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The diagnosis and treatment of multiple myeloma (MM) are progressing continuously. This article aims at summarizing the current status in the diagnosis and treatment of MM, emphasizing a clinical point of view. Prognostic factors can be determined by clinical parameters, molecular analyses and patient characteristics (e.g. age and comorbidities). The international staging system (ISS) and cytogenetics, such as the high-risk aberrations 17p deletion, translocation (4;14) and insertion 1q21 > 2 copies, are key factors in risk stratification of MM patients. Induction therapy based on novel agents, namely bortezomib, followed by subsequent high-dose melphalan and autologous stem cell transplantation is considered the standard of care for younger, newly diagnosed MM patients (≤ 70 years). Transplant-ineligible patients should receive thalidomide or bortezomib-based chemotherapy. The combination of bortezomib, melphalan and prednisone (VMP) was shown to significantly improve overall survival (OS) compared to melphalan and prednisone (MP, 56.4 vs. 43.1 months, p = < 0.01). Recent results suggest that lenalidomide-based therapy not incorporating alkylating agents might be a competitive alternative with a favorable toxicity profile for transplant-ineligible patients. Maintenance therapies are of increasing clinical significance in MM as they have the ability to prolong overall survival; however, thalidomide maintenance therapy should not be used in MM patients with high-risk cytogenetics as it shortens OS. Refractory or relapsed MM treatment continues to improve with the development of second and third generation immunomodulatory agents and proteasome inhibitors. For example, pomalidomide and dexamethasone vs. high-dose dexamethasone significantly improved OS (12.7 vs. 8.1 months, p = 0.03). Novel therapy strategies include targeted and stroma-directed approaches. Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.
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An association has been suggested between asthma and orbital immunoglobulin G4-related disease (IgG4-RD).
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Globe prolapse into the maxillary sinus after trauma is rare and usually portends a very poor visual prognosis. The authors present an unusual case of late restoration of central vision after such trauma. A 20-year-old man presented after motorcycle injury with a large right floor and medial orbital wall fracture with displacement of the globe into the maxillary sinus. The patient had no light perception on initial exam and was emergently taken to the operating room for globe exploration. No globe rupture was found, and the right orbital floor and medial wall fractures were repaired. Three days of intravenous methylprednisolone at 250 mg every 6 hours was administered postoperatively with no change in visual status, and the patient was discharged home on a rapid oral prednisone taper. At postoperative week 6, vision had returned to 20/20 OD centrally. Visual field testing revealed a central tunnel of vision. The patient's visual function continues to remain stable 2 years after the initial trauma.
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Optimal salvage chemotherapy has not been established for lymphoid malignancy, which is refractory to the conventional cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. To explore an effective regimen, we conducted a phase I pilot study of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD), which are unaffected by MDR1-encoded P-glycoprotein. A total of 18 patients with lethal lymphoid malignancy were enrolled over a 2-yr period. The median age was 63 yr. Eleven patients had T/NK-cell malignancies, six had B-cell malignancies, and one was diagnosed with a blastic plasmacytoid dendritic cell neoplasm. Patients aged >/=60 and <60 yr were planned to receive a set of starting doses of methotrexate and ifosfamide, which should induce myelosuppression. Eleven patients completed two courses of MILD therapy. Treatment-related death because of systemic mucormycosis was observed in one patient. Major treatment-related adverse events were grade 3 or more hematologic toxicities, which included lymphopenia corresponding to dose-limiting toxicity. The most common grade 3 non-hematologic toxicity was febrile neutropenia. Of the 14 evaluated patients, three achieved a complete response, and four showed a partial response. The overall response rate was 57%. It was very interesting that all of seven responders had T/NK-cell malignancies. MILD therapy was feasible and presented acceptable toxicity in patients with refractory or lethal lymphoid malignancies. The efficacy for T/NK-cell malignancies should be further evaluated.
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To describe a clinical practice with leflunomide (LEF) in juvenile idiopathic arthritis (JIA).
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Twenty-one patients with PG referred to our department during the last 3½ years were prospectively studied. They were subdivided into three subsets - localized, multilesional and disseminated - on the basis of the number of lesions and percentage of involved body surface area.
Varenicline is a nicotinic receptor partial agonist indicated for the cessation of smoking. It is regarded as having no or minimal renal toxicity. A single case report has linked it to acute interstitial nephritis.
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In this multicenter trial, patients with newly diagnosed or relapsing TAK were treated with abatacept 10 mg/kg intravenously on days 1, 15, and 29 and week 8, together with prednisone administered daily. At week 12, patients in remission underwent a double-blinded randomization to continue to receive abatacept monthly or switch to placebo. Patients in both study arms received a standardized prednisone taper, reaching a dosage of 20 mg daily at week 12, with discontinuation of prednisone at week 28. All patients remained on their randomized assignment until meeting criteria for early termination or until 12 months after enrollment of the last patient. The primary end point was duration of remission (relapse-free survival).
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Most cases of chronic ocular sarcoidosis respond well to immunosuppressive therapy. However, patients may require combination therapy to achieve and maintain disease control. The use of anti-TNF agents for refractory disease is encouraging but can be accompanied by significant toxicity.
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Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6-12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving ≥ 5 mg of prednisone equivalent daily for > 3 months) can be screened earlier (for example, 3-6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.
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Our case confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this type of pemphigus is needed. Physicians should keep IgA pemphigus in mind when approaching patients with bullous eruption.
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To summarize the clinical and pathological features of all reported Langerhans cell histiocytosis (LCH) cases of female genital tract and to provide our additional three cases, and the emphasis is put on the pathological diagnosis to remind both gynecologists and pathologists of this rare disease.
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Disease activity decreased over time with treatment. At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9 (19.6%) moderate disease activity. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up (p<0.0001).
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TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker.
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Pyoderma gangrenosum (PG) is an uncommon extensive cutaneous ulceration belonging to the neutrophilic disease spectrum. It is associated to a systemic disease in almost 50% of cases. The diagnosis primarily relies on clinico-pathological features and the treatment is empirical. We report a retrospective series of 6 observations of PG (4 women and 2 men, median age = 43 years) enrolled over 15 years. The diagnosis was established based on the presence of 2 major criteria and 2 minor criteria of the disease. In 3 patients, PG was associated to an already known ulcerative colitis. The treatment consisted in general corticotherapy.
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Two review authors extracted the data (RH, NvA) and two authors assessed study quality and performed data extraction independently (NvA, BvE).
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In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the maintenance phase was 33 months. Now, we report the long-term outcome of maintenance treatment, with a median follow-up of 6 years.
To evaluate adalimumab therapy in refractory uveitis.
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The aim of this study was to validate an alternative post-market surveillance model to complement existing models.
Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis with no standard therapy. Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function. All patients were examined for response, toxicity and survival. The most significant toxicities (≥ grade 2) were infection (16.7%), renal insufficiency (8.3%), hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection. Treatment-related death was not observed. The overall response rate was 75.0% (complete response, 33.3%; partial response, 41.7%). With a median follow-up of 25.5 months, the median duration of response was 20 months (range, 12 to 49 months) and the median progression-free survival (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%. Our findings indicate the combination of CsA, PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.
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Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It is usually self-limiting and is characterized by an immune complex-mediated vasculitis associated with IgA deposition. We present an unusual case of HSP with mucosal lesions and coronary artery thickening.
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To evaluate the efficacy and safety of corticoid in combination with an antibiotic in the treatment of chronic nonbacterial prostatitis (CNP).
Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon.
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Paralysie laryngée bilatérale chez un chien secondaire à la métaplasie osseuse. Une chienne Lurcher stérilisée âgée de 7 ans a été évaluée pour une anamnèse chronique de bruit des voies respiratoires supérieures. Une imagerie avancée, dont une radiographie numérique et une image par tomodensitométrie avant et après contraste a confirmé la présence d’une masse minéralisée floue de tissus mous dans le larynx ventral. Unexamen histopathologique a démontré une myosite pléocellulaire et une fasciite avec une métaplasie osseuse.(Traduit par Isabelle Vallières).
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Grade III thrombocytopenia is a rare paraneoplastic syndrome in patients with NPC. These patients can tolerate the aggressive definitive management of radiotherapy and chemotherapy with supportive care.
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In these cases, a high index of suspicion is required if one is to avoid a delay in diagnosis, and the importance of correct early diagnosis is obvious.