling of Human Phonation

    Xue, Qian; Zheng, Xudong; University of Maine Team


    Phonation is a common biological process resulted from the complex nonlinear coupling between glottal aerodynamics and vocal fold vibrations. In the past, the simplified symmetric straight geometric models were commonly employed for experimental and computational studies. The shape of larynx lumen and vocal folds are highly three-dimensional indeed and the complex realistic geometry produces profound impacts on both glottal flow and vocal fold vibrations. To elucidate the effect of geometric complexity on voice production and improve the fundamental understanding of human phonation, a full flow-structure interaction simulation is carried out on a patient-specific larynx model. To the best of our knowledge, this is the first patient-specific flow-structure interaction study of human phonation. The simulation results are well compared to the established human data. The effects of realistic geometry on glottal flow and vocal fold dynamics are investigated. It is found that both glottal flow and vocal fold dynamics present a high level of difference from the previous simplified model. This study also paved the important step toward the development of computer model for voice disease diagnosis and surgical planning. The project described was supported by Grant Number ROlDC007125 from the National Institute on Deafness and Other Communication Disorders (NIDCD).

  10. Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field

    Canto-Soler M Valeria


    Full Text Available Abstract Background The use of Specific Pathogen Free (SPF eggs in combination with RCAS retrovirus, a member of the Avian Sarcoma-Leukosis Virus (ASLV family, is of standard practice to study gene function and development. SPF eggs are certified free of infection by specific pathogen viruses of either exogenous or endogenous origin, including those belonging to the ASLV family. Based on this, SPF embryos are considered to be free of ASLV viral protein expression, and consequently in developmental research studies RCAS infected cells are routinely identified by immunohistochemistry against the ASLV viral proteins p19 and p27. Contrary to this generally accepted notion, observations in our laboratory suggested that certified SPF chicken embryos may endogenously express ASLV viral proteins p19 and p27. Since these observations may have significant implications for the developmental research field we further investigated this possibility. Results We demonstrate that certified SPF chicken embryos have transcriptionally active endogenous ASLV loci (ev loci capable of expressing ASLV viral proteins, such as p19 and p27, even when those loci are not capable of producing viral particles. We also show that the extent of viral protein expression in embryonic tissues varies not only among flocks but also between embryos of the same flock. In addition, our genetic screening revealed significant heterogeneity in ev loci composition even among embryos of the same flock. Conclusions These observations have critical implications for the developmental biology research field, since they strongly suggest that the current standard methodology used in experimental studies using the chick embryo and RCAS vectors may lead to inaccurate interpretation of results. Retrospectively, our observations suggest that studies in which infected cells have been identified simply by pan-ASLV viral protein expression may need to be considered with caution. For future studies, they

  11. End of Life Planning and its Relevance for Patients and Oncologists’ Decisions in Choosing Cancer Therapy

    Saraiya, Biren; Bodnar-Deren, Susan; Leventhal, Elaine; Leventhal, Howard


    The goal of end of life (EoL) planning is to provide individuals with tools to control their financial and health care decisions when they are incapacitated. When an elderly patient is diagnosed with advanced cancer, the possible treatment options are: palliative care with curative intent or prolongation of life or palliative care only. Treatment of cancer in elderly patients creates a significant array of monetary and symptom burdens. The question is whether advance care planning (ACP), part of EoL planning, allows patients families and communities to control and reduce these burdens. Although the number of patients completing advance directives has increased in recent years, there are multiple barriers to the implementation of patients’ wishes such as limited knowledge of patient wishes by proxy and physician and inadequate communication regarding prognosis. We propose that improvements in patient decision making and clinical practice can reduce the burden of symptoms for patients if clinicians better understood patients’ models and expectations respecting the longer term consequences of diagnosis and treatment. This understanding can arise from improved information exchange and constant updating of the information as the disease and treatment evolves. Clinicians also need better prognostication tools and better training in effective communication skills to elicit patient goals and make appropriate recommendations. PMID:19058149

  12. Is Barthel index a relevant measure for measuring prevalence of urinary incontinence in stroke patients?

    Tibaek, Sigrid; Dehlendorff, Christian


    To compare the prevalence of urinary incontinence (UI) measured by Barthel Index and the Danish Prostate Symptom Score (DAN‐PSS‐1) questionnaire in stroke patients. A cross‐sectional, hospital based survey was initiated whereby 407 stroke patients, average age 67 (SD 12) years with a mean interval...

  13. Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis.

    Nagarajan, Radhakrishnan; Miller, Craig S; Dawson, Dolph; Al-Sabbagh, Mohanad; Ebersole, Jeffrey L


    This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group) A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA) framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM]) as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM). Our findings demonstrate that performance measures (sensitivity, specificity and accuracy) of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly elucidate the

  14. Patient-Specific Variations in Biomarkers across Gingivitis and Periodontitis.

    Radhakrishnan Nagarajan

    Full Text Available This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification algorithms (LDA: Linear Discriminant Analysis [LDA], Quadratic Discriminant Analysis [QDA], Naïve Bayes Classifier [NBC] and Support Vector Machines [SVM] as traditional single classifiers and within the SVA framework (SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Our findings demonstrate that performance measures (sensitivity, specificity and accuracy of traditional classification as single classifier were comparable to that of the SVA counterparts using clinical labels of the samples as ground truth. However, unlike traditional single classifier approaches, the normalized ensemble vote-counts from SVA revealed varying proclivity of the subjects for each of the disease groups. More importantly, the SVA identified a subset of gingivitis and periodontitis samples that demonstrated a biological proclivity commensurate with the other clinical group. This subset was confirmed across SVA-LDA, SVA-QDA, SVA-NB and SVA-SVM. Heatmap visualization of their ensemble sets revealed lack of consensus between these subsets and the rest of the samples within the respective disease groups indicating the unique nature of the patients in these subsets. While the source of variation is not known, the results presented clearly

  15. Nutritional risk and status of surgical patients; the relevance of nutrition training of medical students.

    Ferreira, C; Lavinhas, C; Fernandes, L; Camilo, Ma; Ravasco, P


    The prevalence of undernutrition among surgical patients is thought to be high, and negatively influencing outcomes. However, recent evidence shows the increase of overweight/obesity in hospitalised patients. A pilot cross-sectional study was conducted in 50 patients of a Surgical Department of the University Hospital of Santa Maria (CHLN) that aimed: 1) to assess nutritional risk and status through validated methods; 2) to explore the presence of overweight/obesity; 3) to evaluate the prevalence of metabolic risk associated with obesity. Nutritional risk was assessed by Malnutrition Universal Screening Tool (MUST), nutritional status by Body Mass Index (BMI), waist circumference (WC), & Subjective Global Assessment (SGA). Statistical significance was set for p nutrition discipline in the medical curricula, limits the multiprofessional management and a better understanding of the more adequate approaches to these patients. Further, the change in the clinical scenario argues for more studies to clarify the prevalence and consequences of sarcopenic obesity in surgical patients.

  16. Species-specific differences in adaptive phenotypic plasticity in an ecologically relevant trophic trait: hypertrophic lips in Midas cichlid fishes.

    Machado-Schiaffino, Gonzalo; Henning, Frederico; Meyer, Axel


    The spectacular species richness of cichlids and their diversity in morphology, coloration, and behavior have made them an ideal model for the study of speciation and adaptive evolution. Hypertrophic lips evolved repeatedly and independently in African and Neotropical cichlid radiations. Cichlids with hypertrophic lips forage predominantly in rocky crevices and it has been hypothesized that mechanical stress caused by friction could result in larger lips through phenotypic plasticity. To test the influence of the environment on the size and development of lips, we conducted a series of breeding and feeding experiments on Midas cichlids. Full-sibs of Amphilophus labiatus (thick-lipped) and Amphilophus citrinellus (thin-lipped) each were split into a control group which was fed food from the water column and a treatment group whose food was fixed to substrates. We found strong evidence for phenotypic plasticity on lip area in the thick-lipped species, but not in the thin-lipped species. Intermediate phenotypic values were observed in hybrids from thick- and thin-lipped species reared under "control" conditions. Thus, both a genetic, but also a phenotypic plastic component is involved in the development of hypertrophic lips in Neotropical cichlids. Moreover, species-specific adaptive phenotypic plasticity was found, suggesting that plasticity is selected for in recent thick-lipped species.

  17. The future of the patient-specific Body-on-a-chip.

    Williamson, Adam; Singh, Sukhdeep; Fernekorn, Uta; Schober, Andreas


    As significant advancements in technology focused on Organ-on-a-chip continue, it is feasible to consider the future of Body-on-a-chip technology. With serious work being done to realize functioning artificial livers, kidneys, hearts, and lungs on chips, the next step is not only to interconnect these organs but also to consider the integration of stem cell technology to create interconnected patient-specific organs. Such a patient-specific Body-on-a-chip requires a sophisticated set of tools for micropattering cell cultures in 3D to create interconnected tissue-like organ structures. This review discusses advanced methods of the past two years in on-Chip organs, the complex 3D patterning of cultures and state-of-the-art scaffolding, and discusses some of the most relevant advancements in human-induced pluripotent stem cell (hiPSC) research applied to these organs and scaffolds for the future of a patient-specific Body-on-a-chip. We anticipate that such a technology would have a wide area of application, primarily benefiting drug development, chemical safety testing, and disease modeling.

  18. Relevance of Bacteroidales and F-Specific RNA Bacteriophages for Efficient Fecal Contamination Tracking at the Level of a Catchment in France

    Mauffret, Aourell; Caprais, Marie-Paule


    The relevance of three host-associated Bacteroidales markers (HF183, Rum2Bac, and Pig2Bac) and four F-specific RNA bacteriophage genogroups (FRNAPH I to IV) as microbial source tracking markers was assessed at the level of a catchment (Daoulas, France). They were monitored together with fecal indicators (Escherichia coli and enterococci) and chemophysical parameters (rainfall, temperature, salinity, pH, and turbidity) by monthly sampling over 2 years (n = 240 water samples) and one specific sampling following an accidental pig manure spillage (n = 5 samples). During the 2-year regular monitoring, levels of E. coli, enterococci, total F-specific RNA bacteriophages, and the general Bacteroidales marker AllBac were strongly correlated with one another and with Rum2Bac (r = 0.37 to 0.50, P catchment. PMID:22610433

  19. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun [Dept. of Radiology, Graduate School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul (Korea, Republic of)


    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  20. [Relevance of preoperative anxiety for postoperative outcome in urological surgery patients: A prospective observational study].

    Laufenberg-Feldmann, R; Kappis, B; Schuster, M; Ferner, M


    Preoperative anxiety is not systematically assessed during premedication appointments, although it may influence the postoperative course and outcome. The aim of this study was to assess preoperative anxiety in a sample of patients before major urological surgery and to characterize the impact on postoperative pain. An additional aim was to analyze the agreement between patients' self-ratings and physicians' anxiety ratings. In all, 127 male and 27 female patients participated in a prospective observational study. Preoperative anxiety was assessed with two validated instruments - the APAIS (Amsterdam Preoperative Anxiety and Information Scale) and the State Scale of the STOA questionnaire (State-Trait Operation Anxiety) - during the premedication appointment. Physicians provided their subjective ratings on patients' anxiety and need for information using the APAIS. The predictive value of preoperative anxiety for postoperative pain was evaluated. Nearly four out of ten patients were identified as "anxiety cases"; thereof women were more afraid than men were. Preoperative anxiety was not correctly assessed by physicians, who overestimated patients' anxiety. In female patients, preoperative anxiety was predictive of increased postoperative pain scores. Preoperative anxiety is a frequent concern and often not correctly assessed by physicians. The use of scoring systems to detect preoperative anxiety is useful in clinical routine and helps to decide on therapeutic interventions.

  1. Study Gaps Relevant to Use of Complementary Medicine in Patients With Leukemia: A Review Study



    Full Text Available Context A review of the literature of recent decades has shown that few studies have been conducted on the effects of various types of complementary medicine on patients with leukemia. Therefore, the present study aimed to find research gaps in the use of different types of complementary medicine in patients with leukemia to be applied in future studies. Evidence Acquisition The present study was a review-type design based on a review of the literature on different types of complementary medicine in patients with leukemia, up to 2015. The search was conducted through electronic databases and search engines. According to the inclusion and exclusion criteria, 8 studies which had been conducted on the use of complementary medicine in patients with leukemia were selected for the identification of gaps. Results The overall results showed that few studies have been conducted on the use of exercise, massage therapy, music therapy, acupressure, and healing touch in patients with leukemia, and these subjects are potential research areas for many different studies. However, no studies have been carried out on the effects of acupuncture, relaxation, and yoga on these patients. Conclusions The results of this review showed that the number of studies on the use of complementary medicine in leukemia patients is very limited (especially in Iran, and it can be the subject of numerous studies in the future.

  2. Pharmacological levels of Withaferin A (Withania somnifera trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    Katarzyna Szarc vel Szic

    Full Text Available Withaferin A (WA isolated from Withania somnifera (Ashwagandha has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8, cell adhesion molecules (integrins, laminins, pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1. In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors

  3. Ventriculoperitoneal shunt complications in hydrocephalus patients with intracranial tumors: an analysis of relevant risk factors.

    Reddy, G Kesava; Bollam, Papireddy; Caldito, Gloria; Willis, Brian; Guthikonda, Bharat; Nanda, Anil


    Patients with intracranial tumors are predisposed to persistent hydrocephalus, often requiring a permanent CSF diversion procedure with shunts. This study reviews the long-term experience with ventriculoperitoneal shunts for the management of hydrocephalus in patients with intracranial tumors. Patients with intracranial tumors who underwent ventriculoperitoneal shunt placement for hydrocephalus from October 1990 to October 2009 were included in this study. During the 19-year period, medical charts, operative reports, imaging studies, and clinical follow- up evaluations were reviewed and analyzed retrospectively for all patients. A total of 187 intracranial tumor patients with hydrocephalus were included. The median follow up was 391 days. Malignant tumors were present in 40% of the patients. Overall shunt failure was 27.8%. Single shunt revision occurred in 13% of the patients and 14% had multiple shunt revision. Tumor histology, age and a procedure prior to shunt placement (ventriculostomy/Ommaya reservoirs) were significantly associated with the shunt revisions. Shunt system replacement and proximal shunt complication were significantly attributed to multiple shunt revisions. The overall shunt revision within 3 months, 6 months, 1 year and 5 years was 17.7%, 18.7%, 19.8% and 24.1%, respectively. The results of the study demonstrate that VP shunting is an effective for the management of hydrocephalus in patients with intracranial tumors. The overall incidence of shunt revision was 27.8%. Age, tumor histology, and a procedure prior to shunt placement (ventriculostomy/Ommaya reservoirs) were significantly associated with the shunt revisions. Additional studies using minimally invasive techniques are being explored for the management of hydrocephalus in patients with intracranial tumors.

  4. Relevance of surgery in patients with non-variceal upper gastrointestinal bleeding.

    Dango, S; Beißbarth, T; Weiss, E; Seif Amir Hosseini, A; Raddatz, D; Ellenrieder, V; Lotz, J; Ghadimi, B M; Beham, A


    Upper GI bleeding remains one of the most common emergencies with a substantial overall mortality rate of up to 30%. In severe ill patients, death does not occur due to failure of hemostasis, either medical or surgical, but mainly from comorbidities, treatment complications, and decreased tolerated blood loss. Management strategies have changed dramatically over the last two decades and include primarily endoscopic intervention in combination with acid-suppressive therapy and decrease in surgical intervention. Herein, we present one of the largest patient-based analysis assessing clinical parameters and outcome in patients undergoing endoscopy with an upper GI bleeding. Data were further analyzed to identify potential new risk factors and to investigate the role of surgery. In this retrospective study, we aimed to analyze outcome of patients with an UGIB and data were analyzed to identify potential new risk factors and the role of surgery. Data collection included demographic data, laboratory results, endoscopy reports, and details of management including blood administration, and surgery was carried out. Patient events were grouped and defined as "overall" events and "operated," "non-operated," and "operated and death" as well as "non-operated and death" where appropriate. Blatchford, clinical as well as complete Rockall-score analysis, risk stratification, and disease-related mortality rate were calculated for each group for comparison. Overall, 253 patients were eligible for analysis: endoscopy was carried out in 96% of all patients, 17% needed surgical intervention after endoscopic failure of bleeding control due to persistent bleeding, and the remaining 4% of patients were subjected directly to surgery. The median length of stay to discharge was 26 days. Overall mortality was 22%; out of them, almost 5% were operated and died. Anticoagulation was associated with a high in-hospital mortality risk (23%) and was increased once patients were taken to surgery (43

  5. Association between depression, patient scar assessment and burn-specific health in hospitalized burn patients.

    Roh, Young Sook; Chung, Hyun Soo; Kwon, Boeun; Kim, Giyon


    Depression is one of the most common psychological problems arising after a burn, but its relationship with patient scar assessment and burn-specific health are poorly understood. The aim of this study was to identify the incidence of in-hospital symptoms of depression, compare level of patient scar assessment, and burn-specific health by depression cutoff point, and identify the relationship between depression and these variables. In a cross-sectional descriptive study, 113 burn patients from two inpatient burn centers were divided into two groups based on the cutoff point of the Korean Center for Epidemiologic Studies Depression Scale (Korean CES-D): ≥25 or Patient Scar Assessment Scale and Korean Burn-Specific Health Scale-Brief (BSHS-B-K) were used to identify associations with depression. Incidence of severe, definite depression as assessed by a score of 25 or above on the Korean CES-D was approximately 50% on an average at 60.9 days after injury. Burn patients with the Korean CES-D≥25 had significantly higher total mean patient scar assessment scores (43.34±11.49 vs. 36.84±9.56, t=3.265, p=.001), and lower burn-specific health subscale scores compared to patients with Korean CES-DPatient Scar Assessment, ranging from r=.196 to .335 except scar color. Depression was significantly correlated with all subscales of the BSHS-B-K, range from r=-.320 to -.725. Results indicate that incidence of symptoms of depression is relatively high, and depressed burn patients report worse burn scar or sensation and lower levels of burn-specific health. Early, timely recognition and management of depression in these patients are warranted. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  6. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel


    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. Successful treatment of a guanidinoacetate methyltransferase deficient patient : Findings with relevance to treatment strategy and pathophysiology

    Verbruggen, Krijn T.; Sijens, Paul E.; Schulze, Andreas; Lunsing, Roelineke J.; Jakobs, Cornelis; Salomons, Gajja S.; van Spronsen, Francian J.


    Biochemical and developmental results of treatment of a guanidinoacetate methyltransferase (GAMT) deficient patient with a mild clinical presentation and remarkable developmental improvement after treatment are presented. Treatment with creatine (Cr) supplementation resulted in partial normalization

  8. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2

    Peters Ansgar J


    Full Text Available Abstract Objective The influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2. Background It is known that patients with diabetes (DM have abnormal metabolic and hemostatic parameters Methods Of 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA, plasminogen-activator-inhibitor (PAI, plasmin-a-antiplasmin (PAP, prothrombin-fragment 1+2 (F1+2, thrombin-antithrombin (TAT, von-willebrand-factor (vWF, platelet factor 4 (PF4, glykomembranproteine 140 (GMP140 and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association. Results Patients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF, endogenous fibrinolysis (PAI and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p Conclusion Patients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.

  9. Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients

    Ghaleb Elyamany


    Full Text Available The Fms-like tyrosine kinase-3 (FLT3 is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML. AML patients with FLT3 internal tandem duplication (ITD mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835 in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56% was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric. Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female. Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.

  10. Cerebral microbleeds (CMBs) - relevance for mechanisms of cerebral hemorrhage--analysis of 24 MRI evaluated patients.

    Ghelmez, D; Sorin Tuţă, S; Popa, C


    The new MRI techniques introduced in the last decade allowed the detection of cerebral microbleeds (CMBs) in different groups of diseases: stroke, Alzheimer disease, vascular dementia or healthy people of advanced age. CMBs are radiologically defined as small, rounded, homogeneous, hypointense lesions on T2*-weighed gradient-recalled echo (T2*-GRE) sequences. We evaluated the prevalence, number and location of CBMs in a cohort of 26 consecutive cerebral hemorrhage patients admitted in the National Institute of Neurology and Neurovascular Diseases. We also assessed the association between CMB, classical vascular risk factors and small vessel disease. From the 26 patients, 2 patients had secondary intracerebral hemorrhage (ICH) (hemorrhage in metastasis, respectively a cavernoma). From the 24 ICH patients 12 have had at least 1 CMB lesion. The average volume of the cerebral hemorrhage was larger in patients with CMBs, with a relative increase of 42%. Small vessel disease was associated with a significant increase in the presence of CMBs (relative increase of 86%). In both cases, however, since the number of patients enrolled was small, the correlations did not reach statistical significance.

  11. Respiratory gated radiotherapy-pretreatment patient specific quality assurance

    Rajesh Thiyagarajan


    Full Text Available Organ motions during inter-fraction and intra-fraction radiotherapy introduce errors in dose delivery, irradiating excess of normal tissue, and missing target volume. Lung and heart involuntary motions cause above inaccuracies and gated dose delivery try to overcome above effects. Present work attempts a novel method to verify dynamic dose delivery using a four-dimensional (4D phantom. Three patients with mobile target are coached to maintain regular and reproducible breathing pattern. Appropriate intensity projection image set generated from 4D-computed tomography (4D-CT is used for target delineation. Intensity modulated radiotherapy plans were generated on selected phase using CT simulator (Siemens AG, Germany in conjunction with "Real-time position management" (Varian, USA to acquire 4D-CT images. Verification plans were generated for both ion chamber and Gafchromic (EBT film image sets. Gated verification plans were delivered on the phantom moving with patient respiratory pattern. We developed a MATLAB-based software to generate maximum intensity projection, minimum intensity projections, and average intensity projections, also a program to convert patient breathing pattern to phantom compatible format. Dynamic thorax quality assurance (QA phantom (Computerized Imaging Reference Systems type is used to perform the patient specific QA, which holds an ion chamber and film to measure delivered radiation intensity. Exposed EBT films are analyzed and compared with treatment planning system calculated dose. The ion chamber measured dose shows good agreement with planned dose within ± 0.5% (0.203 ± 0.57%. Gamma value evaluated from EBT film shows passing rates 92–99% (96.63 ± 3.84% for 3% dose and 3 mm distance criteria. Respiratory gated treatment delivery accuracy is found to be within clinically acceptable level.

  12. The Relevance of the High Frequency Audiometry in Tinnitus Patients with Normal Hearing in Conventional Pure-Tone Audiometry.

    Vielsmeier, Veronika; Lehner, Astrid; Strutz, Jürgen; Steffens, Thomas; Kreuzer, Peter M; Schecklmann, Martin; Landgrebe, Michael; Langguth, Berthold; Kleinjung, Tobias


    The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz-8 kHz). Here we explored whether the results of the high frequency audiometry (>8 kHz) provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical characteristics. From the database of the Tinnitus Clinic at Regensburg we identified 75 patients with normal hearing thresholds in the conventional pure-tone audiometry. We contrasted these patients with normal and pathological high-frequency audiogram and compared them with respect to gender, age, tinnitus severity, pitch, laterality and duration, comorbid symptoms and triggers for tinnitus onset. Patients with pathological high frequency audiometry were significantly older and had higher scores on the tinnitus questionnaires in comparison to patients with normal high frequency audiometry. Furthermore, there was an association of high frequency audiometry with the laterality of tinnitus. In tinnitus patients with normal pure-tone audiometry the high frequency audiometry provides useful additional information. The association between tinnitus laterality and asymmetry of the high frequency audiometry suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis.

  13. The Relevance of the High Frequency Audiometry in Tinnitus Patients with Normal Hearing in Conventional Pure-Tone Audiometry

    Veronika Vielsmeier


    Full Text Available Objective. The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz–8 kHz. Here we explored whether the results of the high frequency audiometry (>8 kHz provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical characteristics. Subjects and Methods. From the database of the Tinnitus Clinic at Regensburg we identified 75 patients with normal hearing thresholds in the conventional pure-tone audiometry. We contrasted these patients with normal and pathological high-frequency audiogram and compared them with respect to gender, age, tinnitus severity, pitch, laterality and duration, comorbid symptoms and triggers for tinnitus onset. Results. Patients with pathological high frequency audiometry were significantly older and had higher scores on the tinnitus questionnaires in comparison to patients with normal high frequency audiometry. Furthermore, there was an association of high frequency audiometry with the laterality of tinnitus. Conclusion. In tinnitus patients with normal pure-tone audiometry the high frequency audiometry provides useful additional information. The association between tinnitus laterality and asymmetry of the high frequency audiometry suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis.

  14. Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria.

    Jang, Hye Ryoun; Jeon, Junseok; Park, Ji Hyeon; Lee, Jung Eun; Huh, Wooseong; Oh, Ha Young; Kim, Yoon-Goo


    Urinary angiotensinogen (AGT) and renin have been reported to reflect the intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and clinical significance of these markers have not been evaluated in overtly proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary renin/Cr) showed positive correlations with urinary P/Cr. There was a positive correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary renin/Cr) was not affected by ln (plasma renin) regardless of the degree of proteinuria. The treatment response to RAS inhibitors was greatest in patients with high urinary AGT and renin. However, the predictive value of those parameters was no longer present when the values were adjusted by the degree of proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated with persistent overt proteinuria after 1 year. Our study suggests that urinary renin may be a better marker in heavy proteinuria, and the treatment response to RAS inhibitors may be enhanced in patients with high urinary renin and AGT. Further studies will be necessary to explore the value of urinary AGT and renin.

  15. Septic liver - Clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis

    Han, Ga Jin; Lee, Nam Kyung; Kim, Suk [Dept. of Radiology, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)], e-mail:; Kim, Tae Un [Dept. of Radiology, Pusan National Univ. Yangsan Hospital, Pusan National Univ. School of Medicine, Yangsan (Korea, Republic of); Song, Sang Heon [Dept. of Internal Medicine, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of); Kim, Hyun Sung; Jo, Hong Jae [Dept. of Surgery, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)


    Background: CT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease. Purpose: To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis. Material and Methods: This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test. Results: Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040). Conclusion: Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive

  16. Quality of Life among Family Caregivers of Patients on Hemodialysis and its Relevant Factors: A Systematic Review

    Seyedeh Azam Sajadi


    Full Text Available Background: Family caregivers are considered as hidden patients experiencing physical and mental disorders. This affects the quality of not only their lives but also the health care provided to patients.This study aimed to investigate the quality of life (QOL and its related factors among the caregivers of patients undergoing hemodialysis. Methods: This systematic review was conducted based on the eight-step guidelines presented by the York University. The databases relevant to the medical field including Nursing and Allied Health, Web of Science, Scopus, Pubmed, Embase, PsycINFO and Psychology Library were used. Finally, 12 articles observing the inclusion criteria and with regard to the research questions were found. The data obtained from these articles were summarized, classified, and analyzed. Results: QOL among Family Caregivers of Patients on Hemodialysis is low, compared to the general population; however, their QOL is higher than the patients under their care. Factors relevant to the QOL for caregivers including age, gender, perceived social support, perceived burden of care, affliction with other diseases (lupus, hypertension, hypothyroidism and depression, intellectual understanding of the limitations of the patient’s disease in their daily life, employment of adaptation strategies, better marital relationships, accepting self and family relationship with the patient (mother and wife. Furthermore, the factors associated with care takers affecting the quality of caregivers’ lives were age, QOL and the type of treatment. Conclusions: Caregivers of patients undergoing hemodialysis enjoyed low QOL. Since there is a direct relationship between family caregivers’ quality and patients’ QOL, health care system and health policy makers should pay more attention to family caregivers.

  17. Risk-Adjusted Analysis of Relevant Outcome Drivers for Patients after More Than Two Kidney Transplants

    Lampros Kousoulas


    Full Text Available Renal transplantation is the treatment of choice for patients suffering end-stage renal disease, but as the long-term renal allograft survival is limited, most transplant recipients will face graft loss and will be considered for a retransplantation. The goal of this study was to evaluate the patient and graft survival of the 61 renal transplant recipients after second or subsequent renal transplantation, transplanted in our institution between 1990 and 2010, and to identify risk factors related to inferior outcomes. Actuarial patient survival was 98.3%, 94.8%, and 88.2% after one, three, and five years, respectively. Actuarial graft survival was 86.8%, 80%, and 78.1% after one, three, and five years, respectively. Risk-adjusted analysis revealed that only age at the time of last transplantation had a significant influence on patient survival, whereas graft survival was influenced by multiple immunological and surgical factors, such as the number of HLA mismatches, the type of immunosuppression, the number of surgical complications, need of reoperation, primary graft nonfunction, and acute rejection episodes. In conclusion, third and subsequent renal transplantation constitute a valid therapeutic option, but inferior outcomes should be expected among elderly patients, hyperimmunized recipients, and recipients with multiple operations at the site of last renal transplantation.

  18. Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

    Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja


    Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; Phypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

  19. Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

    Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco


    Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.


    Florin-Alexandru LUCA


    Full Text Available A survey in 2013 of Division Market Research Group Rentrop Straton Romanian-German - "state services and private clinics. Comparative Analysis ", highlights the fact that into urban population in Romania, the internet is the most popular source of information on health services. According to the survey, 81.9% of respondents use the Internet to find out about the best doctors available to them. Preferences of respondents to the online environment as the main source of information translates into ease of access and the possibility of interaction, but also trust recommendations based on personal experiences, recommendations can be found through discussion forums, mostly or comments left on pages on social networking sites. In the present study we try to emphasize the specificity of communication physician - patient online through social networks.

  1. A patient-specific scatter artifacts correction method

    Zhao, Wei; Niu, Kai; Schafer, Sebastian; Royalty, Kevin; Chen, Guang-Hong


    This paper provides a fast and patient-specific scatter artifact correction method for cone-beam computed tomography (CBCT) used in image-guided interventional procedures. Due to increased irradiated volume of interest in CBCT imaging, scatter radiation has increased dramatically compared to 2D imaging, leading to a degradation of image quality. In this study, we propose a scatter artifact correction strategy using an analytical convolution-based model whose free parameters are estimated using a rough estimation of scatter profiles from the acquired cone-beam projections. It was evaluated using Monte Carlo simulations with both monochromatic and polychromatic X-ray sources. The results demonstrated that the proposed method significantly reduced the scatter-induced shading artifacts and recovered CT numbers.

  2. Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls

    Holtze, Maria; Saetre, Peter; Engberg, Göran;


    on the activity of kynurenine 3-monooxygenase (KMO), the enzyme converting kynurenine to 3-hydroxykynurenine. Methods: We analyzed the association between KMO gene polymorphisms and CSF concentrations of KYNA in patients with schizophrenia and healthy controls. Fifteen single nucleotide polymorphisms (SNPs) were......Background: Patients with schizophrenia show increased brain and cerebrospinal fluid (CSF) concentrations of the endogenous N-methyl-D-aspartate receptor antagonist kynurenic acid (KYNA). This compound is an end-metabolite of the kynurenine pathway, and its formation indirectly depends...... selected covering KMO and were analyzed in UNPHASED. Results: We included 17 patients with schizophrenia and 33 controls in our study. We found an association between a KMO SNP (rs1053230), encoding an amino acid change of potential importance for substrate interaction, and CSF concentrations of KYNA...

  3. Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

    Angelika Copija


    Full Text Available Microsatellite instability (MSI is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR, resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies.

  4. Prognostic relevance of pretherapeutic gamma-glutamyltransferase in patients with primary metastatic breast cancer.

    Christine Staudigl

    Full Text Available Gamma-glutamyltransferase (GGT is a known marker for apoptotic balance and cell detoxification. Recently, an association of baseline GGT levels and breast cancer incidence, tumor progression and chemotherapy resistance was shown. The purpose of this study was to evaluate the association of pre-therapeutic GGT levels, clinical-pathological parameters and survival in patients with primary metastatic breast cancer (PMBC.In this multicenter analysis, pre-therapeutic GGT levels and clinical-pathological parameters of 114 patients diagnosed with PMBC between 1996 and 2012 were evaluated. The association between GGT levels and clinical-pathological parameters were analysed. Patients were stratified into four GGT risk-groups (GGT < 18.00 U/L: normal low, 18.00 to 35.99 U/L: normal high, 36.00 to 71.99 U/L: elevated and ≥ 72.00 U/L: highly elevated and survival analyses were performed.Patients in the high risk GGT group had a poorer overall survival, when compared to the low risk group with five-year overall survival rates of 39.5% and 53.7% (p = 0.04, respectively. Patients with larger breast tumors had a trend towards higher GGT levels (p = 0.053. Pre-therapeutic GGT levels were not associated with indicators of aggressive tumor biology such as HER2-status, triple negative histology, or poorly differentiated cancers.Pre-therapeutic GGT serum level might serve as a novel prognostic factor for overall-survival in patients with PMBC.

  5. Dentists' knowledge and opinions of oral-systemic disease relationships: relevance to patient care and education.

    Paquette, David W; Bell, Kathryn P; Phillips, Ceib; Offenbacher, Steven; Wilder, Rebecca S


    Population studies consistently support associations between poor oral (periodontal) health and systemic diseases such as cardiovascular disease (CVD) and diabetes. The aim of this study was to assess the knowledge of dentists and document their opinions regarding the evidence on oral-systemic disease relationships. A survey consisting of 39 items was developed and mailed to 1,350 licensed dentists in North Carolina. After three mailings, 667 dentists (49%) meeting inclusion criteria responded. The respondents were predominantly male (76.3%), in solo practice (59.5%), and in non-rural settings (74%). More than 75% of these dentists correctly identified risk factors like diet, genetics, smoking, obesity, and physical inactivity for CVD and diabetes. The majority rated the evidence linking periodontal disease with CVD and diabetes as strong (71% and 67%, respectively). These dentists were most comfortable inquiring about patients' tobacco habits (93%), treating patients with diabetes (89%) or CVD (84%) and concurrent periodontal disease, and discussing diabetes-periodontal disease risks with patients (88%). Fewer respondents were comfortable asking patients about alcohol consumption (54%) or providing alcohol counseling (49%). Most agreed that dentists should be trained to identify risk factors (96%) or actively manage systemically diseased patients (74%). Over 90% agreed that medical and dental professionals should be taught to practice more collaboratively. These data indicate that these dentists were knowledgeable about oral-systemic health associations, had mixed comfort levels translating the evidence into clinical practice, but expressed support for interprofessional education to improve their readiness to actively participate in their patients' overall health management.

  6. A Patient-Specific Airway Branching Model for Mechanically Ventilated Patients

    Nor Salwa Damanhuri


    Full Text Available Background. Respiratory mechanics models have the potential to guide mechanical ventilation. Airway branching models (ABMs were developed from classical fluid mechanics models but do not provide accurate models of in vivo behaviour. Hence, the ABM was improved to include patient-specific parameters and better model observed behaviour (ABMps. Methods. The airway pressure drop of the ABMps was compared with the well-accepted dynostatic algorithm (DSA in patients diagnosed with acute respiratory distress syndrome (ARDS. A scaling factor (α was used to equate the area under the pressure curve (AUC from the ABMps to the AUC of the DSA and was linked to patient state. Results. The ABMps recorded a median α value of 0.58 (IQR: 0.54–0.63; range: 0.45–0.66 for these ARDS patients. Significantly lower α values were found for individuals with chronic obstructive pulmonary disease (P<0.001. Conclusion. The ABMps model allows the estimation of airway pressure drop at each bronchial generation with patient-specific physiological measurements and can be generated from data measured at the bedside. The distribution of patient-specific α values indicates that the overall ABM can be readily improved to better match observed data and capture patient condition.

  7. Is the Internet a useful and relevant source for health and health care information retrieval for German cardiothoracic patients? First results from a prospective survey among 255 Patients at a German cardiothoracic surgical clinic

    Diez Claudius


    Full Text Available Abstract Background It is not clear how prevalent Internet use among cardiopathic patients in Germany is and what impact it has on the health care utilisation. We measured the extent of Internet use among cardiopathic patients and examined the effects that Internet use has on users' knowledge about their cardiac disease, health care matters and their use of the health care system. Methods We conducted a prospective survey among 255 cardiopathic patients at a German university hospital. Results Forty seven respondents (18 % used the internet and 8,8 % (n = 23 went online more than 20 hours per month. The most frequent reason for not using the internet was disinterest (52,3 %. Fourteen patients (5,4 % searched for specific disease-related information and valued the retrieved information on an analogous scale (1 = not relevant, 5 = very relevant on median with 4,0. Internet use is age and education dependent. Only 36 (14,1 % respondents found the internet useful, whereas the vast majority would not use it. Electronic scheduling for ambulatory visits or postoperative telemedical monitoring were rather disapproved. Conclusion We conclude that Internet use is infrequent among our study population and the search for relevant health and disease related information is not well established.

  8. [Stages of 3,547 patients with chronic kidney disease and relevant factor analysis].

    Liu, Hong; Peng, Youming; Li, Juan; Liu, Yinghong; Cheng, Meichu; Yuan, Fang; Liu, Fuyou


    To investigate the prevalence and distribution of chronic kidney disease(CKD) in Second Xiangya Hospital of Central South University. We retrospectively analyzed the medical records of 3547 CKD patients (>or=14 years old) admitted to Second Xiangya Hospital for the 1st time from January 2003 to December 2008. Glomerular filtration rate (GFR) was estimated by using the MDRD equation abbreviated [eGFR=186.3*SCr-1.154*age-0.203*0.742 (for women) mL/min.1.73 m2]. Data of patients' gender, age, admission number, etiologic and functional diagnose, course of disease, blood pressure, hemoglobin, urine, renal function, blood albumin, and kidney ultra-B were collected. (1) The most common causes for CKD were primary glomerulonephritis(55.20%), hypertension (14.55%) and diabetes (11.78%). The composition of the causes during this 6 years was not significantly different (P>0.05). The proportion of chronic glomerulonephritis declined while that of hypertensive nephropathy and diabetic nephropathy increased as time passed. (2) Patients were respectively distributed from stage 3 to stage 5 at the following percentages: 11.59% (stage 3), 23.03% (stage 4), and 65.38% (stage 5). Middle-aged and young patients (41 years60 years) accounted for 36.88% of the CKD patients. Chronic glomerulonephritis was often seen at 21-40 and 41-60 year olds. Patients with lupus nephritis were younger, 48.35% of whom were 21-40 years old. On the contrary, patients with hypertensive nephropathy and diabetic nephropathy were much older. They were mainly seen in older than 40 year groups. (3) Obstructive nephropathy and gout nephropathy occurred mainly in men while it seemed much easier for women to suffer from lupus nephritis. (4) The majority of CKD patients was accompanied by anemia (94.28%) and hypertension (56.91%), and the incidence and degree of anemia and hypertension increased as CKD developed (P<0.005). The top 3 causes of CKD are chronic glomerulonephritis, hypertensive nephropathy, and

  9. Research on relevant factors affecting results of extubation of trachea cannula in neurocritical care patients



    Objective To explore the relative factors which caused the extubation failure in neurological intensive care unit(NICU). Methods It was a retrospective study. 40 cases of patients who met the criteria,were brought into statistical analysis. They were admitted in NICU in

  10. Relevance of a laboratory physician's report to patient care in a ...


    Oct 23, 2015 ... laboratory report services by physicians. ... The data was analyzed using ... customer.[1] Clinicians are interested in service quality, ... significantly to the provision of high quality efficient ... Do you feel satisfied about improvement in patient's .... tests results and is better trained to determine the effect of.

  11. Relevance of echocardiographic evaluation of right ventricular function in patients undergoing cardiac resynchronization therapy.

    Scuteri, Lea; Rordorf, Roberto; Marsan, Nina Ajmone; Landolina, Maurizio; Magrini, Giulia; Klersy, Catherine; Frattini, Folco; Petracci, Barbara; Vicentini, Alessandro; Campana, Carlo; Tavazzi, Luigi; Ghio, Stefano


    Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT). Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction > or =15% at 6 months. All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 +/- 4 mm vs 20 +/- 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 +/- 14 mmHg vs 27 +/- 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 +/- 6 cm(2) vs 16 +/- 3 cm(2) P 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001). Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline.

  12. Changes of IL-6 and relevant cytokines in patients with hepatocellularcarcinoma and their clinical significance

    Cai Yah Zhao; Yue Lin Li; Su Xia Liu; Zhong Jun Feng


    AIM To study the changes of IL-6,IL-2, sIL-2R and TNF ir patients with hepatocellular carcinoma(HCC)and their clinical significance.METHODS IL-6, IL-2, sIL-2R and TNF were detected by avidin-biotin-system ELISA, double-sandwichELISA respectively in 60 patients with HCC and 36 patients with liver cirrhosis (LC) and 66 healthy persons.RESULTS The levels of IL-6, sIL-2R and TNF increased, but IL-2 level was lower in patients with HCCthan that in normal controls (NC) (t test, t=8.21, 4.71, 3.87, 2.13, P<0.01 or 0.05). IL-6 level in HCCwas 10 fold higher than NC, and also much higher than LC. IL-6 level was higher in later stage than that inearlier stage. There was a positive correlation between IL-6 and sIL-2R, TNF, while no positive correlationwas found between IL-2 and IL-6, sIL-2R in HCC.CONCLUSION The remarkably higher level of IL-6 is helpful for the early diagnosis of HCC.

  13. Unsupervised analysis of classical biomedical markers: robustness and medical relevance of patient clustering using bioinformatics tools.

    Michal Markovich Gordon

    Full Text Available MOTIVATION: It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples. METHOD: Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES. The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set. RESULTS: The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered. CONCLUSIONS: Clustering according to classical clinical biomarkers is a robust

  14. Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer.

    Bin, Wu; He, Wang; Feng, Zhang; Xiangdong, Lu; Yong, Chen; Lele, Kou; Hongbin, Zhang; Honglin, Guo


    Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients' survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.

  15. Relevance of low-pressure compression corsets in physiotherapeutic treatment of patients after mastectomy and lymphadenectomy

    Hansdorfer-Korzon R


    Full Text Available Rita Hansdorfer-Korzon,1 Jacek Teodorczyk,2 Agnieszka Gruszecka,3 Jacek Wydra,4 Piotr Lass2,5 1Department of Physiotherapy, 2Depart­ment of Nuclear Medicine, 3Department of Informatics and Statistics, Medical University of Gdansk, Gdansk, 4Department of Oncological Surgery, “Szpital Morski im. PCK” Hospital in Gdynia, 5Department of Molecular Spectroscopy, Institute of Experimental Physics, University of Gdansk, Gdansk, Poland Abstract: There is no fully effective treatment for secondary lymphedema. In patients with breast cancer, lymphedema may present immediately after axillary dissection or years later. It typically occurs in a limb (such as an arm, but it can also occur in the torso, especially in breast cancer patients. It is, therefore, essential to prevent or minimize the condition. The currently used compression therapy has varying efficiency. Thus, researchers are still looking for better solutions, especially for primary prevention. The aim of this study was to find whether compression corsets therapy with a class I compression garment could prevent truncal lymphedema on the operated side in females who underwent mastectomy and axillary lymph node dissection as the standard of care for breast cancer treatment without subsequent reconstruction. We also investigated whether this therapy is efficient in prevention and treatment of truncal lymphedema in patients who underwent mastectomy and additional radiotherapy, and finally whether this method could be implemented for pain reduction strategies in this treatment group. The study was carried out in 50 randomly selected breast cancer patients classified by the oncologist as candidates for surgery. The final study was completed in 37 patients who underwent mastectomy and lymphadenectomy. The study group was randomly divided into two subgroups: subgroup G (received compression corsets 1 month following the surgery and subgroup K (control in which the patients underwent no

  16. Individualized patient-centered lifestyle recommendations: an expert system for communicating patient specific cardiovascular risk information and prioritizing lifestyle options.

    Chi, Chih-Lin; Nick Street, W; Robinson, Jennifer G; Crawford, Matthew A


    We propose a proof-of-concept machine-learning expert system that learned knowledge of lifestyle and the associated 10-year cardiovascular disease (CVD) risks from individual-level data (i.e., Atherosclerosis Risk in Communities Study, ARIC). The expert system prioritizes lifestyle options and identifies the one that maximally reduce an individual's 10-year CVD risk by (1) using the knowledge learned from the ARIC data and (2) communicating for patient-specific cardiovascular risk information and personal limitations and preferences (as defined by variables used in this study). As a result, the optimal lifestyle is not only prioritized based on an individual's characteristics but is also relevant to personal circumstances. We also explored probable uses and tested the system in several examples using real-world scenarios and patient preferences. For example, the system identifies the most effective lifestyle activities as the starting point for an individual's behavior change, shows different levels of BMI changes and the associated CVD risk reductions to encourage weight loss, identifies whether weight loss or smoking cessation is the most urgent change for a diabetes patient, etc. Answers to the questions noted above vary based on an individual's characteristics. Our validation results from clinical trial simulations, which compared original with the optimal lifestyle using an independent dataset, show that the optimal individualized patient-centered lifestyle consistently reduced 10-year CVD risks. Copyright © 2012. Published by Elsevier Inc.

  17. Enteral Nutrition Related Complications Relevant to Alteration of Formulas in Two Critically Ill Pediatric Patients

    Akuzawa, Nobuhiro; Takeuchi, Aya Murata; Tsukagoshi, Jun; Kaneko, Ryoko; Naito, Hiroshi; Mizuno, Takahisa; Sunaga, Yasuo; Tashiro, Masahiko


    The early institution of enteral nutrition is associated with beneficial outcomes and intestinal growth in pediatric patients. However, the number, frequency, and types of unfavorable events occurring with particular formulas are undefined. We experienced unexpected complications in two cases following a change in formula. One case diagnosed with myotubular myopathy experienced highly-increased gastric residuals and watery diarrhea leading to decreased calorie intake and weight loss. The second case with campomelic dysplasia suffered liver dysfunction and fever. In both cases, symptoms developed soon after of the change in formula and improved after resumption of the previous formula. Both cases had undergone tracheostomy and artificial ventilation, and had a history of feeding the same formula for an extended period of time. In chronic care patients such as ours, a change in formula may cause unexpected adverse events; therefore, caution is warranted.

  18. Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors

    Sellgren, C M; Sheridan, S D; Gracias, J; Xuan, D; Fu, T; Perlis, R H


    Engulfment of synapses and neural progenitor cells (NPCs) by microglia is critical for the development and maintenance of proper brain circuitry, and has been implicated in neurodevelopmental as well as neurodegenerative disease etiology. We have developed and validated models of these mechanisms by reprogramming microglia-like cells from peripheral blood mononuclear cells, and combining them with NPCs and neurons derived from induced pluripotent stem cells to create patient-specific cellular models of complement-dependent synaptic pruning and elimination of NPCs. The resulting microglia-like cells express appropriate markers and function as primary human microglia, while patient-matched macrophages differ markedly. As a demonstration of disease-relevant application, we studied the role of C4, recently implicated in schizophrenia, in engulfment of synaptic structures by human microglia. The ability to create complete patient-specific cellular models of critical microglial functions utilizing samples taken during a single clinical visit will extend the ability to model central nervous system disease while facilitating high-throughput screening. PMID:27956744

  19. Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease

    D.R.S. Souza


    Full Text Available Apolipoprotein E (apoE - e2, e3, e4 alleles plays a role in the regulation of lipid metabolism, with the e4 considered to be a risk factor for coronary artery disease (CAD. We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking. Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the e3 allele was prevalent in the CAD (0.87 and non-CAD groups (0.81; P = 0.099, followed by the e4 allele (0.09 and 0.14, respectively; P = 0.158. The e3/3 (76 and 78% and e3/4 (16 and 23% were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05, independently of the e4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232. The frequency of risk factors was higher in the CAD group (P < 0.05, but their association with the lipid profile was not demonstrable in e4 carriers. In conclusion, the e4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the e4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account.


    B. S. Belov


    Full Text Available The past decades are marked by the obvious progress in rheumatology, which is related to the practical introduction of biological agents. At the same time the use of these drugs is associated with the increasing risk of infections of different nature and locations, including opportunistic ones (invasive mycoses, Pneumocystis pneumonia, etc., and with the greater risk of reactivation of latent infection, primary with that of tuberculosis. Beyond that point, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc., including those with a fatal outcome. This review analyzes mainly the past 3-year literature data on the rate and location of infections treated with biologics, which have been obtained in the placebo-controlled and direct comparative studies of patients with rheuma- toid arthritis. It characterizes the importance of different infections (tuberculosis, pneumonia, chronic viral hepati- tides, herpesvirus infections, etc. for treatment policy in the above patients. This underlines the need for wider immu- nization with different vaccines (chiefly against pneumococcus and influenza in patients with autoimmune inflam- matory rheumatic diseases. 

  1. A Systematic Review of Web-Based Interventions for Patient Empowerment and Physical Activity in Chronic Diseases: Relevance for Cancer Survivors

    Kuijpers, Wilma; Groen, Wim G; Aaronson, Neil K


    -management training, personal exercise program, and communication (eg, chat, email) with either health care providers or patients. Limited information was found on barriers, facilitators, and users’ experiences. Methodological quality varied, with 13 studies being of moderate quality. The reported Web-based intervention elements appeared to be highly relevant to address the specific needs of cancer survivors as indicated by the IOM. Conclusions We identified 7 common elements of interactive, Web-based interventions in chronic disease settings that could possibly be translated into eHealth recommendations for cancer survivors. While further work is needed to determine optimal intervention characteristics, the work performed in other chronic disease settings provides a basis for the design of an interactive eHealth approach to improve patient empowerment and physical activity in cancer survivors. This may subsequently improve their health status and quality of life and reduce their need for supportive care. PMID:23425685

  2. Fuzzy control for closed-loop, patient-specific hypnosis in intraoperative patients: a simulation study.

    Moore, Brett L; Pyeatt, Larry D; Doufas, Anthony G


    Research has demonstrated the efficacy of closed-loop control of anesthesia using bispectral index (BIS) as the controlled variable, and the recent development of model-based, patient-adaptive systems has considerably improved anesthetic control. To further explore the use of model-based control in anesthesia, we investigated the application of fuzzy control in the delivery of patient-specific propofol-induced hypnosis. In simulated intraoperative patients, the fuzzy controller demonstrated clinically acceptable performance, suggesting that further study is warranted.

  3. The relevance of Rawls' principle of justice for research on cognitively impaired patients.

    Maio, Giovanni


    An ethical conflict arises when we must perform research in the interest of future patients, but that this may occasionally injure the interests of today's patients. In the case of cognitively impaired persons, the question arises whether it is compatible with humane healthcare not only to treat, but also to use these patients for research purposes. Some bioethicists and theologians have formulated a general duty of solidarity, also pertaining to cognitively impaired persons, as a justification for research on these persons. If one examines this thesis from the theory of justice according to John Rawls, it is revealed that such a duty of solidarity cannot necessarily be extrapolated from Rawls' conception of justice. This is at least true of Rawls' difference principle, because according to the difference principle only those measures are justifiable which serve the interest of the respective least well off. Those measures which would engender additional injury for the least well off could not be balanced by any utility according to Rawls. However, John Rawls' difference principle is subordinate to the first principle, which is that each person has an equal right to the most extensive basic liberty compatible with the same liberty for others. These "primary goods" are determined by the freedom and integrity of the person. This integrity of decisionally impaired persons would be in danger if one would abstain from research and thus forego the increase in knowledge related to their disease. Thus one could conclude, at least from Rawls' first principle, that society must take on a duty to guarantee the degrees of freedom for cognitively impaired persons and thus also support the efforts for their healing.

  4. Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

    Izquierdo JL


    Full Text Available José Luis Izquierdo,1 José Manuel Paredero,2 Raul Piedra3 1Department of Pneumology, Hospital Universitario de Guadalajara, 2Department of Pharmacy, 3Department of Primary Care, Guadalajara Integrated Care Management, Guadalajara, Spain Introduction: The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence.Methods: We used long-acting anticholinergics (LAMAs as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014.Results: During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours versus twice-daily (every 12 hours administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014.Conclusion: The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. Keywords: COPD, treatment, adherence, LABAs, LAMAs, PDC, asthma

  5. Clinical relevance of plasma prostaglandin F2α metabolite concentrations in patients with idiopathic pulmonary fibrosis.

    Kensaku Aihara

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F2α (PGF2α in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α. METHODS: We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25. We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality. RESULTS: Plasma concentrations of 15-keto-dihydro PGF2α were significantly higher in IPF patients than controls (p<0.001. Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = -0.34, p = 0.004, forced vital capacity (Rs = -0.33, p = 0.005, diffusing capacity for carbon monoxide (Rs = -0.36, p = 0.003, the composite physiologic index (Rs = 0.40, p = 0.001, 6-minute walk distance (Rs = -0.24, p = 0.04 and end-exercise oxygen saturation (Rs = -0.25, p = 0.04 when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002 and plasma 15-keto-dihydro PGF2α concentrations (relative risk = 1.005, p = 0.002 were independently associated with an increased risk of mortality. CONCLUSIONS: We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF.

  6. The relevance of the Rorschach and patient-examiner relationship in treatment planning and outcome assessment.

    Bram, Anthony D


    In this era of evidence-based mental health care, traditional forms of depth-oriented psychotherapy and psychological assessment have been marginalized in graduate training in clinical psychology. As a counterpoint, this article presents the evaluation and treatment of an adolescent client, along with an outcome assessment, and illustrates ways that aspects of traditional psychological testing, including the Rorschach (Exner, 1986) and the patient-examiner relationship, can enhance psychodiagnosis and treatment planning. Additionally, this case illustrates ways that test data can illuminate the concept of underlying disturbance and its utility in diagnostic formulation, treatment planning, and outcome assessment.

  7. Patterns of patient specific dosimetry in total body irradiation

    Akino, Yuichi [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States); Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); McMullen, Kevin P.; Das, Indra J. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States)


    Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

  8. The relevance of different trust models for representation in patient organizations: conceptual considerations.

    Gerhards, Helene; Jongsma, Karin; Schicktanz, Silke


    Trust within organizations is important for ensuring members' acceptance of the organization's activities and to expand their scope of action. Remarkably, Patient Organizations (POs) that often both function as a forum for self-help and represent patients on the health-political level, have been understudied in this respect. This paper analyzes the relation between trust and representation in POs. We distinguish between two models of representation originating from political theory: the trustee and delegate model and between two types of trust: horizontal and vertical trust. Our theoretical approach is illustrated with an analysis of 13 interviews with representatives of German POs. We have found that the delegate model requires horizontal trust and the trustee model vertical trust. Both models: horizontal/delegate and vertical/trustee exist within single POs. The representation process within POs demands a balancing act between inclusion of affected persons and strategically aggregating a clear-cut political claim. Trust plays in that process of coming from individual wishes to collective and political standpoints a major role both in terms of horizontal as well as vertical trust. Horizontal trust serves the communication between affected members, and vertical trust allows representatives to be decisive.

  9. The Antibacterial Activity of Acetic Acid against Biofilm-Producing Pathogens of Relevance to Burns Patients.

    Fenella D Halstead

    Full Text Available Localised infections, and burn wound sepsis are key concerns in the treatment of burns patients, and prevention of colonisation largely relies on biocides. Acetic acid has been shown to have good antibacterial activity against various planktonic organisms, however data is limited on efficacy, and few studies have been performed on biofilms.We sought to investigate the antibacterial activity of acetic acid against important burn wound colonising organisms growing planktonically and as biofilms.Laboratory experiments were performed to test the ability of acetic acid to inhibit growth of pathogens, inhibit the formation of biofilms, and eradicate pre-formed biofilms.Twenty-nine isolates of common wound-infecting pathogens were tested. Acetic acid was antibacterial against planktonic growth, with an minimum inhibitory concentration of 0.16-0.31% for all isolates, and was also able to prevent formation of biofilms (at 0.31%. Eradication of mature biofilms was observed for all isolates after three hours of exposure.This study provides evidence that acetic acid can inhibit growth of key burn wound pathogens when used at very dilute concentrations. Owing to current concerns of the reducing efficacy of systemic antibiotics, this novel biocide application offers great promise as a cheap and effective measure to treat infections in burns patients.

  10. Violence and Personality in Forensic Patients: Is There a Forensic Patient-Specific Personality Profile?

    Stupperich, Alexandra; Ihm, Helga; Strack, Micha


    Concerning the discussion about the connection of personality traits, personality disorders, and mental illness, this study focused on the personality profiles of male forensic patients, prison inmates, and young men without criminal reports. The main topic centered on group-specific personality profiles and identifying personality facets…

  11. Anatomic variations of the pancreatic duct and their relevance with the Cambridge classification system: MRCP findings of 1158 consecutive patients.

    Adibelli, Zehra Hilal; Adatepe, Mustafa; Imamoglu, Cetin; Esen, Ozgur Sipahi; Erkan, Nazif; Yildirim, Mehmet


    The study was conducted to evaluate the frequencies of the anatomic variations and the gender distributions of these variations of the pancreatic duct and their relevance with the Cambridge classification system as morphological sign of chronic pancreatitis using magnetic resonance cholangiopancreatography (MRCP). We retrospectively reviewed 1312 consecutive patients who referred to our department for MRCP between January 2013 and August 2015. We excluded 154 patients from the study because of less than optimal results due to imaging limitations or a history of surgery on pancreas. Finally a total of 1158 patients were included in the study. Among the 1158 patients included in the study, 54 (4.6%) patients showed pancreas divisum, 13 patients (1.2%) were defined as ansa pancreatica. When we evaluated the course of the pancreatic duct, we found the prevalence 62.5% for descending, 30% for sigmoid, 5.5% for vertical and 2% for loop. The most commonly observed pancreatic duct configuration was Type 3 in 528 patients (45.6%) where 521 patients (45%) had Type 1 configuration. Vertical course (p = 0.004) and Type 2 (p = 0.03) configuration of pancreatic duct were more frequent in females than males. There were no statistically significant differences between the gender for the other pancreatic duct variations such as pancreas divisium, ansa pancreatica and course types other than vertical course (p > 0.05 for all). Variants of pancreas divisum and normal pancreatic duct variants were not associated with morphologic findings of chronic pancreatitis by using the Cambridge classification system. The ansa pancreatica is a rare type of anatomical variation of the pancreatic duct, which might be considered as a predisposing factor to the onset of idiopathic pancreatitis.

  12. Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain patients?

    Raffa, Robert B; Pergolizzi, Joseph V


    There is a curious and paradoxic phenomenon, reliably demonstrated in animal models, that consists of an increased sensitivity to pain that is apparently induced by the very opioid drugs used to ameliorate the pain. This phenomenon is termed "opioid-induced hyperalgesia." Whether opioid-induced hyperalgesia occurs in humans, and, if so, to what extent and consequence, is far less established. This is a critical question for attempting to treat pain. If opioid-induced hyperalgesia develops in a patient, it would masquerade as tolerance (because the clinical effectiveness of the opioid would be diminished), yet the appropriate clinical adjustment would be precisely the opposite to that of tolerance. It would be to decrease, rather than increase, the dose of opioid. We review the evidence, particularly the clinical evidence, about opioid-induced hyperalgesia and the postulated mechanisms. We conclude that given the clinical ramifications, opioid-induced hyperalgesia is one of the most understudied important aspects of opioid research.

  13. Additive manufacturing of patient-specific tubular continuum manipulators

    Amanov, Ernar; Nguyen, Thien-Dang; Burgner-Kahrs, Jessica


    Tubular continuum robots, which are composed of multiple concentric, precurved, elastic tubes, provide more dexterity than traditional surgical instruments at the same diameter. The tubes can be precurved such that the resulting manipulator fulfills surgical task requirements. Up to now the only material used for the component tubes of those manipulators is NiTi, a super-elastic shape-memory alloy of nickel and titan. NiTi is a cost-intensive material and fabrication processes are complex, requiring (proprietary) technology, e.g. for shape setting. In this paper, we evaluate component tubes made of 3 different thermoplastic materials (PLA, PCL and nylon) using fused filament fabrication technology (3D printing). This enables quick and cost-effective production of custom, patient-specific continuum manipulators, produced on site on demand. Stress-strain and deformation characteristics are evaluated experimentally for 16 fabricated tubes of each thermoplastic with diameters and shapes equivalent to those of NiTi tubes. Tubes made of PCL and nylon exhibit properties comparable to those made of NiTi. We further demonstrate a tubular continuum manipulator composed of 3 nylon tubes in a transnasal, transsphenoidal skull base surgery scenario in vitro.

  14. Characterization of Bet v 1-related allergens from kiwifruit relevant for patients with combined kiwifruit and birch pollen allergy.

    Oberhuber, Christina; Bulley, Sean M; Ballmer-Weber, Barbara K; Bublin, Merima; Gaier, Sonja; DeWitt, Asa Marknell; Briza, Peter; Hofstetter, Gerlinde; Lidholm, Jonas; Vieths, Stefan; Hoffmann-Sommergruber, Karin


    Allergy to kiwifruit appears to have become more common in Europe and elsewhere during the past several years. Seven allergens have been identified from kiwifruit so far, with actinidin, kiwellin and the thaumatin-like protein as the most relevant ones. In contrast to other fruits, no Bet v 1 homologues were characterized from kiwifruit so far. We cloned, purified, and characterized recombinant Bet v 1-homologous allergens from green (Actinidia deliciosa, Act d 8) and gold (Actinidia chinensis, Act c 8) kiwifruit, and confirmed the presence of its natural counterpart by inhibition assays. Well-characterized recombinant Act d 8 and Act c 8 were recognized by birch pollen/kiwifruit (confirmed by double-blind placebo-controlled food challenge) allergic patients in IgE immunoblots and ELISA experiments. The present data point out that Bet v 1 homologues are allergens in kiwifruit and of relevance for patients sensitized to tree pollen and kiwifruit, and might have been neglected so far due to low abundance in the conventional extracts used for diagnosis.

  15. Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance

    Hundeshagen Alexander


    Full Text Available Abstract Background A subset of patients with multiple sclerosis (MS shows an increased endogenous IFN-like activity before initiation of IFN-beta treatment. The molecular basis of this phenomenon and its relevance to predict individual therapy outcomes are not yet fully understood. We studied the expression patterns of these patients, the prognostic value of an elevated IFN-like activity, and the gene regulatory effects of exogenously administered IFN-beta. Methods Microarray gene expression profiling was performed for 61 MS patients using peripheral blood mononuclear cells obtained before and after 1 month of IFN-beta therapy. Expression levels of genes involved in pathways either inducing or being activated by IFN-beta were compared between patients with high (MX1high cohort and low (MX1low cohort endogenous IFN-like activity. Patients were followed for 5 years and relapses as well as progression on the expanded disability status scale (EDSS were documented. Results Before the start of therapy, 11 patients presented elevated mRNA levels of IFN-stimulated genes indicative of a relatively high endogenous IFN-like activity (MX1high. In these patients, pathogen receptors (for example, TLR7, RIG-I and IFIH1 and transcription factors were also expressed more strongly, which could be attributed to an overactivity of IFN-stimulated gene factor 3 (ISGF3, a complex formed by STAT1, STAT2 and IFN regulatory factor 9. After 1 month of IFN-beta therapy, the expression of many pathway genes was significantly induced in MX1low patients, but remained unaltered in MX1high patients. During follow-up, relapse rate and changes in EDSS were comparable between both patient groups, with differences seen between different types of IFN-beta drug application. Conclusions Therapeutic IFN-beta induces the transcription of several genes involved in IFN-related pathways. In a subgroup of MS patients, the expression of these genes is already increased before therapy

  16. The patient's perspective of the feasibility of a patient-specific instrument in physiotherapy goal setting: a qualitative study

    Stevens, A.; Moser, A.; Koke, A.; Weijden, T.T. van der; Beurskens, A.


    BACKGROUND: Patient participation in goal setting is important to deliver client-centered care. In daily practice, however, patient involvement in goal setting is not optimal. Patient-specific instruments, such as the Patient Specific Complaints (PSC) instrument, can support the goal-setting process

  17. The patient's perspective of the feasibility of a patient-specific instrument in physiotherapy goal setting : a qualitative study

    Stevens, Anita; Moser, Albine; Köke, Albère; Weijden, Trudy van der; Beurskens, Anna


    Background: Patient participation in goal setting is important to deliver client-centered care. In daily practice, however, patient involvement in goal setting is not optimal. Patient-specific instruments, such as the Patient Specific Complaints (PSC) instrument, can support the goal-setting process

  18. UK practice regarding reversal of vasectomy 2001-2010: relevance to best contemporary patient management.

    Grey, Benjamin R; Thompson, Andrew; Jenkins, Ben L D; Payne, Stephen R


    Study Type - Practice trends (survey) Level of Evidence 2c What's known on the subject? and What does the study add? Approximately 6% of men who have had a vasectomy subsequently decide to have it reversed. For such men there are various options available, including vasal reconstruction, surgical sperm retrieval with assisted reproductive techniques, use of donated sperm or adoption. The decision-making process with regard to the most appropriate management is challenging and the urologist requires both an intimate knowledge of the advantages and disadvantages of each of the available options and the opportunity to counsel a couple appropriately. The study confirms that patient management after previous vasectomy is a complex process, demanding detailed knowledge about the availability and outcomes of alternatives to vasectomy reversal. It recommends that couples should not be seen by urologists with diverse interests but by those with appropriate knowledge of all of the factors influencing outcome and the available management options and their costs. Urologists should also have appropriate facilities to offer intra-operative demonstration of and, potentially, storage of sperm. To review the management of men presenting for reversal of vasectomy amongst consultant members of the British Association of Urological Surgeons (BAUS) between 2001 and 2010. • To make recommendations for contemporary practice. Three consecutive questionnaire-based surveys were undertaken by BAUS consultant members in 2001, 2005 and 2010. • Standard questionnaires were sent on each occasion asking urologists about their counselling of couples regarding options in achieving a conception, expectation of outcome from reconstructive surgery and the techniques of vaso-vasostomy used. • In 2005 additional information was obtained about the availability of fertility treatments and sub-specialization of the urologist and in 2010 about the eligibility criteria for in-vitro fertilization (IVF

  19. Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

    Bianco, Henrique Tria, E-mail:; Izar, Maria Cristina; Fonseca, Henrique Andrade; Póvoa, Rui Manuel [Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Saraiva, José Francisco [Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, SP (Brazil); Forti, Adriana [Centro de Diabetes e Hipertensão de Fortaleza, Fortaleza, CE (Brazil); Jardim, Paulo Cesar B. V. [Universidade Federal de Goiânia, Goiânia, GO (Brazil); Introcaso, Luis [Centro de Investigação Clínica de Brasília, Brasília, DF (Brazil); Yugar-Toledo, Juan [Escola de Medicina de São José do Rio Preto, São José do Rio Preto, SP (Brazil); Xavier, Hermes Tóros [Centro de Investigação Clínica de Santos, Santos, SP (Brazil); Universidade de São Paulo (USP), São Paulo, SP (Brazil); Faludi, André Arpad [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil); Fonseca, Francisco A. H. [Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil)


    Patients with diabetes are in extract higher risk for fatal cardiovascular events. To evaluate major predictors of mortality in subjects with type 2 diabetes. A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality. After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017). Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

  20. Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus

    Henrique Tria Bianco


    Full Text Available Background: Patients with diabetes are in extract higher risk for fatal cardiovascular events. Objective: To evaluate major predictors of mortality in subjects with type 2 diabetes. Methods: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR and confidence interval (CI related to cardiovascular and total mortality. Results: After 9.2 years of follow-up (median, 33 subjects died (17 from cardiovascular causes. Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019; prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007; eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001; long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004; and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002. Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030; smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046; prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005, and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017. Conclusions: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

  1. Readability, relevance and quality of the information in Spanish on the Web for patients with rheumatoid arthritis.

    Castillo-Ortiz, Jose Dionisio; Valdivia-Nuno, Jose de Jesus; Ramirez-Gomez, Andrea; Garagarza-Mariscal, Heber; Gallegos-Rios, Carlos; Flores-Hernandez, Gabriel; Hernandez-Sanchez, Luis; Brambila-Barba, Victor; Castaneda-Sanchez, Jose Juan; Barajas-Ochoa, Zalathiel; Suarez-Rico, Angel; Sanchez-Gonzalez, Jorge Manuel; Ramos-Remus, Cesar

    Education is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. To assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. The search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre-established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. The Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. There is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  2. Characteristics and risk factors of major and clinically relevant non-major bleeding in cancer patients receiving anticoagulant treatment for acute venous thromboembolism-the CATCH study

    Kamphuisen, P.W.; Lee, A.Y.Y.; Meyer, Guy; Bauersachs, R.; Janas, M.S.; Jarner, M.F.; Khorana, A.A.


    Background: Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have a substantial risk of bleeding complications. Aims: To assess the rate, site and risk factors of clinically relevant bleeding (CRB; major or clinically relevant non-major bleeding) in cancer pa

  3. Initial diagnosis of therapeutically relevant thoracic lesions in polytraumatised patients; Zur Akutdiagnostik therapierelevanter Thoraxverletzungen bei schwer- und polytraumatisierten Patienten

    Danz, B. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany); Biehl, C. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany); Baehren, W. [Radiologische Abt., Bundeswehrkrankenhaus Ulm (Germany)


    To determine the value of supine chest radiography in comparison to orientating chest CT in the initial diagnostic evaluation of severely polytraumatised patients. 303 patients with primary indication for a cranial CT following trauma were investigated between 1988 and 1993. After performing the cranial CT all patients underwent a chest CT with an average of 6 CT slices without changing the position of the patient and with a median scan time of 4 minutes. The results of the chest CT were correlated with the findings of the supine chest radiography in regard to therapeutically relevant pathological changes. The sensitivity in detection of pneumothorax in supine chest radiography was 53% versus 97% in CT, atelectasis 20% versus 94%, lung contusion 79% versus 99%, haemotothorax 62% versus 97%. More fractures were found conventionally (sensitivity 94%) than by chest CT (sensitivity 44%). Supine chest radiography of polytraumatised patients is clearly inferior to orientating chest CT in demonstrating posttraumatic lesions; obtaining therapeutically relevant information justifies the additionally needed small amount of time. (orig.) [Deutsch] Das Ziel dieser retrospektiven Untersuchung bestand darin, die Wertigkeit der a.p. Thoraxaufnahme im Liegen im Vergleich zur orientierenden Computertomographie der Thoraxorgane im Rahmen der Akutdiagnostik bei schwer- und polytraumatisierten Patienten zu analysieren. Im Zeitraum von 1988 bis 1993 bestand bei 303 Patienten wegen eines Schaedel-Hirn-Traumas die primaere Indikation zu einem CCT. Im Anschluss an das CCT wurde routinemaessig ein orientierendes CT der Thoraxorgane mit im Durchschnitt 6 Schichten ohne Umlagerung und einem medianen Zeitaufwand von 4 Minuten durchgefuehrt. Die Befunde des CT des Thorax wurden mit den Ergebnissen der durchgefuehrten a.p. Thoraxliegendaufnahmen im Hinblick auf die Erfassung therapierelevanter pathologischer Veraenderungen verglichen. Die Sensitivitaet fuer die Erkennung eines Pneumothorax in

  4. Clinical Relevance of Specific Cognitive Complaints in Determining Mild Cognitive Impairment from Cognitively Normal States in a Study of Healthy Elderly Controls

    Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M.; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A.


    Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints. PMID:27757082

  5. Clinical Relevance of Specific Cognitive Complaints in Determining Mild Cognitive Impairment from Cognitively Normal States in a Study of Healthy Elderly Controls.

    Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A


    Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.

  6. Autobiographical memory specificity in patients with tinnitus versus patients with depression and normal controls.

    Andersson, Gerhard; Hesser, Hugo; Cima, Rilana F F; Weise, Cornelia


    Several studies show that patients with depression and post-traumatic stress disorder respond with fewer specific autobiographical memories in a cued memory task (i.e. the autobiographical memory test; AMT) compared to healthy controls. One previous study found this phenomenon among tinnitus patients as well (Andersson, Ingerholt, & Jansson, 2003). The aim of this study was to replicate the previous study with an additional control group of depressed patients and memory errors as measured with the AMT as an additional outcome. We included 20 normal hearing tinnitus patients, 20 healthy controls and 20 persons diagnosed with clinical depression. The AMT was administered together with self-report measures of depression, anxiety and tinnitus distress. Both the tinnitus and depression groups differed from the healthy control group in that they reported fewer specific autobiographical memories. There were, however, differences between the tinnitus and depression groups in terms of the errors made on the AMT. The depression group had more overgeneral memories than the normal control group, whereas the tinnitus group did not differ from the control group on this memory error. The tinnitus group had more semantic associations and non-memories than the other two groups, suggesting that executive functioning may play a role for the tinnitus group when completing the AMT. Clinical and theoretical implications of the findings are discussed.

  7. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Saleem A


    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  8. End-stage rheumatoid arthritis: specific features of patient management

    Nadezhda Aleksandrovna Shostak


    Full Text Available The paper provides data on the treatment of patients with end-stage rheumatoid arthritis (RA and a rationale for the long-term treatment with disease-modifying antirheumatic drugs, including leflunomide as a first-line agent. It describes a clinical case of a patient with end-stage RA during arava treatment.

  9. Feasibility of a 3D-printed anthropomorphic patient-specific head phantom for patient-specific quality assurance of intensity-modulated radiotherapy

    Yea, Ji Woon; Park, Jae Won; Kim, Sung Kyu; Kim, Dong Youn; Kim, Jae Gu; Seo, Chan Young; Jeong, Won Hyo; Jeong, Man Youl


    This study evaluated the feasibility of utilizing a 3D-printed anthropomorphic patient-specific head phantom for patient-specific quality assurance (QA) in intensity-modulated radiotherapy (IMRT). Contoured left and right head phantoms were converted from DICOM to STL format. Fused deposition modeling (FDM) was used to construct an anthropomorphic patient-specific head phantom with a 3D printer. An established QA technique and the patient-specific head phantom were used to compare the calculated and measured doses. When the established technique was used to compare the calculated and measured doses, the gamma passing rate for γ ≤ 1 was 97.28%, while the gamma failure rate for γ > 1 was 2.72%. When the 3D-printed patient-specific head phantom was used, the gamma passing rate for γ ≤ 1 was 95.97%, and the gamma failure rate for γ > 1 was 4.03%. The 3D printed patient-specific head phantom was concluded to be highly feasible for patient-specific QA prior to complicated radiotherapy procedures such as IMRT. PMID:28727787

  10. Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants.

    Peel, Sean; Bhatia, Satyajeet; Eggbeer, Dominic; Morris, Daniel S; Hayhurst, Caroline


    Previously published evidence has established major clinical benefits from using computer-aided design, computer-aided manufacturing, and additive manufacturing to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use, particularly by the UK National Health Service. Oft-cited reasons for this slow uptake include the following: a higher up-front cost than conventionally fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This article identifies a further gap in current knowledge - that of design rules, or key specification considerations for complex computer-aided design/computer-aided manufacturing/additive manufacturing devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised additive manufacturing to fabricate titanium implants. One implant was machined from polyether ether ketone. From the literature, articles with relevant abstracts were analysed to extract design considerations. In all, 19 frequently recurring design considerations were extracted from previous publications. Nine new design considerations were extracted from the case studies - on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed.

  11. Improved patient specific seizure detection during pre-surgical evaluation.

    Chua, Eric C-P


    There is considerable interest in improved off-line automated seizure detection methods that will decrease the workload of EEG monitoring units. Subject-specific approaches have been demonstrated to perform better than subject-independent ones. However, for pre-surgical diagnostics, the traditional method of obtaining a priori data to train subject-specific classifiers is not practical. We present an alternative method that works by adapting the threshold of a subject-independent to a specific subject based on feedback from the user.

  12. Influence of ginkgo leaf tablets combined with nifedipine tablets treatment on relevant indexes of prethrombotic state in hypertension patients

    Ping Zhou; Xiu-Hong Liu; Ya-Ping Du; Xiao-Xia Han; Guo-Mei Dan


    Objective:To explore the influence of ginkgo leaf tablets combined with nifedipine tablets treatment on the relevant indexes of prethrombotic state in hypertension patients.Methods:A total of 80 cases with hypertension were selected, who were admitted in our hospital from May 2014 to June 2015, and all of whom was randomly divided into study group and control group (n=40). Patients in study group were given ginkgo leaf tablets combined with nifedipine tablets treatment, while patients in control group were given nifedipine tablets treatment only. The changes of blood pressure indexes between groups before and after treatment were compared. the changes of hemodynamic indexes between groups before and after treatment were analyzed. And the changes of molecular markers of prethrombotic state between groups before and after treatment were observed.Results:Before treatment, comparative difference of systolic pressure, diastolic pressure levels, hemodynamic indexes(MH, ML, MP, HCT, ESR, AI), VWF, GMP, D-dimer and PAI-1 levels between groups had no statistical significance (P>0.05); while after treatment, systolic pressure, diastolic pressure levels, hemodynamic indexes(MH, ML, MP, HCT, ESR, AI), VWF, GMP, D-dimer and PAI-1 levels in both groups were obviously lower than before treatment (P<0.05), but systolic pressure, diastolic pressure levels, MH, ML, MP, ESR, VWF, GMP, D-dimer and PAI-1 levels in study group were lower than that in control group, and the difference had statistical significance (P<0.05), after treatment, the four index levels in both groups were significantly lower than before treatment (P<0.05).Conclusions:Ginkgo leaf tablets combined with nifedipine tablets in the treatment of hypertension patients could significantly reduce the systolic pressure, diastolic pressure levels, reduce the levels of hemodynamic indexes (MH, ML, MP, HCT, ESR, AI) and reduce the levels of molecular markers (VWF, GMP, D-dimer , PAI-1) of prethrombotic state, which was an

  13. Mobile applications in oncology: is it possible for patients and healthcare professionals to easily identify relevant tools?

    Brouard, Benoit; Bardo, Pascale; Bonnet, Clément; Mounier, Nicolas; Vignot, Marina; Vignot, Stéphane


    Mobile applications represent promising tools in management of chronic diseases, both for patients and healthcare professionals, and especially in oncology. Among the large number of mobile health (mhealth) applications available in mobile stores, it could be difficult for users to identify the most relevant ones. This study evaluated the business model and the scientific validation for mobile applications related to oncology. A systematic review was performed over the two major marketplaces. Purpose, scientific validation, and source of funding were evaluated according to the description of applications in stores. Results were stratified according to targeted audience (general population/patients/healthcare professionals). Five hundred and thirty-nine applications related to oncology were identified: 46.8% dedicated to healthcare professionals, 31.5% to general population, and 21.7% to patients. A lack of information about healthcare professionals' involvement in the development process was noted since only 36.5% of applications mentioned an obvious scientific validation. Most apps were free (72.2%) and without explicit support by industry (94.2%). There is a need to enforce independent review of mhealth applications in oncology. The economic model could be questioned and the source of funding should be clarified. Meanwhile, patients and healthcare professionals should remain cautious about applications' contents. Key messages A systematic review was performed to describe the mobile applications related to oncology and it revealed a lack of information on scientific validation and funding. Independent scientific review and the reporting of conflicts of interest should be encouraged. Users, and all health professionals, should be aware that health applications, whatever the quality of their content, do not actually embrace such an approach.

  14. Frequency, determinants, and clinical relevance of acute coronary syndrome-like electrocardiographic findings in patients with acute aortic syndrome.

    Biagini, Elena; Lofiego, Carla; Ferlito, Marinella; Fattori, Rossella; Rocchi, Guido; Graziosi, Maddalena; Lovato, Luigi; di Diodoro, Lara; Cooke, Robin M T; Petracci, Elisabetta; Bacchi-Reggiani, Letizia; Zannoli, Romano; Branzi, Angelo; Rapezzi, Claudio


    We investigated frequency/characteristics of acute coronary syndrome-like (ACS-like) electrocardiographic (ECG) profiles among patients with a final diagnosis of acute aortic syndrome (AAS), and explored pathophysiologic determinants and prognostic relevance within each Stanford subtype. We blindly reviewed presentation electrocardiograms of 233 consecutive patients with final diagnosis of AAS (164 Stanford type A) at a regional treatment center. Prevalence of ACS-like ECG findings was 27% (type A, 26%, type B, 29%); most were non-ST-elevation myocardial infarction-like. Patients with ACS-like ECG findings more often had coronary ostia involvement (p=0.002), pleural effusion (p=0.02), significant aortic regurgitation (p=0.01), and troponin positivity (p=0.001). ACS-like ECG profile in type A disease was independently associated with coronary ostia involvement (odds ratio [OR] 5.27, 95% confidence interval [CI] 1.75 to 15.88). ACS-like ECG profile predicted in-hospital mortality (OR 2.90, 95% CI 1.24 to 6.12), as did age (each incremental 10-year: OR 1.59, 95% CI 1.14 to 2.22), and syncope at presentation (OR 2.90, 95% CI 1.16 to 7.24). In conclusion, about 25% of our AAS patients (in either Stanford subtype) presented ACS-like ECG patterns-often with non-ST-elevation myocardial infarction characteristics-which could cause misdiagnosis. ACS-like ECG profile was associated with more complicated disease, and in type A disease was a strong independent predictor of in-hospital mortality.

  15. Patient perspectives on peer support for adults with type 1 diabetes: a need for diabetes-specific social capital

    Joensen LE


    Full Text Available Lene E Joensen,1 Tine Filges,2 Ingrid Willaing1 1Health Promotion Research, Steno Diabetes Center, Gentofte, 2Filges Analysis, Hellerup, Denmark Aim: To explore the function of peer support from the perspective of adults with type 1 diabetes in Denmark. Methods: The study population consisted of 20 adults with type 1 diabetes. The sample was diverse in relation to educational background, age, sex, and cohabitation status. Inspired by action research, several methods and perspectives on peer support were explored and tested. Workshops and group and individual interviews were performed. Systematic text condensation was used to analyze data, supplemented with theory-based interpretive analysis. Results: Adults with type 1 diabetes found peer support highly relevant to reduce a burdensome feeling of diabetes-specific loneliness. Peer support showed potential to create diabetes-specific social capital not only by creating reciprocal social support between peers but also, more importantly, by creating space for genuine trust and a feeling of communality. There was a widespread feeling of the pervasive impact of diabetes on daily life and thus the relevance of discussing all aspects of life. However, participants perceived peer support as particularly relevant in relation to big changes in life, for example, in family life, at work, or through treatment events such as getting an insulin pump. Conclusion: Peer support programs focusing on creating and establishing diabetes-specific social capital using participatory approaches seem highly relevant among adults with type 1 diabetes. Content, methods, and effects of peer support need further exploration in collaboration with adults with type 1 diabetes. Keywords: type 1 diabetes mellitus, adult, psychosocial support systems, patient preferences, peer support, diabetes-specific social capital, diabetes-specific loneliness

  16. [Gender-specific aspects of the physician-patient interaction].

    Cronauer, C Klöckner; Schmid Mast, M


    This article aims at shedding light on the role of physician and patient gender in the medical consultation. Because of the scarce amount of studies concentrating on gender aspects of the physician-patient interaction in rehabilitation or chronic disease, mostly results from general medicine are reported. Female physicians have a more emotional and less dominant communication style. Female patients bring up more psychosocial topics and disclose more information about themselves in general. Both female and male physicians give more information and apply a more partnership-oriented communication style when seeing a female patient. Female and male patients communicate more partnership-oriented with female physicians and share more psychosocial and medical information with them. Same-gender dyads seem beneficial most of the time for physician-patient communication. Mixed-gender dyads are more difficult, especially when a younger female physician sees a male patient. There is no single good communication style recommendable for all physicians. Rather, the research results presented should be applied to communication trainings for physicians. This could provide physicians with a flexible choice of communication styles to apply according to different situations.

  17. Combining population and patient-specific characteristics for prostate segmentation on 3D CT images

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei


    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

  18. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Vuento, R


    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

  19. Patient specific 3D visualisation of human brain


    These simulators produce a virtual representation of the patient within which users can ..... Simulation”, Medecine Meets Virtual Reality (MMVR), Volume 125, pp. 13-18,. 2007 ... technology and informatics, volume 111, pp. 342-348, 2005.

  20. Hemodynamics of patient-specific aorta-pulmonary shunt configurations

    Pekkan, Kerem; Pişkin, Senol; Altın, H. Fırat; Yıldız, Okan; Bakır, İhsan


    Optimal hemodynamics in aorta-pulmonary shunt reconstruction is essential for improved post-operative recovery of the newborn congenital heart disease patient. However, prior to in vivo execution, the prediction of post-operative hemodynamics is extremely challenging due to the interplay of multiple confounding physiological factors. It is hypothesized that the post-operative performance of the surgical shunt can be predicted through computational blood flow simulations that consider patient ...

  1. [Amoebic liver abscess in a patient initially diagnosed with pneumonia: case report and discussion of relevant literature].

    Kurt, Özgür; Aktaş, Neslihan; Çalışkan, Can; Karatuna, Onur; Aygün, Hande; Akyar, Işın


    In one-third of the patients with amoebiasis, amoebic liver abscess (ALA) may occur after the penetration of amoebic trophozoites through the intestinal wall. ALA is seen mostly among men aged 20-45 years with a serious clinical outcome, with fever and abdominal pain on the right upper quadrant. Most patients have no recent history of amoebic colitis; indeed, they have neither gastrointestinal complaints nor Entamoeba histolytica (E. histolytica) cysts/trophozoites in their stools. Therefore, ultrasonography and serology are primary in ALA diagnosis, while searching for E. histolytica DNA in abscess fluid using PCR has been preferred as an effective and reliable method, lately. Early antimicrobial therapy is effective; however, for cases irresponsive to therapy after 72 hours and with large abscess, drainage or surgical intervention is indicated. If left untreated, ALA may disseminate to other organs and cause death. The data concerning the extra-intestinal manifestations of amebiasis in Turkey are limited. Here, a rare case of a young man with an initial diagnosis of pneumonia followed by the identification of ALA after radiological interventions and laboratory tests is presented and the relevant literature is discussed.

  2. Characteristics and clinical relevance of late gadolinium enhancement in cardiac magnetic resonance in patients with systemic sclerosis.

    Sano, Makoto; Satoh, Hiroshi; Suwa, Kenichiro; Nobuhara, Mamoru; Saitoh, Takeji; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Shimoyama, Kumiko; Suzuki, Daisuke; Ogawa, Noriyoshi; Takehara, Yasuo; Sakahara, Harumi; Hayashi, Hideharu


    Cardiac involvement in systemic sclerosis (SSc) is considerably frequent in autopsy, but the early identification is clinically difficult. Recent advantages in cardiac magnetic resonance (CMR) enabled to detect myocardial fibrotic scar as late gadolinium enhancement (LGE). We aimed to examine the prevalence and distribution of LGE in patients with SSc, and associate them with clinical features, electrocardiographic abnormalities and cardiac function. Forty patients with SSc (58 ± 14 years-old, 35 females, limited/diffuse 25/15, disease duration 106 ± 113 months) underwent serological tests, 12-lead electrocardiogram (ECG) and CMR. Seven patients (17.5 %) showed LGE in 26 segments of left ventricle (LV). LGE distributed mainly in the basal to mid inter-ventricular septum and the right ventricular (RV) insertion points, but involved all the myocardial regions. More patients with LGE showed NYHA functional class II and more (71 vs. 21 %, p 125 pg/ml). When cardiac involvement of SSc was defined as low LVEF, ECG abnormalities or high NT-proBNP, the sensitivity, specificity positive and negative predictive values of LGE were 36, 92, 71 and 72 %, respectively. We could clarify the prevalence and distribution of LGE in Japanese patients with SSc. The presence of LGE was associated with cardiac symptom, conduction disturbance and impaired LV/RV contraction.

  3. High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients; results of the REACT-2 trial

    Treskes, K.; Bos, S.A.; Sierink, J.C.; Luitse, J.S.K.; Goslings, J.C. [Academic Medical Center, Trauma Unit, Department of Surgery, Amsterdam (Netherlands); Beenen, L.F.M. [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Edwards, M.J.R. [Radboud University Medical Center, Department of Trauma and emergency surgery, Nijmegen (Netherlands); Beuker, B.J.A. [University Medical Center Groningen, Trauma Unit, Department of Surgery, Groningen (Netherlands); Muradin, G.S.R. [University Medical Center Rotterdam, Department of Radiology, Erasmus MC, Rotterdam (Netherlands); Hohmann, J. [University of Basel Hospital, Department of Radiology and Nuclear Medicine, Basel (Switzerland); Hollmann, M.W. [Academic Medical Center, Department of Anaesthesiology, Amsterdam (Netherlands); Dijkgraaf, M.G.W. [Academic Medical Center, Clinical Research Unit, Amsterdam (Netherlands); Collaboration: REACT-2 study group


    To determine whether there is a difference in frequency and clinical relevance of incidental findings detected by total-body computed tomography scanning (TBCT) compared to those by the standard work-up (STWU) with selective computed tomography (CT) scanning. Trauma patients from five trauma centres were randomized between April 2011 and January 2014 to TBCT imaging or STWU consisting of conventional imaging with selective CT scanning. Incidental findings were divided into three categories: 1) major finding, may cause mortality; 2) moderate finding, may cause morbidity; and 3) minor finding, hardly relevant. Generalized estimating equations were applied to assess differences in incidental findings. In total, 1083 patients were enrolled, of which 541 patients (49.9 %) were randomized for TBCT and 542 patients (50.1 %) for STWU. Major findings were detected in 23 patients (4.3 %) in the TBCT group compared to 9 patients (1.7 %) in the STWU group (adjusted rate ratio 2.851; 95%CI 1.337-6.077; p < 0.007). Findings of moderate relevance were detected in 120 patients (22.2 %) in the TBCT group compared to 86 patients (15.9 %) in the STWU group (adjusted rate ratio 1.421; 95%CI 1.088-1.854; p < 0.010). Compared to selective CT scanning, more patients with clinically relevant incidental findings can be expected by TBCT scanning. (orig.)

  4. Validation of a population of patient-specific adult acquired flatfoot deformity models.

    Spratley, E Meade; Matheis, Erika A; Hayes, Curtis W; Adelaar, Robert S; Wayne, Jennifer S


    Adult acquired flatfoot deformity (AAFD) is a degenerative disease resulting in malalignment of the mid- and hindfoot secondary to posterior tibial tendon dysfunction and increasing implication of ligament pathologies. Despite the complex 3D nature of AAFD, 2D radiographs are still employed to diagnose and stage the disease. Computer modeling techniques allow for accurate 3D recreations of musculoskeletal systems for the investigation of biomechanical factors contributing to disease. Following Institutional Review Board approval, the lower limbs of six diagnosed AAFD sufferers were imaged with MRI, photographs, and X-ray. Next, a radiologist graded the MRI attenuation of eight soft-tissues implicated in AAFD. Six patient-specific rigid-body models were then created and loaded according to patient weight, graded soft-tissues, and extrinsic muscles. Model function was validated using clinically relevant kinematic measures in three planes. Agreement varied depending on the measure, with average absolute deviations of < 7° for angles and <4 mm for distances. Additionally, the clinically favored AP talonavicular coverage angle, ML talo-1st metatarsal angle, and ML 1st cuneiform height showed strong correlations of R(2) = 0.63, 0.75, and 0.85, respectively. Thus, computer modeling offers a promising methodology for the non-invasive investigation of in vivo kinematic behavior in pathologic feet and, once validated, may further be used to investigate biomechanical parameters that are difficult to measure clinically.

  5. Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

    Young, Eric D; Ingram, Davis; Metcalf-Doetsch, William; Khan, Dilshad; Al Sannaa, Ghadah; Le Loarer, Francois; Lazar, Alexander J F; Slopis, John; Torres, Keila E; Lev, Dina; Pollock, Raphael E; McCutcheon, Ian E


    OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidural growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidural growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these

  6. Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients

    Durner Jürgen


    Full Text Available Abstract Background Transarterial chemoembolization (TACE therapy is an effective locoregional treatment in hepatocellular cancer (HCC patients. For early modification of therapy, markers predicting therapy response are urgently required. Methods Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1, alpha fetoprotein (AFP, C-reactive protein (CRP and several liver biomarkers, and to compare these with radiological response to therapy. Results While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT and alkaline phosphatase (AP significantly indicated the later therapy response (39 progression versus 32 no progression. In multivariate analysis, nucleosomes (24 h, AP (24 h and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity. Conclusion Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

  7. Generating patient-specific pulmonary vascular models for surgical planning

    Murff, Daniel; Co-Vu, Jennifer; O'Dell, Walter G.


    Each year in the U.S., 7.4 million surgical procedures involving the major vessels are performed. Many of our patients require multiple surgeries, and many of the procedures include "surgical exploration". Procedures of this kind come with a significant amount of risk, carrying up to a 17.4% predicted mortality rate. This is especially concerning for our target population of pediatric patients with congenital abnormalities of the heart and major pulmonary vessels. This paper offers a novel approach to surgical planning which includes studying virtual and physical models of pulmonary vasculature of an individual patient before operation obtained from conventional 3D X-ray computed tomography (CT) scans of the chest. These models would provide clinicians with a non-invasive, intricately detailed representation of patient anatomy, and could reduce the need for invasive planning procedures such as exploratory surgery. Researchers involved in the AirPROM project have already demonstrated the utility of virtual and physical models in treatment planning of the airways of the chest. Clinicians have acknowledged the potential benefit from such a technology. A method for creating patient-derived physical models is demonstrated on pulmonary vasculature extracted from a CT scan with contrast of an adult human. Using a modified version of the NIH ImageJ program, a series of image processing functions are used to extract and mathematically reconstruct the vasculature tree structures of interest. An auto-generated STL file is sent to a 3D printer to create a physical model of the major pulmonary vasculature generated from 3D CT scans of patients.

  8. [Specifics of Analgesia in Palliative Care Patients at Home].

    Pautex, Sophie


    Pain management at home for a patient, suffering from one or more advanced progressive diseases, goes beyond the prescription of an opioid. Apart from the importance of finding the most suitable analgesic drug (controlled pain with least possible adverse effects), three important dimensions will be addressed: interprofessionnal care (shared care goals, evaluation, monitoring of pain and other symptoms; physiotherapy, etc.) information, education and support for patients and relatives in particular on the use of opioids, and finally the importance of anticipation. This includes for example the requirement of breakthrough pain treatment in case of pain exacerbation or the definition of the place of hospitalization in case of worsening general condition or of death.

  9. On the evaluation of patient specific IMRT QA using EPID, dynalog files and patient anatomy

    Dewayne Lee Defoor


    Full Text Available Purpose: This research, investigates the viability of using the Electronic portal imaging device (EPID coupled with the treatment planning system (TPS, to calculate the doses delivered and verify agreement with the treatment plan. The results of QA analysis using the EPID, Delta4 and fluence calculations using the multi-leaf collimator (MLC dynalog files on 10 IMRT patients are presented in this study.Methods: EPID Fluence Images in integrated mode and Dynalog files for each field were acquired for 10 IMRT (6MV patients and processed through an in house MatLab program to create an opening density matrix (ODM which was used as the input fluence for dose calculation with the TPS (Pinnacle3, Philips. The EPID used in this study was the aSi1000 Varian on a Novalis TX linac equipped with high definition MLC. The resulting dose distributions were then exported to VeriSoft (PTW where a 3D gamma was calculated using 3 mm-3% criteria. The Scandidos Delta4 phantom was also used to measure a 2D dose distribution for all 10 patients and a 2D gamma was calculated for each patient using the Delta4 software.Results: The average 3D gamma for all 10 patients using the EPID images was 98.2% ± 2.6%. The average 3D gamma using the dynalog files was 94.6% ± 4.9%. The average 2D gamma from the Delta4 was 98.1% ± 2.5%. The minimum 3D gamma for the EPID and dynalog reconstructed dose distributions was found on the same patient which had a very large PTV, requiring the jaws to open to the maximum field size. Conclusion: Use of the EPID, combined with a TPS is a viable method for QA of IMRT plans. A larger ODM size can be implemented to accommodate larger field sizes. An adaptation of this process to Volumetric Arc Therapy (VMAT is currently under way.-----------------------------Cite this article as: Defoor D, Mavroidis P, Quino L, Gutierrez A, Papanikolaou N, Stathakis S. On the evaluation of patient specific IMRT QA using EPID, dynalog files and patient anatomy

  10. Relevance of CT and MRI in retinoblastoma for the diagnosis of postlaminar invasion with normal-size optic nerve: a retrospective study of 150 patients with histological comparison

    Brisse, Herve J.; Guesmi, Myriam; Neuenschwander, Sylvia [Institute Curie, Department of Radiology, Paris (France); Aerts, Isabelle [Institute Curie, Department of Paediatric Oncology, Paris (France); Sastre-Garau, Xavier [Institute Curie, Department of Pathology, Paris (France); Savignoni, Alexia; Asselain, Bernard; Bours, Daniele [Institute Curie, Department of Biostatistics, Paris (France); Lumbroso-Le Rouic, Livia; Desjardins, Laurence [Institute Curie, Department of Ocular Oncology, Paris (France); Doz, Francois [Institute Curie, Department of Paediatric Oncology, Paris (France); Faculty of Medicine, Department of Paediatrics, Paris (France)


    Detection of optic nerve invasion is mandatory in children primarily enucleated for retinoblastoma to ensure a free resection margin. To assess the accuracy of CT and MRI for the detection of postlaminar invasion in normal-size nerves. A total of 150 patients enucleated for retinoblastoma were included. Imaging data (119 CT and 46 MRI) were retrospectively reviewed and compared with histological findings. Abnormal contrast enhancement of the optic nerve was used as diagnostic criterion for invasion. The associations between postlaminar invasion and several indirect signs were also assessed. Statistical analysis was performed with the Kruskal-Wallis and Fisher exact tests. Postlaminar invasion on histology was observed in 8% (12/150). The sensitivity, specificity, accuracy and negative and positive predictive values were 60%, 95%, 91%, 95% and 60% for MRI, and 0%, 100%, 94% and 94% (PPV not assessable) for CT, respectively. Tumour diameter was the only indirect radiological sign significantly associated with postlaminar optic nerve invasion (P=0.002). Our results suggest that MRI is more relevant than CT for preoperative detection of optic nerve invasion in patients with retinoblastoma. Tumour diameter is the only indirect sign significantly associated with postlaminar invasion. (orig.)

  11. Introducing the Concept of the Minimally Important Difference to Determine a Clinically Relevant Change on Patient-Reported Outcome Measures in Patients with Intermittent Claudication

    Conijn, Anne P., E-mail: [Academic Medical Center, Departments of Vascular Surgery and Interventional Radiology (Netherlands); Jonkers, Wilma, E-mail: [Achmea Insurances, Division of Health Care (Netherlands); Rouwet, Ellen V., E-mail: [Erasmus Medical Center, Department of Vascular Surgery (Netherlands); Vahl, Anco C., E-mail: [Onze Lieve Vrouwe Gasthuis, Department of Vascular Surgery (Netherlands); Reekers, Jim A., E-mail: [Academic Medical Center, Department of Radiology (Netherlands); Koelemay, Mark J. W., E-mail: [Academic Medical Center, Department of vascular surgery (Netherlands)


    PurposeThe minimally important difference (MID) represents the smallest change in score on patient-reported outcome measures that is relevant to patients. The aim of this study was to introduce the MID for the Vascular Quality of Life Questionnaire (VascuQol) and the walking impairment questionnaire (WIQ) for patients with intermittent claudication (IC).MethodsIn this multicenter study, we recruited 294 patients with IC between July and October 2012. Patients completed the VascuQol, with scores ranging from 1 to 7 (worst to best), and the WIQ, with scores ranging from 0 to 1 (worst to best) at first visit and after 4 months follow-up. In addition, patients answered an anchor-question rating their health status compared to baseline, as being improved, unchanged, or deteriorated. The MID for improvement and deterioration was calculated by an anchor-based approach, and determined with the upper and lower limits of the 95 % confidence interval of the mean change of the group who had not changed according to the anchor-question.ResultsFor the MID analyses of the VascuQol and WIQ, 163 and 134 patients were included, respectively. The MID values for the VascuQol (mean baseline score 4.25) were 0.87 for improvement and 0.23 for deterioration. For the WIQ (mean baseline score 0.39), we found MID values of 0.11 and −0.03 for improvement and deterioration, respectively.ConclusionIn this study, we calculated the MID for the VascuQol and the WIQ. Applying these MID facilitates better interpretation of treatment outcomes and can help to set treatment goals for individual care.

  12. Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model.

    Maria Cristina Colombo

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient's prognosis.

  13. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

    Sumila Marcin


    Full Text Available Abstract Background and Purpose Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Materials and methods For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. Results The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. Conclusions In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For

  14. Cause-specific mortality among spouses of Parkinson disease patients

    Nielsen, Malene; Hansen, Johnni; Ritz, Beate


    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  15. Respiratory gated radiotherapy-pretreatment patient specific quality assurance

    Rajesh Thiyagarajan; Sujit Nath Sinha; Ramamoorthy Ravichandran; Kothandaraman Samuvel; Girigesh Yadav; Ashok Kumar Sigamani; Vikraman Subramani; N Arunai Nambi Raj


    Organ motions during inter-fraction and intra-fraction radiotherapy introduce errors in dose delivery, irradiating excess of normal tissue, and missing target volume. Lung and heart involuntary motions cause above inaccuracies and gated dose delivery try to overcome above effects. Present work attempts a novel method to verify dynamic dose delivery using a four-dimensional (4D) phantom. Three patients with mobile target are coached to maintain regular and reproducible breathing pattern. Appro...

  16. Patient knowledge, perceptions, expectations and satisfaction on allergen-specific immunotherapy : A survey

    Baiardini, Ilaria; Puggioni, Francesca; Menoni, Stefania; Boot, Johan Diderik; Diamant, Zuzana; Braido, Fulvio; Canonica, Giorgio Walter


    Background: Assessing patient's perspective provides useful information enabling a customized approach which has been advocated by current guidelines. In this multicentre cross-sectional study we evaluated personal viewpoints on allergen-specific immunotherapy (SIT) in patients treated with subcutan

  17. New frontier in regenerative medicine: site-specific gene correction in patient-specific induced pluripotent stem cells.

    Garate, Zita; Davis, Brian R; Quintana-Bustamante, Oscar; Segovia, Jose C


    Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle, to differentiate into any cell type of the human body. Since Yamanaka and colleagues first reported the generation of hiPSCs in 2007, significant efforts have been made to understand the reprogramming process and to generate hiPSCs with potential for clinical use. On the other hand, the development of gene-editing platforms to increase homologous recombination efficiency, namely DNA nucleases (zinc finger nucleases, TAL effector nucleases, and meganucleases), is making the application of locus-specific gene therapy in human cells an achievable goal. The generation of patient-specific hiPSC, together with gene correction by homologous recombination, will potentially allow for their clinical application in the near future. In fact, reports have shown targeted gene correction through DNA-Nucleases in patient-specific hiPSCs. Various technologies have been described to reprogram patient cells and to correct these patient hiPSCs. However, no approach has been clearly more efficient and safer than the others. In addition, there are still significant challenges for the clinical application of these technologies, such as inefficient differentiation protocols, genetic instability resulting from the reprogramming process and hiPSC culture itself, the efficacy and specificity of the engineered DNA nucleases, and the overall homologous recombination efficiency. To summarize advances in the generation of gene corrected patient-specific hiPSCs, this review focuses on the available technological platforms, including their strengths and limitations regarding future therapeutic use of gene-corrected hiPSCs.

  18. Cause-specific mortality among spouses of Parkinson disease patients.

    Nielsen, Malene; Hansen, Johnni; Ritz, Beate; Nordahl, Helene; Schernhammer, Eva; Wermuth, Lene; Rod, Naja Hulvej


    Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. All patients in Denmark with a first-time hospitalization for Parkinson disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. Among men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1.05-3.42]) and death from undefined symptoms/abnormal findings (1.25 [1.07-1.47]). Censoring at the time of death of the patient attenuated the findings for all-cause mortality in husbands (1.02 [0.95-1.09]), indicating that part of the association is with bereavement. Still, living with a person with Parkinson disease 5 years after first Parkinson hospitalization was associated with higher risk of all-cause mortality for both husbands (1.15 [1.07-1.23]) and wives (1.11 [1.04-1.17]). Caring for a spouse with a serious chronic illness is associated with a slight but consistent elevation in mortality risk.

  19. Specific changes of serum proteins in Parkinson's disease patients.

    Wenwen Lu

    Full Text Available The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen γ-chain (FGG appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4 was found to exist two forms in serum. The full size (120 kDa of the protein was increased and the fragmented ITI-H4 (35 kDa was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85 ± 0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (∼ 26 kDa was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ∼ 26 kDa Apo A-IV disappear would provide strong evidence for PD.

  20. Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients.

    Kanbay, Mehmet; Afsar, Baris; Siriopol, Dimitrie; Unal, Hilmi Umut; Karaman, Murat; Saglam, Mutlu; Eyileten, Tayfun; Gezer, Mustafa; Verim, Samet; Oguz, Yusuf; Vural, Abdulgaffar; Ortiz, Alberto; Johnson, Richard J; Covic, Adrian; Yilmaz, Mahmut Ilker


    Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD). A total of 259 patients with CKD stages 1-5 were followed up in a time-to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)]. As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01-12.76; HR 4.75, 95 % CI 2.98-7.59; and HR 4.13, 95 % CI 2.66-6.43, respectively). However, after adjustment for renal-specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes. Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts.

  1. Analysis of radiographic parameters relevant to the lowest instrumented vertebrae and postoperative coronal balance in Lenke 5C patients.

    Li, Jingfeng; Hwang, Steven W; Shi, Zhicai; Yan, Ning; Yang, Changwei; Wang, Chuanfeng; Zhu, Xiaodong; Hou, Tiesheng; Li, Ming


    A retrospective radiographic study. To investigate which preoperative radiographic parameters best correlate with the angulation and translation of the lowest instrumented vertebra (LIV) and global coronal balance after posterior spinal pedicle screw fixation for thoracolumbar/lumbar (TL/L) adolescent idiopathic scoliosis. Lenke 5C patients with a single, structural TL/L curve can be treated by either an anterior or posterior approach. One of the operative goals when treating Lenke 5C patients is to level and center the LIV, thereby achieving a better global coronal balance. To our knowledge, no study has investigated which specific radiographic parameters correlate with these surgical outcomes after posterior pedicle screw fixation. Twenty-seven patients with TL/L adolescent idiopathic scoliosis were identified in this study, and they underwent posterior fixation and fusion by pedicle screws with a minimum 2-year follow-up. Preoperative and postoperative radiographs were reviewed measuring various radiographic parameters as well as specific measurements related to the LIV. Correlation of these parameters to LIV translation and global and regional coronal balance (C7-central sacral vertical line [CSVL], LIV-CSVL distance) were then evaluated. Four patients demonstrated global coronal imbalance postoperatively by radiographic and clinical evaluation. Regression analysis identified three radiographic parameters that correlated significantly with the postoperative global coronal balance (C7-CSVL): preoperative C7-CSVL (r = 0.44, P = 0.023), preoperative LIV tilt (r = 0.60, P = 0.001), and postoperative LIV tilt (r = 0.65, P = 0.0002). The radiographic parameters that correlated with postoperative LIV-CSVL were: preoperative LIV-CSVL (r = 0.57, P = 0.017), preoperative LIV tilt (r = 0.40, P = 0.04), and postoperative LIV tilt (r = 0.46, P = 0.015). The radiographic parameters correlating to LIV translation were preoperative LIV-CSVL (r = 0.88, P balance. In patients

  2. Increased literacy of the best evidence base optimizes patient-clinician communication in convergent translational health care: Relevance for patient-centered modalities

    Allen Khakshooy


    Full Text Available Introduction: Dentistry in particular and biomedicine in general have undergone a fundamental transformation over the recent decades, which have been formalized by the Affordable Care Act, 2010. In brief, modern contemporary health care has evolved from procedure-driven and intervention-centered care based on research evidence to the administration and delivery of care that is patient-centered, effectiveness-focused, and that utilizes the best evidence base generated by systematic research synthesis (i.e., evidence-based. The present conceptualization of health care integrates translational research and translational effectiveness, and allows convergence of the multiple specialization fields of biomedicine (e.g., dentistry, internal medicine, and psychiatry as well as the various medical traditions globally (i.e., Western, Ayurvedic, and Chinese medical traditions, etc.. The Hypothesis: Here, we propose the hypothesis that increased literacy of the best evidence base optimizes patient-clinician communication in the current convergent translational health care model including dental care. Evaluation of the Hypothesis: We discuss the salient points of this proposition, and outline the relevance of certain salient convergent patient-centered modalities of health care that intimately intertwine medicine and dentistry.

  3. The relevance of MRI for patient modeling in head and neck hyperthermia treatment planning: A comparison of CT and CT-MRI based tissue segmentation on simulated temperature

    Verhaart, René F., E-mail:; Paulides, Margarethus M. [Hyperthermia Unit, Department of Radiation Oncology, Erasmus MC - Cancer Institute, Groene Hilledijk 301, Rotterdam 3008 AE (Netherlands); Fortunati, Valerio; Walsum, Theo van; Veenland, Jifke F. [Biomedical Imaging Group of Rotterdam, Department of Medical Informatics and Radiology, Erasmus MC, Dr. Molewaterplein 50/60, Rotterdam 3015 GE (Netherlands); Verduijn, Gerda M. [Department of Radiation Oncology, Erasmus MC - Cancer Institute, Groene Hilledijk 301, Rotterdam 3008 AE (Netherlands); Lugt, Aad van der [Department of Radiology, Erasmus MC, Dr. Molewaterplein 50/60, Rotterdam 3015 GE (Netherlands)


    Purpose: In current clinical practice, head and neck (H and N) hyperthermia treatment planning (HTP) is solely based on computed tomography (CT) images. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast over CT. The purpose of the authors’ study is to investigate the relevance of using MRI in addition to CT for patient modeling in H and N HTP. Methods: CT and MRI scans were acquired for 11 patients in an immobilization mask. Three observers manually segmented on CT, MRI T1 weighted (MRI-T1w), and MRI T2 weighted (MRI-T2w) images the following thermo-sensitive tissues: cerebrum, cerebellum, brainstem, myelum, sclera, lens, vitreous humor, and the optical nerve. For these tissues that are used for patient modeling in H and N HTP, the interobserver variation of manual tissue segmentation in CT and MRI was quantified with the mean surface distance (MSD). Next, the authors compared the impact of CT and CT and MRI based patient models on the predicted temperatures. For each tissue, the modality was selected that led to the lowest observer variation and inserted this in the combined CT and MRI based patient model (CT and MRI), after a deformable image registration. In addition, a patient model with a detailed segmentation of brain tissues (including white matter, gray matter, and cerebrospinal fluid) was created (CT and MRI{sub db}). To quantify the relevance of MRI based segmentation for H and N HTP, the authors compared the predicted maximum temperatures in the segmented tissues (T{sub max}) and the corresponding specific absorption rate (SAR) of the patient models based on (1) CT, (2) CT and MRI, and (3) CT and MRI{sub db}. Results: In MRI, a similar or reduced interobserver variation was found compared to CT (maximum of median MSD in CT: 0.93 mm, MRI-T1w: 0.72 mm, MRI-T2w: 0.66 mm). Only for the optical nerve the interobserver variation is significantly lower in CT compared to MRI (median MSD in CT: 0.58 mm, MRI-T1w: 1.27 mm, MRI-T2w: 1.40 mm

  4. Hemodynamic Assessment of Compliance of Pre-Stressed Pulmonary Valve-Vasculature in Patient Specific Geometry Using an Inverse Algorithm

    Hebbar, Ullhas; Paul, Anup; Banerjee, Rupak


    Image based modeling is finding increasing relevance in assisting diagnosis of Pulmonary Valve-Vasculature Dysfunction (PVD) in congenital heart disease patients. This research presents compliant artery - blood interaction in a patient specific Pulmonary Artery (PA) model. This is an improvement over our previous numerical studies which assumed rigid walled arteries. The impedance of the arteries and the energy transfer from the Right Ventricle (RV) to PA is governed by compliance, which in turn is influenced by the level of pre-stress in the arteries. In order to evaluate the pre-stress, an inverse algorithm was developed using an in-house script written in MATLAB and Python, and implemented using the Finite Element Method (FEM). This analysis used a patient specific material model developed by our group, in conjunction with measured pressure (invasive) and velocity (non-invasive) values. The analysis was performed on an FEM solver, and preliminary results indicated that the Main PA (MPA) exhibited higher compliance as well as increased hysteresis over the cardiac cycle when compared with the Left PA (LPA). The computed compliance values for the MPA and LPA were 14% and 34% lesser than the corresponding measured values. Further, the computed pressure drop and flow waveforms were in close agreement with the measured values. In conclusion, compliant artery - blood interaction models of patient specific geometries can play an important role in hemodynamics based diagnosis of PVD.

  5. Diabetes Mellitus Increased Mortality Rates More in Gender-Specific than in Nongender-Specific Cancer Patients: A Retrospective Study of 149,491 Patients

    Wen-Ko Chiou


    Full Text Available Aims. Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM. Methods. We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM. Results. Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98% were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33 to 5.04% (ovary, HR: 1.49. Conclusion. Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.

  6. Establishing construct validity for the thyroid-specific patient reported outcome measure (ThyPRO)

    Watt, Torquil; Bjorner, Jakob Bue; Groenvold, Mogens;


    To establish a reliable and valid scale structure of a patient-reported outcome measuring thyroid-specific quality of life.......To establish a reliable and valid scale structure of a patient-reported outcome measuring thyroid-specific quality of life....

  7. 进展性卒中的相关因素研究%Relevent Factors stroke in progression Patients

    刘俊艳; 董玉娟; 李娜; 任士卿; 李育臣; 王建茹; 刘好文; 王冰


    Objective: In order to prophylactic treat stroke in progression (SIP), we analysed risk factors and imagery characters of SIP patients. Methods: retrospectively study 58 cases SIP patients, and analysis relevent factors of SIP, which includ blood pressure(systolic pressure and diastolic pressure), blood glucose and blood lipid level, the changes of magnetic resonance angiography and transcranial Dopple. All data were analysed by chi-test. Results: 1. Results showed that 46 patients of 58 SIP were accompanied with hypertension. among them, 18 patients` systolic prssure were less than 150 mmHg and 13 cases with a decrement of pulse pressure (P<0.001). and patients with a long course history and informal treatment hypertension, especially those patients accompanied by low systolic pressure, were easy suffer from SIP. 2. In SIP group, 31 pateints were accompanied wiht DM, the morbidity was obviously higher than that of control (P<0.000). 3. Among 21 SIP patients examined by MRA or/and TCD, 14 patients showed intracranial of/and extracraial vascular stenosis of occlusion. there were only 4 cases in control group. In thosse patients, low perfusion pressure that resulting from artery trunk stenosis or occlusion and decrement of pulse pressure was main cause of SIP. 4. On image, most common infarction site of SIP were in body of lateral ventricles and water-shed territoy, which is usually suggesting large vessel disease. Conclusion: HT, especially the hypertension whth lower systolic pressure, DM, intra-or extracranial vascular stenosis/occlusion and severely function defciency in neurologic system are associated whth SIP. The latter ply a main role in progressive of late phase in first week. About treatment therapy of SIP patients, we emphasize not to reduce blood pressure, excessively meanwhile giving anticoagulation, we should apply for a MRA or TCD exam and early find vascular change, further prevent relapse with cerebral vascular diseases.%目的:寻找引起进

  8. Measures and time points relevant for post-surgical follow-up in patients with inflammatory arthritis: a pilot study

    Tägil Magnus


    Full Text Available Abstract Background Rheumatic diseases commonly affect joints and other structures in the hand. Surgery is a traditional way to treat hand problems in inflammatory rheumatic diseases with the purposes of pain relief, restore function and prevent progression. There are numerous measures to choose from, and a combination of outcome measures is recommended. This study evaluated if instruments commonly used in rheumatologic clinical practice are suitable to measure outcome of hand surgery and to identify time points relevant for follow-up. Methods Thirty-one patients (median age 56 years, median disease duration 15 years with inflammatory rheumatic disease and need for post-surgical occupational therapy intervention formed this pilot study group. Hand function was assessed regarding grip strength (Grippit, pain (VAS, range of motion (ROM (Signals of Functional Impairment (SOFI and grip ability (Grip Ability Test (GAT. Activities of daily life (ADL were assessed by means of Disabilities of the Arm, Shoulder and Hand Outcome (DASH and Canadian Occupational Performance Measure (COPM. The instruments were evaluated by responsiveness and feasibility; follow-up points were 0, 3, 6 and 12 months. Results All instruments showed significant change at one or more follow-up points. Satisfaction with activities (COPM showed the best responsiveness (SMR>0.8, while ROM measured with SOFI had low responsiveness at most follow-up time points. The responsiveness of the instruments was stable between 6 and 12 month follow-up which imply that 6 month is an appropriate time for evaluating short-term effect of hand surgery in rheumatic diseases. Conclusion We suggest a core set of instruments measuring pain, grip strength, grip ability, perceived symptoms and self-defined daily activities. This study has shown that VAS pain, the Grippit instrument, GAT, DASH symptom scale and COPM are suitable outcome instruments for hand surgery, while SOFI may be a more insensitive

  9. 缺氧导致压疮的研究及护理%Specific Weight Oxygen Deficit Creates Presses the Relevance Whichthe Boils Occurs and Nursing



    Objective The discussion presses the boils to occur nurses with thespecific weight oxygen deficit relevance and the pointed prevention. Methods Uses the review investigation method the blocking pulmonaryemphysema patient's oxygen deficit degree which occurs to 38examplespresses the boils, shows 2Braden to grade, presses boils danger tograde, after appears the skin partial pressure red extension to turnover to 65 examples blocking pulmonary emphysema patient al ocatedproportion comparison which is hospitalized with the same time. Results Presses the boils after statistics processing to have thegroup and the comparison group oxygen deficit degree dif erence hasextremely obviously ( <0.01);Braden grades the dif erence to have extremelyobviously ( <0.01);Presses boils danger to grade has the dif erence( <0.05);Afterappears the skin partial pressure red extension to turn over to thedif erence to have obvious( <0.05). Conclusion The oxygen deficit regulationgoes past heavily, patient's acute physiology grades (Braden) lowly,it presses the risk which the boils occurs to be bigger, in nurses inthe work to have to use the document method to appear the partialpressure red skin promptly to take the remedial treatment.%目的探讨压疮发生与重度缺氧的相关性并针对性的预防护理。方法采用回顾性调查方法对38例发生压疮的慢性阻塞性肺气肿患者的缺氧程度,Braden评分参考表,压疮危险度评分,出现皮肤局部压红后转归与同期住院的65例慢性阻塞性肺气肿患者配比对照。结果经统计学处理压疮发生组与对照组缺氧程度差异有非常显著性(<0.01);Braden评分差异有非常显著性(<0.01);压疮危险度评分差异有显著性(<0.05);出现皮肤局部压红后转归差异有显著性(<0.05)。结论缺氧程度越重,患者的压疮发生的危险性越大,在护理工作中需采用个案化的方法对出现局部压红的皮肤及时采取补救措施。

  10. Wall Shear Stress Distribution in Patient Specific Coronary Artery Bifurcation

    Vahab Dehlaghi


    Full Text Available Problem statement: Atherogenesis is affected by hemodynamic parameters, such as wall shear stress and wall shear stress spatial gradient. These parameters are largely dependent on the geometry of arterial tree. Arterial bifurcations contain significant flow disturbances. Approach: The effects of branch angle and vessel diameter ratio at the bifurcations on the wall shear stress distribution in the coronary arterial tree based on CT images were studied. CT images were digitally processed to extract geometrical contours representing the coronary vessel walls. The lumen of the coronary arteries of the patients was segmented using the open source software package (VMTK. The resulting lumens of coronary arteries were fed into a commercial mesh generator (GAMBIT, Fluent Inc. to generate a volume that was filled with tetrahedral elements. The FIDAP software (Fluent Corp. was used to carry out the simulation by solving Navier-Stokes equations. The FIELDVIEW software (Version 10.0, Intelligent Light, Lyndhurst, NJ was used for the visualization of flow patterns and the quantification of wall shear stress. Post processing was done with VMTK and MATLAB. A parabolic velocity profile was prescribed at the inlets and outlets, except for 1. Stress free outlet was assigned to the remaining outlet. Results: The results show that for angle lower than 90°, low shear stress regions are observed at the non-flow divider and the apex. For angle larger than 90°, low shear stress regions only at the non-flow divider. By increasing of diameter of side branch ratio, low shear stress regions in the side branch appear at the non-flow divider. Conclusion: It is concluded that not only angle and diameter are important, but also the overall 3D shape of the artery. More research is required to further quantify the effects angle and diameter on shear stress patterns in coronaries.

  11. Multi-channel MRI segmentation of eye structures and tumors using patient-specific features.

    Ciller, Carlos; De Zanet, Sandro; Kamnitsas, Konstantinos; Maeder, Philippe; Glocker, Ben; Munier, Francis L; Rueckert, Daniel; Thiran, Jean-Philippe; Bach Cuadra, Meritxell; Sznitman, Raphael


    Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously. This situation, and the lack of tools for accurate eye MRI analysis, reduces the interest in MRI beyond the qualitative evaluation of the optic nerve invasion and the confirmation of recurrent malignancies below calcified tumors. In this manuscript, we propose a new framework for the automatic segmentation of eye structures and ocular tumors in multi-sequence MRI. Our key contribution is the introduction of a pathological eye model from which Eye Patient-Specific Features (EPSF) can be computed. These features combine intensity and shape information of pathological tissue while embedded in healthy structures of the eye. We assess our work on a dataset of pathological patient eyes by computing the Dice Similarity Coefficient (DSC) of the sclera, the cornea, the vitreous humor, the lens and the tumor. In addition, we quantitatively show the superior performance of our pathological eye model as compared to the segmentation obtained by using a healthy model (over 4% DSC) and demonstrate the relevance of our EPSF, which improve the final segmentation regardless of the classifier employed.

  12. Patient specific root-analogue dental implants – additive manufacturing and finite element analysis

    Gattinger Johannes; Bullemer Christian N.; Harrysson Ola L. A.


    Aim of this study was to prove the possibility of manufacturing patient specific root analogue two-part (implant and abutment) implants by direct metal laser sintering. The two-part implant design enables covered healing of the implant. Therefore, CT-scans of three patients are used for reverse engineering of the implants, abutments and crowns. Patient specific implants are manufactured and measured concerning dimensional accuracy and surface roughness. Impacts of occlusal forces are simulate...

  13. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.


    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  14. Psychosocial risk factors, interventions and comorbidity in patients with non-specific low back pain in primary care: need for comprehensive and patient-centered care.

    Aline eRamond-Roquin


    Full Text Available Non-specific low back pain (LBP affects many people and has major socio-economic consequences. Traditional therapeutic strategies, mainly focused on biomechanical factors, have had moderate and short-term impact. Certain psychosocial factors have been linked to poor prognosis of LBP and they are increasingly considered as promising targets for management of LBP. Primary health care providers (HCPs are involved in most of the management of people with LBP and they are skilled in providing comprehensive care, including consideration of psychosocial dimensions. This review aims to discuss three pieces of recent research focusing on psychosocial issues in LBP patients in primary care. In the first systematic review, the patients’ or HCPs’ overall judgment about the likely evolution of LBP was the factor most strongly linked to poor outcome, with predictive validity similar to that of multidimensional scales. This result may be explained by the implicit aggregation of many prognostic factors underlying this judgment and suggests the relevance of considering the patients from biopsychosocial and longitudinal points of view. The second review showed that most of the interventions targeting psychosocial factors in LBP in primary care have to date focused on the cognitive-behavioral factors, resulting in little impact. It is unlikely that any intervention focusing on a single factor would ever fit the needs of most patients; interventions targeting determinants from several fields (mainly psychosocial, biomechanical and occupational may be more relevant. Should multiple stakeholders be involved in such interventions, enhanced interprofessional collaboration would be critical to ensure the delivery of coordinated care. Finally, in the third study, the prevalence of psychosocial comorbidity in chronic LBP patients was not found to be significantly higher than in other patients consulting in primary care. Rather than specifically screening for

  15. Elucidating the immunological effects of 5-azacytidine treatment in patients with myelodysplastic syndrome and identifying new conditional ligands and T-cell epitopes of relevance in melanoma.

    Frøsig, Thomas Mørch


    This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery of new conditional ligands (reported in Paper IV). Many melanoma-associated T-cell epitopes have been described, but 45% of these are restricted to human leukocyte antigen (HLA)-A2, leaving the remaining 36 different HLA molecules with only a few described T-cell epitopes each. Therefore we wanted to expand the number of T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7, all HLA molecules frequently expressed in Caucasians in Western Europe and Northern America. In Paper I we focused on the proteins gp100, Mart1, MAGE-A3, NY-ESO-1, tyrosinase and TRP-2, all melanoma-associated antigens frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory by an ELISA-based method and used for flow cytometry-based detection of specific T-cell responses by use of combinatorial encoded major histocompatibility (MHC) class I multimers. This procedure resulted in 127 (Paper I) and 32 (Paper II) confirmed HLA ligands, respectively, which we used for screening of the T-cell recognition within peripheral blood mononuclear cell samples from melanoma patients. As spontaneous tumor-specific T-cell responses tend to be of very low frequency and probably below the detection threshold of the method, we incorporated a T-cell enrichment step prior to the detection of these responses. Our screening of 39 melanoma patients resulted in 26 (17 different) T-cell responses against the common melanoma-associated antigens and 10 (8 different) T

  16. Predicting changes in blood flow in patient-specific operative plans for treating aortoiliac occlusive disease.

    Wilson, Nathan M; Arko, Frank R; Taylor, Charles A


    Traditionally, a surgeon will select a procedure for a particular patient on the basis of past experience with patients with a similar state of disease. The experience gained from this patient will be selectively used when treating the next patient with similar symptoms. This article describes a surgical planning system that was developed to enable a vascular surgeon to create and test alternative operative plans prior to surgery for a given patient. One-dimensional and three-dimensional hemodynamic (i.e., blood flow) simulations were performed for rest and exercise for operative plans for two aorto-femoral bypass patients and compared with actual postoperative data. The information obtained from one-dimensional (volume flow distribution and pressure losses) and three-dimensional (flow, pressure, and wall shear stress) hemodynamic simulations may be clinically relevant to vascular surgeons planning interventions.

  17. Aspects of spirituality in medical doctors and their relation to specific views of illness and dealing with their patients' individual situation

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus


    We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction...... they assume that they would deal with their patients' individual situation. Of interest, the specific aspects of spirituality were negatively correlated with the view of "illness as a meaningless interruption" of life, indicating that physicians with a spiritual attitude would see illness also as a chance...... for an "individual development" and associated with a "biographical meaning" rather than just a "useless interruption" of life....

  18. Effect of therapeutic infra-red in patients with non-specific low back pain: a pilot study.

    Ansari, Noureddin Nakhostin; Naghdi, Soofia; Naseri, Nasrin; Entezary, Ebrahim; Irani, Shahnur; Jalaie, Shohreh; Hasson, Scott


    The purpose of this study was to investigate the effect of infra-red (IR) in patients with chronic non-specific low back pain (NSLBP). Ten patients with NSLBP (5 men and 5 women) and disease duration of 21.7 ± 11.50 months participated in this pilot study. Patients had a mean age of 36.40 ± 10.11 years (range = 25-55). Patients were treated with infra-red (IR) for 10 sessions, each for 15 min, 3 days per week, for a period of 4 weeks. Outcome measures were the Numerical Rating Scale (NRS), the Functional Rating Index (FRI), the Modified-Modified Schober Test (MMST), and the Biering-Sorensen test to assess pain severity, disability, lumbar flexion and extension range of motion (ROM), and back extensor endurance, respectively. Data were collected at: baseline - study entry (T0); end of 5th treatment session after 2 weeks (T1); and end of the treatment after 4 weeks (T2). The results of the ANOVA demonstrated a statistically significant main effect of IR on all outcomes of pain, function, lumbar flexion-extension ROM, and back extensor endurance. The treatment effect sizes ranged from large to small. IR was effective in improving pain, function, lumbar ROM, and back extensor endurance in a sample of patients with NSLBP. Treatment effect sizes ranged from large to small indicating clinically relevant improvements primarily in pain and function for patients with NSLBP. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Depression Is Associated with Repeat Emergency Department Visits in Patients with Non-specific Abdominal Pain

    Andrew Charles Meltzer


    Full Text Available Introduction: Patients with abdominal pain often return multiple times despite no definitive diagnosis. Our objective was to determine if repeat emergency department (ED use among patients with non-specific abdominal pain might be associated with a diagnosis of moderate to severe depressive disorder. Methods: We screened 987 ED patients for major depression during weekday daytime hours from June 2011 through November 2011 using a validated depression screening tool, the PHQ-9. Each subject was classified as either no depression, mild depression or moderate/ severe depression based on the screening tool. Within this group, we identified 83 patients with non-specific abdominal pain by either primary or secondary diagnosis. Comparing depressed patients versus non-depressed patients, we analyzed demographic characteristics and number of prior ED visits in the past year. Results: In patients with non-specific abdominal pain, 61.9% of patients with moderate or severe depression (PHQ9≥10 had at least one visit to our ED for the same complaint within a 365-day period, as compared to 29.2% of patients with no depression (PHQ9<5, (p=0.013. Conclusion: Repeat ED use among patients with non-specific abdominal pain is associated with moderate to severe depressive disorder. Patients with multiple visits for abdominal pain may benefit from targeted ED screening for depression.

  20. The effectiveness of specific exercise types on cardiopulmonary functions in patients with ankylosing spondylitis: a systematic review.

    Saracoglu, Ismail; Kurt, Gamze; Okur, Eda Ozge; Afsar, Emrah; Seyyar, Gulce Kallem; Calik, Bilge Basakci; Taspinar, Ferruh


    The aim of this review was to assess the effectiveness of specific exercise types on pulmonary functions, aerobic and functional capacity in patients with ankylosing spondylitis (AS). A systematic search of Cochrane Database of Systematic Review, MEDLINE (EBSCO), Physiotherapy Evidence Database (PEDro), CINAHL (EBSCO), PUBMED, AMED, EMBASE (OVID) was conducted in January 2016. The outcome measures were spirometric measurements, chest expansion, 6 minute walk distance (6MWD), pVO2, Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The search strategy was applied with limitation of date and language and this initial electronic search resulted in 143 relevant studies. After duplicates were removed, the titles and abstracts of 52 articles were screened. Of these, 14 full-text articles met initial criteria and were retrieved for review, with eight studies meeting final inclusion criteria. Both specific and conventional exercise groups showed significant improvements in BASDAI and BASFI scores (p  0.05). Specific exercises are an effective adjuvant therapy to enhance cardiopulmonary functions in patients with AS; therefore, it is assumed that in addition to the medical treatments, specific exercise therapy might reduce the cardiopulmonary complications related with AS.

  1. 3D reconstruction of patient-specific femurs using Coherent Point Drift

    Shaobin Sun


    Full Text Available This paper dealt with the problem that the overlapping digital radiographs couldn`t reflect the 3D space information of the patient-specific femur in the orthopaedic surgery diagnosis. A 2D-3D non-rigid registration method based on Coherent Point Drift was proposed to realize the 3D reconstruction of the patient-specific femur before the surgery, which used biplanar digital radiographs of the patient-specific femur and the CT volume data of a generic femur. With the advantages of low cost, fast imaging speed and little radiation to the patients and doctors, this method provided more effective 3D imaging information for the femur diagnosis and preoperative plans. The registration experiments showed that the proposed method recovered the 3D model and the pose of the patient-specific femur effectively with a fast, accurate and robust registration result, which had satisfied the needs of clinical application.

  2. Realizing Relevance: The Influence of Domain-Specific Information on Generation of New Knowledge through Integration in 4- to 8-Year-Old Children

    Bauer, Patricia J.; Larkina, Marina


    In accumulating knowledge, direct modes of learning are complemented by productive processes, including self-generation based on integration of separate episodes. Effects of the number of potentially relevant episodes on integration were examined in 4- to 8-year-olds (N = 121; racially/ethnically heterogeneous sample, English speakers, from large…

  3. Which domains of thyroid-related quality of life are most relevant?

    Watt, Torquil; Hegedüs, Laszlo; Rasmussen, Ase Krogh


    To identify how thyroid diseases impact the patients' lives and to select the most relevant quality of life (QoL) issues for a thyroid-specific questionnaire.......To identify how thyroid diseases impact the patients' lives and to select the most relevant quality of life (QoL) issues for a thyroid-specific questionnaire....

  4. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias


    PURPOSE: It is well known that a significant proportion of heart failure patients (10-44 %) do not show improvement in symptoms or functioning from cardiac resynchronization therapy (CRT), yet no study has examined patient-reported health status trajectories after implantation. METHODS: A cohort...... levels after implantation. CONCLUSIONS: Levels of disease-specific health status vary considerably across subgroups of CRT-D patients. Classification into poorer disease-specific health status trajectories was particularly associated with patients' psychological profile and NYHA classification...

  5. Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment.

    de Glas, N A; Hamaker, M E; Kiderlen, M; de Craen, A J M; Mooijaart, S P; van de Velde, C J H; van Munster, B C; Portielje, J E A; Liefers, G J; Bastiaannet, E


    With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of older patients. The aim of this study was to present an overview of trial characteristics and endpoints of all currently running clinical trials in breast cancer, particularly in older patients. The clinical trial register of the United States National Institutes of Health Differences was searched for all current clinical trials on breast cancer treatment. Trial characteristics and endpoints were retrieved from the register and differences in characteristics between studies in older patients specifically (defined as a lower age-limit of 60 years or older) and trials in all patients were assessed using χ(2) tests. We included 463 clinical trials. Nine trials (2 %) specifically investigated breast cancer treatment in older patients. Ninety-one breast cancer trials included any patient-related endpoint (20 %), while five trials specifically addressing older patients included any patient-related endpoint (56 %, P = 0.02). Five of the trials in older patients incorporated a geriatric assessment (56 %). Clinical trials still rarely incorporate patient-related endpoints, even in trials that specifically address older patients. Trials that are specifically designed for older patients do not often incorporate a geriatric assessment in their design. This implicates that current clinical studies are not expected to fill the gap in knowledge concerning treatment of older breast cancer patients in the next decade.

  6. IMRT patient-specific QA using the Delta4 dosimetry system and evaluation based on ICRU 83 recommendations

    Nilsson, J.; Karlsson Hauer, A.; Bäck, A.


    Patient-specific IMRT QA is dependent on the dosimetry system and the evaluation procedure. The ICRU report 83 provides recommendations of tolerated deviations between measured and calculated absorbed dose distributions for QA of IMRT treatment plans. The result of doing IMRT patient-specific QA with the Delta4 dosimetry system and using the ICRU recommendations for evaluation is studied. To be able to investigate the QA procedure the original IMRT treatment plans were modified in the treatment planning system to create calculated dose distributions with dosimetric deviations from the original treatment plans. The modified dose distributions were compared to the dose distributions from the Delta4 measurements of the original treatment plans and the differences were evaluated with criteria and tolerance levels according to the recommendations from ICRU. The evaluation for all 28 modified dose distributions have gamma passing rates higher than the tolerance level recommended from ICRU and will therefore pass the patient-specific QA. More than half of the evaluations have a gamma passing rate of 100 %. Evaluation of the differences between the modified and the original calculated dose distributions revealed in several cases large unacceptable dose differences in the PTV volumes and the organs at risk, for example an increase in the near-maximum dose D2% to the spinal cord of 5.5 Gy. This study indicates that patient-specific QA with the Delta4 dosimetry system and the ICRU recommendations for evaluation can not be used to distinguish differences between planned and measured dose of dosimetrical relevance.

  7. Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy.

    Song, Ting; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Zhou, Linghong; Jiang, Steve B; Gu, Xuejun


    In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient's unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient's geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control.

  8. Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

    Michael C. Gong


    Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

  9. From Patient-Specific Mathematical Neuro-Oncology to Precision Medicine

    Anne eBaldock


    Full Text Available Gliomas are notoriously aggressive, malignant brain tumors that have variable response to treatment. These patients often have poor prognosis, informed primarily by histopathology. Mathematical neuro-oncology (MNO is a young and burgeoning field that leverages mathematical models to predict and quantify response to therapies. These mathematical models can form the basis of modern precision medicine approaches to tailor therapy in a patient-specific manner. Patient specific models (PSMs can be used to overcome imaging limitations, improve prognostic predictions, stratify patients and assess treatment response in silico. The information gleaned from such models can aid in the construction and efficacy of clinical trials and treatment protocols, accelerating the pace of clinical research in the war on cancer. This review focuses on the growing translation of PSM to clinical neuro-oncology. It will also provide a forward-looking view on a new era of patient-specific mathematical neuro-oncology.

  10. Development of disease-specific quality indicators for danish chiropractic patients with low back pain

    Sorensen, Line P; Krog, Birgitte R; Kongsted, Alice;


    The purpose of this study is to develop disease-specific quality indicators for Danish chiropractic patients with low back pain (LBP) as an initial effort to include chiropractors in the Danish Health Care Quality Programme.......The purpose of this study is to develop disease-specific quality indicators for Danish chiropractic patients with low back pain (LBP) as an initial effort to include chiropractors in the Danish Health Care Quality Programme....

  11. Inter-therapist agreement in classifying patients with cervical radiculopathy and patients with non-specific neck-arm pain.

    Tampin, Brigitte; Briffa, Noelle Kathryn; Hall, Toby; Lee, Gabriel; Slater, Helen


    Identification of differences in clinical presentation and underlying pain mechanisms may assist the classification of patients with neck-arm pain which is important for the provision of targeted best evidence based management. The aim of this study was to: (i) assess the inter-examiner agreement in using specific systems to classify patients with cervical radiculopathy and patients with non-specific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP); (ii) assess the agreement between two clinical examiners and two clinical experts in classifying these patients, and (iii) assess the diagnostic accuracy of the two clinical examiners. Forty patients with unilateral neck-arm pain were examined by two clinicians and classified into (i) cervical radiculopathy, (ii) NSNAP, (iii) other. The classifications were compared to those made independently by two experts, based on a review of patients' clinical assessment notes. The experts' opinion was used as the reference criterion to assess the diagnostic accuracy of the clinical examiners in classifying each patient group. There was an 80% agreement between clinical examiners, and between experts and 70%-80% between clinical examiners and experts in classifying patients with cervical radiculopathy (kappa between 0.41 and 0.61). Agreement was 72.5%-80% in classifying patients with NSNAP (kappa between 0.43 and 0.52). Clinical examiners' diagnostic accuracy was high (radiculopathy: sensitivity 79%-84%; specificity 76%-81%; NSNAP: sensitivity 78%-100%; specificity 71%-81%). Compared to expert opinion, clinicians were able to identify patients with cervical radiculopathy and patients with NSNAP in 80% of cases, our data supporting the reliability of these classification systems.


    Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen

    the immune response in allergic patients and results in an inhibition of the specific type 1 allergic response. This inhibition is mainly brought about by a change in the immunoglobulin response pattern from allergen specific IgE towards predominantly IgG. Seven days after vaccination with tetanus vaccine...

  13. Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

    Brimnes, J; Halberg, P; Jacobsen, Søren;


    The objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins...

  14. Tuberculosis-specific CD8 cells in HLA A*02-positive TB- and LTBI patients

    Fløe, Andreas; Brix, Liselotte; Wejse, Christian;

    on a flow cytometer. The MTB epitopes were analyzed in 5 pools (3-7 epitopes each). Positive responses included >0.001 % of CD8+, CD3+ cells, supported by inspection of flow cytometry plots. Results: MTB-specific CD8+ T-cells were detected more often in TB patients (57%) than in LTBI patients (41...

  15. Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures.

    Pan, Xuequn; Cimino, James J


    Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

  16. Enabling intra-DHB patient-specific care for patients with intestinal failure

    Fraser-Irwin, Cate; McLeod, Briar; Evans, Helen; Herbison, Kim; Kostrzewski, Amy; McIlroy, Kerry; Makam, Vidhya


    Patients with intestinal failure are medically fragile and need timely intervention when and wherever they present. Care is often fragmented across the care settings e.g. Starship (tertiary), DHBs (secondary) and GPs (primary) due to poor information systems interoperability. Patients want to be cared for in their own communities with the ability to access specialist care.The National Intestinal Failure Service’s connected care pilot supports patients with intestinal failure to have care deli...

  17. [Prognostic relevance of body mass index and rash for patients with metastatic non-small-cell lung cancer under therapy with erlotinib].

    Böker, B; Lüders, H; Grohé, C


    Tyrosine kinase inhibition (TKI) such as erlotinib is a well established treatment option in the palliative care of patients with non small cell lung cancer (NSCLC). Histology and sex have been associated with different prognostic outcome measures in patients treated with erlotinib. Furthermore, the degree of rash, developed during treatment might be a relevant marker in respect to tumor response. To dissect these clinical relevant features we analysed a cohort of 275 patients treated with erlotinib in different lines of chemotherapy in our hospital. Nutrition status plays an important role in the prognosis of patients in a palliative chemotherapeutic setting, we therefore included body mass index measurements (BMI) in our analysis. We found that BMI and smoking status influence different survival patterns. Male patients have a poorer survival based on low BMI, rash development and smoking status. We therefore conclude that both nutritional and smoking status should be taken into account in the surveillance of patients with NSCLC in a palliative therapeutic setting under TKI treatment.

  18. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  19. Patient specific root-analogue dental implants – additive manufacturing and finite element analysis

    Gattinger Johannes


    Full Text Available Aim of this study was to prove the possibility of manufacturing patient specific root analogue two-part (implant and abutment implants by direct metal laser sintering. The two-part implant design enables covered healing of the implant. Therefore, CT-scans of three patients are used for reverse engineering of the implants, abutments and crowns. Patient specific implants are manufactured and measured concerning dimensional accuracy and surface roughness. Impacts of occlusal forces are simulated via FEA and compared to those of standard implants.

  20. Development of an integrated CAD-FEA system for patient-specific design of spinal cages.

    Zhang, Mingzheng; Pu, Fang; Xu, Liqiang; Zhang, Linlin; Liang, Hang; Li, Deyu; Wang, Yu; Fan, Yubo


    Spinal cages are used to create a suitable mechanical environment for interbody fusion in cases of degenerative spinal instability. Due to individual variations in bone structures and pathological conditions, patient-specific cages can provide optimal biomechanical conditions for fusion, strengthening patient recovery. Finite element analysis (FEA) is a valuable tool in the biomechanical evaluation of patient-specific cage designs, but the time- and labor-intensive process of modeling limits its clinical application. In an effort to facilitate the design and analysis of patient-specific spinal cages, an integrated CAD-FEA system (CASCaDeS, comprehensive analytical spinal cage design system) was developed. This system produces a biomechanical-based patient-specific design of spinal cages and is capable of rapid implementation of finite element modeling. By comparison with commercial software, this system was validated and proven to be both accurate and efficient. CASCaDeS can be used to design patient-specific cages with a superior biomechanical performance to commercial spinal cages.

  1. Disclosure of Leprosy by Health Care Providers in South-India: Patients' Perception and Relevance to Leprosy Control, Tamil Nadu.

    Thilakavathi, S; Manickam, P; Mehendale, S M


    Stigma, isoIation and discrimination are typically associated with diagnosis of leprosy and its disclosure. Health care providers (HCPs) find it challenging to disclose the diagnosis of leprosy to patients and their family members. A qualitative study was done in a rural community near Chennai in Tamil Nadu, from August 2011 to March 2012, covering 155 out of 648 (23.9%) purposively selected leprosy patients from 53 out of 148 panchayats, representing 264 villages in the study area; Out of these 155 patients, 59% were males; 30% were illiterates; 70% were married; 56% were living in nuclear families; half the leprosy patients were either agricultural labourers or skilled workers (50%).Thirty two percent were multibacillary (MB) cases and 68% were pauci bacillary (PB) cases; 77% were old patients and 23% were new patients; 22% had leprosy deformity 12% had disfiguration; 23% had anaesthesia and 3% were with lagophthalmous. Of the 155 patients, 31 (20%) reported that they were not informed about diagnosis of their disease by the concerned HCPs. They were informed to be having a skin disease or a skin patch. Of these 31 patients, 22 (71%) were women; all except one with PB leprosy. Seven patients (23%) had not yet started on treatment 3 patients (10%) were given treatment when they were young and neither, them nor their parents were informed about this disease. Seven (33%) of the married patients who had the disease during their child had or when they were young, were not informed of the diagnosis by the HCPs. Ten respondents (32%) were neither bothered nor concerned about non disclosure of the disease by HCPs. Now, after knowing the diagnosis of the disease 4 females (13%) mentioned that they were having some fear, worry or stigma. As non-disclosure of leprosy by HCPs may adversely affect acceptance and adherence, to treatment by the patients, appropriate communication strategies should be developed and implemented.

  2. Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and malignant peripheral nerve sheath tumours

    Brenner, Winfried; Buchert, Ralph; Clausen, Malte [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Friedrich, Reinhard E.; Mautner, Victor F. [University Medical Center Hamburg-Eppendorf, Department of Oral and Maxillofacial Surgery, Hamburg (Germany); Gawad, Karim A. [University Medical Center Hamburg-Eppendorf, Department of General, Visceral and Thoracic Surgery, Hamburg (Germany); Hagel, Christian [University Medical Center Hamburg-Eppendorf, Institute of Neuropathology, Hamburg (Germany); Deimling, Andreas von [Charite Universitaetsmedizin, Department of Neuropathology, Berlin (Germany); Wit, Maike de [University Medical Center Hamburg-Eppendorf, Department of Medicine II, Hamburg (Germany)


    In patients with neurofibromatosis type-1 (NF1) and malignant peripheral nerve sheath tumours (MPNSTs), survival rates are low and time to death is often less than 2 years. However, there are patients with a more favourable prognosis who develop metastases rather late or not at all. Since histopathology and tumour grading are not well correlated with prognosis, we aimed to evaluate the potential of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) for prediction of patient outcome in MPNST. FDG PET was performed in 16 patients with NF1 and MPNSTs. Standardised uptake values (SUVs) were calculated for each tumour and correlated to tumour grade and patient outcome in terms of survival or death. Three patients with tumour grade II had an SUV <3. None of these patients developed metastases or died during a follow-up of 41-62 months. Thirteen patients with tumour grades II and III had an SUV >3. Only one of these patients is still alive after 20 months; the remaining 12 died within 4-33 months. SUV predicted long-term survival with an accuracy of 94%, compared with 69% for tumour grade. In Kaplan-Meier survival analysis, patients with an SUV >3 had a significantly shorter mean survival time, 13 months, than patients with an SUV <3, in whom the mean survival time was 52 months. Tumour grading did not reveal differences in survival time (15 vs 12 months). Tumour SUV obtained by FDG PET was a significant parameter for prediction of survival in NF1 patients with MPNSTs while histopathological tumour grading did not predict outcome. (orig.)

  3. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan


    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  4. Identification of aspects of functioning, disability and health relevant to patients experiencing vertigo: a qualitative study using the international classification of functioning, disability and health


    Purpose Aims of this study were to identify aspects of functioning and health relevant to patients with vertigo expressed by ICF categories and to explore the potential of the ICF to describe the patient perspective in vertigo. Methods We conducted a series of qualitative semi-structured face-to-face interviews using a descriptive approach. Data was analyzed using the meaning condensation procedure and then linked to categories of the International Classification of Functioning, Disability and Health (ICF). Results From May to July 2010 12 interviews were carried out until saturation was reached. Four hundred and seventy-one single concepts were extracted which were linked to 142 different ICF categories. 40 of those belonged to the component body functions, 62 to the component activity and participation, and 40 to the component environmental factors. Besides the most prominent aspect “dizziness” most participants reported problems within “Emotional functions (b152), problems related to mobility and carrying out the daily routine. Almost all participants reported “Immediate family (e310)” as a relevant modifying environmental factor. Conclusions From the patients’ perspective, vertigo has impact on multifaceted aspects of functioning and disability, mainly body functions and activities and participation. Modifying contextual factors have to be taken into account to cover the complex interaction between the health condition of vertigo on the individuals’ daily life. The results of this study will contribute to developing standards for the measurement of functioning, disability and health relevant for patients suffering from vertigo. PMID:22738067

  5. The relevance of patient-reported outcomes in a grass pollen immunotherapy trial in children and adolescents with rhinoconjunctivitis

    Roder, Esther; Berger, Marjolein Y.; Hop, Wim C. J.; de Groot, Hans; van Wijk, Roy Gerth


    Background: Patient-reported outcomes (PROs) are the only instruments available to assess the efficacy of an intervention in patients with allergic rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is now recommended to use not only PROs focusing at classical symptoms, b

  6. Age-specific mortality among TB patients in Denmark 1998-2010

    Fløe, Andreas; Løkke, Anders; Ibsen, Rikke

    Objective: To evaluate the age-specific mortality in a national TB cohort, and to estimate relative age-specific mortality compared with matched controls, in a retrospective case-control study. Methods: Using Danish National Patient Registry, we retrospectively identified TB-patients between 1998...... followed for max. 12 (span: 0-12) years. Mortality was higher for cases than controls in all age groups, and significantly so for age groups above 20 years, peaking at a Hazard Ratio of 8.7 (95% CI: 5.53;16.69) in the 30-39 years age Conclusion: Cumulative mortality of TB-patients is significantly inferior...... to matched controls. While the difference in survival is substantial among elderly patients, a high relative risk of dying is particularly of concern among young and middle-aged adult TB patients....

  7. Allergen-Specific Immunotherapy in Patients 55 Years and Older: Results and Review of Literature

    Baptistella, Eduardo


    Full Text Available Introduction: Over the years the immune system suffers many morphologic and functional alterations, which result in a peak of function in puberty and a gradual decrease in the elderly. Aim: Treat patients 55 years or older with allergic rhinitis with immunotherapy and then analyze the response to allergens. Materials and Methods: From June 2009 to July 2010, 104 charts of patients 55 years or older with allergic complaints were evaluated. The patients were selected by anamnesis, physical examination, and otorhinolaryngologic exam. The patients had cutaneous test for mites before and after 1 year of sublingual specific immunotherapy. The cutaneous response was classified as negative (absent, light, moderate, or severe. Results: Before vaccination, 42 (40.4% patients were classified as having a severe form of allergy and 62 (59.6% as having a moderate allergy. After the specific therapy, 40 (38.4% patients were classified as negative (absent, 37 (35.6% as light, 19 (18.3% as moderate, and 8 (7.7% as severe responses. Conclusion: Immunotherapy, a desensitization technique, is indicated in cases which patients cannot avoid the exposure to allergens and in situations where pharmacologic therapy is not ideal. Specific immunotherapy to treat the allergic rhinitis in elderly patients was efficient and had no collateral effects, and in addition to the clinical benefit, improvement in the cutaneous test could also be observed.

  8. Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

    Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia


    Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed.

  9. S-100b and neuron-specific enolase in patients with fulminant hepatic failure

    Strauss, Gitte Irene; Christiansen, Michael; Møller, Kirsten


    Patients with fulminant hepatic failure (FHF) frequently develop cerebral edema and intracranial hypertension. The aim of this study was to evaluate circulating S-100b and neuron-specific enolase (NSE) levels as markers of neurological outcome in patients with FHF. In a subgroup of patients......, the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery...... and internal jugular bulb. The net cerebral flux of S-100b and NSE was measured, and the effect of short-term hyperventilation, as well as the effect of high-volume plasmapheresis, on circulating levels of these two biomarkers was determined. Blood levels of S-100b were greater in patients with FHF and AOCLD...

  10. Biotypes of Gardnerella vaginalis isolated from non-specific vaginitis patients in Bombay.

    Pandit, D V; Barve, S M; Deodhar, L P


    The incidence and prevalent biotypes of G. vaginalis in patients with non-specific vaginitis from Bombay, was studied. Of 300 patients screened, 105 were diagnosed to have nonspecific vaginitis (NSV). G. vaginalis was isolated from 71 per cent patients with NSV; 34.6 and 29.3 per cent G. vaginalis were belonging to biotypes 5 and 1 respectively. In 55 per cent patient, G. vaginalis was associated with anaerobes. None of the isolated strains of G. vaginalis was sensitive to 5 micrograms metronidazole disc whereas 93 per cent of the strains were sensitive to 50 micrograms metronidazole disc.

  11. Clinical and prognostic relevance of echocardiographic evaluation of right ventricular geometry in patients with idiopathic pulmonary arterial hypertension.

    Ghio, Stefano; Pazzano, Anna Sara; Klersy, Catherine; Scelsi, Laura; Raineri, Claudia; Camporotondo, Rita; D'Armini, Andrea; Visconti, Luigi Oltrona


    The aim of the present study was to assess the clinical and prognostic significance of right ventricular (RV) dilation and RV hypertrophy at echocardiography in patients with idiopathic pulmonary arterial hypertension. Echocardiography and right heart catheterization were performed in 72 consecutive patients with idiopathic pulmonary arterial hypertension admitted to our institution. The median follow-up period was 38 months. The patients were grouped according to the median value of RV wall thickness (6.6 mm) and the median value of the RV diameter (36.5 mm). On multivariate analysis, the mean pulmonary artery pressure (p = 0.018) was the only independent predictor of RV wall thickness, and age (p = 0.011) and moderate to severe tricuspid regurgitation (p = 0.027) were the independent predictors of RV diameter. During follow-up, 22 patients died. The death rate was greater in the patients with a RV diameter >36.5 mm than in patients with a RV diameter ≤36.5 mm: 15.9 (95% confidence interval 9.4 to 26.8) vs 6.6 (95% confidence interval 3.3 to 13.2) events per 100-person years (p = 0.0442). In contrast, the death rate was similar in patients with RV wall thickness above or below the median value. However, among the patients with a RV wall thickness >6.6 mm, a RV diameter >36 mm was not associated with a poorer prognosis (p = 0.6837). In conclusion, in patients with idiopathic pulmonary arterial hypertension, a larger RV diameter is a marker of a poor prognosis but a greater RV wall thickness reduces the risk of death associated with a dilated right ventricle.

  12. A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference.

    Lombardi, Maria Stella; Jaspers, Leonie; Spronkmans, Christine; Gellera, Cinzia; Taroni, Franco; Di Maria, Emilio; Donato, Stefano Di; Kaemmerer, William F


    Use of RNA interference to reduce huntingtin protein (htt) expression in affected brain regions may provide an effective treatment for Huntington disease (HD), but it remains uncertain whether suppression of both wild-type and mutant alleles in a heterozygous patient will provide more benefit than harm. Previous research has shown suppression of just the mutant allele is achievable using siRNA targeted to regions of HD mRNA containing single nucleotide polymorphisms (SNPs). To determine whether more than a minority of patients may be eligible for an allele-specific therapy, we genotyped DNA from 327 unrelated European Caucasian HD patients at 26 SNP sites in the HD gene. Over 86% of the patients were found to be heterozygous for at least one SNP among those tested. Because the sites are genetically linked, one cannot use the heterozygosity rates of the individual SNPs to predict how many sites (and corresponding allele-specific siRNA) would be needed to provide at least one treatment possibility for this percentage of patients. By computing all combinations, we found that a repertoire of allele-specific siRNA corresponding to seven sites can provide at least one allele-specific siRNA treatment option for 85.6% of our sample. Moreover, we provide evidence that allele-specific siRNA targeting these sites are readily identifiable using a high throughput screening method, and that allele-specific siRNA identified using this method indeed show selective suppression of endogenous mutant htt protein in fibroblast cells from HD patients. Therefore, allele-specific siRNA are not so rare as to be impractical to find and use therapeutically.

  13. [Histamine liberation and specific IgE against Dermatophagoides pteronyssinus in parasitized patients].

    Moneo, I; Puente, S; Subirats, M; Ruiz, A; Lozano, M; González-Muñoz, M


    We studied 98 patients with different parasitosis, without clinical symptoms of mite sensitization, most of them coming from Guinea. Histamine release to Dermatophagoides pteronyssinus was performed using whole blood. Specific IgE to the same antigen was measured by EAST, as well as by an immunodot with the same antigen extract employed for the histamine release test. Finally, the EAST positive sera were studied by immunoblotting. The presence of specific IgE by EAST could be proved in 31 patients, but these antibodies were nor detected by dot, blot and histamine release. On the other hand, only two patients showed a positive histamine release test to D. pteronyssinus and in these two cases the EAST to mites was negative. There was no relation between total IgE levels and specific IgE to mites. The presence of mite-specific IgE showed a significative association to the parasite Trichuris trichiura (odds ratio 3.09). This fact suggest that the specific IgE values found in this population can reflect some cross-reaction between parasites and allergens. It is the author's opinion that the same study should be performed in european patients in order to test the relationship between mite-specific antibodies and the presence of parasites, specially of Trichuris trichiura.

  14. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Hannah K Bayes

    Full Text Available BACKGROUND: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. METHODS: Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. RESULTS: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. CONCLUSIONS: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  15. Patient-specific assessment of hemodynamics by computational fluid dynamics in patients with bicuspid aortopathy.

    Kimura, Naoyuki; Nakamura, Masanori; Komiya, Kenji; Nishi, Satoshi; Yamaguchi, Atsushi; Tanaka, Osamu; Misawa, Yoshio; Adachi, Hideo; Kawahito, Koji


    Hemodynamics related to eccentric blood flow may factor into the development of bicuspid aortic valve aortopathy. We investigated wall shear stress distribution by means of magnetic resonance imaging-based computational fluid dynamics in patients with a bicuspid aortic valve. Included were 12 patients with a bicuspid aortic valve (aortic stenosis, n = 11; root enlargement, n = 1). Three patients with a normal tricuspid aortic valve (arch aneurysm, n = 1; descending aortic aneurysm, n = 2) were included for comparison. The thoracic aorta geometry was reconstructed by means of 3-dimensional computed tomography angiography, and the bicuspid aortic valve orifice was modeled. Flow rates at the sinotubular junction and 3 aortic branches were measured at various time points by cine phase-contrast magnetic resonance imaging to define boundary conditions for computational fluid dynamics, and the flow was simulated. Bicuspid aortic valve cusp configurations were type 0 lateral (n = 4), type 0 anterior-posterior (n = 2), type 1 L-R (n = 4), and type 1 R-N (n = 2). Abnormal aortic helical flow was seen in the ascending aorta and transverse arch in all patients with bicuspid aortic valves and was right handed in 11 patients (91%). No such flow was seen in the patients with tricuspid aortic valves. The patients with bicuspid aortic valves were likely to have jet flow/wall impingement against the greater curvature of the proximal ascending aorta, resulting in remarkably increased wall shear stress around the impingement area. Computational fluid dynamics simulation is useful for precise evaluation of hemodynamics related to bicuspid aortic valve aortopathy. Such evaluation will advance our understanding of the disease pathophysiology and may facilitate molecular biological investigation. Copyright © 2017. Published by Elsevier Inc.

  16. Patient-specific instrumentation does not improve radiographic alignment or clinical outcomes after total knee arthroplasty.

    Huijbregts, Henricus J T A M; Khan, Riaz J K; Sorensen, Emma; Fick, Daniel P; Haebich, Samantha


    Background and purpose - Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA) has been introduced to improve alignment and reduce outliers, increase efficiency, and reduce operation time. In order to improve our understanding of the outcomes of patient-specific instrumentation, we conducted a meta-analysis. Patients and methods - We identified randomized and quasi-randomized controlled trials (RCTs) comparing patient-specific and conventional instrumentation in TKA. Weighted mean differences and risk ratios were determined for radiographic accuracy, operation time, hospital stay, blood loss, number of surgical trays required, and patient-reported outcome measures. Results - 21 RCTs involving 1,587 TKAs were included. Patient-specific instrumentation resulted in slightly more accurate hip-knee-ankle axis (0.3°), coronal femoral alignment (0.3°, femoral flexion (0.9°), tibial slope (0.7°), and femoral component rotation (0.5°). The risk ratio of a coronal plane outlier (> 3° deviation of chosen target) for the tibial component was statistically significantly increased in the PSI group (RR =1.64). No significance was found for other radiographic measures. Operation time, blood loss, and transfusion rate were similar. Hospital stay was significantly shortened, by approximately 8 h, and the number of surgical trays used decreased by 4 in the PSI group. Knee Society scores and Oxford knee scores were similar. Interpretation - Patient-specific instrumentation does not result in clinically meaningful improvement in alignment, fewer outliers, or better early patient-reported outcome measures. Efficiency is improved by reducing the number of trays used, but PSI does not reduce operation time.

  17. The relevance of performing exercise test before starting supervised physical exercise in asymptomatic cardiovascular patients with rheumatic diseases.

    Klemz, Bárbara Nascimento de Carvalho; Reis-Neto, Edgard Torres Dos; Jennings, Fábio; Siqueira, Usmary Sardinha; Klemz, Fábio Kadratz; Pinheiro, Helder Henrique Costa; Sato, Emília Inoue; Natour, Jamil; Szejnfeld, Vera Lúcia; Pinheiro, Marcelo de Medeiros


    To evaluate the impact and risk factors associated with an abnormal exercise test (ET) in systemic inflammatory rheumatic disease (SIRD) patients before commencing supervised physical exercise. A total of 235 SIRD patients were enrolled in three controlled clinical trials, including 103 RA, 42 SLE and 57 AS patients. The control group consisted of 231 healthy, sedentary subjects matched for age, gender and BMI. All performed an ET, according to Bruce's or Ellestad's protocol. Cardiovascular disease risk factors, medications, comorbidities and details of each SIRD were assessed. SIRD patients had a higher percentage of abnormal ETs compared with the control group, especially exercise hypertensive behaviour, higher oxygen consumption, higher resting heart rate and heart rate at the first minute of recovery, and chronotropic incompetence (C-Inc) (P exercise. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:

  18. Characteristics and Clinical Relevance of the Osseous Spur in Patients with Congenital Scoliosis and Split Spinal Cord Malformation.

    Feng, Fan; Shen, Jianxiong; Zhang, Jianguo; Li, Shugang; Yu, Keyi; Tan, Haining


    The natural history of split spinal cord malformation (SCM) is still unclear. Knowledge of the characteristics of the osseous spur and its relationship with the spinal deformity may allow early identification of patients with a higher risk of a neurological deficit and enhance surgical decision-making. Eighty-five consecutive patients with congenital scoliosis and type-I SCM who had undergone surgical treatment at our hospital from May 2000 to December 2013 were identified retrospectively. There were 22 male and 63 female patients with an average age of 13.9 years at the time of surgery. Preoperative clinical and radiographic data were collected to investigate the characteristics of the scoliosis and the osseous spur. Two groups were identified on the basis of whether the patients had intact neurological function (Group A) or a neurological deficit (Group B). There were 52 patients (61%) in Group A (intact neurological function) and 33 patients (39%) in Group B (neurological deficit). There were no significant differences in the demographic distribution, curve magnitude, or length and thickness of the osseous spur between the 2 groups. In Group A, the location of the osseous spur relative to the apex of the major curve was proximal in 13 patients (25%), distal in 28 (54%), and central in 11 (21%). In Group B, the osseous spur was proximal in 7 (21%), distal in 8 (24%), and central in 18 (55%). The 2 groups differed significantly with respect to the location of the osseous spur (chi square = 10.898, p = 0.004). Group-B patients had a higher proportion of patients with kyphotic deformity (42%) than Group A (10%). The ratio of the diameters of the hemicords (concave side divided by convex side) differed significantly between the 2 groups (0.98 for Group A versus 0.89 for Group B, p = 0.030). The neurological status in patients with congenital scoliosis and type-I SCM appears to be closely related to the location of the osseous spur relative to the congenital scoliosis

  19. Clinically relevant RHD-CE genotypes in patients with sickle cell disease and in African Brazilian donors

    Gaspardi, Ane C.; Sippert, Emília A.; de Macedo, Mayra Dorigan; Pellegrino, Jordão; Costa, Fernando F.; Castilho, Lilian


    Background As a consequence of the homology and opposite orientation of RHD and RHCE, numerous gene rearrangements have occurred in Africans and resulted in altered RH alleles that predict partial antigens, contributing to the high rate of Rh alloimmunisation among patients with sickle cell disease (SCD). In this study, we characterised variant RH alleles encoding partial antigens and/or lacking high prevalence antigens in patients with SCD and in African Brazilian donors, in order to support antigen-matched blood for transfusion. Material and methods RH genotypes were determined in 168 DNA samples from SCD patients and 280 DNA samples from African Brazilian donors. Laboratory developed tests, RHD BeadChipTM, RHCE BeadChipTM, cloning and sequencing were used to determine RHD-CE genotypes among patients and African Brazilian blood donors. Results The distributions of RHD and RHCE alleles in donors and patients were similar. We found RHCE variant alleles inherited with altered RHD alleles in 25 out of 168 patients (15%) and in 22 out of 280 (7.8%) African Brazilian donors. The RHD and RHCE allele combinations found in the population studied were: RHD*DAR with RHCE*ceAR; RHD*weak D type 4.2.2 with RHCE*ceAR, RHD*weak D type 4.0 with RHCE*ceVS.01 and RHCE*ceVS.02; RHD*DIIIa with RHCE*ceVS.02. Thirteen patients and six donors had RHD-CE genotypes with homozygous or compound heterozygous alleles predicting partial antigens and/or lacking high prevalence antigens. Eleven patients were alloimmunised to Rh antigens. For six patients with RHD-CE genotypes predicting partial antigens, no donors with similar genotypes were found. Discussion Knowledge of the distribution and prevalence of RH alleles in patients with SCD and donors of African origin may be important for implementing a programme for RH genotype matching in SCD patients with RH variant alleles and clinically significant Rh antibodies. PMID:27177398

  20. Assessment of compliance-relevant indispensable knowledge to cope with epilepsy in epileptic patients in Xi'an

    DENG Yan-chun; XIA Feng; HUANG Yuan-gui; LI Ning-xiu; ZHENG Shu-ping


    Objective: To investigate the knowledge level related to compliance in patients with epilepsy. Methods: Eighty-seven patients with epilepsy were tested in the city of Xi'an with a knowledge questionnaire containing 21 questions related to compliance. Results: Over 39.5% of patients did not know that epilepsy is the result of abnormal firing of neurons, while 29.9% were uncertain or did not realize that epilepsy attacks can bring up accidents such as traffic accidents, drowning and trauma. A total of 36.6% of responders thought that the best therapy for epilepsy could be found in Traditional Chinese Medicine. As many as 36.8% of tested patients were uncertain or did not know that frequent epilepsy attacks can affect their intelligence. Up to 36% were unaware of the possible consequence of sudden withdrawal of anti-epileptic drugs (AED). Among responders, 39.1% did not know the right treatment method of epilepsy. That AED can control seizure attacks were doubted in 57.5% of epileptic patients. Furthermore, 32.2% did not know whether the disease could be cured. Conclusion: In this group of epileptic patients, generally they do not have enough indispensable knowledge to cope with epilepsy. They urgently need for proper health education besides effective AED to control seizure attacks and improve their quality of life.

  1. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Ritch Robert


    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  2. Cerebral microbleeds (CMBs) – relevance for mechanisms of cerebral hemorrhage – analysis of 24 MRI evaluated patients

    Ghelmez, D; Sorin Tuţă, S; Popa, C


    Abstract Introduction. The new MRI techniques introduced in the last decade allowed the detection of cerebral microbleeds (CMBs) in different groups of diseases: stroke, Alzheimer disease, vascular dementia or healthy people of advanced age. CMBs are radiologically defined as small, rounded, homogeneous, hypointense lesions on T2*-weighed gradient-recalled echo (T2*-GRE) sequences. Objective and Method. We evaluated the prevalence, number and location of CBMs in a cohort of 26 consecutive cerebral hemorrhage patients admitted in the National Institute of Neurology and Neurovascular Diseases. We also assessed the association between CMB, classical vascular risk factors and small vessel disease. Results and Conclusions. From the 26 patients, 2 patients had secondary intracerebral hemorrhage (ICH) (hemorrhage in metastasis, respectively a cavernoma). From the 24 ICH patients 12 have had at least 1 CMB lesion. The average volume of the cerebral hemorrhage was larger in patients with CMBs, with a relative increase of 42%. Small vessel disease was associated with a significant increase in the presence of CMBs (relative increase of 86%). In both cases, however, since the number of patients enrolled was small, the correlations did not reach statistical significance. PMID:24868257

  3. {sup 18}F-FDG PET/CT for initial staging in breast cancer patients. Is there a relevant impact on treatment planning compared to conventional staging modalities?

    Krammer, J.; Schnitzer, A.; Kaiser, C.G.; Buesing, K.A.; Schoenberg, S.O.; Wasser, K. [University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Sperk, E. [University of Heidelberg, Department of Radiation Oncology, University Medical Centre Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Brade, J. [University of Heidelberg, Institute of Medical Statistics, Biomathematics and Data Processing, Medical Faculty Mannheim, Mannheim (Germany); Wasgindt, S.; Suetterlin, M. [University of Heidelberg, Department of Gynaecology and Obstetrics, University Medical Centre Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Sutton, E.J. [Memorial Sloan-Kettering Cancer Center, Evelyn H. Lauder Breast Center, Department of Radiology, New York, NY (United States)


    To evaluate the impact of whole-body {sup 18}F-FDG PET/CT on initial staging of breast cancer in comparison to conventional staging modalities. This study included 102 breast cancer patients, 101 patients were eligible for evaluation. Preoperative whole-body staging with PET/CT was performed in patients with clinical stage ≥ T2 tumours or positive local lymph nodes (n = 91). Postoperative PET/CT was performed in patients without these criteria but positive sentinel lymph node biopsy (n = 10). All patients underwent PET/CT and a conventional staging algorithm, which included bone scan, chest X-ray and abdominal ultrasound. PET/CT findings were compared to conventional staging and the impact on therapeutic management was evaluated. PET/CT led to an upgrade of the N or M stage in overall 19 patients (19 %) and newly identified manifestation of breast cancer in two patients (2 %). PET/CT findings caused a change in treatment of 11 patients (11 %). This is within the range of recent studies, all applying conventional inclusion criteria based on the initial T and N status. PET/CT has a relevant impact on initial staging and treatment of breast cancer when compared to conventional modalities. Further studies should assess inclusion criteria beyond the conventional T and N status, e.g. tumour grading and receptor status. (orig.)

  4. Analysis of HBV-specific cytotoxic T lymphocytes in patients with hepatitis B

    Ning DING


    Full Text Available Objective To investigate the expression feature of hepatitis B virus(HBV-specific cytotoxic T lymphocytes(CTL,and analyze the role of CTL in immune response.Methods Peripheral venous blood was collected from 40 acute hepatitis B(AHB patients hospitalized from Oct.2008 to Jun.2010 in 302 Hospital of PLA for the detection of human leucocyte antigen-A2(HLA-A2.Out of the 40 patients,18 were HLA-A2-positive,and their peripheral blood mononuclear cells were isolated at acute phase and convalescent phase if the patients could be contacted.Six HLA-A2-negative AHB patients,18 HLA-A2-positive chronic HB patients and 6 HLA-A2-positive normal persons served as controls.The CTL was stained by fluorescence-labeled anti-CD3 monoclonal antibody,anti-CD8 monoclonal antibody and HBV epitopic pentamers(S183-191,S335-343,and examined with flow cytometry,then analyzed by software Cell-quest.The peak value of alanine aminotransferase(ALT and HBV load was detected at acute phase of patients,and the correlation was analyzed.Results The average frequencies were 0.23%±0.18% for HBsAg183-191-specific CTL and 0.49%±0.31% for HBsAg335-343-specific CTL at the acute phase of the 18 AHB patients,and they were significantly higher than those in patients with chronic HB,in whom CTL frequencies were 0.07%±0.03% for HBsAg183-191-specific CTL and 0.08%±0.04% for HBsAg335-343-specific CTL(P < 0.01.There was no correlation between the frequency of HBsAg183-191-specific CTL and the peak value of ALT(r=0.4506,P=0.0528,while the frequency of HBsAg335-343-specific CTL was correlated with ALT level(r=0.5642,P=0.0119.Neither the two CTL frequencies showed correlation with virus load.Compared with the acute phase,the CTL frequencies obviously decreased at convalescent phase(P=0.011.Both kinds of CTL were not detectable in HLA-A2-negative AHB patients and HLA-A2-positive healthy individuals.Conclusion HBV-specific CTL may play an important role in both virus clearance and liver

  5. Modeling retinal degeneration using patient-specific induced pluripotent stem cells.

    Zi-Bing Jin

    Full Text Available Retinitis pigmentosa (RP is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patient-specific induced pluripotent stem (iPS cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP.

  6. Patient- and Disease-Specific Factors Associated With Operative Management of de Quervain Tendinopathy.

    Kazmers, Nikolas H; Liu, Tiffany C; Gordon, Joshua A; Bozentka, David J; Steinberg, David R; Gray, Benjamin L


    It remains unclear which factors, patient- or disease-specific, are associated with electing to undergo operative management for de Quervain tendinopathy. Our null hypothesis was that no patient- or disease-specific factors would be associated with the choice of surgical treatment of de Quervain tendinopathy. We performed a retrospective review of consecutive patients diagnosed with de Quervain tendinopathy over 3 years by 1 of 3 fellowship-trained hand surgeons at an urban academic institution. Descriptive statistics were calculated for patient baseline and disease-specific characteristics. Cohorts were compared using bivariate analysis for all collected variables. Binary logistic regression with backward stepwise term selection was performed including independent predictors identified by bivariate analysis. A total of 200 patients were identified for inclusion. Bivariate analysis revealed that surgically treated patients were significantly more likely to have Medicaid insurance, psychiatric illness history, and disabled work status. Regression analysis revealed an association between surgical treatment and 2 of the factors evaluated: Medicaid insurance status and psychiatric illness history. Psychiatric illness and Medicaid insurance status are associated with undergoing surgical release of the first dorsal compartment. These findings support the use of a biopsychosocial framework when treating patients with de Quervain tendinopathy. Prognostic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  7. Development and validation of a condition-specific diary to measure severity, bothersomeness and impact on daily activities for patients with acute urinary tract infection in primary care

    Holm, Anne; Cordoba, Gloria; Siersma, Volkert


    Background: Urinary tract infection (UTI) is a common condition in primary care. Patient-reported outcome measures (PROMs) are crucial in the evaluation of interventions to improve diagnosis, treatment and prognosis of UTI. The aim of this study was to identify an existing condition-specific PROM...... to measure symptom severity, bothersomeness and impact on daily activities for adult patients with suspected urinary tract infection in primary care; or, in the absence of such a PROM, to test items identified from existing PROMs for coverage and relevance in single and group interviews...

  8. Development of a patient specific artificial tracheal prosthesis: design, mechanical behavior analysis and manufacturing.

    Chua C H, Matthew; Chui, Chee Kong; Rai, Bina; Lau D P, David


    There is a need to create patient specific organ replacements as there are differences in the anatomical dimensions among individuals. High failure rates in tracheal prosthesis are attributed to the lack of mechanical strength and flexibility, slow rate of growth of ciliated epithelium and leakage of interstitial fluid into the lumen. This paper proposes a methodology of design, simulations and fabrication of a patient specific artificial tracheal prosthesis for implantation to closely mimic the biomechanical properties of the natural trachea, and describes the prototype device and its materials. Results show that the patient-specific trachea prosthesis has mechanical properties approximate that of normal tracheal rings. The user centric tracheal prosthesis is demonstrated to be a promising candidate for tracheal replacement.

  9. Cephalic arch stenosis in dialysis patients: review of clinical relevance, anatomy, current theories on etiology and management.

    Sivananthan, Gajan; Menashe, Leo; Halin, Neil J


    Arteriovenous hemodialysis fistulas (AVFs) serve as a lifeline for many individuals with end-stage renal failure. A common cause of AVF failure is cephalic arch stenosis. Its high prevalence compounded with its resistance to treatment makes cephalic arch stenosis important to understand. Proposed etiologies include altered flow in a fistulized cephalic vein, external compression by fascia, the unique morphology of the cephalic arch, large number of valves in the cephalic outflow tract and biochemical changes that accompany renal failure. Management options are also in debate and include angioplasty, cutting balloon angioplasty, bare metal stents, stent grafts and surgical techniques including flow reduction with minimally invasive banding as well as more invasive venovenostomy with transposition surgeries for refractory cases. In this review, the evidence for the clinical relevance of cephalic arch stenosis, its etiology and management are summarized.

  10. Comparing the abuse potential of methylphenidate versus other stimulants: a review of available evidence and relevance to the ADHD patient.

    Kollins, Scott H


    The use of psychostimulants to treat attention-deficit/hyperactivity disorder (ADHD) has been controversial for a number of reasons. In an effort to clarify the extent to which the psychostimulant methylphenidate has abuse potential, the existing published evidence has been reviewed and is summarized here, with an emphasis on delineating a number of related but independent issues that are often confused. Methylphenidate produces behavioral effects associated with abuse potential as assessed by traditional assays, but the relevance of this literature to the clinical use of the drug in the treatment of ADHD is ambiguous at best. Existing neuropharmacologic data suggest that methylphenidate has pharmacokinetic properties that reduce its abuse potential as compared with other stimulant drugs of abuse, such as cocaine.

  11. Closeness and distance in the nurse-patient relation. The relevance of Edith Stein's concept of empathy.

    Määttä, Sylvia M


    This paper emanates from the concept of empathy as understood by the German philosopher Edith Stein. It begins by highlighting different interpretations of empathy. According to the German philosopher Martin Buber, empathy cannot be achieved as an act of will. In contrast, the psychologist Carl Rogers believes that empathy is identical with dialogue and is the outcome of a cognitive act of active listening. The empathy concept of Edith Stein, philosopher and follower of Edmund Husserl's phenomenology, goes beyond these conflicting views and offers a more complex interpretation, with relevance for both healthcare and nursing education. When studying Stein's three-level model of empathy, a field of tension between perspectives of closeness and distance becomes apparent. The paper concludes by suggesting Stein's model of empathy as a strategy to overcome the tension and meet the demands of empathy.

  12. The relevance of specific c-reactive protein genetic variants towards cardiovascular disease risk in a black South African population undergoing an epidemiological transition / Bianca Swanepoel.

    Swanepoel, Bianca


    Introduction: In Africa, it is estimated that cardiovascular disease (CVD) will affect approximately 1.3 million people per annum over the following 20 years. C-reactive protein (CRP) is a predictor of CVD risk and certain CRP gene polymorphisms can result in altered CRP concentrations. The distribution of CRP gene polymorphisms is ethnic-specific and extrapolating information from other populations to the black South African population, reported to harbour considerable genetic variation, sho...

  13. Factors associated with functional capacity test results in patients with non-specific chronic low back pain: a systematic review.

    van Abbema, Renske; Lakke, Sandra E; Reneman, Michiel F; van der Schans, Cees P; van Haastert, Corrien J M; Geertzen, Jan H B; Wittink, Harriët


    Functional capacity tests are standardized instruments to evaluate patients' capacities to execute work-related activities. Functional capacity test results are associated with biopsychosocial factors, making it unclear what is being measured in capacity testing. An overview of these factors was missing. The objective of this review was to investigate the level of evidence for factors that are associated with functional capacity test results in patients with non-specific chronic low back pain. A systematic literature review was performed identifying relevant studies from an electronic journal databases search. Candidate studies employed a cross-sectional or RCT design and were published between 1980 and October 2010. The quality of these studies was determined and level of evidence was reported for factors that were associated with capacity results in at least 3 studies. Twenty-two studies were included. The level of evidence was reported for lifting low, lifting high, carrying, and static lifting capacity. Lifting low test results were associated with self-reported disability and specific self-efficacy but not with pain duration. There was conflicting evidence for associations of lifting low with pain intensity, fear of movement/(re)injury, depression, gender and age. Lifting high was associated with gender and specific self-efficacy, but not with pain intensity or age. There is conflicting evidence for the association of lifting high with the factors self-reported disability, pain duration and depression. Carrying was associated with self-reported disability and not with pain intensity and there is conflicting evidence for associations with specific self-efficacy, gender and age. Static lifting was associated with fear of movement/(re)injury. Much heterogeneity was observed in investigated capacity tests and candidate associated factors. There was some evidence for biological and psychological factors that are or are not associated with capacity results but there

  14. A polynomial model of patient-specific breathing effort during controlled mechanical ventilation.

    Redmond, Daniel P; Docherty, Paul D; Yeong Shiong Chiew; Chase, J Geoffrey


    Patient breathing efforts occurring during controlled ventilation causes perturbations in pressure data, which cause erroneous parameter estimation in conventional models of respiratory mechanics. A polynomial model of patient effort can be used to capture breath-specific effort and underlying lung condition. An iterative multiple linear regression is used to identify the model in clinical volume controlled data. The polynomial model has lower fitting error and more stable estimates of respiratory elastance and resistance in the presence of patient effort than the conventional single compartment model. However, the polynomial model can converge to poor parameter estimation when patient efforts occur very early in the breath, or for long duration. The model of patient effort can provide clinical benefits by providing accurate respiratory mechanics estimation and monitoring of breath-to-breath patient effort, which can be used by clinicians to guide treatment.

  15. Relevance of radiological and clinical measurements in predicting difficult intubation using light wand (Surch-lite™) in adult patients.

    Kim, Joungmin; Im, Kyong Shil; Lee, Jae Myeong; Ro, Jaehun; Yoo, Kyung Yeon; Kim, Jong Bun


    To determine the correlation between anatomical features of the upper airway (evaluated via computed tomography imaging) and the ease of light wand-assisted endotracheal intubation in patients undergoing ear, nose and throat surgery under general anaesthesia. Mallampati class, laryngoscopic grade, thyromental distance, neck circumference, body mass index, mouth opening and upper lip bite class were assessed. Epiglottis length and angle, tongue size and narrowest pharyngeal distance were determined using computed tomography imaging. Intubation success rate, time to successful intubation (intubating time) and postoperative throat symptoms were documented. Of 152 patients, 148 (97.4%) were successfully intubated on the first attempt (mean intubating time 11.5 ± 6.7 s). Intubating time was positively correlated with laryngoscopic grade and body mass index in both male and female patients, and Mallampati class and neck circumference in male patients. Epiglottis length was positively correlated with intubating time. Ease of intubation was influenced by epiglottis length. Radiological evaluation may be useful for preoperative assessment of patients undergoing endotracheal intubation with light wand. © The Author(s) 2015.

  16. Microbial profile comparisons of saliva, pooled and site-specific subgingival samples in periodontitis patients

    Belstrøm, Daniel; Sembler-Møller, Maria Lynn; Grande, Maria Anastasia


    OBJECTIVES: The purpose of this study was to compare microbial profiles of saliva, pooled and site-specific subgingival samples in patients with periodontitis. We tested the hypotheses that saliva can be an alternative to pooled subgingival samples, when screening for presence of periopathogens....... DESIGN: Site specific subgingival plaque samples (n = 54), pooled subgingival plaque samples (n = 18) and stimulated saliva samples (n = 18) were collected from 18 patients with generalized chronic periodontitis. Subgingival and salivary microbiotas were characterized by means of HOMINGS (Human Oral...... to an AUC of 0.76 (sensitivity: 0.56, specificity: 0.94) in pooled subgingival samples. CONCLUSIONS: Site-specific presence of periodontal pathogens was detected with comparable accuracy in stimulated saliva samples and pooled subgingival plaque samples. Consequently, saliva may be a reasonable surrogate...

  17. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J


    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  18. Computational biomechanics for medicine fundamental science and patient-specific applications

    Miller, Karol; Wittek, Adam; Nielsen, Poul


    One of the greatest challenges facing the computational engineering community is to extend the success of computational mechanics to fields outside traditional engineering, in particular to biology, the biomedical sciences, and medicine. The Computational Biomechanics for Medicine titles provide an opportunity for specialists in computational biomechanics to present their latest methodologies and advancements. This latest installment comprises nine of the latest developments in both fundamental science and patient-specific applications, from researchers in Australia, New Zealand, USA, UK, France, Ireland, and China. Some of the interesting topics discussed are: cellular mechanics; tumor growth and modeling; medical image analysis; and both patient-specific fluid dynamics and solid mechanics simulations.

  19. The clinical-immunological analysis of a specific and combined immunotherapy of patients with cervical cancer

    D. K. Kenbayeva


    Full Text Available Research objective is the comparative assessment of efficiency of two various ways of an immunotherapy of patients with cervical cancer. 57 patients with cervical cancer, the III stages, distributed on 3 groups – combined radiotherapy, a combination of a radiotherapy and specific immunotherapy, and also a radiotherapy, specific and adaptive immunotherapy are surveyed. Clinical efficiency of treatment was estimated by means of primary tumor regression and 3-year survival rate. The scheme of combined immunotherapy was shown to possess the most clinical efficiency. Positive dynamics of cell immunity indicators was accompanied to clinical efficiency of treatment.

  20. Mesh structure-independent modeling of patient-specific atrial fiber orientation

    Wachter Andreas


    Full Text Available The fiber orientation in the atria has a significant contribution to the electrophysiologic behavior of the heart and to the genesis of arrhythmia. Atrial fiber orientation has a direct effect on excitation propagation, activation patterns and the P-wave. We present a rule-based algorithm that works robustly on different volumetric meshes composed of either isotropic hexahedra or arbitrary tetrahedra as well as on 3-dimensional triangular surface meshes in patient-specific geometric models. This method fosters the understanding of general proarrhythmic mechanisms and enhances patient-specific modeling approaches.

  1. Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome – Is There a Clinical Relevance?

    Manousek, Jan; Stejskal, Vera; Kubena, Petr; Jarkovsky, Jiri; Nemec, Petr; Lokaj, Petr; Dostalova, Ludmila; Zadakova, Andrea; Pavlusova, Marie; Benesova, Klara; Kala, Petr; Miklik, Roman; Spinar, Jindrich; Parenica, Jiri


    Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients. PMID:27824862

  2. [Establishment of hemophilia A patient-specific inducible pluripotent stem cells with urine cells].

    Hu, Zhiqing; Hu, Xuyun; Pang, Jialun; Wang, Xiaolin; Lin Peng, Siyuan; Li, Zhuo; Wu, Yong; Wu, Lingqian; Liang, Desheng


    OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.

  3. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

    Sebastian Kobold


    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  4. Patient Specification Quality Assurance for Glioblastoma Multiforme Brain Tumors Treated with Intensity Modulated Radiation Therapy

    Al-Mohammed, H. I.


    The aim of this study was to evaluate the significance of performing patient specification quality assurance for patients diagnosed with glioblastoma multiforme treated with intensity modulated radiation therapy. The study evaluated ten intensity modulated radiation therapy treatment plans using 10 MV beams, a total dose of 60 Gy (2 Gy/fraction, five fractions a week for a total of six weeks treatment). For the quality assurance protocol we used a two-dimensional ionization-chamber array (2D-...

  5. Elucidating the immunological effects of 5-azacytidine treatment in patients with myelodysplastic syndrome and identifying new conditional ligands and T-cell epitopes of relevance in melanoma

    Frøsig, Thomas Mørch


    This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery...... frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory...... describe Nodal as a new immunological antigen found of relevance in melanoma patients. In Paper III we wanted to investigate if the hypomethylating drug 5-azactytidine (Vidaza, Celgene Inc.) modulates the immune system in patients with myeloproliferative diseases. It has previ-ously been shown that 5...

  6. Correlations Between Allergen-Specific IgE Serum Levels in Patients With Ocular Allergy.

    Polido, Júlia Gomes Fernandes; Cabral, Thiago; Perini, Paula de Resende Campos; Fernandes, Maria de Fátima Marcelos; de Freitas, Denise; dos Santos Araújo, Maria Emília Xavier; Serracarbassa, Pedro Durães


    To evaluate ocular allergies in patients at the Hospital do Servidor Publico Estadual de Sao Paulo (HSPE) and the correlations with serum allergen-specific immunoglobulin E levels. We performed a longitudinal study of patients with ocular allergies who were treated at the Cornea and Immunology and Allergy Department. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 4 groups. We conducted the following laboratory tests and measurements: blood count, eosinophil count, total serum IgE, and specific IgE. Among 61 patients, 16 (26.2%) had a clinical diagnosis of seasonal allergic conjunctivitis, 23 (37.7%) had perennial allergic conjunctivitis, 19 (31.1%) had vernal keratoconjunctivitis, and 3 (4.9%) had atopic keratoconjunctivitis. Mixed dust mites were positive in 94.9% of patients. Dermatophagoides pteronyssinus (dp) and Dermatophagoides farinae (df) antigens were positive in 93.2% of patients followed by Blattella germanica, Blomia tropicalis, and mixed animal epithelia (81%, 75.9%, and 25.8%, respectively). Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.

  7. Domain-specific cognitive impairment in patients with COPD and control subjects

    Cleutjens, Fiona AHM; Franssen, Frits ME; Spruit, Martijn A; Vanfleteren, Lowie EGW; Gijsen, Candy; Dijkstra, Jeanette B; Ponds, Rudolf WHM; Wouters, Emiel FM; Janssen, Daisy JA


    Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. PMID:28031706

  8. Copy number variants in a sample of patients with psychotic disorders: is standard screening relevant for actual clinical practice?

    Van de Kerkhof, Noortje WA; Feenstra, Ilse; van der Heijden, Frank MMA; de Leeuw, Nicole; Pfundt, Rolph; Stöber, Gerald; Egger, Jos IM; Verhoeven, Willem MA


    With the introduction of new genetic techniques such as genome-wide array comparative genomic hybridization, studies on the putative genetic etiology of schizophrenia have focused on the detection of copy number variants (CNVs), ie, microdeletions and/or microduplications, that are estimated to be present in up to 3% of patients with schizophrenia. In this study, out of a sample of 100 patients with psychotic disorders, 80 were investigated by array for the presence of CNVs. The assessment of the severity of psychiatric symptoms was performed using standardized instruments and ICD-10 was applied for diagnostic classification. In three patients, a submicroscopic CNV was demonstrated, one with a loss in 1q21.1 and two with a gain in 1p13.3 and 7q11.2, respectively. The association between these or other CNVs and schizophrenia or schizophrenia-like psychoses and their clinical implications still remain equivocal. While the CNV affected genes may enhance the vulnerability for psychiatric disorders via effects on neuronal architecture, these insights have not resulted in major changes in clinical practice as yet. Therefore, genome-wide array analysis should presently be restricted to those patients in whom psychotic symptoms are paired with other signs, particularly dysmorphisms and intellectual impairment. PMID:22848183

  9. [The relevance and prospects of introducing a uniform federal register of patients with viral hepatitis B and C in Russia].

    Pimenov, N N; Vdovin, A V; Komarova, S V; Mamonova, N A; Chulanov, V P; Pokrovskiĭ, V I


    The article provides the current epidemiological characteristics of viral hepatitis B and C and the existing problems of registering parenteral viral hepatitides in Russia. It justifies the need for introducing a uniform federal registry of patients with viral hepatitis B and C and shows prospects for its introduction.

  10. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    Viehoff, P.B.; Potijk, F.; Damstra, R.J.; Heerkens, Y.F.; Ravensberg, C.D. van; Berkel, D.M. van; Neumann, H.A.


    BACKGROUND: To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema. METHODS: Cross-s

  11. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    P.B. Viehoff (Peter); F. Potijk; R.J. Damstra (Robert); Y.F. Heerkens (Yvonne); C.D. van Ravensberg (Dorine); D.M. Van Berkel; H.A.M. Neumann (Martino)


    textabstractBackground. To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema.Metho

  12. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    Viehoff, P.B.; Potijk, F.; Damstra, R.J.; Heerkens, Y.F.; Ravensberg, C.D. van; Berkel, D.M. van; Neumann, H.A.


    BACKGROUND: To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for lymphedema. METHODS:

  13. Identification of relevant ICF (International Classification of Functioning, Disability and Health) categories in lymphedema patients: A cross-sectional study

    P.B. Viehoff (Peter); F. Potijk; R.J. Damstra (Robert); Y.F. Heerkens (Yvonne); C.D. van Ravensberg (Dorine); D.M. Van Berkel; H.A.M. Neumann (Martino)


    textabstractBackground. To describe functioning and health of lymphedema patients and to identify their most common problems using the International Classification of Functioning, Disability and Health (ICF) as part of the preparatory studies for the development of ICF Core Sets for

  14. ICF Core Set for Head and Neck Cancer: Do the Categories Discriminate Among Clinically Relevant Subgroups of Patients?

    Tschiesner, Uta; Oberhauser, Cornelia; Cieza, Alarcos


    The multidisciplinary assessment of functioning in patients with head and neck cancer (HNC) according to the "ICF Core Set for Head and Neck Cancer" (ICF-HNC) was developed in an international and multi-disciplinary approach. The ICF-HNC is an application of the ICF that was adopted by the World Health Organization. The objective of this study was…

  15. The relevance of uniform reporting in oral leukoplakia: definition, certainty factor and staging based on experience with 275 patients.

    Brouns, Elisabeth-R E A; Baart, Jacques-A; Bloemena, Elisabeth; Karagozoglu, Hakki; van der Waal, Isaäc


    The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be established. In the period 1997-2012 a hospital-based population of 275 consecutive patients with a provisional diagnosis of oral leukoplakia has been examined. In only 176 patients of these 275 patients a firm diagnosis of leukoplakia has been established based on strict clinicopathological criteria. The 176 patients have subsequently been staged using a classification and staging system based on size and histopathologic features. For use in epidemiological studies it seems acceptable to accept a diagnosis of leukoplakia based on a single oral examination (Certainty level 1). For studies on management and malignant transformation rate the recommendation is made to include the requirement of histopathologic examination of an incisional or excisional biopsy, representing Certainty level 3 and 4, respectively. This recommendation results in the following definition of oral leukoplakia: "A predominantly white lesion or plaque of questionable behaviour having excluded, clinically and histopathologically, any other definable white disease or disorder". Furthermore, we recommend the use of strict diagnostic criteria for predominantly white lesions for which a causative factor has been identified, e.g. smokers' lesion, frictional lesion and dental restoration associated lesion.

  16. Changes across Three Editions of "The Suicidal Patient: Clinical and Legal Standards of Care": Relevance to Counseling Centers

    Polychronis, Paul D.


    Treating suicidality is one of the most challenging situations managed by college and university counseling centers. The first edition of Bongar's (1991) "The Suicidal Patient: Clinical and Legal Standards of Care," a compendium of empirical knowledge and clinical research regarding standard of care in the treatment of suicidality, was…

  17. Structural characterization of mouse neutrophil serine proteases and identification of their substrate specificities: relevance to mouse models of human inflammatory diseases.

    Kalupov, Timofey; Brillard-Bourdet, Michèle; Dadé, Sébastien; Serrano, Hélène; Wartelle, Julien; Guyot, Nicolas; Juliano, Luiz; Moreau, Thierry; Belaaouaj, Azzaq; Gauthier, Francis


    It is widely accepted that neutrophil serine proteases (NSPs) play a critical role in neutrophil-associated lung inflammatory and tissue-destructive diseases. To investigate NSP pathogenic role(s), various mouse experimental models have been developed that mimic acutely or chronically injured human lungs. We and others are using mouse exposure to cigarette smoke as a model for chronic obstructive pulmonary disease with or without exacerbation. However, the relative contribution of NSPs to lung disease processes as well as their underlying mechanisms remains still poorly understood. And the lack of purified mouse NSPs and their specific substrates have hampered advances in these studies. In this work, we compared mouse and human NSPs and generated three-dimensional models of murine NSPs based on three-dimensional structures of their human homologs. Analyses of these models provided compelling evidence that peptide substrate specificities of human and mouse NSPs are different despite their conserved cleft and close structural resemblance. These studies allowed us to synthesize for the first time novel sensitive fluorescence resonance energy transfer substrates for individual mouse NSPs. Our findings and the newly identified substrates should better our understanding about the role of NSPs in the pathogenesis of cigarette-associated chronic obstructive pulmonary disease as well as other neutrophils-associated inflammatory diseases.

  18. Health-related quality of life in Huntington's disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington's disease health-related quality of life questionnaire (HDQoL).

    Hocaoglu, Mevhibe B; Gaffan, E A; Ho, Aileen K


    Huntington's disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient-proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient-proxy pairs completed the Huntington's disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy-patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies' ratings were at a similar level to patients' self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients' self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient's disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients' self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient-proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report.

  19. Making inpatient medication reconciliation patient centered, clinically relevant and implementable: a consensus statement on key principles and necessary first steps.

    Greenwald, Jeffrey L; Halasyamani, Lakshmi; Greene, Jan; LaCivita, Cynthia; Stucky, Erin; Benjamin, Bona; Reid, William; Griffin, Frances A; Vaida, Allen J; Williams, Mark V


    Medication errors and adverse events caused by them are common during and after a hospitalization. The impact of these events on patient welfare and the financial burden, both to the patient and the healthcare system, are significant. In 2005, The Joint Commission put forth medication reconciliation as National Patient Safety Goal (NPSG) No. 8 in an effort to minimize adverse events caused during these types of care transitions. However, the meaningful and systematic implementation of medication reconciliation, as expressed through NPSG No. 8, proved to be extraordinarily difficult for healthcare institutions around the country. Given the importance of accurate and complete medication reconciliation for patient safety occurring across the continuum of care, the Society of Hospital Medicine convened a stakeholder conference in 2009 to begin to identify and address: (1) barriers to implementation; (2) opportunities to identify best practices surrounding medication reconciliation; (3) the role of partnerships among traditional healthcare sites and nonclinical and other community-based organizations; and (4) metrics for measuring the processes involved in medication reconciliation and their impact on preventing harm to patients. The focus of the conference was oriented toward medication reconciliation for a hospitalized patient population; however, many of the themes and concepts derived would also apply to other care settings. This paper highlights the key domains needing to be addressed and suggests first steps toward doing so. An overarching principle derived at the conference is that medication reconciliation should not be viewed as an accreditation function. It must, first and foremost, be recognized as an important element of patient safety. From this principle, the participants identified ten key areas requiring further attention in order to move medication reconciliation toward this focus. 1 There is need for a uniformly acceptable and accepted definition of

  20. Effectiveness of Specific Sublingual Immunotherapy in Korean Patients with Atopic Dermatitis

    You, Hyang-Suk; Yang, Min-Young; Kim, Gun-Wook; Cho, Hyun-Ho; Kim, Won-Jeong; Mun, Je-Ho; Song, Margaret; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum


    Background Sublingual immunotherapy (SLIT) with house dust mites (HDM) preparation has recently been proven to be beneficial for treating allergic rhinitis and asthma. However, there has been no report regarding the efficacy and safety of SLIT in Korean patients with atopic dermatitis (AD). Objective We intended to investigate the efficacy and safety of SLIT in Korean patients with AD. Methods A total of 34 patients with AD and immunoglobulin E (IgE)-proven HDM sensitization (Class ≥3) were recruited. Eczema area and severity index (EASI) score, total serum IgE level, specific IgE assays to Dermatophagoides pteronyssinus, D. farinae, and adverse effects were recorded during follow-up. "Responder" was defined as a patient with ≥30% improvement in EASI score after SLIT. Results Twenty-three patients continued SLIT for 12 months or more, whereas 3 patients (8.8%) dropped out because of exacerbation of dermatitis, and 8 patients (23.5%) were lost to follow-up. The average duration of SLIT treatment was 22.4 months (range, 12~32 months). EASI scores reduced significantly after 6 months of treatment (p<0.05) compared with those at baseline. A total of 18 patients were determined to be responders to SLIT after 6 months. Total and specific IgE serum levels did not significantly reduce after SLIT. No patients experienced serious adverse events, with the exception of two patients who developed transient lip and tongue swelling. Conclusion Our study demonstrated that SLIT with HDM extracts is effective and tolerable in Korean patients with AD. Further controlled long-term trials are required to reinforce the current results. PMID:28223739

  1. Assessment of CT dose to the fetus and pregnant female patient using patient-specific computational models.

    Xie, Tianwu; Poletti, Pierre-Alexandre; Platon, Alexandra; Becker, Christoph D; Zaidi, Habib


    This work provides detailed estimates of the foetal dose from diagnostic CT imaging of pregnant patients to enable the assessment of the diagnostic benefits considering the associated radiation risks. To produce realistic biological and physical representations of pregnant patients and the embedded foetus, we developed a methodology for construction of patient-specific voxel-based computational phantoms based on existing standardised hybrid computational pregnant female phantoms. We estimated the maternal absorbed dose and foetal organ dose for 30 pregnant patients referred to the emergency unit of Geneva University Hospital for abdominal CT scans. The effective dose to the mother varied from 1.1 mSv to 2.0 mSv with an average of 1.6 mSv, while commercial dose-tracking software reported an average effective dose of 1.9 mSv (range 1.7-2.3 mSv). The foetal dose normalised to CTDIvol varies between 0.85 and 1.63 with an average of 1.17. The methodology for construction of personalised computational models can be exploited to estimate the patient-specific radiation dose from CT imaging procedures. Likewise, the dosimetric data can be used for assessment of the radiation risks to pregnant patients and the foetus from various CT scanning protocols, thus guiding the decision-making process. • In CT examinations, the absorbed dose is non-uniformly distributed within foetal organs. • This work reports, for the first time, estimates of foetal organ-level dose. • The foetal brain and skeleton doses present significant correlation with gestational age. • The conceptus dose normalised to CTDI vol varies between 0.85 and 1.63. • The developed methodology is adequate for patient-specific CT radiation dosimetry.

  2. Feasibility study of patient-specific quality assurance system for high-dose-rate brachytherapy in patients with cervical cancer

    Lee, Boram; Ahn, Sung Hwan; Kim, Hyeyoung; Han, Youngyih; Huh, Seung Jae; Kim, Jin Sung; Kim, Dong Wook; Sim, Jina; Yoon, Myonggeun


    This study was conducted for the purpose of establishing a quality-assurance (QA) system for brachytherapy that can ensure patient-specific QA by enhancing dosimetric accuracy for the patient's therapy plan. To measure the point-absorbed dose and the 2D dose distribution for the patient's therapy plan, we fabricated a solid phantom that allowed for the insertion of an applicator for patient-specific QA and used an ion chamber and a film as measuring devices. The patient treatment plan was exported to the QA dose-calculation software, which calculated the time weight of dwell position stored in the plan DICOM (Digital Imaging and Communications in Medicine) file to obtain an overall beam quality correction factor, and that correction was applied to the dose calculations. Experiments were conducted after importing the patient's treatment planning source data for the fabricated phantom and inserting the applicator, ion chamber, and film into the phantom. On completion of dose delivery, the doses to the ion chamber and film were checked against the corresponding treatment plan to evaluate the dosimetric accuracy. For experimental purposes, five treatment plans were randomly selected. The beam quality correction factors for ovoid and tandem brachytherapy applicators were found to be 1.15 and 1.10 - 1.12, respectively. The beam quality correction factor in tandem fluctuated by approximately 2%, depending on the changes in the dwell position. The doses measured by using the ion chamber showed differences ranging from -2.4% to 0.6%, compared to the planned doses. As for the film, the passing rate was 90% or higher when assessed using a gamma value of the local dose difference of 3% and a distance to agreement of 3 mm. The results show that the self-fabricated phantom was suitable for QA in clinical settings. The proposed patient-specific QA for the treatment planning is expected to contribute to reduce dosimetric errors in brachytherapy and, thus, to enhancing treatment

  3. Disentangling breast cancer patients' perceptions and experiences with regard to endocrine therapy: nature and relevance for non-adherence.

    Wouters, Hans; van Geffen, Erica C G; Baas-Thijssen, Monique C; Krol-Warmerdam, Elly M; Stiggelbout, Anne M; Belitser, Svetlana; Bouvy, Marcel L; van Dijk, Liset


    Adjuvant endocrine therapy effectively prevents recurrence and progression of estrogen-receptor positive breast cancer. However, studies reveal substantial non-adherence. The objective was therefore to identify the nature of the experiences and beliefs of women treated with endocrine therapy in an attempt to find potential determinants of non-adherence. Online Focus Groups (OFGs) and individual interviews were conducted with 37 women who were treated with endocrine therapy. Sixty-three statements derived from the OFGs and 11 belief items from the Beliefs about Medicines Questionnaire (BMQ) were used in a Q-sorting task conducted with 14 of the women. The quantitative Q-sorting data were statistically analyzed with Hierarchical Cluster Analysis. A six cluster solution was revealed that included the clusters 'information', 'efficacy', 'tenacity', 'coping', 'side effects' and 'usage'. Women's own experiences and perceptions were not clearly delineated from the beliefs measured with the BMQ. However, women judged their own experiences and perceptions with regard to endocrine therapy as more relevant for adherence than the BMQ beliefs. In order to understand and to improve women's adherence to endocrine therapy, women's own perceptions and experiences about endocrine therapy should be targeted in addition to common beliefs that apply to a wide range of medicines. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Patient-specific independent 3D GammaPlan quality assurance for Gamma Knife Perfexion radiosurgery.

    Mamalui-Hunter, Maria; Yaddanapudi, Sridhar; Zhao, Tianyu; Mutic, Sasa; Low, Daniel A; Drzymala, Robert E


    One of the most important aspects of quality assurance (QA) in radiation therapy is redundancy of patient treatment dose calculation. This work is focused on the patient-specific time and 3D dose treatment plan verification for stereotactic radiosurgery using Leksell Gamma Knife Perfexion (LGK PFX). The virtual model of LGK PFX was developed in MATLAB, based on the physical dimensions provided by the manufacturer. The ring-specific linear attenuation coefficients (LAC) and output factors (OFs) reported by the manufacturer were replaced by the measurement-based collimator size-specific OFs and a single LAC = 0.0065 mm-1. Calculation depths for each LGK PFX shot were obtained by ray-tracing technique, and the dose calculation formalism was similar to the one used by GammaPlan treatment planning software versions 8 and 9. The architecture of the QA process was based on the in-house online database search of the LGK PFX database search for plan-specific information. A series of QA phantom plans was examined to verify geometric and dosimetric accuracy of the software. The accuracy of the QA process was further evaluated through evaluation of a series of patient plans. The shot time/focus point dose verification for each shot took less than 1 sec/shot with full 3D isodose verification taking about 30 sec/shot on a desktop PC. GammaPlan database access time took less than 0.05 sec. The geometric accuracy (location of the point of maximum dose) of the phantom and patient plan was dependent on the resolution of the original dose matrix and was of the order of 1 dose element. Dosimetric accuracy of the independently calculated phantom and patient point (focus) doses was within 3.5% from the GammaPlan, with the mean = 2.3% and SD= 1.1%. The process for independent pretreatment patient-specific Gamma Knife Perfexion time and dose verification was created and validated.

  5. Evaluation of ocular defects and its relevant factors in patients with beta thalassemia major in Sari Boo Ali Sina hospital, (2006-2008

    hosein Karami


    Full Text Available Background: As There is not accurate information about ocular defects in Thalassemia Major (TM patients in Mazandaran province ,this study was designed to assess the prevalence of ophtalmopathies in thalassemic patients and also recognize its relevant factors in Sari Boo Ali Sina hospital. Sari. Materials and Methods: This descriptive Cross-sectional was Carried out on 60 TM patients in Thalassemia center at Sari Boo Ali Sina hospital. Subjects were selected by systematic sampling. After gathering demographic data , patients were evaluated about their illness and its complications from their medical records. Their visual acuity was assessed using Snell chart by an optometrist. Evaluation of retina was done by our ophthalmologist colleague. Visual evoked potential (VEP was assessed by TOENEES instrument made in Italy which had the ability to assess both VEP and P300 . Findings were analyzed by SPSS13 software and Chi square and Mann-whitney tests. Results: 60 patients underwen this study that 33 of them (55% were male. 4 of them (6.6% had problems in visual acuity . 3 of these became normal after refractive correction. 3 patients (5% had Inferior Posterior Cortical Cataract. 2 of them (3.3% had punctuate lens cortical opacity and one (1.7% had mild nuclear sclerosis. 4 patients( 6.7% had macular pigmentation and one (1.7% had left optic nerve head pit. No abnormal finding was detected in VEP, such as latency in voltage. Conclusion: Totally 20 patients had ocular complications. These defects can be a result of desferal toxicity or Iron toxicity and drug effects on binding to cupper and zinc and removing them from retinal cells or extramedulary hematopoesis. So based on the results, ophthalmologic evaluation of TM patients and tight desferal dose adjustment in these patients seems necessary.

  6. Are specific antiretrovirals associated with an increased risk of discontinuation due to toxicities or patient/physician choice in patients with hepatitis C virus coinfection?

    Mocroft, A; Rockstroh, J; Soriano, V


    clinical trials as patients with HCV are often excluded. AIMS: To compare incidence rates of discontinuation due to TOXPC associated with specific antiretrovial drugs in patients with or without HCV. PATIENTS/METHODS: A total of 4929 patients from EuroSIDA under follow-up from January 1999 on a specific...

  7. Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

    Kathleen M. Keefe


    Full Text Available Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI. We focus on nerve growth factor (NGF, brain derived neurotrophic factor (BDNF, and neurotrophin-3 (NT-3, and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

  8. Sensitivity and specificity of the Distress Thermometer for depression in newly diagnosed breast cancer patients.

    Hegel, Mark T; Collins, E Dale; Kearing, Stephen; Gillock, Karen L; Moore, Caroline P; Ahles, Tim A


    Receiving a new diagnosis of breast cancer is a distressing experience that may precipitate an episode of major depressive disorder. Efficient screening methods for detecting depression in the oncology setting are needed. This study evaluated the receiver operating characteristics (ROC) of the single-item Distress Thermometer (DT) for detecting depression in women newly diagnosed with Stage I-III breast cancer. We assessed 321 patients (of 345 consecutive patients) at the time of their pre-surgical consultation at a Comprehensive Breast Cancer Program. Patients were administered the DT along with the Patient Health Questionnaire 9-Item Depression Module (PHQ-9) as a gold standard diagnostic assessment of depression status. Mean DT scores (11-point scale, 0-10) were significantly higher for depressed versus non-depressed patients (8.1 versus 4.4). In ROC analyses the DT showed strong discriminatory power relative to the PHQ-9-derived diagnosis of depression, with an area under the curve of 0.87. Patient age, education, marital status and stage of disease resulted in similar operating characteristics. A score of 7 represented the optimal trade-off between sensitivity (0.81) and specificity (0.85) characteristics for detecting depression. The single-item DT performs satisfactorily relative to the PHQ-9 for detecting depression in newly diagnosed breast cancer patients. A cutoff score of 7 on the DT possesses the optimal sensitivity and specificity characteristics. The strength of these findings suggests that a careful psychosocial evaluation should follow a positive screen.

  9. Relevance of weight in the management of patients with type 2 diabetes mellitus: towards an adipocentric approach to diabetes.

    Gorgojo Martínez, Juan José


    In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia. Intensive intervention on lifestyle induces an overall benefit in patients with T2DM, but long-term weight loss is modest and has not been shown to reduce CV morbidity and mortality. The emergence of new therapeutic classes for T2DM and obesity, which simultaneously improve HbA1c, weight and other CV risk factors without inducing hypoglycaemia, represents a major change in the management of patients with diabesity. A sodium-glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been shown to decrease CV and total mortality in type 2 diabetic patients with CV disease. Furthermore, bariatric surgery rapidly induces remission or improvement of T2DM in a large percentage of patients and reduces diabetes-related mortality. The emergence of new therapies raises the possibility of changing the current glucose-centred therapeutic strategy for a weight-centred approach. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  10. Patient-Specific Predictive Modeling Using Random Forests: An Observational Study for the Critically Ill


    Background With a large-scale electronic health record repository, it is feasible to build a customized patient outcome prediction model specifically for a given patient. This approach involves identifying past patients who are similar to the present patient and using their data to train a personalized predictive model. Our previous work investigated a cosine-similarity patient similarity metric (PSM) for such patient-specific predictive modeling. Objective The objective of the study is to investigate the random forest (RF) proximity measure as a PSM in the context of personalized mortality prediction for intensive care unit (ICU) patients. Methods A total of 17,152 ICU admissions were extracted from the Multiparameter Intelligent Monitoring in Intensive Care II database. A number of predictor variables were extracted from the first 24 hours in the ICU. Outcome to be predicted was 30-day mortality. A patient-specific predictive model was trained for each ICU admission using an RF PSM inspired by the RF proximity measure. Death counting, logistic regression, decision tree, and RF models were studied with a hard threshold applied to RF PSM values to only include the M most similar patients in model training, where M was varied. In addition, case-specific random forests (CSRFs), which uses RF proximity for weighted bootstrapping, were trained. Results Compared to our previous study that investigated a cosine similarity PSM, the RF PSM resulted in superior or comparable predictive performance. RF and CSRF exhibited the best performances (in terms of mean area under the receiver operating characteristic curve [95% confidence interval], RF: 0.839 [0.835-0.844]; CSRF: 0.832 [0.821-0.843]). RF and CSRF did not benefit from personalization via the use of the RF PSM, while the other models did. Conclusions The RF PSM led to good mortality prediction performance for several predictive models, although it failed to induce improved performance in RF and CSRF. The distinction

  11. Apoptotic Microparticles as Predicted Biomarkers in Patients with Chronic Heart Failure – Relevance to Inflammatory Cytokines and Outcomes

    Alexander E Berezin


    Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating EMPs in survivor and non-survivor patient cohorts were 0.286 n/mL (95% CI = 0.271-0.309 n/mL and 0.673 n/mL (95% CI = 0.65-0.74 n/mL (P<0.001. There was a significantly lower concentration of sRANKL, OPG, TNF-alpha, sFAS, and sFAS ligand in the survivor patients when compared with those who met composed endpoints. The sFAS/sFAS ligand ratio in the non-survivor patient cohort was significantly higher than in the survivor cohort (P<0.001. In multivariate model EPMs, NYHA class, NT-pro-BNP, TNF-alpha, sFAS/sFAS ligand ratio, and OPG remained statistically significant for the cumulative endpoint: all-cause mortality, CHF-related death, and CHF-related readmission.

  12. Patient-Specific Therapy via Cell-Reprogramming Technology: a Curative Potential for Patients with Diabetes

    Luo, Haizhao; Wang, Xianbao; Zhang, Ruyi; Chen, Youping; Shu, Yi; Li, Huixian; Chen, Hong


    Gene therapeutics provides great opportunities for curing diabetes. Numerous attempts have been made to establish a safe and high-efficiency gene delivery strategy, but all of them are unsuccessful. To achieve an ideal transfection, a novel gene delivery strategy was presented in this research. The novel system proposed was transfection mediated by the combination of ultrasound with microbubbles and cross-linked polyethylenimines (PEIs). Ultrasound with microbubbles enhances the permeability of target cells; moreover, cross-linked PEIs enabled DNA to escape from endosomes into the cytoplasm. If the proposed method is feasible and effective, the endogenous secretion system of insulin would be re-established in patients with diabetes.

  13. Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities.

    Sgarbossa, E B; Pinski, S L; Maloney, J D; Simmons, T W; Wilkoff, B L; Castle, L W; Trohman, R G


    The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis. From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Cox's proportional hazards model, were history of paroxysmal atrial fibrillation (P < .001; hazard ratio [HR] = 16.84), use of antiarrhythmic drugs before pacemaker implant (P < .001; HR = 2.25), ventricular pacing mode (P = .003; HR = 1.98), age (P = .005; HR = 1.03), and valvular heart disease (P = .008; HR = 2.05). For patients with preimplant history of paroxysmal atrial fibrillation, independent predictors were prolonged episodes of paroxysmal atrial fibrillation (P < .001; HR = 2.56), long history of paroxysmal atrial fibrillation (P = .004; HR = 2.05), ventricular pacing mode (P = .025; HR = 1.69), use of antiarrhythmic drugs before pacemaker implant (P = .024; HR = 1.71), and age (P = .04; HR = 1.02). Actuarial incidence of stroke was 3% at 1 year, 5% at 5 years, and 13% at 10 years. Independent predictors for stroke were history of cerebrovascular disease (P < .001; HR = 5.22), ventricular pacing mode (P = .008; HR = 2.61), and history of paroxysmal atrial fibrillation (P = .037; HR = 2.81). Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation

  14. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    Elting, JW; De Keyser, J; Sulter, G.


    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a cereb

  15. Patient-Specific Simulation of Implant Placement and Function for Cochlear Implantation Surgery Planning

    Ceresa, Mario; Mangado Lopez, Nerea; Dejea Velardo, Hector;


    We present a framework for patient specific electrical stimulation of the cochlea, that allows to perform in-silico analysis of implant placement and function before surgery. A Statistical Shape Model (SSM) is created from high-resolution human μCT data to capture important anatomical details...

  16. An effective algorithm for the generation of patient-specific Purkinje networks in computational electrocardiology

    Palamara, Simone; Vergara, Christian; Faggiano, Elena; Nobile, Fabio


    The Purkinje network is responsible for the fast and coordinated distribution of the electrical impulse in the ventricle that triggers its contraction. Therefore, it is necessary to model its presence to obtain an accurate patient-specific model of the ventricular electrical activation. In this paper, we present an efficient algorithm for the generation of a patient-specific Purkinje network, driven by measures of the electrical activation acquired on the endocardium. The proposed method provides a correction of an initial network, generated by means of a fractal law, and it is based on the solution of Eikonal problems both in the muscle and in the Purkinje network. We present several numerical results both in an ideal geometry with synthetic data and in a real geometry with patient-specific clinical measures. These results highlight an improvement of the accuracy provided by the patient-specific Purkinje network with respect to the initial one. In particular, a cross-validation test shows an accuracy increase of 19% when only the 3% of the total points are used to generate the network, whereas an increment of 44% is observed when a random noise equal to 20% of the maximum value of the clinical data is added to the measures.

  17. Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute ischemic brain disease

    Selaković Vesna M.


    Full Text Available The objective of this research was to determine the dynamics of change of neuron-specific enolase concentration in patients with acute ischemic brain disease in cerebrospinal fluid and plasma. The study included 103 patients, their mean age 58-66 years. The control group consisted of 16 patients, of matching age and sex, with radicular lesions of discal origin, subjected to diagnostic radiculography. Concentration of neuron-specific enolase was measured by a flouroimmunometric method. The results showed that the concentration of neuron-specific enolase in cerebrospinal fluid and plasma of patients with brain ischemic disease within first seven days significantly increased compared to the control. The highest increase of concentration was established in brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack. Maximal concentration was established on the 3rd-4th day upon the brain infarction. Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an indicator of pathophysiological processes in the acute phase of brain ischemia and is significant in early diagnostics and therapy of the disease.

  18. Immune responses and immigration of Mycobacterium tuberculosis-specific T lymphocytes in patients with tuberculous pleuritis



    Objective To compare the immune responses of Mycobacterium tuberculosis(M.tb)-specific T lymphocy between the peripheral blood and pleural effusion in patients with tuberculous pleurisy.Methods Twelve initially treated cases of tuberculous pleurisy who were hospitalized in Wuxi No.5 People’s Hospital from Oct 2012 to Apr 2013

  19. Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients.

    Chris Cheadle

    Full Text Available BACKGROUND: Gene expression profiling of peripheral blood mononuclear cells (PBMCs is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells. METHODOLOGY/PRINCIPAL FINDINGS: The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH, 19 patients with systemic sclerosis without pulmonary hypertension (SSc, 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH, and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease. CONCLUSIONS/SIGNIFICANCE: In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression.

  20. Rotational alignment in patient-specific instrumentation in TKA: MRI or CT?

    Silva, Alcindo; Pinto, Elisabete; Sampaio, Ricardo


    To compare CT-guided and MRI-guided patient-specific instrumentation in total knee arthroplasty (TKA). Forty-four patients underwent primary TKA using either CT-guided or MR-guided Signature™ patient-specific instrumentation. They were prospectively assigned into two groups: 23 patients into the MR-guided instrumentation (group A) and 21 patients into the CT-guided patient-specific instrumentation (group B). All patients underwent computed tomography of the operated knee in the first week after the surgery to measure the components rotation. The femoral component rotation was 0.0° (0.0, 1.0) in group A and 0.0° (-2.0, 1.0) in group B. The tibial component rotation was -16.0° (-19.0, -14.0) in group A and -15.0° (-18.0, -8.0) in group B. In both components, there were no significant differences between the two groups. The difference between the tibial component rotation and the neutral tibial rotation was similar in both groups [2.0° (-1.4, 4.0) in group A and 3.0° (-0.5, 5.0) in group B], but the dispersion around the median was different between the two groups, with the amplitude of the difference between tibial rotation and neutral position 9° (-3.0, 6.0) in group A and 27° (-9.0, 18.0) in group B. MRI may be more accurate than CT using the Signature™ system when planning the surgical guides for TKA, with fewer patients with malrotation of the tibial component. II.

  1. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease.

    Moos, Verena; Kunkel, Désirée; Marth, Thomas; Feurle, Gerhard E; LaScola, Bernard; Ignatius, Ralf; Zeitz, Martin; Schneider, Thomas


    Whipple's disease is a rare infectious disorder caused by Tropheryma whipplei. Major symptoms are arthropathy, weight loss, and diarrhea, but the CNS and other organs may be affected, too. The incidence of Whipple's disease is very low despite the ubiquitous presence of T. whipplei in the environment. Therefore, it has been suggested that host factors indicated by immune deficiencies are responsible for the development of Whipple's disease. However, T. whipplei-specific T cell responses could not be studied until now, because cultivation of the bacteria was established only recently. Thus, the availability of T. whipplei Twist-Marseille(T) has enabled the first analysis of T. whipplei-specific reactivity of CD4(+) T cells. A robust T. whipplei-specific CD4(+) Th1 reactivity and activation (expression of CD154) was detected in peripheral and duodenal lymphocytes of all healthy (16 young, 27 age-matched, 11 triathletes) and disease controls (17 patients with tuberculosis) tested. However, 32 Whipple's disease patients showed reduced or absent T. whipplei-specific Th1 responses, whereas their capacity to react to other common Ags like tetanus toxoid, tuberculin, actinomycetes, Giardia lamblia, or CMV was not reduced compared with controls. Hence, we conclude that an insufficient T. whipplei-specific Th1 response may be responsible for an impaired immunological clearance of T. whipplei in Whipple's disease patients and may contribute to the fatal natural course of the disease.

  2. Longitudinal Analysis of Tetanus- and Influenza-Specific IgG Antibodies in Myeloma Patients

    Sebastian Kobold


    Full Text Available Background. Multiple myeloma (MM and its therapies may induce a severely compromised humoral immunity. We have performed a longitudinal analysis of IgG-antibody responses against influenza virus (FLU and tetanus toxoid (TT as surrogate markers for the B cell-mediated immunity in MM patients. Methods. 1094 serum samples of 190 MM patients and samples from 100 healthy donors were analyzed by ELISA for FLU- and TT-specific antibodies. Results. MM patients evidenced lower levels of FLU- and TT-specific antibodies than healthy controls (P<0.001. Immunoreactivity decreased with progressing disease and worsening clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6 months after alloSCT (P<0.001, a time-period during which intravenous immunoglobulin (IVIG is routinely applied. Thereafter, antibody concentrations declined and remained suppressed for 3 years in the case of FLU-specific and for more than 5 years in the case of TT-specific antibodies. Conclusions. We found that MM is associated with a profound disease- and therapy-related immunosuppression, which is compensated for a few months after alloSCT, most likely by application of IVIG. This and the differences regarding the recovery of anti-FLU and anti-TT antibody titers during the following years need to be taken into account for optimizing IVIG application and immunization after alloSCT.

  3. Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels

    Bo Dai; Ding-Wei Ye; Yun-Yi Kong; Yi-Jin Shen; Bo-Hua Wang


    Aim: To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. Methods: The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones.The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific anitgen (PSA) levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. Results: The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% (6/90) in our patients (P 50 ng/mL (P 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy > 10 years and the sextant strategy should be applied in those with life expectancy < 10 years.

  4. Patient-specific rigorously methodological test of the mean phase coherence

    Henriksen, Jonas

    respectively together with at least 24 h of interictal data from each individual. With a variant of the leave-one-out training and test method, the optimal amount of training seizures was determined. Results: The generic test on the FSPEEG database resulted in a {sensitivity, false prediction ratio} of {0.......55, 0.3/h}. For the 4 new patients the generic results were {0.91, 0.55/h}, {0.85, 0.71/h}, {0.29, 0.49/h}, and {0, 0.36/h} which is comparable to the FSPEEG database. The patient-specific approach yielded {0.81, 0.17/h}, {0.57, 0.13/h}, {0.81, 0.13/h}, and {0.60, 0.50/h} respectively, meaning...... that the patient-specific approach resulted in a mean improvement of {0.19, 0.30/h}. It was found that 4 seizures were optimal for training. Conclusions: By making the seizure prediction algorithm patient-specific, great improvements were obtained in this preliminary study. 3 out of 4 patients showed clinically...

  5. Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks

    Canals, Isaac; Soriano, Jordi; Orlandi, Javier G.; Torrent, Roger; Richaud-Patin, Yvonne; Jiménez-Delgado, Senda; Merlin, Simone; Follenzi, Antonia; Consiglio, Antonella; Vilageliu, Lluïsa; Grinberg, Daniel; Raya, Angel


    Summary Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration. PMID:26411903

  6. Patient-specific simulations of stenting procedures in coronary bifurcations: two clinical cases.

    Morlacchi, Stefano; Colleoni, Sebastian George; Cárdenes, Rubén; Chiastra, Claudio; Diez, Jose Luis; Larrabide, Ignacio; Migliavacca, Francesco


    Computational simulations of stenting procedures in idealized geometries can only provide general guidelines and their use in the patient-specific planning of percutaneous treatments is inadequate. Conversely, image-based patient-specific tools that are able to realistically simulate different interventional options might facilitate clinical decision-making and provide useful insights on the treatment for each individual patient. The aim of this work is the implementation of a patient-specific model that uses image-based reconstructions of coronary bifurcations and is able to replicate real stenting procedures following clinical indications. Two clinical cases are investigated focusing the attention on the open problems of coronary bifurcations and their main treatment, the provisional side branch approach. Image-based reconstructions are created combining the information from conventional coronary angiography and computed tomography angiography while structural finite element models are implemented to replicate the real procedure performed in the patients. First, numerical results show the biomechanical influence of stents deployment in the coronary bifurcations during and after the procedures. In particular, the straightening of the arterial wall and the influence of two overlapping stents on stress fields are investigated here. Results show that a sensible decrease of the vessel tortuosity occurs after stent implantation and that overlapping devices result in an increased stress state of both the artery and the stents. Lastly, the comparison between numerical and image-based post-stenting configurations proved the reliability of such models while replicating stent deployment in coronary arteries.

  7. Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks

    Isaac Canals


    Full Text Available Induced pluripotent stem cell (iPSC technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration.

  8. Activity and High-Order Effective Connectivity Alterations in Sanfilippo C Patient-Specific Neuronal Networks.

    Canals, Isaac; Soriano, Jordi; Orlandi, Javier G; Torrent, Roger; Richaud-Patin, Yvonne; Jiménez-Delgado, Senda; Merlin, Simone; Follenzi, Antonia; Consiglio, Antonella; Vilageliu, Lluïsa; Grinberg, Daniel; Raya, Angel


    Induced pluripotent stem cell (iPSC) technology has been successfully used to recapitulate phenotypic traits of several human diseases in vitro. Patient-specific iPSC-based disease models are also expected to reveal early functional phenotypes, although this remains to be proved. Here, we generated iPSC lines from two patients with Sanfilippo type C syndrome, a lysosomal storage disorder with inheritable progressive neurodegeneration. Mature neurons obtained from patient-specific iPSC lines recapitulated the main known phenotypes of the disease, not present in genetically corrected patient-specific iPSC-derived cultures. Moreover, neuronal networks organized in vitro from mature patient-derived neurons showed early defects in neuronal activity, network-wide degradation, and altered effective connectivity. Our findings establish the importance of iPSC-based technology to identify early functional phenotypes, which can in turn shed light on the pathological mechanisms occurring in Sanfilippo syndrome. This technology also has the potential to provide valuable readouts to screen compounds, which can prevent the onset of neurodegeneration.

  9. Relevance of monitoring metabolic reduction in patients with relapsed or refractory follicular and mantle cell lymphoma receiving bendamustine: a multicenter study.

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ishizawa, Kenichi; Ogura, Michinori; Tobinai, Kensei


    The aim of the present study was to investigate the relevance of monitoring metabolic reduction evaluated by (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT in relapsed or refractory patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) who received bendamustine. We conducted a phantom study of 18F-FDG PET/CT to ensure quality control for performing a multicenter clinical study. We analyzed 49 patients with relapsed or refractory FL and MCL who received bendamustine (120 mg/m(2)) on days 1-2 of a 21-day cycle for up to six cycles as a licensing phase II study. 18F-FDG PET/CT scans were acquired before the first and after the last cycle. In a total of 175 target lesions, the maximum perpendicular diameter (Max PD), minimum PD (Min PD), sum of the products of the Max PD (SPD), maximum standardized uptake value (SUVmax), and the percentage reduction rates of Max PD (%Max PD), SPD (%SPD) and SUVmax (%SUVmax) were evaluated for the response to treatment. The therapeutic response was assessed after the last cycle of treatment according to the revised response criteria for malignant lymphoma (revised RC). We evaluated 134 lesions in 39 patients (76%) achieving complete response (CR) and 41 lesions in 10 patients (24%) not achieving CR. The Max PD, Min PD, SPD and SUVmax of the lesions after the last cycle were significantly higher in patients with non-CR than in patients with CR. The %MPD, %SPD and %SUVmax of the lesions were significantly greater in patients with CR than in patients with non-CR (P < 0.0001). Metabolic reduction was observed in all target lesions of relapsed or refractory patients with FL and MCL who achieved CR after bendamustine therapy.

  10. Towards patient-specific modelling of lesion formation during radiofrequency catheter ablation for atrial fibrillation

    Soor, Navjeevan; Morgan, Ross; Varela, Marta; Aslanidi, Oleg V.


    Radiofrequency catheter ablation procedures are a first-line method of clinical treatment for atrial fibrillation. However, they suffer from suboptimal success rates and are also prone to potentially serious adverse effects. These limitations can be at least partially attributed to the inter- and intra- patient variations in atrial wall thickness, and could be mitigated by patient-specific approaches to the procedure. In this study, a modelling approach to optimising ablation procedures in subject-specific 3D atrial geometries was applied. The approach enabled the evaluation of optimal ablation times to create lesions for a given wall thickness measured from MRI. A nonliner relationship was revealed between the thickness and catheter contact time required for fully transmural lesions. Hence, our approach based on MRI reconstruction of the atrial wall combined with subject-specific modelling of ablation can provide useful information for improving clinical procedures. PMID:28261003

  11. A specific pattern of splicing for the horse αS1-Casein mRNA and partial genomic characterization of the relevant locus

    Guérin Gérard


    Full Text Available Abstract Mares' milk has a composition very different from that of cows' milk. It is much more similar to human milk, in particular in its casein fraction. This study reports on the sequence of a 994 bp amplified fragment corresponding to a horse αS1-Casein (αS1-Cn cDNA and its comparison with its caprine, pig, rabbit and human counterparts. The alignment of these sequences revealed a specific pattern of splicing for this horse primary transcript. As in humans, exons 3', 6' and 13' are present whereas exons 5, 13 and 14 are absent in this equine mRNA sequence. BAC clones, screened from a horse BAC library, containing the αS1-Cn gene allowed the mapping of its locus by FISH on equine chromosome 3q22.2-q22.3 which is in agreement with the Zoo-FISH results. Genomic analysis of the αS1-Cn gene showed that the region from the second exon to the last exon is scattered within a nucleotide stretch nearly 15-kb in length which is quite similar in size to its ruminant and rabbit counterparts. The region between αS1- and β-Cn genes, suspected to contain cis-acting elements involved in the expression of all clustered casein genes, is similar in size (ca. 15-kb to the caprine and mouse intergenic region.

  12. Neuronal Plasticity Associated with Burn Injury and Its Relevance for Perception and Management of Pain in Burn Patients

    Terence J Coderre


    Full Text Available Through the introduction of the gate control theory and various subsequent works, Ronald Melzack has inspired many investigators worldwide to realize two important facts about pain. First, incoming pain messages are subject to both negative and positive modulation, which significantly affect its perception. Second, the progression of knowledge about the basic mechanisms underlying persistent and chronic pain is critically dependent on the increased understanding of the complexity of the symptoms experienced by pain patients. The present paper examines these two very important issues in an effort to understand better the mechanisms that underlie the pain suffered by burn patients. The physiological responses to burn injury involve many different mediators and mechanisms, all of which contribute to pain perception and development of neuronal plasticity underlying short and long term changes in pain sensitivity. While experimental burn injuries in humans and animals are typically well controlled and mild, in burn victims, the severity is much more variable, and clinical care involves repeated traumas and manipulations of the injured sites. Recurrent inputs from damaged and redamaged tissue impinge on a nervous system that becomes an active participant in the initiation of changes in sensory perception and maintenance of long term sensory disturbances. Recently acquired experimental evidence on postburn hyperalgesia, central hyperexcitability and changes in opioid sensitivity provides strong support that burn patients need an analgesic approach aimed at preventing or reducing the 'neural' memory of pain, including the use of more than one treatment modality. Burn injuries offer a unique opportunity to combine experimental and clinical research to understand pain mechanisms better. Over the years, Ronald Melzack has insisted that one of the most laudable enterprises in research is to span the gap between these two often separate worlds.

  13. IDH1/2 Mutation and MGMT Promoter Methylation - the Relevant Survival Predictors in Czech Patients with Brain Gliomas.

    Kramář, F; Minárik, M; Benešová, L; Halková, T; Netuka, D; Bradáč, O; Beneš, V


    Gliomas are a heterogeneous group of tumours varying in prognosis, treatment approach, and overall survival. Recently, novel markers have been identified which are linked to patient prognosis and therapeutic response. Especially the mutation of the enzyme isocitrate dehydrogenase 1 or 2 (IDH1/2) gene and the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status seem to be the most important predictors of survival. From 2012 to 2015, 94 Czech patients with primary brain tumours were enrolled into the study. The IDH1/2 mutation was detected by denaturing capillary electrophores.The methylation status of the MGMT gene and other 46 genes was revealed by MS-MLPA. In all 94 patients, the clinical data were correlated with molecular markers by Kaplan-Meier analyses and Cox regression model. The MGMT promoter methylation status was established and compared to clinical data. In our study eight different probes were used to elucidate the MGMT methylation status; hypermethylation was proclaimed if four and more probes were positive. This 3 : 5 ratio was tested and confirmed by Kaplan-Meier and Cox analyses. The study confirmed the importance of the IDH1/2 mutation and hypermethylation of the MGMT gene promoter being present in tumour tissue. Both markers are independent positive survival predictors; in the Cox model the IDH hazard ratio was 0.10 and in the case of MGMT methylation it reached 0.32. The methylation analysis of the panel of additional 46 genes did not reveal any other significant epigenetic markers; none of the candidate genes have been confirmed in the Cox regression analyses as an independent prognostic factor.

  14. Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report.

    Baronica, Koraljka Bacić; Ivkić, Goran; Ozretić, David; Milicević, Goran


    Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.

  15. Integral-based identification of patient specific parameters for a minimal cardiac model.

    Hann, C E; Chase, J G; Shaw, G M


    A minimal cardiac model has been developed which accurately captures the essential dynamics of the cardiovascular system (CVS). However, identifying patient specific parameters with the limited measurements often available, hinders the clinical application of the model for diagnosis and therapy selection. This paper presents an integral-based parameter identification method for fast, accurate identification of patient specific parameters using limited measured data. The integral method turns a previously non-linear and non-convex optimization problem into a linear and convex identification problem. The model includes ventricular interaction and physiological valve dynamics. A healthy human state and four disease states, valvular stenosis, pulmonary embolism, cardiogenic shock and septic shock are used to test the method. Parameters for the healthy and disease states are accurately identified using only discretized flows into and out of the two cardiac chambers, the minimum and maximum volumes of the left and right ventricles, and the pressure waveforms through the aorta and pulmonary artery. These input values can be readily obtained non-invasively using echo-cardiography and ultra-sound, or invasively via catheters that are often used in Intensive Care. The method enables rapid identification of model parameters to match a particular patient condition in clinical real time (3-5 min) to within a mean value of 4-10% in the presence of 5-15% uniformly distributed measurement noise. The specific changes made to simulate each disease state are correctly identified in each case to within 10% without false identification of any other patient specific parameters. Clinically, the resulting patient specific model can then be used to assist medical staff in understanding, diagnosis and treatment selection.

  16. Reduced autobiographical memory specificity is associated with impaired discrimination learning in anxiety disorder patients

    Lenaert, Bert; Boddez, Yannick; Vervliet, Bram; Schruers, Koen; Hermans, Dirk


    Associative learning plays an important role in the development of anxiety disorders, but a thorough understanding of the variables that impact such learning is still lacking. We investigated whether individual differences in autobiographical memory specificity are related to discrimination learning and generalization. In an associative learning task, participants learned the association between two pictures of female faces and a non-aversive outcome. Subsequently, six morphed pictures functioning as generalization stimuli (GSs) were introduced. In a sample of healthy participants (Study 1), we did not find evidence for differences in discrimination learning as a function of memory specificity. In a sample of anxiety disorder patients (Study 2), individuals who were characterized by low memory specificity showed deficient discrimination learning relative to high specific individuals. In contrast to previous findings, results revealed no effect of memory specificity on generalization. These results indicate that impaired discrimination learning, previously shown in patients suffering from an anxiety disorder, may be—in part—due to limited memory specificity. Together, these studies emphasize the importance of incorporating cognitive variables in associative learning theories and their implications for the development of anxiety disorders. In addition, re-analyses of the data (Study 3) showed that patients suffering from panic disorder showed higher outcome expectancies in the presence of the stimulus that was never followed by an outcome during discrimination training, relative to patients suffering from other anxiety disorders and healthy participants. Because we used a neutral, non-aversive outcome (i.e., drawing of a lightning bolt), these data suggest that learning abnormalities in panic disorder may not be restricted to fear learning, but rather reflect a more general associative learning deficit that also manifests in fear irrelevant contexts. PMID

  17. A real-time PCR assay with improved specificity for detection and discrimination of all clinically relevant Bordetella species by the presence and distribution of three Insertion Sequence elements

    Ossewaarde Jacobus M


    Full Text Available Abstract Background In Dutch laboratories molecular detection of B. pertussis and B. parapertussis is commonly based on insertion sequences IS481 and IS1001, respectively. Both IS elements are more widely spread among Bordetella species. Both Bordetella holmesii, and B. bronchiseptica can harbour IS481. Also, IS1001 is found among B. bronchiseptica. IS481, and IS1001 based PCR thus lacks specificity when used for detection of specific Bordetella spp. Findings We designed a PCR based on IS1002, another IS element that is present among Bordetella species, and exploited it as a template in combination with PCR for IS481, and IS1001. In combining the PCRs for IS481, IS1001, and IS1002, and including an inhibition control, we were able to detect and discriminate all clinically relevant Bordetella species. Conclusions We developed an improved PCR method for specific detection of B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica.

  18. Clinical impact of sarcopenia and relevance of nutritional intake in patients before and after allogeneic hematopoietic stem cell transplantation.

    Tanaka, Shouichi; Imataki, Osamu; Kitaoka, Atsuo; Fujioka, Shuji; Hanabusa, Etsuyo; Ohbayashi, Yumiko; Uemura, Makiko; Arima, Nobuo; Yamamoto, Tetsuji


    We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy. We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research. We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p sarcopenia prior to allogeneic HSCT. After HSCT, bilateral hand grip strength and bilateral knee extensor strength decreased significantly. The total caloric intakes for pre-conditioning, during preparation regimen, and after transplant were 1709, 1024, and 1445 kcal, respectively, and were significantly attenuated in the post-transplant period. Serum albumin was significantly decreased in the final period. Conversely, C-reactive protein was slightly but significantly increased across the transplantation process. Multivariate regression analysis revealed that oral caloric intake after the transplantation period and sex were significantly related to muscle weakness (p = 0.033 and 0.036, respectively). Sarcopenia during HSCT was affected by oral caloric intake during the preparation regimen and after transplantation. Physical therapy in conjunction with nutritional therapy may help prevent weakness in HSCT recipients.

  19. Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism

    Wei, Zhiliang; Cao, Shougen; Liu, Shanglong; Yao, Zengwu; Sun, Teng; Li, Yi; Li, Jiante; Zhang, Dongfeng; Zhou, Yanbing


    Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan–Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, β-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of β-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum, B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients' prognosis by up-regulating gut inflammation level. PMID:27323816

  20. Medically Relevant Acinetobacter Species Require a Type II Secretion System and Specific Membrane-Associated Chaperones for the Export of Multiple Substrates and Full Virulence.

    Harding, Christian M; Kinsella, Rachel L; Palmer, Lauren D; Skaar, Eric P; Feldman, Mario F


    Acinetobacter baumannii, A. nosocomialis, and A. pittii have recently emerged as opportunistic human pathogens capable of causing severe human disease; however, the molecular mechanisms employed by Acinetobacter to cause disease remain poorly understood. Many pathogenic members of the genus Acinetobacter contain genes predicted to encode proteins required for the biogenesis of a type II secretion system (T2SS), which have been shown to mediate virulence in many Gram-negative organisms. Here we demonstrate that Acinetobacter nosocomialis strain M2 produces a functional T2SS, which is required for full virulence in both the Galleria mellonella and murine pulmonary infection models. Importantly, this is the first bona fide secretion system shown to be required for virulence in Acinetobacter. Using bioinformatics, proteomics, and mutational analyses, we show that Acinetobacter employs its T2SS to export multiple substrates, including the lipases LipA and LipH as well as the protease CpaA. Furthermore, the Acinetobacter T2SS, which is found scattered amongst five distinct loci, does not contain a dedicated pseudopilin peptidase, but instead relies on the type IV prepilin peptidase, reinforcing the common ancestry of these two systems. Lastly, two of the three secreted proteins characterized in this study require specific chaperones for secretion. These chaperones contain an N-terminal transmembrane domain, are encoded adjacently to their cognate effector, and their disruption abolishes type II secretion of their cognate effector. Bioinformatic analysis identified putative chaperones located adjacent to multiple previously known type II effectors from several Gram-negative bacteria, which suggests that T2SS chaperones constitute a separate class of membrane-associated chaperones mediating type II secretion.

  1. Prospective evaluation of patient satisfaction after the use of brachytherapy specific educational materials for cervical cancer.

    Rash, Dominique; Hess, Clayton; Lentz, Susan; Tait, Lauren; Michaud, Anthony; Mayadev, Jyoti


    Cervical cancer patients are faced with an enormous amount of medical information in a complex oncology field with sophisticated treatments including brachytherapy. We investigated the use of enhanced vs. standard brachytherapy-specific educational materials on patient-reported satisfaction during the informed consent process for intracavitary high-dose-rate brachytherapy. A single-institution, prospective, randomized trial was performed to study patient-reported satisfaction with novel educational materials for high-dose-rate brachytherapy in women undergoing definitive radiation for cervical cancer. Fourteen women receiving informed consent with a customized educational booklet were randomized between no further intervention and take-home educational materials. The weighted average for 10 of 11 survey questions was higher in the intervention arm but ranged between 4 (agree) and 5 (strongly agree) for all questions in both arms. The mean weighted patient satisfaction scores ± standard deviations in the control arm and the intervention arms were 54.3 ± 6.4 and 57.5 ± 2.7, respectively (p = 0.26). Knowledge acquisition is presumed to be part of the coping process for women facing increased stress during a cancer diagnosis. A brachytherapy-specific, visual, patient-educational booklet and take-home materials used to supplement the informed consent process for high-dose-rate brachytherapy resulted in high levels of patient-reported satisfaction among women treated with cervical cancer. Published by Elsevier Inc.

  2. Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.

    Jang, Dae-Hyun; Kim, Min-Wook; Park, Kyoung Ha; Lee, Jae Woo


    The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

  3. Nutritional status influences generic and disease-specific quality of life measures in haemodialysis patients.

    Moreira, Ana Catarina; Carolino, Elisabete; Domingos, Fernando; Gaspar, Augusta; Ponce, Pedro; Camilo, María Ermelinda


    Poor nutritional status and worse healthrelated quality of life (QoL) have been reported in haemodialysis (HD) patients. The utilization of generic and disease specific QoL questionnaires in the same population may provide a better understanding of the significance of nutrition in QoL dimensions. To assess nutritional status by easy to use parameters and to evaluate the potential relationship with QoL measured by generic and disease specific questionnaires. Nutritional status was assessed by subjective global assessment adapted to renal patients (SGA), body mass index (BMI), nutritional intake and appetite. QoL was assessed by the generic EuroQoL and disease specific Kidney Disease Quality of Life-Short Form (KDQoL-SF) questionnaires. The study comprised 130 patients of both genders, mean age 62.7 ± 14.7 years. The prevalence of undernutrition ranged from 3.1% by BMI ≤ 18.5 kg/m² to 75.4% for patients below energy and protein intake recommendations. With the exception of BMI classification, undernourished patients had worse scores in nearly all QoL dimensions (EuroQoL and KDQoL-SF), a pattern which was dominantly maintained when adjusted for demographics and disease-related variables. Overweight/ obese patients (BMI ≥ 25) also had worse scores in some QoL dimensions, but after adjustment the pattern was maintained only in the symptoms and problems dimension of KDQoL-SF (p = 0.011). Our study reveals that even in mildly undernourished HD patients, nutritional status has a significant impact in several QoL dimensions. The questionnaires used provided different, almost complementary perspectives, yet for daily practice EuroQoL is simpler. Assuring a good nutritional status, may positively influence QoL. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  4. Effects of pilates on patients with chronic non-specific low back pain: a systematic review.

    Lin, Hui-Ting; Hung, Wei-Ching; Hung, Jia-Ling; Wu, Pei-Shan; Liaw, Li-Jin; Chang, Jia-Hao


    [Purpose] To evaluate the effects of Pilates on patients with chronic low back pain through a systematic review of high-quality articles on randomized controlled trials. [Subjects and Methods] Keywords and synonyms for "Pilates" and "Chronic low back pain" were used in database searches. The databases included PubMed, Physiotherapy Evidence Database (PEDro), Medline, and the Cochrane Library. Articles involving randomized controlled trials with higher than 5 points on the PEDro scale were reviewed for suitability and inclusion. The methodological quality of the included randomized controlled trials was evaluated using the PEDro scale. Relevant information was extracted by 3 reviewers. [Results] Eight randomized controlled trial articles were included. Patients with chronic low back pain showed statistically significant improvement in pain relief and functional ability compared to patients who only performed usual or routine health care. However, other forms of exercise were similar to Pilates in the improvement of pain relief and functional capacity. [Conclusion] In patients with chronic low back pain, Pilates showed significant improvement in pain relief and functional enhancement. Other exercises showed effects similar to those of Pilates, if waist or torso movement was included and the exercises were performed for 20 cumulative hours.

  5. Persistent left superior vena cava: review of the literature, clinical implications, and relevance of alterations in thoracic central venous anatomy as pertaining to the general principles of central venous access device placement and venography in cancer patients.

    Povoski, Stephen P; Khabiri, Hooman


    Persistent left superior vena cava (PLSVC) represents the most common congenital venous anomaly of the thoracic systemic venous return, occurring in 0.3% to 0.5% of individuals in the general population, and in up to 12% of individuals with other documented congential heart abnormalities. In this regard, there is very little in the literature that specifically addresses the potential importance of the incidental finding of PLSVC to surgeons, interventional radiologists, and other physicians actively involved in central venous access device placement in cancer patients. In the current review, we have attempted to comprehensively evaluate the available literature regarding PLSVC. Additionally, we have discussed the clinical implications and relevance of such congenital aberrancies, as well as of treatment-induced or disease-induced alterations in the anatomy of the thoracic central venous system, as they pertain to the general principles of successful placement of central venous access devices in cancer patients. Specifically regarding PLSVC, it is critical to recognize its presence during attempted central venous access device placement and to fully characterize the pattern of cardiac venous return (i.e., to the right atrium or to the left atrium) in any patient suspected of PLSVC prior to initiation of use of their central venous access device.

  6. Cerebral Aneurysm Clipping Surgery Simulation Using Patient-Specific 3D Printing and Silicone Casting.

    Ryan, Justin R; Almefty, Kaith K; Nakaji, Peter; Frakes, David H


    Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience. The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry. A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy. Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum. The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient-derived models for a dynamic learning environment that add value to surgical training and preparation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations

    Tripathy, Anuradha S.; Tandale, Babasaheb V.; Balaji, Saravana S.; Hundekar, Supriya L.; Ramdasi, Ashwini Y.; Arankalle, Vidya A.


    Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients. PMID:25900956

  8. Nonlinear Heart Rate Dynamics in Off-pump Coronary Artery Bypass Grafting Patients and The Relevance with Atrial Fibrillation and Ventricular Tachycardia

    Wu Zhongkai; Yao Jianping; Huang Xiaodan; Jari Laurikka; Saila Vikman; Matti R. Tarkka


    Objectives To elucidate the clinical relevance of nonlinear HRV with postoperative arrhythmias in patients undergoing off-pump CABG. Methods Twenty-seven elective off-pump CABG patients were recruited in the present study. Atrial fibrillation (AF),ventricular tachycardia (VT), linear and nonlinear HRV were analysed using 24-hour electrocardiogram before and after surgery. Results All time domain (SDNN,pNN50 and rMSSD ), frequency domain (LF and HF)of linear measures of HRV variables and nonlinear measures of HRV variable, the short-term fractal-like correlation α1 decreased significantly after surgery. The postoperative nonlinear HRV variable α1 tended to be lower in patients with postoperative AF ( P = 0.056). Significant depressed α1 was found in patients with postoperative VT(P = 0.022 ). Elder patient's age and longer inotropic treatment time negatively correlated with postoperative α1. Conclusions Off-pump CABG procedures resulted in significant depressed of linear and nonlinear HRV variables. The depressed nonlinear HRV variables α1 related to age, inotropic supports and postoperative AF and VT.

  9. Anti-hsp60 antibody responses based on Helicobacter pylori in patients with multiple sclerosis: (ir)Relevance to disease pathogenesis.

    Efthymiou, Georgios; Dardiotis, Efthymios; Liaskos, Christos; Marou, Emmanouela; Tsimourtou, Vana; Scheper, Thomas; Meyer, Wolfgang; Daponte, Alexandros; Sakkas, Lazaros I; Hadjigeorgiou, Georgios; Bogdanos, Dimitrios P


    In view of published data suggesting that Helicobacter pylori (Hp) is a trigger of multiple sclerosis (MS), we assessed anti-heat shock protein 60 (hsp60)Hp antibody reactivity in 129 MS patients and 48 demograpically-matched healthy controls (HCs). Anti-Hp antibodies by ELISA were more elevated in MS than HCs but did not differ between different MS phenotypes. All anti-Hp-positive MS sera, irrespectively of their clinical phenotype, were anti-anti-hsp60 positive. Anti-hsp60 Hp seropositivity correlated with age at disease onset. In conclusion, anti-hsp60 Hp antibodies are present in all anti-Hp positive MS patients, and their relevance to disease pathogenesis is questionable. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. PET and PET/CT - relevance in breast cancer patients; PET und PET/CT - Stellenwert beim Mammakarzinom

    Palmedo, H. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Bonn (Germany)


    Breast cancer is the most frequent malignant tumor of women in Germany. In spite of an increasing incidence mortality has slightly declined most likely due to improvements in diagnosis and therapy of the disease. FDG-PET has a high diagnostic accuracy for the detection of lymph node and distant metastases. However, PET is no alternative to axillary dissection or sentinel node biopsy because sensitivity for small lymph node metastases is limited. For N-staging, FDG-PET delivers valuable information if mammaria-interna or mediastinal lymph node disease has to be proven (1b-indication). Individually, PET can add important diagnostic information in patients with suspected distant metastases but unsuspicious or equivocal conventional imaging (2-indication). FDG-PET shows unique and favourable properties for early therapy monitoring during preoperative chemotherapy. Larger studies have to confirm these results. (orig.)

  11. Novel genes associated with colorectal cancer are revealed by high resolution cytogenetic analysis in a patient specific manner.

    Hisham Eldai

    Full Text Available Genomic abnormalities leading to colorectal cancer (CRC include somatic events causing copy number aberrations (CNAs as well as copy neutral manifestations such as loss of heterozygosity (LOH and uniparental disomy (UPD. We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1 and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1 as novel in their association with CRC. Pathway and target prediction analysis of CNA affected genes and microRNAs, respectively indicates TGF-β signaling pathway to be involved in causing CRC. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of >35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.

  12. Spontaneous presence of FOXO3-specific T cells in cancer patients

    Larsen, Stine Kiaer; Ahmad, Shamaila Munir; Idorn, Manja


    In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic CD8(+) T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity toward FOXO3 among T cells in healthy individuals. FOXO3...... may naturally serve as a target antigen for tumor-reactive T cells as it is frequently over-expressed in cancer cells. In addition, expression of FOXO3 plays a critical role in immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed, FOXO3-specific cytotoxic T lymphocytes (CTLs......) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises...

  13. Specific cytotoxic T lymphocyte responses in Chinese HIV/AIDS patients

    尚红; 韩晓旭; 王亚男; 周立平; 张子宁; 姜拥军; 张旻; 于旭


    Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) are considered to play a central role in the immune response against HIV-1. During untreated acute HIV-1 infection, virus-specific CTL activity is associated with the initial decrease in viremia.1 After HIV infection, those individuals with a slow progressive course develop stronger CTL responses than those with typical disease progression.2,3 Restoring HIV-1-specific CTL responses have been considered a key factor in immune reconstitution and vaccine development. Here we present the analysis of HIV-1 Gag-specific CTL responses in 23 Chinese HIV/AIDS cases in order to take the initial steps at identifying the epitopes that dominate the CTL response in Chinese patients.

  14. Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory

    Jung W


    Full Text Available Wookyoung Jung,1 Seung-Hwan Lee1,2 1Clinical Emotions and Cognition Research Laboratory, Department of Psychiatry, Inje University, Ilsan-Paik Hospital, 2Department of Psychiatry, Inje University, Ilsan-Paik Hospital, Goyang, Korea Abstract: It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed. Keywords: schizophrenia, posttraumatic stress disorder, episodic memory deficit, relational memory, item-specific memory, prefrontal cortex, hippocampus

  15. Patient-specific determinants of responsiveness to robot-enhanced treadmill therapy in children and adolescents with cerebral palsy.

    Schroeder, Andreas Sebastian; Von Kries, Rüdiger; Riedel, Christina; Homburg, Maria; Auffermann, Helene; Blaschek, Astrid; Jahn, Klaus; Heinen, Florian; Borggraefe, Ingo; Berweck, Steffen


    The aim of the study was to evaluate patient-specific determinants of responsiveness to robot-enhanced repetitive treadmill therapy (ROBERT) in patients with early-developed movement disorders. Patients were treated over 12 sessions during a 3-week period. Gross Motor Function Measure-66 (GMFM-66) scores 1 day before ROBERT were compared with scores recorded 1 day after ROBERT. The association of GMFM-66 baseline score, age, sex, aetiology, and add-on botulinum toxin therapy to response to treatment was assessed. Eighty-three patients aged between 4 and 18 years (48 males, 35 females; mean age 10y 8mo, SD 6y 1mo; Gross Motor Function Classification System level I [n=12], II [n=21], III [n=35], IV [n=10], and V [n=1]) were each treated for a total of 7.2 (SD 1.9) treadmill walking hours. Aetiology was bilateral spastic cerebral palsy (BS-CP; n=69), unilateral CP (n=3), ataxic CP (n=3), hereditary spastic paraparesis (n=6), and genetic syndrome including spasticity (n=2). Meaningful improvements were observed in GMFM-66 (+2.5; 95% CI 2.0-3.0), GMFM-D (+5.2; 95% CI 3.6-6.8), and GMFM-E (+4.0; 95% CI 2.8-5.3). There was a high inter-individual variability in treatment response. After multivariable adjustment, the improvements in GMFM-66 and GMFM-E scores were positively associated with the GMFM-66 baseline score. The effect on GMFM-D improvement was inversely associated with age. Gross motor abilities at baseline and age were identified as relevant determinants for the high degree of interpersonal variability in response to ROBERT. © 2014 Mac Keith Press.

  16. Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis

    Sato, Kanako; Masutani, Yoshitaka; Watadani, Takeyuki; Nakata, Yasuhiro; Yoshida, Mariko; Abe, Osamu; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Bunkyo, Tokyo (Japan); Aoki, Shigeki [Juntendo University, Department of Radiology, Bunkyo, Tokyo (Japan); Iwata, Nobue K.; Terao, Yasuo; Tsuji, Shoji [University of Tokyo, Department of Neurology, Graduate School of Medicine, Bunkyo, Tokyo (Japan)


    The uncinate fasciculus (UF) consists of core fibers connecting the frontal and temporal lobes and is considered to be related to cognitive/behavioral function. Using diffusion tensor tractography, we quantitatively evaluated changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the UF by tract-specific analysis to evaluate the damage of the UF in patients with amyotrophic lateral sclerosis (ALS). We obtained diffusion tensor images of 15 patients with ALS and 9 age-matched volunteers. Patients with ALS showed significantly lower mean FA (P = 0.029) compared with controls. No significant difference was seen in mean ADC. The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA. (orig.)

  17. Nationwide Assessment of Cause-Specific Mortality in Patients with Rosacea

    Egeberg, Alexander; Fowler, Joseph F; Gislason, Gunnar H


    BACKGROUND: Emerging data suggest that rosacea is associated with several comorbidities; however, the causes of mortality in patients with rosacea have not yet been investigated. OBJECTIVE: We evaluated all-cause and cause-specific death rates in patients with rosacea in a population-based Danish...... cohort study. METHODS: All Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2012 with rosacea diagnosed by hospital dermatologists were linked in nationwide registers and compared with age- and sex-matched general-population subjects (1:5 ratio). Death rates were calculated per...... 1000 person-years, and hazard ratios (HRs) were estimated using Cox regression models. RESULTS: The total cohort (n = 35,958) included 5993 patients with rosacea and 29,965 age- and sex-matched individuals from the general population. During the maximum 15 years of follow-up, 664 (11.1 %) patients...

  18. Phosphoinositide-specific Phospholipase C β1 gene deletion in bipolar disorder affected patient.

    Lo Vasco, Vincenza Rita; Longo, Lucia; Polonia, Patrizia


    The involvement of phosphoinositides (PI) signal transduction pathway and related molecules, such as the Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes, in the pathophysiology of mood disorders is corroborated by a number of recent evidences. Our previous works identified the deletion of PLCB1 gene, which codifies for the PI-PLC β1 enzyme, in 4 out 15 patients affected with schizophrenia, and no deletion both in major depression affected patients and in normal controls. By using interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 in paraffin embedded samples of orbito-frontal cortex of 15 patients affected with bipolar disorder. Deletion of PLCB1 was identified in one female patient.

  19. [Specificity of spatial organization of evoked EEG rhythms in patients with paranoid schizophrenia].

    Bochkarev, V K; Kirenskaya, A V; Solnceva, S V; Tkachenko, A A

    The study aimed at analyzing the spatial patterns of evoked event-related oscillations in patients with paranoid schizophrenia and their relationship with clinical symptoms of disease. Evoked delta, theta, alpha, beta, and gamma rhythms in response to target auditory stimulus in an oddball paradigm were studied in 21 schizophrenic patients and 22 healthy subjects. The independent spatial patterns were revealed within each of the frequency range using the principal component analysis. Each spatial pattern was characterized by the specificity of intra- and inter-hemispheric relations. The schizophrenic patients were characterized by a decrease in the evoked activity in the theta range with the most pronounced changes in the frontal-central areas of the right hemisphere and parietal-occipital areas bilaterally. Associations of the evoked rhythms with PANSS positive and negative symptoms were identified. The study demonstrated the high functional significance of evoked EEG rhythms changes for neurophysiological characteristics of patients with paranoid schizophrenia.

  20. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

    Haberman, Yael; Tickle, Timothy L.; Dexheimer, Phillip J.; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N.; Noe, Joshua D.; Rosh, Joel; Markowitz, James; Heyman, Melvin B.; Griffiths, Anne M.; Crandall, Wallace V.; Mack, David R.; Baker, Susan S.; Huttenhower, Curtis; Keljo, David J.; Hyams, Jeffrey S.; Kugathasan, Subra; Walters, Thomas D.; Aronow, Bruce; Xavier, Ramnik J.; Gevers, Dirk; Denson, Lee A.


    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches. PMID:25003194

  1. Nutritional status influences generic and disease-specific quality of life measures in haemodialysis patients

    Ana Catarina Moreira


    Full Text Available Background: Poor nutritional status and worse health-related quality of life (QoL have been reported in haemodialysis (HD patients. The utilization of generic and disease specific QoL questionnaires in the same population may provide a better understanding of the significance of nutrition in QoL dimensions. Objective: To assess nutritional status by easy to use parameters and to evaluate the potential relationship with QoL measured by generic and disease specific questionnaires. Methods: Nutritional status was assessed by subjective global assessment adapted to renal patients (SGA, body mass index (BMI, nutritional intake and appetite. QoL was assessed by the generic EuroQoL and disease specific Kidney Disease Quality of Life-Short Form (KDQoL-SF questionnaires. Results: The study comprised 130 patients of both genders, mean age 62.7 ± 14.7 years. The prevalence of undernutrition ranged from 3.1% by BMI 25 also had worse scores in some QoL dimensions, but after adjustment the pattern was maintained only in the symptoms and problems dimension of KDQoL-SF (p = 0.011. Conclusion: Our study reveals that even in mildly undernourished HD patients, nutritional status has a significant impact in several QoL dimensions. The questionnaires used provided different, almost complementary perspectives, yet for daily practice EuroQoL is simpler. Assuring a good nutritional status, may positively influence QoL.

  2. Patient-specific system for prognosis of surgical treatment outcomes of human cardiovascular system

    Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.


    Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.

  3. Patient-specific coronary artery blood flow simulation using myocardial volume partitioning

    Kim, Kyung Hwan; Kang, Dongwoo; Kang, Nahyup; Kim, Ji-Yeon; Lee, Hyong-Euk; Kim, James D. K.


    Using computational simulation, we can analyze cardiovascular disease in non-invasive and quantitative manners. More specifically, computational modeling and simulation technology has enabled us to analyze functional aspect such as blood flow, as well as anatomical aspect such as stenosis, from medical images without invasive measurements. Note that the simplest ways to perform blood flow simulation is to apply patient-specific coronary anatomy with other average-valued properties; in this case, however, such conditions cannot fully reflect accurate physiological properties of patients. To resolve this limitation, we present a new patient-specific coronary blood flow simulation method by myocardial volume partitioning considering artery/myocardium structural correspondence. We focus on that blood supply is closely related to the mass of each myocardial segment corresponding to the artery. Therefore, we applied this concept for setting-up simulation conditions in the way to consider many patient-specific features as possible from medical image: First, we segmented coronary arteries and myocardium separately from cardiac CT; then the myocardium is partitioned into multiple regions based on coronary vasculature. The myocardial mass and required blood mass for each artery are estimated by converting myocardial volume fraction. Finally, the required blood mass is used as boundary conditions for each artery outlet, with given average aortic blood flow rate and pressure. To show effectiveness of the proposed method, fractional flow reserve (FFR) by simulation using CT image has been compared with invasive FFR measurement of real patient data, and as a result, 77% of accuracy has been obtained.

  4. Are Hip-Specific Items Useful in a Quality of Life Questionnaire for Patients with Hip Fractures?

    Yao, Kai-Ping Grace; Lee, Hsin-Yi; Tsauo, Jau-Yih


    Researchers measure the significance of hip fracture by the patient's impairment. The patient's quality of life (QOL) is usually also substantially affected. However, there is no specific quality of life (QOL) questionnaire for patients with hip fractures. This study was designed to determine whether adding a new set of specific questions about…

  5. Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the United States.

    Coghill, Anna E; Shiels, Meredith S; Suneja, Gita; Engels, Eric A


    Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non-AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality. We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected. Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio [HR], 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non-AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73). HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well

  6. Relevance of Adipose Tissue Stiffness Evaluated by Transient Elastography (AdipoScan™) in Morbidly Obese Patients before Bariatric Surgery

    Sasso, Magali; Abdennour, Meriem; Liu, Yuejun; Hazrak, Hecham; Aron-Wisnewsky, Judith; Bouillot, Jean-Luc; Le Naour, Gilles; Bedossa, Pierre; Torjman, Joan; Clément, Karine; Miette, Véronique

    Subcutaneous adipose tissue (scAT) in human obesity undergoes severe alteration such as fibrosis which is related to metabolic alterations and to less efficiency in losing weight after bariatric surgery. There is currently no non-invasive tool to assess fibrosis in scAT. Vibration Controlled Transient Elastography (VCTE) using FibroScan® is widely used to assess liver fibrosis in clinical practice. A novel device named AdipoScan™ which is based on VCTE has been developed by Echosens (Paris) so as to assess scAT. The objective of this study is to show the first AdipoScan clinical results. AdipoScan™ was assessed in vivo on 73 morbidly obese patients candidate for bariatric surgery who were enrolled in the Pitié Salpêtrière hospital. scAT shear wave speed measured by AdipoScan™ is significantly associated with scAT fibrosis, gender, hypertension status, total body fat mass assessed by DXA, hypertension status, glycemic, lipid, hepatic parameters and adiponectin. Results suggest that scAT evaluation before bariatric surgery can be useful in clinical practice since it is related to scAT fibrosis -who plays in role in weight loss resistance after bariatric surgery- and to obesity induced co-morbidities such as diabetes, hypertension liver dysfunction.

  7. Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

    Receveur Marie-Catherine


    Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

  8. Simulated Prosthesis Overlay for Patient-Specific Planning of Transcatheter Aortic Valve Implantation Procedures.

    Sündermann, Simon H; Gessat, Michael; Maier, Willibald; Kempfert, Jörg; Frauenfelder, Thomas; Nguyen, Thi D L; Maisano, Francesco; Falk, Volkmar


    We tested the hypothesis that simulated three-dimensional prosthesis overlay procedure planning may support valve selection in transcatheter aortic valve implantation (TAVI) procedures. Preoperative multidimensional computed tomography (MDCT) data sets from 81 consecutive TAVI patients were included in the study. A planning tool was developed, which semiautomatically creates a three-dimensional model of the aortic root from these data. Three-dimensional templates of the commonly used TAVI implants are spatially registered with the patient data and presented as graphic overlay. Fourteen physicians used the tool to perform retrospective planning of TAVI procedures. Results of prosthesis sizing were compared with the prosthesis size used in the actually performed procedure, and the patients were accordingly divided into three groups: those with equal size (concordance with retrospective planning), oversizing (retrospective planning of a smaller prosthesis), and undersizing (retrospective planning of a larger prosthesis). In the oversizing group, 85% of the patients had new pacemaker implantation. In the undersizing group, in 66%, at least mild paravalvular leakage was observed (greater than grade 1 in one third of the cases). In 46% of the patients in the equal-size group, neither of these complications was observed. Three-dimensional prosthesis overlay in MDCT-derived patient data for patient-specific planning of TAVI procedures is feasible. It may improve valve selection compared with two-dimensional MDCT planning and thus yield better outcomes.

  9. Is nonverbal behavior in patients and interviewers relevant to the assessment of depression and its recovery? A study with Dutch and Brazilian patients.

    Fiquer, Juliana Teixeira; Moreno, Ricardo Alberto; Canales, Janette Z; Cavalcanti, Andre; Gorenstein, Clarice


    Nonverbal behaviors exhibited by patients with depression in their interactions with others may reflect social maladjustment and depression maintenance. Investigations of associations between unipolar depression and both patients' and interviewers' behaviors have been scarce and restricted to European samples. This study examined whether nonverbal behavior in patients and their interviewers is associated with depression severity and recovery. Cultural differences were explored. Seventy-eight depressed outpatients (28 Brazilians, 50 Dutch) were evaluated before and after 8-week pharmacological treatment. Patients were videotaped during the Hamilton Depression Scale interview before treatment, and the Brazilians were also videotaped after treatment. Nonverbal behaviors (patients' speaking effort and interviewers' encouragement) were analyzed using a two-factor ethogram. Results revealed that speaking effort was associated with encouragement and both are not influenced by baseline depression severity. However, from before to after treatment, whereas encouragement remained unchanged, speaking effort increased among unrecovered patients. Speaking effort was associated with patients' culture: Brazilians exhibited higher speaking effort than Dutch. These findings highlight that whereas the supportive nonverbal behavior of the interviewer may be stable, the set of nonverbal behaviors composed by head movements, eye contact and gestures displayed by the patients during their speaking in clinical interviews reflects depression persistence after treatment.

  10. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Kristen J. Brennand


    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  11. Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

    Theodoros A Zografos; Nikolaos Gatselis; Kalliopi Zachou; Christos Liaskos; Stella Gabeta; George K Koukoulis; George N Dalekos


    AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients.METHODS:The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays,dot-blot assays,and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients.In order to specify our results,the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asy.mptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely,autoimmune hepatitis-1 or primary sclerosing cholangitJs (AIH-1/PSC).RESULTS:AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls.The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%,95% confidence interval (CI):12%-28.1% vs 2.5%,95% CI:0.1%-14.7%,P =0.01; 18.8%,95% CI:12%-28.1% vs 0%,95% CI:0%-10.9%,P =0.003,respectively].PBC-specific ANA positivity was observed in only one FDR from a PSC patient.Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio:11.24,95% CI:1.27-25.34,P =0.03) whereas among the investigated comorbidities and risk factors,a positive past history for urinary tract infections (UTI)was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92,95% CI:1.25-12.35,P =0.02).CONCLUSION:In FDRs of Greek PBC patients,AMA prevalence is significantly increased and independently associated with past UTI.PBC-specific ANA were not detected in anyone of PBC FDRs.

  12. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders.

    Brennand, Kristen J; Marchetto, M Carol; Benvenisty, Nissim; Brüstle, Oliver; Ebert, Allison; Izpisua Belmonte, Juan Carlos; Kaykas, Ajamete; Lancaster, Madeline A; Livesey, Frederick J; McConnell, Michael J; McKay, Ronald D; Morrow, Eric M; Muotri, Alysson R; Panchision, David M; Rubin, Lee L; Sawa, Akira; Soldner, Frank; Song, Hongjun; Studer, Lorenz; Temple, Sally; Vaccarino, Flora M; Wu, Jun; Vanderhaeghen, Pierre; Gage, Fred H; Jaenisch, Rudolf


    As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  13. Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

    Xiaojie Wang


    Full Text Available Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.

  14. Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia.

    Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Origa, Raffaella; Karakas, Zeynep; Habr, Dany; Zhu, Zewen; Cappellini, Maria Domenica


    Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non-transfusion-dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade(®) in non-transfusion-dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (2000 μg/l). ( identifier: NCT00873041). © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  15. Association of Specific Immunoglobulin E to Staphylococcal Enterotoxin with Airway Hyperresponsiveness in Asthma Patients

    Kim, Seong Han; Yang, Seo Yeon; You, Jihong; Lee, Sang Bae; You, Jin; Chang, Yoon Soo; Kim, Hyung Jung; Ahn, Chul Min; Byun, Min Kwang; Park, Jung-Won


    Background Specific immunoglobulin E (IgE) sensitization to staphylococcal enterotoxin (SE) has been recently considered to be related to allergic disease, including asthma. Despite studies on specific IgE (sIgE) to SE and its relationship to asthma diagnosis and severity, the association of sIgE to SE with airway hyperresponsiveness (AHR) remains unclear. Methods We enrolled 81 asthma patients admitted to the Severance Hospital in Korea from March 1, 2013, to February 28, 2015 and retrospectively reviewed the electronic medical records of the enrolled subjects. The serum levels of sIgE to SE (A/B) of all subjects was measured using the ImmunoCAP 250 (Phadia) system with SE-sIgE positive defined as >0.10 kU/mL. Results The SE-sIgE level was not significantly correlated with asthma severity (forced expiratory volume in 1 second [FEV1], FEV1/forced vital capacity, sputum eosinophils, and serum eosinophils), whereas the SE-sIgE level in patients with positive AHR (mean±standard error of the mean, 0.606±0.273 kU/mL) was significantly higher than that in patients with negative AHR (0.062±0.015 kU/mL, p=0.034). In regression analysis, SE sensitization (sIgE to SE ≥0.010 kU/mL) was a significant risk factor for AHR, after adjustment for age, sex, FEV1, and sputum eosinophils (odds ratio, 7.090; 95% confidence interval, 1.180–42.600; p=0.032). Prevalence of SE sensitization was higher in patients with allergic rhinitis and non-atopic asthma patients, as compared to patients without allergic rhinitis and atopic asthma patients, respectively, but without statistical significance. Conclusion SE sensitization is significantly associated with AHR.


    V. A. Chumakov


    Full Text Available Abstract. In glioblastoma (GB, it is necessary to take into consideration GB-associated secondary immunodeficiency (SID, so-called syndrome of tumor-associated SID (STASID. Cell subsets having effector and regulatory functions, play an important role in developing STASID, and their proportions in patients with different forms of GB can be of pathogenetic importance and have clinical value for treatment and rehabilitation scheduling as well. The most pathogenically and clinically important features of cell subsets profile of peripheral blood were analyzed in patients with different clinical and morphological types of GB. The patients were divided into three groups, i.e., groups I and II were formed by patients with STASID (marked and slightly marked SID, accordingly; group III – patients with SIDTAS (tumor-associated autoimmune syndrome, associated with SID. Marked suppression of cell immunity is typical of group I - imbalance in T-lymphocytes, in a number of specific subsets, and in subsets clusters, as well as disproportions in the immunoregulatory indexes. In group II, the subset profiles of blood were slightly different from the norm. In patients with SIDTAS, activation of cell immunity was evident, forming SID with signs of autoimmune syndrome, affecting effector and regulatory chains of immunity, and influencing the severity and forecast of the disease. Specific features of the immune status in patients with GB identified can be resulted from different clinicalmorphological types of the tumor; the latter are to be considered in differential diagnostics of clinical course of GB and in scheduling of clinical-immunological efficient anti-tumor pharmacotherapy in pre- and postoperative periods.

  17. MRI is more accurate than CT for patient-specific total knee arthroplasty.

    Frye, Benjamin M; Najim, Amjad A; Adams, Joanne B; Berend, Keith R; Lombardi, Adolph V


    Previous reports have stated that MRI is less accurate than CT for patient specific guide creation in total knee arthroplasty (TKA). Twenty-three TKAs were performed with CT-based guides and 27 with MRI-based guides. A mechanical axis through the central third of the knee was achieved in 88.9% of MRI-guided TKA versus 69.6% of CT-guided TKA (p=0.07). There were nine component outliers in the CT group (39.1%) and two in the MRI group (7.4%, p=0.00768). The relative risk of having an outlier using a CT-based guide was 5.28 times that of an MRI-based guide. Superior overall alignment and fewer outliers were achieved with the use of MRI compared with CT. MRI is the best imaging modality for surgeons wishing to utilize patient specific guides for TKA.

  18. Anisotropic Finite Element Modeling Based on a Harmonic Field for Patient-Specific Sclera

    Xu Jia


    Full Text Available Purpose. This study examined the influence of anisotropic material for human sclera. Method. First, the individual geometry of patient-specific sclera was reproduced from a laser scan. Then, high quality finite element modeling of individual sclera was performed using a convenient automatic hexahedral mesh generator based on harmonic field and integrated with anisotropic material assignment function. Finally, comparison experiments were designed to investigate the effects of anisotropy on finite element modeling of sclera biomechanics. Results. The experimental results show that the presented approach can generate high quality anisotropic hexahedral mesh for patient-specific sclera. Conclusion. The anisotropy shows significant differences for stresses and strain distribution and careful consideration should be given to its use in biomechanical FE studies.

  19. Anisotropic Finite Element Modeling Based on a Harmonic Field for Patient-Specific Sclera.

    Jia, Xu; Liao, Shenghui; Duan, Xuanchu; Zheng, Wanqiu; Zou, Beiji


    Purpose. This study examined the influence of anisotropic material for human sclera. Method. First, the individual geometry of patient-specific sclera was reproduced from a laser scan. Then, high quality finite element modeling of individual sclera was performed using a convenient automatic hexahedral mesh generator based on harmonic field and integrated with anisotropic material assignment function. Finally, comparison experiments were designed to investigate the effects of anisotropy on finite element modeling of sclera biomechanics. Results. The experimental results show that the presented approach can generate high quality anisotropic hexahedral mesh for patient-specific sclera. Conclusion. The anisotropy shows significant differences for stresses and strain distribution and careful consideration should be given to its use in biomechanical FE studies.

  20. A review of rapid prototyped surgical guides for patient-specific total knee replacement.

    Krishnan, S P; Dawood, A; Richards, R; Henckel, J; Hart, A J


    Improvements in the surgical technique of total knee replacement (TKR) are continually being sought. There has recently been interest in three-dimensional (3D) pre-operative planning using magnetic resonance imaging (MRI) and CT. The 3D images are increasingly used for the production of patient-specific models, surgical guides and custom-made implants for TKR. The users of patient-specific instrumentation (PSI) claim that they allow the optimum balance of technology and conventional surgery by reducing the complexity of conventional alignment and sizing tools. In this way the advantages of accuracy and precision claimed by computer navigation techniques are achieved without the disadvantages of additional intra-operative inventory, new skills or surgical time. This review describes the terminology used in this area and debates the advantages and disadvantages of PSI.

  1. [Renal histology in 44 patients with specific antibodies of soluble nuclear antigens].

    Meyer, O; Gaudreau, A; Peltier, A P


    The authors studied the correlations between renal histology and specific antinuclear antibodies of soluble nuclear antigens (anti-Sm, anti-RNP, anti-protein) in 44 patients with such auto-antibodies. They were mostly patients with lupus erythematosus (35/44), more rarely mixed collagen disease or Sjögren's disease. The presence of any one of the specific antibodies of nuclear antigens is not associated with any special renal prognosis; thus the presence of anti-RNP does not mean that there are no histological renal lesions. The renal prognosis depends in fact on the presence of anti-ADN native antibodies. Among the other laboratory parameters (rheumatoid factors, complement levels, cryoglobulinemia) only hypocomplementemia seems to be associated with a poor renal prognosis, the presence of rheumatoid factor has perhaps a protective role.

  2. Evaluation of a patient specific femoral alignment guide for hip resurfacing.

    Olsen, Michael; Naudie, Douglas D; Edwards, Max R; Sellan, Michael E; McCalden, Richard W; Schemitsch, Emil H


    A novel alternative to conventional instrumentation for femoral component insertion in hip resurfacing is a patient specific, computed tomography based femoral alignment guide. A benchside study using cadaveric femora was performed comparing a custom alignment guide to conventional instrumentation and computer navigation. A clinical series of twenty-five hip resurfacings utilizing a custom alignment guide was conducted by three surgeons experienced in hip resurfacing. Using cadaveric femora, the custom guide was comparable to conventional instrumentation with computer navigation proving superior to both. Clinical femoral component alignment accuracy was 3.7° and measured within ± 5° of plan in 20 of 24 cases. Patient specific femoral alignment guides provide a satisfactory level of accuracy and may be a better alternative to conventional instrumentation for initial femoral guidewire placement in hip resurfacing.

  3. Wall-Less Flow Phantoms With Tortuous Vascular Geometries: Design Principles and a Patient-Specific Model Fabrication Example.

    Ho, Chung Kit; Chee, Adrian J Y; Yiu, Billy Y S; Tsang, Anderson C O; Chow, Kwok Wing; Yu, Alfred C H


    Flow phantoms with anatomically realistic geometry and high acoustic compatibility are valuable investigative tools in vascular ultrasound studies. Here, we present a new framework to fabricate ultrasound-compatible flow phantoms to replicate human vasculature that is tortuous, nonplanar, and branching in nature. This framework is based upon the integration of rapid prototyping and investment casting principles. A pedagogical walkthrough of our engineering protocol is presented in this paper using a patient-specific cerebral aneurysm model as an exemplar demonstration. The procedure for constructing the flow circuit component of the phantoms is also presented, including the design of a programmable flow pump system, the fabrication of blood mimicking fluid, and flow rate calibration. Using polyvinyl alcohol cryogel as the tissue mimicking material, phantoms developed with the presented protocol exhibited physiologically relevant acoustic properties [attenuation coefficient: 0.229±0.032 dB/( [Formula: see text]) and acoustic speed: 1535±2.4 m/s], and their pulsatile flow dynamics closely resembled the flow profile input. As a first application of our developed phantoms, the flow pattern of the patient-specific aneurysm model was visualized by performing high-frame-rate color-encoded speckle imaging over multiple time-synchronized scan planes. Persistent recirculation was observed, and the vortex center was found to shift in position over a cardiac cycle, indicating the 3-D nature of flow recirculation inside an aneurysm. These findings suggest that phantoms produced from our reported protocol can serve well as acoustically compatible test beds for vascular ultrasound studies, including 3-D flow imaging.

  4. Pathogen-Specific Local Immune Fingerprints Diagnose Bacterial Infection in Peritoneal Dialysis Patients

    Lin, Chan-Yu; Roberts, Gareth W.; Kift-Morgan, Ann; Donovan, Kieron L.; Topley, Nicholas; Eberl, Matthias


    Accurate and timely diagnosis of bacterial infection is crucial for effective and targeted treatment, yet routine microbiological identification is inefficient and often delayed to an extent that makes it clinically unhelpful. The immune system is capable of a rapid, sensitive and specific detection of a broad spectrum of microbes, which has been optimized over millions of years of evolution. A patient's early immune response is therefore likely to provide far better insight into the true nat...

  5. Linear Elastic Properties of the Facial Soft Tissues Using an Aspiration Device: Towards Patient Specific Characterization.

    Luboz, Vincent; Promayon, Emmanuel; Payan, Yohan


    International audience; Biomechanical modeling of the facial soft tissue behavior is needed in aesthetic or maxillo-facial surgeries where the simulation of the bone displacements cannot accurately predict the visible outcome on the patient's face. Because these tissues have different nature and elastic properties across the face, depending on their thickness, and their content in fat or muscle, individualizing their mechanical parameters could increase the simulation accuracy. Using a specif...

  6. High specificity of a novel Zika virus ELISA in European patients after exposure to different flaviviruses.

    Huzly, Daniela; Hanselmann, Ingeborg; Schmidt-Chanasit, Jonas; Panning, Marcus


    The current Zika virus (ZIKV) epidemic in the Americas caused an increase in diagnostic requests in European countries. Here we demonstrate high specificity of the Euroimmun anti-ZIKV IgG and IgM ELISA tests using putative cross-reacting sera of European patients with antibodies against tick-borne encephalitis virus, dengue virus, yellow fever virus and hepatitis C virus. This test may aid in counselling European travellers returning from regions where ZIKV is endemic.

  7. Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients.

    Laguno, Montserrat; Larrousse, Maria; Blanco, José Luis; Leon, Agathe; Milinkovic, Ana; Martínez-Rebozler, Maria; Loncá, Montserrat; Martinez, Esteban; Sanchez-Tapias, Jose Maria; de Lazzari, Elisa; Gatell, José Maria; Costa, Josep; Mallolas, Josep


    Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies

  8. Experiences of parents and patients with the timing of Mucopolysaccharidosis type I (MPS I) diagnoses and its relevance to the ethical debate on newborn screening.

    de Ru, Minke H; Bouwman, Machtelt G; Wijburg, Frits A; van Zwieten, Myra C B


    Newborn screening (NBS) techniques have been developed for several lysosomal storage disorders (LSDs), including Mucopolysaccharidosis type I (MPS I). MPS I is an LSD with a wide phenotypic spectrum that ranges from the severe Hurler phenotype to the attenuated Scheie phenotype. To improve the ethical discussion about NBS for MPS I, we performed an interview study to explore the experiences of MPS I patients and their parents with the timings of their diagnoses. We used a qualitative research approach consisting of 17 interviews with the parents of patients with all MPS I phenotypes and with patients with attenuated forms of MPS I. The interviews were audio-recorded, transcribed and subsequently analyzed to identify the main themes identified by the participants. Five important themes, focusing on the experienced disadvantages of delayed diagnosis and the advantages and disadvantages of a hypothetical earlier diagnosis, were identified in our group of participants: 1) delayed diagnosis causing parental frustration, 2) delayed diagnosis causing patient frustration, 3) early diagnosis enabling reproductive decision-making, 4) early diagnosis enabling focusing on the diagnosis, and 5) early diagnosis enabling timely initiation of treatment. There was a remarkable similarity in the experiences with timing of diagnosis between parents of patients with the severe and the attenuated forms. This was the first study to explore the personal experiences of MPS I patients and their parents with diagnostic timing. Our study identified five important themes that are highly relevant to the ethical discussion on expanding NBS programs for MPS I. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations

    Hampstead, Benjamin M.; Stringer, Anthony Y.; Stilla, Randall F.; Amaraneni, Akshay; Sathian, K.


    Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer’s disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically-relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-hour delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded novel stimuli vs. repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals. PMID:21530556

  10. Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST).

    de Souza, Jonas A; Yap, Bonnie J; Wroblewski, Kristen; Blinder, Victoria; Araújo, Fabiana S; Hlubocky, Fay J; Nicholas, Lauren H; O'Connor, Jeremy M; Brockstein, Bruce; Ratain, Mark J; Daugherty, Christopher K; Cella, David


    Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; Pfinancial toxicity were race (P = .04), employment status (Pfinancial distress (P = .49). The COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient-centered outcome. Cancer 2017;123:476-484. © 2016 American Cancer Society. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  11. Lung fibrosis quantified by HRCT in scleroderma patients with different disease forms and ANA specificities

    S. Mancin


    Full Text Available Objective: to define the prevalence of interstitial lung fibrosis in systemic sclerosis (SSc and its relationship with the different clinical forms of disease and ANA specificities. Methods: fifty patients with SSc were submitted to pulmonary high resolution computed tomography (HRCT. Lung abnormalities were evaluated according to Warrick’s score that considers both the severity and the extent of fibrotic lesions. Results: pulmonary HRCT abnormalities were observed in 84% of SSc patients. Ground glass aspects (60%, irregular pleural margins (56% and septal/subpleural lines (68% were the most common lesions. The distribution of these abnormalities favoured the posterior basilar segments of both lungs. HRCT findings were significantly more frequent in males and in patients with the cutaneous diffuse form of SSc and with the specific antibody anti-Scl70. Conclusions: HRCT is a very useful method for the diagnosis of interstitial lung fibrosis in SSc. Warrick’s score permits to quantify the HRCT findings and to evaluate their relationship with the disease clinical forms and ANA specificities.

  12. Sensitivity and specificity of the tilt table test in young patients with unexplained syncope.

    Fouad, F M; Sitthisook, S; Vanerio, G; Maloney, J; Okabe, M; Jaeger, F; Schluchter, M; Maloney, J D


    The usefulness of the head-up tilt testing (HUT) has been previously addressed in diagnosing vasovagal neuroregulatory syncope in the teenage population. However, data concerning sensitivity and specificity is deficient due to the lack of control groups. We compared the response to HUT in young patients referred because of syncope or near syncope (n = 44, mean age 16 +/- 3 years SD) to healthy young volunteers with a normal physical examination and no previous history of syncope (n = 18, mean age 16 +/- 2 years) and to determine the sensitivity and specificity of HUT. The graded tilt protocol was performed at 15 degrees, 30 degrees, and 45 degrees (each for 2 min), and then 60 degrees for 20 minutes. Cuff blood pressure was measured every minute and lead II ECG was continuously monitored. 25 of the 44 patients (57%) developed a vasovagal response or became symptomatic after 13.8 +/- 5.7 minutes of HUT. Three of the 18 volunteers (17%) had a vasovagal response and became symptomatic after 9 +/- 3 minutes of HUT. There was no statistical difference among the four groups (with and without tilt induced vasovagal response) in terms of age and baseline hemodynamic data. The sensitivity of 20 minutes HUT was 57% and its specificity was 83%. The presyncopal hemodynamic response in patients with history of syncope that was characterized by a significant decrease in systolic blood pressure and lack of increase of diastolic blood pressure as compared with baseline and with other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. A Numerical Multiscale Framework for Modeling Patient-Specific Coronary Artery Bypass Surgeries

    Ramachandra, Abhay B.; Kahn, Andrew; Marsden, Alison


    Coronary artery bypass graft (CABG) surgery is performed to revascularize diseased coronary arteries, using arterial, venous or synthetic grafts. Vein grafts, used in more than 70% of procedures, have failure rates as high as 50% in less than 10 years. Hemodynamics is known to play a key role in the mechano-biological response of vein grafts, but current non-invasive imaging techniques cannot fully characterize the hemodynamic and biomechanical environment. We numerically compute hemodynamics and wall mechanics in patient-specific 3D CABG geometries using stabilized finite element methods. The 3D patient-specific domain is coupled to a 0D lumped parameter circulatory model and parameters are tuned to match patient-specific blood pressures, stroke volumes, heart rates and heuristic flow-split values. We quantify differences in hemodynamics between arterial and venous grafts and discuss possible correlations to graft failure. Extension to a deformable wall approximation will also be discussed. The quantification of wall mechanics and hemodynamics is a necessary step towards coupling continuum models in solid and fluid mechanics with the cellular and sub-cellular responses of grafts, which in turn, should lead to a more accurate prediction of the long term outcome of CABG surgeries, including predictions of growth and remodeling.

  14. [Oral cavity microflora in patients with non-specific ulcerative colitis and Crohn's disease].

    Kondrakova, O A; Muliar, E A; Voropaeva, E A; Babin, V N; Dubinin, A V; Briko, N I


    Results of study of microecological disorders in oral cavity of patients with non-specific ulcerative colitis (NSUC) and Crohn's disease (CD) and control subjects (patients with hypertension). Condition of mucosa was assessed on the basis of morphological data and electrophoretic mobility of cell nuclei, whereas structure of microbiocenosis and metabolic activity of microflora--on the basis of saliva bacterial culture and contents and profile of volatile fat acids in it. Detection rate of negative charge of the cell nuclei (decrease of functional activity of epithelium) was significantly higher in patients with NSUC and CD (66.6%) compared with controls (10%). This fact was directly related with hypercolonization of oral cavity by Gram-negative microflora. Lesions of mucosa which are characteristic of NSUC and CD and determined by pathologic immune mechanisms correlated with quantity of pathogenic microflora (Staphylococcus aureus and Candida). Marked differences of chromatograms' patterns were observed in patients with NSUC and CD indicating the suppression of anaerobic microflora in patients with CD and hypercolonization of oral cavity by anaerobic microflora in majority of patients with NSUC.

  15. The research of Proactive Coping Behavior of Patients with Chronic Non-Specific Lung Disease

    Marija A. Yaroslavskaya


    Full Text Available The purpose of the research was to study the patterns of using proactive coping and adherences to it's different types in patients with chronic non-specifi c lung diseases. Participants of the study (N=180 were 30 to 60 years old. The Proactive Coping Inventory was used to assess the patients' psychological status. According to the results of the study patients with chronic non-specifi c lung diseases use dif-ferent types of proactive coping behavior while solving problematic and stressful situations. The research revealed that patients with bronchial asthma don't have the skills of independent decision making, definition of objectives, considering of options in solving conflicts or other inconvenient situations sufficiently developed. Patients with chronic obstructive pulmonary disease are less satisfied with the emotional support that they receive from their relatives and closest people, it's harder for them to reveal their feelings and emotions than for those who suffer from bronchial asthma and healthy ones. The results of the study may be useful in developing educational systems of proactive coping behavior skills for patients with chronic non-specific lung diseases for their health and well-being support.

  16. Surface mesh to voxel data registration for patient-specific anatomical modeling

    de Oliveira, Júlia E. E.; Giessler, Paul; Keszei, András.; Herrler, Andreas; Deserno, Thomas M.


    Virtual Physiological Human (VPH) models are frequently used for training, planning, and performing medical procedures. The Regional Anaesthesia Simulator and Assistant (RASimAs) project has the goal of increasing the application and effectiveness of regional anesthesia (RA) by combining a simulator of ultrasound-guided and electrical nerve-stimulated RA procedures and a subject-specific assistance system through an integration of image processing, physiological models, subject-specific data, and virtual reality. Individualized models enrich the virtual training tools for learning and improving regional anaesthesia (RA) skills. Therefore, we suggest patient-specific VPH models that are composed by registering the general mesh-based models with patient voxel data-based recordings. Specifically, the pelvis region has been focused for the support of the femoral nerve block. The processing pipeline is composed of different freely available toolboxes such as MatLab, the open Simulation framework (SOFA), and MeshLab. The approach of Gilles is applied for mesh-to-voxel registration. Personalized VPH models include anatomical as well as mechanical properties of the tissues. Two commercial VPH models (Zygote and Anatomium) were used together with 34 MRI data sets. Results are presented for the skin surface and pelvic bones. Future work will extend the registration procedure to cope with all model tissue (i.e., skin, muscle, bone, vessel, nerve, fascia) in a one-step procedure and extrapolating the personalized models to body regions actually being out of the captured field of view.

  17. WE-D-BRA-05: Pseudo In Vivo Patient Dosimetry Using a 3D-Printed Patient-Specific Phantom

    Ger, R; Craft, DF [The University of Texas Graduate School of Biomedical Sciences (United States); Burgett, EA [Idaho State University, Pocatello, idaho (United States); Price, RR [RANDJ Consulting, Frederick, MD (United States); Kry, SF; Howell, RM [The University of Texas Graduate School of Biomedical Sciences (United States); The University of Texas MD Anderson Cancer Ctr., Houston, TX (United States)


    Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by an ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between

  18. JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients

    Mancuso Roberta


    Full Text Available Abstract Background The use of natalizumab in multiple sclerosis (MS may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML. Methods JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic. Results Perforin- and grazymes-containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a-expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naïve CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed. Conclusion The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.

  19. Computational Simulations of Inferior Vena Cava (IVC) Filter Placement and Hemodynamics in Patient-Specific Geometries

    Aycock, Kenneth; Sastry, Shankar; Kim, Jibum; Shontz, Suzanne; Campbell, Robert; Manning, Keefe; Lynch, Frank; Craven, Brent


    A computational methodology for simulating inferior vena cava (IVC) filter placement and IVC hemodynamics was developed and tested on two patient-specific IVC geometries: a left-sided IVC, and an IVC with a retroaortic left renal vein. Virtual IVC filter placement was performed with finite element analysis (FEA) using non-linear material models and contact modeling, yielding maximum vein displacements of approximately 10% of the IVC diameters. Blood flow was then simulated using computational fluid dynamics (CFD) with four cases for each patient IVC: 1) an IVC only, 2) an IVC with a placed filter, 3) an IVC with a placed filter and a model embolus, all at resting flow conditions, and 4) an IVC with a placed filter and a model embolus at exercise flow conditions. Significant hemodynamic differences were observed between the two patient IVCs, with the development of a right-sided jet (all cases) and a larger stagnation region (cases 3-4) in the left-sided IVC. These results support further investigation of the effects of IVC filter placement on a patient-specific basis.

  20. Importance of patient-specific intraoperative guides in complex maxillofacial reconstruction.

    Rohner, Dennis; Guijarro-Martínez, Raquel; Bucher, Peter; Hammer, Beat


    Conventional maxillofacial reconstruction often leads to suboptimal results due to inaccurate planning or surgical difficulties in adjusting a free flap and osteosynthesis plates into a three-dimensional defect. To justify the importance of patient-specific intraoperative guides in complex maxillofacial reconstruction. CLINICAL EXAMPLE: A 40-year old patient underwent a left hemimaxillectomy for an adenoid cystic carcinoma of the palate. Six years later, massive recurrence required radical resection of the left orbit and reconstruction with cranial bone grafts and a free latissimus dorsi flap. Postoperative radiotherapy resulted in local osteoradionecrosis. Surgical revision and restoration of the maxillary defect with a prefabricated fibula flap was performed. The authors provide ample information on the application of computer-aided design and manufacturing (CAD-CAM) and rapid prototyping at each reconstructive step. Stereolithographic models enable simulation of the resective and reconstructive phases, prebending of reconstruction plates and fabrication of surgical guides. Optimal restitution of complex maxillofacial defects requires meticulous planning of the surgical and prosthetic phases and effective transfer of the plan to the operating room through patient specific guides. CAD-CAM technology and stereolithographic models represent an effective strategy to achieve this. Improved patient outcomes and intraoperative efficiency certainly offset the inherent increase in costs. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  1. Clinical Relevance of CDH1 and CDH13 DNA-Methylation in Serum of Cervical Cancer Patients

    Günther K. Bonn


    Full Text Available This study was designed to investigate the DNA-methylation status of E-cadherin (CDH1 and H-cadherin (CDH13 in serum samples of cervical cancer patients and control patients with no malignant diseases and to evaluate the clinical utility of these markers. DNA-methylation status of CDH1 and CDH13 was analyzed by means of MethyLight-technology in serum samples from 49 cervical cancer patients and 40 patients with diseases other than cancer. To compare this methylation analysis with another technique, we analyzed the samples with a denaturing high performance liquid chromatography (DHPLC PCR-method. The specificity and sensitivity of CDH1 DNA-methylation measured by MethyLight was 75% and 55%, and for CDH13 DNA-methylation 95% and 10%. We identified a specificity of 92.5% and a sensitivity of only 27% for the CDH1 DHPLC-PCR analysis. Multivariate analysis showed that serum CDH1 methylation-positive patients had a 7.8-fold risk for death (95% CI: 2.2–27.7; p = 0.001 and a 92.8-fold risk for relapse (95% CI: 3.9–2207.1; p = 0.005. We concluded that the serological detection of CDH1 and CDH13 DNA-hypermethylation is not an ideal diagnostic tool due to low diagnostic specificity and sensitivity. However, it was validated that CDH1 methylation analysis in serum samples may be of potential use as a prognostic marker for cervical cancer patients.

  2. Surgical management of maxillomandibular advancement in sleep apnea patients: specific technical considerations.

    Gilon, Y; Raskin, S; Heymans, O; Poirrier, R


    Maxillomandibular advancement is an integral part of the surgical treatment of patients suffering from obstructive sleep apnea. A number of publications report its efficacy and have attempted to define predictive success criteria. However, few authors have shown an interest in the surgical specificity of this intervention and in the difficulties that can be encountered, which differ from those seen in conventional orthognathic surgery. In this article, a series of patients treated with maxillomandibular osteotomy to correct obstructive sleep apnea syndrome (n = 17) are compared with patients who underwent surgery for the correction of dentofacial disharmonies (n = 33). Observations emphasized the importance of respecting a strict surgical and postsurgical protocol to avoid any technical traps linked to maxillomandibular advancement, both in preoperative simulations and during and after surgery. Results concerning sleep parameters will be the subject of a future publication.


    T. E. Kissina


    Full Text Available Abstract. The aim of the present study was to determine the different profiles of the immune responsiveness of the patients with fibro-cavernous pulmonary tuberculosis to PPD from M.tuberculosis in comparison with their response to standart mitogen and IFNγ. A pronounced specific Th1 response was found, evidenced by the enhanced proliferation and IL-2 and IFNγ production after contact of their peripheral blood mononuclear cells (PBMCs with PPD. At the same time a high frequency of PPD-anergy was shown: сonsiderable proportion of TB patients was characterized by low proliferative response to PPD coupled with the low levels of IL-2 and IFNγ. Most of the patients revealed failure of monocyte/macrophage oxidative burst in response to PPD. Additionally a positive correlation was found between the levels of their PBMC’s oxidative burst and IL-4 production.

  4. Colorectal cancer driver genes identified by patient specific comparison of cytogenetic microarray

    Mohammad Azhar Aziz


    Full Text Available Colorectal cancer (CRC, which has high prevalence in Saudi Arabia and worldwide, needs better understanding by exploiting the latest available cytogenetic microarrays. We used biopsy tissue from consenting colorectal cancer patients to extract DNA and carry out microarray analysis using a CytoScan HD platform from Affymetrix. Patient specific comparisons of tumor–normal pairs were carried out. To find out the high probability key players, we performed Genomic Identification of Significant Targets in Cancer analysis and found 144 genes to form the list of driver genes. Of these, 24 genes attained high GISTIC scores and suggest being significantly associated with CRC. Loss of heterozygosity and uniparental disomy were found to affect 9 genes and suggest different mechanisms associated with CRC in every patient. Here we present the details of the methods used in carrying out the above analyses. Also, we provide some additional data on biomarker analysis that would complement the findings.

  5. Using an age-specific nursing model to tailor care to the adolescent surgical patient.

    Monahan, Janean Carter


    A surgical experience can be stressful for any patient. When the patient is an adolescent, however, the surgical experience can create significant stress, which is related to normal adolescent development. Perioperative nursing care should address what adolescent patients perceive as stressful and should provide a safe environment so that a successful surgical outcome can be achieved. To accomplish this, a nursing model specific to perioperative nursing practice should be developed to guide nurses when providing care to adolescents. The Adolescent Perioperative System Stability Model based on the Neuman Systems Model provides a framework for defining scope of practice and organizing nursing care that is appropriate for the adolescent during a surgical experience. In addition to guiding nursing practice, this model provides direction and guidance for future studies of adolescents in the perioperative setting.

  6. Specific features of clostridium difficile colitis in patients with inflammatory bowel disease

    Mihai Catalina


    Full Text Available Through its specific biological, epidemiological, diagnostic and infection management features, Clostridium difficile infection (CDI can be considered a major health concern, especially in inflammatory bowel disease (IBD patients. In this particular infection, many IBD risk factors are triggered due to bowel inflammation, antibiotics use, microbiota changes, immunosuppressive therapy use and surgical intervention. Thus, each IBD and diarrhea patient must be tested for CDI. Clinical features show different initial infectious stages such as mild, fulminate and refractory. It has been shown that CDI presents recurrent episodes. CDI treatment consists of metronidazole, vancomycin or fidaxomicin, as well as prophylactic measures. It was recently shown that antibiotic doses must be gradually reduced in order to avoid CDI relapses. Fecal transplantation, effective in CDI management, remains controversial in CDI patients with concurrent IBD.

  7. COPE-ICD: Patient experience of participation in an ICD specific rehabilitation programme

    Berg, Selina Kikkenborg; Pedersen, Birthe Dagmar; Svendsen, Jesper Hastrup


    PURPOSE: Evaluating rehabilitation programmes from the patient's perspective is much needed, as the patients are the most important stakeholders in the health care system. A comprehensive rehabilitation programme, COPE-ICD programme, consists of exercise training and nursing consultations during...... a one year period post ICD implantation. The purpose of this paper is to describe the experience and meaning of participating in a comprehensive ICD-specific rehabilitation programme. METHODS: Qualitative interviews were conducted with 10 patients representing the participating population, and later...... transcribed. The analysis was inspired by Ricoeur's theory of interpretation, which consists of three levels: naive reading, structured analysis and critical interpretation and discussion. RESULTS: The overall concept was that participating in the COPE-ICD programme meant feeling inspired and secure through...

  8. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Qiu Z


    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  9. Women with epilepsy: clinically relevant issues.

    Bangar, S; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E


    Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population.

  10. SU-E-T-603: PBS Prostate Plan Robustness: A Tool for Patient Specific Setup Tolerance

    Tang, S; Song, L; Chen, C; Chang, C; Chon, B; Tsai, H; Soffen, E; Cahlon, O; Mah, D [Procure Proton Therapy Center, Somerset, NJ (United States)


    Purpose: Fiducial markers are commonly used for setup of prostate patients using orthogonal radiographs. After aligned with the markers, the displacement of the bony anatomy relative to the planned DRR can be up to 10 mm. Such offset can potentially have significant dosimetric effects because it changes the radiological path length of protons in differing amounts of bone. It is imperative to develop a method to evaluate its impact on target coverage and hence establish patient specific setup tolerance for prostate proton PBS treatment. Methods: Prostate patients were planned in RayStation according to the PCG protocol with bi-lateral beams. The primary planning objectives are: (1) 100% of CTV receives full prescription dose; (2) 98% of the prescription dose covers at least 98% of the PTV; (3) OARs meet criteria per protocol. For each patient 108 dose perturbations were automatically generated using an in-house script, which considered the isocenter shifting in S-I and A-P directions (up to ±15 mm with an interval of 6mm) as well as the range uncertainty (±3.5%). The target coverage was evaluated on the contour shifted along with prostate to mimic the daily treatment. Results: The minimum CTV coverage as a function of offsets in S-I and A-P directions is presented in a 2D contour map. The offsets along A-P direction generally have greater impact than along S-I direction. Both the CTV D98%>98% or CTV V98%>98% are achievable for most patients if the offset is <10 mm in either direction despite of range uncertainties. Conclusion: We developed a method to evaluate the plan robustness for proton PBS prostate treatment. It can provide patient specific setup tolerance of bony structure offset. For our current planning approach, a 1 cm displacement is acceptable. This approach can be generalized to other target structures that move relative to bony anatomy.

  11. Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.

    Cathomas, R; Klingbiel, D; Geldart, T R; Mead, G M; Ellis, S; Wheater, M; Simmonds, P; Nagaraj, N; von Moos, R; Fehr, M


    Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care. © The Author 2014. Published by Oxford

  12. Interest and attitudes of patients, cancer physicians, medical students and cancer researchers towards a spectrum of genetic tests relevant to breast cancer patients.

    Ngoi, Natalie; Lee, Soo-Chin; Hartman, Mikael; Khin, Lay-Wai; Wong, Andrea


    The perspectives of patients and healthcare professionals towards breast cancer genetic tests that are becoming increasingly available is unexplored in Asians. We surveyed the interest and attitudes of 200 breast cancer patients, 67 cancer physicians, 485 medical students and cancer researchers towards three genetic tests, BRCA1/2 mutation, CYP2D6 genotype and Oncotype DX testing, using hypothetical scenarios. Approximately 60% of patients expressed initial interest in each genetic test, although the majority reversed their decisions once test limitations were conveyed, with <15% maintaining interest in each test. Cancer physicians were most likely to recommend BRCA1/2 mutation testing (73%) and least likely to recommend CYP2D6 genotyping (12%), while patients were more likely to choose Oncotype DX testing (28%) over CYP2D6 (21%) and BRCA1/2 testing (15%). Cost concerns, low educational level and lack of prior awareness of genetic testing were the main barriers against breast cancer genetic testing among Asian patients.

  13. Relevance of water gymnastics in rehabilitation programs in patients with chronic heart failure or coronary artery disease with normal left ventricular function.

    Teffaha, Daline; Mourot, Laurent; Vernochet, Philippe; Ounissi, Fawzi; Regnard, Jacques; Monpère, Catherine; Dugué, Benoit


    Exercise training is included in cardiac rehabilitation programs to enhance physical capacity and cardiovascular function. Among the existing rehabilitation programs, exercises in water are increasingly prescribed. However, it has been questioned whether exercises in water are safe and relevant in patients with stable chronic heart failure (CHF), coronary artery disease (CAD) with normal systolic left ventricular function. The goal was to assess whether a rehabilitation program, including water-based gymnastic exercises, is safe and induces at least similar benefits as a traditional land-based training. Twenty-four male CAD patients and 24 male CHF patients with stable clinical status participated in a 3-week rehabilitation. They were randomized to either a group performing the training program totally on land (CADl, CHFl; endurance + callisthenic exercises) or partly in water (CADw, CHFw; land endurance + water callisthenic exercises). Before and after rehabilitation, left ventricular systolic and cardiorespiratory functions, hemodynamic variables and autonomic nervous activities were measured. No particular complications were associated with both of our programs. At rest, significant improvements were seen in CHF patients after both types of rehabilitation (increases in stroke volume and left ventricular ejection fraction [LVEF]) as well as a decrease in heart rate (HR) and in diastolic arterial pressure. Significant increases in peaks VO(2), HR, and power output were observed in all patients after rehabilitation in exercise test. The increase in LVEF at rest, in HR and power output at the exercise peak were slightly higher in CHFw than in CHFl. Altogether, both land and water-based programs were well tolerated and triggered improvements in cardiorespiratory function. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Study of the anatomical position of the femoral nerve by magnetic resonance imaging in patients with fractured neck of femur: relevance to femoral nerve block.

    Mehmood, Shehzad


    STUDY OBJECTIVE: To determine the anatomical location of the femoral nerve in patients who have sustained fracture of the neck of femur, and its relevance to femoral nerve block technique. DESIGN: Prospective, observational clinical study. SETTING: Orthopedic and Radiology departments of a regional hospital. SUBJECTS: 10 consecutive adult ASA physical status II and III patients (mean age, 78.5 yrs) and 4 adult healthy volunteers. INTERVENTIONS: A T1 magnetic resonance imaging scan was performed of both upper thighs in patients and healthy volunteers successfully. MEASUREMENTS: The distance (mm) between the midpoint of the femoral artery and the midpoint of the femoral nerve, and the distance of the femoral nerve from the skin was measured at the mid-inguinal ligament, the pubic tubercle, and at the mid-inguinal crease. Data are shown as means (SD). Differences between both sides were compared using paired Student\\'s t-tests. P < 0.05 was significant. MAIN RESULTS: In patients the mean distance (mm) between the midpoint of the femoral nerve from the midpoint of femoral artery at the mid-inguinal crease on the fractured and non-fractured sides was 10.7 and 11.0, respectively (P = 0.87). The mean distance (mm) between the midpoint of the femoral nerve from the midpoint of the femoral artery at the mid-inguinal ligament on the fractured and non-fractured sides was 9.64 and 12.5, respectively (P = 0.03). The mean distance (mm) between the midpoint of the femoral nerve from the midpoint of the femoral artery at the pubic tubercle on the fractured and non-fractured sides was 8.74 and 10.49, respectively (P = 0.18). CONCLUSIONS: Blockade of the femoral nerve may be easier to perform at the mid-inguinal crease in patients with fractured neck of femur.

  15. Cause-specific mortality in adult epilepsy patients from Tyrol, Austria: hospital-based study.

    Granbichler, Claudia A; Oberaigner, Willi; Kuchukhidze, Giorgi; Bauer, Gerhard; Ndayisaba, Jean-Pierre; Seppi, Klaus; Trinka, Eugen


    Epilepsy is a devastating condition with a considerable increase in mortality compared to the general population. Few studies have focused on cause-specific mortality which we analyse in detail in over 4,000 well-characterized epilepsy patients. The cohort comprised of epilepsy patients ≥ 18, treated between 1970 and 2009 at the epilepsy clinic of Innsbruck Medical University, Austria, and living in the province of Tyrol, Austria. Epilepsy diagnosis was based on ILAE guidelines (1989); patients with brain tumor were excluded. Deceased patients and causes of death (ICD-codes) were obtained via record linkage to the national death registry. We computed age-, sex-, and period-adjusted standardized mortality rates (SMR) for 36 diagnoses subgroups in four major groups. Additional analyses were performed for an incidence cohort. Overall cohort: 4,295 patients, 60,649.1 person-years, 822 deaths, overall SMR 1.7 (95 % CI 1.6-1.9), highest elevated cause-specific SMR: congenital anomalies [7.1 (95 % CI 2.3-16.6)], suicide [4.2 (95 % CI 2.0-8.1)], alcohol dependence syndrome [3.9 (95 % CI 1.8-7.4)], malignant neoplasm of esophagus [3.1 (95 % CI 1.2-6.4)], pneumonia [2.7 (95 % CI 1.6-4.2)]. Incidence cohort: 1,299 patients, 14,215.4 person-years, 267 deaths, overall SMR 1.8 (95 % CI 1.6-2.1), highest elevated cause-specific SMR congenital anomalies [10.8 (95 % CI 1.3-39.3)], suicide [6.8 (95 % CI 1.4-19.8)], alcohol dependence syndrome (6.4 [95 % CI 1.8-16.5)], pneumonia [3.9 (95 % CI 1.8-7.4)], cerebrovascular disease at 3.5 (95 % CI 2.6-4.6). Mortality due to mental health problems, such as suicide or alcohol dependence syndrome, malignant neoplasms, and cerebrovascular diseases was highly increased in our study. In addition to aim for seizure freedom, we suggest improving general health promotion, including cessation of smoking, lowering of alcohol intake, and reduction of weight as well as early identification of psychiatric comorbidity in patients with epilepsy.

  16. A Review of HIV-Specific Patient-Reported Outcome Measures.

    Engler, Kim; Lessard, David; Lebouché, Bertrand


    The use of patient-reported outcome (PRO) measures to provide added feedback to health providers is receiving interest as a means of improving clinical care and patient outcomes, and contributing to more patient-centered care. In human immunodeficiency virus (HIV), while PROs are used in research, their application in clinical practice has been limited despite their potential utility. PRO selection is an important consideration when contemplating their use. As past reviews of PROs in HIV have focused on particular areas (e.g. disability, satisfaction with care), a more comprehensive review could better inform on the available instruments and their scope. This article reviews HIV-specific PROs to produce an inventory and to identify the central concepts targeted over time. Seven databases were searched (HAPI, MEDLINE, PsychINFO, PubMed, EMBASE, CINAHL, Google Scholar), generating 14,794 records for evaluation. From these records, 117 HIV-specific PROs were identified and categorized based on a content analysis of their targeted concept: Health-Related Quality of Life (23; 20 %), ART and Adherence-Related Views and Experiences (19; 16 %), Healthcare-Related Views and Experiences (15; 13 %), Psychological Challenges (12; 10 %), Symptoms (12; 10 %), Psychological Resources (10; 9 %), HIV Self-Management and Self-Care (8; 7 %), HIV-Related Stigma (8; 7 %), Body and Facial Appearance (4; 3 %), Social Support (3; 3 %), Sexual and Reproductive Health (2; 2 %), and Disability (1; 1 %). This review highlights the variety and evolution of HIV-specific PROs, with the arrival of seven categories of PROs only after the advent of highly-active antiretroviral therapy. Our inventory also offers a useful resource. However, the interest of further HIV-specific PRO development should be explored in sexual health, which received little independent attention.

  17. Allergen micro-array detection of specific IgE-reactivity in Chinese allergy patients

    ZHENG Yi-wu; ZHONG Nan-shan; Michael D Spangfort; LI Jing; LAI Xu-xin; ZHAO De-yu; LIU Xiao-fan; LIN Xiao-ping; Birgitte Gjesing; Paola Palazzo; Adriano Mari


    Background Allergen micro-arrays are powerful tools for screening of serum IgE-reactivity.In this study allergen micro-arrays were used to identify dominating IgE-binding allergens and cross-reactivity patterns among selected Chinese allergy patients.Methods The study was conducted using patient sera from the cities of Guangzhou,Nanjing,Chengdu and Shenyang.In total 100 sera with Dermatophagoides pteronyssinus (Der p) specific IgE-levels higher than 50 kU/L were selected for testing against 103 individual allergens.Results Among 100 selected patients, 95% showed IgE-reactivity towards house-dust mite allergens Dermatophagoides farinae (Der f) 1,Der f 2 and Der p 2 and 94% were IgE positive against Der p 1,and 60% of sera contained IgE reacting against allergen Euroglyphus maynei (Eur m) 2.IgE against cat allergen,Felisdomesticus (Fel d)1,was seen in 20%.Only 2% showed specific IgE-reactivity to Der p 10,a panallergen belonging to the tropomyosin family.Serum IgE-reactivity towards other allergens was in general low.IgE-reactivity against pollen allergens showed geographic differences.Conclusions This study clearly confirms that group 1 and group 2 are major allergens of house dust mites.These selected house-dust mite allergy patients are close to being mono-sensitized.Der p 10 is not an important allergen for cross-reactivity.Specific IgE-sensitization towards pollen allergens is low in southern China compared to other regions.The prevalence of food and stinging insect allergens known to give rise to IgE-mediated cross-reactivity is 2% or less.

  18. Efficient generation of lens progenitor cells from cataract patient-specific induced pluripotent stem cells.

    Xiaodi Qiu

    Full Text Available The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2, and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP. In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT markers compared with human embryonic stem cells (hESCs and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract

  19. Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells.

    Jia, Bei; Chen, Shen; Zhao, Zhiju; Liu, Pengfei; Cai, Jinglei; Qin, Dajiang; Du, Juan; Wu, Changwei; Chen, Qianyu; Cai, Xiujuan; Zhang, Hui; Yu, Yanhong; Pei, Duanqing; Zhong, Mei; Pan, Guangjin


    Hemophilia A (HA) is a severe, congenital bleeding disorder caused by the deficiency of clotting factor VIII (FVIII). For years, traditional laboratory animals have been used to study HA and its therapies, although animal models may not entirely mirror the human pathophysiology. Human induced pluripotent stem cells (iPSCs) can undergo unlimited self-renewal and differentiate into all cell types. This study aims to generate hemophilia A (HA) patient-specific iPSCs that differentiate into disease-affected hepatocyte cells. These hepatocytes are potentially useful for in vitro disease modeling and provide an applicable cell source for autologous cell therapy after genetic correction. In this study, we mainly generated iPSCs from urine collected from HA patients with integration-free episomal vectors PEP4-EO2S-ET2K containing human genes OCT4, SOX2, SV40LT and KLF4, and differentiated these iPSCs into hepatocyte-like cells. We further identified the genetic phenotype of the FVIII genes and the FVIII activity in the patient-specific iPSC derived hepatic cells. HA patient-specific iPSCs (HA-iPSCs) exhibited typical pluripotent properties evident by immunostaining, in vitro assays and in vivo assays. Importantly, we showed that HA-iPSCs could differentiate into functional hepatocyte-like cells and the HA-iPSC-derived hepatocytes failed to produce FVIII, but otherwise functioned normally, recapitulating the phenotype of HA disease in vitro. HA-iPSCs, particular those generated from the urine using a non-viral approach, provide an efficient way for modeling HA in vitro. Furthermore, HA-iPSCs and their derivatives serve as an invaluable cell source that can be used for gene and cell therapy in regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models

    Thom Simon A


    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs. Method Patient-specific AAA models were created from CT scans of three patients. Two simulations were performed on each lumen model, fluid structure interaction (FSI model and static structural (SS model. The AAA wall was created by dilating the lumen with a uniform 1.5 mm thickness, and was modeled as a non-linear hyperelastic material. Commercial finite element code Adina 8.2 was used for all simulations. The results were compared between the FSI and SS simulations. Results Results are presented for the wall stress patterns, wall shear stress patterns, pressure, and velocity fields within the lumen. It is demonstrated that including fluid flow can change local wall stresses slightly. However, as far as the peak wall stress is concerned, this effect is negligible as the difference between SS and FSI models is less than 1%. Conclusion The results suggest that fully coupled FSI simulation, which requires considerable computational power to run, adds little to rupture risk prediction. This justifies the use of SS models in previous studies.

  1. HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins


    Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (χ2 = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, χ2 = 4.057, P = 0.044).Conclusion HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.


    N. M. Mertaniasih


    Full Text Available Background: Indonesia have many different geographic areas which could be various on the variant strains of Mycobacterium tuberculosis. The gyrB gene codes GyrB protein as sub unit compound of Gyrase enzyme that functioning in multiplication of bacteria. Detection of gyrB gene could be a marker of active multiplication of viable bacteria in the specimen from patients; and some of the DNA sequence regions were conserved and specific in the strain of Mycobacterium tuberculosis that would be a marker for identification. This research aims to analyze the sequence of gyrB gene of Mycobacterium tuberculosis clinical isolates from sputum of pulmonary TB patients in Indonesia, and determine the specific region. Method: Mycobacterium tuberculosis clinical isolates have been collected from sputum of the patients with pulmonary TB that live in some area in Indonesia. Isolation and identification of Mycobacterium tuberculosis clinical isolates using standard culture method; sequence analysis using PCR-direct sequencing of the part bases region of gyrB. Results: this study revealed that nucleotide sequence on a fragment 764 bases of gyrB gene Mycobacterium tuberculosis strains among clinical isolates almost identically to a wild type strain Mycobacterium tuberculosis H37Rv and subspecies member of Mycobacterium tuberculosis complex (MTBC, with a little difference of SNPs; there are many difference nucleotide sequence with MOTT and Gram positive or negative bacteria, except Corynebacterium diphtheriae identically with MTBC. Conclusion: the gyrB sequence in Mycobacterium tuberculosis strains among these clinical isolates from sputum of pulmonary TB patients in Indonesia have the conserved specific DNA region that almost identically with wild type strain H37Rv and MTBC.

  3. Patient-specific blood flow simulation to improve intracranial aneurysm diagnosis

    Fenz, Wolfgang; Dirnberger, Johannes


    We present a novel simulation system of blood flow through intracranial aneurysms including the interaction between blood lumen and vessel tissue. It provides the means to estimate rupture risks by calculating the distribution of pressure and shear stresses in the aneurysm, in order to support the planning of clinical interventions. So far, this has only been possible with commercial simulation packages originally targeted at industrial applications, whereas our implementation focuses on the intuitive integration into clinical workflow. Due to the time-critical nature of the application, we exploit most efficient state-of-the-art numerical methods and technologies together with high performance computing infrastructures (Austrian Grid). Our system builds a three-dimensional virtual replica of the patient's cerebrovascular system from X-ray angiography, CT or MR images. The physician can then select a region of interest which is automatically transformed into a tetrahedral mesh. The differential equations for the blood flow and the wall elasticity are discretized via the finite element method (FEM), and the resulting linear equation systems are handled by an algebraic multigrid (AMG) solver. The wall displacement caused by the blood pressure is calculated using an iterative fluid-structure interaction (FSI) algorithm, and the fluid mesh is deformed accordingly. First simulation results on measured patient geometries show good medical relevance for diagnostic decision support.

  4. Wildtype p53-specific antibody and T-cell responses in cancer patients

    Pedersen, Anders Elm; Stryhn, Anette; Justesen, Sune


    Mutation in the p53 gene based on single amino acid substitutions is a frequent event in human cancer. Accumulated mutant p53 protein is released to antigen presenting cells of the immune system and anti-p53 immune responses even against wt p53 is induced and observed in a number of human cancer...... patients. Detection of antibodies against wt p53 protein has been used as a diagnostic and prognostic marker and discovery of new T-cell epitopes has enabled design of cancer vaccination protocols with promising results. Here, we identified wt p53-specific antibodies in various cancer patients......(264-272) in breast cancer patients and against HLA-A*01:01 binding peptide wt p53(226-234) and HLA-B*07:02 binding peptide wt p53(74-82) in renal cell cancer and breast cancer patients, respectively. Finally, we analyzed antibody and T-cell responses against wt p53 15-mer peptides in patients with metastatic renal...

  5. Patient-Specific Modeling of Interventricular Hemodynamics in Single Ventricle Physiology

    Vedula, Vijay; Feinstein, Jeffrey; Marsden, Alison


    Single ventricle (SV) congenital heart defects, in which babies are born with only functional ventricle, lead to significant morbidity and mortality with over 30% of patients developing heart failure prior to adulthood. Newborns with SV physiology typically undergo three palliative surgeries, in which the SV becomes the systemic pumping chamber. Depending on which ventricle performs the systemic function, patients are classified as having either a single left ventricle (SLV) or a single right ventricle (SRV), with SRV patients at higher risk of failure. As the native right ventricles are not designed to meet systemic demands, they undergo remodeling leading to abnormal hemodynamics. The hemodynamic characteristics of SLVs compared with SRVs is not well established. We present a validated computational framework for performing patient-specific modeling of ventricular flows, and apply it across 6 SV patients (3SLV + 3SRV), comparing hemodynamic conditions between the two subgroups. Simulations are performed with a stabilized finite element method coupled with an immersed boundary method for modeling heart valves. We discuss identification of hemodynamic biomarkers of ventricular remodeling for early risk assessment of failure. This research is supported in part by the Stanford Child Health Research Institute and the Stanford NIH-NCATS-CTSA through Grant UL1 TR001085 and due to U.S. National Institute of Health through NIH NHLBI R01 Grants 5R01HL129727-02 and 5R01HL121754-03.

  6. The screen for cognitive impairment in psychiatry: diagnostic-specific standardization in psychiatric ill patients.

    Gómez-Benito, Juana; Guilera, Georgina; Pino, Óscar; Rojo, Emilio; Tabarés-Seisdedos, Rafael; Safont, Gemma; Martínez-Arán, Anabel; Franco, Manuel; Cuesta, Manuel J; Crespo-Facorro, Benedicto; Bernardo, Miguel; Vieta, Eduard; Purdon, Scot E; Mesa, Francisco; Rejas, Javier


    The Screen for Cognitive Impairment in Psychiatry (SCIP) is a simple and easy to administer scale developed for screening cognitive deficits. This study presents the diagnostic-specific standardization data for this scale in a sample of schizophrenia and bipolar I disorder patients. Patients between 18 and 55 years who are in a stable phase of the disease, diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar I disorder were enrolled in this study. The SCIP-S was administered to 514 patients (57.9% male), divided into two age groups (18-39 and 40-55 years) and two educational level groups (less than and secondary or higher education). The performance of the patients on the SCIP-S is described and the transformed scores for each SCIP-S subtest, as well as the total score on the instrument, are presented as a percentile, z-score, T-scores, and IQ quotient. We present the first jointly developed benchmarks for a cognitive screening test exploring functional psychosis (schizophrenia and bipolar disorder), which provide increased information about patient's cognitive abilities. Having guidelines for interpreting SCIP-S scores represents a step forward in the clinical utility of this instrument and adds valuable information for its use.

  7. NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma.

    von Boehmer, Lotta; Mattle, Muriel; Bode, Peter; Landshammer, Alexandro; Schäfer, Carolin; Nuber, Natko; Ritter, Gerd; Old, Lloyd; Moch, Holger; Schäfer, Niklaus; Jäger, Elke; Knuth, Alexander; van den Broek, Maries


    During cancer progression, malignant cells may evade immunosurveillance. However, evidence for immunological escape in humans is scarce. We report here the clinical course of a melanoma patient whose initial tumor was positive for the antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment. After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG response increased. Over the following years, progressing lesions were resected and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan-A, as well as MHC-I. We propose that cancer control and cancer escape in this patient were governed by NY-ESO-1-specific immunological pressure. Our findings provide evidence for the existence of immunoediting and immunoescape in this cancer patient.

  8. Detection of Serum DNA in Cancer Patients by Modified Methylation Specific PCR

    LIYUongchang; SUNJunning; 等


    Ojbective To search for circulating DNA as a biomarker for the cancer burden of patients[1].Methods Methylation specific PCR(MSP),according to Herman et al,was used to identify this epigenetic modification of DNA from serum and tissue of 111 patients with different cancers.In parallel the mutant K-ras gene was analyzed in 55 cases for comparison.Results Methylation of the p16 gene was found in serum or cancer tissue in about 50% of patients with a statistically significant difference Results Methylation of the p16 gene was found in serum or cancer tissue in about 50% of patients with a statistically significant difference to healthy controls(P<0.05).There was no difference between the DNA from the tumor and from the neighboring normal tissue or from sereum in early cancer.The positivity rate increased with progression of the tumor.20 days after the operation methylated DNA nearly disappeared.The positivity rate for mutant K-ras was only 30% and thus much lower than that of methlated DNA.The combination of the two markers increased the positivity rate of tumors by 13%.Conclusion The detection of methylation of the p16 gene by MSP combined with mutant K-ras is serum of cancer patients would be a very effective method to estimate the cancer burden.

  9. SU-E-T-176: Clinical Experience of Brass Mesh Bolus: Patient-Specific Parameters as Predictors of Measured Dosimetric Effect

    Yock, A; Manger, R; Einck, J; Yashar, C; Sanghvi, P; Hattangadi-Gluth, J; Cervino, L [University of California - San Diego, La Jolla, CA (United States)


    Purpose: Increasingly, brass mesh bolus is used to insure dosimetric coverage of the skin for patients treated post-mastectomy for breast cancer. Contribution of photoelectrons from interactions between the bolus and the primary beam increases dose superficially without affecting dose at greater depths. We present our experience using brass mesh bolus – including patients for whom the bolus was dosimetrically inadequate – along with analysis of relevant patient-specific parameters. Methods: Optically-stimulated luminescent dosimeters (OSLDs) were used to determine the effect of the bolus for 15 patients. They were positioned beneath the bolus within the tangent fields at three positions: 1.5–3cm inside the medial and lateral field edges, and midway between the two. All OSLDs were midfield in the cranial-caudal direction. The measurements were compared with patient-specific parameters including separation, chest wall/breast tissue thickness, beam angle incidence, and planned surface dose. Results: The average OSLD measurement at the medial field edge, midfield, and lateral field edge position was 86.8%, 101.8%, and 92.8% of the prescription dose, respectively. A measurement for one patient was low enough (77.0%) to warrant a switch to an alternative type of bolus. Anatomic parameters were analyzed to investigate the low dose in this case, not observed in the planning system. The patient was observed to have a thin chest wall and very oblique beam angles. A second patient was also switched to an alternative type of bolus due to her being high risk and treated with an electron patch that extended onto the breast. Conclusion: Brass mesh bolus increases dose superficially while leaving dose at greater depths unaffected. However, our results suggest that this effect may be insufficient in patients with a thin chest wall or very oblique beam angles. More data and analysis is necessary to proactively identify patients for whom brass mesh bolus is effective.

  10. Pneumonia in nursing home patients: is it time for a specific therapeutic strategy?

    Gualberto Gussoni


    Full Text Available Background: Nursing home-acquired pneumonia (NHAP was described in 1978, but only in 2005 it has been proposed as part of a new category (health care-associated pneumonia distinct from community- or hospital-acquired infections. However, limited clinical data exist to validate this proposal. Aim of the study: To compare characteristics and outcome of patients hospitalised for pneumonia and coming from private residence or nursing home. Methods: Post-hoc analysis of the prospective phase of the FASTCAP study, performed to evaluate the impact of the Recommendations issued by the Italian Federation of Internal Medicine (FADOI in 2002 on the management of hospitalised community-acquired pneumonia (CAP. Results: The study examined 1,219 patients coming from private residence, and 179 with NHAP. Failures of therapy were significantly more frequent in patients with NHAP (35.8% vs 24.9%; Odds Ratio 1.48; 95% confidence interval 1.05-2.09. Mortality was higher in patients coming from nursing home (24.0% vs 9.8%; OR 2.59; 95% CI 1.72-3.90. Antibiotic treatment was more frequently performed as monotherapy in case of NHAP. Conclusions: At the time of FASTCAP, NHAP was included in the category of CAP, and coherently, treatment of NHAP was not more aggressive if compared to community-acquired infections. However, our results confirm that NHAP is at increased risk for worst outcome, and probably worth considering for specific therapeutic strategies. Future studies are needed to better assess the microbiology of NHAP, and to evaluate if specific treatments, as those recommended by recent guidelines, may improve the outcome for these high-risk patients.

  11. Patients with non-specific neck disorders commonly report upper limb disability.

    Osborn, William; Jull, Gwendolen


    Patients with neck disorders can report difficulties with functional use of their upper limb because of their neck pain. Yet, there is little information on the frequency and specifically, the nature of these upper limb activities. This study surveyed patients with neck pain disorders (n = 103) presenting for management at private physiotherapy clinics in a large metropolitan area to investigate the frequency and nature of reduced upper limb function. Participants were asked to complete four questionnaires, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, the Neck Disability Index (NDI), Pictorial Fear of Activity Scale-Cervical (PFActS-C) and Patient Specific Functional Scale (PSFS). Approximately 80% of patients spontaneously reported that upper limb activities aggravated their neck pain (PSFS). Most frequently, these activities involved loading of the upper limb such as lifting. Eight activity items on the DASH were scored positive by ≥50% of participants. Participants had mild to moderately severe neck pain (NDI: range 2-68%). The DASH and NDI were moderately-highly correlated (ρ = 0.669; p neck pain severity the greater the upper limb functional restrictions. There was a low correlation between the NDI and PFActS-C (ρ = 0.319; p = 0.001). These findings provide evidence that upper limb function is often impaired in association with neck pain disorders and suggest clinicians should routinely question patients regarding upper limb function. The DASH could be used as a suitable outcome measure in its current or possibly a modified form.

  12. Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

    Yuan-Yuan Qin; Ya-Peng Li; Shun Zhang; Ying Xiong; Lin-Ying Guo; Shi-Qi Yang; Yi-Hao Yao


    Background:Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network.However,whether the selection of a specific frequency band could impact the topological properties is still not clear.Our hypothesis is that the topological properties of AD patients are also frequency-specific.Methods:Resting state functional magnetic resonance imaging data from l0 right-handed moderate AD patients (mean age:64.3 years; mean mini mental state examination [MMSE]:18.0) and 10 age and gender-matched healthy controls (mean age:63.6 years; mean MMSE:28.2) were enrolled in this study.The global efficiency,the clustering coefficient (CC),the characteristic path length (CpL),and "small-world" property were calculated in a wide range of thresholds and averaged within each group,at three different frequency bands (0.01-0.06 Hz,0.06-0.11 Hz,and 0.11-0.25 Hz).Results:At lower-frequency bands (0.01-0.06 Hz,0.06-0.11 Hz),the global efficiency,the CC and the "small-world" properties of AD patients decreased compared to controls.While at higher-frequency bands (0.11-0.25 Hz),the CpL was much longer,and the "small-world" property was disrupted in AD,particularly at a higher threshold.The topological p