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Sample records for high-risk neuroblastoma patients

  1. Rapid COJEC Induction Therapy for High-risk Neuroblastoma Patients - Cochrane Review.

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    Peinemann, F; van Dalen, E C; Berthold, F

    2016-04-01

    Neuroblastoma is a rare malignant disease and patients with high-risk neuroblastoma have a poor prognosis. Rapid COJEC induction chemotherapy means (almost) the same total doses given within a shorter time period. In theory, rapid COJEC could reduce the risk of drug resistance and it has been considered as a potential candidate for improving the outcome. The objective was to evaluate effects of rapid COJEC compared to standard induction chemotherapy in patients with high-risk neuroblastoma. We searched the databases CENTRAL, MEDLINE, and EMBASE from inception to 11 November 2014 and included randomized controlled trials. We identified one relevant randomized controlled trial with 130 participants receiving rapid COJEC and 132 participants receiving standard OPEC/COJEC induction chemotherapy. There was no statistically significant difference between the treatment groups in complete response (risk ratio 0.99, 95% confidence interval 0.71 to 1.38, P=0.94) and treatment-related mortality (risk ratio 1.21, 95% confidence interval 0.33 to 4.39, P=0.77). A statistically significant difference in favor of the standard treatment arm was identified for the following early toxicities: febrile neutropenia, septicemia, and renal toxicity. The differences in complete response and treatment-related mortality between treatment alternatives were not statistically significantly different. Based on the currently available evidence, we are uncertain about the effects of rapid COJEC induction chemotherapy in patients with high-risk neuroblastoma. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

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    Polishchuk, Alexei L. [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Li, Richard [Division of Radiation Oncology, Dana Farber/Boston Children' s Cancer and Blood Disorders Center, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hill-Kayser, Christine [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Little, Anthony [Division of Oncology, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Hawkins, Randall A. [Department of Radiology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Hamilton, Jeffrey; Lau, Michael [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Tran, Hung Chi [Division of Hematology/Oncology, Children' s Hospital of Los Angeles, Los Angeles, California (United States); Strahlendorf, Caron [Division of Hematology and Oncology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia (Canada); Lemons, Richard S. [Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Matthay, Katherine K.; DuBois, Steven G. [Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); and others

    2014-07-15

    Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore

  3. Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients

    NARCIS (Netherlands)

    Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

    2017-01-01

    Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients

  4. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

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    Li, Richard; Polishchuk, Alexei; DuBois, Steven; Hawkins, Randall; Lee, Stephanie W.; Bagatell, Rochelle; Shusterman, Suzanne; Hill-Kayser, Christine; Al-Sayegh, Hasan; Diller, Lisa; Haas-Kogan, Daphne A.; Matthay, Katherine K.; London, Wendy B.

    2017-01-01

    Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

  5. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

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    Li, Richard [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Polishchuk, Alexei [School of Medicine, University of California San Francisco, San Francisco, California (United States); DuBois, Steven [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hawkins, Randall [School of Medicine, University of California San Francisco, San Francisco, California (United States); Lee, Stephanie W. [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bagatell, Rochelle [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Shusterman, Suzanne [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hill-Kayser, Christine [Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Al-Sayegh, Hasan [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Diller, Lisa [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Haas-Kogan, Daphne A. [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Matthay, Katherine K. [School of Medicine, University of California San Francisco, San Francisco, California (United States); London, Wendy B. [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); and others

    2017-02-01

    Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

  6. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

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    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  7. Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

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    Fischer, Janina; Pohl, Alexandra; Volland, Ruth; Hero, Barbara; Dübbers, Martin; Cernaianu, Grigore; Berthold, Frank; von Schweinitz, Dietrich; Simon, Thorsten

    2017-08-04

    Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of

  8. Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation.

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    Peinemann, Frank; van Dalen, Elvira C; Enk, Heike; Berthold, Frank

    2017-08-25

    Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumours mainly develop in the adrenal medullary tissue, with an abdominal mass as the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterised by metastasis and other features that increase the risk of an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma. This review is an update of a previously published Cochrane Review. To evaluate the efficacy and safety of additional retinoic acid as part of a postconsolidation therapy after high-dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT), compared to placebo retinoic acid or to no additional retinoic acid in people with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 11), MEDLINE in PubMed (1946 to 24 November 2016), and Embase in Ovid (1947 to 24 November 2016). Further searches included trial registries (on 22 December 2016), conference proceedings (on 23 March 2017) and reference lists of recent reviews and relevant studies. We did not apply limits by publication year or languages. Randomised controlled trials (RCTs) evaluating additional retinoic acid after HDCT followed by HSCT for people with high-risk neuroblastoma compared to placebo retinoic acid or to no additional retinoic acid. Primary outcomes were overall survival and treatment-related mortality. Secondary outcomes were progression-free survival, event-free survival, early toxicity, late toxicity, and health-related quality of life. We used standard

  9. Retinoic Acid for High-risk Neuroblastoma Patients after Autologous Stem Cell Transplantation - Cochrane Review Retinsäure nach erfolgter autologer Stammzelltransplantation bei Hochrisiko-Patienten mit Neuroblastom - Cochrane Review

    NARCIS (Netherlands)

    Peinemann, F.; van Dalen, E. C.; Berthold, F.

    2016-01-01

    Neuroblastoma is a rare malignant disease and patients with high-risk neuroblastoma have a poor prognosis. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome. The objective was to evaluate effects of

  10. Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

    Science.gov (United States)

    Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

    2017-10-01

    Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Dinutuximab in the Treatment of High-Risk Neuroblastoma in Children

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    Hazal Gur

    2017-06-01

    Full Text Available Neuroblastoma is the most common extracranial tumor derived from neural crest cells in childhood, and treatment of high-risk neuroblastoma is a difficulty in oncology field. The discovery of new treatment strategies to treat pediatric patients with high-risk neuroblastoma is important. Dinutuximab (ch14.18; Unituxin, a chimeric human-mouse monoclonal antibody, is approved by Food and Drug Administration in 2015 to be used specifically in the treatment of high-risk neuroblastoma. It binds the disialoganglioside (GD2 antigen on the surface of neuroblastoma cells and induces lysis of GD2-expressed neuroblastoma cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. To enhance its activity, it is used with a combination of granulocyte-macrophage colony-stimulating factor, interleukin 2, and 13- cis -retinoic acid. In this review, we discuss the use of dinutuximab in the treatment of high-risk neuroblastoma.

  12. Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.

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    Semeraro, Michaela; Rusakiewicz, Sylvie; Minard-Colin, Véronique; Delahaye, Nicolas F; Enot, David; Vély, Frédéric; Marabelle, Aurélien; Papoular, Benjamin; Piperoglou, Christelle; Ponzoni, Mirco; Perri, Patrizia; Tchirkov, Andrei; Matta, Jessica; Lapierre, Valérie; Shekarian, Tala; Valsesia-Wittmann, Sandrine; Commo, Frédéric; Prada, Nicole; Poirier-Colame, Vichnou; Bressac, Brigitte; Cotteret, Sophie; Brugieres, Laurence; Farace, Françoise; Chaput, Nathalie; Kroemer, Guido; Valteau-Couanet, Dominique; Zitvogel, Laurence

    2015-04-15

    The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner. Serum concentration of soluble B7-H6 correlated with the down-regulation of NKp30, bone marrow metastases, and chemoresistance, and soluble B7-H6 contained in the serum of HR-NB patients inhibited NK cell functions in vitro. The expression of distinct NKp30 isoforms affecting the polarization of NK cell functions correlated with 10-year event-free survival in three independent cohorts of HR-NB in remission from metastases after induction chemotherapy (n = 196, P 18 months. We conclude that the interaction between NKp30 and B7-H6 may contribute to the fate of NB patients and that both the expression of NKp30 isoforms on circulating NK cells and the concentration of soluble B7-H6 in the serum may be clinically useful as biomarkers for risk stratification. Copyright © 2015, American Association for the Advancement of Science.

  13. Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.

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    Amoroso, Loredana; Erminio, Giovanni; Makin, Guy; Pearson, Andrew D J; Brock, Penelope; Valteau-Couanet, Dominique; Castel, Victoria; Pasquet, Marlène; Laureys, Genevieve; Thomas, Caroline; Luksch, Roberto; Ladenstein, Ruth; Haupt, Riccardo; Garaventa, Alberto

    2018-01-01

    Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([ 123 I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m 2 /day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m 2 , and doxorubicin, 45 mg/m 2 . Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

  14. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

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    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  15. Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

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    Barbara Banelli

    Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

  16. Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

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    Sara Stigliani

    2015-01-01

    Full Text Available The prognosis of children with metastatic neuroblastoma (NB > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1, Granzyme B (GRMB, and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.. Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.

  17. Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy

    International Nuclear Information System (INIS)

    Simon, Thorsten; Hero, Barbara; Faldum, Andreas; Handgretinger, Rupert; Schrappe, Martin; Klingebiel, Thomas; Berthold, Frank

    2011-01-01

    The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective

  18. Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy

    Directory of Open Access Journals (Sweden)

    Schrappe Martin

    2011-01-01

    Full Text Available Abstract Background The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide. In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months. Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69 served as controls. Results The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098. In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038. The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4% compared to NB90 MT (34 ± 5%, p = 0.026 and to no consolidation (35 ± 6%, p = 0.019. Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.

  19. The genetic landscape of high-risk neuroblastoma.

    Science.gov (United States)

    Pugh, Trevor J; Morozova, Olena; Attiyeh, Edward F; Asgharzadeh, Shahab; Wei, Jun S; Auclair, Daniel; Carter, Scott L; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D; Hirst, Martin; Jackman, Shaun D; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A; Mungall, Karen L; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A; Diamond, Maura; Diskin, Sharon J; Mosse, Yael P; Wood, Andrew C; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B; Moyer, Yvonne; Gastier-Foster, Julie M; Smith, Malcolm A; Guidry Auvil, Jaime M; Gerhard, Daniela S; Hogarty, Michael D; Jones, Steven J M; Lander, Eric S; Gabriel, Stacey B; Getz, Gad; Seeger, Robert C; Khan, Javed; Marra, Marco A; Meyerson, Matthew; Maris, John M

    2013-03-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

  20. The genetic landscape of high-risk neuroblastoma

    Science.gov (United States)

    Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

    2013-01-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

  1. Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Elzembely

    2018-03-01

    Full Text Available Purpose: High-dose chemotherapy with autologous stem-cell rescue (SCR is a key component of high-risk neuroblastoma (HRNB therapy. Carboplatin, etoposide, and melphalan (CEM or busulfan and melphalan (Bu/Mel are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT. We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt compared with the resource-rich United States. Patients and Methods: We performed a retrospective comparative review of single CEM-based HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research Center (FH in the United States (2005 to 2015 versus Bu/Mel-based HDT at El-Sheikh Zayed Specialized Hospital (SZ in Egypt (2009 to 2015. Results: Forty-four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05, with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12 days v 10 days, respectively; P < .001 and platelets (median 20 days v 18 days, respectively; P < .001. Sinusoidal obstruction syndrome occurred later, after SZ-Bu/Mel therapy (median 19 days v 7 days; P = .033, and four of eight cases were fatal (six of eight patients had underlying hepatitis infection, whereas three of three cases after FH-CEM therapy were moderately severe. Resource utilization associated with the number of days with fever, antibiotic use, and the number of transfusions administered was significantly higher after FH-CEM therapy than after SZ-Bu/Mel therapy. Conclusion: Use of autologous stem-cell transplantation is feasible in the context of a resource-limited country.

  2. Transcription instability in high-risk neuroblastoma is associated with a global perturbation of chromatin domains.

    Science.gov (United States)

    Zanon, Carlo; Tonini, Gian Paolo

    2017-11-01

    Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN-signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN-signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  3. Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

    International Nuclear Information System (INIS)

    Casey, Dana L.; Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel; LaQuaglia, Michael P.; Wolden, Suzanne L.

    2016-01-01

    Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

  4. Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Dana L. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel [Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2016-10-01

    Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

  5. Long-Term Outcome and Toxicities of Intraoperative Radiotherapy for High-Risk Neuroblastoma

    International Nuclear Information System (INIS)

    Gillis, Amy M.; Sutton, Elizabeth; DeWitt, Kelly D.; Matthay, Katherine K.; Weinberg, Vivian; Fisch, Benjamin M.; Chan, Albert; Gooding, Charles; Daldrup-Link, Heike; Wara, William M.; Farmer, Diana L.; Harrison, Michael R.; Haas-Kogan, Daphne

    2007-01-01

    Purpose: To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Methods and Materials: Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Results: Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Conclusions: Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events

  6. Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Rombi, Barbara [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Provincial Agency for Proton Therapy, Trento (Italy); Yock, Torunn I.; Broussard, George [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Friedmann, Alison M.; Huang, Mary [Department of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA (United States); Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy

  7. 18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

    International Nuclear Information System (INIS)

    Piccardo, Arnoldo; Lopci, Egesta; Foppiani, Luca; Morana, Giovanni; Conte, Massimo

    2014-01-01

    Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. 123 I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established. 18 F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with 123 I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of 18 F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of 123 I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

  8. {sup 18}F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Lopci, Egesta [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine and Endocrinology, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Conte, Massimo [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy)

    2014-03-15

    Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. {sup 123}I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.{sup 18}F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with {sup 123}I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of {sup 18}F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of {sup 123}I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

  9. Rapid COJEC versus standard induction therapies for high-risk neuroblastoma.

    Science.gov (United States)

    Peinemann, Frank; Tushabe, Doreen A; van Dalen, Elvira C; Berthold, Frank

    2015-05-19

    Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome. In the rapid COJEC induction schedule, higher single doses of selected drugs than standard induction schedules are administered over a substantially shorter treatment period, with shorter intervals between cycles. Shorter intervals and higher doses increase the dose intensity of chemotherapy and might improve survival. The aim of this study was to evaluate the efficacy and adverse events of the rapid COJEC induction schedule as compared to standard induction schedules in patients with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). Outcomes of interest were complete response, early toxicity and treatment-related mortality as primary endpoints and overall survival, progression- and event-free survival, late non-hematological toxicity, and health-related quality of life as secondary endpoints. We searched the electronic databases CENTRAL (2014, Issue 11), MEDLINE (PubMed), and EMBASE (Ovid) for articles from inception to 11 November 2014. Further searches included trial registries, conference proceedings, and reference lists of recent reviews and relevant articles. We did not apply limits on publication year or languages. Randomized controlled trials evaluating the rapid COJEC induction schedule for high-risk neuroblastoma patients compared to standard induction schedules. Two review authors performed study selection, abstracted data on study and patient characteristics, and assessed risk of bias independently. We resolved differences by discussion or by appeal to a third review author. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic

  10. Rapid COJEC versus standard induction therapies for high-risk neuroblastoma

    NARCIS (Netherlands)

    Peinemann, Frank; Tushabe, Doreen A.; van Dalen, Elvira C.; Berthold, Frank

    2015-01-01

    Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase

  11. High-dose I-131 MIBG treatment for young children with high-risk neuroblastoma, and its practical problem. From the experience of the youngest case in Japan

    International Nuclear Information System (INIS)

    Araki, Raita; Nishimura, Ryosei; Mase, Shintaro

    2012-01-01

    High-dose I-131 MIBG (metaiodobenzylguanidine) therapy combined with auto- or allo-hematopoietic stem cell transplantation is becoming a potential treatment for patients with high-risk neuroblastoma worldwide. However, only older children, who can perform personal care, had been given high-dose I-131 MIBG treatment to avoid the needless radiation exposure to caregivers and medical staff in Japan. In this case report, we have used the high dose MIBG therapy followed by autologous PBSCT (peripheral blood stem cell transplantation) for a 1-year-old boy with a newly diagnosed high-risk neuroblastoma with MYCN amplifications. The total radiation exposure to all parties involved was very limited, even in the youngest case in Japan, probably due to adequate preparations. This encouraging experience may remove the age limit for high-dose I-131 MIBG treatment for the patients with high-risk neuroblastoma in Japan. (author)

  12. Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience.

    Science.gov (United States)

    Moreno, Lucas; Vaidya, Sucheta J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Machin, David; Pearson, Andrew D J

    2013-07-01

    Therapy for high-risk neuroblastoma is intensive and multimodal, and significant long-term adverse effects have been described. The aim of this study was to identify the nature and severity of late complications of metastatic neuroblastoma survivors included in the ENSG5 clinical trial. The trial protocol included induction chemotherapy (randomized "Standard" OPEC/OJEC vs. "Rapid" COJEC), surgery of primary tumor and high-dose melphalan with stem cell rescue. Two hundred and sixty-two children were randomized, 69 survived >5 years, and 57 were analyzed. Data were obtained from the ENSG5 trial database and verified with questionnaires sent to participating centers. Median follow-up was 12.9 (6.9-16.5) years. No differences were found in late toxicities between treatment arms. Twenty-eight children (49.1%) developed hearing loss. Nine patients (15.8%) developed glomerular filtration rate <80 ml/min/1.73 m(2), but no cases of chronic renal failure were documented. Endocrine complications (28.1% of children) included mainly hypogonadism and delayed growth. Four children developed second malignancies, three of them 5 years after diagnosis: one osteosarcoma, one carcinoma of the parotid gland and one ependymoma. There were no hematological malignancies or deaths in remission. This study analyzed a wide cohort of high-risk neuroblastoma survivors from a multi-institutional randomized trial and established the profile of long-term toxicity within the setting of an international clinical trial. Copyright © 2012 Wiley Periodicals, Inc.

  13. High Genomic Instability Predicts Survival in Metastatic High-Risk Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Sara Stigliani

    2012-09-01

    Full Text Available We aimed to identify novel molecular prognostic markers to better predict relapse risk estimate for children with high-risk (HR metastatic neuroblastoma (NB. We performed genome- and/or transcriptome-wide analyses of 129 stage 4 HR NBs. Children older than 1 year of age were categorized as “short survivors” (dead of disease within 5 years from diagnosis and “long survivors” (alive with an overall survival time ≥ 5 years. We reported that patients with less than three segmental copy number aberrations in their tumor represent a molecularly defined subgroup with a high survival probability within the current HR group of patients. The complex genomic pattern is a prognostic marker independent of NB-associated chromosomal aberrations, i.e., MYCN amplification, 1p and 11q losses, and 17q gain. Integrative analysis of genomic and expression signatures demonstrated that fatal outcome is mainly associated with loss of cell cycle control and deregulation of Rho guanosine triphosphates (GTPases functioning in neuritogenesis. Tumors with MYCN amplification show a lower chromosome instability compared to MYCN single-copy NBs (P = .0008, dominated by 17q gain and 1p loss. Moreover, our results suggest that the MYCN amplification mainly drives disruption of neuronal differentiation and reduction of cell adhesion process involved in tumor invasion and metastasis. Further validation studies are warranted to establish this as a risk stratification for patients.

  14. Is complete resection of high-risk stage IV neuroblastoma associated with better survival?

    Science.gov (United States)

    Yeung, Fanny; Chung, Patrick Ho Yu; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen

    2015-12-01

    The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. Copyright © 2015. Published by Elsevier Inc.

  15. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

    Science.gov (United States)

    Arnhold, Viktor; Schmelz, Karin; Proba, Jutta; Winkler, Annika; Wünschel, Jasmin; Toedling, Joern; Deubzer, Hedwig E.; Künkele, Annette; Eggert, Angelika; Schulte, Johannes H.; Hundsdoerfer, Patrick

    2018-01-01

    Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity. PMID:29416773

  16. Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children's Oncology Group.

    Science.gov (United States)

    Park, Julie R; Villablanca, Judith G; London, Wendy B; Gerbing, Robert B; Haas-Kogan, Daphne; Adkins, E Stanton; Attiyeh, Edward F; Maris, John M; Seeger, Robert C; Reynolds, C Patrick; Matthay, Katherine K

    2009-01-01

    The components of therapy required for patients with INSS Stage 3 neuroblastoma and high-risk features remain controversial. A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase 3 CCG-3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59 +/- 6%, respectively (n = 72). Patients randomized to ABMT (n = 20) had 5-year EFS of 65 +/- 11% and OS of 65 +/- 11% compared to 41 +/- 11 (P = 0.21) and 46 +/- 11% (P = 0.23) for patients randomized to CC (n = 23), respectively. Patients randomized to 13-cis-RA (n = 23) had 5-year EFS of 70 +/- 10% and OS of 78 +/- 9% compared to 63 +/- 12% (P = 0.67) and 67 +/- 12% (P = 0.55) for those receiving no further therapy (n = 16), respectively. Patients randomized to both ABMT and 13-cis-RA (n = 6) had a 5-year EFS of 80 +/- 11% and OS of 100%. Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome.

  17. Outcome of High-Risk Stage 3 Neuroblastoma with Myeloablative Therapy and 13-cis-Retinoic Acid: A Report from the Children’s Oncology Group

    Science.gov (United States)

    Park, Julie R.; Villablanca, Judith G.; London, Wendy B.; Gerbing, Robert B.; Haas-Kogan, Daphne; Stanton Adkins, E.; Attiyeh, Edward F.; Maris, John M.; Seeger, Robert C.; Patrick Reynolds, C.; Matthay, Katherine K.

    2009-01-01

    Background The components of therapy required for patients with INSS Stage 3 neuroblastoma and high risk features remain controversial. Procedure A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase III CCG 3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. Results The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59% +/- 6%, respectively (n=72). Patients randomized to ABMT (n=20) had 5-year EFS of 65% +/- 11% and OS of 65% +/- 11% compared to 41% +/- 11 (p=0.21) and 46% +/- 11% (p=0.23) for patients randomized to CC (n=23), respectively. Patients randomized to 13-cis-RA (n=23) had 5-year EFS of 70% +/- 10% and OS of 78% +/- 9% compared to 63% +/- 12% (p=0.67) and 67% +/- 12% (p=0.55) for those receiving no further therapy (n=16), respectively. Patients randomized to both ABMT and 13-cis-RA (n=6) had a 5-year EFS of 80% ± 11% and OS of 100%. Conclusion Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome. PMID:18937318

  18. Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

    2014-11-15

    Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

  19. Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Ferris, Matthew J., E-mail: mjferri@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Danish, Hasan [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia (United States); Deng, Claudia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); George, Bradley A.; Goldsmith, Kelly C.; Wasilewski, Karen J.; Cash, W. Thomas [Aflac Cancer and Blood Disorders Center, Children' s Healthcare of Atlanta, Atlanta, Georgia (United States); Khan, Mohammad K.; Eaton, Bree R.; Esiashvili, Natia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2017-03-15

    Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

  20. Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

    Directory of Open Access Journals (Sweden)

    Gisselsson David

    2007-09-01

    Full Text Available Abstract Background Neuroblastoma (NB is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal sequence in which these imbalances occur during the carcinogenic process. Methods We have reconstructed the appearance of cytogenetic imbalances in 270 NBs by first grouping tumours and imbalances through principal component analysis and then using the number of imbalances in each tumour as an indicator of evolutionary progression. Results Tumours clustered in four sub-groups, dominated respectively by (1 gene amplification in double minute chromosomes and few other aberrations, (2 gene amplification and loss of 1p sequences, (3 loss of 1p and other structural aberrations including gain of 17q, and (4 whole-chromosome gains and losses. Temporal analysis showed that the structural changes in groups 1–3 were acquired in a step-wise fashion, with loss of 1p sequences and the emergence of double minute chromosomes as the earliest cytogenetic events. In contrast, the gains and losses of whole chromosomes in group 4 occurred through multiple simultaneous events leading to a near-triploid chromosome number. Conclusion The finding of different temporal patterns for the acquisition of genomic imbalances in high-risk and low-risk NBs lends strong support to the hypothesis that these tumours are biologically diverse entities, evolving through distinct genetic mechanisms.

  1. Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.

    Science.gov (United States)

    Bosse, Kristopher R; Raman, Pichai; Zhu, Zhongyu; Lane, Maria; Martinez, Daniel; Heitzeneder, Sabine; Rathi, Komal S; Kendsersky, Nathan M; Randall, Michael; Donovan, Laura; Morrissy, Sorana; Sussman, Robyn T; Zhelev, Doncho V; Feng, Yang; Wang, Yanping; Hwang, Jennifer; Lopez, Gonzalo; Harenza, Jo Lynne; Wei, Jun S; Pawel, Bruce; Bhatti, Tricia; Santi, Mariarita; Ganguly, Arupa; Khan, Javed; Marra, Marco A; Taylor, Michael D; Dimitrov, Dimiter S; Mackall, Crystal L; Maris, John M

    2017-09-11

    We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cross-cohort analysis identifies a TEAD4 ↔ MYCN positive-feedback loop as the core regulatory element of high-risk neuroblastoma. | Office of Cancer Genomics

    Science.gov (United States)

    High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator (MR) proteins that were conserved across independent cohorts.

  3. MAX to MYCN intracellular ratio drives the aggressive phenotype and clinical outcome of high risk neuroblastoma.

    Science.gov (United States)

    Ferrucci, Francesca; Ciaccio, Roberto; Monticelli, Sara; Pigini, Paolo; di Giacomo, Simone; Purgato, Stefania; Erriquez, Daniela; Bernardoni, Roberto; Norris, Murray; Haber, Michelle; Milazzo, Giorgio; Perini, Giovanni

    2018-03-01

    Childhood neuroblastoma, a disease of the sympathetic nervous system, is the most common solid tumour of infancy, remarkably refractory to therapeutic treatments. One of the most powerful independent prognostic indicators for this disease is the amplification of the MYCN oncogene, which occurs at high levels in approximately 25% of neuroblastomas. Interestingly, amplification and not just expression of MYCN has a strong prognostic value, although this fact appears quite surprising as MYCN is a transcription factor that requires dimerising with its partner MAX, to exert its function. This observation greatly suggests that the role of MYCN in neuroblastoma should be examined in the context of MAX expression. In this report, we show that, in contrast to what is found in normal cells, MAX expression is significantly different among primary NBs, and that its level appears to correlate with the clinical outcome of the disease. Importantly, controlled modulation of MAX expression in neuroblastoma cells with different extents of MYCN amplification, demonstrates that MAX can instruct gene transcription programs that either reinforce or weaken the oncogenic process enacted by MYCN. In general, our work illustrates that it is the MAX to MYCN ratio that can account for tumour progression and clinical outcome in neuroblastoma and proposes that such a ratio should be considered as an important criterion to the design and development of anti-MYCN therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Logic Learning Machine creates explicit and stable rules stratifying neuroblastoma patients

    NARCIS (Netherlands)

    Cangelosi, Davide; Blengio, Fabiola; Versteeg, Rogier; Eggert, Angelika; Garaventa, Alberto; Gambini, Claudio; Conte, Massimo; Eva, Alessandra; Muselli, Marco; Varesio, Luigi

    2013-01-01

    Neuroblastoma is the most common pediatric solid tumor. About fifty percent of high risk patients die despite treatment making the exploration of new and more effective strategies for improving stratification mandatory. Hypoxia is a condition of low oxygen tension occurring in poorly vascularized

  5. Neuroblastoma

    International Nuclear Information System (INIS)

    Hall-Craggs, M.A.; Finn, J.P.; Dicks-Mireaux, C.; Kiely, E.M.; Pritchard, J.

    1989-01-01

    Twenty-one children with neuroblastoma (mean age, 36.7 months) were examined with high-field strength (1.5 T) MR imaging to define how accurately disease could be documented and to establish optimum sequences. Twenty-eight studies were obtained with T1- and T2-weighted spin-echo and short inversion-recovery (STIR) sequences. Thirteen children underwent surgery, 16 CT. MR imaging exactly predicted tumor extent and involvement of adjacent organs, vessels, and the spine in all patients undergoing surgery. STIR images defined tumor margins and node involvement most clearly. Following chemotherapy, MR imaging could not differentiate active tumor from maturing ganglioneuroma or residual hyperplasia. MR imaging was superior to CT in assessing intraabdominal, marrow, and spinal disease

  6. Laser prostatectomy in high-risk patients

    International Nuclear Information System (INIS)

    Tayib, Abdulmalik M.

    2008-01-01

    Objective was to evaluate the short-term tolerability and outcome of high power green light potassium titanyl phosphate laser prostatectomy in high-risk patients with symptomatic benign prostatic hyperplasia. Eleven high risk operative patients were included in this study at the International Medical Center, Jeddah, Kingdom of Saudi Arabia, between January and September 2007. Patients enrolled in this study underwent preoperative and postoperative, cardiac and anesthesia evaluation. Clinical presentations, ultrasound of urinary tract and preoperative laboratory investigation were recorded. All patients underwent high power green light laser prostatectomy using the green light photo vaporization system with setting of 120 watts. The intraoperative and postoperative complications and follow-up were recorded. The patient's age varied between 65-82 years with a mean age of 75.3+-8.6 years old. Seven patients presented with refractory acute urinary retention and 4 patients presented with severe lower urinary tract symptoms. The average prostate volume was 61.22 cc. All patients had uneventful intra- and postoperative course, without the intensive care. The average blood loss was insignificant and only one of the patients required blood transfusion. Foley catheters were removed one day after the procedure. All patients voided satisfactorily after removal of catheter and 8 patients complained of urgency. High power green light laser prostatectomy is a safe and effective method of treating symptomatic benign prostatic hyperplasia in patients with high operative risk. (author)

  7. Autoantibody signature differentiates Wilms tumor patients from neuroblastoma patients.

    Directory of Open Access Journals (Sweden)

    Jana Schmitt

    Full Text Available Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8%, a sensitivity of 87.0% and a specificity of 86.7%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.

  8. Development of an electronic database for quality assurance of radiotherapy in the International Society of Paediatric Oncology (Europe) high risk neuroblastoma study

    International Nuclear Information System (INIS)

    Gaze, Mark N.; Boterberg, Tom; Dieckmann, Karin; Habrand, Jean-Louis; Helfre, Sylvie; Peylan-Ramu, Nili; Chrzanowska, Elzbieta Korab; Schreier, Guenter; Ladenstein, Ruth

    2010-01-01

    Quality assurance of radiotherapy is an important determinant of outcome in some cancers. SIOPEN-R-NET developed a computerised remote data entry system for recording imaging and treatment parameters for its multimodality high risk neuroblastoma study. This will enable investigation of the relationship between radiotherapy quality and local control.

  9. Results of a Quality Assurance Review of External Beam Radiation Therapy in the International Society of Paediatric Oncology (Europe) Neuroblastoma Group's High-risk Neuroblastoma Trial: A SIOPEN Study

    International Nuclear Information System (INIS)

    Gaze, Mark N.; Boterberg, Tom; Dieckmann, Karin; Hörmann, Marcus; Gains, Jennifer E.; Sullivan, Kevin P.; Ladenstein, Ruth

    2013-01-01

    Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol. Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, and whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score. Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting. Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans.

  10. Results of a Quality Assurance Review of External Beam Radiation Therapy in the International Society of Paediatric Oncology (Europe) Neuroblastoma Group's High-risk Neuroblastoma Trial: A SIOPEN Study

    Energy Technology Data Exchange (ETDEWEB)

    Gaze, Mark N., E-mail: mark.gaze@uclh.nhs.uk [Department of Oncology, University College London Hospitals NHS Foundation Trust, London (United Kingdom); Boterberg, Tom [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Dieckmann, Karin; Hoermann, Marcus [General Hospital Vienna, Medical University Vienna (Austria); Gains, Jennifer E.; Sullivan, Kevin P. [Department of Oncology, University College London Hospitals NHS Foundation Trust, London (United Kingdom); Ladenstein, Ruth [Children' s Cancer Research Institute, St. Anna Children' s Hospital, Vienna (Austria)

    2013-01-01

    Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol. Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, and whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score. Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting. Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans.

  11. Neuroblastoma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Neuroblastoma treatment may include surgery, observation, chemotherapy, radiation therapy, radioactive iodine, and high-dose chemotherapy with stem cell transplant and targeted therapy. Treatment also depends on risk category. Learn more in this expert-reviewed summary.

  12. I-131 metaiodobenzylguanidine: diagnostic use in neuroblastoma patients in relapse

    International Nuclear Information System (INIS)

    Heyman, S.; Evans, A.E.; D'Angio, G.J.

    1988-01-01

    Metaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with 131 I-MIBG used diagnostically in neuroblastoma patients with relapse. Thirty-eight studies were performed in 26 patients. There were 24 children (range 3 months-14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False-negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with 131 I-MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patients as well

  13. Neuroblastoma : Crossing borders in targeted therapy

    NARCIS (Netherlands)

    Bate-Eya, L.T.

    2017-01-01

    Neuroblastoma is the most commonly diagnosed childhood cancer and accounts for about 15% of all pediatric malignancies deaths. Thus far, the treatment options of neuroblastoma is limited with only a 30-40% long term survival rate in high-risk patients. In this thesis, we describe the isolation and

  14. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  15. Fall prevention in high-risk patients.

    Science.gov (United States)

    Shuey, Kathleen M; Balch, Christine

    2014-12-01

    In the oncology population, disease process and treatment factors place patients at risk for falls. Fall bundles provide a framework for developing comprehensive fall programs in oncology. Small sample size of interventional studies and focus on ambulatory and geriatric populations limit the applicability of results. Additional research is needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Patients at high risk of tuberculosis recurrence

    Directory of Open Access Journals (Sweden)

    Mehdi Mirsaeidi

    2018-01-01

    Full Text Available Recurrent tuberculosis (TB continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

  17. Patients at high risk of tuberculosis recurrence.

    Science.gov (United States)

    Mirsaeidi, Mehdi; Sadikot, Ruxana T

    2018-01-01

    Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

  18. Postmastectomy irradiation in high-risk breast cancer patients

    International Nuclear Information System (INIS)

    Overgaard, M.; Juul Christensen, J.; Johansen, H.; Nybo-Rasmussen, A.; Brincker, H.; Kooy, P. van der; Frederiksen, P.L.; Laursen, F.; Panduro, J.; Soerensen, N.E.; Gadeberg, C.C.; Hjelm-Hansen, M.; Overgaard, J.; West Andersen, K.; Zedeler, K.

    1988-01-01

    All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation+CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF+TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation+TAM, TAM or CMF+TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival. (orig.)

  19. Detection of Patients at High Risk of Medication Errors

    DEFF Research Database (Denmark)

    Sædder, Eva Aggerholm; Lisby, Marianne; Nielsen, Lars Peter

    2016-01-01

    Medication errors (MEs) are preventable and can result in patient harm and increased expenses in the healthcare system in terms of hospitalization, prolonged hospitalizations and even death. We aimed to develop a screening tool to detect acutely admitted patients at low or high risk of MEs...

  20. Management of Skin Cancer in the High-Risk Patient.

    Science.gov (United States)

    Behan, James W; Sutton, Adam; Wysong, Ashley

    2016-12-01

    Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

  1. Patients at High-Risk for Surgical Site Infection.

    Science.gov (United States)

    Mueck, Krislynn M; Kao, Lillian S

    Surgical site infections (SSIs) are a significant healthcare quality issue, resulting in increased morbidity, disability, length of stay, resource utilization, and costs. Identification of high-risk patients may improve pre-operative counseling, inform resource utilization, and allow modifications in peri-operative management to optimize outcomes. Review of the pertinent English-language literature. High-risk surgical patients may be identified on the basis of individual risk factors or combinations of factors. In particular, statistical models and risk calculators may be useful in predicting infectious risks, both in general and for SSIs. These models differ in the number of variables; inclusion of pre-operative, intra-operative, or post-operative variables; ease of calculation; and specificity for particular procedures. Furthermore, the models differ in their accuracy in stratifying risk. Biomarkers may be a promising way to identify patients at high risk of infectious complications. Although multiple strategies exist for identifying surgical patients at high risk for SSIs, no one strategy is superior for all patients. Further efforts are necessary to determine if risk stratification in combination with risk modification can reduce SSIs in these patient populations.

  2. Original Research Identifying patients at high risk for obstructive ...

    African Journals Online (AJOL)

    determine the factors associated with high risk for obstructive sleep apnoea and use it to identify patients at risk for the condition in ... mainstay of management is CPAP in addition to behavioral ..... the present study has some potential limitations which ... consequences of obstructive sleep apnea and short sleep duration.

  3. Incidence of infective endocarditis among patients considered at high risk

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Valeur, Nana; Ihlemann, Nikolaj

    2018-01-01

    Aims: Patients with prior infective endocarditis (IE), a prosthetic heart valve, or a cyanotic congenital heart disease (CHD) are considered to be at high risk of IE by guidelines. However, knowledge is sparse on the relative risk of IE between these three groups and compared controls. Methods...

  4. Logic Learning Machine creates explicit and stable rules stratifying neuroblastoma patients.

    Science.gov (United States)

    Cangelosi, Davide; Blengio, Fabiola; Versteeg, Rogier; Eggert, Angelika; Garaventa, Alberto; Gambini, Claudio; Conte, Massimo; Eva, Alessandra; Muselli, Marco; Varesio, Luigi

    2013-01-01

    Neuroblastoma is the most common pediatric solid tumor. About fifty percent of high risk patients die despite treatment making the exploration of new and more effective strategies for improving stratification mandatory. Hypoxia is a condition of low oxygen tension occurring in poorly vascularized areas of the tumor associated with poor prognosis. We had previously defined a robust gene expression signature measuring the hypoxic component of neuroblastoma tumors (NB-hypo) which is a molecular risk factor. We wanted to develop a prognostic classifier of neuroblastoma patients' outcome blending existing knowledge on clinical and molecular risk factors with the prognostic NB-hypo signature. Furthermore, we were interested in classifiers outputting explicit rules that could be easily translated into the clinical setting. Shadow Clustering (SC) technique, which leads to final models called Logic Learning Machine (LLM), exhibits a good accuracy and promises to fulfill the aims of the work. We utilized this algorithm to classify NB-patients on the bases of the following risk factors: Age at diagnosis, INSS stage, MYCN amplification and NB-hypo. The algorithm generated explicit classification rules in good agreement with existing clinical knowledge. Through an iterative procedure we identified and removed from the dataset those examples which caused instability in the rules. This workflow generated a stable classifier very accurate in predicting good and poor outcome patients. The good performance of the classifier was validated in an independent dataset. NB-hypo was an important component of the rules with a strength similar to that of tumor staging. The novelty of our work is to identify stability, explicit rules and blending of molecular and clinical risk factors as the key features to generate classification rules for NB patients to be conveyed to the clinic and to be used to design new therapies. We derived, through LLM, a set of four stable rules identifying a new

  5. Logic Learning Machine creates explicit and stable rules stratifying neuroblastoma patients

    Science.gov (United States)

    2013-01-01

    Background Neuroblastoma is the most common pediatric solid tumor. About fifty percent of high risk patients die despite treatment making the exploration of new and more effective strategies for improving stratification mandatory. Hypoxia is a condition of low oxygen tension occurring in poorly vascularized areas of the tumor associated with poor prognosis. We had previously defined a robust gene expression signature measuring the hypoxic component of neuroblastoma tumors (NB-hypo) which is a molecular risk factor. We wanted to develop a prognostic classifier of neuroblastoma patients' outcome blending existing knowledge on clinical and molecular risk factors with the prognostic NB-hypo signature. Furthermore, we were interested in classifiers outputting explicit rules that could be easily translated into the clinical setting. Results Shadow Clustering (SC) technique, which leads to final models called Logic Learning Machine (LLM), exhibits a good accuracy and promises to fulfill the aims of the work. We utilized this algorithm to classify NB-patients on the bases of the following risk factors: Age at diagnosis, INSS stage, MYCN amplification and NB-hypo. The algorithm generated explicit classification rules in good agreement with existing clinical knowledge. Through an iterative procedure we identified and removed from the dataset those examples which caused instability in the rules. This workflow generated a stable classifier very accurate in predicting good and poor outcome patients. The good performance of the classifier was validated in an independent dataset. NB-hypo was an important component of the rules with a strength similar to that of tumor staging. Conclusions The novelty of our work is to identify stability, explicit rules and blending of molecular and clinical risk factors as the key features to generate classification rules for NB patients to be conveyed to the clinic and to be used to design new therapies. We derived, through LLM, a set of four

  6. High risk factors in patient with carcinoma esophagus

    International Nuclear Information System (INIS)

    Afridi, S.P.; Khan, A.; Waheed, I.

    2000-01-01

    This study was conducted to identify the presence of high risk factors in carcinoma esophagus from February, 1992 to August, 1995 at Surgical unit 1, Jinnah Postgraduate Medical Centre (JPMC), Karachi. In all 37 patients, 22 males and 15 females, were included in the study through outpatient department, surgical emergency and those referred from other cities of the country. All patients were cachectic. Diagnosis was made by detailed history, examination and laboratory investigations. Diagnosis was confirmed on barium swallow and endoscopic biopsy. Highest number of patients were in their 6th decade of life. History of snuff inhalation and opium was present in 2.7% cases each. Lower 3rd of the esophagus was affected in 62.16% middle third in 21.62% and upper third in 16.21% cases. Smoking, pan chewing, naswar eating and snuff inhalation were identified as high risk factors among patients of carcinoma esophagus. (author)

  7. Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma.

    Science.gov (United States)

    Yang, Xinan Holly; Tang, Fangming; Shin, Jisu; Cunningham, John M

    2017-10-03

    Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children. We systematically assembled genomic variants, gene expression changes, priori knowledge of gene functions, and clinical outcomes to identify prognostic multigene signatures. First, we assigned a new, individualized prognostic index using the relative expressions between the poor- and good-outcome signature genes. We then characterized HR-NB aggressiveness beyond these prognostic multigene signatures through the imbalanced effects of MYC and PRC2 signaling. We further analyzed Retinoic acid (RA)-induced HR-NB cells to model tumor cell differentiation. Finally, we performed in vitro validation on ZFHX3, a cell differentiation marker silenced by PRC2, and compared cell morphology changes before and after blocking PRC2 in HR-NB cells. A significant concurrence existed between exons with verified variants and genes showing MYCN-dependent expression in HR-NB. From these biomarker candidates, we identified two novel prognostic gene-set pairs with multi-scale oncogenic defects. Intriguingly, MYC targets over-represented an unfavorable component of the identified prognostic signatures while PRC2 targets over-represented a favorable component. The cell cycle arrest and neuronal differentiation marker ZFHX3 was identified as one of PRC2-silenced tumor suppressor candidates. Blocking PRC2 reduced tumor cell growth and increased the mRNA expression levels of ZFHX3 in an early treatment stage. This hypothesis-driven systems bioinformatics work offered novel insights into

  8. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

    Science.gov (United States)

    Ladenstein, Ruth; Pötschger, Ulrike; Pearson, Andrew D J; Brock, Penelope; Luksch, Roberto; Castel, Victoria; Yaniv, Isaac; Papadakis, Vassilios; Laureys, Geneviève; Malis, Josef; Balwierz, Walentyna; Ruud, Ellen; Kogner, Per; Schroeder, Henrik; de Lacerda, Ana Forjaz; Beck-Popovic, Maja; Bician, Pavel; Garami, Miklós; Trahair, Toby; Canete, Adela; Ambros, Peter F; Holmes, Keith; Gaze, Mark; Schreier, Günter; Garaventa, Alberto; Vassal, Gilles; Michon, Jean; Valteau-Couanet, Dominique

    2017-04-01

    High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m 2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m 2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m 2 per day for 4 days, and melphalan 70 mg/m 2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of

  9. Results of brachytherapy boost in high risk breast cancer patients

    International Nuclear Information System (INIS)

    Battermann, J.J.

    1996-01-01

    Introduction: in breast conserving therapy the role of brachytherapy as a boost after whole breast irradiation is not clear. The series from the Netherlands Cancer Institute show a very high local control rate, but the question could be raised whether all these patients need a brachy boost. Therefore, it was decided at our institute, to deliver a brachy boost only to high risk patients, viz. patients with incomplete resection margins and/or extensive in situ cancer (ECI). Materials and methods: in the period 1988 through 1993 a total of 148 patients with 151 breast tumours received a boost on the tumour bed using brachytherapy. Age varied from 25 till 74 years, with a mean age of 52.3 years. Incomplete resection margins were found in 60 patients, ECI in 31 and both in 49 patients. In the majority of patients, the ECI component was not completely removed. T-stage was unknown in 9 patients. T1 in 83, T2 in 49 and T3 in 10. Nodal status was N0 in 119 and N1 in 33 patients. Infiltrating duct carcinoma was the most common histology. No infiltrating growth was found in 6 patients, but one patient presented a positive node. The interval period between day of operation and day of brachytherapy implantation was between 3 and 4 months in 62%. The mean interval between completion of beam irradiation and day of implantation was 18 days, while 12 patients received their brachytherapy previous to the beam irradiation. External irradiation was with two tangential fields and a total dose of 50 Gy in 25 fractions over 6 weeks (9 fractions in two weeks). The number of needles in two planes. Most patients were implanted under local anaesthesia. Dose rate in 97 patients was 51 - 60 cGy/h. Results: follow-up for patients alive varied from 2 years till 7 years with a mean follow-up period of 4 years. One hundred and twenty five patients are alive, including 6 patients with manifest metastases. Local recurrence was encountered in 8 patients (interval 14 - 60 months, mean 30 months), with

  10. Patients who reattend after head injury: a high risk group.

    Science.gov (United States)

    Voss, M.; Knottenbelt, J. D.; Peden, M. M.

    1995-01-01

    OBJECTIVE--To assess risk factors for important neurosurgical effects in patients who reattend after head injury. DESIGN--Retrospective study. SUBJECTS--606 patients who reattended a trauma unit after minor head injury. MAIN OUTCOME MEASURES--Intracranial abnormality detected on computed tomography or the need for neurosurgical intervention. RESULTS--Five patients died: two from unrelated causes and three from raised intracranial pressure. On multiple regression analysis the only significant predictor for both abnormality on computed tomography (14.4% of reattenders) and the need for operation (5% of reattenders) was vault fracture seen on the skull radiograph (P personality change, and seizures were significantly associated only with abnormality on computed tomography. Headache, dizziness, nausea, and vomiting were common in reattenders but were found to have no independent significance. CONCLUSIONS--All patients who reattend after head injury should undergo computed tomography as at least 14% of scans can be expected to yield positive results. Where this facility is not available patients with predictors for operation should be urgently referred for neurosurgical opinion. Other patients can be readmitted and need referral only if symptoms persist despite symptomatic treatment or there is neurological deterioration while under observation. These patients are a high risk group and should be treated seriously. PMID:8520273

  11. 2017 Taiwan lipid guidelines for high risk patients

    Directory of Open Access Journals (Sweden)

    Yi-Heng Li

    2017-04-01

    lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

  12. Pressure ulcer prevention in high-risk postoperative cardiovascular patients.

    Science.gov (United States)

    Jackson, Melissa; McKenney, Teresa; Drumm, Jennifer; Merrick, Brian; LeMaster, Tamara; VanGilder, Catherine

    2011-08-01

    Little has been published about how to prevent pressure ulcers in severely debilitated, immobile patients in intensive care units. To present a possible prevention strategy for postoperative cardiovascular surgery patients at high risk for development of pressure ulcers. Staff chose to implement air fluidized therapy beds, which provide maximal immersion and envelopment as a measure for preventing pressure ulcers in patients who (1) required vasopressors for at least 24 hours and (2) required mechanical ventilation for at least 24 hours postoperatively. Only 1 of 27 patients had a pressure ulcer develop while on the air fluidized therapy bed (February 2008 through August 2008), and that ulcer was only a stage I ulcer, compared with 40 ulcers in 25 patients before the intervention. Patients spent a mean of 7.9 days on the mattress, and the cost of bed rental was approximately $18000, which was similar to the cost of treatment of 1 pressure ulcer in stage III or IV (about $40000) and was considered cost-effective.

  13. 2017 Taiwan lipid guidelines for high risk patients.

    Science.gov (United States)

    Li, Yi-Heng; Ueng, Kwo-Chang; Jeng, Jiann-Shing; Charng, Min-Ji; Lin, Tsung-Hsien; Chien, Kuo-Liong; Wang, Chih-Yuan; Chao, Ting-Hsing; Liu, Ping-Yen; Su, Cheng-Huang; Chien, Shih-Chieh; Liou, Chia-Wei; Tang, Sung-Chun; Lee, Chun-Chuan; Yu, Tse-Ya; Chen, Jaw-Wen; Wu, Chau-Chung; Yeh, Hung-I

    2017-04-01

    statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia. Copyright © 2016. Published by Elsevier B.V.

  14. Neuroblastoma of the olfactory nerve - radiotherapeutic experiences with six patients

    International Nuclear Information System (INIS)

    Herzog, J.; Schmidt, B.; Petersen, D.; Schabet, M.

    1988-01-01

    Six patients with neuroblastomas of the olfactory nerve (aesthesioneuroblastoma) are presented who were irradiated between 1983 and 1986. Clinical manifestations, diagnostics, histology, therapy, and courses are compared and discused with regard to a survey of literature. An attempt is made to find out the value of radiotherapy in the treatment of this rare disease. In stage A (tumor restricted to the nasal cavity, 1 patient), a local tumor control of up to now 28 months could be achieved by a treatment combination of surgery and radiotherapy. A treatment consisting of surgery or radiotherapy alone should even in this stage only be performed in connection with a close follow-up because of the increased local recurrence risk. Five patients suffered from tumors of stage C (tumor extent beyond the paranasal sinuses). A good palliative effect was obtained temporarily by radiotherapy alone in three out of these patients showing large inoperable tumors and rapidly progressing clinical symptoms. A complete remission now lasting 16 months was achieved only in one patient by radical surgery with unilateral evisceration of orbit and homogenous postirradiation. In case of stage C tumors it is recommended to perform, if possible, a radical tumor excision with evisceration of orbit in case of unilateral manifestation in the orbit and a postirradiation applying a radical, largevolume technique. In order to reduce the risk of radiogenic cerebral necroses, it should be attempted to avoid dose maxima as they can occur when applying a combined ventro-dorsal and lateral irradiation technique. (orig./MG) [de

  15. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma

    International Nuclear Information System (INIS)

    Weltman, Eduardo

    1995-01-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  16. Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma

    International Nuclear Information System (INIS)

    Carén, Helena; Djos, Anna; Nethander, Maria; Sjöberg, Rose-Marie; Kogner, Per; Enström, Camilla; Nilsson, Staffan; Martinsson, Tommy

    2011-01-01

    Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes. In order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation. We present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP). In our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas

  17. Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA.

    Science.gov (United States)

    Duong, Connie; Yoshida, Sakiko; Chen, Cathy; Barisone, Gustavo; Diaz, Elva; Li, Yueju; Beckett, Laurel; Chung, Jong; Antony, Reuben; Nolta, Jan; Nitin, Nitin; Satake, Noriko

    2017-09-01

    BackgroundNeuroblastoma is the second most common extracranial cancer in children. Current therapies for neuroblastoma, which use a combination of chemotherapy drugs, have limitations for high-risk subtypes and can cause significant long-term adverse effects in young patients. Therefore, a new therapy is needed. In this study, we investigated the transcription factor MXD3 as a potential therapeutic target in neuroblastoma.MethodsMXD3 expression was analyzed in five neuroblastoma cell lines by immunocytochemistry and quantitative real-time reverse transcription PCR, and in 18 primary patient tumor samples by immunohistochemistry. We developed nanocomplexes using siRNA and superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell lines in vitro as a single-agent therapeutic and in combination with doxorubicin, vincristine, cisplatin, or maphosphamide-common drugs used in current neuroblastoma treatment.ResultsMXD3 was highly expressed in neuroblastoma cell lines and in patient tumors that had high-risk features. Neuroblastoma cells treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown and resulted in cell apoptosis. Furthermore, on combining MXD3 siRNA nanocomplexes with each of the four drugs, all showed additive efficacy.ConclusionThese results indicate that MXD3 is a potential new target and that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for neuroblastoma.

  18. Rho-associated kinase is a therapeutic target in neuroblastoma.

    Science.gov (United States)

    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  19. A three-gene expression signature model for risk stratification of patients with neuroblastoma.

    Science.gov (United States)

    Garcia, Idoia; Mayol, Gemma; Ríos, José; Domenech, Gema; Cheung, Nai-Kong V; Oberthuer, André; Fischer, Matthias; Maris, John M; Brodeur, Garrett M; Hero, Barbara; Rodríguez, Eva; Suñol, Mariona; Galvan, Patricia; de Torres, Carmen; Mora, Jaume; Lavarino, Cinzia

    2012-04-01

    Neuroblastoma is an embryonal tumor with contrasting clinical courses. Despite elaborate stratification strategies, precise clinical risk assessment still remains a challenge. The purpose of this study was to develop a PCR-based predictor model to improve clinical risk assessment of patients with neuroblastoma. The model was developed using real-time PCR gene expression data from 96 samples and tested on separate expression data sets obtained from real-time PCR and microarray studies comprising 362 patients. On the basis of our prior study of differentially expressed genes in favorable and unfavorable neuroblastoma subgroups, we identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. The expression pattern of these genes was used to develop a PCR-based single-score predictor model. The model discriminated patients into two groups with significantly different clinical outcome [set 1: 5-year overall survival (OS): 0.93 ± 0.03 vs. 0.53 ± 0.06, 5-year event-free survival (EFS): 0.85 ± 0.04 vs. 0.042 ± 0.06, both P model was an independent marker for survival (P model robustly classified patients in the total cohort and in different clinically relevant risk subgroups. We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems. ©2012 AACR.

  20. Pulmonary arteriography in the high-risk patient

    International Nuclear Information System (INIS)

    Perlmutt, L.M.; Braun, S.D.; Newman, G.E.; Dunnick, N.R.

    1986-01-01

    In order to assess the magnitude of risk associated with pulmonary arteriography in patients with pulmonary hypertension and/or right ventricular dysfunction, retrospectively reviewed the incidence of major nonfatal complications and death in patients with these conditions. Of 1,434 examinations, 388 (27%) were performed in patients with pulmonary hypertension and/or elevated right ventricular end-diastolic pressure. Major complications related to contrast agent injection occurred in 30 (2%) of the 1,434 examinations and included chest pain, respiratory distress, arrhythmias, cardiac arrest, and death (two patients). Six (2%) of these complications, including both deaths, occurred in the study group. Both patients who died had severe cardiopulmonary compromise, but most patients with severe cardiopulmonary compromise tolerated angiography well

  1. Image-defined Risk Factors Correlate with Surgical Radicality and Local Recurrence in Patients with Neuroblastoma.

    Science.gov (United States)

    Pohl, A; Erichsen, M; Stehr, M; Hubertus, J; Bergmann, F; Kammer, B; von Schweinitz, D

    2016-04-01

    Neuroblastoma is the second most common solid pediatric tumor and the most common cancer to be detected in children younger than 12 months of age. To date, 2 different staging systems describe the extent of the disease: the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Risk Group Staging System (INRGSS). The INRGSS-system is characterized by the presence or absence of so called image-defined risk factors (IDRFs), which are described as surgical risk factors. We hypothesized that IDRFs correlate with surgical complications, surgical radicality, local recurrence and overall survival (OS). Between 2003 and 2010, 102 patients had neuroblastoma surgery performed in our department. We analyzed medical records for IDRF-status and above named data. 16 patients were IDRF-negative, whereas 86 patients showed one or more IDRF. Intra- or postoperative complications have been reported in 21 patients (21%). 19 of them showed one or more IDRF and 2 patients were IDRF-negative (p=n.s.). Patients who suffered from intra- or postoperative complications demonstrated a decreased OS (p=0.011). Statistical analysis revealed an inverse correlation between the extent of macroscopical removal and IDRF-status (p=0.001). Furthermore, the number of IDRFs were associated with a decreased likelihood of radical tumor resection (p<0.001). 19 patients had local recurrence; all of them were IDRF-positive (p=0.037). Pediatric surgeons should consider IDRFs as a useful tool for risk assessment and therefore planning for neuroblastoma surgery. © Georg Thieme Verlag KG Stuttgart · New York.

  2. The use of both diagnostic and therapeutic MIBG in neuroblastoma patients

    NARCIS (Netherlands)

    Bleeker, G.

    2014-01-01

    Neuroblastoma is the most common extra-cranial malignant solid tumour of childhood. It is an embryonic tumour derived from the sympathetic adrenal lineage of the neural crest. Distant metastases are present at diagnosis in 50% of the patients. Metaiodobenzylguanidine (MIBG) is a compound

  3. Individualized Vascular Disease Prevention in High-Risk Patients

    NARCIS (Netherlands)

    Kaasenbrood, L

    2016-01-01

    In the pharmacologic prevention of vascular events, clinicians need to translate average effects from a clinical trial to the individual patient. Prediction models can contribute to individualized vascular disease prevention by selecting patients for treatment based on estimated risk or expected

  4. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma; Radioterapia do segmento cefalico em pacientes portadores de neuroblastoma avancado

    Energy Technology Data Exchange (ETDEWEB)

    Weltman, Eduardo

    1995-07-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  5. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma; Radioterapia do segmento cefalico em pacientes portadores de neuroblastoma avancado

    Energy Technology Data Exchange (ETDEWEB)

    Weltman, Eduardo

    1995-07-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  6. [Coronary bypass in treatment of high-risk patients].

    Science.gov (United States)

    Avdagić, Harun; Mujanović, Emir; Mesanović, Nihad; Sijereić-Avdagić, Selma; Pirić, Melika

    2009-01-01

    Although it is possible to find a number of comparative studies in the world literature discussing the results of coronary artery bypass surgery (CABG) with and without cardiopulmonary bypass (CPB), until now such analysis has not been made in Bosnia and Herzegovina. The main aim of this scientific work was to compare morbidity and mortality, need for blood transfusions, length of stay in the intensive care unit, total length of hospitalisation and number of complication in two groups of patients operated with these methods. Patients with EuroScore > or =5 with CABG operated in Cardiovascular Clinic Tuzla, from May 2000 to May 2005 divided in two groups, were included in this study. There were 100 patients in the first group operated with CPB and 100 patients in the second group operated without CPB. The average time spent on respirators was shorter in patients operated without CPB (3.7 vs.9.74 hours, p = 0.023) and the time spent in Intensive care shorter too (19 vs. 23 days, p = 0.008). Volume of postoperative bleeding was less in patients operated without CPB (574.9 vs. 988.9 ml, p = 0.038), as volume after blood transfusion (168.8 vs. 350.3 mi, p = 0.001). Intraoperative inotrope support was less in patients operated without CPB (8.0 vs. 19.0%, p = 0.038) as postoperative inotrope support (6.0 vs. 17.0%, p = 0.027). The most usual postoperative complication was atrial fibrillation and there was no difference between patients operated with CPB and without CPB (24% vs. 17%, p = 0.293). Mortality was not different in patients operated with or without CPB (2.0% vs. 6.0%, p = 0.140). The average time of total hospitalisation was also shorter in patients operated without CPB (8.0 vs. 9.5 days, p = 0.039. In conclusion CABG without CPB has many advantages compared to the conventional method. Mortality and morbidity are reduced and there is less need for transfusion. The time spent on mechanical ventilation is reduced and less time is spent in intensive care. The total

  7. Neuroblastoma and MYCN

    Science.gov (United States)

    Huang, Miller; Weiss, William A.

    2013-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to originate from undifferentiated neural crest cells. Amplification of the MYC family member, MYCN, is found in ∼25% of cases and correlates with high-risk disease and poor prognosis. Currently, amplification of MYCN remains the best-characterized genetic marker of risk in neuroblastoma. This article reviews roles for MYCN in neuroblastoma and highlights recent identification of other driver mutations. Strategies to target MYCN at the level of protein stability and transcription are also reviewed. PMID:24086065

  8. Identifying patients at high risk for obstructive sleep apnoea ...

    African Journals Online (AJOL)

    Background: Obstructive sleep apnoea is associated with significant health consequences. A significant proportion of hospitalized patients at risk for obstructive sleep apnoea were never identified and referred for polysomnography for diagnosis. The objective of this study was to determine the factors associated with high ...

  9. how can i recognise the high-risk cardiovascular patient?

    African Journals Online (AJOL)

    Enrique

    disease (CHD) for men at the age of 40 years is 48.6% (95% CI: 45.8 - 51.3) ... ent early in life and associated with increased risk to develop disease) was intro- ... because it has been shown that patients with type 2 diabetes and no history of.

  10. Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2013-01-01

    Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  11. Neuroblastoma trial to overcome a rare malignant disease

    International Nuclear Information System (INIS)

    Fukushima, Takashi; Shichino, Hiroyuki; Kumagai, Masaaki

    2007-01-01

    Neuroblastoma is one of the main causes of children's deaths in Japan and many developed countries, although it is a rather rare pediatric cancer. Many clinical studies have been carried out and reported. The clinical study system of Japan is much different from the systems of the other countries. In Japan, the main hospitals, where clinical study including clinical trials have been conducted, are not only national centers but also many regional or prefectural centers. Progression-free survival has been achieved in over 80% of low-risk patients, and in about 40% of high-risk patients. These are the same as the outcomes of neuroblastoma patients in European countries and North America. Further clinical studies and translational research should be planned especially regarding high-risk neuroblastomas. (author)

  12. Utility of sentinel node biopsy in patients with high-risk cutaneous squamous cell carcinoma

    DEFF Research Database (Denmark)

    Allen, J E; Stolle, L B

    2015-01-01

    BACKGROUND: Currently there is no consensual agreement on the standard use of Sentinel Lymph Node Biopsy (SLNB) in staging of high-risk patients. OBJECTIVE: The objective was to define the predictive value and role of SLNB combined with the different high-risk factors to determine which patients...... cm. Sensitivity, specificity and NPV for a tumor localized at a high-risk area were 72.63%, 100% and 96.74%, respectively. Specificity was 100% as was NPV for immunosuppression. CONCLUSION: SLNB has a high NPV and low false negative rate and carries a low risk of complications. SLNB may prove...

  13. Decreased aortic growth and middle aortic syndrome in patients with neuroblastoma after radiation therapy

    International Nuclear Information System (INIS)

    Sutton, Elizabeth J.; Tong, Ricky T.; Gillis, Amy M.; Haas-Kogan, Daphne A.; Henning, Tobias D.; Boddington, Sophie; Sha, Vinil; Gooding, Charles; Coakley, Fergus V.; Daldrup-Link, Heike; Weinberg, Vivian A.; Matthay, Katherine

    2009-01-01

    Long-term CT follow-up studies are required in pediatric patients who have received intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) to assess vascular toxicities and to determine the exact complication rate. To analyze with CT the effects of radiation therapy (RT) on the growth of the aorta in neuroblastoma patients. Abdominal CT scans of 31 patients with intraabdominal neuroblastoma (stage II-IV), treated with RT (20 IORT±EBRT, 11 EBRT alone), were analyzed retrospectively. The diameter of the abdominal aorta was measured before and after RT. These data were compared to normal and predicted normal aortic diameters of children, according to the model of Fitzgerald, Donaldson and Poznanski (aortic diameter in centimeters = 0.844+0.0599 x age in years), and to the diameters of a control group of children who had not undergone RT. Statistical analyses for the primary aims were performed using the chi-squared test, t-test, Mann-Whitney test, nonparametric Wilcoxon matched-pairs test and analysis of variance for repeated measures. Clinical files and imaging studies were evaluated for signs of late vascular complications of neuroblastoma patients who had received RT. The mean diameter before and after RT and the growth of the aorta were significantly lower than expected in patients with neuroblastoma (P<0.05 for each) and when compared to the growth in a control group with normal and nonirradiated aortas. Among the patients who had received RT, there was no difference due to the type of RT. Seven patients from the IORT±EBRT group developed vascular complications, which included hypertension (five), middle aortic syndrome (two), death due to mesenteric ischemia (one) and critical aortic stenosis, which required aortic bypass surgery (two). Patients with neuroblastoma who had received RT showed impaired growth of the abdominal aorta. Significant long-term vascular complications occurred in seven patients who received IORT±EBRT. Thus

  14. Multidisciplinary perioperative protocol in patients undergoing acute high-risk abdominal surgery

    DEFF Research Database (Denmark)

    Tengberg, L. T.; Bay-Nielsen, M.; Bisgaard, T.

    2017-01-01

    Background: Acute high-risk abdominal (AHA) surgery carries a very high risk of morbidity and mortality and represents a massive healthcare burden. The aim of the present study was to evaluate the effect of a standardized multidisciplinary perioperative protocol in patients undergoing AHA surgery...... = 0·004). Conclusion: The introduction of a multidisciplinary perioperative protocol was associated with a significant reduction in postoperative mortality in patients undergoing AHA surgery. NCT01899885 (http://www.clinicaltrials.gov)....

  15. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2010-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  16. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2008-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  17. Neuroblastoma | Office of Cancer Genomics

    Science.gov (United States)

    The TARGET Neuroblastoma projects elucidate comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers. Neuroblastoma (NBL) is a cancer that arises in immature nerve cells of the sympathetic nervous system, primarily affecting infants and children.

  18. Identifying patients at high risk of tuberculosis recurrence

    Directory of Open Access Journals (Sweden)

    Ruxana T Sadikot

    2016-01-01

    Full Text Available Several studies have been done in relation to recurrence of tuberculosis (TB following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

  19. Identifying patients at high risk of tuberculosis recurrence.

    Science.gov (United States)

    Sadikot, Ruxana T

    2016-12-01

    Several studies have been done in relation to recurrence of tuberculosis (TB) following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence. Copyright © 2016.

  20. Neuroblastoma in a patient with Coffin-Siris syndrome.

    Science.gov (United States)

    Pollono, Daniel; Drut, Ricardo; Cecotti, Norma; Pollono, Agustina

    2009-01-01

    We report the case of an 8-year-old boy with the phenotypic features of Coffin-Siris syndrome diffuse hypertrichosis, flat occiput, scant scalp hair, flat supraorbital arch, triangular eyebrows, horizontal palpebral fissure, anteverted nares, triangular philtrum, coarse lips, high-arched palate, micrognathia, low set and dorsaly rotated ears, short neck, wide thorax, widely set nipples, transverse palmar crease, psychomotor delay, urinary malformations (paraurethral diverticulum, hypoplasia of left kidney associated with vesicoureteral reflux grade 3-4), bilateral inguinal hernia, and dorsolumbar kyphoscoliosis. In the follow-up he presented a retroperitoneal neuroblastoma. Although this type of tumor has been referred to develop in several genetic and mutimalformative syndromes, it seems that present association has not been previously reported.

  1. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial.

    Science.gov (United States)

    Pearson, Andrew D J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Ellershaw, Caroline; Machin, David

    2008-03-01

    The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1.8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2.95 years (range 1.03-20.97), were randomly assigned-132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109

  2. Combined Psoas Compartment-Sciatic Block in a Pediatric Patient with High-Risk Cardiopulmonary

    Directory of Open Access Journals (Sweden)

    Levent Þahin

    2013-03-01

    Full Text Available There is high potential for complications in cardiopulmonary high-risk patients with valvular heart disease at perioperative period. The operation was planned due to pathological fracture of the femoral shaft of a nine year old male patient weighing 26 kilograms. He had 3o tricuspid insufficiency, 3o mitral insufficiency and pulmonary hypertension in preoperative evaluation. Sciatic nerve block and psoas compartment block was performed to patient for anesthesia and analgesia. In conclusion we think that combined psoas compartment-sciatic nerve block may be a good alternative to other methods of anesthesia in high-risk pediatric patients with cardiopulmonary perspective in lower-extremity surgery.

  3. Advances in Risk Classification and Treatment Strategies for Neuroblastoma

    Science.gov (United States)

    Pinto, Navin R.; Applebaum, Mark A.; Volchenboum, Samuel L.; Matthay, Katherine K.; London, Wendy B.; Ambros, Peter F.; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R.; Valteau-Couanet, Dominique; Pearson, Andrew D.J.

    2015-01-01

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  4. Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification.

    Science.gov (United States)

    Oberthuer, André; Berthold, Frank; Warnat, Patrick; Hero, Barbara; Kahlert, Yvonne; Spitz, Rüdiger; Ernestus, Karen; König, Rainer; Haas, Stefan; Eils, Roland; Schwab, Manfred; Brors, Benedikt; Westermann, Frank; Fischer, Matthias

    2006-11-01

    To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease. Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States. The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]). Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.

  5. Toxicity of upfront {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bleeker, Gitta; Schoot, Reineke A.; Caron, Huib N.; Kraker, Jan de; Tytgat, Godelieve A. [Emma Children' s Hospital, Academic Medical Centre (AMC), Department of Paediatric Oncology, PO Box 22700, Amsterdam (Netherlands); Hoefnagel, Cees A. [National Cancer Institute (NKI-AvL), Department of Nuclear Medicine, Amsterdam (Netherlands); Eck, Berthe L. van [Academic Medical Centre (AMC), Department of Nuclear Medicine, Amsterdam (Netherlands)

    2013-10-15

    In the treatment of patients with high-risk neuroblastoma, different doses of {sup 131}I-metaiodobenzylguanidine ({sup 131}I-MIBG) are administered at different time points during treatment. Toxicity, mainly haematological (thrombocytopenia), from {sup 131}I-MIBG therapy is known to occur in extensively chemotherapy pretreated neuroblastoma patients. Up to now, acute toxicity from {sup 131}I-MIBG as initial treatment has never been studied in a large cohort. The aim of this retrospective study was to document acute toxicity related to upfront {sup 131}I-MIBG. All neuroblastoma patients (stages 1-4 and 4S) treated upfront with {sup 131}I-MIBG at the Emma Children's Hospital, Academic Medical Centre (1992 - 2008) were included in this retrospective analysis. The acute toxicity (during therapy) and short-term toxicity (1st month following therapy) of the first two {sup 131}I-MIBG therapies were studied. Of 66 patients (34 boys, 32 girls; median age 2.2 years, range 0.1 - 9.4 years), 49 had stage 4 disease, 5 stage 4S, 6 stage 3, 1 stage 2 and 5 stage 1. The median first dose was 441 MBq/kg (range 157 - 804 MBq/kg). The median second dose was 328 MBq/kg (range 113 - 727 MBq/kg). The most frequently observed symptoms were nausea and vomiting (21 %, maximum grade II). The main toxicity was grade IV haematological, occurring only in stage 4 patients, after the first and second {sup 131}I-MIBG therapies: anaemia (5 % and 4 %, respectively), leucocytopenia (3 % and 4 %) and thrombocytopenia (2 % and 4 %). No stem cell rescue was needed. The main acute toxicity observed was haematological followed by nausea and vomiting. One patient developed posterior reversible encephalopathy syndrome during {sup 131}I-MIBG therapy, possibly related to {sup 131}I-MIBG. We consider {sup 131}I-MIBG therapy to be a safe treatment modality. (orig.)

  6. Identification of high risk patients with hypertrophic cardiomyopathy in a northern Greek population

    Directory of Open Access Journals (Sweden)

    Karvounis Charalambos

    2009-07-01

    Full Text Available Abstract Background The percentage of hypertrophic cardiomyopathy (HCM patients who are in high risk for Sudden Death (SD constitutes only a minority of all HCM population but the incidence of SD in this subset is high (at least 5% annually. The identification of this small but important proportion of high risk HCM patients has been the clue in the clinical evaluation of these patients. Methods Our study cohort consisted from 123 patients with HCM who are currently followed up in our Institution. Five clinical risk factors were assessed: a family history of premature SD, unexplained syncope, Non Sustained Ventricular Tachycardia (NSVT on 24-h ECG monitoring, Abnormal Blood Pressure Response (ABPR during upright exercise testing and Maximum left ventricular Wall Thickness (MWT ≥30 mm. The purpose of our study was the identification of high risk HCM patients coming from Northern Greece. Results Fifteen patients (12.2% of the whole cohort had MWT ≥ 30 mm, 30 patients (24.4% had an ABPR to exercise, 17 patients (13.8% had episodes of NSVT in 24-h Holter monitoring, 17 patients (13.8% suffered from syncope, and 8 patients (6.5% had a positive family history of premature SD. Data analysis revealed that 74 patients (60.1% had none risk factor. Twenty four patients (19.5% had 1 risk factor, 17 patients (13.8% had 2 risk factors, 4 patients (3.25% had 3 risk factors, and 4 patients (3.25% had 4 risk factors, while none patient had 5 risk factors. Twenty five patients (20.3% had 2 or more risk factors. Conclusion This study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion (almost 20% carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation.

  7. TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.

    Science.gov (United States)

    Yáñez, Yania; Hervás, David; Grau, Elena; Oltra, Silvestre; Pérez, Gema; Palanca, Sarai; Bermúdez, Mar; Márquez, Catalina; Cañete, Adela; Castel, Victoria

    2016-03-01

    In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

  8. Treatment and outcome of adult-onset neuroblastoma.

    Science.gov (United States)

    Suzuki, Maya; Kushner, Brian H; Kramer, Kim; Basu, Ellen M; Roberts, Stephen S; Hammond, William J; LaQuaglia, Michael P; Wolden, Suzanne L; Cheung, Nai-Kong V; Modak, Shakeel

    2018-03-25

    Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial. © 2018 UICC.

  9. Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

    Science.gov (United States)

    Marachelian, Araz; Villablanca, Judith G; Liu, Cathy W; Liu, Betty; Goodarzian, Fariba; Lai, Hollie A; Shimada, Hiroyuki; Tran, Hung C; Parra, Jaime A; Gallego, Richard; Bedrossian, Nora; Young, Sabrina; Czarnecki, Scarlett; Kennedy, Rebekah; Weiss, Brian D; Goldsmith, Kelly; Granger, Meaghan; Matthay, Katherine K; Groshen, Susan; Asgharzadeh, Shahab; Sposto, Richard; Seeger, Robert C

    2017-09-15

    Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ C t , for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123 I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ C t and progression-free survival (PFS). Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ C t values were correlated (Spearman r = 0.67, P neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Medical Assistant-based care management for high risk patients in small primary care practices

    DEFF Research Database (Denmark)

    Freund, Tobias; Peters-Klimm, Frank; Boyd, Cynthia M.

    2016-01-01

    Background: Patients with multiple chronic conditions are at high risk of potentially avoidable hospital admissions, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. Objective......: To determine whether protocol-based care management delivered by medical assistants improves patient care in patients at high risk of future hospitalization in primary care. Design: Two-year cluster randomized clinical trial. Setting: 115 primary care practices in Germany. Patients: 2,076 patients with type 2......, and monitoring delivered by medical assistants with usual care. Measurements: All-cause hospitalizations at 12 months (primary outcome) and quality of life scores (Short Form 12 Health Questionnaire [SF-12] and the Euroqol instrument [EQ-5D]). Results: Included patients had, on average, four co-occurring chronic...

  11. A Proactive Approach to High Risk Delirium Patients Undergoing Total Joint Arthroplasty.

    Science.gov (United States)

    Duque, Andres F; Post, Zachary D; Orozco, Fabio R; Lutz, Rex W; Ong, Alvin C

    2018-04-01

    Delirium is a common complication among elderly patients undergoing total joint arthroplasty (TJA). Its incidence has been reported from 4% to 53%. The Centers for Medicare and Medicaid Services consider delirium following TJA a "never-event." The purpose of this study is to evaluate a simple perioperative protocol used to identify delirium risk patients and prevent its incidence following TJA. Our group developed a protocol to identify and prevent delirium in patients undergoing TJA. All patients were screened and scored in the preoperative assessment, on criteria such as age, history of forgetfulness, history of agitation or visual hallucinations, history of falls, history of postoperative confusion, and inability to perform higher brain functions. Patients were scored on performance in a simple mental examination. The patients were classified as low, medium, or high risk. Patients who were identified as high risk were enrolled in a delirium avoidance protocol that minimized narcotics and emphasized nursing involvement and fluids administration. Five of 7659 (0.065%) consecutive TJA patients from 2010 to 2015 developed delirium. A total of 422 patients were identified as high risk. All 5 patients who suffered delirium were within the high risk group. No low or medium risk patients suffered a delirium complication. Three (0.039%) patients suffered drug-induced delirium, 1 (0.013%) had delirium related to alcohol withdrawal, and 1 (0.013%) had delirium after a systemic infection. This protocol is effective in identifying patients at high delirium risk and diminishing the incidence of this complication by utilizing a simple screening tool and perioperative protocol. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  13. Adverse respiratory events after general anesthesia in patients at high risk of obstructive sleep apnea syndrome.

    Science.gov (United States)

    Xará, Daniela; Mendonça, Júlia; Pereira, Helder; Santos, Alice; Abelha, Fernando José

    2015-01-01

    Patients with STOP-BANG score >3 have a high risk of Obstructive sleep apnea. The aim of this study was to evaluate early postoperative respiratory complications in adults with STOP-BANG score >3 after general anesthesia. This is a prospective double cohort study matching 59 pairs of adult patients with STOP-BANG score >3 (high risk of obstructive sleep apnea) and patients with STOP-BANG score <3 (low risk of obstructive sleep apnea), similar with respect to gender, age and type of surgery, admitted after elective surgery in the Post-Anaesthesia Care Unit in May 2011. Primary outcome was the development of adverse respiratory events. Demographics data, perioperative variables, and postoperative length of stay in the Post-Anesthesia Care Unit and in hospital were recorded. The Mann-Whitney test, the chi-square test and the Fisher exact test were used for comparisons. Subjects in both pairs of study subjects had a median age of 56 years, including 25% males, and 59% were submitted to intra-abdominal surgery. High risk of obstructive sleep apnea patients had a higher median body mass index (31 versus 24kg/m(2), p<0.001) and had more frequently co-morbidities, including hypertension (58% versus 24%, p<0.001), dyslipidemia (46% versus 17%, p<0.001) and insulin-treated diabetes mellitus (17% versus 2%, p=0.004). These patients were submitted more frequently to bariatric surgery (20% versus 2%, p=0.002). Patients with high risk of obstructive sleep apnea had more frequently adverse respiratory events (39% versus 10%, p<0.001), mild to moderate desaturation (15% versus 0%, p=0.001) and inability to breathe deeply (34% versus 9%, p=0.001). After general anesthesia high risk of obstructive sleep apnea patients had an increased incidence of postoperative respiratory complications. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  14. [Adverse respiratory events after general anesthesia in patients at high risk of obstructive sleep apnea syndrome].

    Science.gov (United States)

    Xará, Daniela; Mendonça, Júlia; Pereira, Helder; Santos, Alice; Abelha, Fernando José

    2015-01-01

    Patients with STOP-BANG score >3 have a high risk of Obstructive sleep apnea. The aim of this study was to evaluate early postoperative respiratory complications in adults with STOP-BANG score >3 after general anesthesia. This is a prospective double cohort study matching 59 pairs of adult patients with STOP-BANG score >3 (high risk of obstructive sleep apnea) and patients with STOP-BANG score <3 (low risk of obstructive sleep apnea), similar with respect to gender, age and type of surgery, admitted after elective surgery in the Post-Anaesthesia Care Unit in May 2011. Primary outcome was the development of adverse respiratory events. Demographics data, perioperative variables, and postoperative length of stay in the Post-Anesthesia Care Unit and in hospital were recorded. The Mann-Whitney test, the chi-square test and the Fisher exact test were used for comparisons. Subjects in both pairs of study subjects had a median age of 56 years, including 25% males, and 59% were submitted to intra-abdominal surgery. High risk of obstructive sleep apnea patients had a higher median body mass index (31 versus 24kg/m(2), p<0.001) and had more frequently co-morbidities, including hypertension (58% versus 24%, p<0.001), dyslipidemia (46% versus 17%, p<0.001) and insulin-treated diabetes mellitus (17% versus 2%, p=0.004). These patients were submitted more frequently to bariatric surgery (20% versus 2%, p=0.002). Patients with high risk of obstructive sleep apnea had more frequently adverse respiratory events (39% versus 10%, p<0.001), mild to moderate desaturation (15% versus 0%, p=0.001) and inability to breathe deeply (34% versus 9%, p=0.001). After general anesthesia high risk of obstructive sleep apnea patients had an increased incidence of postoperative respiratory complications. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  15. Combined Psoas Compartment-Sciatic Block in a Pediatric Patient with High-Risk Cardiopulmonary

    OpenAIRE

    Levent Þahin

    2013-01-01

    There is high potential for complications in cardiopulmonary high-risk patients with valvular heart disease at perioperative period. The operation was planned due to pathological fracture of the femoral shaft of a nine year old male patient weighing 26 kilograms. He had 3o tricuspid insufficiency, 3o mitral insufficiency and pulmonary hypertension in preoperative evaluation. Sciatic nerve block and psoas compartment block was performed to patient for anesthesia and analgesia. In conclusion we...

  16. Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups

    OpenAIRE

    Marschollek, Michael; Gövercin, Mehmet; Rust, Stefan; Gietzelt, Matthias; Schulze, Mareike; Wolf, Klaus-Hendrik; Steinhagen-Thiessen, Elisabeth

    2012-01-01

    Abstract Background Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). Methods A ...

  17. Social cognition in patients at ultra-high risk for psychosis

    DEFF Research Database (Denmark)

    Glenthøj, Louise B.; Fagerlund, Birgitte; Hjorthøj, Carsten

    2016-01-01

    Objective: Patients at ultra-high risk (UHR) for psychosis show significant impairments in functioning. It is essential to determine which factors influence functioning, as it may have implications for intervention strategies. This study examined whether social cognitive abilities and clinical...

  18. Soluble Urokinase Plasminogen Activator Receptor Levels in Tuberculosis Patients at High Risk for Multidrug Resistance

    Directory of Open Access Journals (Sweden)

    Tri Yudani Mardining Raras

    2012-01-01

    Full Text Available The soluble urokinase plasminogen activator receptor (suPAR has been shown to be a strong prognostic biomarker for tuberculosis (TB. In the present study, the profiles of plasma suPAR levels in pulmonary TB patients at high risk for multidrug resistance were analyzed and compared with those in multidrug resistant (MDR-TB patients. Forty patients were prospectively included, consisting of 10 MDR-TB patients and 30 TB patients at high risk for MDR, underwent clinical assesment. Plasma suPAR levels were measured using ELISA (SUPARnostic, Denmark and bacterial cultures were performed in addition to drug susceptibility tests. All patients of suspected MDR-TB group demonstrated significantly higher suPAR levels compared with the healthy TB-negative group (1.79 ng/mL. Among the three groups at high risk for MDR-TB, only the relapse group (7.87 ng/mL demonstrated suPAR levels comparable with those of MDR-TB patients (7.67 ng/mL. suPAR levels in the two-month negative acid-fast bacilli conversion group (9.29 ng/mL were higher than positive control, whereas levels in the group consisting of therapy failure patients (5.32 ng/mL were lower. Our results strongly suggest that suPAR levels enable rapid screening of suspected MDR-TB patients, but cannot differentiate between groups.

  19. High-Risk Palliative Care Patients' Knowledge and Attitudes about Hereditary Cancer Testing and DNA Banking.

    Science.gov (United States)

    Quillin, John M; Emidio, Oluwabunmi; Ma, Brittany; Bailey, Lauryn; Smith, Thomas J; Kang, In Guk; Yu, Brandon J; Owodunni, Oluwafemi Patrick; Abusamaan, Mohammed; Razzak, Rab; Bodurtha, Joann N

    2017-12-04

    Even at the end of life, testing cancer patients for inherited susceptibility may provide life-saving information to their relatives. Prior research suggests palliative care inpatients have suboptimal understanding of genetic importance, and testing may be underutilized in this clinical setting. These conclusions are based on limited research. This study aimed to estimate genetic testing prevalence among high-risk palliative care patients in a National Cancer Institute-designated comprehensive cancer center. We also aimed to understand these patients' understanding of, and attitudes toward, hereditary cancer testing and DNA banking. Palliative care in-patients with cancer completed structured interviews, and their medical records were reviewed. Among patients at high risk for hereditary cancer, we assessed history of genetic testing/DNA banking; and related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said they/their relatives had genetic testing or they had been referred for a genetics consultation. Of the remaining 10 patients, seven (70%) said they would "probably" or "definitely" get tested. Patients who had not had testing were least concerned about the impact of future testing on their family relationships; two (20%) said they were "extremely concerned" about privacy related to genetic testing. Of patients without prior testing, five (50%) said they had heard or read "a fair amount" about genetic testing. No high-risk patients had banked DNA. Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively little" about DNA banking. Written materials and clinician discussion were most preferred ways to learn about genetic testing and DNA banking. Overall, this study demonstrates underutilization of genetics services at the end of life continues to be problematic, despite high patient interest.

  20. A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

    Directory of Open Access Journals (Sweden)

    Fardin Paolo

    2010-07-01

    Full Text Available Abstract Background Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.

  1. Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients.

    Science.gov (United States)

    Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W

    2017-08-01

    Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effectiveness of 2-hour Troponin in High-risk Patients With Suspected Acute Coronary Syndrome.

    Science.gov (United States)

    Bove, Joseph; Hochman, Steven; Miller, Jacob; Artim, Stephen

    2017-06-01

    Research has shown the safety and effectiveness of drawing a standard troponin level at presentation and again at 2 hours in only low-risk patients. Because high-sensitivity troponins are not currently approved in the United States, we studied the utility of a standard troponin that is presently in use. Our goal was to determine if 2-hour standard troponin would be safe and effective in the evaluation of a high-risk cohort of patients never studied previously. We conducted a single-center prospective observational study of adult patients presenting to the emergency department with signs and symptoms suggestive of acute coronary syndrome. Patients were defined as high risk if the attending physician planned to admit or transfer the patient to the observation unit. History, Electrocardiography, Age, Risk factors, Troponin scores were calculated on all patients to provide verification that the individuals were high risk. The primary outcome was a composite of 30-day myocardial infarction, death, cardiac arrest with return of spontaneous circulation, or dysrhythmia. The secondary outcome was 30-day revascularization. We included a total of 122 patients with an average follow-up of 112 days (minimum 30 days). A total of 86% of cases had History, Electrocardiography, Age, Risk factors, Troponin scores ≥4. The primary outcome was met in 22 (18%) patients, and the secondary outcome occurred in 7 (5.7%) patients. The negative predictive value of negative 2-hour troponins along with no significant delta troponin rise was 98.7%. Discharging patients thought to be high risk who have negative troponins at 0 and 2 hours and no delta troponin rise appears safe. No deaths occurred in follow-up. Larger studies are warranted.

  3. Coronary CT angiography in clinical triage of patients at high risk of coronary artery disease

    DEFF Research Database (Denmark)

    Kühl, J Tobias; Hove, Jens D; Kristensen, Thomas S

    2017-01-01

    OBJECTIVES: To test if cardiac computed tomography angiography (CCTA) can be used in the triage of patients at high risk of coronary artery disease. DESIGN: The diagnostic value of 64-detector CCTA was evaluated in 400 patients presenting with non-ST segment elevation myocardial infarction using...... invasive coronary angiography (ICA) as the reference method. The relation between the severity of disease by CCTA and a combined endpoint of death, re-hospitalization due to new myocardial infarction, or symptom-driven coronary revascularization was assessed. RESULTS: CCTA detects significant (>50...... in patients with high likelihood of coronary artery disease and could, in theory, be used to triage high risk patients. As many obstacles remain, including logistical and safety issues, our study does not support the use of CCTA as an additional diagnostic test before ICA in an all-comer NSTEMI population....

  4. Phase I study of vorinostat in combination with isotretinoin in patients with refractory/recurrent neuroblastoma: A new approaches to Neuroblastoma Therapy (NANT) trial.

    Science.gov (United States)

    Pinto, Navin; DuBois, Steven G; Marachelian, Araz; Diede, Scott J; Taraseviciute, Agne; Glade Bender, Julia L; Tsao-Wei, Denice; Groshen, Susan G; Reid, Joel M; Haas-Kogan, Daphne A; Reynolds, C Patrick; Kang, Min H; Irwin, Meredith S; Macy, Margaret E; Villablanca, Judith G; Matthay, Katherine K; Park, Julie R

    2018-03-30

    Vorinostat combined with retinoids produces additive antitumor effects in preclinical studies of neuroblastoma. Higher systemic exposures of vorinostat than achieved in pediatric phase I trials with continuous daily dosing are necessary for in vivo increased histone acetylation and cytotoxic activity. We conducted a phase I trial in children with relapsed/refractory neuroblastoma to determine the maximum tolerated dose (MTD) of vorinostat on an interrupted schedule, escalating beyond the previously identified pediatric MTD. Isotretinoin (cis-13-retinoic acid) 80 mg/m 2 /dose was administered by mouth twice daily on days 1-14 in combination with escalating doses of daily vorinostat up to 430 mg/m 2 /dose (days 1-4; 8-11) in each 28-day cycle using the standard 3 + 3 design. Vorinostat pharmacokinetic testing and histone acetylation assays were performed. Twenty-nine patients with refractory or relapsed neuroblastoma were enrolled and 28 were evaluable for dose escalation decisions. Median number of cycles completed was two (range 1-15); 11 patients received four or more cycles. Three patients experienced cycle 1 dose-limiting toxicities. A total of 18 patients experienced grade 3/4 toxicities related to study therapy. The maximum intended dose of vorinostat (430 mg/m 2 /day, days 1-4; 8-11) was tolerable and led to increased histone acetylation in surrogate tissues when compared to lower doses of vorinostat (P = 0.009). No objective responses were seen. Increased dose vorinostat (430 mg/m 2 /day) on an interrupted schedule is tolerable in combination with isotretinoin. This dose led to increased vorinostat exposures and demonstrated increased histone acetylation. Prolonged stable disease in patients with minimal residual disease warrants further investigation. © 2018 Wiley Periodicals, Inc.

  5. The patient perspective: utilizing focus groups to inform care coordination for high-risk medicaid populations.

    Science.gov (United States)

    Sheff, Alex; Park, Elyse R; Neagle, Mary; Oreskovic, Nicolas M

    2017-07-25

    Care coordination programs for high-risk, high-cost patients are a critical component of population health management. These programs aim to improve outcomes and reduce costs and have proliferated over the last decade. Some programs, originally designed for Medicare patients, are now transitioning to also serve Medicaid populations. However, there are still gaps in the understanding of what barriers to care Medicaid patients experience, and what supports will be most effective for providing them care coordination. We conducted two focus groups (n = 13) and thematic analyses to assess the outcomes drivers and programmatic preferences of Medicaid patients enrolled in a high-risk care coordination program at a major academic medical center in Boston, MA. Two focus groups identified areas where care coordination efforts were having a positive impact, as well as areas of unmet needs among the Medicaid population. Six themes emerged from the focus groups that clustered in three groupings: In the first group (1) enrollment in an existing medical care coordination programs, and (2) provider communication largely presented as positive accounts of assistance, and good relationships with providers, though participants also pointed to areas where these efforts fell short. In the second group (3) trauma histories, (4) mental health challenges, and (5) executive function difficulties all presented challenges faced by high-risk Medicaid patients that would likely require redress through additional programmatic supports. Finally, in the third group, (6) peer-to-peer support tendencies among patients suggested an untapped resource for care coordination programs. Programs aimed at high-risk Medicaid patients will want to consider programmatic adjustments to attend to patient needs in five areas: (1) provider connection/care coordination, (2) trauma, (3) mental health, (4) executive function/paperwork and coaching support, and (5) peer-to-peer support.

  6. Off-pump versus on-pump CABG in high-risk patients

    DEFF Research Database (Denmark)

    Linde, Jesper; Møller, Christian; Hughes, Pia

    2006-01-01

    During recent years Conventional Coronary Artery Bypass Grafting (cCABG) and Off-Pump Coronary Bypass (OPCAB) have been compared in several randomised and non-randomised studies. Focus has been on postoperative outcome with short-term follow-up in low-risk patients and therefore little is known...... of the effectiveness of OPCAB in high-risk patients. Furthermore, it is unknown if a potential beneficial short-term outcome is consistent over time....

  7. Nonoperative options for management of residual stones after cholecystostomy in high-risk patients

    Science.gov (United States)

    Reed, David M.; Daye, S. S.; Lincer, R. M.

    1993-05-01

    Cholecystostomy is frequently performed to obtain control of sepsis in high risk patients with acute cholecystitis. Retained stones in the gallbladder may cause future clinical problems. We present two patients with cholecystostomy tubes managed non-operatively. A review of other reported methods for stone extraction or destruction is also presented. Knowledge of safe and effective techniques for removal of these stones, using minimally invasive techniques is useful to the general surgeon.

  8. Galectin-3 impairment of MYCN-dependent apoptosis-sensitive phenotype is antagonized by nutlin-3 in neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Veronica Veschi

    Full Text Available MYCN amplification occurs in about 20-25% of human neuroblastomas and characterizes the majority of the high-risk cases, which display less than 50% prolonged survival rate despite intense multimodal treatment. Somehow paradoxically, MYCN also sensitizes neuroblastoma cells to apoptosis, understanding the molecular mechanisms of which might be relevant for the therapy of MYCN amplified neuroblastoma. We recently reported that the apoptosis-sensitive phenotype induced by MYCN is linked to stabilization of p53 and its proapoptotic kinase HIPK2. In MYCN primed neuroblastoma cells, further activation of both HIPK2 and p53 by Nutlin-3 leads to massive apoptosis in vitro and to tumor shrinkage and impairment of metastasis in xenograft models. Here we report that Galectin-3 impairs MYCN-primed and HIPK2-p53-dependent apoptosis in neuroblastoma cells. Galectin-3 is broadly expressed in human neuroblastoma cell lines and tumors and is repressed by MYCN to induce the apoptosis-sensitive phenotype. Despite its reduced levels, Galectin-3 can still exert residual antiapoptotic effects in MYCN amplified neuroblastoma cells, possibly due to its specific subcellular localization. Importantly, Nutlin-3 represses Galectin-3 expression, and this is required for its potent cell killing effect on MYCN amplified cell lines. Our data further characterize the apoptosis-sensitive phenotype induced by MYCN, expand our understanding of the activity of MDM2-p53 antagonists and highlight Galectin-3 as a potential biomarker for the tailored p53 reactivation therapy in patients with high-risk neuroblastomas.

  9. A comparison of targetting of neuroblastoma with MIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Rutgers, M.; Buitenhuis, C.K.M.; Smets, L.A.; Kraker, J. de; Meli, M.; Carrel, F.; Schubiger, P.A.; Novak-Hofer, I.; Amstutz, H.

    2001-01-01

    Modine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131 I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targetting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131 I-MIBG (110 MBq) and with 131 I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131 I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131 I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131 I-mAb chCE7 and of 24 days with 131 I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131 I-chCE7 compared with 131 I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131 I-MIBG and 131 I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131 I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not

  10. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

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    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases.Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients.Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death.Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  11. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases. Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients. Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death. Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  12. Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?

    International Nuclear Information System (INIS)

    Westover, K.D.; Westover, M.B.; Winer, E.P.; Richardson, A.L.; Iglehart, J.D.; Punglia, R.S.

    2011-01-01

    A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded up front exploration of the axilla or comprehensive axillary irradiation

  13. Diagnostic accuracy of high-definition CT coronary angiography in high-risk patients

    International Nuclear Information System (INIS)

    Iyengar, S.S.; Morgan-Hughes, G.; Ukoumunne, O.; Clayton, B.; Davies, E.J.; Nikolaou, V.; Hyde, C.J.; Shore, A.C.; Roobottom, C.A.

    2016-01-01

    Aim: To assess the diagnostic accuracy of computed tomography coronary angiography (CTCA) using a combination of high-definition CT (HD-CTCA) and high level of reader experience, with invasive coronary angiography (ICA) as the reference standard, in high-risk patients for the investigation of coronary artery disease (CAD). Materials and methods: Three hundred high-risk patients underwent HD-CTCA and ICA. Independent experts evaluated the images for the presence of significant CAD, defined primarily as the presence of moderate (≥50%) stenosis and secondarily as the presence of severe (≥70%) stenosis in at least one coronary segment, in a blinded fashion. HD-CTCA was compared to ICA as the reference standard. Results: No patients were excluded. Two hundred and six patients (69%) had moderate and 178 (59%) had severe stenosis in at least one vessel at ICA. The sensitivity, specificity, positive predictive value, and negative predictive value were 97.1%, 97.9%, 99% and 93.9% for moderate stenosis, and 98.9%, 93.4%, 95.7% and 98.3%, for severe stenosis, on a per-patient basis. Conclusion: The combination of HD-CTCA and experienced readers applied to a high-risk population, results in high diagnostic accuracy comparable to ICA. Modern generation CT systems in experienced hands might be considered for an expanded role. - Highlights: • Diagnostic accuracy of High-Definition CT Angiography (HD-CTCA) has been assessed. • Invasive Coronary angiography (ICA) is the reference standard. • Diagnostic accuracy of HD-CTCA is comparable to ICA. • Diagnostic accuracy is not affected by coronary calcium or stents. • HD-CTCA provides a non-invasive alternative in high-risk patients.

  14. Low mortality rates after endovascular aortic repair expand use to high-risk patients.

    Science.gov (United States)

    Adkar, Shaunak S; Turner, Megan C; Leraas, Harold J; Gilmore, Brian F; Nag, Uttara; Turley, Ryan S; Shortell, Cynthia K; Mureebe, Leila

    2018-02-01

    The 2010 endovascular aneurysm repair (EVAR) trial 2 (EVAR 2) reported that patients with comorbidity profiles rendering them unfit for open aneurysm repair who underwent EVAR did not experience a survival advantage compared with those who did not undergo intervention. These patients experienced a 30-day mortality of 7.3%, whereas reports from similar cohorts reported far lower mortality rates. The primary objective of our study was to compare the incidence of 30-day mortality in low- and high-risk patients undergoing EVAR in a contemporary data set, using patient risk stratification criteria from EVAR 2. Secondarily, we sought to identify risk factors associated with a disproportionate contribution to 30-day mortality risk. Data were obtained from the 2005 to 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files (N = 24,813). Patients were included in the high-risk cohort with the presence of renal, respiratory, or cardiac preoperative criteria alone or in combination. Renal impairment criteria were defined as dialysis and creatinine concentration >2.26 mg/dL. Respiratory impairment criteria included history of chronic obstructive pulmonary disease and preoperative ventilator support. Cardiac impairment criteria included history of myocardial infarction, congestive heart failure, angina, and prior coronary intervention. Patient and procedural characteristics and 30-day postoperative outcomes were compared using Pearson χ 2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. Among 24,813 patients undergoing EVAR, 12,043 (48%) patients were characterized as high risk (at least one impairment criterion); 12,770 (52%) patients were stratified as low risk. The 30-day mortality rate was 1.9% in the high-risk cohort compared with the 7.3% reported by EVAR 2, and it was higher in the high-risk cohort compared with the low-risk cohort (1.9% vs 0.9%; P < .001). Whereas the

  15. Percutaneous Endoscopic Colostomy (PEC): An Effective Alternative in High Risk Patients with Recurrent Sigmoid Volvulus

    International Nuclear Information System (INIS)

    Khan, M. A. S.; Ullah, S.; Beckly, D.; Oppong, F. C.

    2013-01-01

    Treatment of recurrent sigmoid volvulus is a major challenge in frail and elderly patients with multiple co-morbidities. Early management involves endoscopic decompression with high success rate, however, its recurrence make it a real challenge as most of these patients are not suitable for major colonic resection. The aim of this study was to assess the role of percutaneous endoscopic colostomy (PEC) in the treatment of recurrent sigmoid volvulus in these patients. Twelve PEC procedures were performed in 8 patients under our care. This prevented major colonic resection in 7 patients. One patient underwent sigmoid resection and died with postoperative complications. Two patients experienced minor complications. Three patients required repeat procedures for permanent PEC tube placement. Six patients managed permanently with PEC procedure. PEC is an effective treatment for recurrent sigmoid volvulus in high-risk elderly patients. (author)

  16. Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups.

    Science.gov (United States)

    Marschollek, Michael; Gövercin, Mehmet; Rust, Stefan; Gietzelt, Matthias; Schulze, Mareike; Wolf, Klaus-Hendrik; Steinhagen-Thiessen, Elisabeth

    2012-03-14

    Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High-risk subgroups may be identified

  17. Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups

    Directory of Open Access Journals (Sweden)

    Marschollek Michael

    2012-03-01

    Full Text Available Abstract Background Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1, and to identify high-risk subgroups from the data (aim#2. Methods A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493. A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. Results The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Conclusions Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack

  18. Guideline adherence for identification and hydration of high-risk hospital patients for contrast-induced nephropathy.

    NARCIS (Netherlands)

    Schilp, J.; Blok, C. de; Langelaan, M.; Spreeuwenberg, P.; Wagner, C.

    2014-01-01

    Background: Contrast-induced nephropathy (CIN) is a common cause of acute renal failure in hospital patients. To prevent CIN, identification and hydration of high-risk patients is important. Prevention of CIN by hydration of high-risk patients was one of the themes to be implemented in the Dutch

  19. Guideline adherence for identification and hydration of high-risk hospital patients for contrast-induced nephropathy

    NARCIS (Netherlands)

    Schilp, J.; de Blok, C.; Langelaan, M.; Spreeuwenberg, P.; Wagner, C.

    2014-01-01

    Background: Contrast-induced nephropathy (CIN) is a common cause of acute renal failure in hospital patients. To prevent CIN, identification and hydration of high-risk patients is important. Prevention of CIN by hydration of high-risk patients was one of the themes to be implemented in the Dutch

  20. Thromboprophylaxis for Patients with High-risk Atrial Fibrillation and Flutter Discharged from the Emergency Department

    Directory of Open Access Journals (Sweden)

    E. Margaret Warton

    2018-02-01

    Full Text Available Introduction: Many patients with atrial fibrillation or atrial flutter (AF/FL who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED. Methods: This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7 who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation. Results: Of 312 eligible patients, 128 (41.0% were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82–0.96; ED cardiology consultation (aOR 1.89, 95% CI [1.10–3.23]; and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35–5.21]. Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%, the most common of which were deferring the shared decision-making process to the patient’s outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm. Conclusion: Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population.

  1. Conjoint moderate or high risk alcohol and tobacco use among male out-patients in Thailand

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    Supa Pengpid

    2016-03-01

    Full Text Available Objective: To better understand conjoint alcohol and tobacco use among male hospital out-patients, the purposes of this study were: (1 to assess the prevalence of conjoint use and (2 to determine the factors associated with the conjoint alcohol use and tobacco use. Methods: In a cross-sectional survey, consecutive male out-patients from four district hospitals in Nakhon Pathom province in Thailand were assessed with the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST, Hospital Anxiety and Depression Scale (HADS, selfreported chronic conditions and health-seeking behaviour. The sample included 2208 study participants, with a mean age of 36.2 years (SD = 11.7 and an age range of 18–60 years. Results: Overall, 34.5% of the male hospital out-patients were conjoint moderate or high-risk alcohol and tobacco users, and 31.1% were moderate or high-risk alcohol or tobacco users. In multivariate analysis, younger age, having primary or less education, being separated, divorced or widowed, not having diabetes and not being obese were associated with conjoint moderate or high-risk alcohol and tobacco use. Conclusion: High prevalence and several risk factors of conjoint alcohol and tobacco use were found among hospital male out-patients. The findings of this study call for dual-intervention approaches for both alcohol and tobacco.

  2. Safe Reentry for False Aneurysm Operations in High-Risk Patients.

    Science.gov (United States)

    Martinelli, Gian Luca; Cotroneo, Attilio; Caimmi, Philippe Primo; Musica, Gabriele; Barillà, David; Stelian, Edmond; Romano, Angelo; Novelli, Eugenio; Renzi, Luca; Diena, Marco

    2017-06-01

    In the absence of a standardized safe surgical reentry strategy for high-risk patients with large or anterior postoperative aortic false aneurysm (PAFA), we aimed to describe an effective and safe approach for such patients. We prospectively analyzed patients treated for PAFA between 2006 and 2015. According to the preoperative computed tomography scan examination, patients were divided into two groups according to the anatomy and extension of PAFA: in group A, high-risk PAFA (diameter ≥3 cm) developed in the anterior mediastinum; in group B, low-risk PAFA (diameter <3 cm) was situated posteriorly. For group A, a safe surgical strategy, including continuous cerebral, visceral, and coronary perfusion was adopted before resternotomy; group B patients underwent conventional surgery. We treated 27 patients (safe reentry, n = 13; standard approach, n = 14). Mean age was 60 years (range, 29 to 80); 17 patients were male. Mean interval between the first operation and the last procedure was 4.3 years. Overall 30-day mortality rate was 7.4% (1 patient in each group). No aorta-related mortality was observed at 1 and 5 years in either group. The Kaplan-Meier overall survival estimates at 1 and 5 years were, respectively, 92.3% ± 7.4% and 73.4% ± 13.4% in group A, and 92.9% ± 6.9% and 72.2% ± 13.9% in group B (log rank test, p = 0.830). Freedom from reoperation for recurrent aortic disease was 100% at 1 year and 88% at 5 years. The safe reentry technique with continuous cerebral, visceral, and coronary perfusion for high-risk patients resulted in early and midterm outcomes similar to those observed for low-risk patients undergoing conventional surgery. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  3. The current contribution of molecular factors to risk estimation in neuroblastoma patients.

    Science.gov (United States)

    Berthold, F; Sahin, K; Hero, B; Christiansen, H; Gehring, M; Harms, D; Horz, S; Lampert, F; Schwab, M; Terpe, J

    1997-10-01

    The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

  4. Clinical application of percutaneous cholecystostomy in the treatment of high-risk patients with acute cholecystitis

    International Nuclear Information System (INIS)

    Qoap Delin; ZZhou Bing; Chen Shiwei; Dong Jiangnan; Hua Yingxue; Chen Bo

    2009-01-01

    Objective: To discuss the therapeutic strategy and the clinical efficacy of percutaneous cholecystostomy in treating high-risk patients with acute cholecystitis. Methods: During the period of Jan. 2006-June 2008, percutaneous cholecystostomy was performed in 27 high-risk patients with acute cholecystitis, consisting of lithic cholecystitis (n = 21) and non-lithic cholecystitis (n = 6). Of 27 patients, percutaneous cholecystostomy via transhepatic approach was performed in 22 and via transperitoneal approach in 5. The 7 F drainage catheter was used. Cholecystography was conducted before the drainage catheter was extracted. Results: Percutaneous cholecystostomy was successfully accomplished in all 27 cases, with a technical success rate of 100%. Postoperative patency of gallbladder drainage was obtained in 25 patients, with the relieving or subsiding of abdominal pain and the restoring of temperature and leukocyte account to normal range within 72 hours. In one patient, as the abdominal pain relief was not obvious 72 hours after the procedure, cholecystography was employed and it revealed the obstruction of the drainage catheter. After reopening of the drainage catheter, the abdominal pain was relieved. In another case, cholecystography was carried out because the abdominal pain became worse after the procedure, and minor bile leak was demonstrated. After powerful anti-infective and symptomatic medication, the abdominal pain was alleviated. The drainage catheter was extracted in 25 patients 6-7 weeks after the treatment. Of these 25 patients, 12 accepted selective cholecystectomy, 7 received percutaneous cholecystolithotomy and 6 with non-lithic cholecystitis did not get any additional surgery. The remaining two patients were living with long-term retention of the indwelling drainage-catheter. Conclusion: Percutaneous cholecystostomy is a simple, safe and effective treatment for acute cholecystitis in high-risk patients. This technique is of great value in clinical

  5. High risk for obstructive sleep apnea in patients with acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Carla Renata Silva Andrechuk

    2015-10-01

    Full Text Available Objectives: to stratify the risk for obstructive sleep apnea in patients with acute myocardial infarction, treated at a public, tertiary, teaching hospital of the state of São Paulo, Brazil, and to identify related sociodemographic and clinical factors.Method: cross-sectional analytical study with 113 patients (mean age 59.57 years, 70.8% male. A specific questionnaire was used for the sociodemographic and clinical characterization and the Berlin Questionnaire for the stratification of the risk of obstructive sleep apnea syndrome.Results: the prevalence of high risk was 60.2% and the outcome of clinical worsening during hospitalization was more frequent among these patients. The factors related to high risk were body mass index over 30 kg/m2, arterial hypertension and waist circumference indicative of cardiovascular risk, while older age (60 years and over constituted a protective factor.Conclusion: considering the high prevalence of obstructive sleep apnea and its relation to clinical worsening, it is suggested that nurses should monitor, in their clinical practice, people at high risk for this syndrome, guiding control measures of modifiable factors and aiming to prevent the associated complications, including worsening of cardiovascular diseases.

  6. Minimally invasive mitral valve surgery expands the surgical options for high-risks patients.

    Science.gov (United States)

    Petracek, Michael R; Leacche, Marzia; Solenkova, Natalia; Umakanthan, Ramanan; Ahmad, Rashid M; Ball, Stephen K; Hoff, Steven J; Absi, Tarek S; Balaguer, Jorge M; Byrne, John G

    2011-10-01

    A simplified minimally invasive mitral valve surgery (MIMVS) approach avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm) right antero-lateral incision was developed. We hypothesized that, in high-risk patients and in patients with prior sternotomy, this approach would yield superior results compared to those predicted by the Society of Thoracic Surgeons (STS) algorithm for standard median sternotomy mitral valve surgery. Five hundred and four consecutive patients (249 males/255 females), median age 65 years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median preoperative New York Heart Association function class was 3 (range 1-4). Eighty-two (16%) patients had an ejection fraction ≤35%. Forty-seven (9%) had a STS predicted mortality ≥10%. Under cold fibrillatory arrest (median temperature 28°C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or replacement (280/504, 56%) was performed. Thirty-day mortality for the entire cohort was 2.2% (11/504). In patients with a STS predicted mortality ≥ 10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the mean STS predicted mortality of 20%. Morbidity in this high-risk group was equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47 (2%) patients suffered a permanent neurologic deficit, none had wound infection. The median length of stay was 8 days (range 1-68 days). This study demonstrates that MIMVS without aortic cross-clamp is reproducible with low mortality and morbidity rates. This approach expands the surgical options for high-risk patients and yields to superior results than the conventional median sternotomy approach.

  7. Podocyturia as a Diagnostic Marker for Preeclampsia amongst High-Risk Pregnant Patients

    Directory of Open Access Journals (Sweden)

    Belinda Jim

    2012-01-01

    Full Text Available Urinary podocyte (podocyturia has been studied as a diagnostic marker for preeclampsia. We sought to validate its use in preeclampsia and in differentiating it from other high risk pregnancy states. We studied an obstetric population at high risk to develop preeclampsia (study group and uncomplicated pregnancies (control group by analyzing their urine sediment for podocytes within 24 hours of delivery. Podocytes were identified by immunohistochemistry using the podocyte-specific protein synaptopodin. Of the 56 patients who were enrolled, 29 patients were diagnosed with preeclampsia, 9 patients had hypertensive conditions such as chronic and gestational hypertension, 6 patients had Type I/II and gestational diabetes mellitus, 3 patients were classified as others, and 9 patients exhibited uncomplicated pregnancies. Podocyturia was identified in 11 out of 29 (38% of patients with preeclampsia/eclampsia, 3 out of 9 (33% with gestational and chronic hypertension, and 3 out of 6 (50% with Type I/II and gestational diabetes mellitus. None of the 9 patients (0% with uncomplicated pregnancies demonstrated podocyturia. The sensitivity and specificity of podocyturia for preeclampsia were found to be 38% and 70%. Our study showed that podocyturia does not appear to be a sensitive nor a specific marker to diagnose preeclampsia.

  8. Off-pump coronary surgery: surgical strategy for the high-risk patient.

    Science.gov (United States)

    Van Belleghem, Y; Caes, F; Maene, L; Van Overbeke, H; Moerman, A; Van Nooten, G

    2003-02-01

    In a retrospective study, we compared two groups of consecutive patients operated by the same team during the year 2000 for coronary artery disease with the use of extracorporeal circulation (group 1, n=230) or on the beating heart using the Octopus II plus stabiliser (group 2, n=228). High-risk patients were identified by a EuroSCORE plus 6. EuroSCORE definitions and predicted risk models were utilized to compare the variables of the groups. There were no significant differences between the preoperative variables of the groups in age, gender, left ventricular function, diabetes and peripheral vascular and renal disease as is indicated by the Euroscore (resp. 4.7/5.1 p=0.107). Calcification of the ascending aorta and chronic obstructive lung disease were statistically significant more prevalent in the beating heart group. No differences in preoperative variables in the high-risk patients group (Euroscore 8.5/8.1 p=0.356) except for calcification of the ascending aorta. All patients underwent a full revascularisation through a midline sternotomy. Significant more distal anastomoses were performed in group 1 (3.7 per patient (1-6)) with regard to group 2 (2.9 per patient (1-6)). Anesthesia, postoperative treatment and follow up were equal for both groups. A significant lower incidence of atrial fibrillation (p=0.010), shorter ICU stay (p=0.031) and renal insufficiency (p=0.033) was reported in group 2. In the low risk group, we could not diagnose any difference between the two groups, except for atrial fibrillation. The benefits of the beating heart surgery however were more pronounced in the high-risk patient as is indicated by a significant reduction of the ICU stay by 1 day (3.5d/2.5d (p=0.028)), better preservation of the renal function (p=0.017) and a significant reduction of the length of hospital stay by more than two days (p=0.040). A lower incidence of atrial fibrillation, however not significant. In our experience, beating heart surgery is a safe

  9. Olfactory neuroblastoma

    International Nuclear Information System (INIS)

    Rashid, D.; Ahmed, B.; Malik, S.M.; Khan, M.

    2000-01-01

    Olfactory neuroblastoma/esthesioneuroblastoma in a rare malignant tumour of the olfactory neuroepithelium. This is a report of 5 cases managed over the last 10 years at Combined Military Hospital, Rawalpindi. Age of the patients at presentation ranged from 27 to 70 years. The main symptoms were unilateral nasal obstruction and intermittent epistaxis. The mean duration of symptoms at presentation was 11 months. Two patients were staged as B and 3 as C at presentation. The stage of the disease correlated with the duration of symptoms. All the cases were diagnosed on histopathology. Three were offered combination of surgery and radiotherapy. One patient received only surgical treatment and one patient received radiotherapy and chemotherapy. Combination of surgery and radiotherapy showed best results. (author)

  10. How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores.

    Science.gov (United States)

    Oku, Kenji; Amengual, Olga; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-08-01

    Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population. It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). Additionally, clinicians may need to be aware of the patient's medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.

  11. Combined surgical and radiological intervention for complicated cholelithiasis in high-risk patients

    International Nuclear Information System (INIS)

    Gibney, R.G.; Fache, J.S.; Becker, C.D.; Nichols, D.M.; Cooperberg, P.L.; Stoller, J.L.; Burhenne, H.J.

    1987-01-01

    Surgical cholecystostomy under local infiltration anesthesia was combined with radiologic removal of gallstones in 36 high-risk patients with acute calculous gallbladder disease. At cholecystostomy, the fundus of the gallbladder was sutured to the anterior abdominal wall, permitting early percutaneous stone removal through the short surgical tract. All gallstones were removed in 31 of 36 patients, for an overall success rate of 86%. The success rate was 97% for gallbladder stones, 86% for cystic duct stones, and 63% for common bile duct stones which were removed by traversing the cystic duct. There were no deaths or serious complications

  12. Endovascular Management of Infected Femoral Artery Pseudoaneurysms in High-Risk Patients: A Case Series

    Energy Technology Data Exchange (ETDEWEB)

    D’Oria, Mario, E-mail: mario.doria88@outlook.com; Sgorlon, Giada; Calvagna, Cristiano; Zamolo, Francesca; Chiarandini, Stefano; Adovasio, Roberto; Griselli, Filippo [University Hospital of Cattinara, Vascular and Endovascular Surgery Unit (Italy)

    2017-04-15

    We report our experience with the urgent treatment of two high-risk patients with infected femoral artery pseudoaneurysms (IFAPs) with the placement of a self-expandable covered stent (SECS). In both cases, there was no perioperative mortality and the aneurysm exclusion was successful without early or late stent thrombosis/stent fracture nor acute or chronic limb ischemia or limb loss. There was no recurrence of local or systemic infection during the follow-up period. Endovascular therapy represents a feasible treatment option for IFAPs in those patients for whom the risk of open surgical repair would be prohibitive, especially under urgent circumstances.

  13. [Renal biopsy in the lateral position in high risk patients: an opportunity to take advantage of].

    Science.gov (United States)

    Dugo, Mauro; Brisotto, Elisa; Vitturi, Nicola; Pasi, Alessandra; Mastrosimone, Stefania; Farneti, Fabrizio; Mangino, Margherita; Virgilio, Bice; Brunello, Anna; Pastori, Giordano; Mazzoli, Matteo; Laurino, Licia; Cova, Giandavide; Beniamin, Francesco; Maresca, Maria Cristina

    2015-01-01

    Percutaneous ultrasound-guided renal biopsy (RB) is the gold standard for diagnosis of renal diseases. The standard procedure involves biopsy in the prone position (PP) for the native kidneys. In high risk patients, transjugular and laparoscopic RB have been proposed. In patients suffering from obesity or respiratory diseases, the RB of the native kidney in the supine anterolateral position (SALP) represents an alternative to these invasive and expensive methods. We illustrate the technique of execution of RB in the lateral position (LP) on native kidneys. The procedure is safe, effective and has reduced the path travelled by the needle biopsy compared with PP and SALP.

  14. Feasibility of performing 123I MIBG scintigraphy in patients with neuroblastoma in the Maltese Islands

    International Nuclear Information System (INIS)

    Samuel, A.; Debattista, A.; Delia, M.; Grima, K.; Apap Bologna, G.

    2004-01-01

    Full text: The Maltese Islands lie in the middle of the Mediterranean Sea, 90 km south of Sicily and 300 km north of Libya. The supply of short-lived radioisotopes for medical use from mainland Europe is therefore logistically difficult. Due to this, several of our patients in the past were sent to centers in UK for various nuclear medicine procedures. Neuroblastoma is the commonest paediatric malignancy with an incidence in the Maltese islands similar to the figures in Western European. Tc-99m MDP and I-123 MIBG scans are important diagnostic tools in the management of these patients. We report our experience of I-123 MIBG scanning in paediatric patients with neuroblastoma. Between March 1997 and March 2003, 4 patients were examined and a total 8 scans were performed at the time of initial diagnosis and follow-up period. All these patients also underwent bone scintigraphy as a part of the protocol used in our hospital. We will discuss the problems encountered by us in obtaining the radiopharmaceutical and how these were circumvented. The procedure in place requires excellent coordination between all links of the supply chain namely manufacturers, overseas transporters, local customs officials, local delivery men, hospital staff and last but not least the patients (or their parents) themselves. Nowadays, these scans are performed on a routine basis whenever requested by the paediatric department and no patient in the last 4 years required rescheduling of the scan. The facts that the procedures are performed in the patient's own country rather than overseas reduces the psychological trauma that both the children as well as the parents go through. Furthermore, the convenience of performing the scans locally has resulted in significant cost savings to the National Health Service. (author)

  15. Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    Veness, M.J.

    2005-01-01

    Non-melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature. Copyright (2005) Blackwell Science Pty Ltd

  16. Serum-Based Quantification of MYCN Gene Amplification in Young Patients with Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Shigeki Yagyu

    Full Text Available We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB. Here, we analyzed the relationship between MYCN amplification (MNA status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86% and very high specificity (95%. The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4. MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01. The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00-24.78, and 1.41 (95% confidence interval, 0.63-3.14 for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status.

  17. Value of breast MRI as supplement to mammography and sonography for high risk breast cancer patients

    International Nuclear Information System (INIS)

    Schlossbauer, T.; Hellerhoff, K.; Reiser, M.

    2008-01-01

    The aim of this study is to give an overview on early detection of breast cancer in patients with an increased risk of breast cancer. Sensitivities and diagnostic accuracies of breast MRI, mammography and ultrasound were compared. A systematic literature search of the past 3 years was performed. Studies which compared breast imaging modalities and used image-guided biopsy results as standard of reference were included. Patients included had to have had an increased lifetime risk for breast cancer (>15%). Regarding sensitivity and diagnostic accuracy, breast MRI performed best in comparison to the other modalities within this collective of patients. Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and ultrasound, respectively Breast MRI is a well established tool for screening in patients at high risk for developing breast cancer and is a valuable supplement to mammography and ultrasound within this selected cohort of patients. (orig.) [de

  18. High-risk respiratory patients' experiences of bronchoscopy with conscious sedation and analgesia: A qualitative study.

    Science.gov (United States)

    Saxon, Catherine; Fulbrook, Paul; Fong, Kwun M; Ski, Chantal F

    2017-10-20

    To understand the experiences of high-risk respiratory patients undergoing bronchoscopy with conscious sedation. Due to possible complications, high-risk respiratory patients are usually given smaller, cautious doses of sedation and analgesia for bronchoscopy. Described as "conscious sedation," this facilitates depression of the patient's consciousness without causing respiratory compromise. Previously, studies have investigated patient experience using quantitative methods. This is the first study that has explored the patient experience during bronchoscopy from a qualitative perspective. Qualitative, phenomenological approach as described by Van Manen. The setting was an endoscopy unit within an Australian tertiary hospital. Unstructured interviews were conducted with 13 patients with chronic obstructive pulmonary disease who underwent day-case bronchoscopy. All participants received conscious sedation. They were interviewed twice, within a week, postprocedure. Interviews were transcribed verbatim and analysed using Van Manen's interpretive approach. Participants had varying experiences. Five themes emerged from the analysis: Frustration and fear; Comfort and safety; Choking and coughing; Being aware; and Consequences. Whilst not all participants experienced procedural awareness or remembered it, for those who did it was a significant event. Overall, experiences were found to be negative; however, participants accepted and tolerated them, perceiving them as necessary to obtain a diagnostic result. The findings demonstrate that often patients are aware during the procedure and their experience may be uncomfortable and distressing. These findings have implications for patient preparation pre- and post-bronchoscopy in terms of what they might expect, and to discuss what has happened after the procedure. Some practices of the bronchoscopy team during the procedure may need modification. For example, in anticipation of the possibility that the patient may be aware

  19. [Preventive efficacy of ondansetron and granisetron for postoperative nausea and vomiting in high risk patients].

    Science.gov (United States)

    Quan, Xiang; Zhu, Bo; Ye, Tie-hu

    2011-08-01

    To compare the efficacy of ondansetron and granisetron in the prevention of postoperative nausea and vomiting (PONV) in high-risk patients. Totally 200 patients with three key risk factors for PONV (female, non-smoking and postoperative opioid use) were equally randomized into ondansetron group and granisetron group. Ondansetron (4 mg) or granisetron (3 mg) was intravenously administered upon the completion of surgery. The episodes of nausea and vomiting were observed for 24 hours after surgery. A significantly greater proportion of patients in granisetron group achieved a complete response (i.e., no PONV or rescue medication) during the first 24 hours postoperatively versus those in ondansetron group (62.6% vs. 46.9%, respectively; P=0.048). There were no significant differences in terms of postoperative nausea incidences (42.9% vs. 34.3%, respectively), postoperative vomiting incidences (25.5% vs. 20.2%, respectively) and postoperative rescue anti-emetics incidences (19.4% vs. 15.2%, respectively) (P>0.05). Granisetron is more effective than ondansetron in preventing PONV in high-risk patients during the first 24 hours postoperatively.

  20. Identification of patients with cancer with a high risk to develop delirium.

    Science.gov (United States)

    Neefjes, Elisabeth C W; van der Vorst, Maurice J D L; Verdegaal, Bertha A T T; Beekman, Aartjan T F; Berkhof, Johannes; Verheul, Henk M W

    2017-08-01

    Delirium deteriorates the quality of life in patients with cancer, but is frequently underdiagnosed and not adequately treated. In this study, we evaluated the occurrence of delirium and its risk factors in patients admitted to the hospital for treatment or palliative care in order to develop a prediction model to identify patients at high risk for delirium. In a period of 1.5 years, we evaluated the risk of developing delirium in 574 consecutively admitted patients with cancer to our academic oncology department with the Delirium Observation Screening Scale. Risk factors for delirium were extracted from the patient's chart. A delirium prediction algorithm was constructed using tree analysis, and validated with fivefold cross-validation. A total of 574 patients with cancer were acutely (42%) or electively (58%) admitted 1733 times. The incidence rate of delirium was 3.5 per 100 admittances. Tree analysis revealed that the predisposing factors of an unscheduled admittance and a metabolic imbalance accurately predicted the development of delirium. In this group the incidence rate of delirium was 33 per 100 patients (1:3). The AUC of the model was 0.81, and 0.65 after fivefold cross-validation. We identified that especially patients undergoing an unscheduled admittance with a metabolic imbalance do have a clinically relevant high risk to develop a delirium. Based on these factors, we propose to evaluate preventive treatment of these patients when admitted to the hospital in order to improve their quality of life. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma

    NARCIS (Netherlands)

    Kroesen, M.; Bull, C.; Gielen, P.R.; Brok, I.C.; Armandari, I.; Wassink, M.; Looman, M.W.G.; Boon, L.; Brok, M.H.M.G.M. den; Hoogerbrugge, P.M.; Adema, G.J.

    2016-01-01

    Neuroblastoma (NBL) is a childhood malignancy of the sympathetic nervous system. For high-risk NBL patients, the mortality rate is still over 50%, despite intensive multimodal treatment. Anti-GD2 monoclonal antibody (mAB) in combination with systemic cytokine immunotherapy has shown clinical

  2. Sevoflurane-Based Inhalation Induction in High-Risk Elderly Patients During Noncardiac Surgery

    Directory of Open Access Journals (Sweden)

    O. A. Grebenchikov

    2011-01-01

    Full Text Available Objective: to study the hemodynamic effects of sevoflurane during the induction of anesthesia in elderly patients at high risk for cardiac events. Subjects and methods. This study enrolled 32 patients who had a left ventricular ejection fraction of <30% during preoperative examination. According to the presumptive type of anesthesia, the patients were randomized to one of the study groups: In the sevoflurane group receiving infusion of fentanyl (1 ig^kg”‘^hr”‘, anesthesia was induced by sevoflurane at the maximum concentration of 8 vol% at first inspiration, without the respiratory circuit being prefilled. After loss of consciousness, further saturation was carried out using Fianesth, 5 vol%. Combination anesthesia (CA was that which was induced by successive administration of dormicum, ketamine, propo-fol, and fentanyl. The trachea was intubated during total myoplegia under the control of TOF (TOF-Watch, Organon, the Netherlands. Results. In all the patients under CA, its induction was made during infusion of dopamine (5 lg^kg”‘^min”‘, the dose of which had to be increased up to 10 ig • kg-1 • min-1 in 6 (75% patients. Nevertheless, there were decreases in mean blood pressure (BPmean to 46±6 mm Hg and in cardiac index (CI to 1.5±0.3 fig • kg-1 • min-1 (by 32% of the outcome value. In the sevoflurane inhalation induction group, only 3 (12.5% patients needed dopamine. Its dose producing a cardiotonic effect was near-minimal; its average maintenance infusion rate was 5.3±0.3 ig^kg”‘^min”‘. The reduction in CI was statistically insignificant; despite a 9% decrease in BPmean, this indicator in the sevoflurane group remained within acceptable ranges. Conclusion. The use of a sevoflurane-based inhalation induction technique permits higher hemodynamic stability in patients at high risk for cardiac events. Key words: inhalation induction, sevoflurane, ketamine, elderly patients.

  3. Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture

    Energy Technology Data Exchange (ETDEWEB)

    Pusceddu, Claudio, E-mail: clapusceddu@gmail.com [Regional Referral Center for Oncologic Diseases, Division of Interventional Radiology, Department of Oncological Radiology, Ocological Hospital “A. Businco” (Italy); Sotgia, Barbara, E-mail: barbara.sotgia@gmail.com; Fele, Rosa Maria, E-mail: rosellafele@tiscali.it [Regional Referral Center for Oncological Diseases, Department of Oncological Radiology, Oncological Hospital “A. Businco” (Italy); Ballicu, Nicola, E-mail: nicolaballicu77@gmail.com [Regional Referral Center for Oncologic Diseases, Division of Interventional Radiology, Department of Oncological Radiology, Ocological Hospital “A. Businco” (Italy); Melis, Luca, E-mail: doclucamelis@tiscali.it [Regional Referral Center for Oncological Diseases, Department of Oncological Radiology, Oncological Hospital “A. Businco” (Italy)

    2016-01-15

    PurposeTo retrospectively evaluate the effectiveness of computed tomography-guided percutaneous microwave ablation (MWA) and cementoplasty in patients with painful bone metastases at high risk of fracture.Materials and MethodsThirty-five patients with 37 metastatic bone lesions underwent computed tomography-guided MWA combined with cementoplasty (polymethylmethacrylate injection). Vertebrae, femur, and acetabulum were the intervention sites and the primary end point was pain relief. Pain severity was estimated by visual analog scale (VAS) before treatment; 1 week post-treatment; and 1, 6, and 12 months post-treatment. Functional outcome was assessed by improved patient walking ability. Radiological evaluation was performed at baseline and 3 and 12 months post-procedure.ResultsIn all patients, pain reduction occurred from the first week after treatment. The mean reduction in the VAS score was 84, 90, 90 % at week 1, month 1, and month 6, respectively. Improved walking ability occurred in 100 and 98 % of cases at the 1- and 6-month functional outcome evaluations, respectively. At the 1-year evaluation, 25 patients were alive, and 10 patients (28 %) had died because of widespread disease. The mean reduction in the VAS score and improvement in surviving patients’ walking ability were 90 and 100 %, respectively. No patients showed evidence of local tumor recurrence or progression and pathological fracture in the treated sites.ConclusionOur results suggest that MWA combined with osteoplasty is safe and effective when treating painful bone metastases at high risk of fracture. The number of surviving patients at the 1-year evaluation confirms the need for an effective and long-lasting treatment.

  4. Intertrochanteric fractures in elderly high risk patients treated with Ender nails and compression screw

    Directory of Open Access Journals (Sweden)

    Gangadharan Sidhartha

    2010-01-01

    Full Text Available Background: Ender and Simon Weidner popularized the concept of closed condylocephlic nailing for intertrochanteric fractures in 1970. The clinical experience of authors revealed that Ender nailing alone cannot provide secure fixation in elderly patients with osteoporosis. Hence we conducted a study to evaluate the efficacy of a combined fixation procedure using Ender nails and a cannulated compression screw for intertrochanteric fractures. Materials and Methods: 76 patients with intertrochanteric fractures were treated using intramedullary Ender nails and cannulated compression screw from January 2004 to December 2007. The mean age of the patients was 80 years (range 70-105 years.Using the Evan′s system of classification 49 were stable and 27 unstable fractures. Inclusion criteria was high risk elderly patients (age > 70 years with intertrochanteric fracture. The exclusion criteria included patients with pressure sores over the trochanteric region. Many patients had pre-existing co-morbidities like diabetes mellitus, hypertension, COPD, ischemic heart disease, CVA and coronary artery bypass surgery. The two Ender nails of 4.5mm each were passed across the fracture site into the proximal neck. This was reinforced with a 6.5 mm cannulated compression screw passed from the sub trochanteric region, across the fracture into the head. Results: The mean follow-up was 14 months (range 9-19 months Average time to fracture union was 10 weeks (range 6-16 weeks. The mean knee ROM was 130o (± 5o. There was no case of nail penetration into hip joint. In five cases with advanced osteoporosis there was minimal migration of Ender nails distally. Conclusions: The Ender nailing combined with compression screw fixation in cases of intertrochanteric fractures in high risk elderly patients could achieve reliable fracture stability with minimal complications.

  5. Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C

    2016-10-07

    Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

  6. [The cellular factors of innate immunity in nonpsychotic patients at high risk for schizophrenia].

    Science.gov (United States)

    Vasilyeva, E F; Kushner, S G; Factor, M I; Omelchenko, M A; Bogdanova, E D; Petrakova, L N; Brusov, O S

    Changes in the parameters of innate immunity in patients with schizophrenia are observed already in the first episode. The study was performed to find out whether these changes take place prior to disease manifestation, and what role do they play in the pathogenesis of schizophrenia. Thirty-five male nonpsychotic patients at high risk of psychosis, aged between 17 to 23 years, were examined. Phagocyte activity (PA) of neutrophils in the blood serum was evaluated by the number of active neutrophils, i.e. phagocytic index (PhI), and phagocytic number (PhN), which was determined by counting latex particles absorbed with a single phagocytic cell. Cytotoxic activity of natural killer lymphocytes (NK CA) was evaluated by the number of cell targets K-562, which remained non-degraded after the contact with natural killer cells. The influence of monocytes on NKCA was determined as well. Compared to controls, patients had the lower PhI level (pschizophrenia.

  7. Value of improved lipid control in patients at high risk for adverse cardiac events.

    Science.gov (United States)

    Jena, Anupam B; Blumenthal, Daniel M; Stevens, Warren; Chou, Jacquelyn W; Ton, Thanh G N; Goldman, Dana P

    2016-06-01

    Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. Simulation model. We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select.

  8. Identification of the high risk emergency surgical patient: Which risk prediction model should be used?

    Science.gov (United States)

    Stonelake, Stephen; Thomson, Peter; Suggett, Nigel

    2015-09-01

    National guidance states that all patients having emergency surgery should have a mortality risk assessment calculated on admission so that the 'high risk' patient can receive the appropriate seniority and level of care. We aimed to assess if peri-operative risk scoring tools could accurately calculate mortality and morbidity risk. Mortality risk scores for 86 consecutive emergency laparotomies, were calculated using pre-operative (ASA, Lee index) and post-operative (POSSUM, P-POSSUM and CR-POSSUM) risk calculation tools. Morbidity risk scores were calculated using the POSSUM predicted morbidity and compared against actual morbidity according to the Clavien-Dindo classification. The actual mortality was 10.5%. The average predicted risk scores for all laparotomies were: ASA 26.5%, Lee Index 2.5%, POSSUM 29.5%, P-POSSUM 18.5%, CR-POSSUM 10.5%. Complications occurred following 67 laparotomies (78%). The majority (51%) of complications were classified as Clavien-Dindo grade 2-3 (non-life-threatening). Patients having a POSSUM morbidity risk of greater than 50% developed significantly more life-threatening complications (CD 4-5) compared with those who predicted less than or equal to 50% morbidity risk (P = 0.01). Pre-operative risk stratification remains a challenge because the Lee Index under-predicts and ASA over-predicts mortality risk. Post-operative risk scoring using the CR-POSSUM is more accurate and we suggest can be used to identify patients who require intensive care post-operatively. In the absence of accurate risk scoring tools that can be used on admission to hospital it is not possible to reliably audit the achievement of national standards of care for the 'high-risk' patient.

  9. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

    NARCIS (Netherlands)

    H.N. Caron (Huib); P. van Sluis (Peter); J. de Kraker (Jan); J.P. Bökkerink (Jos); R.M. Egeler (Maarten); G. Laureys (Geneviève); R. Slater (Rosalyn); A. Westerveld (Andries); M.T. Voûte (Michiel); R. Versteeg (Rogier)

    1996-01-01

    textabstractBackground. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic

  10. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

    NARCIS (Netherlands)

    Caron, H.; van Sluis, P.; de Kraker, J.; Bökkerink, J.; Egeler, M.; Laureys, G.; Slater, R.; Westerveld, A.; Voûte, P. A.; Versteeg, R.

    1996-01-01

    Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in

  11. Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk

    DEFF Research Database (Denmark)

    Gaede, P; Pedersen, O

    2005-01-01

    Results from many single risk factor intervention trials and the multi-targeted Steno-2 trial in the last few years have provided a strong case that management of type 2 diabetes in all age groups requires a structured and intensified approach that is far more than just glucocentric, an approach...... addressing additional cardiovascular risk factors including hypertension, dyslipidaemia, sedentary behaviour, smoking and dietary habits causing insulin resistance and pro-inflammation. This type of integrated therapy applied for almost 8 years to high-risk type 2 diabetic patients has cut the relative risk......-driven polypharmacy and simple but focused behaviour modelling with continuous education, motivation and trouble-shooting for treatment barriers identified for the patient and the care giver. It is high time we transfer these experiences and major health benefits gained in the 'green house' of controlled clinical...

  12. Selection of high risk groups among prognostically favorable patients with breast cancer.

    Science.gov (United States)

    Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

    1981-01-01

    In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

  13. Patients with a high risk for obstructive sleep apnea syndrome: postoperative respiratory complications.

    Science.gov (United States)

    Pereira, H; Xará, D; Mendonça, J; Santos, A; Abelha, F J

    2013-01-01

    STOP-BANG score (snore; tired; observed apnea; arterial pressure; body mass index; age; neck circumference and gender) can predict the risk of a patient having Obstructive Syndrome Apnea (OSA). The aim of this study was to evaluate the incidence STOP-BANG score≥3, in surgical patients admitted to the Post-Anesthesia Care Unit (PACU). Observational, prospective study conducted in a post-anesthesia care unit (PACU) during three weeks (2011). The study population consisted of adult patients after noncardiac and non-neurological surgery. Patients were classified as high risk of OSA (HR-OSA) if STOP-BANG score≥3 and Low-risk of OSA (LR-OSA) if STOP-BANG score<3 (LR-OSA). Patient demographics, intraoperative and postoperative data were collected. Patient characteristics were compared using Mann-Whitney U-test, t-test for independent groups, and chi-square or Fisher's exact test. A total of 357 patients were admitted to PACU; 340 met the inclusion criteria. 179 (52%) were considered HR-OSA. These patients were older, more likely to be masculine, had higher BMI, higher ASA physical status, higher incidence of ischemic heart disease, heart failure, hypertension, dyslipidemia and underwent more frequently insulin treatment for diabetes. These patients had more frequently mild/moderated hypoxia in the PACU (9% vs. 3%, p=0.012) and had a higher incidence of residual neuromuscular blockade (NMB) (20% vs. 16%, p=0.035). Patients with HR-OSA had a longer hospital stay. Patients with HR-OSA had an important incidence among patients scheduled for surgery in our hospital. These patients had more co-morbidities and were more prone to post-operative complications. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  14. Midterm results of endovascular stent graft treatment for descending aortic aneurysms including high-risk patients

    Directory of Open Access Journals (Sweden)

    Gussmann, Andreas

    2006-04-01

    Full Text Available Methods: 21 patients (17 men, 4 women; mean age 66.1 years, range 29-90 years with 15 true aneurysms, and 6 type B-dissections were treated by implantation of a TalentTM Endoluminal Stentgraft System from February 2000 to July 2003. In 3 cases it was necessary to overstent the left subclavian artery, in 1 case to overstent the left common carotid. Results: 2 patients (9.5% died during the first 30 days (1 myocardial infarction, 1 pneumonia. Two patients (9.5% suffered from cerebral ischemia and needed revascularisation. No paraplegia, no stroke occurred. One endoleak required additional stenting. No patient needed conversion. Follow-up, average 25.4 months (range 0-39, was 100% complete. During this another two patients died of myocardial infarction i.e. 9.5% (the above mentioned endoleak, but no late migration were detected in the remaining patients. In all cases the graft lumen stayed patent. Conclusions: Treatment of descending thoracic aortic aneurysm with an endovascular approach has acceptable mortality and morbidity-rates even in high risk patients. Procedural overstenting of the subclavian artery requires subclavian revascularisation in a minority of cases.

  15. Characterizing the High-Risk Homebound Patients in Need of Nurse Practitioner Co-Management

    Science.gov (United States)

    Jones, Masha G.; Ornstein, Katherine A.; Skovran, David M.; Soriano, Theresa A.; DeCherrie, Linda V.

    2016-01-01

    By providing more frequent provider visits, prompt responses to acute issues, and care coordination, nurse practitioner (NP) co-management has been beneficial for the care of chronically ill older adults. This paper describes the homebound patients with high symptom burden and healthcare utilization who were referred to an NP co-management intervention and outlines key features of the intervention. We compared demographic, clinical, and healthcare utilization data of patients referred for NP co-management within a large home-based primary care (HBPC) program (n=87) to patients in the HBPC program not referred for co-management (n=1027). A physician survey found recurrent hospitalizations to be the top reason for co-management referral and a focus group with nurses and social workers noted that co-management patients are typically those with active medical issues more so than psychosocial needs. Co-management patients are younger than non-co-management patients (72.31 vs. 80.30 years old, P<0.001), with a higher mean Charlson comorbidity score (3.53 vs. 2.47, P=0.0001). They have higher baseline annual hospitalization rates (2.27 vs. 0.61, P=0.0005) and total annual home visit rates (13.1 vs. 6.60, P=0.0001). NP co-management can be utilized in HBPC to provide intensive medical management to high-risk homebound patients. PMID:27876403

  16. Anesthetic approach to high-risk patients and prolonged awake craniotomy using dexmedetomidine and scalp block.

    Science.gov (United States)

    Garavaglia, Marco M; Das, Sunit; Cusimano, Michael D; Crescini, Charmagne; Mazer, C David; Hare, Gregory M T; Rigamonti, Andrea

    2014-07-01

    Awake craniotomy with intraoperative speech or motor testing is relatively contraindicated in cases requiring prolonged operative times and in patients with severe medical comorbidities including anxiety, anticipated difficult airway, obesity, large tumors, and intracranial hypertension. The anesthetic management of neurosurgical patients who possess these contraindications but would be optimally treated by an awake procedure remains unclear. We describe a new anesthetic approach for awake craniotomy that did not require any airway manipulation, utilizing a bupivacaine-based scalp nerve block, and dexmedetomidine as the primary hypnotic-sedative agent. Using this technique, we provided optimal operative conditions to perform awake craniotomy facilitating safe tumor resection, while utilizing intraoperative electrocorticography for motor and speech mapping in a cohort of 10 patients at a high risk for airway compromise and complications associated with patient comorbidities. All patients underwent successful awake craniotomy, intraoperative mapping, and tumor resection with adequate sedation for up to 9 hours (median 3.5 h, range 3 to 9 h) without any loss of neurological function, airway competency, or the need to provide any active rescue airway management. We report 4 of these cases that highlight our experience: 1 case required prolonged surgery because of the complexity of tumor resection and 3 patients had important medical comorbidities and/or relative contraindication for an awake procedure. Dexmedetomidine, with concurrent scalp block, is an effective and safe anesthetic approach for awake craniotomy. Dexmedetomidine facilitates the extension procedure complexity and duration in patients who might traditionally not be considered to be candidates for this procedure.

  17. Neoadjuvant treatment and adjuvant radiotherapy for patients with high risk prostate cancer and radical prostatectomy

    International Nuclear Information System (INIS)

    Scorticati, Carlos; Aguilar, Jorge A.; Gonzalez Granda, Pablo; Mendez, Fernando; Montiel, Raul; Rege, Eduardo; Alvarez, Patricio; Lopez, Miguel A.; Rizzi, Alfredo; Mazza, Osvaldo

    2009-01-01

    Introduction and Objectives: To analyze the results of the treatment in patients with cancer of prostate of high risk. Material and Method: Retrospective and observational analysis of 130 patients operated by CAP of high risk (criteria of D'Amico) average 41,48 months, divided in form nonrandomized in three groups 1: radical prostatectomy, 2: neoadjuvant hormonoterapy (BAC) + PR, 3: BAC + PR + x-ray (RT). Statistical analysis: multivaried, test of curved Chi2 and p statistical and of Kaplan Meier. Results: Biochemical relapse 68 patients (52.3%), average 23,37 months. Without differences according to therapeutic modality (p: 0.043). In the multivaried analysis of the 3 factors of presurgical, single risk we found a statistically significant relation in the coexistence of the 3 factors with the presence of positive margin in the PR piece. (p: 0,002). The analysis to make or not, neoadjuvant BAC without significant difference (p: 0,403) evaluating in such the rate of M+, actuarial global survival according to curves of Kaplan Meier to 5 and 10 years (P: 0,5257) and survival 5 actuarial specific cancer to and 10a (P: 0,2165). Conclusions: Without significant differences in: RB, clinical progression, pathological relapse, global and specific survival, rate of positive surgical margins. The 3 criteria of D'Amico were predictive of positive surgical margins and RB, the patients with RB in group 2 presented/displayed greater risk of clinical progression, the PR demonstrated a global survival and specify actuarial to 10 years greater to 50%, considering it therapeutic an option been worth. (authors) [es

  18. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD in Patients Receiving Intensive Statin Treatment

    Directory of Open Access Journals (Sweden)

    Demetrios G. Vavvas

    2016-03-01

    Conclusions: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

  19. Predictors of Early Rebleeding after Endoscopic Therapy in Patients with Nonvariceal Upper Gastrointestinal Bleeding Secondary to High-Risk Lesions

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    Davide Maggio

    2013-01-01

    Full Text Available BACKGROUND: In an era of increasingly shortened admissions, data regarding predictors of early rebleeding among patients with nonvariceal upper gastrointestinal bleeding (NVUGIB exhibiting high-risk stigmata (HRS having undergone endoscopic hemostasis are lacking.

  20. A Patient Navigator Intervention to Reduce Hospital Readmissions among High-Risk Safety-Net Patients: A Randomized Controlled Trial.

    Science.gov (United States)

    Balaban, Richard B; Galbraith, Alison A; Burns, Marguerite E; Vialle-Valentin, Catherine E; Larochelle, Marc R; Ross-Degnan, Dennis

    2015-07-01

    Evidence-based interventions to reduce hospital readmissions may not generalize to resource-constrained safety-net hospitals. To determine if an intervention by patient navigators (PNs), hospital-based Community Health Workers, reduces readmissions among high risk, low socioeconomic status patients. Randomized controlled trial. General medicine inpatients having at least one of the following readmission risk factors: (1) age ≥60 years, (2) any in-network inpatient admission within the past 6 months, (3) length of stay ≥3 days, (4) admission diagnosis of heart failure, or (5) chronic obstructive pulmonary disease. The analytic sample included 585 intervention patients and 925 controls. PNs provided coaching and assistance in navigating the transition from hospital to home through hospital visits and weekly telephone outreach, supporting patients for 30 days post-discharge with discharge preparation, medication management, scheduling of follow-up appointments, communication with primary care, and symptom management. The primary outcome was in-network 30-day hospital readmissions. Secondary outcomes included rates of outpatient follow-up. We evaluated outcomes for the entire cohort and stratified by patient age >60 years (425 intervention/584 controls) and ≤60 years (160 intervention/341 controls). Overall, 30-day readmission rates did not differ between intervention and control patients. However, the two age groups demonstrated marked differences. Intervention patients >60 years showed a statistically significant adjusted absolute 4.1% decrease [95% CI: -8.0%, -0.2%] in readmission with an increase in 30-day outpatient follow-up. Intervention patients ≤60 years showed a statistically significant adjusted absolute 11.8% increase [95% CI: 4.4%, 19.0%] in readmission with no change in 30-day outpatient follow-up. A patient navigator intervention among high risk, safety-net patients decreased readmission among older patients while increasing readmissions

  1. Haloperidol prophylaxis in critically ill patients with a high risk for delirium

    Science.gov (United States)

    2013-01-01

    Introduction Delirium is associated with increased morbidity and mortality. We implemented a delirium prevention policy in intensive care unit (ICU) patients with a high risk of developing delirium, and evaluated if our policy resulted in quality improvement of relevant delirium outcome measures. Methods This study was a before/after evaluation of a delirium prevention project using prophylactic treatment with haloperidol. Patients with a predicted risk for delirium of ≥ 50%, or with a history of alcohol abuse or dementia, were identified. According to the prevention protocol these patients received haloperidol 1 mg/8 h. Evaluation was primarily focused on delirium incidence, delirium free days without coma and 28-day mortality. Results of prophylactic treatment were compared with a historical control group and a contemporary group that did not receive haloperidol prophylaxis mainly due to non-compliance to the protocol mostly during the implementation phase. Results In 12 months, 177 patients received haloperidol prophylaxis. Except for sepsis, patient characteristics were comparable between the prevention and the historical (n = 299) groups. Predicted chance to develop delirium was 75 ± 19% and 73 ± 22%, respectively. Haloperidol prophylaxis resulted in a lower delirium incidence (65% vs. 75%, P = 0.01), and more delirium-free-days (median 20 days (IQR 8 to 27) vs. median 13 days (3 to 27), P = 0.003) in the intervention group compared to the control group. Cox-regression analysis adjusted for sepsis showed a hazard rate of 0.80 (95% confidence interval 0.66 to 0.98) for 28-day mortality. Beneficial effects of haloperidol appeared most pronounced in the patients with the highest risk for delirium. Furthermore, haloperidol prophylaxis resulted in less ICU re-admissions (11% vs. 18%, P = 0.03) and unplanned removal of tubes/lines (12% vs. 19%, P = 0.02). Haloperidol was stopped in 12 patients because of QTc-time prolongation (n = 9), renal failure (n = 1) or

  2. Contrast nephropathy in high-risk patients undergoing coronary angiography and intervention

    International Nuclear Information System (INIS)

    Uddin, M.A.; Rabbani, M.A.; Jafary, F.H.; Bhatti, M.A.; Islam, M.

    2005-01-01

    Objective: To determine the incidence of contrast nephropathy in high-risk patients undergoing coronary angiography and percutaneous coronary intervention (PCI), and to define the characteristics of this cohort. Design: Descriptive study. Place and Duration of Study: The Aga Khan University Hospital, Karachi from January to December 2002. Patients and Methods: One hundred and fifteen patients with serum creatinine greater than 1.4mg/dl who underwent coronary angiography or PCI were included. All patients received non-ionic contrast dye. Acute contrast nephropathy was defined as rise in serum creatinine of >0.5mg/dl within 48 hours following the index procedure. Means and standard deviations were calculated for continuous variables and frequencies for categorical variables. Results: Mean age of patients was 62.3 year + 8.83. Mean pre-contrast creatinine was 1.9+0.9mg/dl. Eleven (9.65%) patients developed contrast nephropathy. 4.4% of patients with serum creatinine 4.0(p-value 0.001). 11.9% diabetic patients developed nephropathy compared to 6.3% of non-diabetics (p-value 0.355). 11.4% of hypertensive and 3.7% of non-hypertensive patients developed contrast-nephropathy (p-value 0.454). 12.9% of low dose group ( 100ml) developed nephropathy (p-value 0.188). Mean serum creatinine in low dose group was higher (3.0mg/dl vs. 1.7 mg/dl). Conclusion: The incidence of contrast nephropathy in this study was similar to that reported in literature. Risk of CIN was found to be significantly proportional to the severity of baseline renal disease. Trends towards higher risk of CIN were seen in patients with diabetes and hypertension. Higher incidence of CIN in patients receiving low-dose contrast was confounded by higher baseline serum creatinine in that group. (author)

  3. Percutaneous cardiopulmonary support for catheter ablation of unstable ventricular arrhythmias in high-risk patients.

    Science.gov (United States)

    Carbucicchio, Corrado; Della Bella, Paolo; Fassini, Gaetano; Trevisi, Nicola; Riva, Stefania; Giraldi, Francesco; Baratto, Francesca; Marenzi, Giancarlo; Sisillo, Erminio; Bartorelli, Antonio; Alamanni, Francesco

    2009-11-01

    two patients (11%); one patient (5%) with persistent VT episodes acutely died after heart transplant. At a mean follow-up of 42 months (range 15-60 months), 5/18 patients (28%) were free from VT recurrence, 7/18 (39%) had a clear clinical improvement with reduced implantable cardioverter defibrillator interventions. 5/14 patients (36%) had ES recurrence; among them, three died because of acute heart failure. No serious CPS-related complications were observed. The CPS warrants acceptable hemodynamic stabilization and efficacious mapping in high-risk patients undergoing CA for unstable VT in the emergency setting. Safety and efficacy of this technique translate into significant clinical improvement in the majority of patients. Even if only relatively invasive, CPS should be reserved to patients with ES or intractable arrhythmia causing acute heart failure; moreover, the need for an experienced team of multidisciplinary operators implies that its use is restricted to selected high-competency institutions.

  4. Outcomes of implementation of enhanced goal directed therapy in high-risk patients undergoing abdominal surgery

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    Lakshmi Kumar

    2015-01-01

    Full Text Available Background and Aims: Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients. We aimed to assess the impact of goal directed therapy (GDT targeting cardiac index (CI and oxygen extraction ratio (O 2 ER on outcomes of high-risk patients undergoing abdominal surgery. Methods: In a prospective randomised trial, forty patients (American Society of Anaesthesiologists II and III undergoing major abdominal surgeries were randomised into two groups. In-Group A mean arterial pressure ≥ 65 mmHg, central venous pressure ≥ 8-10 mmHg, urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70% were targeted intra-operatively and 12 h postoperatively. In-Group-B (enhanced GDT, in addition to the monitoring in-Group-A, CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27% were targeted. The end-points were lactate levels and base deficit during and after surgery. The secondary end points were length of Intensive Care Unit (ICU and hospital stay and postoperative complications. Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment. Results: Lactate levels postoperatively at 4 and 8 h were lower in-Group-B (P < 0.05. The mean base deficit at 3, 4, 5 and 6 h intra-operatively and postoperatively after 4, 8 and 12 h were lower in-Group-B (P < 0.05. There were no significant differences in ICU stay (2.10 ± 1.52 vs. 2.90 ± 2.51 days or hospital stay (10.85 + 4.39 vs. 13.35 + 6.77 days between Group A and B. Conclusions: Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation.

  5. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    NARCIS (Netherlands)

    Hoefnagel, C. A.; Rutgers, M.; Buitenhuis, C. K.; Smets, L. A.; de Kraker, J.; Meli, M.; Carrel, F.; Amstutz, H.; Schubiger, P. A.; Novak-Hofer, I.

    2001-01-01

    Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in

  6. Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.

    Science.gov (United States)

    Li, Xiaobo; Branch, Craig A; Nierenberg, Jay; Delisi, Lynn E

    2010-03-01

    Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

  7. Ultrasound guided percutaneous cholecystostomy in high-risk patients for surgical intervention.

    Science.gov (United States)

    Bakkaloglu, Huseyin; Yanar, Hakan; Guloglu, Recep; Taviloglu, Korhan; Tunca, Fatih; Aksoy, Murat; Ertekin, Cemalettin; Poyanli, Arzu

    2006-11-28

    To assess the efficacy and safety of ultrasound guided percutaneous cholecystostomy (PC) in the treatment of acute cholecystitis in a well-defined high risk patients under general anesthesia. The data of 27 consecutive patients who underwent percutaneous transhepatic cholecystostomy for the management of acute cholecystitis from January 1999 to June 2003 was retrospectively evaluated. All of the patients had both clinical and sonographic signs of acute cholecystitis and had comorbid diseases. Ultrasound revealed gallbladder stones in 25 patients and acalculous cholecystitis in two patients. Cholecystostomy catheters were removed 14-32 d (mean 23 d) after the procedure in cases where complete regression of all symptoms was achieved. There were statistically significant reductions in leukocytosis, (13.7 x 10(3)+/-1.3 x 10(3) microg/L vs 13 x 10(3)+/-1 x 10(3) microg/L, P extraction was performed successfully with endoscopic retrograde cholangio-pancreatography (ERCP) in three patients. After cholecystostomy, 5 (18%) patients underwent delayed cholecystectomy without any complications. Three out of 22 patients were admitted with recurrent acute cholecystitis during the follow-up and recovered with medical treatment. Catheter dislodgement occurred in three patients spontaneously, and two of them were managed by reinsertion of the catheter. As an alternative to surgery, percutaneous cholecystostomy seems to be a safe method in critically ill patients with acute cholecystitis and can be performed with low mortality and morbidity. Delayed cholecystectomy and ERCP, if needed, can be performed after the acute period has been resolved by percutaneous cholecystostomy.

  8. Adjuvant radiochemotherapy in patients with locally advanced high-risk cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Heinzelmann, F.; Henke, G.; Grafenstein, M. von; Weidner, N.; Paulsen, F.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Staebler, A. [Tuebingen Univ. (Germany). Div. of Gynecologic Pathology; Brucker, S. [Tuebingen Univ. (Germany). Dept. of Gynecology

    2012-07-15

    Background and purpose: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. Patients and methods: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. Results: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic ({proportional_to}30%) and gastrointestinal ({proportional_to}30%) grade 3 toxicity. Small bowel obstruction ({proportional_to}6%) was the only important late sequelae. Conclusion: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity. (orig.)

  9. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.

    Science.gov (United States)

    Jamerson, Kenneth; Weber, Michael A; Bakris, George L; Dahlöf, Björn; Pitt, Bertram; Shi, Victor; Hester, Allen; Gupte, Jitendra; Gatlin, Marjorie; Velazquez, Eric J

    2008-12-04

    The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; Pbenazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.) 2008 Massachusetts Medical Society

  10. What Do High-Risk Patients Value? Perspectives on a Care Management Program.

    Science.gov (United States)

    Ganguli, Ishani; Orav, E John; Weil, Eric; Ferris, Timothy G; Vogeli, Christine

    2018-01-01

    There is growing interest in coordinating care for high-risk patients through care management programs despite inconsistent results on cost reduction. Early evidence suggests patient-centered benefits, but we know little about how participants engage with the programs and what aspects they value. To explore care management program participants' awareness and perceived utility of program offerings. Cross-sectional telephone survey administered December 2015-January 2016. Patients enrolled in a Boston-area primary care-based care management program. Our main outcome was the number of topics in which patients reported having "very helpful" interactions with their care team in the past year. We analyzed awareness of one's care manager as an intermediate outcome, and then as a primary predictor of the main outcome, along with patient demographics, years in the program, attitudes, and worries as secondary predictors. The survey response rate was 45.8% (n = 1220); non-respondents were similar to respondents. More respondents reported worrying about family (72.8%) or financial issues (52.5%) than about their own health (41.6%). Seventy-four percent reported care manager awareness, particularly women (OR 1.33, 95% CI 1.01-1.77) and those with more years in the program (OR 1.16, 95% CI 1.03-1.30). While interaction rates ranged from 19.8% to 72.4% across topics, 81.3% rated at least one interaction as very helpful. Those who were aware of their care manager reported very helpful interactions on more topics (OR 2.77, 95% CI 2.15-3.56), as did women (OR 1.25, 95% CI 1.00-1.55), younger respondents (OR 0.98 for older age, 95% CI 0.97-0.99), and those with higher risk scores (OR 1.04, 95% CI 1.02-1.06), preference for deferring treatment decisions to doctors (OR 2.00, 95% CI 1.60-2.50), and reported control over their health (OR 1.67, 95% CI 1.33-2.10). High-risk patients reported helpful interactions with their care team around medical and social determinants of health

  11. The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality

    International Nuclear Information System (INIS)

    Nieminen, Tuomo; Turjanmaa, Väinö; Kähönen, Mika; Lehtinen, Rami; Viik, Jari; Lehtimäki, Terho; Niemelä, Kari; Nikus, Kjell; Niemi, Mari; Kallio, Janne; Kööbi, Tiit

    2006-01-01

    The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile – using genetic, haemodynamic and electrocardiographic (ECG) markers – of individuals at high risk of cardiovascular diseases, events and deaths. All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications. FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers

  12. Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

    Science.gov (United States)

    Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

    2014-05-01

    We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

  13. Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review.

    Science.gov (United States)

    Lane, D A; Raichand, S; Moore, D; Connock, M; Fry-Smith, A; Fitzmaurice, D A

    2013-07-01

    Previous research suggests uncertainty whether or not there is any additional benefit in adding antiplatelet therapy (APT) to anticoagulation therapy (ACT) in patients with high-risk atrial fibrillation (AF) in terms of reduction in vascular events, including stroke. The existing guidelines acknowledge an increased risk of bleeding associated with such a strategy; however, there is no consensus on the treatment pathway. To determine, by undertaking a systematic review, if the addition of APT to ACT is beneficial compared with ACT alone in patients with AF who are considered to be at high risk of thromboembolic events (TEs). Data sources included bibliographic databases {the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)], MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, ClinicalTrials.gov, National Institute for Health Research (NIHR) Clinical Research Network Portfolio, Current Controlled Trials (CCT) and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP)}, reference lists from identified systematic reviews and relevant studies, and contact with clinical experts. Searches were from inception to September 2010 and did not use language restrictions or study design filters. Studies of any design were included to evaluate clinical effectiveness, including randomised controlled trials (RCTs), non-randomised comparisons, cohort studies, case series or registries, longitudinal studies, systematic reviews and meta-analyses, and conference abstracts published after 2008. Inclusion criteria consisted of a population with AF, at high-risk of TEs, aged ≥ 18 years, on combined ACT and APT compared with others on ACT alone or ACT plus placebo. Inclusion decisions, assessment of study quality and data extraction were undertaken using methods to minimise bias. Fifty-three publications were included, reporting five RCTs (11 publications), 18 non-randomised comparisons (24 publications) and 18

  14. Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

    Science.gov (United States)

    Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

    2009-09-01

    For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

  15. Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

    International Nuclear Information System (INIS)

    Saulnier Sholler, Giselle L; Bond, Jeffrey P; Bergendahl, Genevieve; Dutta, Akshita; Dragon, Julie

    2015-01-01

    The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients

  16. Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

    Science.gov (United States)

    Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

    2017-01-01

    Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, pgastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all pgastritis classification may thus be useful for detecting these patients.

  17. A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients.

    Science.gov (United States)

    Denault, André Y; Bussières, Jean S; Arellano, Ramiro; Finegan, Barry; Gavra, Paul; Haddad, François; Nguyen, Anne Q N; Varin, France; Fortier, Annik; Levesque, Sylvie; Shi, Yanfen; Elmi-Sarabi, Mahsa; Tardif, Jean-Claude; Perrault, Louis P; Lambert, Jean

    2016-10-01

    Inhaled milrinone (iMil) has been used for the treatment of pulmonary hypertension (PH) but its efficacy, safety, and prophylactic effects in facilitating separation from cardiopulmonary bypass (CPB) and preventing right ventricular (RV) dysfunction have not yet been evaluated in a clinical trial. The purpose of this study was to investigate if iMil administered before CPB would be superior to placebo in facilitating separation from CPB. High-risk cardiac surgical patients with PH were randomized to receive iMil or placebo after the induction of anesthesia and before CPB. Hemodynamic parameters and RV function were evaluated by means of pulmonary artery catheterization and transesophageal echocardiography. The groups were compared for the primary outcome of the level of difficulty in weaning from CPB. Among the secondary outcomes examined were the reduction in the severity of PH, the incidence of RV failure, and mortality. Of the 124 patients randomized, the mean (standard deviation [SD]) EuroSCORE II was 8.0 (2.6), and the baseline mean (SD) systolic pulmonary artery pressure (SPAP) was 53 (9) mmHg. The use of iMil was associated with increases in cardiac output (P = 0.03) and a reduction in SPAP (P = 0.04) with no systemic hypotension. Nevertheless, there was no difference in the combined incidence of difficult or complex separation from CPB between the iMil and control groups (30% vs 28%, respectively; absolute difference, 2%; 95% confidence interval [CI], -14 to 18; P = 0.78). There was also no difference in RV failure between the iMil and control groups (15% vs 14%, respectively; difference, 1%; 95% CI, -13 to 12; P = 0.94). Mortality was increased in patients with RV failure vs those without (22% vs 2%, respectively; P < 0.001). In high-risk cardiac surgery patients with PH, the prophylactic use of iMil was associated with favourable hemodynamic effects that did not translate into improvement of clinically relevant endpoints. This trial was registered at

  18. Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

    International Nuclear Information System (INIS)

    Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

    2016-01-01

    Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

  19. An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

    Science.gov (United States)

    Alghamdi, Majed; Taggar, Amandeep; Tilley, Derek; Kerba, Marc; Kostaras, Xanthoula; Gotto, Geoffrey; Sia, Michael

    2016-01-01

    We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

  20. Ultrasound guided percutaneous cholecystostomy in high-risk patients for surgical intervention

    Science.gov (United States)

    Bakkaloglu, Huseyin; Yanar, Hakan; Guloglu, Recep; Taviloglu, Korhan; Tunca, Fatih; Aksoy, Murat; Ertekin, Cemalettin; Poyanli, Arzu

    2006-01-01

    AIM: To assess the efficacy and safety of ultrasound guided percutaneous cholecystostomy (PC) in the treatment of acute cholecystitis in a well-defined high risk patients under general anesthesia. METHODS: The data of 27 consecutive patients who underwent percutaneous transhepatic cholecystostomy for the management of acute cholecystitis from January 1999 to June 2003 was retrospectively evaluated. All of the patients had both clinical and sonographic signs of acute cholecystitis and had comorbid diseases. RESULTS: Ultrasound revealed gallbladder stones in 25 patients and acalculous cholecystitis in two patients. Cholecystostomy catheters were removed 14-32 d (mean 23 d) after the procedure in cases where complete regression of all symptoms was achieved. There were statistically significant reductions in leukocytosis, (13.7 × 103 ± 1.3 × 103 μg/L vs 13 × 103 ± 1 × 103 μg/L, P < 0.05 for 24 h after PC; 13.7 × 103 ± 1.3 × 103 μg/L vs 8.3 × 103 ± 1.2 × 103 μg/L, P < 0.0001 for 72 h after PC), C -reactive protein (51.2 ± 18.5 mg/L vs 27.3 ± 10.4 mg/L, P < 0.05 for 24 h after PC; 51.2 ± 18.5 mg/L vs 5.4 ± 1.5 mg/L, P < 0.0001 for 72 h after PC), and fever (38 ± 0.35°C vs 37.3 ± 0.32°C, P < 0.05 for 24 h after PC; 38 ± 0.35°C vs 36.9 ± 0.15°C, P < 0.0001 for 72 h after PC). Sphincterotomy and stone extraction was performed successfully with endoscopic retrograde cholangio-pancreatography (ERCP) in three patients. After cholecystostomy, 5 (18%) patients underwent delayed cholecystectomy without any complications. Three out of 22 patients were admitted with recurrent acute cholecystitis during the follow-up and recovered with medical treatment. Catheter dislodgement occurred in three patients spontaneously, and two of them were managed by reinsertion of the catheter. CONCLUSION: As an alternative to surgery, percutan-eous cholecystostomy seems to be a safe method in critically ill patients with acute cholecystitis and can be performed with low

  1. Factors associated with high risk of marginal hyperthermia in elderly patients living in an institution.

    Science.gov (United States)

    Vassallo, M.; Gera, K. N.; Allen, S.

    1995-01-01

    The elderly, the very young, and the sick are known to be adversely affected by high environmental temperatures. In a retrospective open case-note review of 872 patients in a large institution during a hot summer we identified characteristics in the elderly that increase the risk of marginal hyperthermia. Women were more likely to be affected than men (25.6% vs 16.9%). We found an age-related increase in marginal hyperthermia, 15.7% of those below 60 years developed a hyperthermia compared to 18.9% in those between 70-79 years (non-significant), 28.3% in those between 80-89 years (p = 0.01) and 50% in those above 90 years (p bedridden group, p < 0.01, and 20.4% of the semi-dependent, p < 0.01, compared to 11.1% of the mobile group). These factors were more significant as predictors of risk than the diagnosis. Identifying high risk patients early and taking appropriate measures to avoid hyperthermia and dehydration is important to try to decrease mortality during heatwaves. PMID:7784280

  2. Benefits of statin therapy and compliance in high risk cardiovascular patients

    Directory of Open Access Journals (Sweden)

    Joel A Lardizabal

    2010-09-01

    Full Text Available Joel A Lardizabal1, Prakash C Deedwania21Division of Cardiology, Department of Medicine, University of California in San Francisco (Fresno-MEP, Fresno, CA, USA; 2University of California in San Francisco, Chief of Cardiology, Veterans Affairs Central California System, Fresno, CA, USAAbstract: Cardiovascular disease (CVD remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.Keywords: cardiovascular disease, statin therapy, coronary heart disease, long-term treatment compliance

  3. Contrast-enhanced spectral mammography (CESM) versus MRI in the high-risk screening setting: patient preferences and attitudes.

    Science.gov (United States)

    Phillips, Jordana; Miller, Matthew M; Mehta, Tejas S; Fein-Zachary, Valerie; Nathanson, Audrey; Hori, Wendy; Monahan-Earley, Rita; Slanetz, Priscilla J

    Our study evaluates patient preferences toward screening CESM versus MRI. As part of a prospective study, high-risk patients had breast MRI and CESM. Patients completed an anonymous survey to evaluate preferences regarding the two modalities. 88% of participants completed the survey. 79% preferred CESM over MRI if the exams had equal sensitivity. 89% would be comfortable receiving contrast as part of an annual screening test. High-risk populations may accept CESM as a screening exam and may prefer it over screening MRI if ongoing trials demonstrate screening CESM to be clinically non-inferior MRI. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients.

    Science.gov (United States)

    Harricharan, S; Biederman, K; Bombassaro, A M; Lazo-Langner, A; Elsayed, S; Fulford, A; Delport, J A; Xenocostas, A

    2018-04-01

    A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

  5. Tratamento do paciente com mielodisplasia de alto risco Treatment of myelodysplastic syndrome in high risk patients

    Directory of Open Access Journals (Sweden)

    Evandro M. Fagundes

    2006-09-01

    Full Text Available O tratamento do paciente com mielodisplasia deve ser feito considerando o risco biológico da doença, a idade e as condições clínicas do paciente. De um modo geral, uma doença de alto risco necessitaria de um tratamento mais agressivo. Porém, devido à elevada idade mediana no diagnóstico, a maioria dos pacientes não tolera tratamentos intensivos. O transplante de células-tronco hematopoiéticas é a única opção para aqueles que objetivam a cura da doença. Para aqueles que não podem se submeter a um transplante, as opções incluem o uso de quimioterapia intensiva, agentes hipometilantes, tratamento suportivo e/ou inclusão em estudos clínicos. A quimioterapia intensiva semelhante à utilizada para leucemia mielóide aguda é uma boa opção para pacientes em boas condições clínicas e com menos de 65 anos de idade.To initiate a treatment for myelodysplastic syndrome, the physician should consider the patient's age, status performance and the risk of transformation to acute myeloid leukemia (AML and death. In theory, a high risk disease should be approached with intense treatment however most patients are not healthy enough to receive aggressive treatment with chemotherapy or stem cell transplantation. For those who are not able to receive a transplantation, the treatment options include AML-like chemotherapy, hypomethylating agents, supportive care alone or participation in a clinical trial. AML-like chemotherapy is still a reasonable choice for those patients who are in good clinical conditions and are younger than 65 years of age.

  6. Vibratory perception threshold in young and middle-aged patients at high risk of knee osteoarthritis compared to controls

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Shakoor, Najia; Ageberg, Eva

    2012-01-01

    Vibratory perception threshold (VPT) is impaired in patients with knee osteoarthritis (OA). It is, however, not known if sensory deficits precede or follow as a consequence of OA. The aim of this study was to investigate VPT in 2 independent groups of patients with high risk of future OA (young a...

  7. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    Gast, M.C.; van Tinteren, H.; Bontenbal, M.; van Hoesel, R.Q.; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; de Vries, E.G.; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

    2008-01-01

    Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

  8. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

    2008-01-01

    textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

  9. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    NARCIS (Netherlands)

    Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

    2008-01-01

    ABSTRACT: BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

  10. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

    NARCIS (Netherlands)

    Gast, M.C.; Tinteren, H. van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

    2008-01-01

    BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

  11. Perceived usability and use of custom-made footwear in diabetic patients at high risk for foot ulceration

    NARCIS (Netherlands)

    Arts, Mark L. J.; de Haart, Mirjam; Bus, Sicco A.; Bakker, Jan P. J.; Hacking, Hub G. A.; Nollet, Frans

    2014-01-01

    To assess the perceived usability and use of custom- made footwear in diabetic patients who are at high-risk for foot ulceration, and to elucidate the determinants of usability and use. Survey. A total of 153 patients with diabetes, peripheral neuropathy, prior plantar foot ulceration and newly

  12. Increased Saccadic Rate during Smooth Pursuit Eye Movements in Patients at Ultra High Risk for Developing a Psychosis

    Science.gov (United States)

    van Tricht, M. J.; Nieman, D. H.; Bour, L. J.; Boeree, T.; Koelman, J. H. T. M.; de Haan, L.; Linszen, D. H.

    2010-01-01

    Abnormalities in eye tracking are consistently observed in schizophrenia patients and their relatives and have been proposed as an endophenotype of the disease. The aim of this study was to investigate the performance of patients at Ultra High Risk (UHR) for developing psychosis on a task of smooth pursuit eye movement (SPEM). Forty-six UHR…

  13. Integrating Social Services and Home-Based Primary Care for High-Risk Patients.

    Science.gov (United States)

    Feinglass, Joe; Norman, Greg; Golden, Robyn L; Muramatsu, Naoko; Gelder, Michael; Cornwell, Thomas

    2018-04-01

    There is a consensus that our current hospital-intensive approach to care is deeply flawed. This review article describes the research evidence for developing a better system of care for high-cost, high-risk patients. It reviews the evidence that home-centered care and integration of health care with social services are the cornerstones of a more humane and efficient system. The article describes the strengths and weaknesses of research evaluating the effects of social services in addressing social determinants of health, and how social support is critical to successful acute care transition programs. It reviews the history of incorporating social services into care management, and the prospects that recent payment reforms and regulatory initiatives can succeed in stimulating the financial integration of social services into new care coordination initiatives. The article reviews the literature on home-based primary care for the chronically ill and disabled, and suggests that it is the emergence of this care modality that holds the greatest promise for delivery system reform. In the hope of stimulating further discussion and debate, the authors summarize existing viewpoints on how a home-centered system, which integrates social and medical services, might emerge in the next few years.

  14. Communication and information-giving in high-risk breast cancer consultations: influence on patient outcomes.

    Science.gov (United States)

    Lobb, E A; Butow, P N; Barratt, A; Meiser, B; Gaff, C; Young, M A; Haan, E; Suthers, G; Gattas, M; Tucker, K

    2004-01-26

    This longitudinal study aimed to document (i) the information-giving and patient-communication styles of clinical geneticists and genetic counsellors (consultants) in familial breast cancer clinics and (ii) assess the effect of these styles on women's knowledge, whether their expectations were met, satisfaction, risk perception and psychological status. A total of 158 women from high-risk breast cancer families completed self-report questionnaires at 2 weeks preconsultation and 4 weeks postconsultation. The consultations were audiotaped, transcribed and coded. Multivariate logistic regressions showed that discussing prophylactic mastectomy (P=0.00) and oophorectomy (P=0.01) led to women having significantly more expectations met; discussing genetic testing significantly decreased anxiety (P=0.03) and facilitating understanding significantly decreased depression (P=0.05). Receiving a summary letter of the consultation significantly lowered anxiety (P=0.01) and significantly increased the accuracy of perceived risk (P=0.02). Women whose consultant used more supportive communications experienced significantly more anxiety about breast cancer at the 4 weeks follow-up (P=0.00). These women were not significantly more anxious before genetic counselling. In conclusion, this study found that consultants vary in the amount of information they give and the way they communicate; and this variation can result in better or worse psychosocial outcomes. Greater use of supportive and counselling communications appeared to increase anxiety about breast cancer. Identifying methods to assist consultants to address emotional issues effectively may be helpful.

  15. Varenicline treatment for smoking cessation in high risk patients: a budget impact analysis

    Directory of Open Access Journals (Sweden)

    Federico Spandonaro

    2017-10-01

    CONCLUSIONS: The financial impact on the Italian NHS of the reimbursement of varenicline for the treatment of high risk smoking population would be a sustainable healthcare policy, resulting in cost savings starting from the fourth year.

  16. Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

    Science.gov (United States)

    Monclair, Tom; Mosseri, Véronique; Cecchetto, Giovanni; De Bernardi, Bruno; Michon, Jean; Holmes, Keith

    2015-09-01

    The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning. © 2015 Wiley Periodicals, Inc.

  17. Just-in-Time Training for High-Risk Low-Volume Therapies: An Approach to Ensure Patient Safety.

    Science.gov (United States)

    Helman, Stephanie; Lisanti, Amy Jo; Adams, Ann; Field, Cynthia; Davis, Katherine Finn

    2016-01-01

    High-risk low-volume therapies are those therapies that are practiced infrequently and yet carry an increased risk to patients because of their complexity. Staff nurses are required to competently manage these therapies to treat patients' unique needs and optimize outcomes; however, maintaining competence is challenging. This article describes implementation of Just-in-Time Training, which requires validation of minimum competency of bedside nurses managing high-risk low-volume therapies through direct observation of a return-demonstration competency checklist.

  18. Carotid Stenting in Patients With High Risk Versus Standard Risk for Open Carotid Endarterectomy (REAL-1 Trial).

    Science.gov (United States)

    De Haro, Joaquin; Michel, Ignacio; Bleda, Silvia; Cañibano, Cristina; Acin, Francisco

    2017-07-15

    Carotid stenting (CAS) has been mainly offered to those patients considered at "high risk" for open carotid endarterectomy based on available data from large randomized clinical trials. However, several recent studies have called medical "high risk" into question for CAS indication. The REAL-1 trial evaluated the safety and perioperative and long-term effectiveness in patients with significant carotid artery stenosis with "high-risk" criteria treated with CAS and proximal protection device (MOMA) compared with those with standard surgical-risk features. This nonrandomized double-arm registry included 125 patients (40% symptomatic), 71 (56%) with "standard-risk" and 54 (44%) with "high-risk" criteria. The primary end point was the cumulative incidence of any major adverse event, a composite of stroke, myocardial infarction, and death within 30 days after the intervention or ipsilateral stroke after 30 days and up to 4 years. There was no significant difference in primary end point rate at 30 days between patients at "standard risk" and those with "high risk" (1.4% vs 1.9% respectively; hazard ratio for "standard risk" 1.1; 95% CI 0.8 to 1.2, p = 0.77) nor estimated 4-year rate of ipsilateral stroke (1.3% vs 1.8%; hazard ratio for "standard risk" 1.05, 95% CI 0.86 to 1.14, p = 0.9). In conclusion, 4-year postprocedure results demonstrated that CAS with proximal device (MOMA) is safe and effective for patients with and without "high-risk" for carotid endarterectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Giselle L Saulnier Sholler

    Full Text Available Neuroblastoma (NB is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO ± etoposide for patients with relapsed or refractory NB.Twenty-one patients participated in a phase I study of daily oral DFMO alone for three weeks, followed by additional three-week cycles of DFMO plus daily oral etoposide. No dose limiting toxicities (DLTs were identified in patients taking doses of DFMO between 500-1500 mg/m2 orally twice a day. DFMO pharmacokinetics, single nucleotide polymorphisms (SNPs in the ODC gene and urinary levels of substrates for the tissue polyamine exporter were measured. Urinary polyamine levels varied among patients at baseline. Patients with the minor T-allele at rs2302616 of the ODC gene had higher baseline levels (p=0.02 of, and larger decreases in, total urinary polyamines during the first cycle of DFMO therapy (p=0.003 and had median progression free survival (PFS that was over three times longer, compared to patients with the major G allele at this locus although this last result was not statistically significant (p=0.07. Six of 18 evaluable patients were progression free during the trial period with three patients continuing progression free at 663, 1559 and 1573 days after initiating treatment. Median progression-free survival was less among patients having increased urinary polyamines, especially diacetylspermine, although this result was not statistically significant (p=0.056.DFMO doses of 500-1500 mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary

  20. Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

    International Nuclear Information System (INIS)

    Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

    2011-01-01

    Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

  1. Clinical characteristics and outcome of patients with neuroblastoma presenting genomic amplification of loci other than MYCN.

    Directory of Open Access Journals (Sweden)

    Anne Guimier

    Full Text Available Somatically acquired genomic alterations with MYCN amplification (MNA are key features of neuroblastoma (NB, the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s distinct from MYCN.Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected.In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8 presented regional amplification(s without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases. This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26 had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22. Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05.NBs harbouring regional amplification(s without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy.

  2. Clinical Characteristics and Outcome of Patients with Neuroblastoma Presenting Genomic Amplification of Loci Other than MYCN

    Science.gov (United States)

    Guimier, Anne; Ferrand, Sandrine; Pierron, Gaëlle; Couturier, Jérôme; Janoueix-Lerosey, Isabelle; Combaret, Valérie; Mosseri, Véronique; Thebaud, Estelle; Gambart, Marion; Plantaz, Dominique; Marabelle, Aurélien; Coze, Carole; Rialland, Xavier; Fasola, Sylvie; Lapouble, Eve; Fréneaux, Paul; Peuchmaur, Michel; Michon, Jean; Delattre, Olivier; Schleiermacher, Gudrun

    2014-01-01

    Background Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. PMID:25013904

  3. Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin's lymphoma.

    Science.gov (United States)

    Crocchiolo, R; Castagna, L; Fürst, S; El-Cheikh, J; Faucher, C; Oudin, C; Granata, A; Bouabdallah, R; Coso, D; Chabannon, C; Balzarotti, M; Santoro, A; Blaise, D

    2013-02-01

    Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.

  4. The high-risk polytrauma patient and inferior vena cava filter use.

    Science.gov (United States)

    Berber, Onur; Vasireddy, Aswin; Nzeako, Obi; Tavakkolizadeh, Adel

    2017-07-01

    The aim of this study was to assess the impact on practice of vena cava filter insertion guidelines (Eastern Association for the Surgery of Trauma: practice management guidelines). The study was performed at a level 1 trauma centre with data from the 'Trauma Audit and Research Network' cross-referenced to hospital data. A total of 1138 specific 'high-risk' major trauma patients were identified over a 6-year period. The mean age was 46 years (18-102) and the male to female ratio was 3.3:1. The average Injury Severity Score was 23.6 (4-75). The overall DVT rate was 2.6% and the PE rate was 1.8%. A retrievable IVC filter was inserted in 42 cases (3.8%). The filter retrieval rate was 23.8% at a mean of 68.5days (4-107). Only one complication was reported of a breakthrough PE despite filter. Applying the EAST guidelines to this cohort would have suggested filter insertion in 279 (24.6%) cases. The kappa concordance value between observed practice and the 'EAST filter group' was 0.103 (poor). The PE rate in the 'EAST filter group' was 2.2% vs 1.6% in the 'no filter group' (p=0.601, no statistical difference) and the observed odds ratio was 0.814 (95% CI 0.413, 1.602). The EAST guidelines are useful but may be overestimating the need for filter insertion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?

    Science.gov (United States)

    Thompson, Andrew; Nelson, Barnaby; Bruxner, Annie; O'Connor, Karen; Mossaheb, Nilufar; Simmons, Magenta B; Yung, Alison

    2013-04-01

    Studies have attempted to identify additional risk factors within the group identified as 'ultra high risk' (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. A retrospective 'case-control' methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.

  6. The application of paravertebral block in high-risk patient with cardiorespiratory, liver and kidney problems: a case report

    OpenAIRE

    ŽUPČIĆ, MIROSLAV; GRAF ŽUPČIĆ, SANDRA; BRUNDULA, ANA; ZRINJŠČAK, IVA KOREČIĆ; PERŠEC, JASMINKA; HUSEDŽINOVIĆ1, INO

    2015-01-01

    Background and Purpose: We present a case report of a patient of the American Society of Anesthesiologists’ (ASA) IV scheduled for a modified radical mastectomy (MRM) due to malignant disease. The patient was a high risk patient for general anesthesia and we opted for the application of unilateral paravertebral block on several levels. Case report. A 86-year-old female was scheduled for a surgery due to recurrent malignant process on her right breast. She was an ASA IV patie...

  7. Incidence of Clostridium difficile infection in patients receiving high-risk antibiotics with or without a proton pump inhibitor.

    Science.gov (United States)

    Gordon, D; Young, L R; Reddy, S; Bergman, C; Young, J D

    2016-02-01

    Considering the incidence and severity of Clostridium difficile infection (CDI), risk reduction strategies are crucial. Prior studies suggest that proton pump inhibitor (PPI) use can increase the risk of CDI over antibiotics alone; however, data and guidelines have been conflicting. The aim was to compare CDI incidence in patients receiving high-risk antibiotics, comparing rates in those prescribed a PPI versus those without overlapping PPI exposure. This retrospective cohort study assessed the incidence of CDI in veterans receiving high-risk antibiotics over an approximately three-year period. High-risk antibiotics were defined as: ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, ceftriaxone, cefotaxime, ceftazidime, or cefixime. We identified subjects who were prescribed any high-risk antibiotic, finding 3513 on a concomitant PPI and 6149 not taking a PPI. Of these subjects, 111 were diagnosed with CDI and met inclusion criteria. Baseline characteristics, CDI severity, length of hospitalization and antibiotic therapy prior to infection were similar in both groups. The incidence of CDI was significantly higher in patients prescribed a PPI (odds ratio: 2.2; 95% confidence interval: 1.52-3.23; P=0.0001). A strong association was found between concurrent PPI use with fluoroquinolones (P=0.005) and clindamycin (P=0.045). The use of PPIs together with high-risk antibiotics was associated with a significantly higher incidence of CDI. Our study provides further support for the CDI prevention strategy of judicious PPI use, especially in patients receiving high-risk antibiotics. Prudent avoidance of PPIs may reduce the incidence of CDI, a major cause of morbidity and mortality worldwide. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  8. Depression and social anxiety in help-seeking patients with an ultra-high risk for developing psychosis

    NARCIS (Netherlands)

    Rietdijk, J.; Ising, H.K.; Dragt, S.; Klaassen, R.; Nieman, D.; Wunderink, L.; Cuijpers, P.; Linszen, D.; van der Gaag, M.

    2013-01-01

    Knowledge on associations between ultra-high risk (UHR) for developing psychosis and on non-psychotic psychopathology in help-seeking populations is limited with respect to differences between male and female patients. The present study tests the hypothesis that both social anxiety and depression

  9. Endovascular treatment of the subclavian artery aneurysm in high-risk patient - a single-center experience

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2016-01-01

    Full Text Available We present our first experience with endovascular treatment of 6 subclavian artery aneurysms (SAA occurring in five male and one female patient. All patients, in our studies, according to ASA classification were high risk for open repair of SAA. The etiology of the all aneurysms was atherosclerosis degeneration of the artery. Two aneurysms were of intrathoracic location, then the other were extrathoracic. Symptoms related to subclavian artery aneurysms were present in two patients, compression and chest pain in one, and hemorrhage shock in second, while the remaining patients were asymptomatic. We preferred the Viabhan endoprosthesis for endovascular repair in 5 cases. In one patient with ruptured of subclavian artery aneurysm who was high-risk for open repair we made combined endovascular procedure. First at all, we covered the origin of left subclavian artery with thoracic stent graft and after that we put two coils in proximal part of subclavian artery. There was no operative mortality, and the early patency rate was 100%. The follow-up period was from 3 months to 3 years. During this period, one patient died of heart failure and one patient required endovascular reoperation due to endoleak type I. Endovascular treatment is recommended for all patients with subclavian artery aneurysm whenever this is possible due to anatomical reasons especially in high-risk patient with intrathoracic localization of aneurysm, to prevent potential complications.

  10. Volume of hospital is important for the prognosis of high-risk patients with nonvariceal upper gastrointestinal bleeding (NVUGIB).

    Science.gov (United States)

    Choi, Jin Woo; Jeon, Seong Woo; Kwon, Jung Gu; Lee, Dong Wook; Ha, Chang Yoon; Cho, Kwang Bum; Jang, Byung Ik; Park, Jung Bae; Park, Youn Sun

    2017-08-01

    Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a potentially life-threatening hospital emergency requiring hemodynamic stabilization and resuscitation. This study is carried out to determine whether hospital volume can influence outcome in patients with NVUGIB. This is a retrospective study with a prospective cohort database (KCT 0000514. cris.nih.go.kr). Eight teaching hospitals were divided into two different groups: high-volume centers (HVC, ≥60 NVUGIB patients/year, four clinics) and low-volume centers (LVC, bleeding after treatment, re-bleeding, necessity for surgical/other retreatments, and death within 30 days. Similar baseline characters for patients were observed in both groups. There was a significant difference in the incidence of poor outcome between the HVC and LVC groups (9.06 vs. 13.69%, P = 0.014). The incidence rate of poor outcome in high-risk patients (Rockall score ≥8) in HVC was lower than that in high-risk patients in LVC (16.07 vs. 26.92%, P = 0.048); however, there was no significant difference in poor outcome in the lower-risk patients in either group (8.72 vs. 10.42%, P = 0.370). Significant correlation between hospital volume and outcome in NVUGIB patients was observed. Referral to HVC for the management of high-risk NVUGIB patients should be considered in clinical practice.

  11. High Risk Human Papilloma Virus Genotypes in Kurdistan Region in Patients with Vaginal Discharge.

    Science.gov (United States)

    Hussein, Nawfal R; Balatay, Amer A; Assafi, Mahde S; AlMufty, Tamara Abdulezel

    2016-01-01

    The human papilloma virus (HPV) is considered as the major risk factor for the development of cervical cancer. This virus is of different genotypes and generally can be classified into high and low risk types. To determine the rate of high risk HPV genotypes in women with vaginal discharge and lower abdominal pain in Kurdistan region, Iraq. Cervical swabs were taken from 104 women. DNA was extracted and the polymerase chain reaction (PCR) technique was used to determine the presence of high risk genotypes. It was found that 13/104 (12.5%) of the samples were positive for high risk HPV genotypes. Amongst those who were positive, 4/13 (30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On the other hand, genotypes 53 and 56 were found in only one sample each. High risk HPV genotypes are not uncommon and further community based study is needed to determine the prevalence of HPV and its genotypes and plan for prevention of infection.

  12. Staircase falls: High-risk groups and injury characteristics in 464 patients

    NARCIS (Netherlands)

    Boele van Hensbroek, P.; Mulder, S.; Luitse, J. S. K.; van Ooijen, M. R.; Goslings, J. C.

    2009-01-01

    Introduction: Few data are available about the epidemiology and injury characteristics in staircase falls. The available literature mainly concerns children and autopsy studies. Objective: To describe the epidemiology and injury characteristics of staircase falls, and to identify high-risk groups

  13. Patients with a high risk for obstructive sleep apnea syndrome: Postoperative respiratory complications

    Directory of Open Access Journals (Sweden)

    H. Pereira

    2013-07-01

    Full Text Available Background: STOP-BANG score (snore; tired; observed apnea; arterial pressure; body mass index; age; neck circumference and gender can predict the risk of a patient having Obstructive Syndrome Apnea (OSA. The aim of this study was to evaluate the incidence STOP-BANG score ≥ 3, in surgical patients admitted to the Post-Anesthesia Care Unit (PACU. Methods: Observational, prospective study conducted in a post-anesthesia care unit (PACU during three weeks (2011. The study population consisted of adult patients after noncardiac and non-neurological surgery. Patients were classified as high risk of OSA (HR-OSA if STOP-BANG score ≥ 3 and Low-risk of OSA (LR-OSA if STOP-BANG score  3, em pacientes cirúrgicos internados na Unidade de Cuidados Pós-Anestésica (UCPA. Métodos: Estudo observacional e prospectivo conduzido numa UCPA, durante três semanas (2011. A população de estudo consistiu em doentes adultos após cirurgia não cardíaca e não neurológica. Os doentes foram considerados com alto risco de SAOS (AR-SAOS se tinham um score de STOP-BANG ≥3 e de baixo risco de SAOS (BR-SAOS se tinham score de STOP-BANG <3. Foram avaliados dados demográficos dos doentes e colhidas variáveis intraoperatórias e pós-operatórias. As características dos doentes foram comparadas através do teste de Mann-Whitney, teste t, qui-quadrado ou teste exato de Fisher. Resultados: Um total de 357 doentes foram admitidos de UCPA e 340 preencheram os critérios de inclusão. Cento e setenta e nove (52% tinham AR-SAOS. Estes doentes eram mais velhos, tinham maior probabilidade de serem do sexo masculino, tinham um Índice Massa Corporal superior, tiveram uma classificação maior no estado físico American Society Anesthesiologists, uma maior incidência de doença cardíaca isquémica, insuficiência cardíaca, hipertensão, dislipidemia e eram mais frequentemente doentes

  14. Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials

    DEFF Research Database (Denmark)

    Jensen, Maj Britt; Nielsen, Torsten O.; Knoop, Ann S.

    2018-01-01

    Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characte......Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient...... and EGFR positive. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics. Results: In a multivariate model, mortality rate was significantly associated with age, tumor size, nodal status, invasion, histological type...

  15. High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

    International Nuclear Information System (INIS)

    Dreilich, Martin; Bergqvist, Michael; Moberg, Martin; Brattström, Daniel; Gustavsson, Inger; Bergström, Stefan; Wanders, Alkwin; Hesselius, Patrik; Wagenius, Gunnar; Gyllensten, Ulf

    2006-01-01

    Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma

  16. Graphene Oxide Nanoribbons Induce Autophagic Vacuoles in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Emanuela Mari

    2016-11-01

    Full Text Available Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2 and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS, mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells.

  17. Associations between alcohol, heroin, and cocaine use and high risk sexual behaviors among detoxification patients.

    Science.gov (United States)

    Raj, Anita; Saitz, Richard; Cheng, Debbie M; Winter, Michael; Samet, Jeffrey H

    2007-01-01

    The purpose of this study was to assess associations between substance use (alcohol to intoxication, heroin, and cocaine) and sexual activity, high risk sexual behaviors, and STD among detoxification inpatients (n = 470). Participants were surveyed on past 30 day substance use, past 6 month sexual behaviors, and STD in the past 6 months and/or over 24 months of follow-up. Logistic regression models adjusted for demographics found that cocaine use was significantly associated with being sexually active (OR(adj) = 2.3, 95% CI = 1.1-4.8) and selling sex (OR(adj) = 2.6, 95% CI = 1.3-5.3). Alcohol and heroin were not significantly associated with sexual activity, high risk sexual behaviors or STD in this sample.

  18. An intervention to improve care and reduce costs for high-risk patients with frequent hospital admissions: a pilot study

    Directory of Open Access Journals (Sweden)

    Kostrowski Shannon

    2011-10-01

    Full Text Available Abstract Background A small percentage of high-risk patients accounts for a large proportion of Medicaid spending in the United States, which has become an urgent policy issue. Our objective was to pilot a novel patient-centered intervention for high-risk patients with frequent hospital admissions to determine its potential to improve care and reduce costs. Methods Community and hospital-based care management and coordination intervention with pre-post analysis of health care utilization. We enrolled Medicaid fee-for-service patients aged 18-64 who were admitted to an urban public hospital and identified as being at high risk for hospital readmission by a validated predictive algorithm. Enrolled patients were evaluated using qualitative and quantitative interview techniques to identify needs such as transportation to/advocacy during medical appointments, mental health/substance use treatment, and home visits. A community housing partner initiated housing applications in-hospital for homeless patients. Care managers facilitated appropriate discharge plans then worked closely with patients in the community using a harm reduction approach. Results Nineteen patients were enrolled; all were male, 18/19 were substance users, and 17/19 were homeless. Patients had a total of 64 inpatient admissions in the 12 months before the intervention, versus 40 in the following 12 months, a 37.5% reduction. Most patients (73.3% had fewer inpatient admissions in the year after the intervention compared to the prior year. Overall ED visits also decreased after study enrollment, while outpatient clinic visits increased. Yearly study hospital Medicaid reimbursements fell an average of $16,383 per patient. Conclusions A pilot intervention for high-cost patients shows promising results for health services usage. We are currently expanding our model to serve more patients at additional hospitals to see if the pilot's success can be replicated. Trial registration

  19. c.1810C>T Polymorphism of NTRK1 Gene is associated with reduced Survival in Neuroblastoma Patients

    International Nuclear Information System (INIS)

    Lipska, Beata S; Biernat, Wojciech; Limon, Janusz; Drożynska, Elżbieta; Scaruffi, Paola; Tonini, Gian Paolo; Iżycka-Świeszewska, Ewa; Ziętkiewicz, Szymon; Balcerska, Anna; Perek, Danuta; Chybicka, Alicja

    2009-01-01

    TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported to be associated with a favourable prognosis in neuroblastoma. Therefore, the entire coding sequence of NTRK1 gene has been analysed in order to identify mutations and/or polymorphisms which may alter TrkA receptor expression. DNA was extracted from neuroblastomas of 55 Polish and 114 Italian patients and from peripheral blood leukocytes of 158 healthy controls. Denaturing High-Performance Liquid Chromatography (DHPLC) and Single-Strand Conformation Polymorphism (SSCP) analysis were used to screen for sequence variants. Genetic changes were confirmed by direct sequencing and correlated with biological and clinical data. Three previously reported and nine new single nucleotide polymorphisms were detected. c.1810C>T polymorphism present in 8.7% of cases was found to be an independent marker of disease recurrence (OR = 13.3; p = 0.009) associated with lower survival rates (HR = 4.45 p = 0.041). c.1810C>T polymorphism's unfavourable prognostic value was most significant in patients under 18 months of age with no MYCN amplification (HR = 26; p = 0.008). In-silico analysis of the c.1810C>T polymorphism suggests that the substitution of the corresponding amino acid residue within the conservative region of the tyrosine kinase domain might theoretically interfere with the functioning of the TrkA protein. NTRK1 c.1810C>T polymorphism appears to be a new independent prognostic factor of poor outcome in neuroblastoma, especially in children under 18 months of age with no MYCN amplification

  20. Cost-effectiveness Analysis of Nutritional Support for the Prevention of Pressure Ulcers in High-Risk Hospitalized Patients.

    Science.gov (United States)

    Tuffaha, Haitham W; Roberts, Shelley; Chaboyer, Wendy; Gordon, Louisa G; Scuffham, Paul A

    2016-06-01

    To evaluate the cost-effectiveness of nutritional support compared with standard care in preventing pressure ulcers (PrUs) in high-risk hospitalized patients. An economic model using data from a systematic literature review. A meta-analysis of randomized controlled trials on the efficacy of nutritional support in reducing the incidence of PrUs was conducted. Modeled cohort of hospitalized patients at high risk of developing PrUs and malnutrition simulated during their hospital stay and up to 1 year. Standard care included PrU prevention strategies, such as redistribution surfaces, repositioning, and skin protection strategies, along with standard hospital diet. In addition to the standard care, the intervention group received nutritional support comprising patient education, nutrition goal setting, and the consumption of high-protein supplements. The analysis was from a healthcare payer perspective. Key outcomes of the model included the average costs and quality-adjusted life years. Model results were tested in univariate sensitivity analyses, and decision uncertainty was characterized using a probabilistic sensitivity analysis. Compared with standard care, nutritional support was cost saving at AU $425 per patient and marginally more effective with an average 0.005 quality-adjusted life years gained. The probability of nutritional support being cost-effective was 87%. Nutritional support to prevent PrUs in high-risk hospitalized patients is cost-effective with substantial cost savings predicted. Hospitals should implement the recommendations from the current PrU practice guidelines and offer nutritional support to high-risk patients.

  1. Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV

    International Nuclear Information System (INIS)

    Voute, P.A.; Kleij, A.J. van der; De Kraker, J.; Hoefnagel, C.A.; Tiel-van Buul, M.M.C.; Gennip, H. van

    1995-01-01

    The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [ 131 I]MIBG and hyperbaric oxygen compared to 12% for [ 131 I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain. (Author)

  2. ARID1B alterations identify aggressive tumors in neuroblastoma.

    Science.gov (United States)

    Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

    2017-07-11

    Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

  3. Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma.

    Science.gov (United States)

    Dolman, M Emmy M; Poon, Evon; Ebus, Marli E; den Hartog, Ilona J M; van Noesel, Carel J M; Jamin, Yann; Hallsworth, Albert; Robinson, Simon P; Petrie, Kevin; Sparidans, Rolf W; Kok, Robbert J; Versteeg, Rogier; Caron, Huib N; Chesler, Louis; Molenaar, Jan J

    2015-11-15

    MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted inhibition of cyclin-dependent kinase 2 (CDK2) resulted in specific killing of MYCN-amplified neuroblastoma cells. This study describes the in vivo preclinical evaluation of the CDK inhibitor AT7519. Preclinical drug testing was performed using a panel of MYCN-amplified and MYCN single copy neuroblastoma cell lines and different MYCN-dependent mouse models of neuroblastoma. AT7519 killed MYCN-amplified neuroblastoma cell lines more potently than MYCN single copy cell lines with a median LC50 value of 1.7 compared to 8.1 μmol/L (P = 0.0053) and a significantly stronger induction of apoptosis. Preclinical studies in female NMRI homozygous (nu/nu) mice with neuroblastoma patient-derived MYCN-amplified AMC711T xenografts revealed dose-dependent growth inhibition, which correlated with intratumoral AT7519 levels. CDK2 target inhibition by AT7519 was confirmed by significant reductions in levels of phosphorylated retinoblastoma (p-Rb) and nucleophosmin (p-NPM). AT7519 treatment of Th-MYCN transgenic mice resulted in improved survival and clinically significant tumor regression (average tumor size reduction of 86% at day 7 after treatment initiation). The improved efficacy of AT7519 observed in Th-MYCN mice correlated with higher tumor exposure to the drug. This study strongly suggests that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. ©2015 American Association for Cancer Research.

  4. LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

    Science.gov (United States)

    Zhang, Zhuorong; Chang, Yitian; Jia, Wei; Zhang, Jiao; Zhang, Ruizhong; Zhu, Jinhong; Yang, Tianyou; Xia, Huimin; Zou, Yan; He, Jing

    2018-02-28

    Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95% confidence interval (CI) =1.06-3.06, P =0.029; TT/CT compared with CC: adjusted OR =1.31, 95% CI =1.02-1.67, P =0.033; and T compared with C: adjusted OR =1.29, 95% CI =1.06-1.58, P =0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR =1.51, 95% CI =1.06-2.14, P =0.021) and International Neuroblastoma Staging System (INSS) stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P =0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings. © 2018 The Author(s).

  5. Health behavior and health-related quality of life in patients with a high risk of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Petek Davorina

    2018-01-01

    Full Text Available Health-related quality of life (HRQoL is measuring a patient’s experience of his health status and represents an outcome of medical interventions. Existing data proves that a healthy lifestyle is positively associated with HRQoL in all age groups. Patients with a high risk for cardiovascular disease typically led an unhealthy lifestyle combined with risk diseases. We aimed to analyse these characteristics and their reflection in HRQoL.

  6. Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis

    International Nuclear Information System (INIS)

    Kim, Young Hwan; Kim, Yong Joo; Shin, Tae Beom

    2011-01-01

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis. Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique. Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days). Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis

  7. High-risk angina patient: identification by clinical features, hospital course, electrocardiography, and technetium-99m stannous pyrophosphate scintigraphy

    International Nuclear Information System (INIS)

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-01-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p < 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p < 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup, with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients

  8. High-risk angina patient. Identification by clinical features, hospital course, electrocardiography and technetium-99m stannous pyrophosphate scintigraphy

    International Nuclear Information System (INIS)

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-01-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +/- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p less than 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p less than 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients

  9. Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan [Keimyung University, College of Medicine, Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andong (Korea, Republic of); Shin, Tae Beom [Gyeonsang National University, College of Medicine, Jinju (Korea, Republic of)

    2011-04-15

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis. Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique. Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days). Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis

  10. The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN

    Directory of Open Access Journals (Sweden)

    J. Guan

    2016-09-01

    Full Text Available The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori, has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo. In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants. In contrast to crizotinib, single agent administration of PF-06463922 caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts as well as a mouse model of high-risk neuroblastoma driven by Th-ALKF1174L/MYCN. Taken together, our results suggest PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients.

  11. Asymmetry of salivary gland I123 Metaiodobenzylguanidine (MIBG) uptake in a patient with cervical neuroblastoma and Horner's syndrome - possible etiologic mechanisms

    International Nuclear Information System (INIS)

    Sandler, E.D.; Hattner, R.S.; Parisi, M.T.

    1992-01-01

    Horner's syndrome may be due to a variety of serious underlying disorders including cervical neuroblastoma. Horner's syndrome results from a unilateral disruption of the sympathetic innervation to the head and neck. We report a patient with cervical neuroblastoma in whom post operative metaiodobenzylguanidine (MIBG) scans showed a striking decrease in uptake in the ipselateral salivary glands. Since the biodistribution of I 123 metaiodobenzylguanidine in the salivary glands is also dependent on sympathetic innervation, the presence of Horner's syndrome can be reflected in the MIBG scan. (orig.)

  12. Thirty-day outcomes of direct carotid artery stenting with cerebral protection in high-risk patients

    International Nuclear Information System (INIS)

    Veselka, J.; Cerna, D.; Zimolova, P.; Blasko, P.; Fiedler, J.; Hajek, P.; Maly, M.; Zemanek, D.; Duchonova, R.

    2007-01-01

    Implantation of a carotid artery stent after predilation is a standard approach in the endovascular treatment of carotid artery stenoses. Stenting without predilation may be an alternative approach in a certain subset of patients. The present prospective, single-center registry was designed to evaluate the feasibility and safety of direct carotid artery stenting (DCAS) in high-risk patients. Symptomatic patients with stenosis >50% and asymptomatic patients with stenosis >70% were eligible for enrolment. Criteria for high-risk patients included: need or history of open heart surgery, history of myocardial infarction, multivessel coronary artery disease, left ventricular dysfunction (ejection fraction ≤40%), severe pulmonary or renal disease, significant contralateral carotid disease, previous endarterectomy, and age ≥80 years. All procedures were performed using a filter protection device. Patients underwent complete clinical examination before and after DCAS and at 30-day follow-up. A total of 83 consecutive patients (45 males, 68±9 years, 33% symptomatic) underwent 100 procedures and 103 stents were deployed successfully. The technical success rate of stenting was 100%. Predilation of carotid stenosis was necessary in 1 (1%) procedure. Carotid-artery stenoses before and after DCAS were 80±9% and 7±9%, respectively. The median fluoroscopic time for DCAS was 7 min. The overall rate of in-hospital major adverse cerebrovascular events (death, stroke, myocardial infarction) was 5% (2 minor strokes, 3 transient attacks). There was 1 (1%) minor stroke within the 30-day follow-up. DCAS is feasible and can be performed with an acceptable risk in high-risk patients. (author)

  13. Ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study

    Science.gov (United States)

    Burger, Jan A.; Keating, Michael J.; Wierda, William G.; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y.; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M.; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O’Brien, Susan

    2014-01-01

    Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), is an effective therapy for patients with relapsed chronic lymphocytic leukemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab (iR) in patients with high-risk CLL. Methods In this single-arm, phase 2 studywe enrolled 40 patients with high-risk CLL at MD Anderson Cancer Center, Houston, Texas, USA. Patients with symptomatic CLL requiring therapy received 28 day cycles of once-daily ibrutinib 420 mg , together with rituximab (weekly during cycle 1, then once per cycle until cycle 6), followed by continuous single-agent ibrutinib. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01520519 and is no longer accruing patients. Findings Between February 28, 2012 and September 11, 2012, we enrolled 40 CLL patients with high-risk disease features. 20 patients had del17p or TP53 mutations (16 previously treated, 4 untreated), 13 had relapsed CLL with del11q, and 7 patients a PFS infections occurred in 4 patients (10%), no grade 4 or 5 infections occurred. At 18 months, the Kaplan Meier estimate of progression-free survival was 78% (95% CI 60.6–88.5) (del[17p] or TP53 mutation: 72%, 95% CI: 45.6–87.6) Interpretation Ibrutinib in combination with rituximab is a well-tolerated regimen for patients with high-risk CLL. It induces high rates of remissions and has positive impact on QOL in this difficult-to-treat patient population. These encouraging data merit further investigation of the added benefit of rituximab as combination partner for ibrutinib in an ongoing randomized trial, in which single-agent ibrutinib is compared to iR combination therapy (NCT02007044). Funding Pharmacyclics, Inc., Cancer Prevention and Research Institute of Texas (CPRIT), Leukemia & Lymphoma Society, NCI Grant P30 CA

  14. A constitutional translocation t(1;17(p36.2;q11.2 in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes.

    Directory of Open Access Journals (Sweden)

    Karl Vandepoele

    Full Text Available The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17(p36.2;q11.2 may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.

  15. Innovative practice model to optimize resource utilization and improve access to care for high-risk and BRCA+ patients.

    Science.gov (United States)

    Head, Linden; Nessim, Carolyn; Usher Boyd, Kirsty

    2017-02-01

    Bilateral prophylactic mastectomy (BPM) has demonstrated breast cancer risk reduction in high-risk/ BRCA + patients. However, priority of active cancers coupled with inefficient use of operating room (OR) resources presents challenges in offering BPM in a timely manner. To address these challenges, a rapid access prophylactic mastectomy and immediate reconstruction (RAPMIR) program was innovated. The purpose of this study was to evaluate RAPMIR with regards to access to care and efficiency. We retrospectively reviewed the cases of all high-risk/ BRCA + patients having had BPM between September 2012 and August 2014. Patients were divided into 2 groups: those managed through the traditional model and those managed through the RAPMIR model. RAPMIR leverages 2 concurrently running ORs with surgical oncology and plastic surgery moving between rooms to complete 3 combined BPMs with immediate reconstruction in addition to 1-2 independent cases each operative day. RAPMIR eligibility criteria included high-risk/ BRCA + status; BPM with immediate, implant-based reconstruction; and day surgery candidacy. Wait times, case volumes and patient throughput were measured and compared. There were 16 traditional patients and 13 RAPMIR patients. Mean wait time (days from referral to surgery) for RAPMIR was significantly shorter than for the traditional model (165.4 v. 309.2 d, p = 0.027). Daily patient throughput (4.3 v. 2.8), plastic surgery case volume (3.7 v. 1.6) and surgical oncology case volume (3.0 v. 2.2) were significantly greater in the RAPMIR model than the traditional model ( p = 0.003, p < 0.001 and p = 0.015, respectively). A multidisciplinary model with optimized scheduling has the potential to improve access to care and optimize resource utilization.

  16. Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients

    International Nuclear Information System (INIS)

    MacLennan, I.; Keys, H.M.; Evarts, C.M.; Rubin, P.

    1984-01-01

    Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible on postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized

  17. A case of neonatal neuroblastoma

    International Nuclear Information System (INIS)

    Nounaka, Osamu; Gotoh, Toshiaki; Takahashi, Kazuaki; Koyanagi, Tomohiko; Kakizaki, Hidehiro; Nakanishi, Shoichiro.

    1987-01-01

    A two-day-old male infant was referred to us for probable neuroblastoma, because of upper abdominal mass and positive urinary vanillylmandelic acid (VMA). Primary site of neuroblastoma was not found, but clinically IV-S stage neuroblastoma was strongly suspected, so 131 I-metaiodobenzylguanidine (MIBG) scan was performed. RI accumulation was found near the left adrenal region. Thus laparotomy was performed and left adrenal was resected. Liver biopsy was also performed. Microscopically multiple in situ foci of neuroblastoma cells were found in the left adrenal and tumor involvement was also seen in the liver. Skin and bone marrow metastasis were ruled out. Minimal chemotherapy was intended but abandoned soon because of possible spontaneous regression of stage IV-S neuroblastoma. Thereafter liver has been getting smaller and the patient has been doing well. Urinary VMA and homovanillic acid (HVA) per creatinine, which were used for follow-up, have also normalized after 3 months. Treatment of stage IV-S neuroblastoma and early diagnosis by 131 I-MIBG scan were reviewed. (author)

  18. Finding the High-Risk Patient in Primary Prevention Is Not as Easy as a Conventional Risk Score!

    Science.gov (United States)

    Ambrose, John A; Acharya, Tushar; Roberts, Micah J

    2016-12-01

    Patients with coronary artery disease or its equivalent are an appropriate target for guideline-directed therapy. However, finding and treating the individuals at risk for myocardial infarction or sudden death in primary prevention has been problematic. Most initial cardiovascular events are acute syndromes, and only a minority of these occurs in those deemed high risk by contemporary algorithms. Even newer noninvasive modalities cannot detect a majority of those at risk. Furthermore, accurate and early detection of high risk/vulnerability does not guarantee event prevention. Until new tools can be identified, one should consider a few simplistic solutions. In addition to a greater emphasis on lifestyle, earlier use of statins than currently recommended and a direct assault on tobacco could go a long way in reducing acute syndromes and cardiovascular mortality. To achieve the tobacco goal, the medical community would have to be directly and communally engaged. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

    2010-04-07

    Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

  20. High risk of malnutrition is associated with low muscle mass in older hospitalized patients - a prospective cohort study.

    Science.gov (United States)

    Pierik, Vincent D; Meskers, Carel G M; Van Ancum, Jeanine M; Numans, Siger T; Verlaan, Sjors; Scheerman, Kira; Kruizinga, Roeliene C; Maier, Andrea B

    2017-06-05

    Malnutrition, low muscle strength and muscle mass are highly prevalent in older hospitalized patients and associated with adverse outcomes. Malnutrition may be a risk factor for developing low muscle mass. We aimed to investigate the association between the risk of malnutrition and 1) muscle strength and muscle mass at admission and 2) the change of muscle strength and muscle mass during hospitalization in older patients. The EMPOWER study included 378 patients aged seventy years or older who were acutely or electively admitted to four different wards of an academic teaching hospital in Amsterdam. Patients were grouped into low risk of malnutrition and high risk of malnutrition based on the Short Nutritional Assessment Questionnaire (SNAQ) score and were assessed for hand grip strength and muscle mass using hand held dynamometry respectively bioelectrical impedance analysis (BIA) within 48 h after admission and at day seven, or earlier at the day of discharge. Muscle mass was expressed as skeletal muscle mass, appendicular lean mass, fat free mass and the skeletal muscle index. The mean age of the patients was 79.7 years (SD 6.39), 48.9% were female. At admission, being at high risk of malnutrition was significantly associated with lower muscle mass (Odds Ratio, 95% CI, 0.90, 0.85-0.96), but not with muscle strength. Muscle strength and muscle mass did not change significantly during hospitalization in both groups. In older hospitalized patients, a high risk of malnutrition is associated with lower muscle mass at admission, but not with muscle strength nor with change of either muscle strength or muscle mass during hospitalization.

  1. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

    International Nuclear Information System (INIS)

    Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

    2007-01-01

    Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

  2. Hybrid approach for transcatheter paravalvular leak closure of mitral prosthesis in high-risk patients through transapical access.

    Science.gov (United States)

    Davidavicius, Giedrius; Rucinskas, Kestutis; Drasutiene, Agne; Samalavicius, Robertas; Bilkis, Valdas; Zakarkaite, Diana; Aidietis, Audrius

    2014-11-01

    To report "hybrid" procedure feasibility and the clinical success of transcatheter paravalvular leak closure through apical access. Seven patients (73.6±6.1 years; 4 men) with severe mitral prosthesis paravalvular leak were selected. All patients were at high risk for open surgery because of severe comorbidities and heart failure (New York Heart Association class III-IV). The defect size was 25±7.8 mm in the long axis and 9.3±2 mm in the short axis. Two defects were detected in 2 patients. The transapical procedure was performed in a "hybrid" surgery room using minithoracotomy and general anesthesia. Three-dimensional transesophageal echocardiography and fluoroscopy were used for imaging. A total of 19 Amplatzer Vascular Plug III devices (St Jude Medical) were implanted in 7 patients, 2.7/patient and 1 to 3/fistula. The procedure time was 150.7±66.8 minutes. In 6 of 7 patients (85.7%), the paravalvular leak was successfully closed, resulting in no or mild residual regurgitation. One patient had moderate regurgitation despite deployment of 3 Amplatzer Vascular Plug III devices. Two patients required blood transfusion related to procedural blood loss. The patients were discharged at 15.3±6.5 days and followed up at 215.7±138.6 days. All but 1 patient reported symptomatic improvement by ≥1 New York Heart Association class at follow-up. One patient died 216 days postoperatively. A "hybrid approach" for transcatheter paravalvular leak closure of mitral prosthesis from the apical route is effective in reducing the regurgitation grade and improving functional capacity in high-risk patients. Complete closure of the defect was maintained at follow-up in most patients. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: Prospective follow-up of 245 clinical high-risk outpatients in four countries

    NARCIS (Netherlands)

    Salokangas, Raimo K. R.; Ruhrmann, Stephan; von Reventlow, Heinrich Graf; Heinimaa, Markus; Svirskis, Tanja; From, Tiina; Luutonen, Sinikka; Juckel, Georg; Linszen, Don; Dingemans, Peter; Birchwood, Max; Patterson, Paul; Schultze-Lutter, Frauke; Klosterkötter, Joachim; Picke, Heinz; Neumann, Meike; Brockhaus-Dumke, Anke; Pukrop, Ralf; Huttunen, Jukka; Laine, Tiina; Ilonen, Tuula; Ristkari, Terja; Hietala, Jarmo; Becker, Hiske; Nieman, Dorien; Skeate, Amanda; Gudlowski, Yehonala; Ozgürdal, Seza; Witthaus, Henning; French, Paul; Stevens, Helen

    2012-01-01

    Background: In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to

  4. Sutureless versus Conventional Aortic Valve Replacement: Outcomes in 70 High-Risk Patients Undergoing Concomitant Cardiac Procedures.

    Science.gov (United States)

    Hanedan, Muhammet Onur; Yuruk, Mehmet Ali; Parlar, Ali Ihsan; Ziyrek, Ugur; Arslan, Ali Kemal; Sayar, Ufuk; Mataraci, Ilker

    2018-02-01

    In elderly, high-risk surgical patients, sutureless aortic valve replacement (AVR) can often be an alternative to conventional AVR; shorter aortic cross-clamp and cardiopulmonary bypass times are the chief advantages. We compared the outcomes of sutureless AVR with those of conventional AVR in 70 elderly patients who underwent concomitant cardiac surgical procedures. We retrospectively analyzed the cases of 42 men and 28 women (mean age, 70.4 ± 10.3 yr; range, 34-93 yr) who underwent cardiac operations plus AVR with either a sutureless valve (group 1, n=38) or a conventional bioprosthetic or mechanical valve (group 2, n=32). Baseline patient characteristics were similar except for worse New York Heart Association functional status and the prevalence of diabetes mellitus in group 1. In group 1, the operative, cross-clamp, and cardiopulmonary bypass times were shorter (all P =0.001), postoperative drainage amounts were lower ( P =0.009), hospital stays were shorter ( P =0.004), and less red blood cell transfusion was needed ( P =0.037). Echocardiograms before patients' discharge from the hospital showed lower peak and mean aortic gradients in group 1 (mean transvalvular gradient, 8.4 ± 2.8 vs 12.2 ± 5.2 mmHg; P =0.012). We found that elderly, high-risk patients who underwent multiple cardiac surgical procedures and sutureless AVR had better hemodynamic outcomes and shorter ischemic times than did patients who underwent conventional AVR.

  5. Clinical efficacy of transcatheter aortic valve replacement for severe aortic stenosis in high-risk patients: the PREVAIL JAPAN trial.

    Science.gov (United States)

    Sawa, Yoshiki; Takayama, Morimasa; Mitsudo, Kazuaki; Nanto, Shinsuke; Takanashi, Shuichiro; Komiya, Tatsuhiko; Kuratani, Toru; Tobaru, Tetsuya; Goto, Tsuyoshi

    2015-01-01

    Transcatheter aortic valve replacement (TAVR) is suggested to be less invasive and/or equally effective in comparison to conventional aortic valve replacement for high-risk symptomatic aortic stenosis patients. We herein report the initial results of a pivotal clinical trial of TAVR in Japan (the PREVAIL JAPAN). Sixty-four aortic stenosis patients (mean age 84.3 ± 6.1 years) not suitable for surgery were enrolled at three centers in Japan, with a primary composite endpoint of the 6-month post-procedure improvements in the aortic valve area and New York Heart Association (NYHA) functional classification. A transfemoral approach was used in 37 patients and a transapical approach was used in 27. The device success rate was 91.9 %. After 30 days and 6 months, the rates of mortality from any cause were 8.1 and 11.3 %, respectively. At 6 months, symptomatic stroke was found in 3.1 % of the patients, and silent infarction in 7.8 %. The aortic valve area and mean pressure gradient were significantly improved over time with both approaches (p < 0.001). At 6 months, the NYHA functional classification based on a conventional physician's assessment was improved in 87.9 % of the patients. We found results that were equivalent to those in other major TAVR trials, such as an acceptable 30-day survival (91.9 %), suggesting that balloon-expandable TAVR is effective for small Japanese AS patients classified as high-risk or inoperable.

  6. PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma.

    Science.gov (United States)

    Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

    2017-08-01

    Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (LAG3) on tumor-infiltrating lymphocytes to better define patient risk stratification and understand whether this tumor may benefit from therapies targeting immune checkpoint molecules. Experimental Design: In situ IHC staining for PD-L1, HLA class I, PD-1, and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T-cell density and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow cytometry and IHC in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC, and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients ( P = 0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

    Science.gov (United States)

    Gauguet, Jean-Marc; Pace-Emerson, Tamara; Grant, Frederick D; Shusterman, Suzanne; DuBois, Steven G; Frazier, A Lindsay; Voss, Stephan D

    2017-11-01

    Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma. A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management. One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation. In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm. © 2017 Wiley Periodicals, Inc.

  8. Effectiveness of haloperidol prophylaxis in critically ill patients with a high risk of delirium: a systematic review.

    Science.gov (United States)

    Santos, Eduardo; Cardoso, Daniela; Neves, Hugo; Cunha, Madalena; Rodrigues, Manuel; Apóstolo, João

    2017-05-01

    Delirium is associated with increased intensive care unit and hospital length of stay, prolonged duration of mechanical ventilation, unplanned removal of tubes and catheters, and increased morbidity and mortality. Prophylactic treatment with low-dose haloperidol may have beneficial effects for critically ill patients with a high risk of delirium. To identify the effectiveness of haloperidol prophylaxis in critically ill patients with a high risk for delirium. Patients with a predicted high risk of delirium, aged 18 years or over, and in intensive care units. Patients with a history of concurrent antipsychotic medication use were excluded. Haloperidol prophylaxis for preventing delirium. Experimental and epidemiological study designs. Primary outcome is the incidence of delirium. Secondary outcomes are duration of mechanical ventilation, incidence of re-intubation, incidence of unplanned/accidental removal of tubes/lines and catheters, intensive care unit and hospital length of stay, and re-admissions to both settings. An initial search of MEDLINE and CINAHL was undertaken, followed by a second search for published and unpublished studies from January 1967 to September 2015 in major healthcare-related electronic databases. Studies in English, Spanish and Portuguese were included. Two independent reviewers assessed the methodological quality of five studies using the standardized critical appraisal instrument from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. There was general agreement among the reviewers to exclude one relevant study due to methodological quality. Data were extracted using the JBI data extraction form for experimental studies and included details about the interventions, populations, study methods and outcomes of significance to the review questions. Significant differences were found between participants, interventions, outcome measures (clinical heterogeneity) and designs (methodological heterogeneity

  9. Azithromycin add-on therapy in high-risk postendoscopic sinus surgery patients failing corticosteroid irrigations: A clinical practice audit.

    Science.gov (United States)

    Maniakas, Anastasios; Desrosiers, Martin

    2014-01-01

    Chronic rhinosinusitis (CRS) has a high potential for recurrence after endoscopic sinus surgery (ESS), despite a postoperative therapy of topical corticosteroid irrigations. Azithromycin (AZI) is a macrolide antibiotic with anti-inflammatory properties that may be of benefit in such steroid-unresponsive patients. Follow-up study was performed to (1) review the effectiveness of the management strategy of adding AZI in high-risk post-ESS patients failing standard management and (2) identify predictive factors for steroid nonresponsiveness. A retrospective audit of the postoperative evolution of all patients undergoing ESS for CRS in 2010 by a single surgeon was undertaken. Patients deemed at high risk of recurrence based on preoperative history and/or perioperative findings received nasal irrigation with 0.5 mg of budesonide (BUD) in 240 mL of saline twice daily after ESS. Patients showing signs of endoscopic recurrence at 4 months, despite BUD, had AZI at 250 mg three times a week added to their treatment regimen. A total of 57 high-risk patients underwent ESS during this period. At 4 months, 63.2% (36/57) had a favorable outcome solely with BUD. Twelve of the 21 nonresponders received AZI, with an additional 66.7% (8/12) subsequently showing a favorable response. Failure of BUD was associated with female gender (p = 0.048), having elevated alpha-1-antitrypsin levels (p = 0.037) and lower recovery rates of Staphylococcus aureus (p = 0.063). Although the AZI subgroup was too small for statistical analysis, female gender was more frequently associated with failure of both BUD and AZI, while IgE was not useful. A significant subgroup of high-risk patients showing disease recurrence after ESS despite topical corticosteroid therapy may respond to the addition of AZI as part of their therapy. These findings suggest that topical steroid-unresponsive CRS may represent a distinct entity and that alternate anti-inflammatory agents may be required for optimal management.

  10. CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Snider, James W.; Oermann, Eric K.; Chen, Viola; Rabin, Jennifer; Suy, Simeng; Yu, Xia [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

    2012-06-29

    Standard treatment for operable patients with single peripheral lung metastases is metastasectomy. We report mature CyberKnife outcomes for high-risk surgical patients with biopsy proven single peripheral lung metastases. Twenty-four patients (median age 73 years) with a mean maximum tumor diameter of 2.5 cm (range, 0.8–4.5 cm) were treated over a 6-year period extending from September 2004 to September 2010 and followed for a minimum of 1 year or until death. A mean dose of 52 Gy (range, 45–60 Gy) was delivered to the prescription isodose line in three fractions over a 3–11 day period (mean, 7 days). At a median follow-up of 20 months, the 2-year Kaplan–Meier local control and overall survival rates were 87 and 50%, respectively. CyberKnife with fiducial tracking is an effective treatment for high-risk surgical patients with single small peripheral lung metastases. Trials comparing CyberKnife with metastasectomy for operable patients are necessary to confirm equivalence.

  11. 10-Year Survival and Quality of Life in Patients With High-Risk PN0 Prostate Cancer Following Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Berg, Arne; Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

    2007-01-01

    Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T 1-4p N 0 M 0 prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T 3-4 or Gleason score (GS) ≥7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T 1-2 and GS ≤7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p p N 0 , RT with dosage 3-4 or GS ≥7B

  12. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

    Science.gov (United States)

    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  13. Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.

    Science.gov (United States)

    Barnes, Rosemary A; Stocking, Kate; Bowden, Sarah; Poynton, Matthew H; White, P Lewis

    2013-09-01

    The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  15. Mechanisms of neuroblastoma regression

    Science.gov (United States)

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

  16. Comparison of ramosetron with ondansetron for the prevention of post-operative nausea and vomiting in high-risk patients

    Directory of Open Access Journals (Sweden)

    Sandip Agarkar

    2015-01-01

    Full Text Available Background and Aims: Post-operative nausea and vomiting (PONV has an 80% incidence in high-risk patients. This is despite the availability of several antiemetic drugs. Selective 5-hydroxytryptamine type 3 (5-HT 3 receptor antagonists are considered first-line for prophylaxis, ondansetron being the most commonly used agent. Ramosetron, another selective 5-HT 3 receptor antagonist, is more potent and longer acting than ondansetron. This study was conducted to evaluate the antiemetic efficacy of ramosetron in comparison with ondansetron in patients at a high risk of PONV. Methods: This was a prospective randomised double-blind study carried out over a 6-month period in which 206 patients with at least two risk factors for PONV were randomised to receive ramosetron 0.3 mg or ondansetron 8 mg, 30 min before the end of surgery. The incidence of PONV, severity of nausea and need for rescue antiemetic were recorded over the next 24 h. Primary outcome was the incidence of PONV. Secondary outcomes included severity of nausea and need for rescue. The data were analysed using the Predictive Analytics Software (PASW, version 18: Chicago, IL, USA. Results: The incidence of PONV was found to be 35% in the ramosetron group as opposed to 43.7% in the ondansetron group (P = 0.199. Need for rescue antiemetic was 23.3% in the ramosetron group and 32% in the ondansetron group (P = 0.156 in the 24 h following surgery. Conclusion: Ramosetron 0.3 mg and ondansetron 8 mg were equally effective in reducing the incidence of PONV in high risk patients.

  17. Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.

    Science.gov (United States)

    Bodem, Jens Philipp; Kargus, Steffen; Eckstein, Stefanie; Saure, Daniel; Engel, Michael; Hoffmann, Jürgen; Freudlsperger, Christian

    2015-05-01

    As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. The perioperative adjuvant treatment included intravenous antibiotic prophylaxis starting at least 24 h before surgery, a gastric feeding tube and mouth rinses with chlorhexidine (0.12%) three times a day. In the follow-up period patients were examined every 4 weeks for the development of BRONJ. Minimum follow-up was 12 weeks. In 61 patients a total number of 184 teeth were removed from 102 separate extraction sites. In eight patients (13.1%) BRONJ developed during the follow-up. A higher risk for developing BRONJ was found in patients where an additional osteotomy was necessary (21.4% vs. 8.0%; p = 0.0577), especially for an osteotomy of the mandible (33.3% vs. 7.3%; p = 0.0268). Parameters including duration of intravenous antibiotic prophylaxis, the use of a gastric feeding tube and the duration of intravenous BP therapy showed no statistical impact on the development of BRONJ. Furthermore, patients currently undergoing intravenous BP therapy showed no higher risk for BRONJ compared with patients who have paused or completed their intravenous BP therapy (p = 0.4232). This study presents a protocol for surgical tooth extraction in high-risk BP patients in combination with a perioperative adjuvant treatment setting, which reduced the risk for postoperative BRONJ to a minimum. However, the risk for BRONJ increases significantly if an additional osteotomy is necessary

  18. Intensive case management for high-risk patients with first-episode psychosis: service model and outcomes.

    Science.gov (United States)

    Brewer, Warrick J; Lambert, Timothy J; Witt, Katrina; Dileo, John; Duff, Cameron; Crlenjak, Carol; McGorry, Patrick D; Murphy, Brendan P

    2015-01-01

    The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis

  19. Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

    Science.gov (United States)

    Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith

    2017-09-01

    Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Hoskin, Peter [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Rojas, Ana, E-mail: arc03@btconnect.com [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Lowe, Gerry; Bryant, Linda; Ostler, Peter; Hughes, Rob; Milner, Jessica; Cladd, Helen [Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom)

    2012-03-15

    Purpose: To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. Methods and Materials: A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Results: Incidence of early Grade {>=} 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02). Conclusions: There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.

  1. Patients with eating disorders. A high-risk group for fractures

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Emborg, C.; Stoving, R.K.

    2003-01-01

    PURPOSE: To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). DESIGN: Clinical overview. FINDINGS: Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa....... In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. CONCLUSIONS: Fracture risk is increased...

  2. Case report: value of gene expression profiling in the diagnosis of atypical neuroblastoma.

    Science.gov (United States)

    Harttrampf, Anne C; Chen, Qingrong; Jüttner, Eva; Geiger, Julia; Vansant, Gordon; Khan, Javed; Kontny, Udo

    2017-08-17

    Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases. We report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma. Imaging studies showed tumor extension into the inferior vena cava and bilateral lung metastases while urine catecholamines and MIBG-scintigraphy were negative. Preoperative chemotherapy with vincristine, actinomycine D and adriamycin according to the SIOP2001/GPOH protocol for the treatment of nephroblastoma was initiated and followed by surgical tumor resection. Histopathology revealed an undifferentiated tumor with expression of neuronal markers, suggestive of neuroblastoma. MYCN amplification could not be detected. DNA-microarray analysis was performed using Affymetrix genechip human genome U133 plus 2.0 and artificial neural network analysis. Results were confirmed by multiplex RT-PCR. Principal component analysis using 84 genes showed that the patient sample was clearly clustering with neuroblastoma tumors. This was confirmed by hierarchical clustering of the multiplex RT-PCR data. The patient underwent treatment for high-risk neuroblastoma comprising chemotherapy including cisplatin, etoposide, vindesine, dacarbacine, ifosfamide, vincristine, adriamycine and autologous stem cell transplantation followed by maintenance therapy with 13-cis retinoic acid (GPOH NB2004 High Risk Trial Protocol) and is in complete long-term remission. The use of gene expression profiling in an individual patient strongly contributed to clarification in a diagnostic dilemma which finally led to a change of

  3. Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease.

    Science.gov (United States)

    Dedic, Admir; Ten Kate, Gert-Jan R; Roos, Cornelis J; Neefjes, Lisan A; de Graaf, Michiel A; Spronk, Angela; Delgado, Victoria; van Lennep, Jeanine E Roeters; Moelker, Adriaan; Ouhlous, Mohamed; Scholte, Arthur J H A; Boersma, Eric; Sijbrands, Eric J G; Nieman, Koen; Bax, Jeroen J; de Feijter, Pim J

    2016-03-01

    At present, traditional risk factors are used to guide cardiovascular management of asymptomatic subjects. Intensified surveillance may be warranted in those identified as high risk of developing cardiovascular disease (CVD). This study aims to determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high CVD risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (≥50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p value and risk reclassification benefit beyond CACS in patients without CAD symptoms but with high risk of developing CVD. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Constitutional 11q14-q22 chromosome deletion syndrome in a child with neuroblastoma MYCN single copy.

    Science.gov (United States)

    Passariello, Annalisa; De Brasi, Daniele; Defferrari, Raffaella; Genesio, Rita; Tufano, Maria; Mazzocco, Katia; Capasso, Maria; Migliorati, Roberta; Martinsson, Tommy; Siani, Paolo; Nitsch, Lucio; Tonini, Gian Paolo

    2013-11-01

    Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR patients analyzed for chromosomal anomalies. Its role in determining the phenotype depends on extension and position of deleted region. Loss of heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the most frequent extra cranial cancer in children. It represents one of the most frequent cytogenetic abnormalities observed in the tumor of patients with high-risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby, we describe a 18 months old girl presenting with trigonocephaly and dysmorphic facial features, including hypotelorism, broad depressed nasal bridge, micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3), outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The role of 11q deletion in determining the clinical phenotype and its association with neuroblastoma development in the patient are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Patients at high risk of adverse events from intravenous contrast media after computed tomography examination

    Energy Technology Data Exchange (ETDEWEB)

    Reddan, Donal [University College Galway Hospitals, Unit 7, Merlin Park Hospital, Galway (Ireland)]. E-mail: donal.reddan@mailn.hse.ie

    2007-05-15

    Adverse reactions to iodinated contrast media (CM) may occur and require prompt recognition and treatment. Although adverse reactions to radiocontrast agents cannot be eliminated, an important first step toward reducing their incidence is to identify patients at greatest risk. Prior to examinations using CM, patients should be adequately assessed by obtaining thorough medical histories and using simple screening tests. Studies have demonstrated that patients with a history of asthma, allergy, hyperthyroidism, and previous reaction to CM are at risk for severe reactions to iodinated CM. Renal adverse reactions reportedly occur more frequently in patients with pre-existing chronic kidney disease, especially those with diabetic nephropathy. Patients with congestive heart failure, dehydration, older age, and those who use nephrotoxic medications are also at risk for developing contrast-associated nephropathy. The occurrence of adverse events may be further increased in patients with multiple risk factors. As the number of patients undergoing computed tomography procedures continues to increase, it is essential for physicians to be able to identify patients at risk for adverse events of CM. Patient-related risk factors are discussed and simple tools for risk stratification presented.

  6. Audit of co-management and critical care outreach for high risk postoperative patients (The POST audit).

    Science.gov (United States)

    Story, D A; Shelton, A; Jones, D; Heland, M; Belomo, R

    2013-11-01

    Co-management and critical care outreach for high risk surgical patients have been proposed to decrease postoperative complications and mortality. We proposed that a clinical project with postoperative comanagement and critical care outreach, the Post Operative Surveillance Team: (POST), would be associated with decreased hospital length of stay. We conducted a retrospective before (control group) and after (POST group) audit of this hospital program. POST was staffed for four months in 2010 by two intensive care nurses and two senior registrars who conducted daily ward rounds for the first five postoperative days on high risk patients undergoing inpatient general or urological surgery. The primary endpoint was length of hospital stay and secondary endpoints were Medical Emergency Team (MET) calls, cardiac arrests and in-hospital mortality. There were 194 patients in the POST group and 1,185 in the control group. The length of stay in the POST group, median nine days (Inter-quartile range [IQR]: 5 to 17 days), was longer than the control group, median seven days (IQR: 4 to 13 days): difference two days longer (95.0% confidence interval [95.0% CI]: 1 to 3 days longer, P audit found that the POST service was not associated with reduced length of stay. Models of co-management, different to POST, or with different performance metrics, could be tested.

  7. Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index.

    Science.gov (United States)

    Tanaka, Aki; Kamada, Tomoari; Inoue, Kazuhiko; Shiotani, Akiko; Kusunoki, Hiroaki; Manabe, Noriaki; Ito, Masanori; Hata, Jiro; Haruma, Ken

    2011-06-15

    Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa. The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514±2.03) and I-GCa (6.836±2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071±2.07; p=0.0005, pcancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI. Copyright © 2011 Elsevier GmbH. All rights reserved.

  8. Venom Immunotherapy in High-Risk Patients: The Advantage of the Rush Build-Up Protocol.

    Science.gov (United States)

    Rosman, Yossi; Confino-Cohen, Ronit; Goldberg, Arnon

    2017-01-01

    Venom immunotherapy (VIT) is considered to be the gold standard treatment for patients with hymenoptera venom allergy. This treatment induces systemic reactions (SR) in a significant number of patients. To evaluate the outcome of VIT in patients with known risk factors for VIT-induced SR and to compare rush VIT (RVIT) and conventional VIT (CVIT). All of the patients who received VIT and had at least one of the following risk factors were included: current cardiovascular disease, uncontrolled asthma, high basal serum tryptase, current treatment with β-blockers or angiotensin-converting enzyme inhibitors, and age >70 or bee venom. Thirty-five (54.7%) patients underwent RVIT and 29 CVIT. The incidence of patients who developed SR during the build-up phase was similar for RVIT and CVIT (25.7 and 27.5%, respectively; p = 1). However, the incidence of SR per injection was significantly higher in CVIT than in RVIT (5.6 and 2.75%, respectively; p = 0.01). Most reactions (79.1%) were mild, limited to the skin. Most of the patients (92.1%) reached the full maintenance dose of 100 μg. This dose was reached by a significantly larger number of patients receiving RVIT compared to CVIT (100 and 82.7%, respectively; p = 0.01). None of the patients experienced exacerbation of their concurrent chronic disease during VIT. VIT can be performed safely and efficiently in patients with risk factors for immunotherapy. In these patients RVIT appears to be safer and more efficient than CVIT. © 2017 S. Karger AG, Basel.

  9. Identification of high-risk subgroups in very elderly intensive care unit patients

    NARCIS (Netherlands)

    de Rooij, Sophia E.; Abu-Hanna, Ameen; Levi, Marcel; de Jonge, Evert

    2007-01-01

    INTRODUCTION: Current prognostic models for intensive care unit (ICU) patients have not been specifically developed or validated in the very elderly. The aim of this study was to develop a prognostic model for ICU patients 80 years old or older to predict in-hospital mortality by means of data

  10. Procalcitonin increase in early identification of critically ill patients at high risk of mortality

    DEFF Research Database (Denmark)

    Jensen, Jens Ulrik; Heslet, Lars; Jensen, Tom Hartvig

    2006-01-01

    To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.......To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients....

  11. Tailored cognitive-behavioral therapy and exercise training for high-risk patients with fibromyalgia.

    NARCIS (Netherlands)

    Koulil, S. van; Lankveld, W.G.J.M. van; Kraaimaat, F.W.; Helmond, T. van; Vedder, A.; Hoorn, H. van; Donders, R.; Jong, A.J.L. de; Haverman, J.F.; Korff, K.J.; Riel, P.L.C.M. van; Cats, H.A.; Evers, A.W.M.

    2010-01-01

    OBJECTIVE: The treatment of patients with fibromyalgia (FM), a high-prevalence chronic pain condition with a high impact on both patients and society, poses a great challenge to clinicians due to a lack of effective treatments. In view of the large individual variability in outcome, selecting

  12. Percutaneous nephrolithotripsy under assisted local anaesthesia for high risk patients: Is it effective?

    Directory of Open Access Journals (Sweden)

    T.KH. Fathelbab

    2013-12-01

    Conclusion: Our results demonstrated that PNL under local anesthesia with narcotics and sedatives seems to be a satisfying solution for the treatment of a selected group of patients with renal pelvic stones and who have high anesthetic risk. However, additional studies with different groups of patients are required to validate our results.

  13. High risk of ischemic heart disease in patients with lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Starklint, Henrik

    2011-01-01

    To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN).......To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN)....

  14. Social cognition in patients at ultra-high risk for psychosis: What is the relation to social skills and functioning?

    Science.gov (United States)

    Glenthøj, Louise B; Fagerlund, Birgitte; Hjorthøj, Carsten; Jepsen, Jens R M; Bak, Nikolaj; Kristensen, Tina D; Wenneberg, Christina; Krakauer, Kristine; Roberts, David L; Nordentoft, Merete

    2016-09-01

    Patients at ultra-high risk (UHR) for psychosis show significant impairments in functioning. It is essential to determine which factors influence functioning, as it may have implications for intervention strategies. This study examined whether social cognitive abilities and clinical symptoms are associated with functioning and social skills. The study included 65 UHR patients and 30 healthy controls. Social cognitive function, social skills, and a broad range of functioning measures were assessed. The UHR patients demonstrated significant decrements on The Awareness of Social Inferences Task total score (p = .046, d  = .51), and on the CANTAB emotion recognition task total percent correct (p = .023, d  = .54) displaying particular difficulties in negative affect recognition. The patients exhibited significant impairments in social skills measured with the High Risk Social Challenge (p˂.001, d  = 1.05). Aspects of emotion recognition were associated with role functioning and social skill performance. The level of attributional bias was associated with overall functioning, and theory of mind ability was associated with self-reported functioning. Negative symptoms were associated with all measures of functioning (p ≤ .05). Significant impairments in social cognition and social skills were found in UHR patients. The patients' social cognitive function was associated with overall functioning and social skills. Negative symptoms appear to play an important role for functioning. Research is needed to investigate how the relations between social cognition, social skills and functioning develop from the UHR state to the stage of manifest illness. Research into how deficits in social cognition and social skills can be ameliorated in UHR patients is warranted.

  15. Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis.

    Science.gov (United States)

    Padula, Maria Carmela; Schaer, Marie; Armando, Marco; Sandini, Corrado; Zöller, Daniela; Scariati, Elisa; Schneider, Maude; Eliez, Stephan

    2018-01-17

    Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile. In this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach. Our results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS. These results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.

  16. A polyvalent vaccine for high-risk prostate patients: "are more antigens better?"

    DEFF Research Database (Denmark)

    Slovin, Susan F; Ragupathi, Govind; Fernandez, Celina

    2007-01-01

    vaccine of synthetic "self" antigens broke immunologic tolerance against two or more antigens in all 30 vaccinated patients, was safe, but antibody titers against several of the antigens were lower than those seen in individual monovalent trials. No impact on PSA slope was detected. We address......We have shown the immunogenicity and safety of synthetic carbohydrate vaccines when conjugated to the carrier keyhole limpet hemocyanin (KLH) and given with the adjuvant, QS-21, in patients with biochemically relapsed prostate cancer. To determine whether immune response could be further enhanced...... and mixed with QS-21. Eight vaccinations were administered over 13 months. All 30 patients had significant elevations in antibody titers to at least two of the six antigens; 22 patients had increased reactivity with FACS. These serologic responses were lower than that seen previously in patients treated...

  17. Procalcitonin increase in early identification of critically ill patients at high risk of mortality

    DEFF Research Database (Denmark)

    Jensen, Jens Ulrik; Heslet, L; Jensen, TH

    2006-01-01

    OBJECTIVE: To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients. DESIGN: Prospective observational cohort study. SETTING:: Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital......, a tertiary reference hospital in Denmark. PATIENTS: Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit. INTERVENTIONS: Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level. MEASUREMENTS AND MAIN RESULTS: Daily...... in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality...

  18. Femoral Access PCI in a Default Radial Center Identifies High-Risk Patients With Poor Outcomes.

    Science.gov (United States)

    Uddin, Muezz; Bundhoo, Shantu; Mitra, Rito; Ossei-Gerning, Nicholas; Morris, Keith; Anderson, Richard; Kinnaird, Tim

    2015-10-01

    Increasingly the trans-radial route (TRR) is preferred over the trans-femoral route (TFR) for PCI. However, even in high volume default TRR centers a cohort of patients undergo TFR PCI. We examined the demographics, procedural characteristics, and outcomes of patients undergoing PCI via the TF. The patient demographics, procedural data, and outcomes of 5,379 consecutive patients undergoing PCI at a default radial center between 2009 and 2012 were examined. Major bleeding (MB) was classified by ACUITY and BARC definitions. A total of 559 (10.4%) patients underwent PCI via the TFR and 4,820 patients via the TRR (89.6%). Baseline variables associated with TFR were shock, previous CABG, chronic total occlusion intervention, rotablation/laser use, female sex, and renal failure. Sixty-five patients of the TFR cohort (11.6%) experienced MB with 27 (41.5%) being access site related. MB was significantly more frequent than in the radial cohort. The variables independently associated with MB in the TFR cohort were renal failure, acute presentation, shock, and age. In the TFR, patients with MB mortality was high at 30 days (17.2% vs 2.6% for no MB, P default radial PCI center 10% of patients undergo PCI via the femoral artery. These patients have high baseline bleeding risk and undergo complex interventions. As a result the incidence of major bleeding, transfusion and death are high. Alternative strategies are required to optimize outcomes in this select group. © 2015, Wiley Periodicals, Inc.

  19. Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?

    Science.gov (United States)

    Ramaswamy, Vijay; Remke, Marc; Adamski, Jennifer; Bartels, Ute; Tabori, Uri; Wang, Xin; Huang, Annie; Hawkins, Cynthia; Mabbott, Donald; Laperriere, Normand; Taylor, Michael D; Bouffet, Eric

    2016-02-01

    The advent of integrated genomics has fundamentally changed our understanding of medulloblastoma. Although survival differences exist among the 4 principal subgroups, this has yet to be elucidated in a North American cohort of irradiated patients. Ninety-two consecutive patients between the ages of 3 and 17 treated with surgery, craniospinal irradiation, and chemotherapy were identified at the Hospital for Sick Children. Molecular subgrouping was performed using nanoString. Two treatment periods were identified: prior to 2006 as per the protocols of the Children's Oncology Group, and after 2006 per the St Jude Medulloblastoma 03 protocol. Five-year progression-free survival (PFS) over the entire cohort was 0.801 (95% CI: 0.692-0.875) with no significant difference between treatment protocols. Strikingly, we found that Group 4 patients had excellent 5-year PFS of 0.959 (95% CI: 0.744-0.994) for average risk and 0.887 (95% CI: 0.727-0.956) across all Group 4 patients. Group 3 patients had 5-year PFS of 0.733 (95% CI: 0.436-0.891). Sonic hedgehog patients did poorly across both treatment protocols, with 5-year PFS of 0.613 (95% CI: 0.333-0.804), likely owing to a high proportion of TP53 mutated patients in this age group. In a cohort of irradiated patients over 3 years of age, PFS for Group 4 patients was significantly improved compared with initial reports. The impact of subgroup affiliation in these children needs to be assessed in large prospectively treated cooperative protocols to determine if more than just WNT patients can be safely selected for de-escalation of therapy. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Secretory leukocyte protease inhibitor expression and high-risk HPV infection in anal lesions of HIV positive patients

    Science.gov (United States)

    NUOVO, Gerard J.; GRINSZTEJN, Beatriz; FRIEDMAN, Ruth K.; VELOSO, Valdiléa G.; CUNHA, Cynthia B.; COUTINHO, José R.; VIANNA-ANDRADE, Cecilia; OLIVEIRA, Nathalia S.; WOODHAM, Andrew W.; DA SILVA, Diane M.; KAST, W. Martin

    2016-01-01

    Objective The aim of the current study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. Design This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. Methods The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade anal intraepithelial neoplasia (AIN1), high-grade anal intraepithelial neoplasia (AIN2/3), or normal squamous epithelium. Additionally, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. Results Histologically normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2-3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (p=0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI expressing tissues than that in tissues with high SLPI expression (p=0.040). Conclusion Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN. PMID:27149102

  1. Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists.

    Science.gov (United States)

    Cannesson, Maxime; Pestel, Gunther; Ricks, Cameron; Hoeft, Andreas; Perel, Azriel

    2011-08-15

    Several studies have demonstrated that perioperative hemodynamic optimization has the ability to improve postoperative outcome in high-risk surgical patients. All of these studies aimed at optimizing cardiac output and/or oxygen delivery in the perioperative period. We conducted a survey with the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology (ESA) to assess current hemodynamic management practices in patients undergoing high-risk surgery in Europe and in the United States. A survey including 33 specific questions was emailed to 2,500 randomly selected active members of the ASA and to active ESA members. Overall, 368 questionnaires were completed, 57.1% from ASA and 42.9% from ESA members. Cardiac output is monitored by only 34% of ASA and ESA respondents (P = 0.49) while central venous pressure is monitored by 73% of ASA respondents and 84% of ESA respondents (P < 0.01). Specifically, the pulmonary artery catheter is being used much more frequently in the US than in Europe in the setup of high-risk surgery (85.1% vs. 55.3% respectively, P < 0.001). Clinical experience, blood pressure, central venous pressure, and urine output are the most widely indicators of volume expansion. Finally, 86.5% of ASA respondents and 98.1% of ESA respondents believe that their current hemodynamic management could be improved. In conclusion, these results point to a considerable gap between the accumulating evidence about the benefits of perioperative hemodynamic optimization and the available technologies that may facilitate its clinical implementation, and clinical practices in both Europe and the United States.

  2. Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients.

    Science.gov (United States)

    Ely, Scott; Forsberg, Peter; Ouansafi, Ihsane; Rossi, Adriana; Modin, Alvin; Pearse, Roger; Pekle, Karen; Perry, Arthur; Coleman, Morton; Jayabalan, David; Di Liberto, Maurizio; Chen-Kiang, Selina; Niesvizky, Ruben; Mark, Tomer M

    2017-12-01

    Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138 + ) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Audit of the management of patients at high risk of carbapenemase-producing enterobacteriaceae (CPE): Are we ready?

    Science.gov (United States)

    Ratnayake, Lasantha; Harris, Amy; Ko, Doreen; Hawtin, Linda

    2017-11-01

    Incidence of carbapenemase-producing enterobacteriaceae (CPE) in the UK is increasing. In 2013, Public Health England (PHE) published a toolkit to control spread of CPE within healthcare settings. To assess compliance to hospital CPE policy (adapted from PHE) in the identification, isolation and screening of suspected CPE patients. Admission booklets of 150 patients were evaluated to see whether the relevant section had been completed to identify high-risk CPE patients. Where necessary, patients were interviewed or their GPs were contacted to assess their CPE risk. Additionally, 28 patients screened for CPE were audited to assess compliance to screening and isolation. Only 23 patients out of 147 (15.6%) were risk assessed on admission. Risk status of 27 (18.4%) patients could not be assessed due to lack of data. Fifteen patients out of 28 (54%) screened for CPE were identified and isolated on admission. Ten out of 19 patients (53%) had three screens 48 h apart. This audit highlights difficulties in screening based on individual risk factors as the majority of patients were not screened on admission and documentation on isolation and screening was poor. More needs to be done to raise awareness of the requirements for routine assessment, isolation and screening.

  4. Advances in the translational genomics of neuroblastoma

    Science.gov (United States)

    Bosse, Kristopher R.; Maris, John M.

    2015-01-01

    Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus, which has catalyzed not only a more comprehensive understanding of neuroblastoma tumorigenesis, but has also revealed novel oncogenic vulnerabilities that are being leveraged therapeutically. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN amplification, for risk stratification. Given the relative paucity of recurrent activating somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed towards aberrantly regulated pathways in relapsed disease. This review will summarize the current state of knowledge of neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma. PMID:26539795

  5. The ARTICO study: identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke.

    Science.gov (United States)

    Serena, Joaquín; Segura, Tomás; Roquer, Jaume; García-Gil, María; Castillo, José

    2015-03-11

    About 20% of patients with a first ischaemic stroke will experience a new vascular event within the first year. The atherosclerotic burden, an indicator of the extension of atherosclerosis in a patient, has been associated with the risk of new cardiovascular events in the general population. However, no predictive models reliably identify groups at a high risk of recurrence. The ARTICO study prospectively analysed the predictive value for the risk of recurrence of specific atherosclerotic markers. The multicentre ARTICO study included 620 consecutive independent patients older than 60 years suffering from a first non-cardioembolic stroke. We analysed classical stroke risk factors; duplex study of supraaortic trunk including intima-media thickness (IMT) measurement; quantification of internal carotid (ICA) stenosis; number, morphology and surface characteristics of carotid plaques; ankle brachial index (ABI); and the presence of microalbuminuria. Patients were followed up at 6 and 12 months after inclusion. The primary end-point was death or major cardiovascular events. Any vascular event or death at 12 months occurred in 78 (13.8%) patients. In 40 (7.1%) of these the vascular event was a stroke recurrence. Weight, history of diabetes mellitus, history of symptomatic PAD, ABI 50%) were associated with a higher risk of vascular events on follow-up in the bivariate analysis. In the final Cox regression analysis, body mass index (BMI), systolic blood pressure, history of diabetes mellitus, symptomatic PAD (HR, 2.76; 95% CI, 1.10-6.95; p=0.03), and particularly patients with both ICA stenosis >50% and PAD (HR 4.52; 95% CI, 2.14-9.53; p50% nor isolated abnormal ABI remained associated with an increased risk of recurrence in comparison with the whole population. Symptomatic PAD identifies a high risk group of vascular recurrence after a first non-cardioembolic stroke. The associated increased risk was particularly high in patients with both ICA stenosis and either

  6. Attitudes toward anticoagulant treatment among nonvalvular atrial fibrillation patients at high risk of stroke and low risk of bleed

    Directory of Open Access Journals (Sweden)

    Crivera C

    2016-05-01

    Full Text Available Concetta Crivera,1 Winnie W Nelson,1 Jeff R Schein,1 Edward A Witt2 1Janssen Scientific Affairs, LLC, Raritan, 2Kantar Health, Princeton, NJ, USA Background: Atrial fibrillation (AF is associated with an increased risk of stroke. Anticoagulant (AC therapies are effective at treating AF, but carry with them an increased risk of bleed. Research suggests that a large proportion of AF patients who have high risk of stroke and low risk of bleeding are not currently receiving AC treatment. The goal of this study was to understand the reasons why these patients do not engage in this potentially life-saving treatment.Method: Through a self-report online survey, using validated instruments, 1,184 US adults who self-reported a diagnosis of AF were screened for the risk of stroke and bleed. Of these patients, 230 (19.4% were at high risk of stroke, low risk of bleed, and not currently using an AC treatment, and were asked follow-up questions to assess their reasons for nontreatment, attitudes toward treatment, and attitudes toward dosing regimens.Results: The most common reasons patients stopped AC treatment were concerns regarding bleeding (27.8% and other medical concerns (26.6%, whereas the most common reason cited for not being prescribed an AC in the first place was the use of antiplatelet therapy as an alternative (57.1%. In both cases, potentially erroneous decisions regarding perceived stoke and/or bleeding risk were also a factor. Finally, the largest factors regarding attitudes toward treatment and dosing regimen were instructions from an authority figure (eg, physician, pharmacist and ease of use, respectively.Conclusion: Results suggest that many AF patients who are at high risk of stroke but at low risk of bleed may not be receiving AC due to potentially inaccurate beliefs about risk. This study also found that AF patients place trust in physicians above other factors such as cost when making treatment decisions. Increased education of

  7. The reliability of echocardiographic left ventricular wall motion index to identify high-risk patients for multicenter studies

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Gadsbøll, Niels; Quinones, Miguel A

    2006-01-01

    that were screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16-segment LV model. RESULTS: The external echocardiographer systematically found lower values of WMI than the core laboratory. The average...... difference in WMI was 0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI ... overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV-WMI as a useful tool for selecting high-risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment...

  8. Toxoplasma gondii seropositivity and co-infection with TORCH pathogens in high-risk patients from Qatar.

    Science.gov (United States)

    Abu-Madi, Marawan A; Behnke, Jerzy M; Dabritz, Haydee A

    2010-04-01

    Testing of patients who are deemed to be at high risk for TORCH pathogens, e.g., pregnant women, their fetuses, neonates, and acquired immunodeficiency syndrome (AIDS) patients, is important so that specific treatment can be initiated. This study included 1,857 such patients between 2005 and 2008. Logistic regression was used to evaluate factors associated with Toxoplasma gondii seropositivity. Among 823 women of childbearing age, 35.1% and 5.2% tested positive for T. gondii IgG and IgM, respectively. Three infants nationality, positive cytomegalovirus (CMV) and herpes simplex virus (HSV)-1 serostatus, and negative rubella IgG results. The decreasing prevalence of IgM antibodies between 2005 and 2008 suggested that exposure to T. gondii from food or environmental sources declined over this period in Qatar. Population-based studies of newborns would be helpful to accurately estimate incidence of congenital toxoplasmosis.

  9. Radiological changes of bones and soft tissues after irradiation therapy in patients with Wilms' tumor and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Hiroaki; Okabe, Ikuo

    1989-04-01

    Late effects of tele cobalt 60 therapy on bones and soft tissues were studied radiologically in 24 patients with neuroblastoma and Wilms' tumor. The degree of changes in spinal bodies was influenced by the dose of irradiation as well as the age of patients at the time of irradiation. In patients who had 15 to 19 Gy of irradiation at the ages under one year old, a moderate to severe degree of changes was observed. Many patients showed atrophies of iliac bone, ribs, and erector spinae and psoas muscles on the side of the irradiation. In patients who were equal to or over 12 y.o. at the time of the examination, the degree of atrophy of erector spinae muscles on the side of the irradiation was greater than that of the patients who were less than 12 y.o.. Scoliosis was observed in 71% of patients and it had a tendency to aggravate at puberty. Because there was a significant correlation between the degree of scoliosis and the severity of the atrophic erector spinae muscle, the latter was thought to contribute much to the development of the former. At present, all patients are living with no limitation of their daily activities and no one needs medical care. (author).

  10. Identification of the high risk emergency surgical patient: Which risk prediction model should be used?

    Directory of Open Access Journals (Sweden)

    Stephen Stonelake

    2015-09-01

    Conclusions: In the absence of accurate risk scoring tools that can be used on admission to hospital it is not possible to reliably audit the achievement of national standards of care for the ‘high-risk’ patient.

  11. Case Study: Nutritional management of a patient at high risk of ...

    African Journals Online (AJOL)

    2015-08-14

    Aug 14, 2015 ... refeeding (either enteral or parenteral).3 Critically ill patients, such as oncology .... calculated basal energy expenditure.4 Universally, it is recommended ... It was decided to calculate the protein requirement at 20% of total.

  12. Trial of a "credit card" asthma self-management plan in a high-risk group of patients with asthma.

    Science.gov (United States)

    D'Souza, W; Burgess, C; Ayson, M; Crane, J; Pearce, N; Beasley, R

    1996-05-01

    The "credit card" asthma self-management plan provides the adult asthmatic patient with simple guidelines for the self-management of asthma, which are based on the self-assessment of peak expiratory flow rate recordings and symptoms. The study was a trial of the clinical efficacy of the credit card plan in a high-risk group of asthmatic patients. In this "before-and-after" trial, patients discharged from the emergency department of Wellington Hospital, after treatment for severe asthma were invited to attend a series of hospital outpatient clinics at which the credit card plan was introduced. Questionnaires were used to compare markers of asthma morbidity, requirement for emergency medical care, and medication use during the 6-month period before and after intervention with the credit card plan. Of the 30 patients with asthma who attended the first outpatient clinic, 26 (17 women and 9 men) completed the program. In these 26 participants, there was a reduction in both morbidity and requirement for acute medical services: specifically, the proportion waking with asthma more than once a week decreased from 65% to 23% (p = 0.005) and the proportion visiting the emergency department for treatment of severe asthma decreased from 58% to 15% (p = 0.004). The patients attending the clinics commented favorably on the plan, in particular on its usefulness as an educational tool for monitoring and treating their asthma. Although the interpretation of this study is limited by the lack of a randomized control group, the findings are consistent with other evidence that the credit card asthma self-management plan can be an effective and acceptable system for improving asthma care in a high-risk group of adult patients with asthma.

  13. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-01-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  14. Improving Dialysis Adherence for High Risk Patients Using Automated Messaging: Proof of Concept

    OpenAIRE

    Som, A.; Groenendyk, J.; An, T.; Patel, K.; Peters, R.; Polites, G.; Ross, W. R.

    2017-01-01

    Comorbidities and socioeconomic barriers often limit patient adherence and self-management with hemodialysis. Missed sessions, often associated with communication barriers, can result in emergency dialysis and avoidable hospitalizations. This proof of concept study explored using a novel digital-messaging platform, EpxDialysis, to improve patient-to-dialysis center communication via widely available text messaging and telephone technology. A randomized controlled trial was conducted through W...

  15. High risk of renal dysfunction in patients with fulminant type 1 diabetes

    OpenAIRE

    Takahashi, Nobuyuki; Tsujimoto, Tetsuro; Chujo, Daisuke; Kajio, Hiroshi

    2017-01-01

    Abstract Aims/Introduction To compare the incidence rate of renal dysfunction between patients with fulminant type 1 diabetes and those with acute‐onset type 1 diabetes. Materials and Methods The present retrospective cohort study included patients with fulminant type 1 diabetes and acute‐onset type 1 diabetes diagnosed during April 1993 to March 2016 at a national center in Japan. Glycated hemoglobin levels, incidence rates of renal dysfunction defined as an estimated glomerular filtration r...

  16. Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

    Science.gov (United States)

    Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

    2001-05-01

    Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

  17. Role of 131-1 MIBG Therapy in the Treatment of Advanced Neuroblastoma

    International Nuclear Information System (INIS)

    Riad, R.; Kotb, M.; Omar, W.; Zaher, A.; Khalafalla, Kh.; Fawzy, M.; Ebeid, E.; El-Wakil, M.

    2009-01-01

    Introduction: Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most extra-cranial malignant solid tumor of childhood. Many therapeutic strategies has evolved over the last 20 years, based upon work by international cooperative groups and smaller cohort studies. Novel therapies to improve initial disease response and treatment of minimal residual disease are required to improve survival for these children with high-risk neuroblastoma. Radio-labeled MIBG therapy has been tried in the treatment of advanced stage 3 and 4 neuroblastoma in an attempt to improve patients outcome. The use of radio-labeled MIBG to treat neuroblastoma has arisen from the high sensitivity and specificity of in-vivo MIBG imaging for detection of primary and metastatic tumors. Aim of the Work: To determine the impact of MIBG therapy on neuroblastoma patients outcome and its impact on their quality of life. Patients and Methods: Thirty pediatric patients with stage 4 pathologically proven neuroblastoma are included in this study. Eighteen of the study patients (60%) were males and 12 (40%) were females. All the patients had partially responsive tumor to first-line therapy + surgery. 131-1 Mibg doses ranged from 100 to 150 mCi with number of courses ranged from 1-7 according to response and toxicity. Results: Two patients achieved complete remission (CR) and were still disease-free after 64 and 69 months. Nine patients showed partial remission (PR) to 131-1 MIBG, all the nine patients were alive at 16-57 months (mean 30.6 months) among whom seven were alive with stable disease and two patients were alive with progressive disease (PD) at the end of study. Eighteen patients remained stable after 131-I MIBG therapy, among them six were alive with PD and four were alive with stable disease at the end of study, while the remaining eight patients died. The last patient developed PD and died within 15 months. The 5 years event free survival (EPS) was 48.2% and the overall

  18. Expressive writing for high-risk drug dependent patients in a primary care clinic: A pilot study

    Directory of Open Access Journals (Sweden)

    Wedgwood Lucinda

    2006-11-01

    Full Text Available Abstract Background Previous research has shown that expressive writing is beneficial in terms of both physical and emotional health outcomes. This study aimed to investigate the effectiveness and acceptability of a brief expressive writing intervention for high-risk drug dependent patients in a primary care clinic, and to determine the relationship between linguistic features of writing and health outcomes. Methods Participants completed four 15-minute expressive writing tasks over a week, in which they described their thoughts and feelings about a recent stressful event. Self-report measures of physical (SF-12 and psychological health (DASS-21 were administered at baseline and at a two-week follow-up. Fifty-three participants were recruited and 14 (26% completed all measures. Results No statistically significant benefits in physical or psychological health were found, although all outcomes changed in the direction of improvement. The intervention was well-received and was rated as beneficial by participants. The use of more positive emotion words in writing was associated with improvements in depression and stress, and flexibility in first person pronoun use was associated with improvements in anxiety. Increasing use of cognitive process words was associated with worsening depressive mood. Conclusion Although no significant benefits in physical and psychological health were found, improvements in psychological wellbeing were associated with certain writing styles and expressive writing was deemed acceptable by high-risk drug dependent patients. Given the difficulties in implementing psychosocial interventions in this population, further research using a larger sample is warranted.

  19. Liver transplantation may prevent neurodevelopmental deterioration in high-risk patients with urea cycle disorders.

    Science.gov (United States)

    Kido, Jun; Matsumoto, Shirou; Momosaki, Ken; Sakamoto, Rieko; Mitsubuchi, Hiroshi; Endo, Fumio; Nakamura, Kimitoshi

    2017-09-01

    UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living-donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non-LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non-transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Combined PCI and minimally invasive heart valve surgery for high-risk patients.

    Science.gov (United States)

    Umakanthan, Ramanan; Leacche, Marzia; Petracek, Michael R; Zhao, David X; Byrne, John G

    2009-12-01

    Combined coronary artery valvular heart disease is a major cause of morbidity and mortality in the adult patient population. The standard treatment for such disease has been open heart surgery in which coronary artery bypass grafting (CABG) is performed concurrently with valve surgery using a median sternotomy and cardiopulmonary bypass. With the increasing complexity of patients referred to surgery, some patients may prove to be poor surgical candidates for combined valve and CABG surgery. In certain selected patients who fall into this category, valve surgery and percutaneous coronary intervention (PCI) have been considered a feasible alternative. Conventionally, valve surgery is performed in the cardiac surgical operating room, whereas PCI is carried out in the cardiac catheterization laboratory. Separation of these two procedural suites has presented a logistic limitation because it impedes the concomitant performance of both procedures in one setting. Hence, PCI and valve surgery usually have been performed as a "two-stage" procedure in two different operative suites, with the procedures being separated by hours, days, or weeks. Technologic advancements have made possible the construction of a "hybrid" procedural suite that combines the facilities of a cardiac surgical operating room with those of a cardiac catheterization laboratory. This design has enabled the concept of "one-stage" or "one-stop" PCI and valve surgery, allowing both procedures to be performed in a hybrid suite in one setting, separated by minutes. The advantages of such a method could prove to be multifold by enabling a less invasive surgical approach and improving logistics, patient satisfaction, and outcomes in selected patients.

  1. Characteristics of elderly fall patients with baseline mental status: high-risk features for intracranial injury.

    Science.gov (United States)

    Hamden, Khalief; Agresti, Darin; Jeanmonod, Rebecca; Woods, Dexter; Reiter, Mark; Jeanmonod, Donald

    2014-08-01

    Falls are a major cause of morbidity in the elderly. We describe the low-acuity elderly fall population and study which historical and clinical features predict traumatic intracranial injuries (ICIs). This is a prospective observational study of patients at least 65 years old presenting with fall to a tertiary care facility. Patients were eligible if they were at baseline mental status and were not triaged to the trauma bay. At presentation, a data form was completed by treating physicians regarding mechanism and position of fall, history of head strike, headache, loss of consciousness (LOC), and signs of head trauma. Radiographic imaging was obtained at the discretion of treating physicians. Medical records were subsequently reviewed to determine imaging results. All patients were called in follow-up at 30 days to determine outcome in those not imaged. The study was institutional review board approved. A total of 799 patients were enrolled; 79.5% of patients underwent imaging. Twenty-seven had ICIs (3.4%). Fourteen had subdural hematoma, 7 had subarachnoid hemorrhage, 3 had cerebral contusion, and 3 had a combination of injuries. Logistic regression demonstrated 2 study variables that were associated with ICIs: LOC (odds ratio, 2.8; confidence interval, 1.2-6.3) and signs of head trauma (odds ratio, 13.2; confidence interval, 2.7-64.1). History of head strike, mechanism and position, headache, and anticoagulant and antiplatelet use were not associated with ICIs. Elderly fall patients who are at their baseline mental status have a low incidence of ICIs. The best predictors of ICIs are physical findings of trauma to the head and history of LOC. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Management of stroke prevention in canadian patients with atrial fibrillation at moderate to high risk of stroke.

    Science.gov (United States)

    Semchuk, William M; Levac, Brandon; Lara, Muria; Shakespeare, Annabelle; Evers, Thomas; Bolt, Jennifer

    2013-09-01

    Many patients with atrial fibrillation who are at moderate to high risk of stroke do not receive anticoagulation with vitamin K antagonists (VKAs) in accordance with recommendations. To determine (1) why Canadian patients with atrial fibrillation who are potentially eligible for VKA do not receive this therapy, (2) why Canadian primary care physicians discontinue VKA therapy, and (3) why VKA therapy is perceived as difficult to manage. The study involved a chart review of 3 cohorts of patients with nonvalvular atrial fibrillation at moderate to high risk of stroke: patients who had never received VKA treatment (VKA-naive), those whose treatment had been discontinued, and those whose VKA treatment was considered difficult to manage. Charts for 187 patients (mean age 78.4 years, standard deviation 8.9 years) treated at 39 primary care sites were reviewed (62 treatment-naive, 42 with therapy discontinued, and 83 whose therapy was considered difficult to manage). Atrial fibrillation was paroxysmal in 82 (44%) of the patients, persistent in 47 patients (25%), and permanent in 58 (31%). One patient in each of the 3 cohorts had experienced a stroke during the 6 months before study participation. Bleeding events were more frequent among patients who had discontinued VKA therapy than in the other 2 groups. Among those whose therapy was discontinued and those whose therapy was difficult to manage, the mean time in the therapeutic range was 46.3% and 56.4%, respectively. The most common reason for not initiating VKA therapy in treatment-naive patients was the transient nature of atrial fibrillation (25/62 [40%]). The most common reason for discontinuation of VKA therapy was a bleeding event (10/42 [24%]). The presence of a concomitant chronic disease was the most common reason that a patient's therapy was considered difficult to manage (46/83 [55%]). VKA therapy was not initiated or was discontinued for various reasons. Multiple comorbid conditions made management of VKA

  3. The value of FDG-PET/CT in assessing single pulmonary nodules in patients at high risk of lung cancer

    International Nuclear Information System (INIS)

    Kagna, Olga; Solomonov, Anna; Fruchter, Oren; Keidar, Zohar; Bar-Shalom, Rachel; Israel, Ora; Yigla, Mordechai; Guralnik, Luda

    2009-01-01

    To evaluate whether PET/low-dose CT (ldCT) using 18 F-fluorodeoxyglucose (FDG) improves characterization of indeterminate single pulmonary nodules (SPNs) in patients at high risk of lung cancer. Retrospective analysis of 307 patients who underwent FDG-PET/CT for indeterminate SPNs identified 93 (70 men, age range 46-90 years) at high risk of lung cancer (age >40 years, minimum 10 pack-year smokers). SPNs were evaluated for the presence and intensity of FDG avidity and ldCT patterns. The performance of visual and semiquantitative FDG-PET/ldCT algorithms for characterization of SPNs was compared to that of ldCT. Incongruent FDG-PET and ldCT patterns were analyzed for significance in further patient management. Malignancy was diagnosed in 38% patients. FDG avidity defined 33 SPNs as true-positive (TP) and 2 as false-negative (FN) (malignant), and 41 as true-negative (TN) and 17 as false-positive (FP) (benign). For SUVmax of 2.2 (by ROC analysis) there were 27 TP, 8 FN, 48 TN and 10 FP SPNs. LdCT defined 34 TP, 1 FN, 28 TN and 30 FP lesions. Of the FP lesions on ldCT, 60% were FDG-negative. Visual PET/ldCT analysis had a sensitivity of 94%, a specificity of 70%, an accuracy of 80%, a positive predictive value (PPV) of 66%, and a negative predictive value (NPV) of 95% as compared to 77%, 83%, 81%, 73%, 86% for semiquantitative PET/ldCT and 97%, 48%, 66%, 53%, 96% for ldCT, respectively. Both PET/ldCT algorithms had statistically significantly higher specificity and accuracy than ldCT. Semiquantitative analysis showed significantly higher PPV and lower sensitivity and NPV than found with ldCT. A single screening procedure encompassing FDG-PET and ldCT may improve screening for lung cancer in high-risk patients. The significantly improved specificity may potentially reduce FP ldCT results and further unnecessary invasive procedures. (orig.)

  4. Identification of high-risk patients and outcome in chronic thromboembolic pulmonary hypertension

    NARCIS (Netherlands)

    Surie, S.

    2016-01-01

    CTEPH is life threatening, but by means of PEA potentially a curable form of pulmonary hypertension. We studied whether the current detection strategies are sufficient to recognize CTEPH patients, or should a more extensive systematic search be adopted. We concluded that current detection strategies

  5. The cardiac safety of aripiprazole treatment in patients at high risk for torsade

    DEFF Research Database (Denmark)

    Polcwiartek, Christoffer; Sneider, Benjamin; Graff, Claus

    2015-01-01

    RATIONALE: Certain antipsychotics increase the risk of heart rate-corrected QT (QTc) prolongation and consequently Torsades de Pointes (TdP) and sudden cardiac death (SCD). Drug-induced Brugada syndrome (BrS) is also associated with SCD. Most SCDs occur in patients with additional cardiac risk fa...

  6. Evaluation of cervical cerclage for sonographically incompetent cervix in at high risk patients

    International Nuclear Information System (INIS)

    Mustajab, Y.; Jehanzaib, M.

    2008-01-01

    To determine the impact of Cervical Cerclage (CC) for prolongation of pregnancy, maternal and foetal outcome. This Descriptive cross-sectional study was conducted over a period of 2 years patients with history of two or more recurrent midtrimester abortions/preterm deliveries were included. Those with abnormal foetus, vaginal bleeding and choreoamneonitis were excluded. All patients were subjected to transvaginal sonography. Those having sonographic evidence of cervical shortening/dilatation/cone formation were subjected to McDonald suture. Age, parity, period of gestation and aetiological factors were determined. Results were evaluated on the basis of pregnancy prolongation, 14-28 weeks (7.5%), 28-36 weeks (18.7%), 35-37 weeks (73.7%), vaginal delivery in (70%), instrumental (1305%), Caesarean section (17.5%),miscarriage (7.5%), prematurity (18.7%), term delivery (73.7%), prenatal death (13.7%), foetal survival rate (85.1%). No intraoperative complication found. During pregnancy premature rupture of membrane (3.7%), abruption (2.5%), severe pre-eclampsia (3.7%). During labour cervical dystocia was found in (2.5%), foetal distress (8.7%), mal-presentations (6.2%), cervical trauma (3.7%). We determined a high success rate of cervical cerclage on properly selected patients with sonographic evidence of cervical changes. Cervical sonography can be a valuable adjunct to clinical evaluation of these patients. (author)

  7. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

    DEFF Research Database (Denmark)

    Ridker, Paul M; Revkin, James; Amarenco, Pierre

    2017-01-01

    BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In tw...

  8. High risk of ischemic heart disease in patients with lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Starklint, Henrik

    2011-01-01

    Abstract OBJECTIVE: To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN). METHODS: Information on all hospitalizations in Denmark for IHD between 1977 and 2006 was obtained from the Danish National Hospital Regist...

  9. CT diagnosis of neuroblastoma in childhood

    International Nuclear Information System (INIS)

    Li Xin; Zhang Liqun; Yang Zhiyong

    1997-01-01

    Purpose: To evaluate CT in the diagnosis of neuroblastoma in childhood. Materials and methods: Analysis of CT manifestations in 26 cases proved by operation and pathology, including neuroblastoma 21 cases, ganglioneuroblastoma 5 cases. Thorax 7 cases (27%), adrenal gland 16 cases (62%), abdomen-pelvis paravertebral sympathetic chain 3 cases (11%). Bolus injection of contrast medium was given in all cases. Results: Adrenal gland and posterior superior mediastinum were the most common sites for neuroblastoma. 73% of neuroblastoma had calcifications. Neuroblastoma was more commonly calcified than ganglioneuroblastoma. Metastases were also calcified. Degree of enhancement was associated with the type of neuroblastoma. Tumor extension into the spinal canal was seen in 2 cases. 43% neuroblastoma of adrenal directly invaded the kidney in 7 cases. Right lobe of liver was involved in 3 cases, metastases to liver in 1 case, enlargement of lymph nodes 19 cases. Approximately 68% of patients showed increase of urinary Vanilly-mandelic acid (VMA). Preoperative diagnostic accuracy was 92%. Conclusion: CT is recognized as a useful technique for the diagnosis of neuroblastoma. The site of predilection, calcification, lymph node metastases and VMA increase in urine or serum are important basis for diagnosis

  10. Magnitude and consequences of undertreatment of high-risk patients with non-ST segment elevation acute coronary syndromes: insights from the DESCARTES Registry.

    Science.gov (United States)

    Heras, M; Bueno, H; Bardají, A; Fernández-Ortiz, A; Martí, H; Marrugat, J

    2006-11-01

    To analyse intensity of treatment of high-risk patients with non-ST elevation acute coronary syndromes (NSTEACS) included in the DESCARTES (Descripción del Estado de los Sindromes Coronarios Agudos en un Registro Temporal Español) registry. Patients with NSTEACS (n = 1877) admitted to 45 randomly selected Spanish hospitals in April and May 2002 were studied. Patients with ST segment depression and troponin rise were considered high risk (n = 478) and were compared with non-high risk patients (n = 1399). 46.9% of high-risk patients versus 39.5% of non-high-risk patients underwent angiography (p = 0.005), 23.2% versus 18.8% (p = 0.038) underwent percutaneous revascularisation, and 24.9% versus 7.4% (p or = 4, 2-3 and or = 4 (OR 2.87, 95% CI 1.27 to 6.52, p = 0.012). Class I recommended treatments were underused in high-risk patients in the DESCARTES registry. This undertreatment was an independent predictor of death of patients with an acute coronary syndrome.

  11. Management of Stroke Prevention in Canadian Patients with Atrial Fibrillation at Moderate to High Risk of Stroke

    Science.gov (United States)

    Semchuk, William M; Levac, Brandon; Lara, Muria; Shakespeare, Annabelle; Evers, Thomas; Bolt, Jennifer

    2013-01-01

    Background Many patients with atrial fibrillation who are at moderate to high risk of stroke do not receive anticoagulation with vitamin K antagonists (VKAs) in accordance with recommendations. Objective: To determine (1) why Canadian patients with atrial fibrillation who are potentially eligible for VKA do not receive this therapy, (2) why Canadian primary care physicians discontinue VKA therapy, and (3) why VKA therapy is perceived as difficult to manage. Methods: The study involved a chart review of 3 cohorts of patients with nonvalvular atrial fibrillation at moderate to high risk of stroke: patients who had never received VKA treatment (VKA-naive), those whose treatment had been discontinued, and those whose VKA treatment was considered difficult to manage. Results: Charts for 187 patients (mean age 78.4 years, standard deviation 8.9 years) treated at 39 primary care sites were reviewed (62 treatment-naive, 42 with therapy discontinued, and 83 whose therapy was considered difficult to manage). Atrial fibrillation was paroxysmal in 82 (44%) of the patients, persistent in 47 patients (25%), and permanent in 58 (31%). One patient in each of the 3 cohorts had experienced a stroke during the 6 months before study participation. Bleeding events were more frequent among patients who had discontinued VKA therapy than in the other 2 groups. Among those whose therapy was discontinued and those whose therapy was difficult to manage, the mean time in the therapeutic range was 46.3% and 56.4%, respectively. The most common reason for not initiating VKA therapy in treatment-naive patients was the transient nature of atrial fibrillation (25/62 [40%]). The most common reason for discontinuation of VKA therapy was a bleeding event (10/42 [24%]). The presence of a concomitant chronic disease was the most common reason that a patient’s therapy was considered difficult to manage (46/83 [55%]). Conclusions: VKA therapy was not initiated or was discontinued for various reasons

  12. Comparison of benazepril plus amlodipine or hydrochlorothiazide in high-risk patients with hypertension and coronary artery disease.

    Science.gov (United States)

    Bakris, George; Briasoulis, Alexandros; Dahlof, Bjorn; Jamerson, Kenneth; Weber, Michael A; Kelly, Roxzana Y; Hester, Allen; Hua, Tsushung; Zappe, Dion; Pitt, Bertram

    2013-07-15

    Combination therapy with benazepril 40 mg and amlodipine 10 mg (B+A) has been shown to be more effective than benazepril 40 mg and hydrochlorothiazide (HCTZ) 25 mg (B+H) in reducing cardiovascular (CV) events in high-risk patients with stage 2 hypertension with similar blood pressure reductions. In the present post hoc analysis, we evaluated whether B+A is more effective than B+H for reducing CV events in patients with known coronary artery disease (CAD) at baseline in a subgroup analysis of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study. The main trial randomized 11,506 patients. Of those, 5,744 received B+A and 5,762 received B+H. Of the 11,506 patients, 5,314 (46%) were classified as having CAD at baseline. The mean patient follow-up period was 35.7 months for the B+A group and 35.6 months for the B+H group. The primary end point was the interval to the first event of composite CV morbidity and mortality. At baseline, significant differences were present between the 5,314 with CAD and the 6,192 without CAD. The patients with CAD had a lower systolic blood pressure and heart rate, a lower incidence of diabetes, and greater incidence of dyslipidemia. However, no baseline differences were found between the randomized B+A and B+H groups. In the patients with CAD, an 18% reduction occurred in the hazard ratio for CV events (primary end point) with B+A versus B+H (p = 0.0016). In a prespecified secondary analysis of the composite end point, including only CV death, myocardial infarction, and stroke, the hazard ratio in the patients with CAD was reduced by 25% (p = 0.0033) in the B+A group compared with the B+H group. B+A was more effective than B+H at comparable blood pressure reductions for reducing CV events in patients, regardless of the presence of CAD. In conclusion, our findings suggest that the combination of B+A should be preferentially used for older patients with high-risk

  13. Hybrid endovascular treatment of an aortic root and thoracoabdominal aneurysm in a high-risk patient with Marfan syndrome.

    Science.gov (United States)

    Gelpi, Guido; Mazzaccaro, Daniela; Romagnoni, Claudia; Contino, Monica; Antona, Carlo

    2013-05-01

    This report describes the hybrid endovascular treatment of an aortic root dilatation and a thoracoabdominal aneurysm in a high-risk patient with Marfan syndrome. A 50-year-old male, in hemodialysis for polycystic kidney and polycystic liver, was referred to our department for aortic root dilatation of 5 cm and a 6.3-cm thoracoabdominal aneurysm . He already underwent surgical repair of abdominal aortic aneurysm 10 years ago, complicated by pseudoaneurysm of the proximal anastomosis that had been treated in another center, with an endoprosthesis. The patient underwent aortic root replacement, aortic valve sparing operation, and rerouting of the superior mesenteric artery and celiac trunk to the ascending aorta. The thoracoabdominal aneurysm was excluded with an endoprosthesis few days after the surgical step. The 12-month computed tomography scan confirmed the complete exclusion of the thoracoabdominal aneurysm.

  14. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt

    2010-01-01

    BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...

  15. Definition and Validation of “Favorable High-Risk Prostate Cancer”: Implications for Personalizing Treatment of Radiation-Managed Patients

    International Nuclear Information System (INIS)

    Muralidhar, Vinayak; Chen, Ming-Hui; Reznor, Gally; Moran, Brian J.; Braccioforte, Michelle H.; Beard, Clair J.; Feng, Felix Y.; Hoffman, Karen E.; Choueiri, Toni K.; Martin, Neil E.; Sweeney, Christopher J.; Trinh, Quoc-Dien; Nguyen, Paul L.

    2015-01-01

    Purpose: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. Methods and Materials: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen 20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer–specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Results: Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268). Conclusions: Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.

  16. Definition and Validation of “Favorable High-Risk Prostate Cancer”: Implications for Personalizing Treatment of Radiation-Managed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Muralidhar, Vinayak [Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts (United States); Chen, Ming-Hui [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Reznor, Gally [Center for Surgery and Public Health, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Moran, Brian J.; Braccioforte, Michelle H. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Choueiri, Toni K. [Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Martin, Neil E. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Sweeney, Christopher J. [Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Department of Urology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2015-11-15

    Purpose: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. Methods and Materials: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer–specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Results: Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268). Conclusions: Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.

  17. [The change of vaginal lactobacillus in patients with high-risk human papillomavirus infection].

    Science.gov (United States)

    Zhou, D; Cui, Y; Wu, F L; Deng, W H

    2016-07-05

    To study the distribution characteristics of lactobacillus in the vaginal mucosa of patients with HPV infection. The planting density of lactobacillus in vaginal secretions of 95 cases with HPV16/18 infection and 90 cases of normal women of childbearing age were observed by oil microscope. And the strains of vaginal lactobacilli in two groups were analyzed using species-specific polymerase chain reaction (Species-specific PCR) and the distribution of vaginal lactobacilli in patients with HPV16/18 infection were investigated. In HPV16/18 infective groups, the planting density of lactobacillus in the vaginal mucosa was 104 (68-186)/HP. It was significantly lower than that of the normal group (234 (161-326)/HP, Pinfection group (Pinfection is associated with the decreased number of lactobacillus and the imbalance of vaginal flora; Lactobacillus iners, lactobacillus crispatus, and lactobacillus gasseri may play a key role in maintaining the vaginal micro ecological environment.

  18. Application of an artificial intelligence program to therapy of high-risk surgical patients.

    Science.gov (United States)

    Patil, R S; Adibi, J; Shoemaker, W C

    1996-11-01

    We developed an artificial intelligence program from a large computerized database of hemodynamic and oxygen transport measurements together with prior studies defining survivors' values, outcome predictors, and a branched-chain decision tree. The artificial intelligence program was then tested on the data of 100 survivors and 100 nonsurvivors not used for the development of the program or other analyses. Using the predictor as a surrogate outcome measure, the therapy recommended by the program improved the predicted outcome 3.16% per therapeutic intervention while the actual therapy given increased outcome 1.86% in surviving patients; the artificial intelligence-recommended therapy improved outcome 7.9% in nonsurvivors, while the actual therapy given increased predicted outcome -0.29% in nonsurvivors (p < .05). There were fewer patients whose predicted outcome decreased after recommended treatment (14%) than after the actual therapy given (37%). Review of therapy recommended by the program did not reveal instances of inappropriate or potentially harmful recommendations.

  19. Combined duodenal and pancreatic major trauma in high risk patients: can a partial reconstruction be safe?

    Science.gov (United States)

    Toro, A; Li Destri, G; Mannino, M; Arcerito, M C; Ardiri, A; Politi, A; Bertino, G; Di Carlo, I

    2014-04-01

    Pancreatic trauma is an uncommon injury, occurring in only about 0.2% of blunt abdominal injuries, while duodenal injuries represent approximately 4% of all blunt abdominal injuries. When trauma of the pancreas and duodenum do not permit reparation, pancreatoduodenectomy (PD) is mandatory. In the reconstructive phase, the use of ductal ligation as an alternative to standard pancreaticojejunostomy has been reported by some authors. We report a case of polytrauma with pancreatic and duodenal injury in which the initial diagnosis failed to recognize the catastrophic duodenal and pancreatic situation. The patient was submitted for PD and the pancreatic stump was abandoned in the abdominal cavity after main pancreatic ductal ligation. This technique can minimize the morbidity and mortality of PD in patients with other organs or apparatus involved severely and extensively in trauma.

  20. Transfusion algorithms and how they apply to blood conservation: the high-risk cardiac surgical patient.

    Science.gov (United States)

    Steiner, Marie E; Despotis, George John

    2007-02-01

    Considerable blood product support is administered to the cardiac surgery population. Due to the multifactorial etiology of bleeding in the cardiac bypass patient, blood products frequently and empirically are infused to correct bleeding, with varying success. Several studies have demonstrated the benefit of algorithm-guided transfusion in reducing blood loss, transfusion exposure, or rate of surgical re-exploration for bleeding. Some transfusion algorithms also incorporate laboratory-based decision points in their guidelines. Despite published success with standardized transfusion practices, generalized change in blood use has not been realized, and it is evident that current laboratory-guided hemostasis measures are inadequate to define and address the bleeding etiology in these patients.

  1. Liberal or restrictive transfusion in high-risk patients after hip surgery.

    Science.gov (United States)

    Carson, Jeffrey L; Terrin, Michael L; Noveck, Helaine; Sanders, David W; Chaitman, Bernard R; Rhoads, George G; Nemo, George; Dragert, Karen; Beaupre, Lauren; Hildebrand, Kevin; Macaulay, William; Lewis, Courtland; Cook, Donald Richard; Dobbin, Gwendolyn; Zakriya, Khwaja J; Apple, Fred S; Horney, Rebecca A; Magaziner, Jay

    2011-12-29

    The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

  2. Clinical Use of Ultrasensitive Cardiac Troponin I Assay in Intermediate- and High-Risk Surgery Patients

    Directory of Open Access Journals (Sweden)

    Flávia Kessler Borges

    2013-01-01

    Full Text Available Background. Cardiac troponin levels have been reported to add value in the detection of cardiovascular complications in noncardiac surgery. A sensitive cardiac troponin I (cTnI assay could provide more accurate prognostic information. Methods. This study prospectively enrolled 142 patients with at least one Revised Cardiac Risk Index risk factor who underwent noncardiac surgery. cTnI levels were measured postoperatively. Short-term cardiac outcome predictors were evaluated. Results. cTnI elevation was observed in 47 patients, among whom 14 were diagnosed as having myocardial infarction (MI. After 30 days, 16 patients had major adverse cardiac events (MACE. Excluding patients with a final diagnosis of MI, predictors of cTnI elevation included dialysis, history of heart failure, transoperative major bleeding, and elevated levels of pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP. Maximal cTnI values showed the highest sensitivity (94%, specificity (75%, and overall accuracy (AUC 0.89; 95% CI 0.80–0.98 for postoperative MACE. Postoperative cTnI peak level (OR 9.4; 95% CI 2.3–39.2 and a preoperative NT-proBNP level ≥917 pg/mL (OR 3.47; 95% CI 1.05–11.6 were independent risk factors for MACE. Conclusions. cTnI was shown to be an independent prognostic factor for cardiac outcomes and should be considered as a component of perioperative risk assessment.

  3. Identification of high-risk patients with aplastic anaemia in selection for allogeneic 0one-marrow transplantation.

    Science.gov (United States)

    Lohrmann, H P; Kern, P; Niethammer, D; Heimpel, H

    1976-09-25

    Of 75 patients with asplastic anaemia treated between 1968 and 1975, 33 were retrospectively considered as potential candidates for allogenegic bone-marrow transplantation on the basis of their age and severity of marrow failure. The prognosis of these patients with conservative treatment was assessed from parameters obtained at the time of the initial diagnosis. Initial peripheral-blood granulocyte or platelet concentrations were not of porgnostic value. In contrast, initial reticulocyte concentrations, allowed separation of the patients into two groups with poor and good prognosis. Low initial reticulocyte concentrations (less than 10 000/mu1) indicated those patients at extremely high risk of succumbing to their marrow aplasia (there were no survivors 36 months after disgnosis). In contrast, 75% of those patients with more than 10 000 reticulocytes per mu1 at diagnosis survived for 3 years. Initial peripheral-blood reticulocyte concentrations thus appear to indicate the extent of the marrow failure in aplastic anaemia more accurately than granulocytes or platelets. Low initial reticulocyte concentrations may indicate, among patients with severe aplastic anaemia, those for whom allogeneic bone-marrow transplantation should be seriously considered; patients with higher initial reticulocyte concentrations may benefit from conservation treatment.

  4. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  5. A systematic review of basic life support training targeted to family members of high-risk cardiac patients.

    Science.gov (United States)

    Cartledge, Susie; Bray, Janet E; Leary, Marion; Stub, Dion; Finn, Judith

    2016-08-01

    Targeting basic life support (BLS) training to bystanders who are most likely to witness an out of hospital cardiac arrest (OHCA) is an important public health intervention. We performed a systematic review examining the evidence of the effectiveness of providing BLS training to family members of high-risk cardiac patients. A search of Ovid MEDLINE, CINAL, EMBASE, Informit, Cochrane Library, Web of Science, Scopus, ERIC and ProQuest Dissertations and Theses Global was conducted. We included all studies training adult family members of high-risk cardiac patients regardless of methods used for cardiopulmonary resuscitation (CPR) or BLS training. Two reviewers independently extracted data and evaluated the quality of evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We included 26 of the 1172 studies identified. The majority of studies were non-randomised controlled trials (n=18), of very low to moderate quality. Currently, there is insufficient evidence to indicate a benefit of this intervention for patients; largely because of low numbers of OHCA events and high loss to follow-up. However, the majority of trained individuals were able to competently perform BLS skills, reported a willingness to use these skills and experienced lower anxiety. Whilst there is no current evidence for improvement in patient outcomes from targeted BLS training for family members, this group are willing and capable to learn these skills. Future research may need to examine longer periods of follow-up using alternate methods (e.g. cardiac arrest registries), and examine the effectiveness of training in the modern era. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Universal screening for alcohol misuse in acute medical admissions is feasible and identifies patients at high risk of liver disease.

    Science.gov (United States)

    Westwood, Greta; Meredith, Paul; Atkins, Susan; Greengross, Peter; Schmidt, Paul E; Aspinall, Richard J

    2017-09-01

    Many people who die from alcohol related liver disease (ARLD) have a history of recurrent admissions to hospital, representing potential missed opportunities for intervention. Universal screening for alcohol misuse has been advocated but it is not known if this is achievable or effective at detecting individuals at high risk of ARLD. We systematically screened all admissions to the Acute Medical Unit (AMU) of a large acute hospital using an electronic data capture system in real time. Patients at an increasing risk of alcohol harm were referred for either brief intervention (BI) or further assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were recorded on admission diagnoses, alcohol unit consumption, previous attendances, previous admissions, length of stay and mortality. Between July 2011 and March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening. Of these, 1,122 (2.3%) were classified as "increasing", and 1,921 (4.0%) as "high" risk of alcohol harm. High risk patients had more hospital admissions in the three previous years (average 4.74) than the low (3.00) and increasing (2.92) risk groups (prisk patients also had more frequent emergency department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81) groups (prisk group were seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40. Compared to the other groups, high risk patients had a distinct profile of admissions with the most common diagnoses being mental health disorders, gastro-intestinal bleeding, poisoning and liver disease. Universal screening of admissions for alcohol misuse is feasible and identifies a cohort with frequent ED attendances, recurrent admissions and an elevated risk of ARLD. An additional group of patients at an increasing risk of alcohol harm can be identified in a range of common presentations. These patients can be

  7. Outcome of intraoperative goal-directed therapy using Vigileo/FloTrac in high-risk patients scheduled for major abdominal surgeries: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mohammed A. Elgendy

    2017-07-01

    Conclusion: The applied protocol for intraoperative GDT provided significant reduction of PO morbidities, ICU and hospital LOS but couldn‘t significantly reduce mortality rates in high risk patients scheduled for major abdominal surgeries.

  8. A predictive model to identify patients with suspected acute coronary syndromes at high risk of cardiac arrest or in-hospital mortality: An IMMEDIATE Trial sub-study

    Directory of Open Access Journals (Sweden)

    Madhab Ray

    2015-12-01

    Conclusions: The multivariable predictive model developed identified patients with very early ACS at high risk of cardiac arrest or death. Using this model could assist treating those with greatest potential benefit from GIK.

  9. Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

    Science.gov (United States)

    Lee, Suh-Young; Yang, Min Suk; Choi, Young-Hoon; Park, Chang Min; Park, Heung-Woo; Cho, Sang Heon; Kang, Hye-Ryun

    2017-03-01

    Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Effects of extended-release niacin with laropiprant in high-risk patients

    DEFF Research Database (Denmark)

    Landray, Martin J; Haynes, Richard; Hopewell, Jemma C

    2014-01-01

    BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) choleste......-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.)....

  11. Iodinated contrast media and patients with high-risk kidneys. Aiming at rational prevention

    International Nuclear Information System (INIS)

    Fontaine, B.; Frouge, C.; Gagey, N.

    1994-01-01

    Acute renal failure induced by iodinated contrast media (CM) accounts for about 10% of all hospital cases of renal failure, especially in azotemic patients. The specific anatomy and physiology of the inner medulla renalis render it particularly sensitive to even a moderate reduction in blood supply. Renal function will be estimated by measuring serum creatinine levels, before and within 72 hours after administration of the iodinated contrast medium. Hypovolaemia, diabetes mellitus-induced microangiopathy, nephrotoxic drugs and especially dehydratation may provoke renal accidents. Proper hydration, choosing a low osmolality medium and adequately spacing exposures to CM are elementary measures to be adopted to prevent renal failure. (authors)

  12. Transversus abdominis plane block for an emergency laparotomy in a high-risk, elderly patient

    Directory of Open Access Journals (Sweden)

    Surekha S Patil

    2010-01-01

    Full Text Available A 72-year-old male patient with gall bladder perforation and small intestinal obstruction from impacted gall stone was posted for emergency laparotomy. He had congestive heart failure, severe hypertension at admission and history of multiple other coexisting diseases. On admission, he developed pulmonary oedema from systolic hypertension which was controlled by ventilatory support, nitroglycerine and furosemide. Preoperative international normalized ratio was 2.34 and left ventricular ejection fraction was only 20%. Because of risk of exaggerated fall in blood pressure during induction of anaesthesia (general or neuraxial, a transversus abdominis plane block via combined Petit triangle and subcostal technique was administered and supplemented with Propofol sedation.

  13. High-Risk Coronary Plaques Complicated with Acute Coronary Syndrome in Young Patients

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    Opincariu Diana

    2017-06-01

    Full Text Available Coronary computed tomography angiography (CCTA has evolved notably over the last decade, gaining an increased amount of temporo-spatial resolution in combination with decreased radiation exposure. The importance of CCTA is emerging especially in vulnerable and young patients who might not have developed a viable collateral vascular network to sustain the circulation to an infarction area during a major adverse coronary event. There are a few well-known markers by which a vulnerable plaque can be assessed and that can predict the subsequent events of sudden myocardial ischemia, such as an increased positive remodeling index (cut-off >1.4, low-attenuation plaque (cut-off 0.7, and napkin-ring sign (NRS. This manuscript presents a series of 3 clinical cases of young patients experiencing symptoms and signs of myocardial ischemia who underwent CCTA in order to assess the composition and functional characteristics of atherosclerotic plaques and their repercussion in developing an acute coronary syndrome.

  14. MR imaging of bone marrow metastasis in patients with neuroblastoma. Comparison between mass-screened cases and clinically detected cases

    International Nuclear Information System (INIS)

    Kanegawa, Kimio; Akasaka, Yoshinori; Kawasaki, Ryuta; Nishiyama, Shoji; Mabuchi, Osamu; Muraji, Toshihiro

    1999-01-01

    Seventy-six patients with neuroblastoma who underwent bone marrow MRI were divided into two groups: the first group consisted of patients detected by mass screening (M group, n=55), and the second group of patients detected clinically (non-M group, n=21). Bone marrow metastasis was morphologically classified into two types, nodular type and diffuse type. We studied the incidence of bone marrow metastasis, relationship between the patterns of bone marrow metastasis and the presence of bone metastasis, and morphological changes of bone marrow metastasis after chemotherapy. In M group, the incidence of bone marrow metastasis was 7.3% (4 patients) and the patterns of bone marrow metastases were all nodular type not accompanied with bone metastasis and disappeared after chemotherapy. In non-M group, the incidence of bone marrow metastasis was 52.4% (11 patients). Bone marrow metastases had both patterns of metastasis. Forty-five per cent of diffuse type of bone marrow metastasis were accompanied with bone metastasis. All bone marrow metastases disappeared after chemotherapy, but in one of 11, there was recurrence of bone marrow metastasis. (author)

  15. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P

    2013-01-01

    Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?......Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?...

  16. Ultrasound-guided transversus abdominis plane block in combination with ilioinguinal-iliohypogastric block in a high risk cardiac patient for inguinal hernia repair: a case report

    OpenAIRE

    BARISIN, STJEPAN; DUZEL, VIKTOR; SAKIC, LIVIJA

    2015-01-01

    Background and Purpose: A high risk cardiac patient, ASA IV, was planned for inguinal hernia repair. Since general anaesthesia presented a high risk, anaesthesia was conducted with a transversus abdominis plane (TAP) in combination with ilioinguinal-iliohypogastric (ILIH) block. Material and Methods: A 70-year old male patient with severe CAD and previous LAD PTCA, AVR, in situ PPM and severe MR and TR 3+, was planned for elective inguinal hernia repair. The preoperative ECH...

  17. Targeting neuroblastoma stem cells with retinoic acid and proteasome inhibitor.

    Directory of Open Access Journals (Sweden)

    Barbara Hämmerle

    Full Text Available Neuroblastma cell lines contain a side-population of cells which express stemness markers. These stem-like cells may represent the potential underlying mechanism for resistance to conventional therapy and recurrence of neuroblastoma in patients.To develop novel strategies for targeting the side-population of neurobastomas, we analyzed the effects of 13-cis-retinoic acid (RA combined with the proteasome inhibitor MG132. The short-term action of the treatment was compared with effects after a 5-day recovery period during which both chemicals were withdrawn. RA induced growth arrest and differentiation of SH-SY5Y and SK-N-BE(2 neuroblastoma cell lines. Inhibition of the proteasome caused apoptosis in both cell lines, thus, revealing the critical role of this pathway in the regulated degradation of proteins involved in neuroblastoma proliferation and survival. The combination of RA with MG132 induced apoptosis in a dose-dependent manner, in addition to promoting G2/M arrest in treated cultures. Interestingly, expression of stem cell markers such as Nestin, Sox2, and Oct4 were reduced after the recovery period of combined treatment as compared with untreated cells or treated cells with either compound alone. Consistent with this, neurosphere formation was significantly impaired by the combined treatment of RA and MG132.Given that stem-like cells are associated with resistant to conventional therapy and are thought to be responsible for relapse, our results suggest that dual therapy of RA and proteasome inhibitor might be beneficial for targeting the side-population of cells associated residual disease in high-risk neuroblastoma.

  18. 36. Anesthesia for high risk patients undergoing percutaneous mitral valve repair with the mitraclip system in the catheterization laboratory

    Directory of Open Access Journals (Sweden)

    R. Soliman

    2016-07-01

    Full Text Available MitraClip system implantation is used inhigh-risk patients with severe mitral regurgitation.anesthetic management for mitral clip implantation. The study included 34patients scheduled for MitraClip implantations in the catheterization laboratory. An arterial line and central venous line were inserted under local anesthesia before induction. Epinephrine was started before induction and milrinone infusion was started after induction. The anesthetic technique for induction and maintenance was the same for all patients. All patients were hemodynamically stable intra- and postoperatively. The intervention was successful in 33 cases and aborted in one case because of severe posteromedial leaflet tethering. The epinephrine and milrinone were weaned and all patients were extubated, except, one case mortality happened within the first 8 hours postoperatively. Percutaneous mitral valve repair with MitraClip implantation is a successful alternative in high-risk patients with symptomatic severe mitral regurgitation. Starting epinephrine before anesthetic induction and milrinone infusion induction resulted in decreased pulmonary artery pressure, increased ejection fraction and maintained arterial blood pressure during procedure inspite of worse preoperative conditions.

  19. Adherence to wearing prescription custom-made footwear in patients with diabetes at high risk for plantar foot ulceration.

    Science.gov (United States)

    Waaijman, Roelof; Keukenkamp, Renske; de Haart, Mirjam; Polomski, Wojtek P; Nollet, Frans; Bus, Sicco A

    2013-06-01

    Prescription custom-made footwear can only be effective in preventing diabetic foot ulcers if worn by the patient. Particularly, the high prevalence of recurrent foot ulcers focuses the attention on adherence, for which objective data are nonexisting. We objectively assessed adherence in patients with high risk of ulcer recurrence and evaluated what determines adherence. In 107 patients with diabetes, neuropathy, a recently healed plantar foot ulcer, and custom-made footwear, footwear use was measured during 7 consecutive days using a shoe-worn, temperature-based monitor. Daily step count was measured simultaneously using an ankle-worn activity monitor. Patients logged time away from home. Adherence was calculated as the percentage of steps that prescription footwear was worn. Determinants of adherence were evaluated in multivariate linear regression analysis. Mean ± SD adherence was 71 ± 25%. Adherence at home was 61 ± 32%, over 3,959 ± 2,594 steps, and away from home 87 ± 26%, over 2,604 ± 2,507 steps. In 35 patients with low adherence (footwear were significantly associated with higher adherence. The results show that adherence to wearing custom-made footwear is insufficient, particularly at home where patients exhibit their largest walking activity. This low adherence is a major threat for reulceration. These objective findings provide directions for improvement in adherence, which could include prescribing specific off-loading footwear for indoors, and they set a reference for future comparative research on footwear adherence in diabetes.

  20. Gut-sparing treatment of urinary tract infection in patients at high risk of Clostridium difficile infection.

    Science.gov (United States)

    Staley, Christopher; Vaughn, Byron P; Graiziger, Carolyn T; Sadowsky, Michael J; Khoruts, Alexander

    2017-02-01

    Recipients of faecal microbiota transplantation (FMT) in treatment of recurrent Clostridium difficile infection (RCDI) remain at markedly increased risk of re-infection with C. difficile with new antibiotic provocations. Urinary tract infections (UTIs) are common indications for antibiotics in these patients, often resulting in C. difficile re-infection. We present a case series of 19 patients treated with parenteral aminoglycosides for UTI following FMT for RCDI. A 3 day outpatient regimen of once-daily intramuscular administration of gentamicin was used to treat 18 consecutive FMT recipients with uncomplicated UTI. One other patient was treated for a complicated UTI with intravenous amikacin. Profiling of 16S rRNA genes was used to track changes in faecal microbial community structure during this regimen in three patients. The protocol was highly effective in treating UTI symptoms. None of the patients suffered a re-infection with C. difficile The faecal microbial communities remained undisturbed by treatment with intramuscular administration of gentamicin. Despite falling out of favour in recent years, aminoglycoside antibiotics given parenterally have the advantage of minimal penetration into the gut lumen. A brief (3 day) course of parenteral gentamicin was safe and effective in curing UTI in patients at high risk of C. difficile infection without perturbing their gut microbiota. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    Directory of Open Access Journals (Sweden)

    Harris Nathan

    2008-12-01

    Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

  2. Managing high-risk patients: the Mass General care management programme

    Directory of Open Access Journals (Sweden)

    Dennis L Kodner

    2015-09-01

    Full Text Available The Massachusetts General Care Management Program (Mass General CMP or CMP was designed as a federally supported demonstration to test the impact of intensive, practice-based care management on high-cost Medicare fee-for-service (FFS beneficiaries—primarily older persons—with multiple hospitalisations and multiple chronic conditions. The Massachusetts General Care Management Program operated over a 6-year period in two phases (3 years each. It started during the first phase at Massachusetts General Hospital, a major academic medical centre in Boston, Massachusetts in collaboration with Massachusetts General Physicians Organisation. During the second phase, the programme expanded to two more affiliated sites in and around the Boston area, including a community hospital, as well as incorporated several modifications primarily focused on the management of transitions to post-acute care in skilled nursing facilities. At the close of the demonstration in July 2012, Mass General Massachusetts General Care Management Program became a component of a new Pioneer accountable care organisation (ACO. The Massachusetts General Care Management Program is focused on individuals meeting defined eligibility criteria who are offered care that is integrated by a case manager embedded in a primary care practice. The demonstration project showed substantial cost savings compared to fee-for-service patients served in the traditional Medicare system but no impact on hospital readmissions. The Massachusetts General Care Management Program does not rest upon a “whole systems” approach to integrated care. It is an excellent example of how an innovative care co-ordination programme can be implemented in an existing health-care organisation without making fundamental changes in its underlying structure or the way in which direct patient care services are paid for. The accountable care organisation version of the Massachusetts General Care Management Program

  3. High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

    Science.gov (United States)

    Wadhwa, A; Al Nahhas, M F; Dierkhising, R A; Patel, R; Kashyap, P; Pardi, D S; Khanna, S; Grover, M

    2016-09-01

    Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. To determine the incidence and risk factors for PI-IBS following CDI. A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI. © 2016 John Wiley & Sons Ltd.

  4. Prevalence of Mycoplasma genitalium and other sexually transmitted infections causing urethritis among high-risk heterosexual male patients in Estonia.

    Science.gov (United States)

    Tjagur, Stanislav; Mändar, Reet; Punab, Margus

    2018-02-01

    We aimed to evaluate the prevalence of sexually transmitted infections (STI, including Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis) among high-risk heterosexual male patients and to clarify their potency to cause complaints and inflammation. The study group included 825 men (18.0-49.5 y) consulting andrologist at Tartu University Hospital (Estonia) due to subjectively perceived risk of STI. Patients completed STI risk behaviour questionnaire. First voided urine was analysed for white blood cells and STIs. In total 193 (23.4%) patients were positive for one or multiple STI. The prevalence of C. trachomatis, M. genitalium, N. gonorrhoeae, T. vaginalis and combined STI was 14.3%, 4.4%, 2.7%, 0.7% and 1.3%, respectively. N. gonorrhoeae had the highest potency to generate inflammatory reaction in first voided urine (100%) followed by C. trachomatis (72.0%), M. genitalium (63.9%) and T. vaginalis (33.3%). N. gonorrhoeae and T. vaginalis caused the highest mean number of complaints while half of T. vaginalis cases and nearly fifth of M. genitalium and C. trachomatis cases were asymptomatic. C. trachomatis has the highest prevalence among Estonian high-risk men but M. genitalium holds an important second place. Prevalence of combined STIs is low. N. gonorrhoeae has the highest potency to generate urethral inflammation followed by C. trachomatis and M. genitalium. The highest number of complaints is also associated with N. gonorrhoeae while half of T. vaginalis cases and nearly a fifth of M. genitalium and C. trachomatis cases are asymptomatic.

  5. Optimizing Prophylactic CPAP in Patients Without Obstructive Sleep Apnoea for High-Risk Abdominal Surgeries: A Meta-regression Analysis.

    Science.gov (United States)

    Singh, Preet Mohinder; Borle, Anuradha; Shah, Dipal; Sinha, Ashish; Makkar, Jeetinder Kaur; Trikha, Anjan; Goudra, Basavana Gouda

    2016-04-01

    Prophylactic continuous positive airway pressure (CPAP) can prevent pulmonary adverse events following upper abdominal surgeries. The present meta-regression evaluates and quantifies the effect of degree/duration of (CPAP) on the incidence of postoperative pulmonary events. Medical databases were searched for randomized controlled trials involving adult patients, comparing the outcome in those receiving prophylactic postoperative CPAP versus no CPAP, undergoing high-risk abdominal surgeries. Our meta-analysis evaluated the relationship between the postoperative pulmonary complications and the use of CPAP. Furthermore, meta-regression was used to quantify the effect of cumulative duration and degree of CPAP on the measured outcomes. Seventy-three potentially relevant studies were identified, of which 11 had appropriate data, allowing us to compare a total of 362 and 363 patients in CPAP and control groups, respectively. Qualitatively, Odds ratio for CPAP showed protective effect for pneumonia [0.39 (0.19-0.78)], atelectasis [0.51 (0.32-0.80)] and pulmonary complications [0.37 (0.24-0.56)] with zero heterogeneity. For prevention of pulmonary complications, odds ratio was better for continuous than intermittent CPAP. Meta-regression demonstrated a positive correlation between the degree of CPAP and the incidence of pneumonia with a regression coefficient of +0.61 (95 % CI 0.02-1.21, P = 0.048, τ (2) = 0.078, r (2) = 7.87 %). Overall, adverse effects were similar with or without the use of CPAP. Prophylactic postoperative use of continuous CPAP significantly reduces the incidence of postoperative pneumonia, atelectasis and pulmonary complications in patients undergoing high-risk abdominal surgeries. Quantitatively, increasing the CPAP levels does not necessarily enhance the protective effect against pneumonia. Instead, protective effect diminishes with increasing degree of CPAP.

  6. Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study.

    Science.gov (United States)

    El-Sayed, Mohamed I; Ali, Amany M; Sayed, Heba A; Zaky, Eman M

    2010-12-24

    We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

  7. Cell Proliferation in Neuroblastoma

    Science.gov (United States)

    Stafman, Laura L.; Beierle, Elizabeth A.

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  8. Combined spinal epidural anesthesia during colon surgery in a high-risk patient: case report.

    Science.gov (United States)

    Imbelloni, Luiz Eduardo; Fornasari, Marcos; Fialho, José Carlos

    2009-01-01

    Combined spinal epidural anesthesia (CSEA) has advantages over single injection epidural or subarachnoid blockades. The objective of this report was to present a case in which segmental subarachnoid block can be an effective technique for gastrointestinal surgery with spontaneous respiration. Patient with physical status ASA III, with diabetes mellitus type II, hypertension, and chronic obstructive pulmonary disease was scheduled for resection of a right colon tumor. Combined spinal epidural block was performed in the T5-T6 space and 8 mg of 0.5% isobaric bupivacaine with 50 microg of morphine were injected in the subarachnoid space. The epidural catheter (20G) was introduced four centimeters in the cephalad direction. Sedation was achieved with fractionated doses of 1 mg of midazolam (total of 6 mg). A bolus of 25 mg of 0.5% bupivacaine was administered through the catheter two hours after the subarachnoid block. Vasopressors and atropine were not used. This case provides evidence that segmental spinal block can be the anesthetic technique used in gastrointestinal surgeries with spontaneous respiration.

  9. Association between age and high-risk human papilloma virus in Mexican oral cancer patients.

    Science.gov (United States)

    González-Ramírez, I; Irigoyen-Camacho, M E; Ramírez-Amador, V; Lizano-Soberón, M; Carrillo-García, A; García-Carrancá, A; Sánchez-Pérez, Y; Méndez-Martínez, R; Granados-García, M; Ruíz-Godoy, Lm; García-Cuellar, Cm

    2013-11-01

    Studies reporting low prevalence of HPV in OSCC with declining age at presentation are increasing. The aim of this study was to determine the prevalence of HPV in a group of OSCC cases and controls in a Mexican population. The matched case-control study included 80 OSCC cases and 320 controls. HPV/DNA presence was evaluated through PCR amplification using three sets of consensus primers for the L1 gene. A conditional logistic regression analysis was carried out for the matched OSCC cases and controls. Interactions between risk factors and OCSS were tested in the construction process of the models. HPV prevalence was 5% in OSCC cases and 2.5% in controls. HPV-detected types were 16, 18 and 56. According to conditional logistics regression model, an association was detected between HR-HPV and OSCC. All HR-HPV-positive OSCC cases corresponded to young patients (<45 years), non-smokers and non-alcohol drinkers. The HR-HPV can be a contributing factor to oral carcinogenesis, especially in younger individuals without known risk factors such as tobacco and alcohol. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Vacuum-assisted closure downgrades reconstructive demands in high-risk patients with severe lower extremity injuries.

    Science.gov (United States)

    Kakagia, D; Karadimas, E; Drosos, G; Ververidis, A; Kazakos, D; Lazarides, M; Verettas, D

    2009-01-01

    Primary soft tissue reconstruction in complex leg injuries is mandatory in order to protect exposed tissues; however, it may be precluded by the patient's clinical status or by local wound conditions. This retrospective study aims to evaluate the use of negative pressure as an adjunct to delayed soft tissue reconstruction in patients with complex lower limb trauma. Forty-two patients with 49 complex lower limb injuries were treated with Vacuum assisted closure (VAC) 48 hours after bone fixation, vascular repair and surgical debridement. Wound swab cultures were obtained before and after every VAC application. Duration of therapy, wound flora, final reconstructive technique required, outcome and follow-up period were retrieved from medical records. Twenty-four male and eighteen female patients were recruited, with a mean age of 47 years. All were treated with VAC therapy for 15-42 days. Reconstruction was delayed due to the patients' critical condition, advanced age, medical co-morbidities, heavily exuding wounds and questionable viability of soft tissues. Patients were followed up for 90-895 days. Two wounds healed spontaneously, 6 were managed with delayed direct suture, 31 with split thickness skin grafts and 9 required local cutaneous, fasciocutaneous or muscular flaps. One patient died due to fat embolism. Wound bacterial flora progressively decreased in all but one patient. Scar formation was aesthetically acceptable by the patients while function depended on the initial injury. Negative pressure is a safe and effective adjunct to delayed soft tissue reconstruction in high-risk patients with severe lower extremity injuries, minimizing reconstructive requirements and therefore postoperative morbidity.

  11. Perceived usability and use of custom-made footwear in diabetic patients at high risk for foot ulceration.

    Science.gov (United States)

    Arts, Mark L J; de Haart, Mirjam; Bus, Sicco A; Bakker, Jan P J; Hacking, Hub G A; Nollet, Frans

    2014-04-01

    To assess the perceived usability and use of custom- made footwear in diabetic patients who are at high-risk for foot ulceration, and to elucidate the determinants of usability and use. Survey. A total of 153 patients with diabetes, peripheral neuropathy, prior plantar foot ulceration and newly prescribed custom-made footwear, recruited from 10 Dutch multidisciplinary foot clinics. The Questionnaire of Usability Evaluation was used to assess the patients' perception of weight, appearance, comfort, durability, donning/doffing, stability, benefit and overall appreciation of their prescription footwear (all expressed as visual analogue scores). Data on priorities for usability and footwear use (in h/day) were obtained from patient reports. Multivariate logistic regression analysis was used to assess determinants of usability and use. Median (interquartile range) score for overall appreciation was 8.3 (7.1-9.1). Scores ranged from 6.5 (4.5-8.6) for weight to 9.6 (6.3-9.9) for donning/doffing. Footwear comfort was listed most often (33.3%) as the highest priority. Footwear use was benefit of the footwear (p = 0.045). Perceived usability of footwear was mostly positive, although individual scores and priorities varied considerably. Footwear use was low to moderate and dependent only on the perceived benefit of the footwear. Therefore, practitioners should focus on enhancing the patient's ap-preciation of the therapeutic benefit of custom-made footwear.

  12. Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients.

    Science.gov (United States)

    Hu, Xiang; Li, Ya-Qi; Li, Qing-Guo; Ma, Yan-Lei; Peng, Jun-Jie; Cai, Sanjun

    2018-05-22

    Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

    Science.gov (United States)

    Gringeri, A; Santagostino, E; Mannucci, P M; Siracusano, L; Marinoni, A; Criscuolo, M; Carcagno, M; Fall, L S; M'Bika, J P; Bizzini, B

    1995-05-01

    A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

  14. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

    Science.gov (United States)

    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  15. EEG indices in patients with high risk of ischemic stroke as predictors of initial disturbed cerebral circulation

    Directory of Open Access Journals (Sweden)

    N. A. Isaeva

    2014-01-01

    Full Text Available Abnormal changes were detected in EEG in patients with high risk of ischemic stroke (higher level than in the population. These changes show the disturbances in forming mechanisms of functional condition of cerebrum during the calm wakeful period. Changes were represented by: the registration of EEG IV- type (the E.A. Zhirmunsky type which was characterized by disorganization of alpha activity and of slow waves; the instability of pattern during the record of background activity; the paroxysmal activity in form of flashes of the bilateral synchronized waves; the strengthening of low-frequency and high-amplitude β-activity. Revealed changes in EEG show the presence of initial disturbed cerebral circulation and can be recommended as predictors of these disturbances.

  16. Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer.

    Science.gov (United States)

    Wang, Ming-yi; Chen, Cheng; Gao, Xiao-zhong; Li, Jie; Yue, Jing; Ling, Feng; Wang, Xiao-chun; Shao, Shi-he

    2013-01-01

    Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. CEUS: An essential component in a multimodality approach to small nodules in patients at high-risk for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyun-Jung, E-mail: Hyun-Jung.jang@uhn.ca [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada); Kim, Tae Kyoung, E-mail: Taekyoung.Kim@uhn.ca [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada); Burns, Peter N, E-mail: burns@sri.utoronto.ca [Department of Imaging Research, University of Toronto, Sunnybrook Health Sciences centre, 2075 Bayview Avenue, Toronto ON M4 N 3M5 (Canada); Wilson, Stephanie R, E-mail: Stephanie.wilson@albertahealthservices.ca [Department of Radiology, University of Calgary, Foothills Medical Centre, 1403 29 Street NW, Calgary, AB T2R 1M5 (Canada)

    2015-09-15

    Highlights: • CEUS resolves hypervascular pseudolesions, frequent on CT and MR, from vascular shunts. • US has the advantage of showing a baseline nodule for characterization. • CEUS shows excellent sensitivity to contrast agents, providing superior arterial phase sensitivity. • Real-time CEUS performance shows optimally perfusion patterns of benign tumor nodules. • CEUS performed at surveillance detection of nodules is efficient and effective. - Abstract: Contrast-enhanced ultrasound (CEUS) plays an essential role in the evaluation of small nodules in livers at high-risk for hepatocellular carcinoma (HCC) and offers unique advantages over CT/MRI. These include the sensitive depiction of arterial hypervascularity of HCC, better demonstration of rapid washout for non-HCC malignancy as well as of very late washout of HCC. Visualization of early vascular filling patterns for benign hypervascular lesions is of indisputable value. A frequently uncounted benefit of CEUS includes the value of its performance following nodule detection at ultrasound surveillance, including one-stop exclusion of typical benignancy, preclusion of arterial pseudolesions shown on CT/MR, and the avoidance of miscorrelation of a nodule on surveillance and subsequent diagnostic imaging. Therefore, CEUS can effectively be used in the diagnostic algorithm for new liver nodules detected during HCC surveillance. Despite the fact that CEUS is actively used as a major diagnostic test for HCC in Asia, Europe, and Canada with increasing demands in clinical practice, CEUS is not included in the diagnostic tests for HCC in some major practice guidelines. In this manuscript, we focus on small nodules in patients at high-risk for HCC, and review some of the unique advantages of CEUS that contribute to lesion characterization and subsequent patient management, showing why CEUS should be an essential component of the diagnostic algorithm for HCC.

  18. Depression and social anxiety in help-seeking patients with an ultra-high risk for developing psychosis.

    Science.gov (United States)

    Rietdijk, Judith; Ising, Helga K; Dragt, Sara; Klaassen, Rianne; Nieman, Dorien; Wunderink, Lex; Cuijpers, Pim; Linszen, Don; van der Gaag, Mark

    2013-10-30

    Knowledge on associations between ultra-high risk (UHR) for developing psychosis and on non-psychotic psychopathology in help-seeking populations is limited with respect to differences between male and female patients. The present study tests the hypothesis that both social anxiety and depression are highly prevalent in an UHR population, particularly among women. From February 2008 to February 2010 baseline data were collected from help-seeking subjects (14-35 years) who were included in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial. Two recruiting strategies were used: a two-stage screening strategy in a population of consecutive help-seeking and distressed subjects of secondary mental health services, and a referral strategy. This study included 201 patients with a mean age of 22.7 years. Of these, 102 (51%) were female, 58% of the patients met the criteria for clinical depression on the Beck Depression Inventory and 42% met the criteria for clinical social phobia on the Social Interaction Anxiety Scale. Women showed more depression and social anxiety than men. The results support the hypothesis that UHR is associated with depression and social anxiety, particularly in women. Screening a help-seeking population with depression and anxiety may be effective in detecting patients at UHR for developing psychosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Sibutramine versus Metformin: assessment of anthropometric, lipid and glycemic parameters in obese and overweight high-risk patients

    Directory of Open Access Journals (Sweden)

    Leonardo Regis Leira Pereira

    2012-01-01

    Full Text Available Anthropometric, lipid and glycemic parameters were compared in obese or overweight high-risk patients. This double-blind trial included 16 obese and overweight patients who followed a standard caloriecontrolled diet and received 15mg/day sibutramine or 1700mg/day metformin over three months. The changes observed in the sibutramine and metformin groups were, respectively: body mass index -6.0% and -4.0%; abdominal circumference -7.9% and -6.6%; fatty tissue -10.5% and -1.7%; total cholesterol -2.9% and -2.8%; LDL-C -0.01% and -0.1%; HDL-C -11.0% and -6.8%; total cholesterol/ HDL-C ratio +12.0% and +4.5%; HDL-C-to-LDL-C ratio -7.2% and -0.1%; triglycerides +14.0% and +22.3%; fasting glucose +4.3% and +1.4%; insulin -10.4% and -4.9%; HOMA -8.0% and -3.9%. Although the study was conducted with only 16 patients and the drugs were taken for only three months, we can see that sibutramine-treated obese or overweight highrisk patients showed a reduction of anthropometric parameters and better control of insulin resistance.

  20. TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival.

    Science.gov (United States)

    Chavali, P L; Saini, R K R; Zhai, Q; Vizlin-Hodzic, D; Venkatabalasubramanian, S; Hayashi, A; Johansson, E; Zeng, Z-j; Mohlin, S; Påhlman, S; Hansford, L; Kaplan, D R; Funa, K

    2014-10-30

    Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan-Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.

  1. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

    NARCIS (Netherlands)

    Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

    2005-01-01

    High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

  2. Multidisciplinary management of cervical neuroblastoma in infants.

    Science.gov (United States)

    Csanády, Miklós; Vass, Gábor; Bartyik, Katalin; Majoros, Valéria; Rovó, László

    2014-12-01

    Neuroblastoma is the most common malignancy in infancy, it is a histologically and genetically heterogeneous tumor, the therapy and outcome of which is influenced by age, histological variant and genetic background as well. We present two consecutive infant patients with neuroblastoma of the neck discussing the etiology, the diagnosis and the surgical and oncological treatment of the tumor, which was observed in a relatively rare manifestation in the head-neck region. Our first patient (age: 5.5 months) was MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived) negative, INSS (International Neuroblastoma Staging System) Stage 3 and INRGSS (International Neuroblastoma Risk Group Staging System) Stage 3 because of the contralateral lymph node involvement while the complete gross resection of the primary tumor mass was feasible. The patient is tumor free after three years of follow-up. Our second patient (age: 5 months) was MYCN negative, INSS Stage 2 and INRGSS Stage 1, as both the primary tumor and the ipsilateral lymph nodes were totally removed via a modified radical neck dissection. The patient is tumor free after three years of follow-up. For MYCN negative patients, especially in early age, the prognosis of neuroblastoma is good, surgical resection and chemotherapy together is an adequate treatment protocol (as in our two patients). While MYCN-amplified patients require a combined and aggressive treatment with surgery, chemotherapy, radiotherapy, and immunotherapy to be able to obtain a favorable survival rate according to the literature. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Coagulation Profile Changes Due to Thromboprophylaxis and Platelets in Trauma Patients at High-Risk for Venous Thromboembolism.

    Science.gov (United States)

    Allen, Casey J; Murray, Clark R; Meizoso, Jonathan P; Ray, Juliet J; Teisch, Laura F; Ruiz, Xiomara D; Hanna, Mena M; Guarch, Gerardo A; Manning, Ronald J; Livingstone, Alan S; Ginzburg, Enrique; Schulman, Carl I; Namias, Nicholas; Proctor, Kenneth G

    2015-07-01

    We hypothesize there are coagulation profile changes associated both with initiation of thromboporphylaxis (TPX) and with change in platelet levels in trauma patients at high-risk for venous thromboembolism (VTE). A total of 1203 trauma intensive care unit patients were screened with a VTE risk assessment profile. In all, 302 high-risk patients (risk assessment profile score ≥ 10) were consented for weekly thromboelastography. TPX was initiated between initial and follow-up thromboelastography. Seventy-four patients were analyzed. Upon admission, 87 per cent were hypercoagulable, and 81 per cent remained hypercoagulable by Day 7 (P = 0.504). TPX was initiated 3.4 ± 1.4 days after admission; 68 per cent received unfractionated heparin and 32 per cent received low-molecular-weight heparin. The VTE rate was 18 per cent, length of stay 38 (25-37) days, and mortality of 17.6 per cent. In all, 76 per cent had a rapid clotting time at admission versus 39 per cent at Day 7 (P < 0.001); correcting from 7.75 (6.45-8.90) minutes to 10.45 (7.90-15.25) minutes (P < 0.001). At admission, 41 per cent had an elevated maximum clot formation (MCF) and 85 per cent had at Day 7 (P < 0.001); increasing from 61(55-65) mm to 75(69-80) mm (P < 0.001). Platelets positively correlated with MCF at admission (r = 0.308, R(2) = 0.095, P = 0.008) and at Day 7 (r = 0.516, R(2) = 0.266, P < 0.001). Change in platelet levels correlated with change in MCF (r = 0.332, R(2) = 0.110, P = 0.005). In conclusion, hypercoagulability persists despite the use of TPX. Although clotting time normalizes, MCF increases in correlation with platelet levels. As platelet function is a dominant contributor to sustained trauma-evoked hypercoagulability, antiplatelet therapy may be indicated in the management of severely injured trauma patients.

  4. Low Dose I-131 MIBG therapy as an adjunct for bone pain palliation in pediatric patients with end-stage neuroblastoma: a pilot study

    International Nuclear Information System (INIS)

    Pascual, Thomas; Herbert, Anthony; Howman-Giles, Robert

    2009-01-01

    Full text: Objective: This study describes the initial experience in the use of low-dose 1-131 MIBG in patients with metastaticl refractory Neuroblastoma given at 18.5 Mbql Kg (0.5 mCi/Kg )to (1) achieve disease palliation (i.e., pain I symptom control) and improvement in the quality of life, through subjective response from patient/carers and (2) allow day-admission to minimize hospital stay providing more quality time between the patients and carers. Methods: Patients with refractory and metastatic Neuroblastoma whose primary treatment goal at that particular stage is pain palliation were given low-dose 1-131 M IBG at a dose of 18.5 Mbql Kg ( 0.5 mCil Kg)l. Assessment of subjective pain relief following 1-131 MIBG was done through interviews from hospital visits of the patient and home visits by the team. Results: Four patients underwent Low-Dose 1-131 MIBG Therapy for pain palliation between May 2007- March 2008. Median age was 5.75 years old and median total dose given was 539 Mbql patient (14.5 mCil patient). All patients at a cenain time had relief from disease pain allowing them to communicate with family and participate in physical activities not priyiledged before. Observations gathered from carersl parents revealed that the overall quality-of-life improved after the 1-131 MIBG therapy with concurrent pain medication protocol. Conclusion: This initial I pilot study described achievement of disease palliation (i.e., pain and symptom control) and improvement in the quality of life of Stage IV Neuroblastoma patients and allows day-admissions providing more quality time between the patient and the family and reduces patient anxiety.

  5. Results of high-risk neutropenia therapy of hematology-oncology patients in a university hospital in Uruguay

    Directory of Open Access Journals (Sweden)

    Matilde Boada Burutaran

    2015-02-01

    Full Text Available Background: Febrile neutropenia is an important cause of mortality and morbidity in hematology-oncology patients undergoing chemotherapy. The management of febrile neutropenia is typically algorithm-driven. The aim of this study was to assess the results of a standardized protocol for the treatment of febrile neutropenia. Methods: A retrospective cohort study (2011-2012 was conducted of patients with high-risk neutropenia in a hematology-oncology service. Results: Forty-four episodes of 17 patients with a median age of 48 years (range: 18-78 years were included. The incidence of febrile neutropenia was 61.4%. The presence of febrile neutropenia was associated with both the duration and severity of neutropenia. Microbiological agents were isolated from different sources in 59.3% of the episodes with bacteremia iso- lated from blood being the most prevalent (81.3%. Multiple drug-resistant gram-negative bacilli were isolated in 62.5% of all microbiologically documented infections. Treatment of 63% of the episodes in which the initial treatment was piperacillin/tazobactam needed to be escalated to meropenem. The mortality rate due to febrile neutropenia episodes was 18.5%. Conclusion: The high rate of gram-negative bacilli resistant to piperacillin/tazobactam (frontline antibiotics in our protocol and the early need to escalate to carbapenems raises the question as to whether it is necessary to change the current protocol.

  6. A quality control circle process to improve implementation effect of prevention measures for high-risk patients.

    Science.gov (United States)

    Feng, Haixia; Li, Guohong; Xu, Cuirong; Ju, Changping; Suo, Peiheng

    2017-12-01

    The aim of the study was to analyse the influence of prevention measures on pressure injuries for high-risk patients and to establish the most appropriate methods of implementation. Nurses assessed patients using a checklist and factors influencing the prevention of a pressure injury determined by brain storming. A specific series of measures was drawn up and an estimate of risk of pressure injury determined using the Braden Scale, analysis of nursing documents, implementation of prevention measures for pressure sores and awareness of the system both before and after carrying out a quality control circle (QCC) process. The overall scores of implementation of prevention measures ranged from 74.86 ± 14.24 to 87.06 ± 17.04, a result that was statistically significant (P prevention measure scores ranged from 11.48 ± 4.18 to 13.96 ± 3.92. Differences in all of the above results are statistically significant (P prevention measures for patients who are vulnerable to pressure sores and is of practical importance to their prevention and control. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    International Nuclear Information System (INIS)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K.; Kim, Grace E.; Lin, Lawrence; Giacomini, Kathy; Naranjo, Arlene; Van Ryn, Collin; Yanik, Gregory A.; Kreissman, Susan G.; Hogarty, Michael; DuBois, Steven G.

    2016-01-01

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  8. Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); Kim, Grace E. [UCSF School of Medicine, Department of Pathology, San Francisco, CA (United States); Lin, Lawrence; Giacomini, Kathy [UCSF School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA (United States); Naranjo, Arlene; Van Ryn, Collin [University of Florida, Children' s Oncology Group Statistics and Data Center, Gainesville, FL (United States); Yanik, Gregory A. [University of Michigan, CS Mott Children' s Hospital, Ann Arbor, MI (United States); Kreissman, Susan G. [Duke University Medical Center, Durham, NC (United States); Hogarty, Michael [University of Pennsylvania, Children' s Hospital of Philadelphia and Perelman School of Medicine, Philadelphia, PA (United States); DuBois, Steven G. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); UCSF School of Medicine, San Francisco, CA (United States)

    2016-03-15

    Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

  9. Assessment of independent risk factors of conversion into psychosis in the ultra-high risk state group of patients

    Directory of Open Access Journals (Sweden)

    Marta Gawłowska

    2010-12-01

    Full Text Available Background: The aim of this study was the independent psychosis risk factors assessment in a group of subjects fulfilling the criteria of at risk mental state, under specialist outpatient psychiatric care. Participants: Seventy-one patients – 33 women and 38 men, were involved into this study, aged on average 17.34, all under psychiatric care. The patients were recruited into the study in the sequence of their outpatient clinic admission. The criterion to be included into the study was the diagnosis of ultra-high risk state (UHRS – defined according to the Australian research group principles. Subsequently, the patients were divided into subgroups according to the clinical features of their mental state. Method: The author’s demographic questionnaire was applied in the study. Information regarding the family history of psychosis was obtained from patients and/or their relatives or carers. The patients’ mental state was assessed monthly – according to the presence of psychotic symptoms, change of their incidence and duration, presence of depressive symptoms or aggressive behaviour (measured by a three-level scale. On the basis of the obtained information, we evaluated: 1 conversion into psychosis time – measured from diagnosing of UHRS to the development of full-symptom psychosis, 2 therapeutic methods used (psychotherapy, pharmacotherapy or both, 3 use of psychoactive substances after being diagnosed with UHRS, 4 presence of serious life stressors (the patients’ subjective estimation – during the six-month period preceding the conversion into psychosis. Results: 1 In the UHRS group of patients, staying under professional outpatient psychiatric care, the use of marijuana was an independent risk factor of conversion into psychosis. 2 In the investigated group of patients with at risk mental state we did not find any correlation between modulating factors (including: therapeutic methods used, depressive symptoms, aggression or

  10. Typical skeletal changes due to metastasising neuroblastomas

    International Nuclear Information System (INIS)

    Eggerath, A.; Persigehl, M.; Mertens, R.; Technische Hochschule Aachen

    1983-01-01

    Compared with other solid tumours in childhood, neuroblastomas show a marked tendency to metastasise to the skeleton. The differentiation of these lesions from inflammatory and other malignant bone lesions in this age group is often difficult. The radiological findings in ten patients with metastasing and histologically confirmed neuroblastomas have been reviewed and the typical appearances in the skeleton are described. The most important features in the differential diagnosies are discussed and the significance of bone changes in the diagnosis of neuroblastoma have been evaluated. (orig.) [de

  11. [Prevalence of HPV high-risk serotypes detected by PCR in patients with normal cervical cytology at the Hospital Regional Adolfo López Mateos, ISSSTE].

    Science.gov (United States)

    Martínez-Portilla, R J; López-Velázquez, J L; Martínez-Rojas, G C; Aguilar-Villagómez, M I; De la Torre-Rendón, F E; Villafán-Bernal, J R

    2016-09-01

    Is fundamental to determine the prevalence of human papiloma virus (HVP) high-risk serotypes in local and regional population in order for health providers to offer patients, vaccines and treatments against specific population-based serotypes. To determine the prevalence of HPV High risk serotypes detected by PCR in patients with normal cytology from the ISSSTE Adolfo Lopez Mateos Regional Hospital. An observational, descriptive, prospective study was conducted from cervical cytologies and high risk HPV test by PCR in patients from the Regional Hospital Adolfo López Mateos, ISSSTE, during the period January 2013-December 2015. Cases of patients with negative cervical cytology were included. Information about age, the result of cervical cytology and high risk HPV test by PCR was obtained. The overall prevalence of HPV infection and the most prevalent serotypes by age groups were calculated. A total of 3258 cervical smears were performed, of which 2557 were negative (78.4%), from this, the global prevalence of HPV infection was 10.2% (n=262). We found that 1.8% (n = 45) of negative reports had HPV16 infection, 0.5% (n=13) had HPV18 and 8.9% (n = 227) were infected by Viral Pool of other high-risk serotypes. The prevalence of infection by viral pool of high risk serotypes was 11.5% in women <20 years, 12.9% in women between 20-29 years and 22.2% in women between 30-39 years. This prevalence was lower in patients older than 40 years (p<0.05). A higher prevalence of viral pool high risk serotypes was found in patients with normal cytology, than the HPV16 and HPV-8 prevalence, which was significantly higher in women younger than 40 years.

  12. Nuclear medicine therapy of neuroblastoma

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    1999-01-01

    Specific targeting of radionuclides to neuroblastoma, a neural crest tumor occurring predominantly in young children and associated with a relatively poor prognosis, may be achieved via the metabolic route (Mibg), receptor binding (peptides) or immunological approach (antibodies). The clinical role of 1 31 I -Mibg therapy and radioimmunotherapy in neuroblastoma is discussed. In recurrent or progressive metastatic disease after conventional treatment modalities have failed, 1 31 I -Mibg therapy, with an overall objective response rate of 35%, is probably the best palliative treatment, as the invasiveness and toxicity of this therapy compare favourably with that of chemotherapy, immunotherapy and external beam radiotherapy. In patients presenting with inoperable stage III and IV neuroblastoma, 1 31 I -Mibg therapy at diagnosis is at least as effective as combination chemotherapy but is associated with much less toxicity. In patients with recurrent disease 1 31 I -Mibg therapy in combination with hyperbaric oxygen therapy proved feasible and encouraging effects on survival have ben observed. Attempts to intensify the treatment in relapsed patients by combination of 1 31 I -Mibg therapy with high dose chemotherapy and/or total body irradiation have met with considerable toxicity. Developments in Mibg therapy aiming at improving the therapeutic index are mentioned. Early results of radioimmunotherapy using 1 31 I -UJ13A or 1 31 I -3F8 monoclonal antibodies have shown moderate objective response and considerable side effects in patients with stage IV neuroblastoma, who had relapsed or failed conventional therapy. New developments in radioimmunotherapy of neuroblastoma include the use of chimeric antibodies, the enhancement of tumor uptake by modulation of antigen expression or by increasing the tumor perfusion/vascularity/permeability, the use of other labels and multistep targeting techniques, e.g. using bispecific monoclonal antibodies

  13. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

    Science.gov (United States)

    Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

    2014-02-01

    Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

  14. Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning.

    Science.gov (United States)

    Fusar-Poli, P; Schultze-Lutter, F

    2016-02-01

    Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Homoarginine Associates with Zonulin and Tryptophan - Findings in a High-Risk Cohort of Patients Carrying an AICD.

    Science.gov (United States)

    Mann, Elli; Kluesener, Robert; Boschann, Felix; Ruppert, Jana; Armbruster, Franz P; Meinitzer, Andreas; Melzer, Christoph; Dschietzig, Thomas B

    2017-11-01

    Homoarginine (hArg) is known to have an impact on nitric oxide (NO) metabolism. It seems to increase NO generation and/or availability, thereby enhancing endothelial function. In addition, hArg is connected to energy metabolism since the key enzyme, L-arginine-glycine amidinotransferase (AGAT) for hArg synthesis in the kidneys, is also involved in the synthesis of energy metabolites like guanidinoacetate. Former studies indicate that low levels of hArg are linked to cardiovascular disease and increased all-cause mortality. This study investigated the dependence of plasma hArg on various biochemical and clinical factors in 229 patients carrying an automatic, implantable cardioverter/defibrillator (AICD) using multiple linear regression analysis (Generalized Linear Model, GLM). GLM revealed a highly significant, positive association between hArg and zonulin (p zonulin is a novel finding which may indicate a different meaning of circulating versus local (gut) zonulin. Therefore, further experimental and clinical investigation is needed to explore this association, focusing on possible pathophysiological pathways and the role of circulating zonulin levels in cardiovascular disease. The positive correlation of hArg and Trp also deserves further research because both amino acids might have a protective effect on cardiovascular disease by inhibition of the enzyme alkaline phosphatase. Eventually, our study associates low hArg concentrations with chronic low-grade inflammation and parameters of malnutrition in cardiovascular high-risk patients.

  16. Endovascular Treatment of Infrarenal Abdominal Aortic Aneurysm with Short and Angulated Neck in High-Risk Patient

    Directory of Open Access Journals (Sweden)

    Stylianos Koutsias

    2013-01-01

    Full Text Available Endovascular treatment of abdominal aortic aneurysms (AAA is an established alternative to open repair. However lifelong surveillance is still required to monitor endograft function and signal the need for secondary interventions (Hobo and Buth 2006. Aortic morphology, especially related to the proximal neck, often complicates the procedure or increases the risk for late device-related complications (Hobo et al. 2007 and Chisci et al. 2009. The definition of a short and angulated neck is based on length (60° (Hobo et al. 2007 and Chisci et al. 2009. A challenging neck also offers difficulties during open repairs (OR, necessitating extensive dissection with juxta- or suprarenal aortic cross-clamping. Patients with extensive aneurysmal disease typically have more comorbidities and may not tolerate extensive surgical trauma (Sarac et al. 2002. It is, therefore, unclear whether aneurysms with a challenging proximal neck should be offered EVAR or OR (Cox et al. 2006, Choke et al. 2006, Robbins et al. 2005, Sternbergh III et al. 2002, Dillavou et al. 2003, and Greenberg et al. 2003. In our case the insertion of a thoracic endograft followed by the placement of a bifurcated aortic endograft for the treatment of a very short and severely angulated neck proved to be feasible offering acceptable duration of aneurysm exclusion. This adds up to our armamentarium in the treatment of high-risk patients, and it should be considered in emergency cases when the fenestrated and branched endografts are not available.

  17. Transcatheter, valve-in-valve transapical aortic and mitral valve implantation, in a high risk patient with aortic and mitral prosthetic valve stenoses

    Directory of Open Access Journals (Sweden)

    Harish Ramakrishna

    2015-01-01

    Full Text Available Transcatheter valve implantation continues to grow worldwide and has been used principally for the nonsurgical management of native aortic valvular disease-as a potentially less invasive method of valve replacement in high-risk and inoperable patients with severe aortic valve stenosis. Given the burden of valvular heart disease in the general population and the increasing numbers of patients who have had previous valve operations, we are now seeing a growing number of high-risk patients presenting with prosthetic valve stenosis, who are not potential surgical candidates. For this high-risk subset transcatheter valve delivery may be the only option. Here, we present an inoperable patient with severe, prosthetic valve aortic and mitral stenosis who was successfully treated with a trans catheter based approach, with a valve-in-valve implantation procedure of both aortic and mitral valves.

  18. Predictive value of pretreatment lymphocyte count in stage II colorectal cancer and in high-risk patients treated with adjuvant chemotherapy.

    Science.gov (United States)

    Liang, Lei; Zhu, Ji; Jia, Huixun; Huang, Liyong; Li, Dawei; Li, Qingguo; Li, Xinxiang

    2016-01-05

    Pretreatment lymphocyte count (LC) has been associated with prognosis and chemotherapy response in several cancers. The predictive value of LC for stage II colorectal cancer (CRC) and for high-risk patients treated with adjuvant chemotherapy (AC) has not been determined. A retrospective review of prospectively collected data from 1332 consecutive stage II CRC patients who underwent curative tumor resection was conducted. A pretreatment LC value risk, 459 (62.2%) of whom received AC. Patients with low LCs had significantly worse 5-year OS (74.6% vs. 90.2%, p risk patients with low LCs had the poorest DFS (p value or combined with high-risk status were both independent prognostic factors(p risk, AC-treated patients with high LCs had significantly longer DFS than untreated patients (HR, 0.594; 95% CI, 0.364-0.970; p = 0.035). There was no difference or trend for DFS or OS in patients with low LCs, regardless of the use of AC (DFS, p = 0.692; OS, p = 0.522). Low LC was also independently associated with poorer DFS in high-risk, AC-treated patients (HR, 1.885; 95% CI, 1.112-3.196; p = 0.019). Pretreatment LC is an independent prognostic factor for survival in stage II CRC. Furthermore, pretreatment LC reliably predicts chemotherapeutic efficacy in high-risk patients with stage II CRC.

  19. High-risk human papillomavirus (HPV screening and detection in healthy patient saliva samples: a pilot study

    Directory of Open Access Journals (Sweden)

    Wang Robert C

    2011-10-01

    Full Text Available Abstract Background The human papillomaviruses (HPV are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p Conclusions The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.

  20. Methicillin-resistant Staphylococcus aureus infection and hospitalization in high-risk patients in the year following detection.

    Directory of Open Access Journals (Sweden)

    Susan S Huang

    Full Text Available Many studies have evaluated methicillin-resistant Staphylococcus aureus (MRSA infections during single hospitalizations and subsequent readmissions to the same institution. None have assessed the comprehensive burden of MRSA infection in the period after hospital discharge while accounting for healthcare utilization across institutions.We conducted a retrospective cohort study of adult patients insured by Harvard Pilgrim Health Care who were newly-detected to harbor MRSA between January 1991 and December 2003 at a tertiary care medical center. We evaluated all MRSA-attributable infections associated with hospitalization in the year following new detection, regardless of hospital location. Data were collected on comorbidities, healthcare utilization, mortality and MRSA outcomes. Of 591 newly-detected MRSA carriers, 23% were colonized and 77% were infected upon detection. In the year following detection, 196 (33% patients developed 317 discrete and unrelated MRSA infections. The most common infections were pneumonia (34%, soft tissue (27%, and primary bloodstream (18% infections. Infections occurred a median of 56 days post-detection. Of all infections, 26% involved bacteremia, and 17% caused MRSA-attributable death. During the admission where MRSA was newly-detected, 14% (82/576 developed subsequent infection. Of those surviving to discharge, 24% (114/482 developed post-discharge infections in the year following detection. Half (99/185, 54% of post-discharge infections caused readmission, and most (104/185, 55% occurred over 90 days post-discharge.In high-risk tertiary care patients, newly-detected MRSA carriage confers large risks of infection and substantial attributable mortality in the year following acquisition. Most infections occur post-discharge, and 18% of infections associated with readmission occurred in hospitals other than the one where MRSA was newly-detected. Despite gains in reducing MRSA infections during hospitalization, the

  1. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

    Directory of Open Access Journals (Sweden)

    Dagmar F. Hernandez-Suarez MD

    2016-12-01

    Full Text Available Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1 *2 (g.559C>T, p.P187S polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

  2. Dispersal of antibiotic-resistant high-risk clones by hospital networks : changing the patient direction can make all the difference

    NARCIS (Netherlands)

    Donker, T.; Wallinga, J.; Grundmann, H.

    Background: Patients who seek treatment in hospitals can introduce high-risk clones of hospital-acquired, antibiotic-resistant pathogens from previous admissions. In this manner, different healthcare institutions become linked epidemiologically. All links combined form the national patient referral

  3. Risk Factors Associated with Rebleeding in Patients with High Risk Peptic Ulcer Bleeding: Focusing on the Role of Second Look Endoscopy.

    Science.gov (United States)

    Kim, Sung Bum; Lee, Si Hyung; Kim, Kyeong Ok; Jang, Byung Ik; Kim, Tae Nyeun; Jeon, Seong Woo; Kwon, Joong Goo; Kim, Eun Young; Jung, Jin Tae; Park, Kyung Sik; Cho, Kwang Bum; Kim, Eun Soo; Kim, Hyun Jin; Park, Chang Keun; Park, Jeong Bae; Yang, Chang Heon

    2016-02-01

    Re-bleeding after initial hemostasis in peptic ulcer bleeding can be life threatening. Identification of factors associated with re-bleeding is important. The aims of this study were to determine incidence of rebleeding in patients with high risk peptic ulcer bleeding and to evaluate factors associated with rebleeding. Among patients diagnosed as upper gastrointestinal hemorrhage at seven hospitals in Daegu-Gyeongbuk, and one hospital in Gyeongnam, South Korea, from Feb 2011 to Dec 2013, 699 patients diagnosed as high risk peptic ulcer bleeding with Forrest classification above llb were included. The data were obtained in a prospective manner. Among 699 patients, re-bleeding occurred in 64 (9.2 %) patients. Second look endoscopy was significantly more performed in the non-rebleeding group than the rebleeding group (81.8 vs 62.5 %, p peptic ulcer bleeding. In our study, rebleeding was observed in 9.2 % of patients with high risk peptic ulcer bleeding. Performance of second look endoscopy seems to lower the risk of rebleeding in high risk peptic ulcer bleeding patients and caution should be paid to patients receiving high volume transfusion and on medication with NSAIDs.

  4. Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions

    NARCIS (Netherlands)

    Tersmette, A. C.; Offerhaus, G. J.; Tersmette, K. W.; Giardiello, F. M.; Moore, G. W.; Tytgat, G. N.; Vandenbroucke, J. P.

    1990-01-01

    Controversy about gastric cancer risk after partial gastrectomy exists, especially in the United States. Therefore, we performed a meta-analysis to determine overall relative risk and weighted mean relative risk for subsets of postgastrectomy patients, define possible high risk patients suitable for

  5. Treatment of extradural paraspinal neuroblastoma with an intraspinal component

    International Nuclear Information System (INIS)

    Ho, K.S.Y.; Wara, W.M.; Ablin, A.R.

    1982-01-01

    Neuroblastoma originates from neural crest cells and can be found wherever sympathetic neural tissue is normally located. When the tumor arises from a paraspinal sympathetic ganglion, it has a propensity to extend through the intervertebral foramina, producing an extradural paraspinal neuroblastoma with an interspinal component (''dumbell'' neuroblastoma) which may result in spinal cord compression. The records of all children with neuroblastomas referred to the UCSF Department of Radiation Oncology and the Division of Pediatric Oncology from January 1, 1970, to December 31, 1979, are reviewed in this report. Patients who at initial presentation had a ''dumbell'' neuroblastoma were selected for study. Neuroblastoma was diagnosed histologically in all patients except one. Disease-free interval and length of survival was measured from the date of completion of radiotherapy, mostly after surgery. The results of diagnostic X-rays and laboratory studies are shown. Radiotherapeutic doses and results are tabulated. (Auth.)

  6. Lack of Evidence for a Relationship between High Risk Human Papillomaviruses and Breast Cancer in Iranian Patients.

    Science.gov (United States)

    Doosti, Masoud; Bakhshesh, Mehran; Zahir, Shokouh Taghipour; Shayestehpour, Mohammad; Karimi-Zarchi, Mojgan

    2016-01-01

    Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

  7. How can we identify low- and high-risk patients among unselected patients with possible acute coronary syndrome?

    DEFF Research Database (Denmark)

    Nielsen, Kirsten Melgaard; Færgeman, Ole; Larsen, Mogens Lytken

    2007-01-01

    Objective Prognosis among patients admitted with possible acute coronary syndrome (ACS) may differ from that of patients with definite ACS. The aim of this study was to identify risk factors for mortality among unselected patients and to use the statistical model to identify patients at low or high...... mortality risk. Methods From April 1, 2000, to March 31, 2002, we identified all consecutive patients aged 30 to 69 years admitted to the 2 coronary care units covering the municipality of Aarhus, Denmark (population, 138 290). ACS was considered a possible diagnosis if the physician at admission (1) had...

  8. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    Science.gov (United States)

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

  9. Olfactory Neuroblastoma: Diagnostic Difficulty

    Directory of Open Access Journals (Sweden)

    Vidya MN,

    2011-01-01

    Full Text Available Olfactory neuroblastoma is an uncommon malignant tumor of sinonasal tract arising from the olfactory neuro epithelium. The olfactory neuroblastomas presenting with divergent histomorphologies like, epithelial appearance of cells, lacking a neuro fibrillary background and absence of rosettes are difficult to diagnose. Such cases require immunohistochemistry to establish the diagnosis. We describe the clinical features, pathological and immunohistochemical findings of grade IV Olfactory neuroblastoma in a 57 year old man

  10. Differential expression of miRNAs in the serum of patients with high-risk oral lesions

    International Nuclear Information System (INIS)

    MacLellan, Sara Ann; Lawson, James; Baik, Jonathan; Guillaud, Martial; Poh, Catherine Fang-Yeu; Garnis, Cathie

    2012-01-01

    Oral cancer is one of the most commonly diagnosed cancers worldwide. Disease is often diagnosed at later stages, which is associated with a poor 5-year survival rate and a high rate of local recurrence. MicroRNAs (miRNAs), a group of small, noncoding RNAs, can be isolated from blood serum samples and have demonstrated utility as biomarkers in multiple cancer types. The aim of this study was to examine the expression profiles of circulating miRNAs in the serum of patients with high-risk oral lesions (HRLs; oral cancer or carcinoma in situ) and to explore their utility as potential oral cancer biomarkers. Global serum miRNA profiles were generated using quantitative PCR method from 1) patients diagnosed with HRLs and undergoing intent-to-cure surgical treatment (N = 30) and 2) a demographically matched, noncancer control group (N = 26). We next honed our list of serum miRNAs associated with disease by reducing the effects of interpatient variability; we compared serum miRNA profiles from samples taken both before and after tumor resections (N = 10). Based on these analyses, fifteen miRNAs were significantly upregulated and five were significantly downregulated based on presence of disease (minimum fold-change >2 in at least 50% of samples, P < 0.05, permutation). Five of these miRNAs (miR-16, let-7b, miR-338-3p, miR-223, and miR-29a) yielded an area under the ROC curve (AUC) >0.8, suggesting utility as noninvasive biomarkers for detection of oral cancer or high-grade lesions. Combining these serum miRNA profiles with other screening techniques could greatly improve the sensitivity in oral cancer detection

  11. Neuroblastoma: computed tomographic findings

    International Nuclear Information System (INIS)

    Yoon, Choon Sik; Ahn, Chang Su; Kim, Myung Jun; Oh, Ki Keun

    1994-01-01

    To evaluate the characteristic CT findings of neuroblastoma, we studied neuroblastomas. We analysed CT findings of available 25 cases among pathologically proved 51 neuroblastomas from Jan. 1983 to Sept. 1990. The most frequent site of origin is adrenal gland (40%) and the second is retroperitoneum (32%) and the third ismediastinum (16%). Characteristic CT findings are as follows: Calcifications within the tumor is detected in 86% of abdominal neuroblastomas and 50% of mediastinal origin. Hemorrhagic and necrotic changes within the tumor is noted at 86% in the tumor of abdominal origin and 25% in mediastinal neuroblastomas. Contrast enhanced study showed frequently seperated enhanced appearance with/without solid contrast enhancement. Encasements of major great vessels such as aorta and IVC with/without displacement by metastatic lymph nodes or tumor are frequently seen in 90% of abdominal neuroblastomas. Multiple lymphadenopathy are detected in 95% of abdominal neuroblastomas and 25% of mediastinal neuroblastomas. The most common organ or contiguous direct invasion is kidney in 6 cases and the next one is liver but intraspinal canal invasion is also noted in 2 cases. We concluded that diagnosis of neuroblastoma would be easily obtained in masses of pediatric group from recognition of above characteristic findings

  12. Stage IVN neuroblastoma: MRI diagnosis of left supraclavicular ''Virchow's'' nodal spread

    International Nuclear Information System (INIS)

    Abramson, S.J.; Berdon, W.E.; Stolar, C.; Ruzal-Shapiro, C.; Garvin, J.

    1996-01-01

    Stage IV neuroblastoma is associated with high mortality; an exception are patients whose stage IV status includes distant positive nodes, but no skeletal metastases - stage IVN neuroblastoma. We describe our experience with preoperative MRI in three patients with extensive abdominal neuroblastoma without cortical bony involvement but with unsuspected metastatic involvement to the left supraclavicular (Virchow's) node. We review findings of left supraclavicular nodal spread in five earlier cases of IVN neuroblastoma. (orig.). With 3 figs., 1 tab

  13. Prognostic value of metabolic indices and bone marrow uptake pattern on preoperative 18F-FDG PET/CT in pediatric patients with neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chao; Chen, Suyun; Huang, Shuo; Wu, Shuqi; Zhang, Linlin; Zhang, Fengxian; Wang, Hui [Shanghai Jiao Tong University School of Medicine, Department of Nuclear Medicine, Xinhua Hospital, Shanghai (China); Zhang, Jian [Shanghai Jiao Tong University School of Medicine, Department of Nuclear Medicine, Xinhua Hospital, Shanghai (China); Shanghai Universal Medical Imaging Diagnostic Center, Shanghai (China)

    2018-02-15

    To evaluate the prognostic value of metabolic parameters and bone marrow uptake (BMU) patterns on pretherapeutic 18-F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in pediatric patients with neuroblastoma (NB). Forty-seven pediatric patients with newly diagnosed neuroblastoma who underwent 18F-FDG PET/CT were retrospectively reviewed. Clinicopathological factors and metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and bone marrow uptake patterns on PET/CT were compared to predict recurrence-free survival (RFS) and overall survival (OS) by univariate and multivariate analysis. During the follow-up period, 27 (57.4%) patients experienced recurrence. MTV (P = 0.001), TLG (P = 0.004) and BMU patterns (P = 0.025) remained significant predictive factors for tumor recurrence, along with tumor size, histology, stage, lactate dehydrogenase (LDH) and other distant metastasis (except bone metastasis). Univariate analysis showed that histology, stage, tumor size (>37.25 cm), other distant metastasis, MTV (>88.10cm{sup 3}) and TLG (>1045.2 g) and BMU patterns correlated with both RFS and OS (P < 0.05). On multivariate analysis, TLG remained the only independent prognostic factor for RFS (P = 0.016) and OS (P = 0.012), and BMU patterns and MTV were statistically significant for OS (P = 0.024 and P = 0.038, respectively). Pretherapeutic 18F-FDG PET/CT can provide reliable prognostic information for neuroblastoma pediatric patients, and patients with high MTV, TLG and focal bone marrow (unifocal and multifocal) uptake on PET/CT may have inferior outcomes during subsequent treatment. (orig.)

  14. Impact of Florida's prescription drug monitoring program and pill mill law on high-risk patients: A comparative interrupted time series analysis.

    Science.gov (United States)

    Chang, Hsien-Yen; Murimi, Irene; Faul, Mark; Rutkow, Lainie; Alexander, G Caleb

    2018-04-01

    We quantified the effects of Florida's prescription drug monitoring program and pill mill law on high-risk patients. We used QuintilesIMS LRx Lifelink data to identify patients receiving prescription opioids in Florida (intervention state, N: 1.13 million) and Georgia (control state, N: 0.54 million). The preintervention, intervention, and postintervention periods were July 2010 to June 2011, July 2011 to September 2011, and October 2011 to September 2012. We identified 3 types of high-risk patients: (1) concomitant users: patients with concomitant use of benzodiazepines and opioids; (2) chronic users: long-term, high-dose, opioid users; and (3) opioid shoppers: patients receiving opioids from multiple sources. We compared changes in opioid prescriptions between Florida and Georgia before and after policy implementation among high-risk/low-risk patients. Our monthly measures included (1) average morphine milligram equivalent per transaction, (2) total opioid volume across all prescriptions, (3) average days supplied per transaction, and (4) total number of opioid prescriptions dispensed. Among opioid-receiving individuals in Florida, 6.62% were concomitant users, 1.96% were chronic users, and 0.46% were opioid shoppers. Following policy implementation, Florida's high-risk patients experienced relative reductions in morphine milligram equivalent (opioid shoppers: -1.08 mg/month, 95% confidence interval [CI] -1.62 to -0.54), total opioid volume (chronic users: -4.58 kg/month, CI -5.41 to -3.76), and number of dispensed opioid prescriptions (concomitant users: -640 prescriptions/month, CI -950 to -340). Low-risk patients generally did not experience statistically significantly relative reductions. Compared with Georgia, Florida's prescription drug monitoring program and pill mill law were associated with large relative reductions in prescription opioid utilization among high-risk patients. Copyright © 2018 John Wiley & Sons, Ltd.

  15. {sup 18}F-FDG PET/contrast enhanced CT in the standard surveillance of high risk colorectal cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez Londoño, Germán Andrés, E-mail: gjimenez91@yahoo.com [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); García Vicente, Ana María [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Sánchez Pérez, Victoria [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Jiménez Aragón, Fátima [Department of Radiology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); León Martin, Alberto [Investigation Unit, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Cano Cano, Juana María [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Domínguez Ferreras, Esther [Department of Radiology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Gómez López, Ober Van [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Espinosa Arranz, Javier [Department of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain); Soriano Castrejón, Ángel María [Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real (Spain)

    2014-12-15

    Highlights: • We assessed the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection of unsuspected recurrence of colorectal cancer. In regard to our knowledge, no previous experience has been reported about the combined acquisition and interpretation of a FDG-PET/ceCT in the surveillance of colorectal cancer. • We designed a prospective study and performed an individual and combined assessment of both techniques (PET and ceCT), in a patient-based analysis and a lesion-based analysis. • The value of PET and ceCT was found to be similar in the detection of unsuspected recurrence of CRC in a patient-based analysis. The most interesting of our result, is that the combined assessment of PET/ceCT improves the accuracy in the lesion-based analysis. - Abstract: Objective: To assess the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection of unsuspected recurrence of colorectal cancer (CRC) in patients with high risk of relapse. Methods: Thirty-three patients (14 females and 19 males, mean age: 62, range: 41–78), with CRC in complete remission, were prospectively included. All patients underwent FDG-PET/ceCT (58 studies). FDG-PET/ceCT was requested in the surveillance setting, and performed following a standardized protocol. A portal venous phase CT scan was performed after the injection of iodinated contrast agent. An individual and combined assessment of both techniques (PET and ceCT) was performed. Concordant and discordant findings of PET, ceCT and FDG-PET/ceCT were compared in a patient-based and a lesion-based analysis. The final diagnosis, recurrence or disease free status (DFS), were established by histopathology or clinical/radiological follow-up of at least 6 months. Results: Seven out of 33 patients had a confirmed recurrence and the rest of patients had a DFS. In a patient-based analysis the sensitivity and specificity of PET, ceCT and PET/ceCT was of 86% and 88%, 86% and 92%, 86% and 85%, respectively. Attending to

  16. Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma.

    Science.gov (United States)

    Hansmann, Jan; Evers, Maximilian J; Bui, James T; Lokken, R Peter; Lipnik, Andrew J; Gaba, Ron C; Ray, Charles E

    2017-09-01

    To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). This single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P  .05). ALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  17. Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

    Science.gov (United States)

    Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

    2009-02-01

    This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

  18. Brain structure in people at ultra-high risk of psychosis, patients with first-episode schizophrenia, and healthy controls: a VBM study.

    Science.gov (United States)

    Nenadic, Igor; Dietzek, Maren; Schönfeld, Nils; Lorenz, Carsten; Gussew, Alexander; Reichenbach, Jürgen R; Sauer, Heinrich; Gaser, Christian; Smesny, Stefan

    2015-02-01

    Early intervention research in schizophrenia has suggested that brain structural alterations might be present in subjects at high risk of developing psychosis. The heterogeneity of regional effects of these changes, which is established in schizophrenia, however, has not been explored in prodromal or high-risk populations. We used high-resolution MRI and voxel-based morphometry (VBM8) to analyze grey matter differences in 43 ultra high-risk subjects for psychosis (meeting ARMS criteria, identified through CAARMS interviews), 24 antipsychotic-naïve first-episode schizophrenia patients and 49 healthy controls (groups matched for age and gender). Compared to healthy controls, resp., first-episode schizophrenia patients had reduced regional grey matter in left prefrontal, insula, right parietal and left temporal cortices, while the high-risk group showed reductions in right middle temporal and left anterior frontal cortices. When dividing the ultra-high-risk group in those with a genetic risk vs. those with attenuated psychotic symptoms, the former showed left anterior frontal, right caudate, as well as a smaller right hippocampus, and amygdala reduction, while the latter subgroup showed right middle temporal cortical reductions (each compared to healthy controls). Our findings in a clinical psychosis high-risk cohort demonstrate variability of brain structural changes according to subgroup and background of elevated risk, suggesting frontal and possibly also hippocampal/amygdala changes in individuals with genetic susceptibility. Heterogeneity of structural brain changes (as seen in schizophrenia) appears evident even at high-risk stage, prior to potential onset of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

    International Nuclear Information System (INIS)

    Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew; Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A.; Stephans, Kevin L.

    2016-01-01

    Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

  20. Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A. [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephans, Kevin L., E-mail: stephak@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2016-07-01

    Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

  1. Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K; Sato, Hiro; Suzuki, Yoshiyuki; Saitoh, Jun-ichi; Noda, Shin-ei; Seto, Ken-ichi; Torikai, Kota; Sakurai, Hideyuki; Nakano, Takashi

    2014-01-01

    A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. Eighty-eight patients with large brain metastases ≥10 cm 3 in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm 3 for individual lesions. Univariate and multivariate analyses were conducted. As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm 3 (median, 16.2 cm 3 ) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10–19.9 cm 3 , 2) 20–29.9 cm 3 and 3) ≥30 cm 3 . The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm 3 were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction

  2. COMPARISON OF ANTIEMETIC EFFICACY OF ONDANSETRON, GRANISETRON AND PALONOSETRON IN HIGH-RISK PATIENTS UNDERGOING ABDOMINAL HYSTERECTOMY UNDER GENERAL ANAESTHESIA

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2016-03-01

    Full Text Available BACKGROUND Postoperative nausea and vomiting is (PONV a very distressing complication and preventive measures are justified when the risk of PONV is very high. Ondansetron is the first 5-HT3 antagonist used alone or in combination for prophylaxis of PONV due to its lower cost. Granisetron and palonosetron are recently introduced 5-HT3 antagonists with greater affinity for 5-HT3 receptor and having longer half-life. Aim of the present study is to compare the antiemetic efficacy of ondansetron, granisetron and palonosetron in high-risk patients undergoing abdominal hysterectomy under general anaesthesia. METHODS After obtaining Institutional Ethical Committee approval and written informed consent from all the participants, 150 patients of ASA grade I & II, aged between 20-50 years and weight between 30-60 kg undergoing abdominal hysterectomy under general anaesthesia were assigned randomly in to three groups of 50 patients each using random number table receiving either ondansetron 4 mg (Group O or granisetron 2 mg (Group G or palonosetron 0.75 mg (Group P intravenously just before the induction of anaesthesia. Incidence and severity of nausea and frequency of retching and vomiting were recorded in each group at the end of 2-hour and then at 24-hour and 48-hour intervals. RESULTS The incidence of nausea during first two hours postoperatively was found to be 14(28% in Group O, which was found to be significantly higher than 6(12% in group G and 4(8% in group P (p value = 0.016. The incidence of vomiting was found to be 6(12% in group O, which was found to be significantly higher than 2(4% in both group G and group P (p value = 0.018. Number of complete responders was significantly higher in Group P and group G as compared to group O. Number of patients requiring rescue antiemetic treatment was significantly high in group O{10(20%} as compared to 3(6% in both the group G and group P. CONCLUSIONS Newly introduced 5-HT3 antagonists, granisetron and

  3. Naloxone Distribution and Training for Patients with High-Risk Opioid Use in a Veterans Affairs Community-Based Primary Care Clinic.

    Science.gov (United States)

    Raffel, Katie E; Beach, Leila Y; Lin, John; Berchuck, Jacob E; Abram, Shelly; Markle, Elizabeth; Patel, Shalini

    2018-03-30

    Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. The number of patients identified at high risk and rates of naloxone training/distribution. There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care.

  4. Low Rate of Detection of Mucosal High-Risk-Type Human Papillomavirus in Korean Patients with Extragenital Bowen's Disease and Squamous Cell Carcinoma, Especially in Digital Cases

    Directory of Open Access Journals (Sweden)

    Hye-Rim Park

    2013-01-01

    Full Text Available Human papillomavirus (HPV infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (, squamous cell carcinoma (, bowenoid papulosis (, verrucous carcinoma (, actinic keratosis (, and basal cell carcinoma (. We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease ( nor those with squamous cell carcinoma ( showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6% of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (, while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7% of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.

  5. A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma.

    Science.gov (United States)

    Mitchell, Deanna; Bergendahl, Genevieve; Ferguson, William; Roberts, William; Higgins, Timothy; Ashikaga, Takamaru; DeSarno, Mike; Kaplan, Joel; Kraveka, Jacqueline; Eslin, Don; Werff, Alyssa Vander; Hanna, Gina K; Sholler, Giselle L Saulnier

    2016-01-01

    The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C(max), AUC(0-24), t(1/2), CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma. We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m(2). The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m(2) were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy. Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m(2) IV on days 1, 8, and 15 of a 28 day cycle. © 2015 Wiley Periodicals, Inc.

  6. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy.

    Science.gov (United States)

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-11-13

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein-Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤ 46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT.

  7. Preclinical pharmacology, efficacy, and safety of varenicline in smoking cessation and clinical utility in high risk patients

    Directory of Open Access Journals (Sweden)

    Zheng-Xiong Xi

    2010-04-01

    Full Text Available Zheng-Xiong XiNational Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USAAbstract: Smoking is still the most prominent cause of preventable premature death in the United States and an increasing cause of morbidity and mortality throughout the world. Although the current treatments such as nicotine replacement therapy (NRT and bupropion are effective, long-term abstinence rates are low. Mechanism studies suggest that the pleasurable effects of smoking are mediated predominantly by nicotine, which activates the brain reward system by activation of brain α4β2 nicotinic acetylcholine receptors (nAChRs. Varenicline is a novel α4β2 nAChR partial agonist and has been found to be even more effective than NRT or bupropion in attenuating smoking satisfaction and in relieving craving and withdrawal symptoms after abstinence. Thus, varenicline has been recently approved to be a first-line medication for smoking cessation in the United States and European countries. Varenicline is generally well tolerated in healthy adult smokers, with the most commonly reported adverse effects being nausea, insomnia, and headache. However, growing postmarketing data has linked varenicline to an increase in neuropsychiatric symptoms such as seizures, suicidal attempts, depression, and psychosis as well as serious injuries potentially relating to unconsciousness, dizziness, visual disturbances, or movement disorders. Therefore, new safety warnings are issued to certain high risk populations, such as patients with mental illness and operators of commercial vehicles and heavy machinery. In particular, pilots, air traffic controllers, truck and bus drivers have been banned from taking varenicline.Keywords: nicotine, varenicline, α4β2 nicotinic acetylcholine receptor, nAChRs, partial agonist, smoking cessation

  8. Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients.

    Science.gov (United States)

    Fujimoto, Shinichiro; Kondo, Takeshi; Takamura, Kazuhisa; Baber, Usman; Shinozaki, Tomohiro; Nishizaki, Yuji; Kawaguchi, Yuko; Matsumori, Rie; Hiki, Makoto; Miyauchi, Katsumi; Daida, Hiroyuki; Hecht, Harvey; Stone, Gregg W; Narula, Jagat

    2016-06-01

    The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11–33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer–specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8–3.9, p < 0.0001), salvage ADT use (HR 3.9–6.3, p < 0.0001), metastasis (HR 3.7–6.6, p < 0.0001), and PCSM (HR 3.7–16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19–0.38, p < 0.001) and PCSM (HR 0.38–0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3–4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25–0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  10. Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the Children’s Oncology Group NSC #374551; IND# 40294

    Science.gov (United States)

    Villablanca, Judith G.; London, Wendy B.; Naranjo, Arlene; McGrady, Patrick; Ames, Matthew M.; Reid, Joel M.; McGovern, Renee M.; Buhrow, Sarah A.; Jackson, Hollie; Stranzinger, Enno; Kitchen, Brenda J.; Sondel, Paul M.; Parisi, Marguerite T.; Shulkin, Barry; Yanik, Gregory A.; Cohn, Susan L.; Reynolds, C. Patrick

    2011-01-01

    Purpose To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design Patients received 7 days of fenretinide: 2475 mg/m2/day divided TID (<18 years) or 1800 mg/m2/day divided BID (≥18 years) every 21 days for a maximum of 30