Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

Energy Technology Data Exchange (ETDEWEB)

Waal, Esther G.M. de; Vellenga, Edo [University of Groningen, University Medical Center Groningen, Department of Hematology, PO Box 30001, Groningen (Netherlands); Glaudemans, Andor W.J.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Schroeder, Carolien P. [University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen (Netherlands); Slart, Riemer H.J.A. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging, Enschede (Netherlands)

2017-02-15

Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy. (orig.)

Treatment of extramedullary plasmacytoma

International Nuclear Information System (INIS)

Wang Weihu; Li Suyan; Gao Li; Qu Yuan; Xu Guozhen; Li Yexiong

2004-01-01

Objective: To analyze the clinical feature of extramedullary plasmacytoma (EMP) and treatment results. Methods: From Jan. 1960 to Aug. 2000, 28 EMP patients accumulated in a period of 40 odd years were evaluated retrospectively. Sixteen of them were treated with radiotherapy alone (R group, 57.1%) with a median dose of 50 Gy, 11 with combined modality therapy (CMT group, 39.3%) and 1 with surgery alone (S group, 3.6%). Results: During a median follow-up of 90 months (4-280 months), 2 developed local recurrence and 2 were converted to multiple myeloma. The overall 3-, 5-, and 10-year survival rates were 92.6%, 75.6% and 75.6%, respectively. In the R group, the overall 3-, 5-, and 10-year survival rates were 93.8%, 77.3% and 77.3%, as compared with 90.9%, 72.7% and 72.7% in the CMT group (P>0.05). Conclusions: Extramedullary plasmacytoma may well be cured with small field and limited dose of radiation therapy alone. The diagnosis of extramedullary plasmacytoma requires a complete work-up (including MRI) and strict criteria to exclude multiple myeloma. Close follow-up is necessary in those converted to multiple myeloma. (authors)

Extramedullary leukemia in children with acute myeloid leukemia

DEFF Research Database (Denmark)

Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

2017-01-01

BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...... the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy....

Mass-like extramedullary hematopoiesis: imaging features

Energy Technology Data Exchange (ETDEWEB)

Ginzel, Andrew W. [Synergy Radiology Associates, Houston, TX (United States); Kransdorf, Mark J.; Peterson, Jeffrey J.; Garner, Hillary W. [Mayo Clinic, Department of Radiology, Jacksonville, FL (United States); Murphey, Mark D. [American Institute for Radiologic Pathology, Silver Spring, MD (United States)

2012-08-15

To report the imaging appearances of mass-like extramedullary hematopoiesis (EMH), to identify those features that are sufficiently characteristic to allow a confident diagnosis, and to recognize the clinical conditions associated with EMH and the relative incidence of mass-like disease. We retrospectively identified 44 patients with EMH; 12 of which (27%) had focal mass-like lesions and formed the study group. The study group consisted of 6 male and 6 female subjects with a mean age of 58 years (range 13-80 years). All 12 patients underwent CT imaging and 3 of the 12 patients had undergone additional MR imaging. The imaging characteristics of the extramedullary hematopoiesis lesions in the study group were analyzed and recorded. The patient's clinical presentation, including any condition associated with extramedullary hematopoiesis, was also recorded. Ten of the 12 (83%) patients had one or more masses located along the axial skeleton. Of the 10 patients with axial masses, 9 (90%) had multiple masses and 7 (70%) demonstrated internal fat. Eight patients (80%) had paraspinal masses and 4 patients (40%) had presacral masses. Seven patients (70%) had splenomegaly. Eleven of the 12 patients had a clinical history available for review. A predisposing condition for extramedullary hematopoiesis was present in 10 patients and included various anemias (5 cases; 45%), myelofibrosis/myelodysplastic syndrome (4 cases; 36%), and marrow proliferative disorder (1 case; 9%). One patient had no known predisposing condition. Mass-like extramedullary hematopoiesis most commonly presents as multiple, fat-containing lesions localized to the axial skeleton. When these imaging features are identified, extramedullary hematopoiesis should be strongly considered, particularly when occurring in the setting of a predisposing medical condition. (orig.)

Triple manifestation of extramedullary plasmacytoma in the upper airway: an unusual clinical entity.

LENUS (Irish Health Repository)

Morariu, I

2012-02-01

OBJECTIVE: We report an extremely rare case of extramedullary plasmacytoma. METHOD: Case report and review of the English-literature concerning extramedullary plasmacytoma and multiple myeloma. RESULT: We present an unusual case of multiple extramedullary plasmacytomas, which, over a protracted course of 30 years, presented on different occasions at three separate sites in the head and neck. The patient was managed surgically on all occasions, and was disease-free at the time of writing. CONCLUSION: Following review of the literature, we believe this to be the only case with this extremely unusual presentation. This case is noteworthy, not only because of the rarity of extramedullary plasmacytoma, but also because it highlights a number of important clinical issues. The diagnosis and management of extramedullary plasmacytoma require close cooperation between multiple disciplines.

Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

International Nuclear Information System (INIS)

Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn

2014-01-01

We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, 18 F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. 18 F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that 18 F-FDG PET revealed

Extramedullary hematopoiesis presented as cytopenia and massive paraspinal masses leading to cord compression in a patient with hereditary persistence of fetal hemoglobin.

Science.gov (United States)

Katchi, Tasleem; Kolandaivel, Krishna; Khattar, Pallavi; Farooq, Taliya; Islam, Humayun; Liu, Delong

2016-01-01

Extramedullary hematopoeisis (EMH) can occur in various physiological and pathologic states. The spleen is the most common site of EMH. We report a case with hereditary persistence of fetal hemoglobin with extramedullary hematopoiesis presented as cord compression and cytopenia secondary to multi-paraspinal masses. Treatment can be a challenge. Relapse is a possibility.

Extramedullary hematopoiesis presented as cytopenia and massive paraspinal masses leading to cord compression in a patient with hereditary persistence of fetal hemoglobin

OpenAIRE

Katchi, Tasleem; Kolandaivel, Krishna; Khattar, Pallavi; Farooq, Taliya; Islam, Humayun; Liu, Delong

2016-01-01

Background Extramedullary hematopoeisis (EMH) can occur in various physiological and pathologic states. The spleen is the most common site of EMH. Case presentation We report a case with hereditary persistence of fetal hemoglobin with extramedullary hematopoiesis presented as cord compression and cytopenia secondary to multi-paraspinal masses. Conclusion Treatment can be a challenge. Relapse is a possibility.

Detection of Extramedullary Multiple Myeloma in Liver by FDG-PET/CT

Energy Technology Data Exchange (ETDEWEB)

Kim, Daeweung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Choi, Keum Ha; Kim, Chang Guhn [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

2014-06-15

We present the case of a 42-year-old man with a painful mass lesion in the right shoulder that was detected by contrast-enhanced computed tomography (CT) and {sup 18}F-fluoro-2-deoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/CT. Excisional biopsy revealed infiltration of plasma cells with anaplastic features, consistent with solitary plasmacytoma (PC). Serum analysis showed elevation of serum free lambda light chain levels (27.78 mg/l), with an abnormally high kappa:lambda ratio (2.33) and high total proteins (10.4 g/dl). Serum protein electrophoresis revealed an M spike in the gamma-globulin region (56.1 %=5.8 g/dl). Subsequently, {sup 18}F-FDG PET/CT revealed another hypermetabolic mass in the right lobe of the liver. CT-guided biopsy of the liver lesion revealed plasma cell myeloma, consistent with multiple myeloma. Multiple myeloma presenting as nodular liver masses is very rare in clinical practice. In a retrospective review of more than 2,000 patients, Talamo et al. reported only nine cases where there was nodular involvement of the liver by multiple myeloma. The organ most commonly involved was the liver, followed by pancreas, stomach, peritoneum with malignant ascites, colon, rectum, duodenum and ileum. Therefore, the literature published thus far has been limited to a few reports and case series. Among these reports, some had demonstrated the PET or PET/CT findings of nodular liver involvement of multiple myeloma. About 10 % of the solitary myelomas appeared as extramedullary PC or solitary PC of bone. In spite of the advances in therapy, the treatment of multiple myeloma is still palliative. However, solitary PC could be cured by resection or radiation therapy. Thus, differentiation between PC and multiple myeloma is essential in making a decision for the appropriate therapeutic regimen. {sup 18}F-FDG PET/CT has the unique ability to detect and characterize malignant lesions in one single examination. Schirrmeister et al. reported that

Extramedullary plasmocytomas

International Nuclear Information System (INIS)

Ben Salah, H.; Daoud, J.; Hdiji, S.; Elloumi, M.; Makni, S.; Boudawara, T.; Ghorbel, A.M.

2012-01-01

Purpose. - To study the localization, treatment and prognosis of extramedullary plasmocytoma through a series of eight patients and a literature review. Patients and methods. - Eight patients with extramedullary plasmocytoma were treated in the university's hospital of Sfax in Tunisia. The average age was 57.3 years. Female represented 75% of patients. The diagnosis of plasmocytoma was based on anatomo-pathology and immunohistochemistry of a biopsy or resected tumour. Extramedullary location was confirmed if biological and radiological exams and medullary biopsy were normal. The therapeutic decision was made after multidisciplinary meetings regarding tumour location and anterior treatment. Results. - Solitary extramedullary plasmocytoma was located in nasal cavity, cervical node, testis, ovary, bladder and the tongue. One patient was treated for three simultaneous locations of extramedullary plasmocytoma (node, bowel, pleura) without evidence of myeloma. Radiotherapy was proposed in six cases but refused in one case (plasmocytoma of the bladder is currently receiving radiotherapy). Treatment consisted in chemotherapy in two cases. Evaluation after treatment revealed complete remission in 86% of the cases. Nodal recurrence was noted in two cases. These two patients were lost to follow up. The five other patients were in complete remission after a mean follow up of 5.7 years. No local recurrence or myeloma was noted. Conclusion. - Extramedullary plasmocytoma is a rare affection. It can occur in any region of the body. Head and neck is most frequent localization. The treatment is irradiation or surgery in some localization. Progression to myeloma is the most important factor that influences the prognosis of the disease. (authors)

Extramedullary plasmacytoma involving perirenal space accompanied by extramedullary hematopoiesis and amyloid deposition.

Science.gov (United States)

Mimura, Rie; Kamishima, Tamotsu; Kubota, Kanako C; Nakano, Fumihito; Yabe, Ichiro; Sasaki, Hidenao; Maruyama, Satoru; Shinohara, Nobuo; Harris, Ardene A; Haga, Hironori; Shirato, Hiroki; Terae, Satoshi

2010-05-01

A 62-year-old man was referred to us after unsuccessful treatment of bilateral weakness in his upper and lower extremities with paresthesia in both lower extremities. Computed tomography (CT) revealed soft tissue masses in the left kidney along the capsule and paraaortic region that were of relatively low attenuation with accompanying granular calcifications. Pathological diagnosis of the biopsy specimen was extramedullary plasmacytoma accompanied by extramedullary hematopoiesis and amyloid deposition. Although the CT findings correlated well with the pathological results, the case was extremely atypical for extramedullary plasmacytoma in respect to location and the accompaniment with extramedullary hematopoiesis.

Solitary extramedullary plasmacytoma of the sinonasal region.

Science.gov (United States)

Hazarika, Produl; Balakrishnan, R; Singh, Rohit; Pujary, Kailesh; Aziz, Benazim

2011-07-01

Less than 10% of the patients with plasma cell neoplasms present with a solitary plasmacytoma. Though the nasal cavity is a common extramedullary site, the occurrence is extremely rare. Two cases of solitary extramedullary plasmacytoma of the sinonasal region are reported. The first of which is sinonasal plasmacytoma with concomitant HIV, an association that has been reported rarely in literature to date and is matter of much debate. In the second case report, we present an instance of surgical excision of the tumor using KTP 532 laser. The diagnosis was established using immunohistochemical techniques and multiple myeloma workups were negative in all cases.

Atypical location of extramedullary hematopoietic masses in thalassemia

International Nuclear Information System (INIS)

Gemenis, T.; Philippou, A.; Gouliamos, A.; Kalovidouris, A.; Papavasiliou, C.; Papacharalambus, X.; Panani, A.; Chalevelakis, G.; Raptis, S.

1989-01-01

A case of β-thalassemia with multiple foci of extramedullary hematopoiesis (EH) is reported. EH masses were demonstrated in the presacral and the costovertebral space. EH foci were also encountered in the spleen. (orig.) [de

Focal splenic masses of the extramedullary hematopoiesis

International Nuclear Information System (INIS)

Incedayi, M.; Sivrioglu, A.

2012-01-01

Full text: Extramedullary hematopoiesis arises from pleuripotential stem cells distributed throughout the body. It is most common in patients with congenital hemolytic anemia, such as thalassemia, sickle cell anemia and hereditary spherocytosis as a response to ineffective red blood cell formation. Although microscopic foci of Extramedullary hematopoiesis are commonly seen in the spleen and liver parenchyma, focal mass-like lesion of extramedullary hematopoiesis in the liver and spleen are rare. We report a case of intrasplenic focal extramedullary hematopoiesis lesions and the imaging features of extramedullary hematopoiesis on computed tomography and magnetic resonance imaging. Extramedullary hematopoiesis should always be considered as a diagnosis in a patient with a known hematological disorder

Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

Science.gov (United States)

Kalincik, Tomas

2015-01-01

Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

MRI features of epidural extramedullary hematopoiesis

Energy Technology Data Exchange (ETDEWEB)

Alorainy, Ibrahim A. E-mail: alorainy@ksu.edu.sa; Al-Asmi, Abdullah R.; Carpio, Raquel del

2000-07-01

A case of {beta}-thalassemia intermedia with spinal cord compression due to extramedullary hematopoiesis, which was successfully treated by blood transfusion, is presented. Emphasis was made on the MRI appearance of extramedullary hematopoiesis on different pulse sequences. The theories that aimed to explain the involvement of the epidural space by extramedullary hematopoiesis are discussed.

MRI features of epidural extramedullary hematopoiesis

International Nuclear Information System (INIS)

Alorainy, Ibrahim A.; Al-Asmi, Abdullah R.; Carpio, Raquel del

2000-01-01

A case of β-thalassemia intermedia with spinal cord compression due to extramedullary hematopoiesis, which was successfully treated by blood transfusion, is presented. Emphasis was made on the MRI appearance of extramedullary hematopoiesis on different pulse sequences. The theories that aimed to explain the involvement of the epidural space by extramedullary hematopoiesis are discussed

Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

International Nuclear Information System (INIS)

Niggemann, P.; Krings, T.; Thron, A.; Hans, F.

2005-01-01

A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained

Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

Energy Technology Data Exchange (ETDEWEB)

Niggemann, P.; Krings, T.; Thron, A. [Dept. of Neuroradiology, RWTH-Aachen Hosital (Germany); Hans, F. [Dept. of Neurosurgery, RWTH Aachen Hospital (Germany); 1

2005-04-01

A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained.

Primary extramedullary plasmacytoma of the penis: a case report.

Science.gov (United States)

Wang, Yao; Li, Hong-Yan; Liang, Ting-Ting; Han, Yu-Ping; Wang, Xue-Ju; Wei, Xin; Fan, Li; Wang, Wei-Hua

2013-10-01

Extramedullary plasmacytoma involving the penis is extremely rare. Here, we describe a case of primary extramedullary plasmacytoma of the penis in a 64-year-old man who presented with a palpable penile mass. Nuclear magnetic resonance imaging revealed the presence of a large, round non-encapsulated mass in the perineum. A contrast-enhanced computed tomography scan of the pelvis showed that the mass was located in the tunica albuginea and corpora cavernosa at the base of the penis. The mass encased the urethra and demonstrated no marked enhancement during the arterial phase. The patient underwent successful surgical resection of the tumor. Histologically, the tumor was composed primarily of neoplastic plasma cells that were positive for CD38, vimentin and Ki 67. Postoperatively, the patient recovered well and exhibited no evidence of development of multiple myeloma, local recurrence or distant metastasis at 2 months post-surgery. To the best of our knowledge, our case represents the first documented case of human primary extramedullary plasmacytoma of the penis.

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

NARCIS (Netherlands)

P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

2005-01-01

textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast

Directory of Open Access Journals (Sweden)

Liu Yan-Xue

2009-04-01

Full Text Available Abstract Background Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported. Case presentation A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma. Conclusion In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects.

Extramedullary plasmacytoma of the larynx. A report of three cases

International Nuclear Information System (INIS)

Strojan, P.

2002-01-01

Purpose. To report three cases of extramedullary plasmacytoma of the larynx treated at the Institute of Oncology in Ljubljana between 1969-1999. Results. All three patients were treated with radiotherapy only, which resulted in permanent local and regional control of 7.8, 4.7 and 3.5 years. The function of the larynx was preserved in all of them. Two patients died, both to the causes other than plasmacytoma. In none of the patients disease progressed to multiple myeloma. Conclusions. Extramedullary plasmacytoma of the larynx is a rare disease, highly curable when radiotherapy is used. Moderate radiation doses and limited fields ensure excellent cosmetic and functional result. (author)

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

Science.gov (United States)

Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

2015-01-08

Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

NARCIS (Netherlands)

Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

2006-01-01

BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

Cladribine tablets for relapsing-remitting multiple sclerosis

DEFF Research Database (Denmark)

Rammohan, Kottil; Giovannoni, Gavin; Comi, Giancarlo

2012-01-01

BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses...... of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. METHODS: Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease...... activity at baseline. RESULTS: In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40...

Intrathoracic extramedullary hematopoiesis presenting as tumor-simulating lesions of the mediastinum in α-thalassemia: A case report.

Science.gov (United States)

An, Jun; Weng, Yimin; He, Jinyuan; Li, Yun; Huang, Shaohong; Cai, Songwang; Zhang, Junhang

2015-10-01

Extramedullary hematopoiesis (EMH) is a rare disease, where hematological disorder drives extramedullary hematopoietic tumor formation in multiple regions of the body. The present study reports a case of EMH presenting as multiple tumor-like lesions of mediastinum in a 61-year-old male with α-thalassemia, which was subjected to a video-assisted thoracoscopic surgery tissue biopsy to differentiate it from other mediastinal tumors. To date, only three cases of EMH in patients with α-thalassemia have been described in the literature. Patients with EMH typically exhibit no hematological disorder preoperatively and therefore EMH is frequently misdiagnosed. In the present study, along with a literature review of the clinicopathological features of EMH, the diagnosis and treatment of this rare case was discussed, in order to differentiate diagnosis, and particularly to distinguish EHM from extramedullary myeloid sarcoma.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

DEFF Research Database (Denmark)

Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

2010-01-01

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

Burden of a multiple sclerosis relapse: the patient's perspective.

Science.gov (United States)

Oleen-Burkey, Merrikay; Castelli-Haley, Jane; Lage, Maureen J; Johnson, Kenneth P

2012-01-01

Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the

Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

DEFF Research Database (Denmark)

Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

2012-01-01

The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

DEFF Research Database (Denmark)

Fazekas, F.; Lublin, F.D.; Li, D.

2008-01-01

OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

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Serhan Sevim

2016-09-01

Full Text Available Relapse in multiple sclerosis (MS is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the postpartum first 3 months. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed.

Extramedullary plasmacytoma. Fine needle aspiration findings.

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Kumar, P V; Owji, S M; Talei, A R; Malekhusseini, S A

1997-01-01

To determine the role of fine needle aspiration cytology in the diagnosis of extramedullary plasmacytoma. The study group consisted of 13 patients with palpable masses at various sites. The tumors were aspirated for cytologic study. The smears revealed groups of mature and immature plasma cells at various stages of maturation. Mature plasma cells showed an eccentric nucleus and abundant, deep, basophilic cytoplasm with a paranuclear halo. Plasmablasts (immature plasma cells) showed a prominent, eccentric nucleus with single, large nucleolus and abundant, deep, basophilic cytoplasm with no paranuclear halo. Binucleate and multinucleate forms were also seen quite often. The tumors were excised, and the histologic sections confirmed the cytologic diagnosis. All the patients received radiotherapy. One patient (18 years old) developed recurrence and died due to extensive infiltration into the maxilla and mandible. Two patients (57 and 62 years) developed multiple myeloma one to two years after the excision of tumors, and both died two to three months later. The remaining 10 patients were alive and well at this writing. The smears from all 13 patients were diagnosed as extramedullary plasmacytomas by fine needle aspiration cytology.

Epidural extramedullary haemopoiesis in thalassaemia

International Nuclear Information System (INIS)

Boyacigil, S.; Ali, A.; Ardic, S.; Yuksel, E.

2002-01-01

lntrathoracic extramedullary haematopoiesis is a rare condition. Involvement of the spinal epidural space with haematopoietic tissue is rather unusual. A 31-year-old-man with a known diagnosis of β-thalassaemia was referred with focal back pain. Magnetic resonance imaging revealed diffuse bone-marrow changes, thoracic paraspinal masses and lobulated epidural masses, suggesting extramedullary haemopoiesis. The patient was treated with radiotherapy and blood transfusions. Follow-up MRI was performed for evaluation efficacy of the treatment. Copyright (2002) Blackwell Science Pty Ltd

Extramedullary plasmacytoma of the testicle.

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Carrion, Diego M; Álvarez-Maestro, Mario; Gómez Rivas, Juan; González-Peramato, Pilar; Cisneros Ledo, Jesús

2017-12-01

We present the case of a patient diagnosed with a testicular extramedullary plasmacytoma (EMP), and perform a brief review of the literature of this pathology. A 64 year-old male patient, with history of multiple myeloma successfully treated three years before, presented with left testicular swelling. Initial work-up was compatible with a testicular tumor and radical inguinal orchiectomy was performed. Histologic examination of the testis revealed extensive intertubular infiltration by CD138 and CD56 atypical plasma cells, with diffuse staining for IgA, compatible with EMP. Invasion of the testis in multiple myeloma patients as a recurrence of the disease is an extremely rare condition, as EMPs are more common in other organ systems. Initial treatment should be the same as a primary testicular tumor with radical inguinal orchiectomy, and definitive diagnosis is established in histologic analysis.

Increased multiple sclerosis relapses related to lower prevalence of pain

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José Vinícius Martins da Silva

2015-07-01

Full Text Available Objective The study aims to investigate the presence of pain amongst multiple sclerosis (MS patients. Method One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann–Whitney U, Chi-Square and two-tailed Fisher’s exact tests and multivariate logistic regression. Results Women had a statistically higher prevalence of pain (p = 0.037, and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003, restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS anxiety, and depression. Conclusion Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain.

Surgical treatment of an unusual case of pelvic extramedullary hematopoiesis.

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Khen-Dunlop, Naziha; Girot, Robert; Brunelle, Francis; Révillon, Yann; Nihoul-Fékété, Claire; Sarnacki, Sabine

2006-07-01

Extramedullary hematopoiesis affects about 15% of the patients treated for thalassemia intermedia. Usually seen in adulthood, the most common location is the paraspinal region. Diagnosis and treatment of extramedullary hematopoiesis located in the pelvis of a young 15-year-old girl is discussed. The young age of the patient and the uncommon site of the mass first lead to the diagnosis of an ovarian dermoid cyst. Because of the clinical history and the typical feature on computed tomography scan, extramedullary hematopoiesis was concluded. A specific treatment based on blood transfusion and hydroxyurea was first proposed but remained inefficient. Surgical excision was thus successfully performed. Whereas surgery is limited to spinal cord compression in paraspinal extramedullary hematopoiesis, this observation argues for surgical treatment in symptomatic intraabdominal extramedullary hematopoiesis when medical treatment fails.

Extramedullary paraspinal hematopoiesis in thalassemia: CT and MRI evaluation

International Nuclear Information System (INIS)

Tsitouridis, J.; Stamos, S.; Hassapopoulou, E.; Tsitouridis, K.; Nikolopoulos, P.

1999-01-01

We present a comparative CT and MRI study of the paraspinal extramedullary hematopoiesis in 32 thalassemic patients. The patients were classified into four groups according to the MRI and CT imaging findings. Active recent extramedullary paraspinal hematopoietic masses show soft tissue behavior in both CT and MRI. Older inactive masses reveal iron deposition or fatty replacement. Combined imaging findings of paraspinal extramedullary hematopoiesis revealed the phase of its evolution and the correct diagnosis

Extramedullary paraspinal hematopoiesis in thalassemia: CT and MRI evaluation

Energy Technology Data Exchange (ETDEWEB)

Tsitouridis, J.; Stamos, S.; Hassapopoulou, E.; Tsitouridis, K.; Nikolopoulos, P

1999-04-01

We present a comparative CT and MRI study of the paraspinal extramedullary hematopoiesis in 32 thalassemic patients. The patients were classified into four groups according to the MRI and CT imaging findings. Active recent extramedullary paraspinal hematopoietic masses show soft tissue behavior in both CT and MRI. Older inactive masses reveal iron deposition or fatty replacement. Combined imaging findings of paraspinal extramedullary hematopoiesis revealed the phase of its evolution and the correct diagnosis.

Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

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Genaro Gabriel Ortiz

2009-01-01

Full Text Available Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old and 7 men (5 aged from 20 to 30 and 2 were > 40 years old fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites, lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals, and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.

Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

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Amy ePerrin Ross

2013-03-01

Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

Radiotherapy of extramedullary plasmacytoma of the head and neck

International Nuclear Information System (INIS)

Harwood, A.R.; Knowling, M.A.; Bergsagel, D.E.

1981-01-01

The purpose of this study is to report the results of megavoltage irradiation with cobalt-60 in 23 previously unreported cases of extramedullary plasmacytoma of the head and neck. It has been found that 3500 cGy (rad) in three weeks provides good local control of disease with minimal morbidity and a significant proportion do not go on to multiple myeloma. Prognostic factors of significance with respect to subsequent development of multiple myeloma include site and presence or absence of bone destruction. The presence or absence of an M protein peak appears to be of no significance. (author)

Modifiable factors influencing relapses and disability in multiple sclerosis

NARCIS (Netherlands)

D'hooghe, M. B.; Nagels, G.; Bissay, V.; De Keyser, J.

A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and

Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax infection.

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Flávia Carolina F de Araujo

Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.

Natalizumab for the treatment of relapsing multiple sclerosis

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Richard A Rudick

2008-06-01

Full Text Available Richard A Rudick1, Michael A Panzara21Cleveland Clinic Foundation, Cleveland, OH, USA; 2Biogen Idec, Inc., Cambridge, MA, USAAbstract: Natalizumab is an α4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS, based on demonstrated efficacy in the pivotal AFFIRM study (N = 942. Natalizumab monotherapy reduced risk of disability progression by 42%–54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was also associated with significant reductions in number of T2-hyperintense, gadolinium-enhancing, and T1-hypointense lesions and in volume of T2-hyperintense lesions (all p < 0.001 on magnetic resonance imaging. Furthermore, natalizumab-treated patients in AFFIRM experienced significant improvements from baseline in the physical and mental components of the Short Form-36 (p ≤ 0.01 and a 35% reduction in risk of clinically significant vision loss (p = 0.008 vs placebo. Natalizumab was well tolerated in phase 3 studies. Common adverse events were generally mild and included headache, fatigue, urinary tract infections, and arthralgia. Serious adverse events were similar between treatment groups. The incidence of serious hypersensitivity reactions associated with natalizumab was <1%. Progressive multifocal leukoencephalopathy was a rare complication of treatment, observed in 2 patients with MS who received natalizumab plus interferon β-1a. The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.Keywords: multiple sclerosis, natalizumab, α4-integrin antagonist

Extramedullary Hematopoiesis: An Unusual Finding in Subdural Hematomas

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Rong Li

2011-01-01

Full Text Available We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.

Different cognitive profiles of Brazilian patients with relapsing-remitting and primary progressive multiple sclerosis

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Dóra-Neide Rodrigues

2011-08-01

Full Text Available Cognitive impairment is a symptom of multiple sclerosis (MS. Different clinical forms of multiple sclerosis have different cognitive profiles, according to findings of previous studies which used extensive batteries of neuropsychological tests. OBJECTIVE: To investigate cognitive profiles of Brazilian patients with relapsing-remitting multiple sclerosis (RRMS and primary progressive multiple sclerosis (PPMS by using a brief battery of neuropsychological tests. METHOD: Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired with healthy control subjects, regarding gender, age, and education level. RESULTS: On Symbol Digit Modalities Test and Hooper Visual Organization Test, cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and in 69% of primary progressive. CONCLUSION: Cognitive profiles of relapsing-remitting and primary progressive patients are different

Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis.

Science.gov (United States)

Cario, H; Wegener, M; Debatin, K-M; Kohne, E

2002-08-01

Excessive ineffective erythropoiesis in thalassemia intermedia may cause paravertebral pseudotumors of extramedullary hematopoiesis. Due to the proximity to the spinal canal, these paravertebral masses carry the risk of severe neurological damage. Treatment strategies include hypertransfusion, radiotherapy, and laminectomy. Hydroxyurea, stimulating fetal hemoglobin synthesis, may represent an alternative therapeutic approach. We report on a 26-year-old patient suffering from thalassemia intermedia with progressive anemia symptoms and presenting multiple intrathoracic paravertebral pseudotumors of extramedullary hematopoiesis. Hypertransfusion therapy and splenectomy were followed by regular transfusion (baseline hemoglobin 10 g/dl) and chelation with desferrioxamine. With this treatment, clinical symptoms disappeared, paravertebral hematopoietic masses did not progress, but severe hemosiderosis developed within a few years. Hydroxyurea therapy was initiated to increase the efficacy of erythropoiesis, thereby reducing the required transfusion volume but suppressing concomitantly further expansion of extramedullary hematopoiesis, and finally leading to a reduction of transfusional iron load. Treatment was started with 4 mg/kg per day and stepwise increased to 12.5 mg/kg per day. The fetal hemoglobin concentration increased from 4.5 to 5.5 g/dl after 1 year and to 9.9 g/dl after 2 years of treatment. The yearly transfusion volume was halved during the 1st year of treatment. At present, after 26 months of treatment, the patient has been transfusion-independent for 10 months. Serum ferritin levels decreased from 2844 to 1335 ng/ml. Size and shape of paravertebral hematopoietic pseudotumors remained stable. No side effects of hydroxyurea have been observed. In thalassemia intermedia patients with extramedullary hematopoiesis, hydroxyurea may lead to independence from regular transfusion therapy without further expansion of ectopic hematopoietic tissue.

The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability.

Science.gov (United States)

Scalfari, Antonio; Neuhaus, Anneke; Degenhardt, Alexandra; Rice, George P; Muraro, Paolo A; Daumer, Martin; Ebers, George C

2010-07-01

The relationship of relapses to long-term disability in multiple sclerosis is uncertain. Relapse reduction is a common therapeutic target but clinical trials have shown dissociation between relapse suppression and disability accumulation. We investigated relationships between relapses and disability progression for outcomes of requiring assistance to walk, being bedridden and dying from multiple sclerosis [Disability Status Scale 6, 8, 10] by analysing 28 000 patient-years of evolution in 806-bout onset patients from the London Ontario natural history cohort. Having previously shown no effect of relapse frequency among progressive multiple sclerosis subtypes, here we examined these measures in the pre-progressive or relapsing-remitting phase. Survival was compared among groups stratified by (i) early relapses--number of attacks during the first 2 years of multiple sclerosis; (ii) length of first inter-attack interval; (iii) interval between onset and Disability Status Scale 3 (moderate disability); (iv) number of attacks from the third year of disease up to onset of progression; and (v) during the entire relapsing-remitting phase. Early clinical features can predict hard disability outcomes. Frequent relapses in the first 2 years and shorter first inter-attack intervals predicted shorter times to reach hard disability endpoints. Attack frequencies, in the first 2 years, of 1 versus >or=3, gave differences of 7.6, 12.8 and 20.3 years in times from disease onset to Disability Status Scale 6, 8 and 10, respectively. Time to Disability Status Scale 3 highly and independently predicted time to Disability Status Scale 6, 8 and 10. In contrast, neither total number of relapsing-remitting phase attacks nor of relapses experienced during the relapsing-remitting phase after the second year up to onset of progression showed a deleterious effect on times from disease onset, from progression onset and from Disability Status Scale 3 to these hard endpoints. The failure of a

Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin's lymphoma: 1985. A report from the Childrens Cancer Study Group

International Nuclear Information System (INIS)

Bleyer, W.A.; Sather, H.; Hammond, G.D.

1986-01-01

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy

Intracranial extramedullary hematopoiesis: a rare cause of headaches.

Science.gov (United States)

Singer, Adam; Quencer, Robert

2014-01-01

Ectopic bone marrow production, known as extramedullary hematopoiesis, may result in symptoms due to compression on normal structures. We present the multimodality imaging findings and subsequent management of a rare case of symptomatic extramedullary hematopoiesis within the calvarium. Case report. A 54-year-old male with a history of myelofibrosis and no previous diagnosis of a headache disorder presented to the emergency department with worsening severe bilateral headaches. A nonenhanced CT of the brain was performed and diffuse extra-axial nodular hyperdensities were visualized. MRI of the brain demonstrated diffuse extra-axial avidly enhancing nodular masses, dural thickening and marked susceptibility. No paravertebral masses, typical for extramedullary hematopoiesis, were present in the chest or abdomen. Although the clinical team considered a biopsy to confirm the diagnosis, we suggested a noninvasive confirmatory test. The subsequent Tc99m sulfur colloid scan corroborated the diagnosis. The patient was then referred to radiation oncology for treatment. In summary, extramedullary hematopoiesis is a hematologic compensatory disorder that rarely occurs within the CNS and may cause neurological compromise due to compression on underlying structures. The diagnosis can be made with noninvasive imaging and treated with low dose radiation therapy. Copyright © 2013 by the American Society of Neuroimaging.

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Biggins, J.A.; Taylor, A.; Caspary, E.A.

1978-01-01

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

Extramedullary versus intramedullary tibial cutting guides in megaprosthetic total knee replacement

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Karade Vikas

2012-10-01

Full Text Available Abstract Background In a standard total knee replacement, tibial component alignment is a key factor for the long term success of the surgery. The purpose of this study is to compare the accuracy of extramedullary and intramedullary tibial cutting guides used in indigenous and imported implants respectively, in positioning of the tibial components in megaprosthetic knee replacements. Methods A comparative study of the accuracy of extramedullary and intramedullary tibial cutting guides was carried out in 92 megaprosthetic knee replacements for distal femoral tumors. For the proximal tibia cut for tibial component placement, an extramedullary guide was used in 65 patients and an intramedullary guide was used in 27 patients. Tibial component alignment angles were measured in postoperative X-rays with the help of CAD software. Results There was more varus placement in coronal plane with extramedullary cutting guide (−1.18 +/− 2.4 degrees than the intramedullary guide (−0.34 +/− 2.31 degrees but this did not reach statistical significance. The goal of 90 +/− 2 degrees alignment of tibial component was achieved in 54% of patients in the extramedullary group versus 67% in the intramedullary group. In terms of sagittal plane alignment, extramedullary guide showed less accurate results (2.09 +/− 2.4 degrees than intramedullary guide (0.50 +/− 3.80 degrees for tibial component alignment, though 78% of patients were aligned within the goal of 0–5 degrees of tibial slope angle in extramedullary group versus 63% in intramedullary group. The mean error in the measurements due to rotation of the knee during taking the X-rays was less than 0.1 degrees and distribution of the X-rays with the rotation of knee was similar in both the groups. Conclusions Overall, in megaprosthetic knee replacement intramedullary guides gave more accurate results in sagittal plane and exhibited similar variability as of extramedullary guides in coronal plane.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

DEFF Research Database (Denmark)

Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

2010-01-01

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

Science.gov (United States)

Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

2016-05-01

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

Science.gov (United States)

Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

2010-01-01

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

Evolving concepts in the treatment of relapsing multiple sclerosis

DEFF Research Database (Denmark)

Comi, Giancarlo; Radaelli, Marta; Soelberg Sørensen, Per

2017-01-01

In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical...... or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started...... as early as possible and aim to re-establish the normal complex interactions in the immune system. Before starting a treatment, neurologists should carefully consider the state of the disease, its prognostic factors and comorbidities, the patient's response to previous treatments, and whether the patient...

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

Science.gov (United States)

Kalincik, Tomas; Brown, J William L; Robertson, Neil; Willis, Mark; Scolding, Neil; Rice, Claire M; Wilkins, Alastair; Pearson, Owen; Ziemssen, Tjalf; Hutchinson, Michael; McGuigan, Christopher; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Alroughani, Raed; Pucci, Eugenio; Sola, Patrizia; Hupperts, Raymond; Lechner-Scott, Jeannette; Terzi, Murat; Van Pesch, Vincent; Rozsa, Csilla; Grand'Maison, François; Boz, Cavit; Granella, Franco; Slee, Mark; Spitaleri, Daniele; Olascoaga, Javier; Bergamaschi, Roberto; Verheul, Freek; Vucic, Steve; McCombe, Pamela; Hodgkinson, Suzanne; Sanchez-Menoyo, Jose Luis; Ampapa, Radek; Simo, Magdolna; Csepany, Tunde; Ramo, Cristina; Cristiano, Edgardo; Barnett, Michael; Butzkueven, Helmut; Coles, Alasdair

2017-04-01

Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], pmultiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly

Extramedullary plasmacytoma in the trachea of a dog.

Science.gov (United States)

Chaffin, K; Cross, A R; Allen, S W; Mahaffey, E A; Watson, S K

1998-05-15

A 10-year-old spayed female mixed-breed dog was examined because of acute inspiratory dyspnea. Radiography and tracheoscopy revealed a discrete, solitary mass originating from the membranous portion of the trachea at the level of the thoracic inlet. Tracheal resection and anastomosis were performed, and on histologic examination of the resected tissue, extramedullary plasmacytoma was diagnosed. Although tracheal tumors are rare in dogs, they should be considered during evaluation of dogs with signs of airway obstruction. Prognosis is excellent for dogs with extramedullary plasmacytoma in which surgical excision is complete.

Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

Science.gov (United States)

Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

2014-01-01

For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of �

[A case of cutaneous extramedullary hematopoiesis associated with idiopathic myelofibrosis].

Science.gov (United States)

Corella, F; Barnadas, M A; Bordes, R; Curell, R; Espinosa, I; Vergara, C; Alomar, A

2008-05-01

Cutaneous extramedullary hematopoiesis is a rare manifestation of chronic myeloproliferative processes, mainly chronic idiopathic myelofibrosis. In adults, it manifests as macules, papules, nodules, and ulcers on the trunk. The lesions usually appear soon after diagnosis and the possibility of a relationship between splenectomy and the appearance of extramedullary foci of hematopoiesis is still debated. Diagnosis is based on histopathology showing an infiltrate with different combinations of myeloid and erythroid cell precursors and megakaryocytes. Symptomatic treatment is provided alongside treatment of the underlying disease. We report a new case associated with chronic idiopathic myelofibrosis in which foci of cutaneous extramedullary hematopoiesis were observed 9 years after initial diagnosis. The lesions were progressive and the patient went on to develop acute myeloid leukemia.

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

Science.gov (United States)

Cohan, Stanley

2016-01-01

Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

NARCIS (Netherlands)

De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

Pulmonary Extramedullary Hematopoiesis in a Patient with Chronic Asthma Resembling Lung Cancer: A Case Report

Directory of Open Access Journals (Sweden)

Massood Hosseinzadeh

2012-01-01

Full Text Available Background. Extramedullary hematopoiesis is most often seen in reticuloendothelial organs specially spleen, liver, or lymph nodes, and it is rarely seen in lung parenchyma. Almost all reported cases of pulmonary extramedullary hematopoiesis occurred following myeloproliferative disorders specially myelofibrosis. Other less common underlying causes are thalassemia syndromes and other hemoglobinopathies. There was not any reported case of pulmonary extramedullary hematopoiesis in asthmatic patients in the medical literature. Case. Here we reported a 65-year-old lady who was a known case of bronchial asthma with recent developed right lower lobe lung mass. Chest X-ray and CT studies showed an infiltrating mass resembling malignancy. Fine needle aspiration cytology of mass revealed pulmonary extramedullary hematopoiesis. The patient followed for 10 months with serial physical examination and laboratory evaluations which were unremarkable. Conclusion. Extramedullary hematopoiesis of lung parenchyma can be mistaken for lung cancer radiologically. Although previous reported cases occurred with myelofibrosis or hemoglobinopathies, we are reporting the first case of asthma-associated extramedullary hematopoiesis.

Extramedullary hematopoiesis: A report of two cases.

Science.gov (United States)

Zhang, Huan-Zhu; Li, Ying; Liu, Xin; Chen, Bao-Rong; Yao, Guo-Hua; Peng, Yu-Na

2016-12-01

Extramedullary hematopoiesis (EMH) is defined as hematopoiesis occurring in organs outside of the bone marrow. The present report describes two cases of thalassemic patients with paraspinal medullary hematopoiesis and analyzes the clinical manifestations, imaging, pathology, diagnosis and treatment of EMH. In addition, a supplementary review of previously published cases is provided along with a review of the related literature. Computed tomography (CT) of the first case revealed multiple paraspinal masses, and the largest was 6.2×8.0 cm in diameter. Likewise, CT of the second patient revealed multiple paraspinal masses in the bottom of the left thoracic cavity, and the largest was measured 10.1×10.5 cm. The two cases underwent surgical biopsy and the findings were compatible with a diagnosis of EMH. In conclusion, EMH is a compatible and rare disease, and should be distinguished from other neoplasms. EMH must considered when masses with characteristic radiologic appearance are detected in patients with thalassemia intermedia.

Soft Tissue Extramedullary Plasmacytoma

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Fernando Ruiz Santiago

2010-01-01

Full Text Available We present the uncommon case of a subcutaneous fascia-based extramedullary plasmacytoma in the leg, which was confirmed by the pathology report and followed up until its remission. We report the differential diagnosis with other more common soft tissue masses. Imaging findings are nonspecific but are important to determine the tumour extension and to plan the biopsy.

Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

Science.gov (United States)

Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

2015-12-01

Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

Science.gov (United States)

Li, Xiao-ling; Zhang, Zhen-chang; Zhang, Bo; Jiang, Hua; Yu, Chun-mei; Zhang, Wen-jing; Yan, Xiang; Wang, Man-xia

2014-12-01

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Spinal cord compression due to epidural extramedullary haematopoiesis in thalassaemia: MRI

International Nuclear Information System (INIS)

Aydingoez, Ue.; Oto, A.; Cila, A.

1997-01-01

Spinal epidural extramedullary haematopoiesis is very rare in thalassaemia. A 27-year-old man with thalassaemia intermedia presented with symptoms and signs of spinal cord compression. MRI showed a thoracic spinal epidural mass, representing extramedullary haematopoietic tissue, compressing the spinal cord. Following radiotherapy, serial MRI revealed regression of the epidural mass and gradual resolution of spinal cord oedema. (orig.)

Second auto-SCT for treatment of relapsed multiple myeloma.

Science.gov (United States)

Gonsalves, W I; Gertz, M A; Lacy, M Q; Dispenzieri, A; Hayman, S R; Buadi, F K; Dingli, D; Hogan, W J; Kumar, S K

2013-04-01

High-dose therapy and auto-SCT remain integral in the initial treatment of multiple myeloma (MM), and are increasingly being applied for management of relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto-SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1) between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74). The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130). Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was 10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2 was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher number of treatment regimens before auto-SCT2 and a higher plasma cell labeling index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an effective and feasible therapeutic option for MM patients relapsing after other treatments, especially in patients who had a TTP of at least 12 months after their auto-SCT1.

Sacral Myeloid Sarcoma Manifesting as Radiculopathy in a Pediatric Patient: An Unusual Form of Myeloid Leukemia Relapse

Directory of Open Access Journals (Sweden)

Joana Ruivo Rodrigues

2018-01-01

Full Text Available Myeloid sarcoma (MS, granulocytic sarcoma or chloroma, is defined as a localized extramedullary mass of blasts of granulocytic lineage with or without maturation, occurring outside the bone marrow. MS can be diagnosed concurrently with acute myeloid leukemia (AML or myelodysplastic syndrome (MDS. The authors report a case of sacral MS occurring as a relapse of myeloid leukemia in a 5-year-old girl who was taken to the emergency department with radiculopathy symptoms.

MRI findings of extramedullary haemopoiesis

International Nuclear Information System (INIS)

Chourmouzi, D.; Pistevou-Gompaki, K.; Plataniotis, G.; Skaragas, G.; Papadopoulos, L.; Drevelegas, A.

2001-01-01

Extramedullary haemopoiesis (EH) is a compensatory process associated with chronic haemolytic anaemia. It is rare, however, for such an abnormality to cause spinal cord compression. We present two patients with known beta-thalassaemia intermedia who developed spinal cord compression due to masses of extramedullary haematopoietic tissue in the epidural space of the thoracic spine. The EH masses were diagnosed by MRI as an isointense epidural lesion on both T1- and T2-weighted images, compressing severely the spinal cord. After administration of a paramagnetic agent, an intermediate enhancement of the masses was evident. All the vertebral bodies had low to intermediate signal intensity as a result of displacement of fatty marrow by haematopoietic marrow. Expansion of thoracic ribs with bilateral paravertebral masses were characteristic. A small dose of radiotherapy was given and marked improvement in neurological symptoms was evident. An MRI examination established shrinkage of the mass and decompression of spinal cord. The role of MRI in diagnosis of EH masses is essential and radiation therapy is a very effective treatment for this rare complication. (orig.)

Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

Science.gov (United States)

Vercellino, Marco; Fenoglio, Chiara; Galimberti, Daniela; Mattioda, Alessandra; Chiavazza, Carlotta; Binello, Eleonora; Pinessi, Lorenzo; Giobbe, Dario; Scarpini, Elio; Cavalla, Paola

2016-07-01

Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia. In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers. We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01). GRN genetic polymorphisms likely influence disease course and relapse recovery in MS. © The Author(s), 2015.

Spinal cord compression due to epidural extramedullary haematopoiesis in thalassaemia: MRI

Energy Technology Data Exchange (ETDEWEB)

Aydingoez, Ue.; Oto, A.; Cila, A. [Department of Radiology, Hacettepe University School of Medicine, Ankara (Turkey)

1997-12-01

Spinal epidural extramedullary haematopoiesis is very rare in thalassaemia. A 27-year-old man with thalassaemia intermedia presented with symptoms and signs of spinal cord compression. MRI showed a thoracic spinal epidural mass, representing extramedullary haematopoietic tissue, compressing the spinal cord. Following radiotherapy, serial MRI revealed regression of the epidural mass and gradual resolution of spinal cord oedema. (orig.) With 3 figs., 6 refs.

Daclizumab for the treatment of relapsing-remitting multiple sclerosis.

Science.gov (United States)

Herwerth, Marina; Hemmer, Bernhard

2017-06-01

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Over the last two decades, the number of therapeutic options for the treatment of relapsing remitting MS (RRMS) has been constantly growing, providing new treatment options to patients. Areas covered: Herein, the authors review the recently approved monoclonal antibody daclizumab for the treatment of RRMS. Based on original articles, they discuss its mode of action and evaluate its efficacy and safety profile compared to other available agents. Expert opinion: The IL-2 receptor modulator daclizumab is a new highly effective agent for the treatment of RRMS with novel immunomodulatory properties. Compared to interferon-beta i.m., daclizumab is more effective in reducing relapse rates and MRI activity. However, its use is limited by the risk of autoimmune disorders and hepatotoxicity. Similar to other monoclonal antibodies for RRMS, therapy with daclizumab needs a strict preselection and monitoring of patients based on individual risk benefit assessment. Given its substantial effectiveness, daclizumab can be an attractive option for patients with highly active MS.

Cost analysis of glatiramer acetate versus interferon-β for relapsing-remitting multiple sclerosis in patients with spasticity: the Escala study.

Science.gov (United States)

Sánchez-de la Rosa, Rainel; García-Bujalance, Laura; Meca-Lallana, José

2015-12-01

The Escala Study evidenced that the administration of glatiramer acetate for relapsing-remitting multiple sclerosis improved the spasticity of patients previously treated with interferon-β. However, whether such an improvement was translated into cost savings remained unclear. We therefore conducted a cost analysis of glatiramer acetate versus interferon-β in these patients with multiple sclerosis and spasticity. This cost analysis encompassed data from the observational Escala Study, which included patients with relapsing-remitting multiple sclerosis and spasticity whose treatment had been switched from interferon-β to glatiramer acetate. Costs prior to starting glatiramer acetate (interferon-β period) were compared to the subsequent six months on glatiramer acetate (glatiramer acetate period). The analysis was carried out following the recommendations for conducting pharmacoeconomic studies and from the Spanish National Health System perspective. Costs associated with multiple sclerosis treatment, spasticity treatment and relapse management were expressed in 2014 euros (€); a 7.5 % discount was applied-when needed-as stipulated in Spanish law. The management of relapsing-remitting multiple sclerosis, spasticity and relapses accounted for a 6-month cost per patient of 7,078.02€ when using interferon-β and 4,671.31€ when using glatiramer acetate. Switching from interferon-β to glatiramer acetate therefore represented a cost saving of 2,406.72€ per patient in favour of glatiramer acetate, which resulted from savings in treatment costs, relapse management and spasticity treatment of 1,890.02€, 430.48€ and 86.21€, respectively. The ratio of the costs during interferon-β was 1.5 times the costs during glatiramer acetate; thus, a fixed budget of 5,000,000€ would enable 1,070 patients to be treated with glatiramer acetate and only 706 patients with interferon-β. The treatment of relapsing-remitting multiple sclerosis with glatiramer acetate

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

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McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

1993-01-01

Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

International Nuclear Information System (INIS)

McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M.; Blackman, G.

1993-01-01

Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received αIFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. αIFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance αIFN therapy could not be fully evaluated. (author)

Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.

Science.gov (United States)

Stone, Lael Anne; Cutter, Gary Raymond; Fisher, Elizabeth; Richert, Nancy; McCartin, Jennifer; Ohayon, Joan; Bash, Craig; McFarland, Henry

2016-05-01

Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years. Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated. While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS. While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted. Copyright © 2015 by the American Society of Neuroimaging.

Extramedullary plasmacytoma of small bowel mesentery in associated with cecal cancer: a case report

International Nuclear Information System (INIS)

Kim, Sung Kyu; Kim, Yong Soo; Kim, Young Sun; Cho, On Koo; Koh, Byung Hee; Rhim, Hyun Chul; Park, Choog Ki; Park, Dong Woo; Park, Yong Wook; Oh, Young Ha

2005-01-01

Extramedullary plasmacytoma is a rare disease that is histopathologically defined as a solitary tumor composed of a monoclonal proliferation of cells with plasmacytic differentiation in an extramedullary site. Most of these tumors occur in the submucosa of the upper aerodigestive tract, and they rarely occur in the small bowel mesentery. We report here on a case of extramedullary plasmacytoma of the small bowel mesentery that was in association with a cecal cancer. Abdominal ultrasound and CT revealed a lobulated soft tissue mass with a cystic portion and peripheral calcification. In this case, the preoperative radiological diagnosis was difficult due to accompanying cecal cancer

Extramedullary plasmacytoma of small bowel mesentery in associated with cecal cancer: a case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Kyu; Kim, Yong Soo; Kim, Young Sun; Cho, On Koo; Koh, Byung Hee; Rhim, Hyun Chul; Park, Choog Ki; Park, Dong Woo [Hanyang University College of Medicine, Seoul (Korea, Republic of); Park, Yong Wook; Oh, Young Ha [Hanyang University Guri Hospital, Guri (Korea, Republic of)

2005-07-15

Extramedullary plasmacytoma is a rare disease that is histopathologically defined as a solitary tumor composed of a monoclonal proliferation of cells with plasmacytic differentiation in an extramedullary site. Most of these tumors occur in the submucosa of the upper aerodigestive tract, and they rarely occur in the small bowel mesentery. We report here on a case of extramedullary plasmacytoma of the small bowel mesentery that was in association with a cecal cancer. Abdominal ultrasound and CT revealed a lobulated soft tissue mass with a cystic portion and peripheral calcification. In this case, the preoperative radiological diagnosis was difficult due to accompanying cecal cancer.

An exploration of the lived experiences of individuals with relapsed multiple myeloma.

LENUS (Irish Health Repository)

Maher, K

2012-02-01

The experience of living with relapsed Multiple Myeloma (myeloma) for eight patients accessing treatment within a haematology unit in a large London hospital is explored in this study. Myeloma is recognised as incurable and is sometimes described as an \\'incurable chronic disease\\' with a main treatment option of chemotherapy. Hermeneutic phenomenology was the methodology used in conducting the study and data were collected through open-ended, unstructured interviews. Findings suggest that living with relapsed myeloma in the context of a chronic illness causes an ever-shifting perspective between illness and wellness consequently maintaining a state of uncertainty. The patients in this study placed importance on the emotional aspect of their experience. Hope, intuitive knowing and a fighting spirit were expressed as required positive elements that enabled living with relapsed myeloma. These assisted in maintaining normality, coping with bad news and adjusting to the illness. Pervading through the themes was the need to control uncertainty. Having strong support from significant others provided something to live for and the necessary social support required to promote a new orientation to life.

Mixed phenotype (T/B/myeloid) extramedullary blast crisis as an initial presentation of chronic myelogenous leukemia.

Science.gov (United States)

Qing, Xin; Qing, Annie; Ji, Ping; French, Samuel W; Mason, Holli

2018-04-01

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome generated by the reciprocal translocation t(9,22)(q34;q11). The natural progression of the disease follows a biphasic or triphasic course. Most cases of CML are diagnosed in the chronic phase. Extramedullary blast crisis rarely occurs during the course of CML, and is extremely rare as the initial presentation of CML. Here, we report the case of a 32-year-old female with enlarged neck lymph nodes and fatigue. She was diagnosed with B-lymphoblastic leukemia/lymphoma with possible mixed phenotype (B/myeloid) by right neck lymph node biopsy at an outside hospital. However, review of her peripheral blood smear and her bone marrow aspirate and biopsy showed features consistent with CML, which was confirmed by PCR and karyotyping. An ultrasound-guided right cervical lymph node core biopsy showed a diffuse infiltrate of blasts, near totally replacing the normal lymph node tissue, admixed with some hematopoietic cells including megakaryocytes, erythroid precursors and maturing myeloid cells. By flow cytometry and immunohistochemistry, the blasts expressed CD2, cytoplasmic CD3, CD5, CD7, CD56, TdT, CD10 (weak, subset), CD19 (subset), CD79a, PAX-5 (subset), CD34, CD38, CD117 (subset), HLA-DR (subset), CD11b, CD13 (subset), CD33 (subset), and weak cytoplasmic myeloperoxidase, without co-expression of surface CD3, CD4, CD8, CD20, CD22, CD14, CD15, CD16 and CD64, consistent with blasts with mixed phenotype (T/B/myeloid). A diagnosis of extramedullary blast crisis of CML was made. Chromosomal analysis performed on the lymph node biopsy tissue revealed multiple numerical and structural abnormalities including the Ph chromosome (46-49,XX,add(1)(p34),add(3)(p25),add(5)(q13),-6,t(9;22)(q34;q11.2),+10,-15,add(17)(p11.2),+19, +der(22)t(9;22),+mar[cp8]). After completion of one cycle of combined chemotherapy plus dasatinib treatment, she was transferred to City of Hope

Nasal septum extramedullary plasmacytoma

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Belić Branislav

2013-01-01

Full Text Available Introduction. Plasmacytomas are malignant tumors characterized by abnormal monoclonal proliferation of plasma cells. They originate in either bone - solitary osseous plasmacytoma, or in soft tissue - extramedullary plasmacytoma (EMP. EMP represents less than 1% of all head and neck malignancies. Case report. We presented a case of EMP of the nasal septum in a 44-year-old male who had progressive difficulty in breathing through the nose and frequent heavy epistaxis on the right side. Nasal endoscopy showed dark red, soft, polypoid tumor in the last third of the right nasal cavity arising from the nasal septum. The biopsy showed that it was plasmacytoma. Bence Jones protein in the urine, serum electrophoresis, bone marrow biopsy, skeletal survey and other screening tests failed to detect multiple myeloma. This confirmed the diagnosis of EMP. The mass was completely removed via an endoscopic approach, and then, 4 week later, radiotherapy was conducted with a radiation dose of 50 Gray. No recurrence was noted in a 3-year follow- up period. Conclusion. EMP of the nasal cavity, being rare and having long natural history, represents a diagnostic and therapeutic challenge for any ear, nose and throat surgeon. Depending on the resectability of the lesion, a combined therapy is the accepted treatment.

Extramedullary plasmacytoma: clinical and histopathologic study.

Science.gov (United States)

Strojan, Primoz; Soba, Erika; Lamovec, Janez; Munda, Anton

2002-07-01

To review the histories of extramedullary plasmacytoma patients diagnosed in Slovenia between 1969 and 1999, to determine the relationship between radiotherapy (XRT) dose and local tumor control, and to clarify the role of elective nodal XRT and the prognostic value of Bartl's histologic grading criteria (originally devised for multiple myeloma [MM]). The database of the Cancer Registry of Slovenia was used for the identification of patients. The inclusion criteria were as follows: bone marrow biopsy showing less than 10% plasma cells, normal skeletal survey, and immunohistochemically determined tumor monoclonality. Simulation/portal films were reviewed to assess the extent of elective nodal XRT. Twenty-six patients with 31 tumors fulfilled the inclusion criteria. In 4 patients, nine metachronously appearing solitary tumors were diagnosed. The head-and-neck region and other body sites were the sites of origin of primary tumors in 84% and 16% of patients, respectively, whereas in the two regions, regional disease was seen in 15% and 60% of patients, respectively. Therapy was as follows: XRT, 12 patients; surgery and postoperative XRT, 15 patients; and surgery, 4 patients. Ultimate local and regional control rates were 90% and 97%, respectively, and MM developed in 2 (8%) patients. The 10-year disease-specific and overall survival rates were 87% and 61%, respectively. The analysis of the dose-effect relationship showed that more conservative treatment is justified: for macroscopic disease, 40-50 Gy (2 Gy/day), adjusted to the bulk of disease; for microscopic disease, 36-40 Gy; after R0 surgery, no XRT is required, but close observation is needed. No attempts should be made to treat uninvolved nodal regions. Using Bartl's histologic grading criteria, trends were detected in patients with higher tumor grades: regional lymph node involvement (p = 0.04) and shorter disease-specific survival (p = 0.08). Extramedullary plasmacytoma is a highly curable disease when XRT is

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

Science.gov (United States)

Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

2017-07-01

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis

DEFF Research Database (Denmark)

Madsen, Claus

2017-01-01

The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease...... modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading...

"Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

Science.gov (United States)

Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

2017-06-22

The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study

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Rocco Totaro

2015-01-01

Full Text Available Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months. The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

Trichurs suis ova theraphy in relapsing multiple sclerosis is safe but without signals of beneficial effect

DEFF Research Database (Denmark)

Voldsgaard, A.; Bager, P.; Garde, E.

2015-01-01

revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did...... not change. CONCLUSIONS: In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect....

Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

DEFF Research Database (Denmark)

Lyksborg, Mark; Siebner, Hartwig R.; Sørensen, Per S.

2014-01-01

Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy...

Extramedullary intradural spinal tumors; Extramedullaere intradurale spinale Tumoren

Energy Technology Data Exchange (ETDEWEB)

Papanagiotou, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

2011-12-15

The category of extramedullary intradural tumors includes a variety of lesions ranging from meningiomas originating from meningeal cells and nerve sheath tumors (neurofibromas, schwannomas) to less common primary tumors, such as lipomas, ependymomas, hemangiopericytomas, epidermoid cysts and dermoid cysts. Extramedullary metastases can occur as transcoelomic metastases in tumors of the central nervous system (CNS) or metastasization from other tumors. Magnetic resonance imaging (MRI) is the method of choice for localization and characterization of these lesions before treatment. (orig.) [German] Die Kategorie der extramedullaeren intraduralen Tumoren enthaelt Laesionen, die von den Nervenhuellen (Schwannome und Neurofibrome) oder von den meningealen Zellen ausgehen (Meningeome). Ependymome, Lipome, Haemangioperizytome, Epidermoidzysten und Dermoidzysten entsprechen selteneren primaeren Tumoren. Extramedullaere Metastasen koennen als Abtropfmetastasen bei ZNS-Tumoren oder als Metastasierung anderer Karzinomerkrankungen auftreten. Die Magnetresonanztomographie (MRT) ist die Methode der Wahl zur Abklaerung einer intraduralen Raumforderung. (orig.)

Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

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Damiano Paolicelli

2009-07-01

Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

OpenAIRE

Messinis, L.; Kosmidis, M. H.; Vlahou, C.; Malegiannaki, A. C.; Gatzounis, G.; Dimisianos, N.; Karra, A.; Kiosseoglou, G.; Gourzis, P.; Papathanasopoulos, P.

2013-01-01

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensi...

Use of fingolimod in patients with relapsing remitting multiple sclerosis in Kuwait.

Science.gov (United States)

Alroughani, R; Ahmed, S F; Behbehani, R; Al-Hashel, J

2014-04-01

Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). 76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1). Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

2003-01-01

Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An insolite occurrence during splenectomy for myelofibrosis

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Marco Casaccia

Full Text Available Introduction: Primary myelofibrosis (MF is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. Case presentation: We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT. A laparotomic splenectomy and excision of whitish wide-spread peritoneal and omental nodulations was performed. There were no operative complications and the surgery was completed with minimal blood loss. The histopathological exam revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules. Conclusion: In primary myelofibrosis it must always be kept in mind the possible presence of peritoneal implants of extramedullary hematopoiesis and ascites of reactive genesis. We report a rare case of peritoneal carcinomatosis-like implants of extramedullary hematopoiesis found at splenectomy for MF. Keywords: Myelofibrosis, Splenomegaly, Splenectomy, Extramedullary hematopoiesis

[Neuropsychology of mildly disabled patients with relapsing-remitting multiple sclerosis].

Science.gov (United States)

Santiago Rolanía, Olga; Guàrdia Olmos, Joan; Arbizu Urdiain, Txomin

2006-02-01

Previous papers have mainly demonstrated the presence of cognitive impairment in patients with multiple sclerosis (MS), these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to 216 relapsing-remitting MS patients with mild clinical disability (EDSSreproduction visual memory; and long term verbal memory of texts, and information processing speed. We also observed greeter incidence of depressive symptoms in patients. And a little relation of the cognitive deficits with the clinical variables in these phase of the disease.

Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per S; Lisby, Steen; Grove, Richard

2014-01-01

OBJECTIVES: We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple sclerosis (RRMS). METHODS: In this randomized, double-blind, placebo-controlled study, patients received 2 ofatumumab infusions (100 mg, 300 mg......, or 700 mg) or placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety and efficacy were assessed. RESULTS: Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients in the 300-mg group...

Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis.

Science.gov (United States)

Chiao, Evelyn; Meyer, Kellie

2009-06-01

Disease-modifying therapy (DMT) is the largest single-cost item that contributes to the total per-patient cost of multiple sclerosis (MS), a disabling disorder of the central nervous system. Natalizumab is the most recent DMT to be approved for the treatment of relapsing MS and may be an attractive alternative to interferon beta and glatiramer acetate (GA). To determine from the perspective of a United States payer (1) the incremental cost effectiveness of natalizumab compared with other DMTs and (2) the budgetary impact of utilization of natalizumab for the treatment of relapsing MS. A combined cost effectiveness and budget impact model was developed. Model inputs were drug acquisition costs (wholesale acquisition cost), costs of drug administration and monitoring, costs of treating relapses, anticipated reduction in relapse rates after 2 years of therapy, and estimated market utilization of natalizumab. Outcomes included total 2-year costs of therapy per patient, costs per relapse avoided for each treatment, and overall 2-year costs to the health plan and per member per month (PMPM) costs. Drug acquisition costs are in 2008 US dollars, and all other costs were inflated to 2008 US dollars when necessary. Univariate sensitivity analyses were performed to determine the model inputs with the greatest influence on the cost per relapse avoided for natalizumab. The overall 2-year cost of therapy per patient was $72,120 for natalizumab, $56,790 for intramuscular (IM) interferon beta-1a (IFNbeta-1a), $56,773 for IFNbeta-1b, $57,180 for GA, and $58,538 for subcutaneous (SC) IFNbeta-1a. The cost per relapse avoided was lowest for natalizumab at $56,594, followed by $87,791 for IFNbeta-1b, $93,306 for IM IFNbeta-1a, $96,178 for SC IFNbeta-1a, and $103,665 for GA. The incremental cost-effectiveness ratios of natalizumab relative to IM IFNbeta-1a, IFNbeta-1b, GA, and SC IFNbeta-1a were $23,029, $24,452, $20,671, and $20,403 per additional relapse avoided, respectively. An

Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

Science.gov (United States)

Miller, Aaron E

2015-10-01

The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

LENUS (Irish Health Repository)

Hutchinson, Michael

2013-09-01

In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides.

Science.gov (United States)

Egan, Jan B; Shi, Chang-Xin; Tembe, Waibhav; Christoforides, Alexis; Kurdoglu, Ahmet; Sinari, Shripad; Middha, Sumit; Asmann, Yan; Schmidt, Jessica; Braggio, Esteban; Keats, Jonathan J; Fonseca, Rafael; Bergsagel, P Leif; Craig, David W; Carpten, John D; Stewart, A Keith

2012-08-02

The longitudinal evolution of a myeloma genome from diagnosis to plasma cell leukemia has not previously been reported. We used whole-genome sequencing (WGS) on 4 purified tumor samples and patient germline DNA drawn over a 5-year period in a t(4;14) multiple myeloma patient. Tumor samples were acquired at diagnosis, first relapse, second relapse, and end-stage secondary plasma cell leukemia (sPCL). In addition to the t(4;14), all tumor time points also shared 10 common single-nucleotide variants (SNVs) on WGS comprising shared initiating events. Interestingly, we observed genomic sequence variants that waxed and waned with time in progressive tumors, suggesting the presence of multiple independent, yet related, clones at diagnosis that rose and fell in dominance. Five newly acquired SNVs, including truncating mutations of RB1 and ZKSCAN3, were observed only in the final sPCL sample suggesting leukemic transformation events. This longitudinal WGS characterization of the natural history of a high-risk myeloma patient demonstrated tumor heterogeneity at diagnosis with shifting dominance of tumor clones over time and has also identified potential mutations contributing to myelomagenesis as well as transformation from myeloma to overt extramedullary disease such as sPCL.

Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

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Torrealdea Javier

2011-07-01

Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

Extramedullary plasmacytoma: clinical and histopathologic study

International Nuclear Information System (INIS)

Strojan, Primoz; Soba, Erika; Lamovec, Janez; Munda, Anton

2002-01-01

Purpose: To review the histories of extramedullary plasmacytoma patients diagnosed in Slovenia between 1969 and 1999, to determine the relationship between radiotherapy (XRT) dose and local tumor control, and to clarify the role of elective nodal XRT and the prognostic value of Bartl's histologic grading criteria (originally devised for multiple myeloma [MM]). Methods and Materials: The database of the Cancer Registry of Slovenia was used for the identification of patients. The inclusion criteria were as follows: bone marrow biopsy showing less than 10% plasma cells, normal skeletal survey, and immunohistochemically determined tumor monoclonality. Simulation/portal films were reviewed to assess the extent of elective nodal XRT. Results: Twenty-six patients with 31 tumors fulfilled the inclusion criteria. In 4 patients, nine metachronously appearing solitary tumors were diagnosed. The head-and-neck region and other body sites were the sites of origin of primary tumors in 84% and 16% of patients, respectively, whereas in the two regions, regional disease was seen in 15% and 60% of patients, respectively. Therapy was as follows: XRT, 12 patients; surgery and postoperative XRT, 15 patients; and surgery, 4 patients. Ultimate local and regional control rates were 90% and 97%, respectively, and MM developed in 2 (8%) patients. The 10-year disease-specific and overall survival rates were 87% and 61%, respectively. The analysis of the dose-effect relationship showed that more conservative treatment is justified: for macroscopic disease, 40-50 Gy (2 Gy/day), adjusted to the bulk of disease; for microscopic disease, 36-40 Gy; after R0 surgery, no XRT is required, but close observation is needed. No attempts should be made to treat uninvolved nodal regions. Using Bartl's histologic grading criteria, trends were detected in patients with higher tumor grades: regional lymph node involvement (p=0.04) and shorter disease-specific survival (p=0.08). Conclusions: Extramedullary

Bilateral Pleural Effusion in a Patient with an Extensive Extramedullary Hematopoietic Mass

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Yun Luo

2013-01-01

Full Text Available We present a 56-year-old woman with bilateral pleural effusions, widespread enlarged lymph nodes, and soft tissue masses located within the renal pelvis. The initially working diagnosis was tuberculosis and lymphoma. Further pathological examination of the lymph node biopsy confirmed a diagnosis of extramedullary hematopoiesis, and a bone marrow biopsy revealed myelofibrosis. Unlike common treatment options such as radiotherapy and/or surgery, intrathoracic cisplatin and dexamethasone for the treatment of pleural effusions secondary to extramedullary hematopoiesis demonstrated an improvement in feasibility and efficacy in the present case.

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

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Aurelio Lopez

2015-01-01

Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations☆

Science.gov (United States)

Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M. Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F.; de la Rubia, Javier

2015-01-01

We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007). PMID:26500850

Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

2017-01-01

New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

Experience of Glatiramer Acetate in the Treatment of Relapsing-Remitting Multiple Sclerosis Patients

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Özlem Taşkapılıoğlu

2012-03-01

Full Text Available OBJECTIVE: Glatiramer acetate (GA has been shown to reduce the number of relapses and improve outcomes in relapsing-remitting multiple sclerosis (RRMS patients. The aim of this study is to investigate the efficacy and side effects of GA in RRMS patients treated with it. METHODS: We retrospectively reviewed all the records of RRMS patients treated with GA in our hospital from January 1990 to December 2010. We evaluated 114 records but 71 patients (48 women, 23 men were included in the study due to incompleteness in the other records. Demographic characteristics, time from first symptom to diagnosis, time from diagnosis to treatment, number of relapses and Expanded Disability Status Scale (EDSS scores before and after the treatment, treatment duration, side effects, the other agents used in MS treatment during the disease duration and the presence of oligoclonal bands were recorded. RESULTS: The mean age of the patients and mean GA treatment duration were 41,85±9,05 years and 28,73 months, respectively. The mean number of relapses before and after the treatment were 2.30±1.16 and 0,52±1.24 respectively. The number of relapses reduced in 64 (90,14%, unchanged in 4 (5,63% and increased in 3 (4,23% patients after GA treatment. The mean EDSS scores before and after the treatment were 2,56±1,46 and 2,04±1,68 respectively. Before GA treatment, 63,4% of all patients had EDSS scores three or more. After the treatment 50,6% of all patients had EDSS scores three or more. GA was the first choice immunomodulatory treatment in 71,8% and the second choice in 28,2% of the patients. The treatment discontinued in 8 (11,3% patients and the reason was the severe side effect in only one patient (1,4%. CONCLUSION: Glatiramer acetate decreased the number of relapses and EDSS score with tolerable side effects.

Effectiveness of rehabilitation in multiple sclerosis relapse on fatigue, self-efficacy and physical activity.

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Nedeljkovic, Una; Raspopovic, Emilija Dubljanin; Ilic, Nela; Vujadinovic, Sanja Tomanovic; Soldatovic, Ivan; Drulovic, Jelena

2016-09-01

Relapse of disease is one of the most prominent characteristics of multiple sclerosis. Effectiveness of rehabilitation programmes on fatigue, self-efficacy (SE) and physical activity (PA) has not been investigated so far in context of relapse. The aim of our study was to examine if rehabilitation programme in addition to high-dose methylprednisolone (HDMP) during relapse of disease can influence fatigue, SE and PA more than corticosteroid therapy alone. Patients were randomized in control group receiving only HDMP and experimental group which was in addition included in rehabilitation programme. Outcome measures used were Fatigue Severity Scale (FSS), Multiple Sclerosis Self- Efficacy scale (MSSES), Godin Leisure-Time Exercise Questionnaire (GLTEQ), completed on baseline, 1 and 3 months later. There was no significant change in FSS in both time points, despite different trend seen between groups. The mean MSSES for function and control improved significantly in treatment group after 1 month (807.1 ± 96.8, p = 0.005; 665.3 ± 145.1, p = 0.05) and 3 months (820 ± 83.5, p = 0.004; 720.0 ± 198.2, p = 0.016.) compared to baseline values. The mean GLTEQ score was significantly higher in the treatment group compared to the control at both follow-up time points (45.7 ± 7.6, p self-efficacy, but effect on fatigue was insufficient.

Electrochemotherapy treatment of oral extramedullary plasmacytoma of the tongue: a retrospective study of three dogs

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Rúbia Monteiro de Castro Cunha

2017-11-01

Full Text Available ABSTRACT: Extramedullary plasmacytomas (EPs are responsible for 2.5% of neoplasms in dogs. They are solitary, smooth, elevated, pink or red nodules, of 1 to 2cm in diameter. Cutaneous and oral extramedullary plasmacytomas in dogs are usually benign tumors, treated with local therapies. Prognosis is generally good. Recurrence and metastatic rates are low. Electrochemotherapy is a local treatment that combines chemotherapy and electroporation and shows objective responses of 70% to 94% with few local and systemic side effects. This scientific communication has the objective to report treatment of three canine patients with oral extramedullary plasmacytoma. Nodules were located on the tongue and patients were submitted to one or two electrochemotherapy sessions, which preserved the tongue without mutilation and cured the patients.

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis.

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Chataway, Jeremy; Martin, Keith; Barrell, Kevin; Sharrack, Basil; Stolt, Pelle; Wraith, David C

2018-03-13

To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions. In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted. This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions. © 2018 American Academy of Neurology.

Cognitive impairment in relapsing remitting Multiple Sclerosis

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Saška Roškar

2003-06-01

Full Text Available The purpose of the study was to identify changes in cognitive abilities that affect patients with relapsing remitting form of multiple sclerosis (MS and to find out which instrument manifests them best. The performance of MS patients was compared to a matched group of healthy people using three neuropsychological tests: Wisconsin card sorting test (WCST, Stroop color and word test and Trail making test (TMT part B. Results on all three tests indicate general cognitive impairments in the group of patients. Compared to the group of healthy people patients with MS exhibited impaired ability of abstract reasoning (WCST, impaired cognitive flexibility and less resistance to irrelevant stimuli (Stroop color and word test, slowed information processing and impaired ability of shifting attention from one symbol to another (TMT. The largest differences between groups occured in Stroop color and word test as well as in TMT. The estimation of cognitive abilities of MS patients is of high importance and sistematicaly observing of changes in those abilities should be considered.

Application of PET/CT in treatment response evaluation and recurrence prediction in patients with newly-diagnosed multiple myeloma.

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Li, Ying; Liu, Junru; Huang, Beihui; Chen, Meilan; Diao, Xiangwen; Li, Juan

2017-04-11

Multiple myeloma (MM) causes osteolytic lesions which can be detected by 18F-fluorodeoxyglucose positron emission tomography/Computed tomography (18F-FDG PET/CT). We prospectively involve 96 Newly diagnosed MM to take PET/CT scan at scheduled treatment time (figure 1), and 18F-FDG uptake of lesion was measured by SUVmax and T/Mmax. All MM patients took bortezomib based chemotherapy as induction and received ASCT and maintenance. All clinical features were analyzed with the PET/CT image changes, and some relationships between treatment response and FDG uptakes changes were found: Osteolytic lesions of MM uptakes higher FDG than healthy volunteers, and this trend is more obvious in extramedullary lesions. Compared to X-ray, PET/CT was more sensitive both in discoering bone as well as extramedullary lesions. In newly diagnosed MM, several adverse clinical factors were related to high FDG uptakes of bone lesions. Bone lesion FDG uptakes of MM with P53 mutation or with hypodiploidy and complex karyotype were also higher than those without such changes. In treatment response, PET/CT showed higher sensitivity in detecting tumor residual disease than immunofixation electrophoresis. But in relapse prediction, it might show false positive disease recurrences and the imaging changes might be influenced by infections and hemoglobulin levels. PET/CT is sensitive in discovering meduallary and extrameduallary lesions of MM, and the 18F-FDG uptake of lesions are related with clinical indictors and biological features of plasma cells. In evaluating treatment response and survival, PET/CT showed its superiority. But in predicting relapse or refractory, it may show false positive results.

MRI of perineural extramedullary granulocytic sarcoma

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Graham, A. [Rehabilitation Medicine, Hunters Moor Neurological Rehabilitation Centre, Newcastle-Upon-Tyne (United Kingdom); Hodgson, T. [Neuroradiology Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom); Jacubowski, J. [Neurosurgical Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom); Norfolk, D. [Haematology Department, Leeds General Infirmary, Leeds LS1 3EX (United Kingdom); Smith, C. [Pathology Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom)

2001-06-01

Granulocytic sarcoma is an extramedullary solid tumour consisting of myelogenous leukaemic blast cells, usually seen in acute myeloid leukaemia and less commonly in patients with chronic myeloid leukaemia or myeloproliferative disorders. Blast cells have a predilection for periosteal and perineural regions and rarely precede evidence of systemic disease. We present two patients, aleukaemic on peripheral blood counts, both at presentation and during subsequent treatment. We present the MRI features of this rare but important condition. (orig.)

The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

LENUS (Irish Health Repository)

Hutchinson, Michael

2012-02-01

The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.

Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs.

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Sarah Gooding

Full Text Available Double relapsed and/or refractory multiple myeloma (DRMM, MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411-£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM.

Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial

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Sorensen, Per Soelberg; Lycke, Jan; Erälinna, Juha-Pekka

2011-01-01

Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.......Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy....

Extramedullary plasmacytoma in the carotid space: Expanding the differential diagnosis

International Nuclear Information System (INIS)

Deshpande, Sneha Satish; Kane, Shubhada; Arya, Supreeta

2014-01-01

Plasma cell neoplasms have been classified into various types, with a range of clinical and radiological presentations. Extramedullary plasmacytoma (EMP) is a subset of plasma cell neoplasms which presents as an isolated non-osseous soft tissue mass. Though carotid space neoplasms are commonly encountered, EMP in the carotid space is rare and seldom considered in the initial differential diagnosis of a carotid space mass. These tumors can be treated by surgery or radiotherapy. On the other hand, the commonly encountered tumors in the carotid space are treated surgically. Also, it is mandatory to exclude multiple myeloma in the patients presenting with EMP. Hence, accurate and early diagnosis has therapeutic and prognostic implications. We report a rare case of EMP of the carotid space, describing the imaging features and the differential diagnoses with clues pointing to this rare entity

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

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O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

2015-04-01

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly

Extramedullary hematopoiesis (EMH) in laboratory animals: offering an insight into stem cell research.

Science.gov (United States)

Chiu, Shao-Chih; Liu, Hua-Hsing; Chen, Chia-Ling; Chen, Pin-Ru; Liu, Ming-Chao; Lin, Shinn-Zong; Chang, Ko-Tung

2015-01-01

Extramedullary hematopoiesis (EMH) is a pathological process secondary to underlying bone marrow (BM) insufficiency in adults. It is characterized by the emergence of multipotent hematopoietic progenitors scattered around the affected tissue, most likely in the spleen, liver, and lymph node, etc. EMH in patients frequently receives less medical attention and is neglected unless a compressive or obstructive hematopoietic mass appears to endanger the patient's life. However, on a biological basis, EMH reflects the alteration of relationships among hematopoietic stem and progenitor cells (HSPCs) and their original and new microenvironments. The ability of hematopoietic stem cells (HSCs) to mobilize from the bone marrow and to accommodate and function in extramedullary tissues is rather complicated and far from our current understanding. Fortunately, many reports from the studies of drugs and genetics using animals have incidentally found EMH to be involved. Thereby, the molecular basis of EMH could further be elucidated from those animals after cross-comparison. A deeper understanding of the extramedullary hematopoietic niche could help expand stem cells in vitro and establish a better treatment in patients for stem cell transplantation.

Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

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Karin van der Hiele

Full Text Available The majority of patients with Multiple Sclerosis (MS are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed. Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53=2.76, p=0.008 and reported more organising and planning problems (χ2(1=6.3, p=0.012, higher distractibility (Kendall's tau-b= -0.24, p=0.03 and more cognitive fatigue (U=205.0, p=0.028, r=-0.30 than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28. Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

Science.gov (United States)

van der Hiele, Karin; van Gorp, Dennis; Ruimschotel, Rob; Kamminga, Noëlle; Visser, Leo; Middelkoop, Huub

2015-01-01

The majority of patients with Multiple Sclerosis (MS) are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed). Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53)=2.76, p=0.008) and reported more organising and planning problems (χ2(1)=6.3, p=0.012), higher distractibility (Kendall's tau-b= -0.24, p=0.03) and more cognitive fatigue (U=205.0, p=0.028, r=-0.30) than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28). Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

Spinal cord compression due to extramedullary hematopoiesis in beta-thalassemia intermedia

International Nuclear Information System (INIS)

Munn, Rita K.; Kramer, Carol A.; Arnold, Susanne M.

1998-01-01

Background: Extramedullary hematopoiesis (EMH) occurs in many disorders, including thalassemias and other hemoglobinopathies, and commonly presents in the spleen and liver. We present a case of spinal cord compression in a patient with beta-thalassemia intermedia, and review the literature and available treatment options. Patient and Methods: A 35-year-old black female with beta-thalassemia intermedia presented with a 3-week history of back pain and lower extremity weakness. Neurologic examination was consistent with spinal cord compression, and gadolinium enhanced magnetic resonance imaging (MRI) confirmed this diagnosis. She was given intravenous steroids and radiotherapy was begun in 200 cGy fractions to a total dose of 2000 cGy. Results: At the completion of radiotherapy the patient was ambulatory with mild residual weakness. MRI scans 16 months later showed smaller, but persistent masses, and she remains asymptomatic 5 years from her diagnosis. Conclusion: Recognition of spinal cord EMH requires prompt physical examination and MRI for accurate diagnosis. EMH can be managed with radiation, surgery, transfusions, or a combination of these therapies. Radiation in conservative doses of (750-3500 cGy) is non-invasive, avoids the surgical risks of potentially severe hemorrhage and incomplete resection, and has a high complete remission rate in the majority of patients. Relapse rates are moderate (37.5%), but retreatment provides excellent chance for second remission

Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

Science.gov (United States)

Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

2011-09-15

Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

Recovery from an acute relapse is associated with changes in motor resting-state connectivity in multiple sclerosis

DEFF Research Database (Denmark)

Dogonowski, Anne-Marie; Blinkenberg, Morten; Paulson, Olaf B.

2016-01-01

Resting-state functional MRI (rs-fMRI) of the brain has been successfully used to identify altered functional connectivity in the motor network in multiple sclerosis (MS).1 In clinically stable patients with MS, we recently demonstrated increased coupling between the basal ganglia and the motor...... network.1 Accordingly, rs-fMRI in MS is particularly suited to investigate functional reorganisation of the motor network in the remission phase after a relapse because the resting-state connectivity pattern is not influenced by interindividual differences in motor ability and task performance....... In this prospective rs-fMRI study, we mapped acute changes in resting-state motor connectivity in 12 patients with relapsing forms of MS presenting with an acute relapse involving an upper limb paresis. Previous functional MRI (fMRI) studies have shown that the activation of sensorimotor areas was stronger and more...

Biomechanical Comparison of an Intramedullary and Extramedullary Free-Tissue Graft Reconstruction of the Acromioclavicular Joint Complex

Science.gov (United States)

Garg, Rishi; Javidan, Pooya; Lee, Thay Q.

2013-01-01

Background Several different surgical techniques have been described to address the coracoclavicular (CC) ligaments in acromioclavicular (AC) joint injuries. However, very few techniques focus on reconstructing the AC ligaments, despite its importance in providing stability. The purpose of our study was to compare the biomechanical properties of two free-tissue graft techniques that reconstruct both the AC and CC ligaments in cadaveric shoulders, one with an extramedullary AC reconstruction and the other with an intramedullary AC reconstruction. We hypothesized intramedullary AC reconstruction will provide greater anteroposterior translational stability and improved load to failure characteristics than an extramedullary technique. Methods Six matched cadaveric shoulders underwent translational testing at 10 N and 15 N in the anteroposterior and superoinferior directions, under AC joint compression loads of 10 N, 20 N, and 30 N. After the AC and CC ligaments were transected, one of the specimens was randomly assigned the intramedullary free-tissue graft reconstruction while its matched pair received the extramedullary graft reconstruction. Both reconstructed specimens then underwent repeat translational testing, followed by load to failure testing, via superior clavicle distraction, at a rate of 50 mm/min. Results Intramedullary reconstruction provided significantly greater translational stability in the anteroposterior direction than the extramedullary technique for four of six loading conditions (p < 0.05). There were no significant differences in translational stability in the superoinferior direction for any loading condition. The intramedullary reconstructed specimens demonstrated improved load to failure characteristics with the intramedullary reconstruction having a lower deformation at yield and a higher ultimate load than the extramedullary reconstruction (p < 0.05). Conclusions Intramedullary reconstruction of the AC joint provides greater stability in the

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

Directory of Open Access Journals (Sweden)

Stephanie Zettner

2014-11-01

Full Text Available Chronic myelogenous leukemia (CML is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia.

Science.gov (United States)

Zettner, Stephanie; Mistry, Sandeep G

2014-11-01

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

In search of the optimal platform for Post-Allogeneic SCT immunotherapy in relapsed multiple myeloma: a systematic review.

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Oostvogels, R; Uniken Venema, S M; de Witte, M; Raymakers, R; Kuball, J; Kröger, N; Minnema, M C

2017-09-01

Allogeneic stem cell transplantation (allo-SCT) has the potential to induce sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT is primarily performed in high-risk MM patients, most often in the setting of early relapse after first-line therapy with autologous SCT. However, the implementation of allo-SCT for MM is jeopardized by high treatment-related mortality (TRM) rates as well as high relapse rates. In this systematic review, we aimed to identify a safe allo-SCT strategy that has optimal 1-year results regarding mortality, relapse and severe GvHD, creating opportunities for post-transplantation strategies to maintain remissions in the high-risk group of relapsed MM patients. Eleven studies were included. Median PFS ranged from 5.2 to 36.8 months and OS was 13.0 to 63.0 months. The relapse related mortality at 1 year varied between 0 and 50% and TRM between 8 and 40%. Lowest GvHD incidences were reported for conditioning regimens with T-cell depletion using ATG or graft CD34+ selection. Similar strategies could lay the foundation for a post-transplant immune platform, this should be further evaluated in prospective clinical trials.

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

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Julie Chevalier

Full Text Available The paper aimed to estimate the incremental cost-effectiveness ratio (ICER at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015.The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results.From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY of 0.281, corresponding to an ICER of €13,110/QALY.Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

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Chevalier, Julie; Chamoux, Catherine; Hammès, Florence; Chicoye, Annie

2016-01-01

The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Solitary extramedullary plasmacytoma of the colon, rectum and anus ...

African Journals Online (AJOL)

Solitary extramedullary plasmacytoma (SEP) is a neoplastic proliferation of a single clone of plasma cells that occur outside of the bone and bone marrow. It is rare, commonly occurring in the head and neck region, followed by the gastrointestinal tract. The aetiology, risk factors, natural history and consequent treatment are ...

QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

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Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

2016-04-01

Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p treatment in important QoL parameters beyond standard measures of relapse and disease severity.

Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

Energy Technology Data Exchange (ETDEWEB)

Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui [Nan fang Hospital, Southern Medical University, Guangzhou (China); Tamrakar, Karuna [Zhujiang Hospital, Southern Medical University, Guangzhou (China)

2012-03-15

Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

Intracranial extramedullary hematopoiesis in beta-thalassemia.

Science.gov (United States)

Karki, Bivek; Xu, Yi-Kai; Tamrakar, Karuna; Wu, Yuan-Kui

2012-01-01

Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

International Nuclear Information System (INIS)

Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui; Tamrakar, Karuna

2012-01-01

Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

Dorsal approaches to intradural extramedullary tumors of the craniovertebral junction

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D Refai

2010-01-01

Full Text Available Tumors of the craniovertebral junction (CVJ pose significant challenges to cranial and spine surgeons. Familiarity with the complex anatomy and avoidance of injury to neurologic and vascular structures are essential to success. Multiple surgical approaches to address lesions at the CVJ have been promoted, including ventral and dorsal-based trajectories. However, optimal selection of the surgical vector to manage the pathology requires a firm understanding of the limitations and advantages of each approach. The selection of the best surgical trajectory must include several factors, such as obtaining the optimal exposure of the region of interest, avoiding injury to critical neurologic or vascular structures, identification of normal anatomical landmarks, the familiarity and comfort level of the surgeon to the approach, and the need for fixation. This review article focuses on dorsal approaches to the CVJ and the advantages and limitations in managing intradural extramedullary tumors.

Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An insolite occurrence during splenectomy for myelofibrosis.

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Casaccia, Marco; Fornaro, Rosario; Frascio, Marco; Palombo, Denise; Stabilini, Cesare; Firpo, Emma; Gianetta, Ezio

2017-01-01

Primary myelofibrosis (MF) is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT). A laparotomic splenectomy and excision of whitish wide-spread peritoneal and omental nodulations was performed. There were no operative complications and the surgery was completed with minimal blood loss. The histopathological exam revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules. In primary myelofibrosis it must always be kept in mind the possible presence of peritoneal implants of extramedullary hematopoiesis and ascites of reactive genesis. We report a rare case of peritoneal carcinomatosis-like implants of extramedullary hematopoiesis found at splenectomy for MF. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

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Burcu Altunrende

2017-12-01

Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease of the central nervous system and is characterized by inflammation, demyelination, and axonal loss. Fingolimod is the first oral drug for the treatment of MS approved by the United States Food and Drug Administration, European Union countries, and various other countries. The compound exerts its effect via interaction with lysophospholipid receptors known as sphingosine-1 phosphate receptors. Although fingolimod has a very convenient daily oral dosing, it may cause development of bradycardia at the first dose, macular edema, infection, all of which require attention. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rates and is beneficial in brain magnetic resonance imaging measures when compared with both placebo and intramuscular interferon β-1a. This review describes the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of the management of MS

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

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Gajofatto A

2015-12-01

Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

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Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

1991-09-01

From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

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Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

2014-05-01

At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Cost of managing an episode of relapse in multiple sclerosis in the United States

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Ward Alexandra J

2003-09-01

Full Text Available Abstract Background The purpose of this study was to determine the direct medical US cost of managing multiple sclerosis relapses. Methods Direct data analysis and cost modeling were employed to derive typical resource use profiles and costs in 2002 US dollars, from the perspective of a third-party payer responsible for comprehensive health-care. The location and scope of health care services provided over a 90-day period were used to define three levels of relapse management. Hospitalization and resulting subsequent care was defined as high intensity management. A medium level of intervention was defined as either use of the emergency room, an observational unit, or administration of acute treatments, such as intravenous methylprednisolone in an outpatient or home setting. The lowest intensity of care comprised physician office visits and symptom-related medications. Data were obtained from many sources including all payer inpatient, ambulatory and emergency room databases from several states, fee schedules, government reports, and literature. All charges were adjusted using cost-to-charge ratios. Results Average cost per person for high management level was $12,870, based on analysis of 4,634 hospital cases (mean age 48 years, 73% female. Hospital care comprised 71% of that cost. At discharge, 36% required inpatient sub-acute care, rehabilitation or home care. The typical cost per moderate episode was $1,847 and mild episode $243. Conclusions Management strategies leading to a reduction in the frequency and severity of a relapse, less reliance on inpatient care, or increased access to steroid infusions in the home, would have a substantial impact on the economic consequences of managing relapses.

Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Yan, Xiaoyu; Clemens, Pamela L; Puchalski, Thomas

2018-01-01

OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, ...

Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

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Stanley Cohan MD, PhD

2015-03-01

Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis.

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Diego Cadavid

Full Text Available There is an unmet need for disease-modifying therapies to improve ambulatory function in disabled subjects with multiple sclerosis.Assess the effects of natalizumab on ambulatory function in disabled subjects with relapsing-remitting multiple sclerosis (RRMS or secondary progressive multiple sclerosis (SPMS.We retrospectively reviewed ambulatory function as measured by timed 25-foot walk (T25FW in clinical trial subjects with an Expanded Disability Status Scale score ≥3.5, including RRMS subjects from the phase 3 AFFIRM and SENTINEL trials, relapsing SPMS subjects from the phase 2 MS231 study, and nonrelapsing SPMS subjects from the phase 1b DELIVER study. For comparison, SPMS subjects from the intramuscular interferon beta-1a (IM IFNβ-1a IMPACT study were also analyzed. Improvement in ambulation was measured using T25FW responder status; response was defined as faster walking times over shorter (6-9-month or longer (24-30-month treatment periods relative to subjects' best predose walking times.There were two to four times more T25FW responders among disabled MS subjects in the natalizumab arms than in the placebo or IM IFNβ-1a arms. Responders walked 25 feet an average of 24%-45% faster than nonresponders.Natalizumab improves ambulatory function in disabled RRMS subjects and may have efficacy in disabled SPMS subjects. Confirmation of the latter finding in a prospective SPMS study is warranted.

Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

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Slobodan M Jankovic

2010-03-01

Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

Interferon-beta for relapsing-remitting multiple sclerosis: a systematic review

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Dian HE

2014-09-01

Full Text Available Objective To assess the efficacy and safety of interferon-beta (IFN-β as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS.  Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL, PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc, as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014. Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Manager software (Version 5.3.3 and the impacts of limitations in study design or execution (risk of bias, inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed.  Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053. All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT principle was not used in data analysis. Data from only 919 patients (43.17% were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated

Clinical features, outcome, and prognostic factors for survival and evolution to multiple myeloma of solitary plasmacytomas: a report of the Greek myeloma study group in 97 patients.

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Katodritou, Eirini; Terpos, Evangelos; Symeonidis, Argiris S; Pouli, Anastasia; Kelaidi, Charikleia; Kyrtsonis, Marie-Christine; Kotsopoulou, Maria; Delimpasi, Sosana; Christoforidou, Anna; Giannakoulas, Nikolaos; Viniou, Nora-Athina; Stefanoudaki, Ekaterini; Hadjiaggelidou, Christina; Christoulas, Dimitrios; Verrou, Evgenia; Gastari, Vassiliki; Papadaki, Sofia; Polychronidou, Genovefa; Papadopoulou, Athina; Giannopoulou, Evlambia; Kastritis, Efstathios; Kouraklis, Alexandra; Konstantinidou, Pavlina; Anagnostopoulos, Achilles; Zervas, Konstantinos; Dimopoulos, Meletios A

2014-08-01

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T. © 2014 Wiley Periodicals, Inc.

[Relapse: causes and consequences].

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Thomas, P

2013-09-01

Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

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Julio Sotelo

2011-01-01

Full Text Available Multiple sclerosis (MS is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS.

Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

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Sotelo, Julio; Corona, Teresa

2011-01-01

Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID:22096629

Prognostic factors and outcome in relapsed multiple myeloma after nonmyeloablative allo-SCT: a single center experience.

Science.gov (United States)

Minnema, M C; van Dorp, S; van de Donk, N W C J; Schouten, F; Kersten, M J; Coenen, J L L M; Schouten, H; Zweegman, S; Schaafsma, R; Lokhorst, H M

2011-02-01

For relapsed multiple myeloma (MM) patients, allo-SCT is a possible treatment option, but recent data obtained using a nonmyeloablative (NMA) conditioning regimen are scarce. We retrospectively collected data from 38 relapsed MM patients who received a NMA allo-SCT from October 2001 to January 2008. In total, 18 patients (48%) were transplanted using a matched unrelated donor. The median follow-up is 2.3 years. In 16 patients (42%) the response improved and eight patients (21%) were rapidly progressive within 6 months after allo-SCT. In total, 15 patients (39%) were in CR after allo-SCT. The median PFS was 1.4 years (range, 0.1-4.9), and having a CR after allo-SCT or having chronic GVHD resulted in longer PFS. Median OS was 3.1 years (range, 0.2-7.2) and again having a CR after allo-SCT or chronic GVHD was associated with a better OS. Six patients (16%) have died from treatment-related diseases. These results indicate that NMA allo-SCT is a treatment option in relapsed MM patients and that results may be improved by strategies that enhance the CR rate after allo-SCT.

Premature epiphyseal fusion and extramedullary hematopoiesis in thalassemia

International Nuclear Information System (INIS)

Colavita, N.; Orazi, C.; Danza, S.M.; Falappa, P.G.; Fabbri, R.

1987-01-01

The main skeletal abnormalities in β-thalassemia are widening of medullary spaces, rarefaction of bone trabeculae, thinning of cortical bone, and perpendicular periosteal spiculation. Premature epiphyseal fusion (PEF) and extramedullary hematopoiesis (EH) are found, though more rarely. The incidence of PEF and EH in 64 patients affected by β-thalassemia is reported. The different incidence of such complications in thalassemia major and intermedia is reported, and a possible correlation with transfusion regimen is also considered. (orig.)

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

Science.gov (United States)

Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

2017-07-01

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

The Cost of Relapse in Schizophrenia.

Science.gov (United States)

Pennington, Mark; McCrone, Paul

2017-09-01

Schizophrenia is a chronic and debilitating mental illness characterised by periods of relapse that require resource intensive management. Quantifying the cost of relapse is central to the evaluation of the cost effectiveness of treating schizophrenia. We aimed to undertake a comprehensive search of the available literature on the cost of relapse. We performed a search on multiple databases (MEDLINE, Embase, PsycINFO and Health Management Information Consortium) for any study reporting a cost of relapse or data from which such a cost could be calculated. Costs are reported in 2015 international dollars. We found 16 studies reporting costs associated with relapse over a defined period of time and identified a cost associated with hospitalisation for relapse in 43 studies. Eight clinical decision analyses also provided cost estimates. Studies from the US report excess costs of relapse of $6033-$32,753 (2015 Purchasing Power Parity dollars [PPP$]) over periods of 12-15 months. European studies report excess costs of $8665-$18,676 (2015 PPP$) over periods of 6-12 months. Estimates of the cost of hospitalisation for relapse are more diverse, and associated with marked differences in typical length of stay across jurisdictions. Wide ranges in the estimated cost of relapse may reflect differences in sample section and relapse definition as well as practice styles and differences in resource costs. Selection of the most appropriate cost estimate should be guided by the definition of relapse and the analysis setting.

Correlation of magnetic resonance imaging findings of spinal intradural extramedullary schwannomas with pathologic findings

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Kim, Yeo Ju; Park, In Suh; Yoon, Seung Hwan; Choi, Suk Jin; Kim, Youn Jeong; Kang, Young Hye; Lee, Ha Young; Kim, Woo Chul; Han, Jun Gu; Cho, Soon Gu [Inha University Hospital, Incheon (Korea, Republic of)

2015-06-15

To evaluate the magnetic resonance imaging (MRI) findings of spinal intradural extramedullary schwannomas with pathologic correlation and to determine whether these schwannomas share the imaging features of schwannomas in the peripheral nerves. The MRIs of 17 cases of pathologically proven spinal intradural extramedullary schwannomas were reviewed retrospectively, and cystic changes, enhancement, and intratumoral hemorrhage of the tumors were evaluated. Imaging features known to be common findings of schwannoma in the peripheral nerves, such as encapsulation, the target sign, the fascicular sign, and visualization of entering or exiting nerve rootlets, were also evaluated. The histopathology of the tumors was correlated with the MRI findings. Cystic changes were detected in 14 cases by MRI and in 16 cases by pathology. The most common pattern of enhancement was a thick peripheral septal pattern (70.59%). Intratumoral hemorrhage was detected in four cases on MRI, but in all cases on pathology. Encapsulation was observed in all cases. The fascicular sign was seen in only four cases, and thickening of an exiting rootlet was visualized in one case. None of the cases showed the target sign. Spinal intradural extramedullary schwannomas were typical encapsulated cystic tumors and had few imaging features of schwannomas in the peripheral nerves.

Intradural extramedullary spinal cord tumours: A retrospective study of sur­gical outcomes

Directory of Open Access Journals (Sweden)

Md. Kamrul Ahsan

2016-07-01

Full Text Available Background: Intradural extramedullary spinal cord tumours (IESCT accounts for approximately two thirds of all intraspinal neoplasm and are of important clinical consideration and surgery is the essence in cases with neurological deterioration.Objective: To share our experience on the outcome of surgical excision of intradural extramedullary spinal cord tumours. Methods: Results of 60 patients surgically treated intradural extramedullary spinal tumours between Octo­ber 2003 and October 2015 at Bangabandhu Sheikh Mujib Medical University and in our private settings, Dhaka, were analyzed retrospectively. There were 32 males, 28 females with an average age of 52.4 years (13-70 years and followed up for at least a year. The preoperative symptom with duration, tumours location and intradural space occupancy and the histopathological diagnosis were analyzed. Pain was evaluated by the visual analogue scale (VAS and the neurologic function was assessed by Nurick's grade.Results: The tumours were located as, thoracic 32 (53.33%, lumbar 16 (26.67%, cervical 04 (6.67%, and junctional 08 (13.33%, CervicoThoracic-01, Thoracolumbar-07. The histopathological diagnosis included schwannoma 35 (58.33%, meningiomas 14 (23.33%, neurofbroma 4 (6.67%, arachnoid cyst and myxopapillary ependymoma 03 (05.00% each and paraganglioma 01 (01.67%. The VAS score was reduced in all cases from 8.0 ± 1.2 to 1.2 ± 0.8 (p < 0.003 and the Nurick's grade was improved in all cases from 3.0 ± 1.3 to 1.0 ± 0.0 (p < 0.005. The preoperative neurological deficit improved within 8 postoperative weeks in most cases and within 1 postoperative year in all cases. Complications included cerebrospinal fluid leakage, parasthesia, dependant bedsore 02 (3.33% each and recurrence 03 (05.00%. and further neurological deterioration 1 (01.67% case.Conclusion: lntradural extramedullary tumors detected by MRI are mostly benign and good clinical results can be obtained when treated surgi

A Computer Navigation System Analysis of the Accuracy of the Extramedullary (Tibial Alignment Technique in Total Knee Arthroplasty (TKA

Directory of Open Access Journals (Sweden)

EK Chee

2010-07-01

Full Text Available In total knee arthroplasty, mechanical alignment guides have improved the accuracy of implant alignment, but errors are not uncommon. In the present study, an image-free computer-assisted navigation system was used to analyse the accuracy of an extramedullary (tibial alignment system, which is based on predetermined, fixed anatomical landmarks. Comparisons were made between two surgeons, with different levels of competency in order to determine if experience affected the accuracy of extramedullary tibial jig placement, in either the coronal and sagittal planes or both planes. The results showed that the accuracy of the extramedullary tibial alignment system, in the coronal plane (in up to 80-87% of cases was much better than for posterior slope, and sagittal plane. Surgeon experience was not a significant factor.

Adrenal extramedullary hematopoiesis associated with β-thalassemia major

OpenAIRE

Bijan Keikhaei; Ahmad Soltani Shirazi; Mahboob Mohammad Pour

2012-01-01

The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hema - topoiesis (EMH). EMH is a rare complication in thalassemia major (TM) and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdomin...

[Extramedullary fixation combined with intramedullary fixation in the surgical reduction of sagittal mandibular condylar fractures].

Science.gov (United States)

Chuanjun, Chen; Xiaoyang, Chen; Jing, Chen

2016-10-01

This study aimed to evaluate the clinical effect of extramedullary fixation combined with intramedullary fixation during the surgical reduction of sagittal mandibular condylar fractures. Twenty-four sagittal fractures of the mandibular condyle in18 patients were fixed by two appliances: intramedullary with one long-screw osteosynthesis or Kirschner wire and extramedullary with one micro-plate. The radiologically-recorded post-operative stability-associated com-plications included the screw/micro-plate loosening, micro-plate twisting, micro-plate fractures, and fragment rotation. The occluding relations, the maximalinter-incisal distances upon mouth opening, and the mandibular deflection upon mouth opening were evaluated based on follow-up clinical examination. Postoperative panoramic X-ray and CT scans showed good repositioning of the fragment, with no redislocation or rotation, no screw/plate loosening, and no plate-twisting or fracture. Clinical examination showed that all patients regained normal mandibular movements, ideal occlusion, and normal maximal inter-incisal distances upon mouth opening. Extramedullary fixation combined with intramedullary fixation is highly recommended for sagittal condylar fractures because of the anti-rotation effect of the fragment and the reasonable place-ment of the fixation appliances.

Idiopathic myelofibrosis accompanied by peritoneal extramedullary hematopoiesis presenting as refractory ascites in a dog.

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Rautenbach, Yolandi; Goddard, Amelia; Clift, Sarah J

2017-03-01

A 2.5-year-old spayed female American Pit Bull Terrier dog presented with a primary complaint of chronic refractory ascites. The dog's CBC displayed a moderate to severe macrocytic, hypochromic, nonregenerative anemia, and a moderate leukopenia as result of a moderate neutropenia and monocytopenia. Microscopic examination of the blood smear showed marked anisocytosis, mild polychromasia, mild acanthocytosis and ovalocytosis, moderate schistocytosis and poikilocytosis, and 4 metarubricytes/100 WBC. Abdominal ultrasonography revealed a homogenous, mild to moderately hyperechoic appearing liver as well as marked amounts of speckled anechoic to slightly hypoechoic peritoneal fluid. Cytology of the ascitic fluid demonstrated a sterile transudate, with evidence of a chronic inflammatory reaction as well as erythroid and myeloid precursor cells, and a few megakaryocytes with occasional micromegakaryocytes. Histologic sections of bone marrow, spleen, and liver were examined, using routine H&E stains, as well as a variety of immunohistochemistry and other special stains. Histopathology of the bone marrow and spleen revealed varying degrees of fibrosis, erythroid, and myeloid hyperplasia, as well as multiple small hyperplastic clusters of megakaryocytes. The megakaryocytes displayed many features of atypia such as increased cytoplasmic basophilia and occasional abnormal chromatin clumping with mitoses. Histopathologic examination of the liver disclosed evidence of mild extramedullary hematopoiesis. This case represents the first report of canine idiopathic myelofibrosis associated with peritoneal extramedullary hematopoiesis, resulting in refractory ascites. Although idiopathic myelofibrosis is a relatively rare condition in dogs, this case demonstrates that ascites caused by peritoneal implants of hematopoietic tissue may be the initial manifestation of myelofibrosis. © 2016 American Society for Veterinary Clinical Pathology.

Ferrokinetic study of splenic erythropoiesis: Relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis

International Nuclear Information System (INIS)

Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y.

1989-01-01

Splenic erythropoiesis was demonstrated by surface counting of 59 Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis (1) is encountered in a variety of clinical conditions; (2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; (3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and (4) can be evaluated in a semiquantitative manner by surface counting

Intramedullary versus extramedullary alignment of the tibial component in the Triathlon knee

LENUS (Irish Health Repository)

Cashman, James P

2011-08-20

Abstract Background Long term survivorship in total knee arthroplasty is significantly dependant on prosthesis alignment. Our aim was determine which alignment guide was more accurate in positioning of the tibial component in total knee arthroplasty. We also aimed to assess whether there was any difference in short term patient outcome. Method A comparison of intramedullary versus extramedullary alignment jig was performed. Radiological alignment of tibial components and patient outcomes of 103 Triathlon total knee arthroplasties were analysed. Results Use of the intramedullary was found to be significantly more accurate in determining coronal alignment (p = 0.02) while use of the extramedullary jig was found to give more accurate results in sagittal alignment (p = 0.04). There was no significant difference in WOMAC or SF-36 at six months. Conclusion Use of an intramedullary jig is preferable for positioning of the tibial component using this knee system.

Extramedullary Solitary Plasmacytoma: Demonstrating the Role of 18F-FDG PET Imaging.

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Gautam, Archana; Sahu, Kamal Kant; Alamgir, Ahsan; Siddiqi, Imran; Ailawadhi, Sikander

2017-04-01

An Extramedullary Plasmacytoma (EMP) is characterized by a neoplastic proliferation of clonal plasma cells outside the medullary cavity. EMPs are a rare occurrence compared to other malignant plasma cell disorders and account for approximately 3-5% of plasma-cell neoplasms. Although most cases of EMP are not immediately life threatening at diagnosis, EMPs can progress to Multiple Myeloma (MM) and thus, warrant monitoring. Currently, there are no standard guidelines for when and how to monitor patients who are diagnosed with or treated for a solitary plasmacytoma. We present a case of solitary EMP who was treated adequately and definitively but developed a distinct, non-contiguous subsequent solitary EMP and was only discovered due to surveillance 18 F-Fludeoxyglucose Positron Emission Tomography ( 18 F-FDG) (PET) scan. Uniform surveillance guidelines should be developed and the potential benefits of PET and other imaging techniques as well as their cost should be considered.

Reduced-intensity conditioning allogeneic SCT as salvage treatment for relapsed multiple myeloma.

Science.gov (United States)

de Lavallade, H; El-Cheikh, J; Faucher, C; Fürst, S; Stoppa, A-M; Coso, D; Bouabdallah, R; Chabannon, C; Gastaut, J-A; Blaise, D; Mohty, M

2008-06-01

The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLA-identical sibling donor ('donor' group), while 13 patients had no donor ('no-donor' group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the 'donor' group could actually proceed to RIC allo-SCT. With a median follow-up of 36 (range, 21-60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11-55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7-48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56-98%; P=0.0003) among the nontransplanted patients. In an 'intention-to-treat' analysis, the Kaplan-Meier estimate of PFS was significantly higher in the 'donor' group as compared to the 'no-donor' group (P=0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15-0.82; P=0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.

Metaplastic carcinoma. Breast. Relapse. Chemotherapy and Radiotherapy

International Nuclear Information System (INIS)

Marquez, A.; Terrasa, J.; Garcia, J.M.; Rifa, J.

1996-01-01

Metaplastic carcinoma of the breast is a rare tumor. The appearance of unexpected mesenchymal elements within the epithelial tumors is the squamous metaplasia. These tumors have a different clinical behaviour that classical breast carcinoma. We present a case of metaplastic mammary carcinoma with multiple relapses treated with a combination of chemotherapy and radiotherapy. The use of chemotherapy after local treatment has enhanced the relapse-free survival. The combined treatment modality seems to produce some benefit in the management of the local relapses of this neoplasms

Radiotherapy for Extramedullary Plasmacytoma of the Head and Neck

International Nuclear Information System (INIS)

Creach, Kimberly M.; Foote, Robert L.; Neben-Wittich, Michelle A.; Kyle, Robert A.

2009-01-01

Purpose: To define the effectiveness of radiotherapy in the treatment of patients with extramedullary plasmacytoma of the head and neck (EMPHN). Methods and Materials: We searched the Mayo Clinic Rochester Department of Radiation Oncology electronic Tumor Registry and identified 18 consecutive patients with a diagnosis of solitary EMPHN. Sixteen patients were treated with radiotherapy at initial diagnosis and 2 received salvage radiotherapy for local failure after surgery. Median dose administered was 50.4 Gy. Median follow-up was 6.8 years. Results: One patient (6%) developed a marginal recurrence 12 months after treatment. Six patients (33%) developed multiple myeloma (2 patients) or plasmacytomas at distant sites (4 patients) at a median of 3.1 years after diagnosis (range, 0.02 to 9.6 years). Median and 5- and 10-year overall survival rates from the date of diagnosis are 12.5 years, 88%, and 55%, respectively. Two patients (11%) developed a radiation-induced malignancy at 6.5 and 6.9 years after treatment. Conclusions: Radiotherapy provides excellent local and regional tumor control and survival in patients with EMPHN. To the best of our knowledge, this is the first report of presumed radiation-induced malignancy in this patient population

Multiple myeloma presenting as CEA-producing rectal cancer.

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Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-03-31

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

Science.gov (United States)

Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

2018-04-14

In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a

A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Hansson, Markus; Gimsing, Peter; Badros, Ashraf

2015-01-01

PURPOSE: This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients. EXPERIMENTAL DESIGN: BI-505 was given intravenously, every 2 weeks...... generally mild to moderate, and those attributed to study medication were mostly limited to the first dose and manageable with premedication and slower infusion. No maximum tolerated dose was identified. BI-505's half-life increased with dose while clearance decreased, suggesting target-mediated clearance...

Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

Directory of Open Access Journals (Sweden)

Takuya Matsushita

Full Text Available BACKGROUND: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO, relapsing remitting multiple sclerosis (RRMS, and primary progressive MS (PPMS, and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. METHODS/PRINCIPAL FINDINGS: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND by multiplexed fluorescent bead-based immunoassay. Interleukin (IL-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. CONCLUSIONS: Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell

Intradural extramedullary Ewing's sarcoma: A case report and review of the literature.

Science.gov (United States)

Paterakis, Konstantinos; Brotis, Alexandros; Tasiou, Anastasia; Kotoula, Vasiliki; Kapsalaki, Eftychia; Vlychou, Marianna

Extra-skeletal Ewing's sarcomas are very rare lesions to the spine surgeon, with the intradural, extramedullary lesions being even rarer. Herein we present a patient with an intradural, extramedullary form of Ewing's sarcoma and review the relevant literature. The medical records, operative reports, radiographical studies and histological examinations of a single patient are retrospectively reviewed. A 31-year old male presented with back-pain, right-leg progressive paraparesis, and inability to walk. Both motor and sensory disturbances were revealed on the right leg at the clinical examination. Lumbar MRI showed two lesions. The first one was an intradural, extramedullary lesion at the L2-L3 level, while the second was smaller, located at the bottom of the dural sac. The patient underwent gross total resection of the L2-L3 lesion after a bilateral laminectomy. Histological examination was compatible with Ewing's sarcoma, and was verified by molecular analysis. No other extra-skeletal or skeletal lesion was found. A chemotherapy scheme was tailored to the patients' histological diagnosis. The patient presented with local recurrence and bone metastasis 2 years after his initial diagnosis. A second operation was performed and the follow up of the patient showed no disease progression 18 months after revision surgery. The spine surgeon should be aware of the existence of such rare entities, in order to timely fulfill the staging process and institute the proper therapy. The management of patients with extra-skeletal Ewing's sarcomas involves professionals as members of a multidisciplinary team, all of which should co-operate for the patient's optimal outcome. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

Science.gov (United States)

There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

Multiple myeloma presenting as CEA-producing rectal cancer

Directory of Open Access Journals (Sweden)

Giampaolo Talamo

2010-03-01

Full Text Available We report the case of a 57-year old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA, a tumor antigen more commonly associated with rectal adenocarcinomas.

The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

Science.gov (United States)

Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

2015-01-01

Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

Spinal cord compression secondary to extramedullary hematopoiesis in a dog.

Science.gov (United States)

Williams, Lindsay M; Skeen, Todd M

2013-03-15

An 11-year-old spayed female Siberian Husky was evaluated because of a 2-week history of progressive paraparesis. Results of neurologic examination were consistent with a T3-L3 myelopathy. There were no abnormalities on CBC, and hypercalcemia was noted on serum biochemical analysis. Several hypoechoic splenic nodules were evident on abdominal ultrasonography, and results of fine-needle aspiration cytology were consistent with splenic extramedullary hematopoiesis (EMH). Two compressive, extradural masses in the dorsal epidural space of the thoracolumbar region of the spinal cord were seen on MRI images. A dorsal laminectomy was performed to remove the extradural spinal masses. Results of histologic examination of tissue samples were consistent with EMH. Following surgery, clinical signs of paraparesis resolved, and there was no recurrence of the masses 24 months after surgery. Extramedullary hematopoesis should be considered as a differential diagnosis in dogs in which results of diagnostic imaging indicate a epidural mass. In human patients, spinal EMH usually occurs secondary to an underlying hematologic disease, but it can also occur spontaneously. Treatment options reported for humans include surgical decompression, radiation therapy, chemotherapy, and blood transfusion. The dog of this report responded favorably to surgical decompression and was clinically normal 2 years after surgery.

A rare case of cervical epidural extramedullary plasmacytoma presenting with monoparesis

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Turk Okan

2017-03-01

Full Text Available Multiple myeloma and other plasma cell disorders are characterized by production of a large number of plasma cells in the bone marrow. On the other hand, plasmacytoma results from proliferation of abnormal plasma cells in the soft tissue or skeletal system. Neurological complications are frequently observed in these diseases. The most commonly known complications among those complications are spine fractures, spinal cord compressions, and peripheral neuropathies. Although neurological involvements are common in plasmacytomas, extramedullary spinal epidural localizations have been reported very rarely. In this case report, we aimed to present a plasmacytoma case that presented with acute onset of upper extremity monoparesis. A 40-year-old woman was admitted to our clinic with complaints of sudden weakness and numbness in her left arm following neck and left arm pain. Emergency cervical magnetic resonance imaging (MRI revealed an epidural mass and the patient underwent emergency surgery. The patient showed improvement post-operatively and the pathology was reported as plasmacytoma. Following hematology consultation, systemic chemotherapy was initiated and radiotherapy was planned after wound healing.

Myeloid Sarcoma Developing in Prexisting Hydroxyurea-Induced Leg Ulcer in a Polycythemia Vera Patient

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Hatim Nafil

2013-01-01

Full Text Available Myeloid sarcoma (MS is an extramedullary tumour consisting of myeloblasts or immature myeloid cells located in an extramedullary site. It may occur at presentation of AML, at relapse, or prior to the onset of frank leukemia. We report a rare case of MS developing in prexisting Hydroxyurea-induced leg Ulcer in a 70-year-old woman.

Thalassemia, extramedullary hematopoiesis, and spinal cord compression: A case report

OpenAIRE

Bukhari, Syed Sarmad; Junaid, Muhammad; Rashid, Mamoon Ur

2016-01-01

Background: Extramedullary hematopoiesis (EMH) refers to hematopoiesis outside of the medulla of the bone. Chronic anemia states such as thalassemia can cause hematopoietic tissue to expand in certain locations. We report a case of spinal cord compression due to recurrent spinal epidural EMH, which was treated with a combination of surgery and radiotherapy. Pakistan has one of the highest incidence and prevalence of thalassemia in the world. We describe published literature on diagnosis and m...

A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis

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Konca Degertekin, Ceyla; Özkurt, Zübeyde Nur; Akyürek, Nalan; Yağcı, Münci

2012-01-01

Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic m...

Solitary extramedullary plasmacytomas of thyroid in Hashimoto's thyroiditis: Mimicking benign cystic nodule on ultrasonography

International Nuclear Information System (INIS)

Kwon, Yohan; Kim, Soo Jin; Hur, Joon Ho; Park, Sung Hee; Lee, Sun Jin; Lee, Tae Jin

2013-01-01

Solitary extramedullary plasmacytoma (SEP) of the thyroid is uncommon and mostly occur in patients with a Hashimoto's thyroiditis (82%). We present a case on SEP of thyroid in Hashimoto's thyroiditis, which mimics growing benign cystic masses on serial ultrasonography.

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

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Bonnier, Guillaume; Maréchal, Benedicte; Fartaria, Mário João; Falkowskiy, Pavel; Marques, José P; Simioni, Samanta; Schluep, Myriam; Du Pasquier, Renaud; Thiran, Jean-Philippe; Krueger, Gunnar; Granziera, Cristina

2017-01-01

Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter ( p  = 0.005) and a decrease of T1 relaxation times in the pallidum ( p  decrease in T1 relaxation time ( p -value  0.4, p  < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

Transjugular Intrahepatic Porto-Systemic Stent-Shunt for Therapy of Bleeding Esophageal Varices Due to Extramedullary Hematopoiesis in Primary Myelofibrosis: A Case Report

OpenAIRE

Phillip, Veit;Berger, Hermann;Straub, Melanie;Saugel, Bernd;Treiber, Matthias;Einwächter, Henrik;Schmid, Roland M.;Huber, Wolfgang

2016-01-01

Background: Primary myelofibrosis belongs to the group of myeloproliferative syndromes. Extramedullary hematopoiesis in the liver can lead to portal hypertension. Patient and Methods: We report a case of a patient with life-threatening, endoscopically not treatable bleeding from esophageal varices due to extramedullary hematopoiesis of the liver that was successfully treated with placement of a transjugular intrahepatic porto-systemic stent-shunt (TIPS). Results: Therapy of variceal bleeding ...

Intramuscular leukemic relapse: clinical signs and imaging findings. A multicentric analysis

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Surov, Alexey [Martin Luther University Halle-Wittenberg, Department of Radiology, Halle (Germany); University of Leipzig, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Kiratli, Hayyam [Hacettepe University School of Medicine, Department of Ophthalmology, Ankara (Turkey); Im, Soo Ah [Seoul St. Mary' s Hospital, Department of Radiology, Seoul (Korea, Republic of); Manabe, Yasuhiro [National Hospital Organization Okayama Medical Center, Department of Neurology, Okayama (Japan); O' Neill, Alibhe; Shinagare, Atul B. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Spielmann, Rolf Peter [Martin Luther University Halle-Wittenberg, Department of Radiology, Halle (Germany)

2014-09-26

Leukemia is a group of malignant diseases involving peripheral blood and bone marrow. Extramedullary tumor manifestation in leukemia can also occur. They more often involve lymph nodes, skin, and bones. Intramuscular leukemic relapse (ILR) is very unusual. The aim of this analysis was to summarize the reported data regarding clinical signs and radiological features of ILR. The PubMed database was searched for publications related to ILR. After an analysis of all identified articles, 20 publications matched the inclusion criteria. The authors of the 20 publications were contacted and provided imaging of their cases for review. The following were recorded: age, gender, primary diagnosis, clinical signs, pattern, localization and size of the intramuscular leukemic relapse. Images of 16 patients were provided [8 computer tomographic (CT) images and 15 magnetic resonance images, MRI]. Furthermore, one patient with ILR was identified in our institutional database. Therefore, images of 17 patients were available for further analysis. Overall, 32 cases with ILR were included in the analysis. In most cases acute myeloid leukemia was diagnosed. Most ILRs were localized in the extremities (44 %) and in the extraocular muscles (44 %). Clinically, ILR manifested as local pain, swelling and muscle weakness. Radiologically, ILR presented most frequently with diffuse muscle infiltration. On postcontrast CT/MRI, most lesions demonstrated homogeneous enhancement. ILRs were hypo-/isointense on T1w and hyperintense on T2w images. ILR manifests commonly as focal pain, swelling and muscle weakness. ILR predominantly involved the extraocular musculature and the extremities. Radiologically, diffuse muscle infiltration was the most common imaging finding. (orig.)

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

OpenAIRE

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on bra...

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

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Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

2017-12-01

To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study.

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Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil W; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Hicking, Christine; Vermersch, Patrick

2018-04-01

In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

DEFF Research Database (Denmark)

Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

2015-01-01

Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse......, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal...

Transjugular intrahepatic porto-systemic stent-shunt for therapy of bleeding esophageal varices due to extramedullary hematopoiesis in primary myelofibrosis: a case report.

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Phillip, Veit; Berger, Hermann; Straub, Melanie; Saugel, Bernd; Treiber, Matthias; Einwächter, Henrik; Schmid, Roland M; Huber, Wolfgang

2012-01-01

Primary myelofibrosis belongs to the group of myeloproliferative syndromes. Extramedullary hematopoiesis in the liver can lead to portal hypertension. We report a case of a patient with life-threatening, endoscopically not treatable bleeding from esophageal varices due to extramedullary hematopoiesis of the liver that was successfully treated with placement of a transjugular intrahepatic porto-systemic stent-shunt (TIPS). Therapy of variceal bleeding by TIPS insertion was successful. During a 29-month follow-up, no hepatic failure, hepatic encephalopathy, or further variceal bleeding episode occurred. TIPS placement is a well-established procedure for the treatment of complications due to portal hypertension mainly due to liver cirrhosis. This report illustrates that TIPS placement can also be a promising treatment option in patients with primary myelofibrosis and portal hypertension due to extramedullary hematopoiesis. Copyright © 2012 S. Karger AG, Basel.

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

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Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-07-01

Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

The role of T2*-weighted gradient echo in the diagnosis of tumefactive intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse hepatic iron overload: a case report and review of the literature.

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Belay, Abel A; Bellizzi, Andrew M; Stolpen, Alan H

2018-01-15

Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been previously described. A 52-year-old white man with myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic lesion on ultrasound during workup for bone marrow transplantation. Magnetic resonance imaging revealed diffuse hepatic iron overload and non-visualization of the lesion on T2* gradient-echo sequence suggesting the presence of iron deposition within the lesion similar to that in background hepatic parenchyma. Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary hematopoiesis. Six months later, while still being evaluated for bone marrow transplant, our patient was found to have poor pulmonary function tests. Follow-up computed tomography angiogram showed a mass within his right main pulmonary artery. Bronchoscopic biopsy of this mass once again revealed extramedullary hematopoiesis. He received radiation therapy to his chest. However, 2 weeks later, he developed mediastinal hematoma and died shortly afterward, secondary to respiratory arrest. Mass-forming extramedullary hematopoiesis is rare; however, our report emphasizes that it needs to be considered in the initial differential

Multiple myeloma in a captive lion (Panthera leo

Directory of Open Access Journals (Sweden)

Adrian S.W. Tordiffe

2013-09-01

Full Text Available Multiple myeloma is a rare, systemic proliferation of neoplastic plasma cells. A case was reported in an 11-year-old male captive lion (Panthera leo at the National Zoological Gardens of South Africa, Pretoria. The classic features of symptomatic multiple myeloma were all evident in this case; namely osteolytic lesions, monoclonal gammopathy in the serum with excretion of monoclonal proteins in the urine, neoplastic plasma cells in the bone marrow and associated renal failure and anaemia. In addition, similar to the common pattern of this disease in domestic felids, at least three extramedullary tumours were found and several organs were infiltrated by neoplastic plasma cells. The cytoplasm of approximately 50%of the neoplastic round cells, including a few giant myeloma cells, stained weakly to strongly using immunohistochemical stains for B-lymphocytes (CD79a. The normal haematological parameters and lack of any osteolytic lesions in the lion at the time of the first evaluation suggest that the primary neoplastic cells could have originated from one of the extramedullary tumour sites. Only two cases of multiple myeloma have previously been reported in captive wild felids. To the authors’ knowledge, there are no case reports of multiple myeloma in lions.

Relevance of brain lesion location to cognition in relapsing multiple sclerosis.

Directory of Open Access Journals (Sweden)

Francesca Rossi

Full Text Available OBJECTIVE: To assess the relationship between cognition and brain white matter (WM lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS. METHODS: MRI-based T2 lesion probability map (LPM was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP and cognitively impaired (CI. RESULTS: Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001, T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major than in CP patients (37% in the posterior corona radiata. The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected. Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions. CONCLUSIONS: Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

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Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Relapse and Craving in Alcohol-Dependent Individuals: A Comparison of Self-Reported Determinants.

Science.gov (United States)

Snelleman, Michelle; Schoenmakers, Tim M; van de Mheen, Dike

2018-06-07

Negative affective states and alcohol-related stimuli increase risk of relapse in alcohol dependence. In research and in clinical practice, craving is often used as another important indicator of relapse, but this lacks a firm empirical foundation. The goal of the present study is to explore and compare determinants for relapse and craving, using Marlatt's (1996) taxonomy of high risk situations as a template. We conducted semi-structured interviews with 20 alcohol-dependent patients about their most recent relapse and craving episodes. Interview transcripts were carefully reviewed for their thematic content, and codes capturing the thematic content were formulated. In total, we formulated 42 relapse-related codes and 33 craving-related codes. Descriptions of craving episodes revealed that these episodes vary in frequency and intensity. The presence of alcohol-related stimuli (n = 11) and experiencing a negative emotional state (n = 11) were often occurring determinants of craving episodes. Both negative emotional states (n = 17) and testing personal control (n = 11) were viewed as important determinants of relapses. Craving was seldom mentioned as a determinant for relapse. Additionally, participants reported multiple determinants preceding a relapse, whereas craving episodes were preceded by only one determinant. Patient reports do not support the claim that craving by itself is an important proximal determinant for relapse. In addition, multiple determinants were present before a relapse. Therefore, future research should focus on a complexity of different determinants.

Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

DEFF Research Database (Denmark)

Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

2011-01-01

On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg...

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

Science.gov (United States)

Hadjigeorgiou, G M; Doxani, C; Miligkos, M; Ziakas, P; Bakalos, G; Papadimitriou, D; Mprotsis, T; Grigoriadis, N; Zintzaras, E

2013-12-01

The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments. © 2013 John Wiley & Sons Ltd.

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

International Nuclear Information System (INIS)

Siegel, D S; Richardson, P; Dimopoulos, M; Moreau, P; Mitsiades, C; Weber, D; Houp, J; Gause, C; Vuocolo, S; Eid, J; Graef, T; Anderson, K C

2014-01-01

The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed

Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal.

Science.gov (United States)

Serafini, Barbara; Scorsi, Eleonora; Rosicarelli, Barbara; Rigau, Valérie; Thouvenot, Eric; Aloisi, Francesca

2017-06-15

Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is a potentially life-threatening event. To verify whether highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during a fulminating MS relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation. Copyright © 2017 Elsevier B.V. All rights reserved.

Temporal bone extramedullary hematopoiesis as a causeof pediatric bilateral conductive hearing loss:Case report and review of the literature.

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Lanigan, Alexander; Fordham, M Taylor

2017-06-01

Extramedullary hematopoiesis occurs in children with hemoglobinopathy and chronic anemia. The liver and spleen are often affected first, but other foci can develop to support erythrocyte demand. We report a case of a nine-year-old with beta thalassemia and temporal bone extramedullary hematopoiesis causing ossicular fixation and bilateral conductive hearing loss. There is only one case in the literature describing this phenomenon in pediatric patients, and this is the first case report of bilateral hearing loss from this physiologic phenomenon. Otolaryngologists should consider this etiology in patients with chronic anemia and conductive hearing loss in the absence of otitis media. Published by Elsevier B.V.

Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis.

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Anne Waschbisch

Full Text Available The expression of selected microRNAs (miRNAs known to be involved in the regulation of immune responses was analyzed in 74 patients with relapsing remitting multiple sclerosis (RRMS and 32 healthy controls. Four miRNAs (miR-326, miR-155, miR-146a, miR-142-3p were aberrantly expressed in peripheral blood mononuclear cells from RRMS patients compared to controls. Although expression of these selected miRNAs did not differ between treatment-naïve (n = 36 and interferon-beta treated RRMS patients (n = 18, expression of miR-146a and miR-142-3p was significantly lower in glatiramer acetate (GA treated RRMS patients (n = 20 suggesting that GA, at least in part, restores the expression of deregulated miRNAs in MS.

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

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Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera

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Shuhei Ito

2017-01-01

Full Text Available Extramedullary hematopoiesis (EMH occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera.

Science.gov (United States)

Ito, Shuhei; Fujita, Nobuyuki; Hosogane, Naobumi; Nagoshi, Narihito; Yagi, Mitsuru; Iwanami, Akio; Watanabe, Kota; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Ishii, Ken

2017-01-01

Extramedullary hematopoiesis (EMH) occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

Myelopathy due to Spinal Extramedullary Hematopoiesis in a Patient with Polycythemia Vera

OpenAIRE

Ito, Shuhei; Fujita, Nobuyuki; Hosogane, Naobumi; Nagoshi, Narihito; Yagi, Mitsuru; Iwanami, Akio; Watanabe, Kota; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Ishii, Ken

2017-01-01

Extramedullary hematopoiesis (EMH) occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH.

Bilateral Pleural Effusion in a Patient with an Extensive Extramedullary Hematopoietic Mass

OpenAIRE

Yun Luo; Ying Zhang; Shi-feng Lou

2013-01-01

We present a 56-year-old woman with bilateral pleural effusions, widespread enlarged lymph nodes, and soft tissue masses located within the renal pelvis. The initially working diagnosis was tuberculosis and lymphoma. Further pathological examination of the lymph node biopsy confirmed a diagnosis of extramedullary hematopoiesis, and a bone marrow biopsy revealed myelofibrosis. Unlike common treatment options such as radiotherapy and/or surgery, intrathoracic cisplatin and dexamethasone for the...

Primary laryngeal localization of multiple myeloma: A case report

OpenAIRE

Allegra, Eugenia; Marino, Nicol?; Modica, Domenico; Emmanuele, Carmela; Saita, Vincenzo

2017-01-01

Multiple myeloma is a lymphoproliferative disease that may involve the bone marrow as well as extramedullary soft tissues. However, laryngeal localization of multiple myeloma is extremely rare. We herein present the case of a 68-year-old male patient with a history of dyspnea, dysphonia and dysphagia. Laryngoscopic examination revealed a lesion involving the right glottis and right vestibular (false) vocal fold, with absence of ipsilateral laryngeal motility and constriction of the airway. Co...

The protumorigenic potential of FTY720 by promoting extramedullary hematopoiesis and MDSC accumulation.

Science.gov (United States)

Li, Y; Zhou, T; Wang, Y; Ning, C; Lv, Z; Han, G; Morris, J C; Taylor, E N; Wang, R; Xiao, H; Hou, C; Ma, Y; Shen, B; Feng, J; Guo, R; Li, Y; Chen, G

2017-06-29

FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses. Granulocyte-macrophage colony-stimulating factor (GM-CSF), mainly produced by MDSCs, was identified as a key factor to mediate these effects of FTY720 in tumor microenvironment. Furthermore, we showed that FTY720 triggers MDSCs to release GM-CSF via S1P receptor 3 (S1pr3) through Rho kinase and extracellular signal-regulated kinase-dependent pathway. Thus, our findings provide mechanistic explanation for the protumorigenic potentials of FTY720 and suggest that targeting S1pr3 simultaneously may be beneficial for the patients receiving FTY720 treatment.

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

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Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V

2015-02-01

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study

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Nasim Tabrizi

2012-01-01

Full Text Available Background: The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Materials and Methods: Forty patients with aggressive relapsing remitting MS were randomly put into two groups. The first group underwent monthly plasma exchange for three successive months, followed by 12 mg/m 2 mitoxantrone at the end of each course and two more doses of 6 mg/m 2 mitoxantrone in 3-month intervals. The second group received the same doses of mitoxantrone only without plasma exchange. At the end of 8 months treatment course, clinical reassessment and neuroimaging was performed and treatment was continued with interferon-β. Results: At the end of induction therapy, Expanded Disability Status Scale score was significantly improved in both groups (P < 0.001. Number of demyelinating and gadolinium-enhancing plaques in brain magnetic resonance imaging (MRI was prominently reduced in group 2 (P ≤ 0.05, but the changes were not statistically significant in group 1, except for juxtacortical plaques. Conclusion: Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.

Solitary extramedullary plasmacytomas of thyroid in Hashimoto's thyroiditis: Mimicking benign cystic nodule on ultrasonography

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Kwon, Yohan; Kim, Soo Jin; Hur, Joon Ho; Park, Sung Hee; Lee, Sun Jin; Lee, Tae Jin [Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul (Korea, Republic of)

2013-11-15

Solitary extramedullary plasmacytoma (SEP) of the thyroid is uncommon and mostly occur in patients with a Hashimoto's thyroiditis (82%). We present a case on SEP of thyroid in Hashimoto's thyroiditis, which mimics growing benign cystic masses on serial ultrasonography.

Adrenal extramedullary hematopoiesis associated with β-thalassemia major.

Science.gov (United States)

Keikhaei, Bijan; Shirazi, Ahmad Soltani; Pour, Mahboob Mohammad

2012-05-10

The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hematopoiesis (EMH). EMH is a rare complication in thalassemia major (TM) and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7×7.3×5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started.

Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia.

Science.gov (United States)

Haidar, Rachid; Mhaidli, Hani; Taher, Ali T

2010-06-01

Ineffective erythropoiesis in patients with thalassemia intermedia drives extramedullary hematopoietic tumor formation in several parts of the body. Paraspinal involvement has received increasing attention due to the associated morbidity secondary to spinal cord compression. Although the history and physical examination may help narrow the differential diagnosis, radiographic imaging remains essential to confirm the existence of hematopoietic tissue. Characteristic appearance has been observed mainly on magnetic resonance imaging. Several treatment options have been described, including transfusion therapy, laminectomy, radiotherapy, and the use of fetal hemoglobin inducing agents that decrease the hematopoietic drive. However, the ideal management scheme remains controversial. Until large prospective trials evaluate the efficacy and safety of the available treatment options, both in single and in combination therapy, an individualized approach should be entertained.

Pharmacometric Analysis of the Relationship Between Absolute Lymphocyte Count and Expanded Disability Status Scale and Relapse Rate, Efficacy End Points, in Multiple Sclerosis Trials.

Science.gov (United States)

Novakovic, A M; Thorsted, A; Schindler, E; Jönsson, S; Munafo, A; Karlsson, M O

2018-05-10

The aim of this work was to assess the relationship between the absolute lymphocyte count (ALC), and disability (as measured by the Expanded Disability Status Scale [EDSS]) and occurrence of relapses, 2 efficacy endpoints, respectively, in patients with remitting-relasping multiple sclerosis. Data for ALC, EDSS, and relapse rate were available from 1319 patients receiving placebo and/or cladribine tablets. Pharmacodynamic models were developed to characterize the time course of the endpoints. ALC-related measures were then evaluated as predictors of the efficacy endpoints. EDSS data were best fitted by a model where the logit-linear disease progression is affected by the dynamics of ALC change from baseline. Relapse rate data were best described by the Weibull hazard function, and the ALC change from baseline was also found to be a significant predictor of time to relapse. Presented models have shown that once cladribine exposure driven ALC-derived measures are included in the model, the need for drug effect components is of less importance (EDSS) or disappears (relapse rate). This simplifies the models and theoretically makes them mechanism specific rather than drug specific. Having a reliable mechanism-specific model would allow leveraging historical data across compounds, to support decision making in drug development and possibly shorten the time to market. © 2018, The American College of Clinical Pharmacology.

A RARE CASE OF EXTRAMEDULLARY PLASMACYTOMA MASQUERADING AS JUVENILE NASOPHARYNGEAL ANGIOFIBROMA

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Harshita V. Sabhahit

2016-09-01

Full Text Available BACKGROUND Plasmacytomas are rare plasma cell tumours occurring consequent to monoclonal proliferation of plasma cells. They are divided into Solitary bone plasmacytoma, Extramedullary plasmacytoma (EMP and Multiple myeloma. EMPs are commonly housed in the head and neck region with a predilection to the mucosa associated lymphoid tissue in the aerodigestive tract. The nasal cavity, paranasal sinuses, and nasopharynx are the most common sites. OBJECTIVE We describe our experience with this tumour owing to its clinical rarity and a different way of presentation. METHODS After complete surgical excision of a nasal mass presenting in a young male with features masquerading that of Juvenile Nasopharyngeal Angiofibroma, a diagnosis of plasma cell tumour was made on histopathological analysis which was confirmed using immunohistochemistry. Serum electrophoresis, urine Bence Jones proteins, complete skeletal survey were done to rule out any progression into multiple myeloma. Radiation therapy was given with 45 Gy in 25 fractions at 1.8 Gy per day, 5 days a week. RESULTS Followup after 2 years showed no recurrence locally as well as in regional nodes. CONCLUSION Given to the rarity of the tumour, undefined manner of presentation and a predominant prevalence in the head and neck region, every otolaryngologist should keep EMP in mind while considering sinonasal masses. A multidisciplinary approach with a combination of surgery and radiotherapy is found to benefit the patient significantly. A long term watch out for progression to MM is mandatory to commence early treatment and thus prolonged disease-free survival from the same.

Phonological fluency strategy of switching differentiates relapsing-remitting and secondary progressive multiple sclerosis patients.

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Messinis, L; Kosmidis, M H; Vlahou, C; Malegiannaki, A C; Gatzounis, G; Dimisianos, N; Karra, A; Kiosseoglou, G; Gourzis, P; Papathanasopoulos, P

2013-01-01

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma

DEFF Research Database (Denmark)

Casneuf, Tineke; Xu, Xu Steven; Adams, Homer C

2017-01-01

Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and......, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy...

Extramedullary plasmocytoma of the rhino pharynx associated to intrathoracic mass - a case report

International Nuclear Information System (INIS)

Souza, Andrea Silveira de; Fernandes, Artur da Rocha Correa; Yamashita, Helio Kiitiro

1996-01-01

The authors report a case of a 56-year-old while male, who had occipital headache, libido and visual acuity (bitemporal field) reduction as the clinical picture, with progressive evolution within a four years period. The image diagnosis methods (roentgenologic studies, (MRI) demonstrated extensive mass involving the sella, clivus and sphenoid sinus, and an intrathoracic mass on the right. The final diagnosis was extramedullary plasmocytoma with rhinopharynx origin. (author)

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

OpenAIRE

Stephanie Zettner; Sandeep G. Mistry

2014-01-01

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospital...

Adrenal extramedullary hematopoiesis associated with β-thalassemia major

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Bijan Keikhaei

2012-01-01

Full Text Available The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hema - topoiesis (EMH. EMH is a rare complication in thalassemia major (TM and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7¥7.3¥5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started.

Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials.

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Shuo Liu

Full Text Available Intravenous glucocorticoids are recommended for multiple sclerosis (MS. However, they can be inconvenient and expensive. Due to their convenience and low cost, oral glucocorticoids may be an alternative treatment. Recently, several studies have shown that there is no difference in efficacy and safety between oral methylprednisolone (oMP and intravenous methylprednisolone (ivMP.We sought to assess the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses in this meta-analysis.Randomized controlled trials (RCTs evaluating the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane Library, Medline, EMBASE and China Biology Medicine until October 25, 2016, without language restrictions. The proportion of patients who had improved by day 28 was chosen as the efficacy outcome. We chose the risk ratio (RR to analyze each trial with the 95% confidence interval (95% CI. We also used the fixed-effects model (Mantel-Haenszel approach to calculate the pooled relative effect estimates.A total of 5 trials were identified, which included 369 patients. The results of our meta-analysis revealed that no significant difference existed in relapse improvement at day 28 between oMP and ivMP (RR 0.96, 95% CI 0.84 to 1.10. No evidence of heterogeneity existed among the trials (P = 0.45, I2 = 0%. Both treatments were equally safe and well tolerated except that insomnia was more likely to occur in the oMP group compared to the ivMP group.Our meta-analysis reveals strong evidence that oMP is not inferior to ivMP in increasing the proportion of patients experiencing clinical improvement at day 28. In addition, both routes of administration are equally well tolerated and safe. These findings suggest that we may be able to replace ivMP with oMP to treat MS relapses.

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

Science.gov (United States)

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

Extramedullary haematopoiesis in Thalassaemia: results of radiotherapy: a report of three patients

International Nuclear Information System (INIS)

Pistevou-Gompaki, K.; Paraskevopoulos, P.; Kotsa, K.; Skaragas, G.; Repanta, E.

1996-01-01

Extramedullary haematopoiesis is sometimes encountered in serve anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication. (Author)

The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

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Morteza Abdar

2017-03-01

Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

[The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)].

Science.gov (United States)

Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine

2014-09-01

The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

Resistance to Change and Relapse of Observing

Science.gov (United States)

Thrailkill, Eric A.; Shahan, Timothy A.

2012-01-01

Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI…

Solitary plasmacytoma of bone and soft tissue

International Nuclear Information System (INIS)

Bolek, Timothy W.; Marcus, Robert B.; Mendenhall, Nancy Price

1996-01-01

Purpose: This retrospective review evaluates the results of radiotherapy used for curative intent in the management of solitary plasmacytoma. Methods and Materials: Between August 1963 and January 1993, 37 patients with a solitary plasmacytoma were treated with curative intent at the University of Florida. Criteria for inclusion in the study were (a) a biopsy-proven plasmacytoma, (b) no tumor in the bone marrow on biopsy, and (c) no evidence of disseminated disease on skeletal survey. The primary site was osseous in 27 patients and extramedullary in 10 patients; 9 of the 10 extramedullary lesions were located in the upper respiratory passages. Treatment consisted of primary radio-therapy. in all but one patient, who received surgical resection alone. Two patients also received adjuvant chemotherapy. The median radiation dose was 43.2 Gy in 1.8-Gy fractions. Absolute survival, progression to myeloma, and local control rates were calculated using the Kaplan-Meier method. A multivariate analysis was performed for prognostic factors predictive of absolute survival. Results: Multivariate analysis revealed tumor type (osseous vs. extramedullary) to be predictive of absolute survival (p = 0.12). Factors not predictive of survival were age, sex, use of chemotherapy, immunoglobulin level, and type of immunoglobulin elevated. Patients with osseous tumors had a lower survival rate than those with extramedullary tumors (55% vs. 80% at 10 years, p = 0.06). Multiple myeloma was more likely to develop in patients with osseous tumors (54% vs. 11% at 10 years, 100% vs. 33% at 15 years, p = 0.03). Of patients in whom multiple myeloma developed, those with osseous tumors had a poorer survival rate after development of myeloma (32% vs. 100% at 5 years, p = 0.11). Local relapse developed in 1 patient with an osseous tumor 10 months after treatment with 28.3 Gy in 14 fractions; this was controlled with an additional 28.3 Gy in 10 fractions. Local failure did not develop in any patient

Functional symptoms in clinically definite MS--pseudo-relapse syndrome.

LENUS (Irish Health Repository)

Merwick, A

2012-02-03

Although the diagnostic criteria for multiple sclerosis (MS) have become more formalized and sensitive in the era of magnetic resonance imaging (MRI) scanning, the assessment of individual relapses may not always be straightforward or easily linked to a particular lesion seen on imaging. In addition, acute episodes often have to be assessed outside of normal working hours or when the individual patients usual medical team is not available. Often the emergency department physicians have little formal neurological training and are under time pressure to get patients through the system as quickly as possible. It is therefore possible to mislabel functional symptoms as being true relapses. To illustrate scenarios of possible pseudo-relapse, three clinical vignettes are described. Misclassification of functional symptoms as relapse carries a number of inherent risks. Functional symptoms can be multifactorial and may cause a burden of disease. A multidisciplinary approach may be useful in minimizing unnecessary harm and identify if there is more than meets the eye to an episode of clinical deterioration.

Extramedullary spinal teratoma presenting with recurrent aseptic meningitis.

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Mpayo, Lucy L; Liu, Xiao-Hong; Xu, Man; Wang, Kai; Wang, Jiao; Yang, Li

2014-06-01

Spinal teratomas are extremely rare; they constitute meningitis. A 7-year-old boy presented with paroxysmal abdominal pain and a history of recurrent aseptic meningitis. Kernig and Brudzinski signs were present. Lumber puncture revealed pleocytosis with no evidence of bacteria growth. Imaging of the spine revealed a cystic lesion in spinal cord at thoracic level 9-11. Endoscopic excision of the cyst was successfully performed. Surgical and histopathological findings confirmed extramedullary matured teratoma. As the symptomatic attacks of spontaneous rupture of spinal teratoma resemble presentations of Mollaret meningitis, spinal teratoma should be considered in the differential diagnosis of Mollaret meningitis. We describe a rare example of spinal teratoma causing recurrent meningitis. Spine imaging should be considered in individuals with recurrent aseptic meningitis as this promotes earlier diagnosis, more appropriate treatment, and improved neurological outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

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Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

2016-05-23

Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

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Richardson PG

2017-08-01

Full Text Available Paul G Richardson,1 Shaji Kumar,2 Jacob P Laubach,1 Claudia Paba-Prada,1 Neeraj Gupta,3 Deborah Berg,3 Helgi van de Velde,3 Philippe Moreau4 1Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA; 4Hematology Department, University Hospital Hotel-Dieu, Nantes, France Abstract: Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months. The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies. Keywords: ixazomib, multiple myeloma, proteasome inhibitor, clinical, efficacy, tolerability, pharmacokinetics 

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

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Georgios Koutsis

2015-01-01

Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

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Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Wechsler Adult Intelligence Scale-Fourth Edition performance in relapsing-remitting multiple sclerosis.

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Ryan, Joseph J; Gontkovsky, Samuel T; Kreiner, David S; Tree, Heather A

2012-01-01

Forty patients with relapsing-remitting multiple sclerosis (MS) completed the 10 core Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests. Means for age and education were 42.05 years (SD = 9.94) and 14.33 years (SD = 2.40). For all participants, the native language was English. The mean duration of MS diagnosis was 8.17 years (SD = 7.75), and the mean Expanded Disability Status Scale (EDSS; Kurtzke, 1983 ) score was 3.73 (SD = 1.41) with a range from 2.0 to 6.5. A control group of healthy individuals with similar demographic characteristics also completed the WAIS-IV and were provided by the test publisher. Compared to controls, patients with MS earned significantly lower subtest and composite scores. The patients' mean scores were consistently in the low-average to average range, and the patterns of performance across groups did not differ significantly, although there was a trend towards higher scores on the Verbal Comprehension Index (VCI) and lower scores on the Processing Speed Index (PSI). Approximately 78% of patients had actual Full Scale IQs that were significantly lower than preillness, demographically based IQ estimates.

Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

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Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

2016-01-01

The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

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Guillaume Bonnier

2017-09-01

Full Text Available ObjectiveQuantitative and semi-quantitative MRI (qMRI metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients.MethodsThirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue.ResultsIn patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005 and a decrease of T1 relaxation times in the pallidum (p < 0.05, which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e−16 and a significant increase in MTR (p-value < 1e−6, suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics—and not changes in lesions or brain volume—were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05. In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at

Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

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Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan

2009-01-01

We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions a...

HOW DOES FINGOLIMOD (GILENYA® FIT IN THE TREATMENT ALGORITHM FOR HIGHLY ACTIVE RELAPSING-REMITTING MULTIPLE SCLEROSIS?

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Franz eFazekas

2013-05-01

Full Text Available Multiple sclerosis (MS is a neurological disorder characterised by inflammatory demyelination and neurodegeneration in the central nervous system (CNS. Until recently, disease modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya® is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS for adult patients with high disease activity despite basic treatment (beta-interferon and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from 10 Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

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Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

2018-03-01

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Intra- and Extramedullary Dumbbell-Shaped Schwannoma of the Medulla Oblongata: A Case Report and Review of the Literature.

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Zhang, Qing; Ni, Ming; Liu, Wei-Ming; Jia, Wang; Jia, Gui-Jun; Zhang, Jun-Ting

2017-02-01

Brainstem intramedullary schwannomas (ISs) are extremely rare. Various theories have been suggested to explain its origin. It was first speculated that ISs arise from the region where the nerve roots lose their sheaths on penetrating the pia mater. Later, it was further predicted that ISs would contain both intra- and extramedullary parts and would be shaped like a dumbbell. However, no cases reported previously can support this assumption adequately. A 40-year-old woman presented with constant cervical pain, accompanied by progressive weakness of upper extremities and glove distribution numbness. Magnetic resonance imaging of the brain revealed a rare intra- and extramedullary dumbbell-shaped lesion of the medulla oblongata, which was partially removed via a midline suboccipital craniectomy. Histologic and immunohistochemical examinations confirmed the diagnosis of schwannoma. Routine imaging performed 20 months after the initial resection revealed a regrowth of the intramedullary part, which was subsequently partially removed through a far-lateral approach, with symptoms alleviated. At 2-year follow-up, there continued to be no radiologic or clinical evidence of regrowth. To date and to our knowledge, there are only 16 reported cases of brainstem ISs, none of which contained both intra- and extramedullary components. We believe this is the first report of dumbbell schwannoma of the medulla oblongata with adequate radiologic evidence. The relevant literature is reviewed, and an assumption has been proposed that dumbbell or surfacing ISs arising near entry zones of sensory nerves, mixed cranial nerves, or ventral root may originate from the aberrant Schwann cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracranial involvement in extramedullary hematopoiesis: case report and review of the literature

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Haidar, Salwa; Ortiz-Neira, Clara; Shroff, Manohar; Gilday, David; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

2005-06-01

Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it should be suspected in patients with myelofibrosis presenting with chronic severe headache. We present a 9-year-old girl with known myelofibrosis whose headaches were unresponsive to routine treatment. CT and MRI studies of the brain showed diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the possibility that the intracranial involvement might also be related to EMH. The diagnosis was confirmed by sulfur colloid isotope scan. (orig.)

Intracranial involvement in extramedullary hematopoiesis: case report and review of the literature

International Nuclear Information System (INIS)

Haidar, Salwa; Ortiz-Neira, Clara; Shroff, Manohar; Gilday, David; Blaser, Susan

2005-01-01

Intracranial involvement in extramedullary hematopoiesis (EMH) is rare, but it should be suspected in patients with myelofibrosis presenting with chronic severe headache. We present a 9-year-old girl with known myelofibrosis whose headaches were unresponsive to routine treatment. CT and MRI studies of the brain showed diffuse pachymeningeal thickening. CT examinations of the chest and abdomen had demonstrated bilateral thoracic paraspinal masses caused by EMH, suggesting the possibility that the intracranial involvement might also be related to EMH. The diagnosis was confirmed by sulfur colloid isotope scan. (orig.)

Intracranial extramedullary hematopoiesis in patients with thalassemia: a case report and review of the literature.

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Eskazan, Ahmet Emre; Ar, Muhlis Cem; Baslar, Zafer

2012-08-01

Extramedullary hematopoiesis (EH) is a compensatory phenomenon that results in the production of blood cell precursors outside the marrow in patients with chronic hemolytic anemia and ineffective erythropoiesis. EH usually involves the liver, spleen, and lymph nodes. It can also be found at paravertebral, intrathoracic, or pelvic locations. Intracranial EH is a rare entity and often asymptomatic but can sometimes lead to symptomatic tumor-like masses. Treatment options are controversial and include hypertransfusion, surgical excision, radiotherapy, and hydroxyurea (HU). Successful treatment of an intracranial EH mass with HU and blood transfusions in a beta-thalassemia major patient was discussed along with a review of the published literature on intracranial EH in thalassemia. In our patient, the extramedullary hematopoietic mass in the interhemispheric fissure showed a marked improvement after 6 months of HU and hypertransfusion therapy. In the English literature, there are a few cases with intracranial EH and thalassemia, which were treated with different treatment modalities, with different outcomes. There is no standard treatment approach in patients with symptomatic EH. HU with hypertransfusion regimen is a reasonable first-choice modality in treating intracranial EH masses. © 2012 American Association of Blood Banks.

Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses.

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Rolla, Simona; De Mercanti, Stefania Federica; Bardina, Valentina; Horakova, Dana; Habek, Mario; Adamec, Ivan; Cocco, Eleonora; Annovazzi, Pietro; Vladic, Anton; Novelli, Francesco; Durelli, Luca; Clerico, Marinella

2017-12-15

Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Primary progressive multiple sclerosis in the Polish population

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Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis.

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Konca Degertekin, Ceyla; Ozkurt, Zübeyde Nur; Akyürek, Nalan; Yağcı, Münci

2014-09-01

Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic myelofibrosis refractory to treatment, developing EMH after splenectomy in various organs, exceptionally the skin and the heart. Along with the case, the clinical presentations, treatment options, prognostic significance of EMH and the role of cytogenetics is discussed in the light of the literature.

Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study.

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Oriol, Albert; Giraldo, Pilar; Kotsianidis, Ioannis; Couturier, Catherine; Olie, Robert; Angermund, Ralf; Corso, Alessandro

2015-08-01

Multiple myeloma remains incurable and retreatment with available therapies is of substantial interest. This retrospective observational study included data from 35 patients treated initially and at the first relapse with bortezomib-containing regimens. Bortezomib retreatment provided a similar depth and time to response as first-line therapy; however, as could be expected, the duration of response was shorter with retreatment. The tolerability profile was similar with bortezomib as the first- and second-line therapy, with no evidence of cumulative toxicity. These findings support bortezomib retreatment after a treatment-free interval of ≥6 months in patients who achieved at least a partial response to the first-line bortezomib-based therapy.

Extramedullary hematopoiesis: a rare occurrence in the sinonasal tract.

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Bizzoni, Andrea; Lombardi, Davide; Maroldi, Roberto; Incardona, Paolo; Nicolai, Piero

2010-04-01

Extramedullary hematopoiesis (EMH) is a systemic reaction to inadequate hematopoiesis. We report two exceedingly rare cases of EMH involving the paranasal sinuses. The first patient, a 30-year-old man, presented with a maxillary sinus mass. The lesion was excised by endoscopic surgery: definitive histology identified foci of EMH within an inflammatory fibromyxoid pseudotumor. The second case occurred in a 29-year-old man affected by intermediate beta-thalassemia. He was hospitalized with a diagnosis of sphenoid sinus mucocele secondary to an ethmoid lesion. The patient underwent endoscopic excision of the mass and drainage of the sphenoid mucocele. At definitive histology, a diagnosis of EMH was established. Herein, the presenting modalities, imaging profile, and treatment options of this rare EMH localization are reviewed. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Ectopic extramedullary hematopoiesis: evaluation and treatment of a rare and benign paraspinal/epidural tumor.

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Mattei, Tobias A; Higgins, Michael; Joseph, Flynn; Mendel, Ehud

2013-03-01

Ectopic extramedullary hematopoiesis (EMH), defined as the formation of blood cells outside the bone marrow, usually occurs in a scenario of chronic anemia when, even after conversion of the bony yellow marrow to red marrow, the body is still unable to meet the demand for red blood cells. Ectopic extramedullary hematopoiesis most commonly occurs in the liver and spleen but may, in fact, occur almost anywhere in the body. Although previous reports have documented EMH presenting as paraspinal masses, such lesions have almost always been associated with a predisposing hematological disorder such as hemolytic anemia, myelofibrosis or myelodysplastic syndromes, thalassemia, polycythemia vera, leukemia, or lymphoma. The authors of this report describe the first reported instance of EMH in a patient presenting with a symptomatic epidural and paraspinal cervical lesion arising from the posterior spinal elements and no known predisposing hematological disease. Initial radiographs revealed a bony lesion arising posteriorly from the C2-3 laminae and spinous processes. Subsequent imaging suggested the diagnosis, which was confirmed by CT-guided biopsy, peripheral blood smears, and bone marrow aspirate. Despite epidural compression and slight displacement of the cervical cord and thecal sac, the patient's symptoms were limited to pain and diminished cervical range of motion. Therefore, surgery was deferred in favor of nonsurgical therapy. Several alternative modalities for the treatment of EMH have been suggested in the literature, including cytotoxic agents and radiotherapy. The authors opted for an approach utilizing directed low-dose radiotherapy of a total of 25 Gy divided in 2.5-Gy fractions. At the 3-month follow-up, the patient continued to be asymptomatic, and MRI demonstrated a significant reduction in the dimensions of the lesion. Extramedullary hematopoiesis with spinal cord compression in the absence of a preexisting hematological disorder has not been described in

Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy

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Foronda Jesus

2004-06-01

Full Text Available Abstract Background What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. Methods Thirty one patients (9 male and 22 female with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0–5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Results A statistically significant correlation was found (r = -0.38 p Conclusions There is correlation between disability (measured by Expanded Disability Scale Score and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor.

Intra-extramedullary drainage as an effective option for treatment of intramedullary ependymal cyst of thoracic spine: technical note.

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Landi, Alessandro; Pietrantonio, Andrea; Marotta, Nicola; Mancarella, Cristina; Delfini, Roberto

2014-03-01

Intramedullary neuroepithelial cysts are extremely rare and only 15 cases have been reported in the literature. Clinico-radiological features are not indicative of a specific diagnosis; for this reason, diagnosis is based mainly on the histological features. In the literature, total surgical removal is considered the treatment of choice. The risk of recurrence is higher after partial removal and in cases of occlusion of intra-extramedullary shunt. For this reason, a surgical strategy that ensures the shunt patency in case of incomplete removal of the cyst becomes a very safe option for treatment of this pathology. We report the case of a 51-year-old woman who was found to have a dorsal (D9) intramedullary neuroepithelial cyst. She underwent surgical treatment with partial removal and placement of a Nelaton drainage device (8 French) inside the intra-extramedullary shunt. The patient experienced a complete regression of preoperative symptoms and magnetic resonance imaging (MRI) follow-up showed no radiological evidence of recurrence 24 months after surgical treatment. Spinal ependymal cysts show a high frequency of recurrence, especially in cases of partial removal of the cyst wall. Unfortunately, the cyst walls are often closely adherent to the spinal cord, making total removal impossible. Intra-extramedullary shunting is a viable option, although there is a high frequency of recurrence in cases of obstruction of the shunt. Placing an 8 Ch Nelaton drain between the dorsal columns is a reliable technique, especially in cases of partial removal. In fact, it allows continuous drainage of cyst fluid and subsequent resolution of symptoms, and it decreases the incidence of recurrences due to obstruction of the shunt. Georg Thieme Verlag KG Stuttgart · New York.

Radiotherapy for solitary plasmacytoma and multiple myeloma

International Nuclear Information System (INIS)

Schmaus, M.C.; Neuhof, D.

2014-01-01

Solitary plasmacytoma and multiple myeloma require a differentiated radiotherapy. The irradiation for plasmacytoma with an adequate total dose (medullary 40-50 Gy or extramedullary 50-60 Gy) leads to a high degree of local control with a low rate of side effects. In cases of multiple myeloma radiotherapy will achieve effective palliation, both in terms of recalcification as well as reduction of neurological symptoms and analgesia. In terms of analgesia the rule is the higher the single dose fraction the faster the reduction of pain. As part of a conditioning treatment prior to stem cell transplantation radiotherapy contributes to the establishment of a graft versus myeloma effect (GVM). (orig.) [de

Ischaemic colitis and lung infiltrates caused by extramedullary haematopoiesis in a patient with an acute erythroid leukaemia following polycythaemia vera

NARCIS (Netherlands)

Brada, SJL; de Wolf, JTM; Poppema, S; Vellenga, E

A patient with 'spent' polycythaemia vera showed extensive extramedullary haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory investigation, the EMH also included immature erythroblasts due to

Paraplegia due to extramedullary hematopoiesis in thalassemia treated successfully with radiation therapy.

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Malik, Monica; Pillai, Lakshmi S; Gogia, Nidhi; Puri, Tarun; Mahapatra, M; Sharma, Daya Nand; Kumar, Rajat

2007-03-01

Spinal cord compression due to extramedullary hematopoiesis (EMH) is a rare complication of thalassemia and generally presents as paraparesis with sensory impairment. Complete paraplegia is extremely rare in EMH due to thalassemia although it is known to occur in polycythemia vera and sickle cell anemia. Treatment options mostly include surgery and/or radiotherapy. Whereas cases presenting with paraparesis have been treated with either surgery or radiotherapy with equal frequency and efficacy, almost all reported cases with paraplegia have been treated with surgery with or without radiation therapy. We hereby report a case of thalassemia intermedia with paraplegia treated successfully with radiotherapy.

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

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García-Sanz, Ramón; Oriol, Albert; Moreno, María J.; de la Rubia, Javier; Payer, Angel R.; Hernández, Miguel T.; Palomera, Luis; Teruel, Ana I.; Blanchard, María J.; Gironella, Mercedes; Ribas, Paz; Bargay, Joan; Abellá, Eugenia; Granell, Miquel; Ocio, Enrique M.; Ribera, Josep M.; San Miguel, Jesús F.; Mateos, María V.

2015-01-01

This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P<0.001). In summary, zoledronic acid monotherapy does not show an antitumor effect on biochemical relapses in multiple myeloma, but does reduce the risk of progression with symptomatic bone disease and skeletal complications. This trial was registered in the ClinicalTrials.gov database with code NCT01087008 PMID:26069291

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation.

NARCIS (Netherlands)

Auner, H.W.; Szydlo, R.; Biezen, A. van; Iacobelli, S.; Gahrton, G.; Milpied, N.; Volin, L.; Janssen, J.; Nguyen Quoc, S.; Michallet, M.; Schoemans, H.; Cheikh, J. El; Petersen, E.; Guilhot, F.; Schonland, S.; Ahlberg, L.; Morris, C.; Garderet, L.; Witte, T.J. de; Kroger, N.

2013-01-01

Outcomes and prognostic factors of reduced intensity-conditioned allo-SCT (RIC allo-SCT) for multiple myeloma (MM) relapsing or progressing after prior autologous (auto)-SCT are not well defined. We performed an analysis of 413 MM patients who received a related or unrelated RIC allo-SCT for the

Spinal cord compression secondary to extramedullary hematopoiesis: A rareness in a young adult with thalassemia major.

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Fareed, Shehab; Soliman, Ashraf T; De Sanctis, Vincenzo; Kohla, Samah; Soliman, Dina; Khirfan, Diala; Tambuerello, Adriana; Talaat, Mohamed; Nashwan, Abdulqadir; Caparrotti, Palmira; Yassin, Mohamed A

2017-08-23

We report a case of a thalassemia major male patient with back pain associated to severe weakness in lower extremities resulting in the ability to ambulate only with assistance. An urgent magnetic resonance imaging (MRI) of  thoracic and lumbosacral spine was requested. A posterior intraspinal extradural mass lesion compressing the spinal cord at the level of thoracic T5-8 was present, suggesting an extramedullary hematopoietic centre, compressing the spinal cord. He was treated successfully with thalassemia major alone. The patient was treated with blood transfusion, dexamethasone, morphine and paracetamol, followed by radiotherapy in 10 fractions to the spine (daily fraction of 2Gy from T3 to T9, total dose 20 Gy). His pain and neurologic examination quickly improved. A new MRI of the spine, one week after radiotherapy, showed an improvement of the extramedullary hematopoietic mass compression. In conclusion, EMH should be considered in every patient with ineffective erythropoiesis and spinal cord symptoms. MRI is the most effective method of demonstrating EMH. The rapid recognition and treatment can dramatically alleviate symptoms. There is still considerable controversy regarding indications, benefits, and risks of each of modality of treatment due to the infrequency of this disorder.

Quantitative diffusion tensor deterministic and probabilistic fiber tractography in relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Hu Bing; Ye Binbin; Yang Yang; Zhu Kangshun; Kang Zhuang; Kuang Sichi; Luo Lin; Shan Hong

2011-01-01

Purpose: Our aim was to study the quantitative fiber tractography variations and patterns in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the correlation between quantitative fiber tractography and Expanded Disability Status Scale (EDSS). Material and methods: Twenty-eight patients with RRMS and 28 age-matched healthy volunteers underwent a diffusion tensor MR imaging study. Quantitative deterministic and probabilistic fiber tractography were generated in all subjects. And mean numbers of tracked lines and fiber density were counted. Paired-samples t tests were used to compare tracked lines and fiber density in RRMS patients with those in controls. Bivariate linear regression model was used to determine the relationship between quantitative fiber tractography and EDSS in RRMS. Results: Both deterministic and probabilistic tractography's tracked lines and fiber density in RRMS patients were less than those in controls (P < .001). Both deterministic and probabilistic tractography's tracked lines and fiber density were found negative correlations with EDSS in RRMS (P < .001). The fiber tract disruptions and reductions in RRMS were directly visualized on fiber tractography. Conclusion: Changes of white matter tracts can be detected by quantitative diffusion tensor fiber tractography, and correlate with clinical impairment in RRMS.

Value of {sup 18}F-fluorodeoxyglucose uptake in positron emission tomography/computed tomography in predicting survival in multiple myeloma

Energy Technology Data Exchange (ETDEWEB)

Haznedar, Rauf; Aki, Sahika Z.; Oezkurt, Zuebeyde N.; Yagci, Muenci; Sucak, Gulsan T. [Gazi University Faculty of Medicine, Department of Hematology, Ankara (Turkey); Akdemir, Oezguer U. [Gazi University Faculty of Medicine, Department of Nuclear Medicine, Ankara (Turkey); Ceneli, Oezcan [Kirikkale University Sueleyman Demirel Hospital, Department of Hematology, Kirikkale (Turkey); Uenlue, Mustafa [Gazi University Faculty of Medicine, Department of Nuclear Medicine, Ankara (Turkey); Gazi University Faculty of Medicine, Ankara (Turkey)

2011-06-15

We assessed the role of the maximum standardized uptake value (SUV{sub max}) of bone marrow and the extramedullary lesion with the highest SUV{sub max} in positron emission tomography/computed tomography (PET/CT) of newly diagnosed multiple myeloma (MM) patients in predicting overall survival (OS). A total of 61 newly diagnosed patients (55 MM and 6 plasmacytoma) were enrolled in the study [37 men and 24 women with a median age of 57 years (range 28-80 years)]. The SUV{sub max} of bone marrow and the extramedullary lesion in PET/CT was correlated with the levels of {beta}{sub 2}-microglobulin, C-reactive protein (CRP), albumin, creatinine, per cent of bone marrow plasma cells, serum free light chain (FLC) ratio, International Staging System (ISS) score and Durie-Salmon stage. The extramedullary lesion with the highest SUV{sub max} showed significant correlation with bone marrow fluorodeoxyglucose (FDG) uptake (p = 0.027) and near significant correlation with ISS (p = 0.048). Bone marrow SUV{sub max} correlated significantly with the per cent of bone marrow plasma cell count (p = 0.024), CRP (p = 0.012) and ISS (p = 0.013). In stage III MM the mean values of SUV{sub max} in extramedullary lesions were significantly higher than stages I and II (6.23 {+-} 6.32 vs 2.85 {+-} 3.44, p = 0.023). The serum FLC ratio did not show any correlation with SUV{sub max} of lesions and bone marrow (p > 0.05). Forty-four MM patients with FDG-positive lesions in PET/CT showed inferior 5-year estimated survival (61.73%) when compared to 11 patients without FDG-positive lesions, all of whom were alive (p = 0.01). In multivariate analysis an extramedullary lesion with the highest SUV{sub max} was the only independent predictor of OS (p = 0.03). PET/CT allows identification of high-risk myeloma patients, and extramedullary lesions with the highest SUV{sub max} independently predict inferior OS. (orig.)

Oral available agents in the treatment of relapsing remitting multiple sclerosis an overview of merits and culprits

Directory of Open Access Journals (Sweden)

Thöne J

2013-02-01

Full Text Available Jan Thöne, Gisa Ellrichmann Department of Neurology, St Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany Abstract: Multiple sclerosis (MS is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles. Keywords: cladribine, fingolimod (FTY, fumaric acid esters (BG-12, laquinimod, teriflunomide

Relapsing-Remitting MS (RRMS)

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Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ... Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the Society ...

Chronic Idiopathic Myelofibrosis Presenting as Cauda Equina Compression due to Extramedullary Hematopoiesis: A Case Report

Science.gov (United States)

Goh, Duck-Ho; Cho, Dae-Chul; Park, Seong-Hyun; Hwang, Jeong-Hyun; Sung, Joo-Kyung

2007-01-01

Extramedullary hematopoiesis (EMH) is occasionally reported in idiopathic myelofibrosis and is generally found in the liver, spleen, and lymph nodes several years after diagnosis. Myelofibrosis presenting as spinal cord compression, resulting from EMH tissue is very rare. A 39-yr-old man presented with back pain, subjective weakness and numbness in both legs. Sagittal magnetic resonance imaging showed multiple anterior epidural mass extending from L4 to S1 with compression of cauda equina and nerve root. The patient underwent gross total removal of the mass via L4, 5, and S1 laminectomy. Histological analysis showed islands of myelopoietic cells surrounded by fatty tissue, consistent with EMH, and bone marrow biopsy performed after surgery revealed hypercellular marrow and megakaryocytic hyperplasia and focal fibrosis. The final diagnosis was chronic idiopathic myelofibrosis leading to EMH in the lumbar spinal canal. Since there were no abnormal hematological findings except mild myelofibrosis, additional treatment such as radiothepary was not administered postoperatively for fear of radiotoxicity. On 6 month follow-up examination, the patient remained clinically stable without recurrence. This is the first case of chronic idiopathic myelofibrosis due to EMH tissue in the lumbar spinal canal in Korea. PMID:18162730

The Value of Fecal Markers in Predicting Relapse in Inflammatory Bowel Diseases

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Bianca J. Galgut

2018-01-01

Full Text Available The inflammatory bowel diseases (IBDs are lifelong chronic illnesses that place an immense burden on patients. The primary aim of therapy is to reduce disease burden and prevent relapse. However, the occurrence of relapses is often unpredictable. Current disease monitoring is primarily by way of clinical indices, with relapses often only recognized once the inflammatory episode is established with subsequent symptoms and gut damage. The window between initial upregulation of the inflammatory response and the recognition of symptoms may provide an opportunity to prevent the relapse and associated morbidity. This review will describe the existing literature surrounding predictive indicators of relapse of IBD with a specific focus on fecal biomarkers. Fecal biomarkers offer promise as a convenient, non-invasive, low cost option for disease monitoring that is predictive of subsequent relapse. To exploit the potential of fecal biomarkers in this role, further research is now required. This research needs to assess multiple fecal markers in context with demographics, disease phenotype, genetics, and intestinal microbiome composition, to build disease behavior models that can provide the clinician with sufficient confidence to intervene and change the long-term disease course.

A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.

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Ogawa, Yoshiaki; Ogura, Michinori; Tobinai, Kensei; Ando, Kiyoshi; Suzuki, Tatsuya; Watanabe, Takashi; Ohmachi, Ken; Uchida, Toshiki; Hanson, Mary E; Tanaka, Yoshinobu; Koh, Yasuhiro; Shimamoto, Takashi; Hotta, Tomomitsu

2016-01-01

This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.3 mg/m(2) intravenous bortezomib (Days 1, 4, 8, and 11) and oral vorinostat 400 mg (Days 1 through 14) and were further evaluated. Vorinostat and bortezomib treatment doses were determined by DLT and safety, tolerability, and treatment response were assessed. Of 7 enrolled patients, 6 were evaluated, and one developed DLTs. The most common adverse events were leukopenia, neutropenia, thrombocytopenia, diarrhea, nausea, decreased appetite, and vomiting. Combination of vorinostat plus bortezomib did not increase vorinostat exposure at Day 11 [AUC0-24 h ratio (95% CI) = 1.08 (0.80, 1.45)]; geometric mean AUC0-24 h ratio for bortezomib (90% CI) was 1.96 (1.24-3.12). Objective therapeutic response occurred in 3 patients, including 1 complete response and 2 partial responses. Vorinostat 400 mg plus bortezomib 1.3 mg/m(2) was safe and well-tolerated in Japanese patients with relapsed or refractory MM not considered bortezomib refractory (NCT00858234).

A case report of craniovertebral junction intradural extramedullary neurenteric cyst

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Rajeshwari S Vhora

2014-01-01

Full Text Available A neurenteric cyst of the craniocervical (CV junction, as a cause of bulbomedullary compression, is very rare. An abnormal communication between the endoderm and neuroectoderm during the third week of embryogenesis may be responsible for its formation. It is a rare spinal condition. The most frequent location is at the lower cervical and higher thoracic spine. Neurenteric cysts of the craniocervical junction are even rarer. We report the case of a CV junction intradural neurenteric cyst. Magnetic Resonance Imaging (MRI of our patient demonstrated an intradural extramedullary process of the craniocervical junction. A surgical posterior approach allowed gross total resection of the lesion. The histopathology of the surgical specimen showed that the cyst wall was made up of fibrocollagen walls lined with a partially ciliated columnar epithelium.

Treatment of multiple sclerosis relapses with high-dose methylprednisolone reduces the evolution of contrast-enhancing lesions into persistent black holes.

Science.gov (United States)

Di Gregorio, Maria; Gaetani, Lorenzo; Eusebi, Paolo; Floridi, Piero; Picchioni, Antonella; Rosi, Giovanni; Mancini, Andrea; Floridi, Chiara; Baschieri, Francesca; Gentili, Lucia; Sarchielli, Paola; Calabresi, Paolo; Di Filippo, Massimiliano

2018-03-01

The MRI evidence of persistent black holes (pBHs) on T1-weighted images reflects brain tissue loss in multiple sclerosis (MS). The evolution of contrast-enhancing lesions (CELs) into pBHs probably depends on the degree and persistence of focal brain inflammation. The aim of our retrospective study was to evaluate the effect of a single cycle of intravenous methylprednisolone (IVMP), as for MS relapse treatment, on the risk of CELs' evolution into pBHs. We selected 57 patients with CELs on the baseline MRI scan. We evaluated the evolution of CELs into pBHs on a follow-up MRI scan performed after ≥ 6 months in patients exposed and not exposed to IVMP for the treatment of relapse after the baseline MRI. In our cohort, 182 CELs were identified in the baseline MRI and 57 of them (31.3%) evolved into pBHs. In the multivariate analysis, the exposure of CELs to IVMP resulted to be a significant independent protective factor against pBHs' formation (OR 0.28, 95% CI 0.11-0.766, p = 0.005), while ring enhancement pattern and the fact of being symptomatic were significant risk factors for CELs' conversion into pBHs (OR 6.42, 95% CI 2.55-17.27, p < 0.001 and OR 13.19, 95% CI 1.56-288.87, p = 0.037). The exposure of CELs to a cycle of IVMP as for relapse treatment is associated with a lower risk of CELs' evolution into pBHs. Future studies are required to confirm the potential independent protective effect of IVMP on CELs' evolution into pBHs.

Incomplete paraplegia caused by extramedullary hematopoiesis in a patient with thalassemia intermedia.

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Hisamud-Din, Nurhasyimah; Mustafah, Nadia Mohd; Fauzi, Aishah Ahmad; Hashim, Natiara Mohamad

2017-01-01

Extramedullary hematopoiesis (EMH) is the production of blood cell precursors outside the bone marrow that occur in various hematological diseases. In patients with thalassemia intermedia, ineffective erythropoiesis drives compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. We describe a patient with thalassemia intermedia who presented with acute neurological symptoms caused by paraspinal EMH, which responded well to combination therapy of steroid, hypertransfusion, laminectomy and excision of pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin. Prompt recognition of EMH based on clinical presentation and typical radiological findings should be made. Early treatment is recommended to prevent irreversible damage to the spinal cord.

The role of family expressed emotion and perceived social support in predicting addiction relapse.

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Atadokht, Akbar; Hajloo, Nader; Karimi, Masoud; Narimani, Mohammad

2015-03-01

Emotional conditions governing the family and patients' perceived social support play important roles in the treatment or relapse process of the chronic disease. The current study aimed to investigate the role of family expressed emotion and perceived social support in prediction of addiction relapse. The descriptive-correlation method was used in the current study. The study population consisted of the individuals referred to the addiction treatment centers in Ardabil from October 2013 to January 2014. The subjects (n = 80) were randomly selected using cluster sampling method. To collect data, expressed emotion test by Cole and Kazaryan, and Multidimensional Scale of Perceived Social Support (MSPSS) were used, and the obtained data was analyzed using the Pearson's correlation coefficient and multiple regression analyses. Results showed a positive relationship between family expressed emotions and the frequency of relapse (r = 0.26, P = 0.011) and a significant negative relationship between perceived social support and the frequency of relapse (r = -0.34, P = 0.001). Multiple regression analysis also showed that perceived social support from family and the family expressed emotions significantly explained 12% of the total variance of relapse frequency. These results have implications for addicted people, their families and professionals working in addiction centers to use the emotional potential of families especially their expressed emotions and the perceived social support of addicts to increase the success rate of addiction treatment.

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

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Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

2018-04-18

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Relapse of Neuromyelitis Optica Spectrum Disorder Associated with Intravenous Lidocaine

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Akiyuki Uzawa

2011-01-01

Full Text Available Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients; however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out.

Extramedullary hematopoiesis within the clivus: an unusual cause of lower cranial nerve palsy.

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Reames, Davis L; Lindstrom, Katherine; Raghavan, Prashant; Jane, John

2010-12-01

We report one year follow up of a case of extramedullary hematopoiesis within the clivus. The imaging findings, brief clinical course, and endoscopic transphenoidal approach are described. A 29-year-old female with thalassemia developed worsening cranial nerve signs. After imaging studies discovered a large clival mass, she underwent endoscopic transphenoidal biopsy of the lesion. Neural compression from exuberant erythrogenesis within tissue normally quiescent of red blood cell production was found to be the etiology of her neural deficit. Treatment for this condition is generally non-operative unless significant neural compression is present. Radiotherapy and anti-neoplastic agents have been used with success.

Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

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Gabriel Bsteh

Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

Predicting Relapse among Young Adults: Psychometric Validation of the Advanced Warning of Relapse (AWARE) Scale

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Kelly, John F.; Hoeppner, Bettina B.; Urbanoski, Karen A.; Slaymaker, Valerie

2011-01-01

Objective Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure - the Advance WArning of RElapse scale (AWARE) scale (Miller and Harris, 2000) in an understudied but clinically important sample of young adults. Method Inpatient youth (N=303; Age 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Results Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. Conclusions The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. PMID:21700396

Predicting relapse among young adults: psychometric validation of the Advanced WArning of RElapse (AWARE) scale.

Science.gov (United States)

Kelly, John F; Hoeppner, Bettina B; Urbanoski, Karen A; Slaymaker, Valerie

2011-10-01

Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure-the Advance WArning of RElapse (AWARE) scale (Miller & Harris, 2000) in an understudied but clinically important sample of young adults. Inpatient youth (N=303; Ages 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

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Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0

The European Medicines Agency Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

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Tzogani, Kyriaki; van Hennik, Paula; Walsh, Ita; De Graeff, Pieter; Folin, Annika; Sjöberg, Jan; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

2017-11-30

On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3-4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3-4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7

Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

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Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin; Edden, Richard A.E.; Li, Hao; Chen, Weibo; Liu, Xiaohui

2018-01-01

To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

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Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin [Shandong University, Shandong Medical Imaging Research Institute, Jinan (China); Edden, Richard A.E. [The Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Kennedy Krieger Institute, FM Kirby Center for Functional Brain Imaging, Baltimore, MD (United States); Li, Hao [Air Force General Hospital PLA, Beijing (China); Chen, Weibo [Philips Healthcare, Shanghai (China); Liu, Xiaohui [Shandong Provincial Hospital Affiliated to Shandong University, Department of Neurology, Jinan (China)

2018-03-15

To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

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Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

2011-01-01

Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

Social settings and addiction relapse.

Science.gov (United States)

Walton, M A; Reischl, T M; Ramanthan, C S

1995-01-01

Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

Relapsing-Remitting MS (RRMS)

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Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens

NARCIS (Netherlands)

Montesinos, Pau; Rayon, Chelo; Vellenga, Edo; Brunet, Salut; Gonzalez, Jose; Gonzalez, Marcos; Holowiecka, Aleksandra; Esteve, Jordi; Bergua, Juan; Gonzalez, Jose D.; Rivas, Concha; Tormo, Mar; Rubio, Vicente; Bueno, Javier; Manso, Felix; Milone, Gustavo; de la Serna, Javier; Perez, Inmaculada; Perez-Encinas, Manuel; Krsnik, Isabel; Ribera, Josep M.; Escoda, Lourdes; Lowenberg, Bob; Sanz, Miguel A.

2011-01-01

The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and

Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

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Juan Ignacio Rojas

2012-08-01

Full Text Available OBJECTIVE: To determine if the presence of oligoclonal bands (OB at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF were included. SIENAX was used for total brain volume (TBV, gray matter volume (GMV, and white matter volume (WMV. RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS, treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6 compared with 1.64 mm³ x 10(6 in the negative ones (p=0.02. GMV was 0.51 mm³ x 10(6 in positive IgG-OB compared with 0.62 mm³ x 10(6 in negative ones (p=0.002. No differences in WMV (p=0.09 were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR markers in early RRMS.

Extramedullary hematopoiesis of the conjunctiva presenting as active systemic disease in a patient with myelofibrosis.

Science.gov (United States)

Cuttler, Nirupa; Heidemann, David; Cendrowski, Christopher; Armin, Ali-Reza; Folberg, Robert

2014-12-01

To report the clinicopathological correlation of extramedullary hematopoiesis (EMH) of the conjunctiva in a patient with a history of myelofibrosis. Case report. Elevated pink conjunctival lesions developed bilaterally in a 73-year-old man who had been treated for myelofibrosis for 13 years. EMH was detected in the examination of tissue from the lesion of the inferior fornix of the right eye. The appearance of conjunctival lesions in a patient with myelofibrosis may indicate underlying pathology of EMH that may necessitate a change in systemic treatment of this condition.

Extramedullary Hematopoiesis in a Man With β-Thalassemia: An Uncommon Cause of an Adrenal Mass

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Zeighami

2015-06-01

Full Text Available Introduction Extramedullary hematopoiesis (EMH commonly occurs in the spleen, liver and lymph nodes. Rare cases of EMH in the adrenal gland have been reported. Case Presentation We report the case of a 33-year-old man from the South of Iran suffering from major β-thalassemia, who underwent open left adrenalectomy and the histopathology revealed EMH. Conclusions In patients in which a history of hematologic disorders exists, careful imaging and hormonal assay should be done to certify a diagnosis of EMH. However, the surgical management becomes inevitable in certain cases.

Exercise identity and attribution properties predict negative self-conscious emotions for exercise relapse.

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Flora, Parminder K; Strachan, Shaelyn M; Brawley, Lawrence R; Spink, Kevin S

2012-10-01

Research on exercise identity (EXID) indicates that it is related to negative affect when exercisers are inconsistent or relapse. Although identity theory suggests that causal attributions about this inconsistency elicit negative self-conscious emotions of shame and guilt, no EXID studies have examined this for exercise relapse. Weiner's attribution-based theory of interpersonal motivation (2010) offers a means of testing the attribution-emotion link. Using both frameworks, we examined whether EXID and attributional properties predicted negative emotions for exercise relapse. Participants (n = 224) read an exercise relapse vignette, and then completed EXID, attributions, and emotion measures. Hierarchical multiple regression models using EXID and the attributional property of controllability significantly predicted each of shame and guilt, R² adjusted = .09, ps ≤ .001. Results support identity theory suggestions and Weiner's specific attribution-emotion hypothesis. This first demonstration of an interlinking of EXID, controllability, and negative self-conscious emotions offers more predictive utility using complementary theories than either theory alone.

Relapsing-Remitting MS (RRMS)

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Extramedullary hematopoiesis with spinal cord compression in a child with thalassemia intermedia.

Science.gov (United States)

Ileri, Talia; Azik, Fatih; Ertem, Mehmet; Uysal, Zumrut; Gozdasoglu, Sevgi

2009-09-01

Spinal cord compression due to extramedullary hematopoiesis is an extremely rare complication of thalassemia intermedia. No cases with this complication have been reported in the first decade of life, because masses of heterotropic marrow developed in patients as a result of continuous erythropoiesis. We report the 9-year-old patient suffering from thalassemia intermedia and presenting spinal cord compression. We also review the literature about treatment options, because there is no consensus about the optimal treatment of these patients. Our patient was successfully treated with radiation therapy followed by hydroxyurea. With this combination therapy, he had no recurrence during the 4-year follow-up period. Clinical awareness of this phenomenon with the early treatment is essential for optimizing the successful outcome.

Extramedullary hematopoiesis and paraplegia in a patient with hemoglobin e-Beta thalassemia.

Science.gov (United States)

Alam, M R; Habib, M S; Dhakal, G P; Khan, M R; Rahim, M A; Chowdhury, A J; Mahmud, T K

2010-07-01

Extramedullary hematopoiesis (EMH) occurs in patients with various hematologic disorders involving a chronic increase in the production of red blood cells, and is often associated polycythemia vera and sickle cell anaemia, but is less common with thalassemia especially with hemoglobin E-beta thalassemia. Spinal cord compression due to EMH is a extremely rare complication of thalassemia and may present with paraparesis or paraplegia with or without sensory impairment. Treatment options mostly include surgery and/or radiotherapy. Whereas cases presenting with paraplegia have been treated with either surgery or radiotherapy with equal frequency and efficacy, almost all reported cases with paraplegia have been treated with surgery with or without radiation therapy. We hereby report a case of hemoglobin E-beta thalassemia with paraplegia treated successfully with radiotherapy.

Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

International Nuclear Information System (INIS)

Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee

2012-01-01

Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee [Dept. of Radiology, Inha University Hospital, Incheon (Korea, Republic of)

2012-03-15

Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

The multicenter experience with bendamustine in the treatment of relapsed and refractory multiple myeloma

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S. V. Voloshin

2015-01-01

Full Text Available Relapsed and refractory (R/R multiple myeloma (MM constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short. In patients with R/R MM after therapy of bortezomib and/or immunomodulators a bendamustine-based treatment can be used as “salvage”.In this retrospective analysis we have identified 32 patients with R/R MM by means of case research, have been bendamustine-based treated at Hematological Clinics of Russian Federation since 2011. Median age was 67 (43–81 years, the female/male ratio was 2.5:1. After in median 2 (1–7 lines of prior therapy patients received in median 3 (1–9 cycles of bendamustine-based therapy. Bendamustine dosage was 70–120 mg/m2 /day on 2 days of each 28-day cycle until progressive disease or intolerability. Overall rate response was 56.2 %: 21.9 % partial response, stable disease 34.4 %. Median time to progression was 5.3 (0.8–18.0 months and median overall survival was 25.4 (0.8–47.1 months. Hematologic toxicity was in 53.2 % of patients.

Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis

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Guilherme Sciascia do Olival

2013-08-01

Full Text Available This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10% patients presented with new attacks. In addition to these patients, 2 (5% patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma.

Science.gov (United States)

Stewart, A Keith; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Buchanan, Jacqui; Cocks, Kim; Yang, Xinqun; Xing, Biao; Zojwalla, Naseem; Tonda, Margaret; Moreau, Philippe; Palumbo, Antonio

2016-11-10

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment

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Leão João

2010-09-01

Full Text Available Abstract Backgroud Extramedullary hematopoiesis (EMH is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors, similarly to that described in this case. Case presentation Hematopoietic stem cells were found in a benign mixed mammary tumor of a 7-year-old female mongrel dog that presents a nodule in the left inguinal mammary gland. The patient did not have any hematological abnormalities. Cytological evaluation demonstrated two distinct cell populations, composed of either epithelial or mesenchymal cells, sometimes associated with a fibrillar acidophilic matrix, apart from megakaryocytes, osteoclasts, metarubricytes, prorubricytes, rubricytes, rubriblasts, promyelocytes, myeloblasts. Histological examination confirmed the presence of an active hematopoietic bone marrow within the bone tissue of a benign mammary mixed tumor. Conclusions EMH is a rare condition described in veterinary medicine that can be associated with mammary mixed tumors. It's detection can be associated with several neoplastic and non-neoplastic mammary lesions, i.e. osteosarcomas, mixed tumors and bone metaplasia.

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

Science.gov (United States)

Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

2015-10-01

To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

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Simon Zhornitsky

Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

Effects of education level and employment status on HRQoL in early relapsing-remitting multiple sclerosis.

Science.gov (United States)

Patti, F; Pozzilli, C; Montanari, E; Pappalardo, A; Piazza, L; Levi, A; Onesti, E; Pesci, I

2007-07-01

To evaluate the effects of education level and employment status on health-related quality of life (HRQoL) in a large cohort of patients affected by relapsing-remitting multiple sclerosis (RRMS). Patients This study included 648 patients with RRMS attending 40 Italian MS centers. Inclusion criteria were an Expanded Disability Status Scale (EDSS) score between 1.0 and 5.5; stable disease on enrollment; and no previous treatment with interferons, glatiramer acetate, or immunosuppressive drugs. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Employed patients scored significantly higher than other patient groups in the majority of MSQoL-54 domains. Similarly, patients with academic degrees and secondary education had higher scores than those with primary education (ie, eight years of education) in several domains of HRQoL. Patients who were employed with a high educational level achieved significantly better scores than unemployed patients with a lower educational level. In multivariate analysis, occupation and educational level were found to be significant and independent predictors of HRQoL. The results of our study suggest the importance of sustaining employment after a recent diagnosis of MS. In addition, education has a great influence on HRQoL; a higher education level may determine a stronger awareness of the disease, and a better ability to cope with the challenges of a chronic disease such as MS.

F-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Appearance of Extramedullary Hematopoesis in a Case of Primary Myelofibrosis

Science.gov (United States)

Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

2017-01-01

A 44-year-old female with known primary myelofibrosis presented with shortness of breath. High Resolution Computed Tomography thorax revealed large heterogeneously enhancing extraparenchymal soft tissue density mass involving bilateral lung fields. F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography revealed mildly FDG avid soft tissue density mass with specks of calcification involving bilateral lung fields, liver, and spleen. Subsequent histopathologic evaluation from the right lung mass was suggestive of extramedullary hematopoesis. PMID:28533647

How We Manage Patients with Plasmacytomas.

Science.gov (United States)

Fotiou, Despina; Dimopoulos, Meletios A; Kastritis, Efstathios

2018-04-17

To discuss the diagnostic approach, treatment options, and future considerations in the management of plasmacytomas, either solitary or in the context of overt multiple myeloma (MM). Advanced imaging techniques such as whole-body magnetic resonance imaging and positron emission tomography/computerized tomography are essential for the diagnostic workup of solitary plasmacytomas (SP) to rule out the presence of other disease foci. The role of flow cytometry and clonal plasma cell detection is currently under study together with other prognostic factors for the identification of patients with SP at high risk of progression to overt MM. Solitary plasmacytomas are treated effectively with local radiotherapy whereas systemic therapy is required at relapse. Clonal plasma cells that accumulate at extramedullary sites have distinct biological characteristics. Patients with MM and soft tissue involvement have poor outcomes and should be treated as ultra-high risk. A revised definition of SP that distinguishes between true solitary clonal PC accumulations and SP with minimal bone marrow involvement should be considered to guide an appropriate therapeutic and follow-up approach. Future studies should be conducted to determine optimum treatment approaches for patients with MM and paraskeletal or extramedullary disease.

Gender differences in alcohol and substance use relapse.

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Walitzer, Kimberly S; Dearing, Ronda L

2006-03-01

This review explores gender differences in relapse and characteristics of relapse events in alcohol and substance use. For alcohol, relapse rates were similar across gender. Although negative mood, childhood sexual abuse, alcohol-related self-efficacy, and poorer coping strategies predicted alcohol relapse, gender did not moderate these effects. Gender did moderate the association between marriage and alcohol relapse. For women, marriage and marital stress were risk factors for alcohol relapse; among men, marriage lowered relapse risk. This gender difference in the role of marriage in relapse may be a result of partner differences in problem drinking. Alcoholic women are more likely to be married to heavy drinking partners than are alcoholic men; thus, alcoholic women may be put at risk of relapse by marriage and alcoholic men may be protected by marriage. There are fewer studies documenting gender differences in substance abuse relapse so conclusions are limited and tentative. In contrast to the lack of gender differences in alcohol relapse rates, women appear less likely to experience relapse to substance use, relative to men. Women relapsing to substance use appear to be more sensitive to negative affect and interpersonal problems. Men, in contrast, may be more likely to have positive experiences prior to relapse.

Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

DEFF Research Database (Denmark)

Kumar, S K; Lee, JH; Lahuerta, J J

2012-01-01

with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis...... was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least...

Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

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Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

2003-02-01

Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

MRI Findings of Early-Stage Hyperacute Hemorrhage Causing Extramedullary Compression of the Cervical Spinal Cord in a Dog with Suspected Steroid-Responsive Meningitis-Arteritis

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Adriano Wang-Leandro

2017-09-01

Full Text Available A 9-month-old female Weimaraner was presented to the emergency service due to episodes of fever and neck pain. Physical examination revealed a stiff neck posture and elevated body temperature. Shortly after clinical examination was performed, the dog developed peracute onset of non-ambulatory tetraparesis compatible with a C1–C5 spinal cord (SC lesion. Immediately thereafter (<1 h, MRI of the cervical SC was performed with a 3-T scanner. A left ventrolateral intradural-extramedullary SC compression caused by a round-shaped structure at the level of C3––C4 was evidenced. The structure was iso- to slightly hyperintense in T1-weighted (T1W sequences compared to SC parenchyma and hyperintense in T2-weighted, gradient echo, and fluid-attenuated inversion recovery. Moreover, the structure showed a strong homogeneous contrast uptake in T1W sequences. Cerebrospinal fluid (CSF analysis revealed a mixed pleocytosis, as well as elevated protein and erythrocyte count. Early-stage hyperacute extramedullary hemorrhage was suspected due to immune mediated vasculitis. The dog was maintained under general anesthesia and artificial ventilation for 24 h and long-term therapy with corticosteroids and physiotherapy was initiated. Eight weeks after initial presentation, the dog was ambulatory, slightly tetraparetic. Follow-up MRI showed a regression of the round-shaped structure and pleocytosis was not evident in CSF analysis. This report describes an early-stage hyperacute extramedullary hemorrhage, a condition rarely recorded in dogs even in experimental settings.

Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

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Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

Background For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse. PMID:24783027

Clinical factors related to schizophrenia relapse.

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Porcelli, Stefano; Bianchini, Oriana; De Girolamo, Giovanni; Aguglia, Eugenio; Crea, Luciana; Serretti, Alessandro

2016-01-01

Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study.

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Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-08-18

Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Forty MMT patients were included and received a 12-month follow-up. All patients were given baseline resting-state fMRI scans by using a 3.0 T GE Signa Excite HD whole-body MRI system. Monthly self-report and urine test were used to assess heroin relapse or non-relapse. Subjective craving was measured with visual analog scale. The correlation between ReHo and the degree of heroin relapse was analyzed. Compared with the non-relapsers, ReHo values were increased in the bilateral medial orbitofrontal cortex, right caudate, and right cerebellum of the heroin relapsers while those in the left parahippocampal gyrus, left middle temporal gyrus, right lingual gyrus, and precuneus were decreased in heroin relapsers. Importantly, altered ReHo in the right caudate were positively correlated with heroin relapse rates or subjective craving response. Using the resting-state fMRI technique by analysis of ReHo, we provided the first resting-state fMRI evidence that right caudate may serve as a potential biomarker for heroin relapse prediction and also as a promising target for reducing relapse risk.

Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers

NARCIS (Netherlands)

Vogt, M.H.J.; ten Kate, J.; Drent, R.J.M.; Polman, C.H.; Hupperts, R.

2010-01-01

The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal

[Research and control of relapse tuberculosis cases].

Science.gov (United States)

Yamagishi, Fumio; Toyota, Makoto

2009-12-01

With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases

New management algorithms in multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg

2014-01-01

complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

Monoclonal Antibodies for Relapsing Multiple Sclerosis

DEFF Research Database (Denmark)

Blinkenberg, Morten; Soelberg Sørensen, Per

2017-01-01

Treatment of multiple sclerosis (MS) has improved considerably over the last decade because of new insights into MS pathology and biotechnological advances. This has led to the development of new potent pharmaceutical compounds targeting different processes in the complex autoimmune pathology...... the context of different treatment strategies. Finally, we consider the most important future developments....

Maxillofacial extramedullary hematopoiesis in a child with sickle cell presenting as bilateral periorbital cellulitis.

Science.gov (United States)

Reiersen, David A; Mandava, Mamatha; Jeroudi, Majed; Gungor, Anil

2014-07-01

Review of a case of paraosseous extramedullary hematopoiesis (EMH) affecting the maxillary sinuses and retro-orbital spaces imitating bilateral orbital cellulitis. Maxillofacial EMH causes diagnostic/therapeutic challenges. This case report describes a 4-year-old African American male with sickle cell disease (HbSS) who presented with bilateral orbitofacial swelling. Diagnosis was made with imaging and confirmed with tissue sampling. Partial exchange transfusion was utilized to stop the progression of maxillofacial EMH and to treat the patient's chronic anemia. Follow-up MRI showed regression of orbital and retro-orbital involvement. Early treatment with conservative modalities and close observation may prevent need for more invasive treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Treatment of Multiple Sclerosis

OpenAIRE

Bošnjak-Pašić, Marija; Vidrih, Branka; Miškov, Snježana; Demarin, Vida

2009-01-01

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system, characterized by multifocal inflammatory destruction of myelin, axonal damage and loss of oligodendrocytes. The disease is carried through two stages: inflammatory and degenerative. The most common form of disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The treatment of MS is divided into: treatment of the acute phase of illness, prevention of new relapses and di...

Relapse prevention and smoking cessation.

Science.gov (United States)

Davis, J R; Glaros, A G

1986-01-01

A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon's (1980) model of the relapse process was developed and evaluated. Behavior-analytic methods were used to develop assessment instruments, training situations, and coping responses. The prevention components were presented in the context of a basic broad-spectrum stop-smoking program, and were compared with the basic program plus discussion control, and the basic program alone. Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up. Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations. These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse. Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer. Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations. Results are discussed in relation to models of compliance with therapeutic regimens.

Fadiga na forma remitente recorrente da esclerose múltipla Fatigue in multiple sclerosis relapsing-remitting form

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MARIA FERNANDA MENDES

2000-06-01

Full Text Available Foram avaliados 95 pacientes com forma remitente-recorrente da esclerose múltipla quanto à presença de fadiga. A Escala de Severidade de Fadiga foi aplicada em todos os pacientes. Em 64 pacientes (67,4% a fadiga foi encontrada. Não observamos diferenças clínicas quanto ao gênero, idade, grau de incapacidade funcional e depressão, nos pacientes com e sem fadiga. Foi encontrada correlação entre ansiedade e tempo de doença com a presença de fadiga. Ao analisarmos estas variáveis quanto à intensidade da fadiga, observamos haver associação entre fadiga grave e maior incapacidade funcional.In 95 patients with the remitting-relapsing form of multiple sclerosis we investigated fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%. Gender, age, depression and fuctional incapacity was not predictive of fatigue occurrence, while anxiety and time of disease seems to be correlated with it. When we analysed the fatigue severity, a correlation between the EDSS and the increasing fatigue severity was found.

Splenomegaly unresponsive to standard and salvage chemotherapy in Langerhans cell histiocytosis: a case of extramedullary hematopoiesis.

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Christiansen, Ellen C; Ellwein, Marcine; Neglia, Joseph P

2012-06-01

Langerhans cell histiocytosis (LCH) is a proliferative disorder of dendritic cells which has evaded efforts to clearly define pathogenesis, diagnostic criteria, and therapeutic response markers. Strides have been made at classification with the recent development of a quantified score of disease severity. Splenic involvement is an indicator of poor prognosis, with spleen size its surrogate marker in evaluation and scoring. We describe a case of pediatric LCH with progressive splenomegaly despite treatment, which when examined at splenectomy revealed no LCH involvement but extramedullary hematopoiesis. These findings thus challenge our understanding of splenomegaly as a marker of disease. Copyright © 2011 Wiley Periodicals, Inc.

Relapsing polychondritis: commentary

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R.D. Altman

2011-09-01

Full Text Available Relapsing Polychondritis (RP is a multisystem disease of unknown etiology characterized by episodic inflammation of cartilage and potentially progressive degeneration of cartilaginous tissue, such as auricular, nasal and laryngotracheobronchial cartilage. However, many other proteoglycan- rich structures may be involved, such as inner ear, eyes, blood vessels, heart and kidneys (1- 4. RP was first described by Jacksh-Wartenhorst in 1923, who named it “polychondropathia” (5. Pearson et al. (6 introduced the term “relapsing polychondritis” in 1960...

Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility.

Science.gov (United States)

Montgomery, Stephen M; Kusel, Jeanette; Nicholas, Richard; Adlard, Nicholas

2017-09-01

Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis. A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs. Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient. When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of

Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

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Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

2009-06-01

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

Immunologic prediction of relapse in patients with pemphigus vulgaris (PV) in clinical remission.

Science.gov (United States)

Daneshpazhooh, Maryam; Zafarmand Sedigh, Vahid; Balighi, Kamran; Hosseini, S Hamed; Ramezani, Ali; Kalantari, Mohammad-Sadegh; Ghandi, Narges; Ghiasi, Maryam; Nikoo, Azita; Chams-Davatchi, Cheyda

2016-06-01

Pemphigus vulgaris (PV) is characterized by multiple relapses, occurring especially in patients on minimal therapy or off therapy. To identify immunologic predictors (anti-desmoglein [Dsg] 1 and 3 antibodies; direct immunofluorescence [DIF]) for relapse in PV patients. Eighty-nine patients in complete clinical remission for at least 6 months and receiving less than or equal to 10 mg prednisolone daily and no immunosuppressive drugs were evaluated using DIF (n=89) and Dsg ELISA (n=46). They were followed until relapse or for at least 18 months. DIF was positive in 44 of 89 patients (49.5%); anti-Dsg 3 antibodies were detected in 18 of 46 patients (39.1%) and anti-Dsg 1 antibodies were detected in 4 of 46 patients (8.7%). Relapse occurred in 38 patients (42.7%). Mean relapse-free time was significantly shorter in anti-Dsg 3-positive patients compared to anti-Dsg 3- negative patients (P = .015) and in DIF-positive patients compared to DIF-negative patients (P = .047), but not in anti-Dsg 1- positive patients compared to anti-Dsg 1-negative patients (P = .501). Sensitivity and predictive values of neither of these tests were high. Small number of anti-Dsg 1-positive patients and use of conventional ELISA. Positive anti-Dsg 3 ELISA and, to a lesser degree, positive DIF are predictors of relapse in PV patients in clinical remission. Decision on discontinuing treatment should be based on the results of these tests as well as on clinical findings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

International Nuclear Information System (INIS)

Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

2009-01-01

Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

Intrathoracic extramedullary hematopoiesis: appearance on /sup 99m/Tc sulfur colloid marrow scan

International Nuclear Information System (INIS)

Bronn, L.J.; Paquelet, J.R.; Tetalman, M.R.

1980-01-01

Imaging of the bone marrow by radionuclide scanning was performed using colloids, which are phagocytized by the reticuloendothelial cells of the marrow, or radioiron, which is incorporated into reticulocytes. The use of the former radiopharmaceutical is based on the assumption, generally valid except in aplastic states or after irradiation, that the distribution of hematopoietic and reticuloendothelial tissue in the marrow is similar. Regardless of the method used, active adult marrow is normally distributed only in the axial skeleton and proximal humeri and femurs. Marrow imaging has been used in the evaluation of myeloproliferative disorders, leukemia, lymphoma, aplastic states, malignancy metastatic to marrow, and hemolytic anemia. We report a case of thalassemia major in which the diagnosis of intrathoracic extramedullary hematopoiesis was confirmed with the /sup 99m/Tc sulfur colloid bone marrow scan

MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Zivadinov, R.; De Masi, R.; Nasuelli, D.; Monti Bragadin, L.; Cazzato, G.; Zorzon, M.; Ukmar, M.; Pozzi-Mucelli, R.S.; Grop, A.

2001-01-01

Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores ≤ 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8 %) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease. (orig.)

Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Yu Chunshui; Lin Fuchun; Liu Yaou; Duan Yunyun; Lei Hao; Li Kuncheng

2008-01-01

Objective: The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases. Materials and methods: DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T 2 WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients. Results: Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS. Conclusion: Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients

Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.

Science.gov (United States)

Botta, Cirino; Ciliberto, Domenico; Rossi, Marco; Staropoli, Nicoletta; Cucè, Maria; Galeano, Teresa; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2017-02-28

Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM.

Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab

DEFF Research Database (Denmark)

Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

2016-01-01

Background Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity.  Objective To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in ...

Gray Matter Correlates of Cognitive Performance Differ between Relapsing-Remitting and Primary-Progressive Multiple Sclerosis.

Directory of Open Access Journals (Sweden)

Laura E Jonkman

Full Text Available Multiple Sclerosis (MS is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS. Most patients experience a relapsing-remitting (RR course, while about 15-20% of patients experience a primary progressive (PP course. Cognitive impairment affects approximately 40-70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS and thirty-eight matched controls underwent neuropsychological (NP testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course.

Fine needle aspiration cytology in feline skeletal muscle as a diagnostic tool for extramedullary plasmacytoma

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D.B. Martins

Full Text Available ABSTRACT Extramedullary noncutaneous plasmacytoma (ENP is a myeloproliferative disorder of plasma cells that rarely affects cats. This paper describes an ENP case revealed by fine needle aspiration cytology (FNAC of the mass in the skeletal muscle of an 8-month-old, male, mixed breed cat, which had a nodule in the left hind limb. The rapid immunoassay test confirmed the presence of feline leukemia virus (FeLV. The animal necropsy macroscopically showed the nodule came from the semimembranosus muscle. Histopathological examination ratified the cytological findings. Thus, this paper alerts to the existence of plasmacytoma located in the skeletal muscle of feline species. FNAC is a quick and efficient method for diagnosis of ENP.

Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure.

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Sumowski, James F; Leavitt, Victoria M

2014-07-01

To investigate whether (1) resting body temperature is elevated in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy individuals and patients with secondary progressive multiple sclerosis (SPMS), and (2) warmer body temperature is linked to worse fatigue in patients with RRMS. Cross-sectional study. Climate-controlled laboratory (∼22°C) within a nonprofit medical rehabilitation research center. Patients with RRMS (n=50), matched healthy controls (n=40), and patients with SPMS (n=22). Not applicable. Body temperature was measured with an aural infrared thermometer (normative body temperature for this thermometer, 36.75°C), and differences were compared across patients with RRMS and SPMS and healthy persons. Patients with RRMS completed measures of general fatigue (Fatigue Severity Scale [FSS]), as well as physical and cognitive fatigue (Modified Fatigue Impact Scale [MFIS]). There was a large effect of group (Pphysical fatigue (physical fatigue subscale of the MFIS; rp=.318, P=.026), but not cognitive fatigue (cognitive fatigue subscale of the MIFS; rp=-.017, P=.909). These are the first-ever demonstrations that body temperature is elevated endogenously in patients with RRMS and linked to worse fatigue. We discuss these findings in the context of failed treatments for fatigue in RRMS, including several failed randomized controlled trials (RCTs) of stimulants (modafinil). In contrast, our findings may help explain how RCTs of cooling garments and antipyretics (aspirin) have effectively reduced MS fatigue, and encourage further research on cooling/antipyretic treatments of fatigue in RRMS. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Immunomodulation of multiple myeloma.

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Tohnya, Tanyifor M; Figg, William D

2004-11-01

Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

High risk of postpartum relapses in neuromyelitis optica spectrum disorder.

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Klawiter, Eric C; Bove, Riley; Elsone, Liene; Alvarez, Enrique; Borisow, Nadja; Cortez, Melissa; Mateen, Farrah; Mealy, Maureen A; Sorum, Jaime; Mutch, Kerry; Tobyne, Sean M; Ruprecht, Klemens; Buckle, Guy; Levy, Michael; Wingerchuk, Dean; Paul, Friedemann; Cross, Anne H; Jacobs, Anu; Chitnis, Tanuja; Weinshenker, Brian

2017-11-28

To study the effect of pregnancy on the frequency of neuromyelitis optica spectrum disorder (NMOSD) relapse and evaluate rates of pregnancy-related complications in an international multicenter setting. We administered a standardized survey to 217 women with NMOSD from 7 medical centers and reviewed their medical records. We compared the annualized relapse rate (ARR) during a baseline period 2 years prior to a participant's first pregnancy to that during pregnancy and to the 9 months postpartum. We also assessed pregnancy-related complications. There were 46 informative pregnancies following symptom onset in 31 women with NMOSD. Compared to baseline (0.17), ARR was increased both during pregnancy (0.44; p = 0.035) and during the postpartum period (0.69; p = 0.009). The highest ARR occurred during the first 3 months postpartum (ARR 1.33). A total of 8 of 76 (10.5%) with onset of NMOSD prior to age 40 experienced their initial symptom during the 3 months postpartum, 2.9 times higher than expected. The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery. © 2017 American Academy of Neurology.

Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece

Directory of Open Access Journals (Sweden)

Fragoulakis V

2013-04-01

Full Text Available V Fragoulakis,1 E Kastritis,2 T Psaltopoulou,3 N Maniadakis1 1National School of Public Health, Athens, Greece; 2Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM, the aim of this study was to assess the cost-effectiveness of the combination of lenalidomide–dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX. Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs was 3.01 (95% UI 2.81–3.20 and 2.22 (95% UI 2.02–2.41 for lenalidomide–dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49–1.06 QALYs in favor of lenalidomide–dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509�

Elevated body temperature is linked to fatigue in an Italian sample of relapsing-remitting multiple sclerosis patients.

Science.gov (United States)

Leavitt, V M; De Meo, E; Riccitelli, G; Rocca, M A; Comi, G; Filippi, M; Sumowski, J F

2015-11-01

Elevated body temperature was recently reported for the first time in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls. In addition, warmer body temperature was associated with worse fatigue. These findings are highly novel, may indicate a novel pathophysiology for MS fatigue, and therefore warrant replication in a geographically separate sample. Here, we investigated body temperature and its association to fatigue in an Italian sample of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with our original report, we found elevated body temperature in the RRMS sample compared to healthy controls. Warmer body temperature was associated with worse fatigue, thereby supporting the notion of endogenous temperature elevations in patients with RRMS as a novel pathophysiological factor underlying fatigue. Our findings highlight a paradigm shift in our understanding of the effect of heat in RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although randomized controlled trials of cooling treatments (i.e., aspirin, cooling garments) to reduce fatigue in RRMS have been successful, consideration of endogenously elevated body temperature as the underlying target will enhance our development of novel treatments.

EХPERIENCE IN INTERFERON β-1A USE FOR TREATMENT OF MULTIPLE SCLEROSIS IN CHILDREN

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L. M. Kuzenkova

2013-01-01

Full Text Available Aim: to evaluate the impact of subcutaneous interferon β-1a on matrix metalloproteinases 3, 8, 9 (MMP, cytokines (tumor necrosis factor α — TNF α, and transforming growth factor β1 — TGF β1 levels in serum of children with relapsing-remitting multiple sclerosis. Patients and methods: the results of treatment of 32 patients with relapsing-remitting multiple sclerosis aged 12–18 years (22 girls and 10 boys were analyzed. Treatment efficacy was assessed by the number of relapsing-remitting multiple sclerosis exacerbations during 12 months, MRI data, MMP and cytokines dynamics in serum. Results: statistical evidence acquired for MMPs, their tissue inhibitor and cytokines levels decrease (p < 0,005 in patients receiving therapy with subcutaneous INF β-1a. Conclusions: subcutaneous interferon β-1а is highly efficient in treatment of relapsing-remitting multiple sclerosis in children and adolescents.

Non-inflammatory causes of emergency consultation in patients with multiple sclerosis.

Science.gov (United States)

Rodríguez de Antonio, L A; García Castañón, I; Aguilar-Amat Prior, M J; Puertas, I; González Suárez, I; Oreja Guevara, C

2018-05-26

To describe non-relapse-related emergency consultations of patients with multiple sclerosis (MS): causes, difficulties in the diagnosis, clinical characteristics, and treatments administered. We performed a retrospective study of patients who attended a multiple sclerosis day hospital due to suspected relapse and received an alternative diagnosis, over a 2-year period. Demographic data, clinical characteristics, final diagnosis, and treatments administered were evaluated. Patients who were initially diagnosed with pseudo-relapse and ultimately diagnosed with true relapse were evaluated specifically. As an exploratory analysis, patients who consulted with non-inflammatory causes were compared with a randomly selected cohort of patients with true relapses who attended the centre in the same period. The study included 50 patients (33 were women; mean age 41.4±11.7years). Four patients (8%) were initially diagnosed with pseudo-relapse and later diagnosed as having a true relapse. Fever and vertigo were the main confounding factors. The non-inflammatory causes of emergency consultation were: neurological, 43.5% (20 patients); infectious, 15.2% (7); psychiatric, 10.9% (5); vertigo, 8.6% (4); trauma, 10.9% (5); and miscellaneous, 10.9% (5). MS-related symptoms constituted the most frequent cause of non-inflammatory emergency consultations. Close follow-up of relapse and pseudo-relapse is necessary to detect incorrect initial diagnoses, avoid unnecessary treatments, and relieve patients' symptoms. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

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Suk-young Lee

2014-01-01

Full Text Available Although hematopoietic stem cell transplantation (HSCT has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML, there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

[Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

Science.gov (United States)

Voltz, R; Goebels, N; Jarius, S; Hohlfeld, R

2002-05-06

The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

[Spinal cord compression due to extramedullary hematopoiesis in a patient with myelofibrosis].

Science.gov (United States)

Hijikata, Yasuhiro; Ando, Tetsuo; Inagaki, Tomonori; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen

2014-01-01

Development and growth of hematopoietic tissue outside of the bone marrow is termed extramedullary hematopoiesis (EMH). It occurs in patients with hematological diseases such as myelofibrosis and thalassemia. Liver and spleen are the usual sites of EMH. However, spinal cord compression caused by EMH is a rare complication. A 65-year-old man with myelofibrosis was admitted to our hospital with progressive paraparesis. Thoracic spine MRI revealed epidural masses causing cord compression. Histological examination of the epidural mass showed evidence of EMH consisting of megakaryocytic and erythroid hyperplasia. After surgical decompression and radiotherapy, lower limb weakness and sensory disturbance were significantly improved. MRI showed disappearance of the spinal cord compression. With this therapy, he had no recurrence until he died of myelofibrosis. Spinal EMH should be considered as a differential diagnosis in patients with hematological diseases presenting with paraparesis. Surgical decompression and radiotherapy are effective approaches for the treatment of paraparesis due to EMH.

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study

OpenAIRE

Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-01-01

Background Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Met...

Post-relapse survival in patients with Ewing sarcoma.

Science.gov (United States)

Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

2015-06-01

Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

The neuropharmacology of relapse to food seeking: methodology, main findings, and comparison with relapse to drug seeking.

Science.gov (United States)

Nair, Sunila G; Adams-Deutsch, Tristan; Epstein, David H; Shaham, Yavin

2009-09-01

Relapse to old, unhealthy eating habits is a major problem in human dietary treatments. The mechanisms underlying this relapse are unknown. Surprisingly, until recently this clinical problem has not been systematically studied in animal models. Here, we review results from recent studies in which a reinstatement model (commonly used to study relapse to abused drugs) was employed to characterize the effect of pharmacological agents on relapse to food seeking induced by either food priming (non-contingent exposure to small amounts of food), cues previously associated with food, or injections of the pharmacological stressor yohimbine. We also address methodological issues related to the use of the reinstatement model to study relapse to food seeking, similarities and differences in mechanisms underlying reinstatement of food seeking versus drug seeking, and the degree to which the reinstatement procedure provides a suitable model for studying relapse in humans. We conclude by discussing implications for medication development and future research. We offer three tentative conclusions: (1)The neuronal mechanisms of food-priming- and cue-induced reinstatement are likely different from those of reinstatement induced by the pharmacological stressor yohimbine. (2)The neuronal mechanisms of reinstatement of food seeking are possibly different from those of ongoing food-reinforced operant responding. (3)The neuronal mechanisms underlying reinstatement of food seeking overlap to some degree with those of reinstatement of drug seeking.

18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study

International Nuclear Information System (INIS)

Cassou-Mounat, Thibaut; Balogova, Sona; Nataf, Valerie; Calzada, Marie; Huchet, Virginie; Kerrou, Khaldoun; Devaux, Jean-Yves; Mohty, Mohamad; Garderet, Laurent; Talbot, Jean-Noel

2016-01-01

Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG. (orig.)

18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study

Energy Technology Data Exchange (ETDEWEB)

Cassou-Mounat, Thibaut [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Balogova, Sona [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Nataf, Valerie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Radiopharmacy, Hopital Tenon, Paris (France); Calzada, Marie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Huchet, Virginie; Kerrou, Khaldoun [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Devaux, Jean-Yves [AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Mohty, Mohamad; Garderet, Laurent [Universite Pierre et Marie Curie (UPMC), Paris (France); INSERM, UMRS 938, Proliferation and Differentiation of Stem Cells, Paris (France); AP-HP, Departement d' Hematologie et de Therapie Cellulaire, Hopital Saint Antoine, Paris (France); Talbot, Jean-Noel [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France)

2016-10-15

Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG. (orig.)

The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis.

Science.gov (United States)

van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H

2015-08-12

Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians

An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

Science.gov (United States)

Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A; Donders, Rogier; van der Zande, Anneke; Visser, Leo H

2016-05-28

In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with

Multicentric malignant transformation of multiple exostoses

International Nuclear Information System (INIS)

Ozaki, T.; Hillmann, A.; Winkelmann, W.; Blasius, S.; Link, T.

1998-01-01

We treated a patient with large multiple chondrosarcomas derived from multiple cartilaginous exostoses. One sarcoma originated in the left pubic bone and the other sarcoma in the posterior aspect of the greater trochanter of the left femur. Thirty months after hindquarter amputation, the patient is alive without relapse. This is the first report of a patient with synchronous multiple malignant transformation of multiple cartilaginous exostoses. (orig.)

Relapsing Polychondritis Following Alopecia Areata

Directory of Open Access Journals (Sweden)

John C. Starr

2010-01-01

Full Text Available A case of alopecia areata followed by relapsing polychondritis is presented. Similar cases from the literature are reviewed and speculation about the relationship of these diseases is offered. Although the occurrence of these diseases together could be coincidental, an association seems immunologically plausible. Thus, relapsing polychondritis might be an unusual systemic manifestation of alopecia areata.

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

2017-10-01

The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim

Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the "no evidence of disease activity" parameter.

Science.gov (United States)

Pato Pato, A; Costa Arpín, E; Rodríguez Regal, A; Rodríguez Constenla, I; Cimas Hernando, I; Muñoz Pousa, I; Naya Ríos, L; Lorenzo González, J R; Amigo Jorrín, M C; Prieto González, J M

2018-05-10

The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. Natalizumab is highly effective as measured by the NEDA long-term remission parameter. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Second allogeneic hematopoietic SCT for relapsed ALL in children.

Science.gov (United States)

Kato, M; Horikoshi, Y; Okamoto, Y; Takahashi, Y; Hasegawa, D; Koh, K; Takita, J; Inoue, M; Kigasawa, H; Ogawa, A; Sasahara, Y; Kawa, K; Yabe, H; Sakamaki, H; Suzuki, R; Kato, K

2012-10-01

A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1 ± 4.0% and non-relapse mortality was 18.8 ± 3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT.

Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

Science.gov (United States)

Eapen, Mary; Raetz, Elizabeth; Zhang, Mei-Jie; Muehlenbein, Catherine; Devidas, Meenakshi; Abshire, Thomas; Billett, Amy; Homans, Alan; Camitta, Bruce; Carroll, William L; Davies, Stella M

2006-06-15

The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.

The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

International Nuclear Information System (INIS)

Mandal, Mili; Gardner, Carol R.; Sun, Richard; Choi, Hyejeong; Lad, Sonali; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

2016-01-01

Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b + infiltrating Ly6G + granulocytic and Ly6G − monocytic cells in the spleen and the liver. The majority of the Ly6G + cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G − cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80 + ) and immature (F4/80 − ) pro-inflammatory Ly6C hi macrophages and mature anti-inflammatory (Ly6C lo ) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3 + macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the bone marrow. • Hepatotoxicity is reduced in

The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury

Energy Technology Data Exchange (ETDEWEB)

Mandal, Mili, E-mail: milimandal@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Gardner, Carol R., E-mail: cgardner@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sun, Richard, E-mail: fishpower52@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Choi, Hyejeong, E-mail: choi@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Lad, Sonali, E-mail: sonurose92@gmail.com [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Mishin, Vladimir, E-mail: mishinv@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

2016-08-01

Macrophages have been shown to play a role in acetaminophen (APAP)-induced hepatotoxicity, contributing to both pro- and anti-inflammatory processes. In these studies, we analyzed the role of the spleen as an extramedullary source of hepatic macrophages. APAP administration (300 mg/kg, i.p.) to control mice resulted in an increase in CD11b{sup +} infiltrating Ly6G{sup +} granulocytic and Ly6G{sup −} monocytic cells in the spleen and the liver. The majority of the Ly6G{sup +} cells were also positive for the monocyte/macrophage activation marker, Ly6C, suggesting a myeloid derived suppressor cell (MDSC) phenotype. By comparison, Ly6G{sup −} cells consisted of 3 subpopulations expressing high, intermediate, and low levels of Ly6C. Splenectomy was associated with increases in mature (F4/80{sup +}) and immature (F4/80{sup −}) pro-inflammatory Ly6C{sup hi} macrophages and mature anti-inflammatory (Ly6C{sup lo}) macrophages in the liver after APAP; increases in MDSCs were also noted in the livers of splenectomized (SPX) mice after APAP. This was associated with increases in APAP-induced expression of chemokine receptors regulating pro-inflammatory (CCR2) and anti-inflammatory (CX3CR1) macrophage trafficking. In contrast, APAP-induced increases in pro-inflammatory galectin-3{sup +} macrophages were blunted in livers of SPX mice relative to control mice, along with hepatic expression of TNF-α, as well as the anti-inflammatory macrophage markers, FIZZ-1 and YM-1. These data demonstrate that multiple subpopulations of pro- and anti-inflammatory cells respond to APAP-induced injury, and that these cells originate from distinct hematopoietic reservoirs. - Highlights: • Multiple inflammatory cell subpopulations accumulate in the spleen and liver following acetaminophen (APAP) intoxication. • Splenectomy alters liver inflammatory cell populations responding to APAP. • Inflammatory cells accumulating in the liver in response to APAP originate from the spleen and the

Hydroxyurea as a first-line treatment of extramedullary hematopoiesis in patients with beta thalassemia: Four case reports.

Science.gov (United States)

Karimi, Mehran; Cohan, Nader; Pishdad, Parisa

2015-01-01

Extramedullary hematopoiesis (EMH) is evidenced by erythropoietic masses, which occurs as a compensatory mechanism to overcome hypoxia during chronic anemia. EMH masses in spinal cord could lead to cord compression and neurological symptoms. Besides transfusion, radiotherapy, and surgery, hydroxyurea (HU) is also a treatment strategy in EMH. We described four cases of beta thalassemia with EMH who were treated with HU as a monotherapy. INTERVENTION (AND TECHNIQUE): HU therapy was done in all patients without any transfusion during therapy. HU is a good treatment option for patients with EMH and it could be a substitute for radiotherapy and invasive surgery or regular blood transfusion.

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce...... in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.......About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity...

Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

Science.gov (United States)

Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

2017-01-01

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Progression of regional grey matter atrophy in multiple sclerosis.

Science.gov (United States)

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple

Progression of regional grey matter atrophy in multiple sclerosis

Science.gov (United States)

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse

Lapse and relapse following inpatient treatment of opiate dependence.

LENUS (Irish Health Repository)

Smyth, B P

2010-06-01

We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.

A classification framework for drug relapse prediction | Salleh ...

African Journals Online (AJOL)

mining algorithms, Artificial Intelligence Neural Network (ANN) is one of the best algorithms to predict relapse among drug addicts. This may help the rehabilitation center to predict relapse individually and the prediction result is hoped to prevent drug addicts from relapse. Keywords: classification; artificial neural network; ...

Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

DEFF Research Database (Denmark)

Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

2016-01-01

Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

Science.gov (United States)

Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan

2009-01-01

We describe a 16 year-old male with β thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment. PMID:22470615

Symptoms and Association with Health Outcomes in Relapsing-Remitting Multiple Sclerosis: Results of a US Patient Survey

Directory of Open Access Journals (Sweden)

Angela E. Williams

2014-01-01

Full Text Available Background. A variety of symptoms have been reported, but the prevalence of specific symptoms in relapsing-remitting multiple sclerosis (RRMS, how they are related to one another, and their impact on patient reported outcomes is not well understood. Objective. To describe how symptoms of RRMS cooccur and their impact on patient-reported outcomes. Methods. Individuals who reported a physician diagnosis of RRMS in a large general health survey in the United States indicated the symptoms they experience because of RRMS and completed validated scales, including the work productivity and activity impairment questionnaire and either the SF-12v2 or SF-36v2. Symptom clusters were identified through hierarchical cluster analysis, and the relationship between clusters and outcomes was assessed through regression. Results. Fatigue, difficulty walking, and numbness were the most commonly reported symptoms. Seven symptom clusters were identified, and several were significantly related to patient reported outcomes. Pain, muscle spasms, and stiffness formed a cluster strongly related to physical quality of life; depression was strongly related to mental quality of life and cognitive difficulty was associated with work impairment. Conclusions. Symptoms in RRMS show a strong relationship with quality of life and should be taken into consideration in treatment decisions and evaluation of treatment success.

Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

2007-01-01

callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated......Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar...... to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical...

Interferon Treatment of Multiple Sclerosis

OpenAIRE

Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

2012-01-01

Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis

Directory of Open Access Journals (Sweden)

Lugaresi A

2013-06-01

Full Text Available Alessandra Lugaresi,1 Maria di Ioia,1 Daniela Travaglini,1 Erika Pietrolongo,1 Eugenio Pucci,2 Marco Onofrj11Department of Neuroscience and Imaging, University “G d’Annunzio”, Chieti, 2Operative Unit Neurologia ASUR Marche Area Vasta 3, Macerata, ItalyAbstract: Multiple sclerosis (MS is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics

Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

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Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

2014-01-01

Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial

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Sorensen, Per Soelberg; Mellgren, Svein Ivar; Svenningsson, Anders

2009-01-01

BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce...... was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; pSleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks......, these findings need to be corroborated in larger cohorts....

Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study

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Fredrikson Sten

2010-11-01

Full Text Available Abstract Background Glatiramer acetate (GA and interferon-beta (INFb are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS. Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. Methods 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32, fatigue (Fatigue Impact Scale [FIS] and depressed mood (Beck Depression Inventory-Short Form [BDI-SF] at baseline and 6 and 12 months after start of GA treatment. Results At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p Conclusions In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue.

Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

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Alan COHLER

2009-01-01

Full Text Available We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH. After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment.

Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

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Hall, Sharon M.; And Others

1984-01-01

Crossed two relapse prevention conditions (skills training-vs-discussion control) with two levels of aversive smoking in volunteer subjects (N=123). Results indicated that relapse-prevention skill training did prevent relapse among cigarette smokers. Lighter smokers were more favorably influenced. (LLL)

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients.

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Wen, Ge; Wang, Weihu; Zhang, Yujing; Niu, Shaoqing; Li, Qiwen; Li, Yexiong

2017-10-01

To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy (RT) in the management of extramedullary plasmacytoma (EMP). Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51 (range, 22-77) years. The median tumor size was 3.5 (range, 1.0-15.0) cm. The median applied dose was 50.0 (range, 30.0-70.0) Gy. Thirty-nine patients (70.9%) presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery (S) alone, 3 received chemotherapy (CT) alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients. The median follow-up duration was 56 months. The 5-year local recurrence-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) rates were 79.8%, 78.6%, 65.2% and 76.0%, respectively. Univariate analysis revealed that RT was a favourable factor for all examined endpoints. Furthermore, head and neck EMPs were associated with superior LRFS, MMFS and PFS. Tumor size <4 cm was associated with superior MMFS, PFS and OS; serum M protein negativity was associated with superior MMFS and PFS; age ≥50 years and local recurrence were associated with poor MMFS. The dose ≥45 Gy group exhibited superior 5-year LRFS, MMFS and PFS rates (94.7%, 94.4%, 90.0%, respectively), while the corresponding values for the dose <45 Gy group were 62.5% (P=0.008), 53.3% (P=0.036) and 41.7% (P<0.001). Involved-site RT of at least 45 Gy should be considered for EMP. Furthermore, patients with head and neck EMP, tumor size <4 cm, age <50 years and serum M protein negativity had better outcomes.

Defining active progressive multiple sclerosis

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Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

2017-01-01

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Comi, G; Martinelli, V; Rodegher, M

2009-01-01

BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis....... treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study.

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Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Adeniji, Abidemi K; Vermersch, Patrick

2017-08-01

In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis--results from the maintenance phase of the EXPO study.

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Labenz, J; Armstrong, D; Zetterstrand, S; Eklund, S; Leodolter, A

2009-06-01

Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

Improvement of driving skills in persons with relapsing-remitting multiple sclerosis: a pilot study.

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Akinwuntan, Abiodun Emmanuel; Devos, Hannes; Baker, Kelly; Phillips, Kendra; Kumar, Vibha; Smith, Suzanne; Williams, Mitzi Joi

2014-03-01

To determine the potential to improve driving-related skills using a simulator-based program in persons with relapsing-remitting multiple sclerosis (RRMS). Pre-post intervention. A university driving simulator laboratory. Participants (N=50) with RRMS and Expanded Disability Status Scale (EDSS) scores between 1 and 7 were enrolled. Pre- and posttraining data from 36 participants (mean age ± SD, 46±11y; 30 women) who received training and 6 participants (mean age ± SD, 48±13y; 5 women) who did not receive training (control group) were compared. Five hours of driving training in a simulator. Performance on a road test at pre- and posttraining. Secondary outcome measures were performance on visual, physical, and cognitive tests. Overall, no significant differences were observed between the training and control groups before and after training. However, 4 of the 7 participants in the training group who failed the road test at pretraining passed posttraining, while the only participant in the control group who failed at pretraining still failed at posttraining. The training group also improved on perception of red and colored numbers, the Paced Auditory Serial Addition Test, and the dot cancellation test of the Stroke Driver Screening Assessment battery and reported less fatigue. These improvements were most pronounced among those with an EDSS score between 3 and 7. This pilot study demonstrates the potential of using a simulator to improve driving-related visual, cognitive, and on-road skills in individuals with RRMS, particularly those with an EDSS score >3. Future randomized controlled trials with adequate power are needed to expand this field of study. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis

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Koch, M; De Keyser, J

2006-01-01

Background: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. Objective: To describe 4 patients with

Infiltración extramedular en la leucemia mielomonocítica crónica (LMMC Extramedullary infiltration in chronic myelomonocytic leukemia (CMML

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Onel Ávila Cabrera

2008-12-01

Full Text Available La leucemia mielomonocítica crónica (LMMC constituye un proceso oncohematológico de naturaleza mixta, mieloproliferativa y mielodisplásica. Su forma habitual de presentación es consecuencia, generalmente, de las citopenias en sangre periférica (síndrome anémico, infecciones o diátesis hemorrágica. La infiltración extramedular en la LMMC frecuentemente involucra el bazo, hígado, piel y nódulos linfáticos; sin embargo, es poco frecuente su localización en otros sitios. Se describe un paciente de 70 años con el diagnóstico de LMMC con infiltración extramedular en piel (nódulos subcutáneos, paladar duro y testículos; se comentan aspectos diagnósticos, terapéuticos y evolutivos.Chronic myelomonocytic leukemia is an oncohematological process of mixed, myeloproliferative and myelodisplastic nature. Its habitual form of presentation generally results from cytopenias in peripheral blood (anemic syndrome, infections or hemorrhagic diathesis. The extramedullary infiltration in the CMML frequently involves the spleen, the liver, the skin and the lymphatic nodules; however, its localization in other sites is not usual. The case of a 70-year-old patient with diagnosis of CMML and with extramedullary infiltration in the skin (subcutaneous nodules, hard palate and testicles is described. Comments on diagnostic, therapeutic and evolutive aspects are made

Clinical, psychological and demographic parameters of body pain in multiple sclerosis

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Ghasem Salehpoor

2017-02-01

Full Text Available Background: Body pain in multiple sclerosis (MS is a common phenomenon that can create or exacerbate by different parameters of clinical, psychological and demographic. The aim of this study was to investigate the relationship between parameters of clinical (fatigue, clinical course, body mass index and duration, psychological (depression, anxiety and stress and demographic (age, gender, marital status and education characters with multiple sclerosis patient’s body pain. Methods: This cross-sectional study has been performed in the Multiple Sclerosis Society of Guilan Province and Imam Reza Specialized and Sub-specialized Clinic, Rasht City, Iran during June to February 2010. In this study 162 patients with MS were selected by consecutive sampling. We used the clinical and demographic variables inventory, body pain subscale of the health survey questionnaire, depression, anxiety and stress scale and fatigue severity scale along with identical analog-spring balance. The data were analyzed by Pearson correlation coefficient and point bi-serial, one-way analysis of variance, Gabriel test and stepwise multiple regression. Results: The findings showed that patients who scored 3 or higher in relapses experienced significantly more body pain than patients who scored 1-2 times of relapses (P= 0.031. In the meantime, significant differences were not found between the two groups of patients with a score of 3 or higher in relapses and non-relapse and between non-relapse patients and with a score 1-2 times of relapses in terms of body pain. Also, significant differences were not found in different groups of hospitalization in terms of body pain. However, anxiety and fatigue together could explain significantly 25% of the shared variance of body pain (F= 26.29, P≤ 0.0009. Conclusion: This study showed the effect of psychological and clinical factors on body pain exacerbation in MS patients. Therefore, it is necessary for clinicians to consider

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

2017-01-01

on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

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Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

2014-11-01

Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

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Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

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Peter Joseph Jongen

2015-01-01

Full Text Available In persons with multiple sclerosis (MS a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS and early Relapsing Remitting MS (eRRMS were assessed for self-efficacy (MSSES-18, cognition (CDR System, fatigue (MFIS-5, depressive symptoms (BDI, disease impact (MSIS-29, and disability (EDSS. Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001, Reaction Time Variability (r= 0.57; P< 0.001, and Speed of Memory (r= 0.53; P< 0.01, and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01. Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy.

Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

Science.gov (United States)

Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

2017-05-20

Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

Gender effects on treatment response to interferon-beta in multiple sclerosis

DEFF Research Database (Denmark)

Magyari, M; Koch-Henriksen, N; Laursen, B

2014-01-01

BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

Thalassemia, extramedullary hematopoiesis, and spinal cord compression: A case report.

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Bukhari, Syed Sarmad; Junaid, Muhammad; Rashid, Mamoon Ur

2016-01-01

Extramedullary hematopoiesis (EMH) refers to hematopoiesis outside of the medulla of the bone. Chronic anemia states such as thalassemia can cause hematopoietic tissue to expand in certain locations. We report a case of spinal cord compression due to recurrent spinal epidural EMH, which was treated with a combination of surgery and radiotherapy. Pakistan has one of the highest incidence and prevalence of thalassemia in the world. We describe published literature on diagnosis and management of such cases. An 18-year-old male presented with bilateral lower limb paresis. He was a known case of homozygous beta thalassemia major. He had undergone surgery for spinal cord compression due to EMH 4 months prior to presentation. Symptom resolution was followed by deterioration 5 days later. He was operated again at our hospital with complete resection of the mass. He underwent local radiotherapy to prevent recurrence. At 2 years follow-up, he showed complete resolution of symptoms. Follow-up imaging demonstrated no residual mass. The possibility of EMH should be considered in every patient with ineffective erythropoiesis as a cause of spinal cord compression. Treatment of such cases is usually done with blood transfusions, which can reduce the hematopoietic drive for EMH. Other options include surgery, hydroxyurea, radiotherapy, or a combination of these on a case to case basis.

C-X-C motif chemokine 12 influences the development of extramedullary hematopoiesis in the spleens of myelofibrosis patients.

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Wang, Xiaoli; Cho, Sool Yeon; Hu, Cing Siang; Chen, Daniel; Roboz, John; Hoffman, Ronald

2015-02-01

Myelofibrosis (MF) is characterized by the constitutive mobilization of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) and the establishment of extramedullary hematopoiesis. The mechanisms underlying this abnormal HSC/HPC trafficking pattern remain poorly understood. We demonstrated that both splenic and peripheral blood (PB) MF CD34(+) cells equally share a defective ability to home to the marrow, but not to the spleens, of NOD/LtSz-Prkdc(scid) mice. This trafficking pattern could not be attributed to discordant expression of integrins or chemokine receptors other than the downregulation of C-X-C chemokine receptor type 4 by both PB and splenic MF CD34(+) cells. The number of both splenic MF CD34(+) cells and HPCs that migrated toward splenic MF plasma was, however, significantly greater than the number that migrated toward PB MF plasma. The concentration of the intact HSC/HPC chemoattractant C-X-C motif chemokine 12 (CXCL12) was greater in splenic MF plasma than PB MF plasma, as quantified using mass spectrometry. Functionally inactive truncated products of CXCL12, which are the product of proteolytic degradation by serine proteases, were detected at similar levels in both splenic and PB MF plasma. Treatment with an anti-CXCL12 neutralizing antibody resulted in a reduction in the degree of migration of splenic MF CD34(+) cells toward both PB and splenic MF plasma, validating the role of CXCL12 as a functional chemoattractant. Our data indicate that the MF splenic microenvironment is characterized by increased levels of intact, functional CXCL12, which contributes to the localization of MF CD34(+) cells to the spleen and the establishment of extramedullary hematopoiesis. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Relapse and craving in alcohol-dependent individuals

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van de Mheen, H,; Snelleman, M.; Schoenmakers, T.M.

2018-01-01

Background: Negative affective states and alcohol-related stimuli increase risk of relapse in alcohol dependence. In research and in clinical practice, craving is often used as another important indicator of relapse, but this lacks a firm empirical foundation. Objectives: The goal of the present

Lenalidomide in relapsed and refractory multiple myeloma disease: feasibility and benefits of long-term treatment.

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Zago, Manola; Oehrlein, Katharina; Rendl, Corinna; Hahn-Ast, Corinna; Kanz, Lothar; Weisel, Katja

2014-12-01

Lenalidomide in combination with dexamethasone is an effective and well-established treatment of relapsed or refractory multiple myeloma (rrMM) disease. Due to the scarcity of reports assessing benefit and risk of long-term lenalidomide treatment in non-selected rrMM patients, we retrospectively analysed the long-term outcome in patients with rrMM treated with lenalidomide and dexamethasone. Sixty-seven patients (pts) who were treated with lenalidomide/dexamethasone for rrMM in the approved indication from 2007 to 2011 were included in this retrospective, single-centre analysis. Kaplan-Meier survival estimates were compared between total population, patients on lenalidomide for more than 12 months (mo) and patients discontinuing therapy earlier than 12 months. Median overall survival (OS) of the total patient population was 33.2 mo. OS of pts treated beyond 12 mo was 42.9 mo compared to 20.2 mo (p = 0.027) for pts stopping lenalidomide earlier than 12 mo for other reasons than progression disease (PD). OS of pts >12 mo on lenalidomide treatment did not significantly differ between pts who had received previous autologous transplantation, allogeneic transplantation or conventional therapy. Main non-hematologic toxicities were infections of grade 3/4 in 25 % and thrombembolic events of all grades in 18 % of patients. To the best of our knowledge, this is the first report on feasibility and efficacy of long-term lenalidomide treatment in a non-selected patient cohort. OS of pts >12 mo on lenalidomide is superior when compared to pts discontinued earlier for reasons other than PD. Our data confirm the current use of lenalidomide as a continuous long-term treatment strategy.

Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

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Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

1999-05-01

Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

[Biological treatment of multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, P.S.; Sellebjerg, F.

2008-01-01

In 1996 interferon (IFN)beta was the first biopharmaceutical product to be approved for the treatment of relapsing-remitting multiple sclerosis (MS). In 2006 the more potent monoclonal antibody natalizumab was approved. Presently, a number of monoclonal antibodies are being studied, including ale...

Cost-effectiveness of family psychoeducation to prevent relapse in major depression: Results from a randomized controlled trial

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Shimodera Shinji

2012-05-01

Full Text Available Abstract Background Family psychoeducation is a relatively simple and straightforward intervention whose prophylactic effectiveness and cost-effectiveness is well-established for schizophrenia. We have recently demonstrated its effectiveness for unipolar depression, but its cost-effectiveness has never been examined. We hereby report a cost-effectiveness analysis alongside a randomized controlled trial in order to assess its cost-effectiveness for preventing relapse/recurrence in depression. Methods Fifty-seven patients diagnosed with major depression and undergoing its maintenance treatment, and their primary family members were randomized to treatment as usual (TAU only or to TAU plus family psychoeducation, which consisted of four 2-hour multiple-family sessions consisting of didactic lectures about depression (30 minutes and group discussion and problem solving (60–90 minutes. The economic analyses were undertaken from the perspective of the National Health Insurance (NHI, assuming the most reasonable price of US$50 per psychoeducation session per patient. The main outcome measures included relapse-free days and direct costs to the NHI. Results The intervention group enjoyed 272 (SD: 7.1 relapse-free days, while the control group spent 214 (SD: 90.8 relapse-free days (Cox proportional hazard ratio = 0.17, 95%CI: 0.04 to 0.75, p = 0.002. Cost-effectiveness acceptability curves suggested that the family psychoeducation has 90% or more chances of being cost-effective if the decision-maker is prepared to pay US$20 for one additional relapse-free day. This cost-effectiveness finding was robust when the price for family psychoeducation ranged between 50% to 150% of the baseline scenario in sensitivity analyses. If a relapse-free day is considered to be worth $30 or more, all the pricing scenarios have a close to 100% probability of being cost-effective. Conclusion Family psychoeducation is effective in the relapse prevention of

Clinical and MRI features in pediatric multiple sclerosis

International Nuclear Information System (INIS)

Zhao Cailei; Xie Sheng; Xiao Jiangxi; Wang Shuang

2011-01-01

Objective: To investigate the clinical and MRI features of multiple sclerosis in children, including the clinically isolated syndrome (CIS) and relapse. Methods: In total, 16 cases of pediatric multiple sclerosis were included in this study. Of them, 11 patients were female and 5 were male, with the mean onset age of 10.1 years. They were followed up for 4 months to 7 years and found to have 1- 5 relapses. The clinical manifestations of CIS and relapse were analyzed by a pediatric neurologist. An experienced neuroradiologist reviewed the MRI images of CIS and relapse. Information on the location, size, and pattern of the lesions was gathered. The location of lesions included subcortical, central, and periventricular white matter, cortex, deep gray matter, brain stem, and cerebellum. Results: CIS episode presented acute onsets in 13/16 cases, with symptoms of cortices in 10 cases and visual impairment in 6 cases. Relapse occurred in 14/16 cases within one year. The incidence of symptoms of cortices was less frequent and severe in the second episode of MS, whereas the visual impairment had a high incidence. All patients had full recovery after the last episode. MRI of CIS showed confluent subcortical white matter lesions in 13/16 cases, abutting on central white matter lesions. The most frequently involved brain part was the frontal lobe, followed by the parietal lobe. Cortical involvement was observed in 9/16 cases. In 6 cases, periventricular white matter lesions were detected. Bilateral deep gray matter was abnormal in 4 cases. Other abnormalities included brain stem lesions in 5 cases, cerebellum lesions in 3 cases, optic nerve involvement in 3 cases, and pyramidal tract lesions in 2 cases. MRI of relapse revealed more small lesions in the subcortical and periventricular white matter in the patients. In the second episode, only 2 cases presented cortical involvement. Lesions were found in the brain stem in 4 cases and in the cerebellum in 5 cases. Pyramidal tract

A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer.

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Miriam Eddyani

2015-11-01

Full Text Available Increased availability of Next Generation Sequencing (NGS techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU episodes.We compared the number and location of single nucleotide polymorphisms (SNPs identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin.The findings suggest that after surgical treatment-without antibiotics-the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse.To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.

Emerging therapies in multiple myeloma.

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El-Amm, Joelle; Tabbara, Imad A

2015-06-01

The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

A persistent cough as atypical clinical presentation of intrathoracic extramedullary hematopoiesis (EMH) in a female with thalassemia intermedia.

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Abdulla, Mohammad Aj; Yassin, Mohamed A; Abdelrazek, Mohamed; Mudawi, Deena; Ibrahim, Firyal; Soliman, Dina S; ElOmri, Halima; Nashwan, Abdulqadir J; Fernihough, Liam; De Sanctis, Vincenzo; Soliman, Ashraf T

2018-02-16

Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance of hematopoietic elements outside the bone marrow or peripheral blood. The most common sites of EMH are liver and spleen, but it has been documented in other organs such as the mediastinum, lymph nodes, breast, and central nervous system. EMH occurs as a compensatory mechanism for bone marrow dysfunction in severe thalassemia. We report a case of EMH presenting as a posterior mediastinal mass in a 34-year-old woman with thalassemia intermedia with chronic cough and shortness of breath on exertion. The diagnosis of EMH was confirmed by a CT-guided fine needle biopsy. All symptoms disappeared after surgical removal of the mass.

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

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Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study.

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Yaldizli, Özgür; Pardini, Matteo; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Tozer, Daniel J; Samson, Rebecca S; Wheeler-Kingshott, Claudia Am; Yousry, Tarek A; Miller, David H; Chard, Declan T

2016-02-01

In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Seventy-two people with MS (46 relapsing-remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability. © The Author(s), 2015.

Extramedullary Plasmacytoma of the Larynx: A Case Report of Subglottic Localization

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Jaqueline Ramírez-Anguiano

2012-01-01

Full Text Available Extramedullary plasmacytoma (EMP is a rare neoplasm of plasma cells, described in soft tissue outside the bone marrow. EMP of the larynx represents 0.04 to 0.45% of malignant tumors of the larynx. A male of 57 years old presented with hoarseness, dyspnea, and biphasic stridor of 2 months. The indirect laryngoscopy (IL revealed severe edema of the posterior commissure and a polypoid mass in the right posterior lateral subglottic wall. A biopsy of the subglottic mass was performed by a direct laryngoscopy (DL. The histopathologic diagnosis was EMP CD138+, therefore radiotherapy was given at 54 Gy in 30 sessions. The patient had an adequate postoperative clinical course and a new biopsy was performed having tumor-free margins. All laryngeal lesions should be biopsied prior to treatment to determine an accurate diagnosis to guide a proper management of the condition. Radiation therapy to the EMP is considered the treatment of choice, having local control rates of 80% to 100%. The subglottis is the least accessible area of view and the least frequent location of a laryngeal mass, nevertheless the otolaryngologist should always do a complete and systematic exam of the larynx when a tumor is suspected, to detect diagnoses such as a subglottic plasmacytoma.

The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant.

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Rodrigue, James R; Hanto, Douglas W; Curry, Michael P

2013-12-01

Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. To develop a scoring system to stratify risk of alcohol relapse after liver transplant. Retrospective medical record review. All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. The incidence of return to any alcohol consumption after liver transplant. Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.

Smoking relapse situations among a community-recruited sample of Spanish daily smokers.

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Piñeiro, Bárbara; López-Durán, Ana; Martínez-Vispo, Carmela; Fernández Del Río, Elena; Martínez, Úrsula; Rodríguez-Cano, Rubén; Míguez, M Carmen; Becoña, Elisardo

2017-12-01

Relapse is a common factor within the behavior change process. However, there is scarce and limited knowledge of smoking relapse situations in population-based samples. The aim of this study was to identify smoking relapse situations among a sample of Spanish relapsers from the general population. A sample of 775 relapsers was recruited among the general population using a snowball method. Participants completed a survey including sociodemographic, smoking-related and psychopathology variables. Smoking relapse situations were identified through specific questions assessing different aspects related to the last relapse episode. The majority of smoking relapse situations were attributed to positive affect (36.6%) and negative affect (34.3%), followed by lack of control (10.1%), smoking habit (6.7%), craving or nicotine withdrawal (6.3%), and social pressure (5.9%). Being unemployed and having a mental disorder in the past increased the likelihood of relapse in situations of negative affect. Being single and having quit smoking to save money were associated with an increased likelihood of relapse in situations of positive affect. Affect plays a significant role in smoking relapse among a community sample of unassisted Spanish smokers. Relapse may be much more of an affective and situational process than a habit, physiological or social pressure. Findings from this study may help develop tailored community smoking relapse prevention strategies or programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Frederiksen, J. L.; Topsøe Mailand, M.

2017-01-01

An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live...

Radiotherapy in the treatment of solitary plasmacytoma.

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Jyothirmayi, R; Gangadharan, V P; Nair, M K; Rajan, B

1997-05-01

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy.

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Oguro, Hideyuki; McDonald, Jeffrey G; Zhao, Zhiyu; Umetani, Michihisa; Shaul, Philip W; Morrison, Sean J

2017-09-01

Extramedullary hematopoiesis (EMH) is induced during pregnancy to support rapid expansion of maternal blood volume. EMH activation requires hematopoietic stem cell (HSC) proliferation and mobilization, processes that depend upon estrogen receptor α (ERα) in HSCs. Here we show that treating mice with estradiol to model estradiol increases during pregnancy induced HSC proliferation in the bone marrow but not HSC mobilization. Treatment with the alternative ERα ligand 27-hydroxycholesterol (27HC) induced ERα-dependent HSC mobilization and EMH but not HSC division in the bone marrow. During pregnancy, 27HC levels increased in hematopoietic stem/progenitor cells as a result of CYP27A1, a cholesterol hydroxylase. Cyp27a1-deficient mice had significantly reduced 27HC levels, HSC mobilization, and EMH during pregnancy but normal bone marrow hematopoiesis and EMH in response to bleeding or G-CSF treatment. Distinct hematopoietic stresses thus induce EMH through different mechanisms. Two different ERα ligands, estradiol and 27HC, work together to promote EMH during pregnancy, revealing a collaboration of hormonal and metabolic mechanisms as well as a physiological function for 27HC in normal mice.

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

Science.gov (United States)

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Multi-Institutional Analysis of Solitary Extramedullary Plasmacytoma of the Head and Neck Treated With Curative Radiotherapy

International Nuclear Information System (INIS)

Sasaki, Ryohei; Yasuda, Koichi; Abe, Eisuke; Uchida, Nobue; Kawashima, Mitsuhiko; Uno, Takashi; Fujiwara, Masayuki; Shioyama, Yoshiyuki; Kagami, Yoshikazu; Shibamoto, Yuta; Nakata, Kensei; Takada, Yoshie; Kawabe, Tetsuya; Uehara, Kazuyuki; Nibu, Kenichi; Yamada, Syogo

2012-01-01

Purpose: The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN). Methods and Materials: Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12–83). The median dose administered was 50 Gy (range, 30–64 Gy). Survival data were calculated by the Kaplan-Meier method. Results: The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity. Conclusions: Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN.

Extinction of relapsed fear does not require the basolateral amygdala.

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Lingawi, Nura W; Westbrook, R Frederick; Laurent, Vincent

2017-03-01

It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear. That is, extinction of spontaneously recovered or renewed fear was spared by BLA inactivation. Yet, this BLA-independent learning of extinction did not protect against further relapse: extinction of relapsed fear conducted without BLA activity was still likely to return after the passage of time or a shift in physical context. These findings have important clinical implications. They indicate that pharmacological agents with anxiolytic properties may disrupt initial cue-exposure therapy but may be useful when therapy is again needed due to relapse. However, they also suggest that these agents will not protect against further relapse, implying the need for developing drugs that target other brain regions involved in fear inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

[Report of Relapse Typhoid Fever Cases from Kolkata, India: Recrudescence or Reinfection?

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Samajpati, Sriparna; Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

2018-05-24

Three relapse cases were reported out of 107 hospital-attending typhoid cases within a period of 2 years (2014-2016) from Apollo Gleneagles Hospital, Kolkata, India. During the first episode of typhoid fever, 2 of the 3 cases were treated with ceftriaxone (CRO) for 7 days, and 1 was treated for 14 days. Six Salmonella Typhi (S. Typhi) isolates, obtained from the 3 patients during both typhoid episodes, were subjected to antimicrobial susceptibility testing, detection of quinolone resistance-determining region (QRDR) mutation and molecular subtyping by pulsed-field gel electrophoresis (PFGE), multiple-locus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), clustered regularly interspaced short palindromic repeats (CRISPR), and H58 haplotyping. Pairs of the S. Typhi strains isolated from two of the patients during the 1st and 2nd episodes were similar with respect to the antimicrobial resistance (AMR) profiles, QRDR mutations, and molecular subtypes; whereas, the S. Typhi strain pair isolated from the 3rd patient were different in their AMR profiles, QRDR mutations, and MLVA profiles. From these observations, it may be concluded that in spite of treating typhoid cases with CRO for 7-14 days, relapse of typhoid fever might occur. The article also showed the advantage of MLVA typing over PFGE, MLST, and CRISPR typing for the discrimination of strains isolated from the same patient in case of relapse of typhoid fever.

Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Chessells, J.; Leiper, A.; Rogers, D.

1984-01-01

Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

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Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

18-FDG-PET in pretherapeutical determination of extra medullary involvement prior to Re-188-antibody guided myeloablative therapy

International Nuclear Information System (INIS)

Hofmann, M.; Boerner, A.R.; Otto, D.; Knapp, W.H.; Hertenstein, B.

2002-01-01

Full text: In relapsed or refractory leukemia it is highly desirable to intensify the conditioning prior to allogenic bone mamarrow transplantation (BMT). Application of the 188-Re-labelled antibody BW 250/183 has proved to be feasible for internal radiation therapy of the bone marrow. Because the number of granulocytes (which express the CD66b antigen targeted) in extramedullary manifestations are usually low, the treatment of extramkedullary lesions will be not effective. This study deals with the pretherapeutical identification of patients with extramedullary involvement via 18-F-FDG-PET. 1-2 weeks prior scheduled 188-Re-therapy 12 patients underwent 18-F-FDG PET (dedicated PET scanner Siemens ECAT EXACT 47). Non physiological tracer accumulations were evaluated by means of SUV and consecutive morphological imaging (CT/MRI). 3 of 11 patients did show non physiological enrichment. 1 patient had enrichment in the upper mediastine, which was confirmed as extramedullary leukemia involvement by cytology. In CT scan these lesions had been identified as small lymphnodes (1-2 cm diameter). 2 Patients did show small lesions in the lung. In one patient they were confirmed to be active fungous infection (pos. sputum culture) and in the other patient they were regarded as regenerative residuals of previous known pneumonic infection not active now (neg. sputum cultures and neg. inflammation markers). 18-F-FDG PET is helpful of identifying extramedullary involvement and gives in addition information on the inflammatory status of patients prior to BMT. (author)

Spatial Correlation of Pathology and Perfusion Changes within the Cortex and White Matter in Multiple Sclerosis.

Science.gov (United States)

Mulholland, A D; Vitorino, R; Hojjat, S-P; Ma, A Y; Zhang, L; Lee, L; Carroll, T J; Cantrell, C G; Figley, C R; Aviv, R I

2018-01-01

The spatial correlation between WM and cortical GM disease in multiple sclerosis is controversial and has not been previously assessed with perfusion MR imaging. We sought to determine the nature of association between lobar WM, cortical GM, volume and perfusion. Nineteen individuals with secondary-progressive multiple sclerosis, 19 with relapsing-remitting multiple sclerosis, and 19 age-matched healthy controls were recruited. Quantitative MR perfusion imaging was used to derive CBF, CBV, and MTT within cortical GM, WM, and T2-hyperintense lesions. A 2-step multivariate linear regression (corrected for age, disease duration, and Expanded Disability Status Scale) was used to assess correlations between perfusion and volume measures in global and lobar normal-appearing WM, cortical GM, and T2-hyperintense lesions. The Bonferroni adjustment was applied as appropriate. Global cortical GM and WM volume was significantly reduced for each group comparison, except cortical GM volume of those with relapsing-remitting multiple sclerosis versus controls. Global and lobar cortical GM CBF and CBV were reduced in secondary-progressive multiple sclerosis compared with other groups but not for relapsing-remitting multiple sclerosis versus controls. Global and lobar WM CBF and CBV were not significantly different across groups. The distribution of lobar cortical GM and WM volume reduction was disparate, except for the occipital lobes in patients with secondary-progressive multiple sclerosis versus those with relapsing-remitting multiple sclerosis. Moderate associations were identified between lobar cortical GM and lobar normal-appearing WM volume in controls and in the left temporal lobe in relapsing-remitting multiple sclerosis. No significant associations occurred between cortical GM and WM perfusion or volume. Strong correlations were observed between cortical-GM perfusion, normal appearing WM and lesional perfusion, with respect to each global and lobar region within HC, and

Preventing relapse after incentivized choice treatment: A laboratory model.

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Bouton, Mark E; Thrailkill, Eric A; Bergeria, Cecilia L; Davis, Danielle R

2017-08-01

Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1. Experiment 1 found that the strength of R1 during relapse testing was not different from that seen in a no treatment control. Experiment 2 found that relapse could nevertheless be reduced by presenting reinforcers not contingent on responding during the test. Either the reinforcer for R1 or the reinforcer for R2 (which were qualitatively different types of food pellets) were effective. The experiments introduce a laboratory method for studying relapse and how to prevent it after contingency management treatments, and suggest at least one treatment that discourages relapse. The incentivized choice paradigm differs from other models of relapse of operant behavior (e.g., resurgence, renewal, reinstatement) in that it does not focus on the return of behaviors that are inhibited by extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

Fecal Calprotectin is an Accurate Tool and Correlated to Seo Index in Prediction of Relapse in Iranian Patients With Ulcerative Colitis.

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Hosseini, Seyed Vahid; Jafari, Peyman; Taghavi, Seyed Alireza; Safarpour, Ali Reza; Rezaianzadeh, Abbas; Moini, Maryam; Mehrabi, Manoosh

2015-02-01

The natural clinical course of Ulcerative Colitis (UC) is characterized by episodes of relapse and remission. Fecal Calprotectin (FC) is a relatively new marker of intestinal inflammation and is an available, non-expensive tool for predicting relapse of quiescent UC. The Seo colitis activity index is a clinical index for assessment of the severity of UC. The present study aimed to evaluate the accuracy of FC and the Seo colitis activity index and their correlation in prediction of UC exacerbation. In this prospective cohort study, 157 patients with clinical and endoscopic diagnosis of UC selected randomly from 1273 registered patients in Fars province's IBD registry center in Shiraz, Iran, were followed from October 2012 to October 2013 for 12 months or shorter, if they had a relapse. Two patients left the study before completion and one patient had relapse because of discontinuation of drugs. The participants' clinical and serum factors were evaluated every three months. Furthermore, stool samples were collected at the beginning of study and every three months and FC concentration (commercially available enzyme linked immunoassay) and the Seo Index were assessed. Then univariate analysis, multiple variable logistic regression, Receiver Operating Characteristics (ROC) curve analysis, and Pearson's correlation test (r) were used for statistical analysis of data. According to the results, 74 patients (48.1%) relapsed during the follow-up (33 men and 41 women). Mean ± SD of FC was 862.82 ± 655.97 μg/g and 163.19 ± 215.85 μg/g in relapsing and non-relapsing patients, respectively (P Seo index were significant predictors of relapse. ROC curve analysis of FC level and Seo activity index for prediction of relapse demonstrated area under the curve of 0.882 (P Seo index was significant in prediction of relapse (r = 0.63, P Seo activity index in prediction of relapse in the course of quiescent UC in Iranian patients.

Multiple sclerosis - etiology and diagnostic potential.

Science.gov (United States)

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Multiple sclerosis - etiology and diagnostic potential

Directory of Open Access Journals (Sweden)

Joanna Kamińska

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Relapsing-Remitting MS (RRMS)

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Full Text Available ... Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation Complementary & Alternative Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care ...

RESULTS OF AN OPEN-LABEL COMPARATIVE RANDOMIZED CLINICAL TRIAL OF AXOGLATIRAN® FS (F-SINTEZ, RUSSIA EFFICIENCY AND SAFETY IN COMPARISON WITH COPAXONE®-TEVA (TEVA PHARMACEUTICAL INDUSTRIES LTD., ISRAEL IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

Directory of Open Access Journals (Sweden)

F. A. Khabirov

2016-01-01

Full Text Available Objective. Comparison of Axoglatiran® FS (F-Sintez,  Russia and Copaxone®-Teva (Teva Pharmaceutical Industries Ltd.,  Israel efficiency and safety in patients with relapsing-remitting multiple sclerosis. Materials and methods. In the study 150 patients with relapsing-remitting multiple sclerosis were randomized into 2 groups: patients in the 1st group (n = 100 received treatment with Axoglatiran® FS, patients in the 2nd group (n = 50 received treatment with Copaxone®-Teva. Vital signs of every patient in the study were monitored accompanied by physical examinations, neurological examinations with EDSS (Expanded Disability Status Scale and MSFC (Multiple Sclerosis Functional Composite evaluations, magnetic resonance imaging of the brain and lab tests. Results. Mean age (M ± SD of the patients in the 1st group was 32.8 ± 8.7 years (20–54  years, percentages of men and women were 34 and 66 % respectively, mean age of multiple sclerosis onset was 27.93 ± 7.72 years (11–48 years. Median (Me, lower and upper quartiles estimates [LQ; UQ] on the EDSS scale were 2 [1.5; 3.0] steps (1.0–4.5  steps. In the 2nd group mean age of the patients was 35.2 ± 9.5 years (18–57  years, percentages of men and women were 24 and 76 % respectively, mean age of multiple sclerosis onset was 26.5 ± 6.9 years (18–47  years, EDSS estimates were 2.25 [1.5; 3.5] steps (1–5  steps. In the 1st group 88 (88 % patients completed the study, in the 2nd  group 44 (88 % patients completed the study. Among them in 73 (82.95 % patients in the 1st group and 34 (77.27 % patients in the 2nd  group the disease didn’t exacerbate (p > 0.05. In both groups no progression according to the EDSS and MSFC scale was observed (p > 0.05. Magnetic resonance imaging data showed that dynamics of the total number of T2 lesions, contrast-enhancing T1 lesions, atrophy degree estimated using internuclear index were comparable in both groups (p > 0.05. Safety profiles of

Radiation therapy for the palliation of multiple myeloma

International Nuclear Information System (INIS)

Leigh, B.R.; Kurtts, T.A.; Mack, C.F.; Matzner, M.B.; Shimm, D.S.

1993-01-01

This study reviews the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma. The records of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990 were reviewed. Three hundred sixteen sites were treated. Ten sites were asymptomatic, including six hemibody fields with advanced disease unresponsive to chemotherapy and four local fields with impending pathological fractures. Three hundred six evaluable symptomatic sites remained. The most common symptom was bone pain. Other symptoms included neurological impairment with a palpable mass. Total tumor dose ranged from 3.0 to 60 Gy, with a mean of 25 Gy. Symptom relief was obtained in 297 of 306 evaluable symptomatic sites (97%). Complete relief of symptoms was obtained in 26% and partial relief in 71%. Symptom relief was obtained in 92% of sites receiving a total dose less than 10 Gy (n = 13) and 98% of sites receiving 10 Gy or more (n = 293). No dose-response could be demonstrated. The likelihood of symptom relief was not influenced by the location of the lesion or the use of concurrent chemotherapy. Of the 297 responding sites, 6% (n = 19) relapsed after a median symptom-free interval of 16 months. Neither the probability of relapse nor the time to relapse was related to the radiation dose. Retreatment of relapsing sites provided effective palliation in all cases. Radiation therapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients. 16 refs., 3 figs., 4 tabs

Diagnostic algorithm for relapsing acquired demyelinating syndromes in children.

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Hacohen, Yael; Mankad, Kshitij; Chong, W K; Barkhof, Frederik; Vincent, Angela; Lim, Ming; Wassmer, Evangeline; Ciccarelli, Olga; Hemingway, Cheryl

2017-07-18

To establish whether children with relapsing acquired demyelinating syndromes (RDS) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) show distinctive clinical and radiologic features and to generate a diagnostic algorithm for the main RDS for clinical use. A panel reviewed the clinical characteristics, MOG-Ab and aquaporin-4 (AQP4) Ab, intrathecal oligoclonal bands, and Epstein-Barr virus serology results of 110 children with RDS. A neuroradiologist blinded to the diagnosis scored the MRI scans. Clinical, radiologic, and serologic tests results were compared. The findings showed that 56.4% of children were diagnosed with multiple sclerosis (MS), 25.4% with neuromyelitis optica spectrum disorder (NMOSD), 12.7% with multiphasic disseminated encephalomyelitis (MDEM), and 5.5% with relapsing optic neuritis (RON). Blinded analysis defined baseline MRI as typical of MS in 93.5% of children with MS. Acute disseminated encephalomyelitis presentation was seen only in the non-MS group. Of NMOSD cases, 30.7% were AQP4-Ab positive. MOG-Ab were found in 83.3% of AQP4-Ab-negative NMOSD, 100% of MDEM, and 33.3% of RON. Children with MOG-Ab were younger, were less likely to present with area postrema syndrome, and had lower disability, longer time to relapse, and more cerebellar peduncle lesions than children with AQP4-Ab NMOSD. A diagnostic algorithm applicable to any episode of CNS demyelination leads to 4 main phenotypes: MS, AQP4-Ab NMOSD, MOG-Ab-associated disease, and antibody-negative RDS. Children with MS and AQP4-Ab NMOSD showed features typical of adult cases. Because MOG-Ab-positive children showed notable and distinctive clinical and MRI features, they were grouped into a unified phenotype (MOG-Ab-associated disease), included in a new diagnostic algorithm. © 2017 American Academy of Neurology.

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

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Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Relapsing tumefactive lesion in an adult with medulloblastoma previously treated with chemoradiotherapy and stem cell transplant.

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Mahta, Ali; Qu, Yan; Nastic, Denis; Sundstrom, Maria; Kim, Ryan Y; Saria, Marlon; Santagata, Sandro; Kesari, Santosh

2012-04-01

Herein, we present an adult case of medulloblastoma who received chemotherapy, radiation therapy and stem cell transplantation, and underwent multiple surgical resections for what were thought to be recurrences; however pathology confirmed a diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a consequence of stem cell transplantation rather than a simple radiation treatment effect.

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

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Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Postpartum smoking relapse--a thematic synthesis of qualitative studies.

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Notley, Caitlin; Blyth, Annie; Craig, Jean; Edwards, Alice; Holland, Richard

2015-11-01

Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on women's experience of postpartum smoking relapse. A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Women's beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse. © 2015 Society for the Study of Addiction.

Spinal tumours in neurofibromatosis type 1: an MRI study of frequency, multiplicity and variety

International Nuclear Information System (INIS)

Thakkar, S.D.; Mautner, V.F.; Feigen, U.

1999-01-01

In neurofibromatosis type 1 (NF1) spinal tumours cause neurological symptoms in about 2 % of patients. Among over 1400 patients with NF1 we saw symptomatic spinal tumours in 23 (1.6 %). MRI of the entire spinal canal was obtained in 54 patients aged 5-56 years with NF1. The number, site, morphology and signal characteristics of the spinal tumours were recorded and analysed. There were 24 patients with symptoms such as sensory impairment or paralysis; 30 patients had no neurological deficits. Of the 24 symptomatic patients, 23 (96 %) had spinal tumours, while we saw spinal tumours in 12 (40 %) of the 30 patients without neurological deficits. No spinal segment was preferred in symptomatic or asymptomatic patients. Most intraspinal extramedullary tumours were primarily extradural and intraforaminal. MRI showed intramedullary tumours in 3 patients (6 %), intraspinal extramedullary tumours in 18 (33 %) and intraforaminal tumours in 31 (57 %). Only neurological deficits in patients with NF1 should prompt further diagnostic clarification. In patients with neurological symptoms there may be a multiplicity of masses in the spinal canal, which can lead to difficulties in attaching symptoms to a certain tumour. In patients who do not satisfy the NIH criteria, it can be a helpful observation that spinal tumours in NF1 are primarily intraforaminal, extending into the spinal canal, while in NF2 they are mostly intraspinal intradural tumours. (orig.)

Relapse Prevention: An Overview of Marlatts Cognitive- Behavioral Model

Directory of Open Access Journals (Sweden)

2008-11-01

Full Text Available Relapse prevention(RPis an important component of alcoholism treatment. The RP model proposed by Marlatt and Gordon suggests that both immediate determinants (e.g.,high- risk situations, coping skills, outcome expectancies, and the abstinence violation effect and covert antecedents (e.g., lifestyle factor and urges and cravings can contribute to relapse.The RP model also incorporates numerous specific and global intervention strategies that allow therapist and client to address each step of the relapse process. Specific interventions include identifying specific high-risk situations for each client and enhancing the client's skills for coping with those situations, increasing the client's self- efficacy, eliminating myths regarding alcohol's effects, managing lapses, and restructuring the client's perceptions of the relapse process. Global strategies comprise balancing the client's lifestyle and helping him or her develop positive addictions, employing stimulus control techniques and urgemanagement techniques, and developing relapse road maps. Several studies have provided theoretical and practical support for the RP model.

Predictive factors for relapse in patients on buprenorphine maintenance.

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Ferri, Michael; Finlayson, Alistair J Reid; Wang, Li; Martin, Peter R

2014-01-01

Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients. In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression. Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose. This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. © American Academy of Addiction Psychiatry.

Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

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Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

2012-12-01

Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

Science.gov (United States)

Borg, Sixten; Nahi, Hareth; Hansson, Markus; Lee, Dawn; Elvidge, Jamie; Persson, Ulf

2016-05-01

Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden. We developed a health-economic discrete event simulation model of a patient's course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature. The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained. In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.

Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.

Science.gov (United States)

Noormohammadi, Mohammad-Reza; Nikfarjam, Masoud; Deris, Fatemeh; Parvin, Neda

2017-03-01

Opioid dependence relapse is a complex and multidimensional problem, and lack of spiritual well-being is a major concern in opioid addicts. This study was conducted to determine spiritual well-being and factors associated with relapse among opioid addicts. This cross-sectional study was conducted from April 2015 to September 2015. According to purposive sampling, 312 eligible addicted patients were enrolled in the study. The patients had at least an attempt of detoxification in the past six months and referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran). They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher-developed questionnaire consisting of demographic characteristics and 20 questions about associated factors with relapse was administered. Data were analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's correlation test, chi-square, Friedman test, and student's t-test. The most important factors associated with opioid dependence relapse consist of relation with an addict friend, unemployment, living expenses, family conflicts, and somatic pain. In the present study, 157 patients had never experienced relapse while the mean of relapse in the rest participants was (3.25±1.53) times. Furthermore, the addicted patients with relapse had significantly lower scores of spiritual well-being and its subscales compared with non-relapse patients (pspiritual well-being, family and economical, personal, and occupational factors as crucial factors in opiate addiction relapse.

Dynamics of intraocular IFN-γ, IL-17 and IL-10-producing cell populations during relapsing and monophasic rat experimental autoimmune uveitis.

Directory of Open Access Journals (Sweden)

Ulrike Kaufmann

Full Text Available A major limitation of most animal models of autoimmune diseases is that they do not reproduce the chronic or relapsing-remitting pattern characteristic of many human autoimmune diseases. This problem has been overcome in our rat models of experimentally induced monophasic or relapsing-remitting autoimmune uveitis (EAU, which depend on the inducing antigen peptides from retinal S-Antigen (monophasic EAU or interphotoreceptor retinoid-binding protein (relapsing EAU. These models enable us to compare autoreactive and regulatory T cell populations. Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN-γ, IL-17 and IL-10 at distinct time points during monophasic or relapsing EAU. Only intraocular T cells concomitantly produced IFN-γ, IL-17 and/or IL-10. Monophasic EAU presented rising numbers of cells expressing IFN-γ and IL-17 (Th1/Th17 and cells expressing IL-10 or Foxp3. During relapsing uveitis an increase of intraocular IFN-γ+ cells and a concomitant decrease of IL-17+ cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and cells expressing IL-10, even in combination with IFN-γ or IL-17, increased during the resolution of monophasic EAU, suggesting a regulatory role for these T cells. In general, cells producing multiple cytokines increased in monophasic and decreased in relapsing EAU. The distinct appearance of certain intraocular populations with characteristics of regulatory cells points to a differential influence of the ocular environment on T cells that induce acute and monophasic or relapsing disease. Here we provide evidence that different autoantigens can elicit distinct and differently regulated immune responses. IFN-γ, but not IL-17 seems to be the key player in relapsing-remitting uveitis, as shown by increased, synchronized relapses after intraocular application of IFN-γ. We demonstrated dynamic changes of the cytokine pattern during monophasic and relapsing-remitting disease

Predictors of Exercise Relapse in a College Population.

Science.gov (United States)

Sullum, Julie; Clark, Matthew M.; King, Teresa K.

2000-01-01

Investigated factors that predicted exercise relapse among college students. Physically active undergraduates completed questionnaires measuring Prochaska's 10 processes for change of exercise, self-efficacy, and decisional balance. Exercise levels were assessed at baseline and 8 weeks later. At baseline, relapsers had significantly lower…

Extramedullary hematopoiesis of the liver in a child with sickle cell disease: A rare complication.

Science.gov (United States)

Barrier, Angela; Willy, Simo; Slone, Jeremy S

2015-08-01

We present the case of a 7-year-old Cameroonian girl with sickle cell disease (SCD) who presented with progressive abdominal distension, fever, severe anemia, respiratory distress, and fatigue. Abdominal ultrasound showed a 15.3 cm × 11.5 cm × 15.5 cm solid echogenic mass within the left lobe of the liver. Fine-needle aspiration showed features of extramedullary hematopoiesis (EMH). Despite transfusions, antibiotics, and initiation of hydroxyurea the patient died of respiratory failure during the hospital stay. There is a paucity of information on EMH in the pediatric sickle cell population, especially from resource-limited settings such as western Africa. EMH, however, is a known complication of SCD and should be considered in patients presenting with mass lesions in the setting of chronic anemia. With limited therapeutic interventions for EMH, including radiation and hydroxyurea, the emphasis should be on improving overall treatment of patients with chronic and untreated hemolytic anemia, especially in low-income countries. © 2015 Japan Pediatric Society.

Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder.

Science.gov (United States)

Bond, David J; Andreazza, Ana C; Hughes, John; Dhanoa, Taj; Torres, Ivan J; Kozicky, Jan-Marie; Young, L Trevor; Lam, Raymond W; Yatham, Lakshmi N

2016-03-01

Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-1 [MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-4 and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (p=.05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (pdepressive relapse in the 12 months after cytokine measurement: IL-1α (pdepressive relapse. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predicting and preventing the future: actively managing multiple sclerosis.

LENUS (Irish Health Repository)

Hutchinson, Michael

2012-02-01

Relapsing-remitting multiple sclerosis (MS) has a highly variable clinical course but a number of demographic, clinical and MRI features can guide the clinician in the assessment of disease activity and likely disability outcome. It is also clear that the inflammatory activity in the first five years of relapsing-remitting MS results in the neurodegenerative changes seen in secondary progressive MS 10-15 years later. While conventional first-line disease modifying therapy has an effect on relapses, about one third of patients have a suboptimal response to treatment. With the advent of highly active second-line therapies with their evident marked suppression of inflammation, the clinician now has the tools to manage the course of relapsing-remitting MS more effectively. The development of treatment optimisation recommendations based on the clinical response to first-line therapies can guide the neurologist in more active management of the early course of relapsing-remitting MS, with the aim of preventing both acute inflammatory axonal injury and the neurodegenerative process which leads to secondary progressive MS.

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity i...

Tumor relapse present in oncologic nasal repair

International Nuclear Information System (INIS)

Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana

2009-01-01

Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors

Effectiveness of Mindfulness-Based Relapse Prevention in opioid Dependence Treatment &Mental Health

Directory of Open Access Journals (Sweden)

2008-11-01

Findings: therapy compliance, retention in treatment, decrease in somatic symptoms, anxiety, social dysfunction and increase in health was significantly in both combination of psychological intervention method than the Naltroxan group. Mindfulness-based on relapse prevention was more effective than CBT relapse prevention in decreasing of, social dysfunction, relapse prevention, increase of therapy compliance, and health. Results: Mindfulness based relapse prevention was superior to CBT and Naltroxan and considerably increased effectiveness of opioid relapse prevention therapy.

Improved outcome after relapse in children with acute myeloid leukaemia

DEFF Research Database (Denmark)

Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran

2007-01-01

investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122......In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...... patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival...

Power2: Relapse Management with Adolescents Who Stutter.

Science.gov (United States)

Blood, Gordon W.

1995-01-01

This article describes a cognitive-behavioral treatment package for relapse management in adolescents who stutter. The package includes game-based training techniques in problem solving, communication skills, and assertiveness; coping responses for stuttering episodes; and realistic expectations for fluency and relapse. Follow-up results with…

A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin

Institute of Scientific and Technical Information of China (English)

Zhi-Gang Cao; Hong-Wei Zhou; Chao-Jin Peng; Mo Liu; Yu Du; Qing-Ming Yang

2013-01-01

At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cel s by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient′s condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.

Update on the cardiovascular profile of fingolimod in the therapy of relapsing-remitting multiple sclerosis (MS).

Science.gov (United States)

Meissner, Axel; Limmroth, Volker

2016-07-01

Fingolimod (FTY720) has been approved as the first oral representative of the class of sphingosine-1-phosphate (S1P) receptor modulators for the treatment of relapsing-remitting multiple sclerosis (MS). Besides inducing vaso-relaxation, fingolimod can also influence electrical conduction in the myocardium and vascular endothelium by having a transient negative chronotropic effect on the sinus node. Cardiac safety and tolerability of fingolimod in the cardiac sense were reviewed by analysing the data collected from the FREEDOMS and TRANSFORMS studies -both relevant studies for marketing authorisation, from their extension studies, as well as the clinical data collected from a practice-related MS patient cohort with cardiovascular risk factors and corresponding co-medication (FIRST study). The safety analyses on file gave no indication of any increased cardiovascular risk. The 2-3mmHg increase in blood pressure observed after the first dose of fingolimod has no therapeutic consequences. The first dose of 0.5mg fingolimod resulted in an average decrease in heart rate of 7-8beats/min. The onset of effect occurred approximately 1-2h after the first dose and the nadir was reached after approximately 4-5h. This negative chronotropic effect returned to normal after internalisation of the S1P1 receptors on maintenance therapy. There were no indications that patients with cardiac risk factors required closer observation beyond the monitoring recommended by the EMA following the first dose of fingolimod. Case study observations from the routine clinical setting show that patients accept this method of monitoring, which they assess as being a positive aspect of attentive medical care and concern. Copyright © 2016 Elsevier B.V. All rights reserved.

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study

NARCIS (Netherlands)

D. Buljevac (Dragan); W.C.J. Hop (Wim); W. Reedeker; A.C.J.W. Janssens (Cécile); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter); R.Q. Hintzen (Rogier)

2003-01-01

textabstractOBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ... a different mechanism of action in order to control the disease activity more effectively and help prevent ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ... and worsening, you and your MS care provider will likely want to consider a more aggressive treatment ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... Rule Out For Clinicians Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation ... Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care Needs Resources for Specific Populations ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... the periods of remission. At different points in time, RRMS can be further characterized as either active ( ... increase in disability over a specified period of time following a relapse) or not worsening . An increase ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... attacks of inflammation (relapses) in the CNS, progressive forms of MS involve much less of this type ... and memory or information processing). People with progressive forms of MS are more likely to experience gradually ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... Team Make the Most of Your Doctor Visits Advance Medical Directives d Find an MS Care Provider ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ...

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... as shown by the arrows, often occur as part of a relapse. However, new MRI lesions indicating ... course of your disease at different points in time helps you and your MS care provider discuss ...

Symptomatic relapse of HIV-associated cryptococcal meningitis in ...

African Journals Online (AJOL)

Objectives. Cryptococcal meningitis is the most common cause of adult meningitis in southern Africa. Much of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We studied the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal ...

Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

Science.gov (United States)

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Novel therapeutic options for relapsed hairy cell leukemia.

Science.gov (United States)

Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

2015-01-01

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT

DEFF Research Database (Denmark)

Grövdal, M; Nahi, H; Gahrton, G

2015-01-01

. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should...

MRI diagnosis of bone marrow relapse in children with ALL

International Nuclear Information System (INIS)