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British Journal of Haematology Jan 2006Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic... (Review)
Review
Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.
Topics: Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Diagnosis, Differential; Humans; Prognosis; Syndrome; Thrombocytopenia
PubMed: 16398647
DOI: 10.1111/j.1365-2141.2005.05809.x -
British Journal of Haematology Sep 2005Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of... (Review)
Review
Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial. We report on a series of 33 patients with TTP who were splenectomised because they were plasma refractory (n = 9) or for relapsed disease (n = 24). Splenectomy generated prompt and unmaintained remissions in all except five patients, in whom remission was delayed (n = 4) or who died with progressive disease (n = 1). Four postoperative complications occurred: one pulmonary embolism and three surgical complications. Median follow-up after splenectomy was 109 months (range 28-230 months). The overall postsplenectomy relapse rate was 0.09 relapses/patient-year and the 10-year relapse-free survival (RFS) was 70% (95% CI 50-83%). In the patients with relapsing TTP, relapse rate fell from 0.74 relapses/patient-year before splenectomy to 0.10 after splenectomy (P < 0.00001). Two patients died from first postsplenectomy relapse. Although these results are based on retrospective data and that the relapse rate may spontaneously decrease with time, we conclude that splenectomy, when performed during stable disease, has an acceptable safety profile and should be considered in cases of plasma refractoriness or relapsing TTP to reach durable remissions and to reduce or prevent future relapses.
Topics: Adolescent; Adult; Aged; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Plasma Exchange; Postoperative Complications; Pulmonary Embolism; Purpura, Thrombotic Thrombocytopenic; Recurrence; Remission Induction; Retrospective Studies; Splenectomy; Treatment Outcome
PubMed: 16115135
DOI: 10.1111/j.1365-2141.2005.05681.x -
Cancer Immunology, Immunotherapy : CII Jul 2007The treatment of myeloid leukaemia has progressed in recent years with the advent of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs) and... (Review)
Review
The treatment of myeloid leukaemia has progressed in recent years with the advent of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs) and targeted therapies. However, relapse has a high associated morbidity rate and a method for removing diseased cells in first remission, when a minimal residual disease state is achieved and tumour load is low, has the potential to extend remission times and prevent relapse especially when used in combination with conventional treatments. Acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are heterogeneous diseases which lack one common molecular target while chronic myeloid leukaemia (CML) patients have experienced prolonged remissions through the use of targeted therapies which remove BCR-ABL(+) cells effectively in early chronic phase. However, escape mutants have arisen and this therapy has little effectivity in the late chronic phase. Here we review the immune therapies which are close to or in clinical trials for the myeloid leukaemias and describe their potential advantages and disadvantages.
Topics: Clinical Trials as Topic; Humans; Immunotherapy; Leukemia, Myeloid
PubMed: 17180671
DOI: 10.1007/s00262-006-0267-y -
Journal of Pediatric Gastroenterology... May 2020Eosinophilic esophagitis (EoE) is characterized by remissions and relapses. Guidelines defining remission do not exist and therefore remission is inconsistently...
OBJECTIVES
Eosinophilic esophagitis (EoE) is characterized by remissions and relapses. Guidelines defining remission do not exist and therefore remission is inconsistently identified. We sought to define histology remission in EoE.
METHODS
Esophageal biopsies, obtained at the time the validated pediatric EoE symptoms scores v2.0 (PEESS v2.0) questionnaire was completed (N = 42), were scored using the validated EoE Histology Scoring System. An EoE Histology Remission Score (EoEHRS) was constructed and specified that in all esophageal sites sampled the peak eosinophil count was <15 per high power field (HPF); in addition, neither the total grade (severity of pathology) nor stage (extent of pathology) scores could exceed 3 (possible total maximum score for each was 24). Spearman correlation coefficients were generated for histology/symptom correlations; coefficient range 0.31 to 0.50 was considered moderate.
RESULTS
EoE Histology Scoring System composite and individual feature scores from proximal and distal esophageal biopsies correlated moderately with PEESS v2.0 mean scores (0.48-0.36, P < 0.01), and with scores in the dysphagia (0.39-0.30, P ≤ 0.01), pain (0.48-0.34, P ≤ 0.01), and gastroesophageal reflux disease (0.51-0.32, P ≤ 0.01) domains. Biopsies that met full EoEHRS criteria had reduced biomarkers, specifically expression of the mast cell markers CPA3 and tryptase mRNA, and reduced eosinophil peroxidase deposition (P < 0.03), compared to those with nonremission scores. Subjects whose biopsies met EoEHRS remission criteria reported reduced symptoms for all domains except nausea and vomiting (P ≤ 0.01).
CONCLUSIONS
The EoEHRS correlated with reduced biomarkers of disease activity and reduced symptoms, and therefore may be useful to inform clinical care and interstudy comparisons.
Topics: Biopsy; Child; Deglutition Disorders; Eosinophilic Esophagitis; Eosinophils; Gastroesophageal Reflux; Humans; Nausea
PubMed: 31977951
DOI: 10.1097/MPG.0000000000002637 -
Diabetic Medicine : a Journal of the... Aug 2021To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial). (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial).
METHODS
Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA <48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss.
RESULTS
Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission.
CONCLUSIONS
Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.
Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Prognosis; Quality of Life; Remission Induction; Weight Loss; Young Adult
PubMed: 32870520
DOI: 10.1111/dme.14395 -
World Journal of Gastroenterology May 2007Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. The degree of inflammation as assessed by conventional...
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. The degree of inflammation as assessed by conventional colonoscopy is a reliable parameter of disease activity. However, even when conventional colonoscopy suggests remission and normal mucosal findings, microscopic abnormalities may persist, and relapse may occur later. Patients with long-standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. Ulcerative colitis-associated colorectal cancer is characterized by an early age at onset, poorly differentiated tumor cells, mucinous carcinoma, and multiple lesions. Early detection of dysplasia and colitic cancer is thus a prerequisite for survival. A relatively new method, magnifying chromoscopy, is thought to be useful for the early detection and diagnosis of dysplasia and colitic cancer, as well as the prediction of relapse.
Topics: Colitis, Ulcerative; Colonoscopes; Colonoscopy; Early Diagnosis; Humans; Recurrence
PubMed: 17551998
DOI: 10.3748/wjg.v13.i18.2523 -
Drugs 2006Wegener's granulomatosis (WG) is the most common pulmonary granulomatous vasculitis and was a uniformly fatal disease prior to the identification of efficacious... (Review)
Review
Wegener's granulomatosis (WG) is the most common pulmonary granulomatous vasculitis and was a uniformly fatal disease prior to the identification of efficacious pharmacological regimens. The pathogenesis of WG remains elusive but proteinase 3-specific anti-neutrophil cytoplasmic antibodies may be involved. Histologically, WG is defined by the triad of small vessel necrotising vasculitis, 'geographic' necrosis and granulomatous inflammation. Organ involvement characteristically includes the upper and lower respiratory tracts and kidney, but virtually any organ can be involved. The severity of the disease varies, ranging from asymptomatic disease to fulminant, fatal vasculitis. Similarly, the degree of organ involvement is highly variable; WG may be limited to a single organ (typically the lungs or upper respiratory tract), or may be systemic. Currently, a regimen consisting of daily cyclophosphamide and corticosteroids, which induces complete remission in the majority of patients, is considered standard therapy. Since approximately 50% of patients experience a relapse following discontinuation of therapy, alternative regimens designed to maintain remissions after using cyclophosphamide and corticosteroids are usually necessary. This 'induction maintenance' approach to treatment has emerged as a central premise in planning therapy for patients with WG.A number of trials have evaluated the efficacy of less toxic immunosuppressants (e.g. methotrexate, azathioprine, mycophenolate mofetil) and antibacterials (i.e. cotrimoxazole [trimethoprim/sulfamethoxazole]) for treating patients with WG, resulting in the identification of effective alternative regimens to induce or maintain remissions in certain sub-populations of patients. Given the efficacy of methotrexate (for early systemic WG) and cotrimoxazole (in WG limited solely to the upper airways) to induce remissions, and the relatively decreased associated morbidity compared with cyclophosphamide, these alternative regimens are preferred in appropriate patients. Similarly, therapeutic options to maintain disease remission that are less toxic than cyclophosphamide should be offered following induction of remission unless a specific contraindication exists. By following this premise, the development of cyclophosphamide-induced morbidities (e.g. haemorrhagic cystitis, uroepithelial cancers and prolonged myelosuppression) may be minimised. Recent investigation has focussed on other immunomodulatory agents (tumour necrosis factor-alpha inhibitors [infliximab and etanercept] and anti-CD20 antibodies [rituximab]) for treating patients with WG. However, the current data are conflicting and difficult to interpret. As a result, these newer agents cannot be recommended for routine use until vigorous clinical study confirms their efficacy.
Topics: Anti-Inflammatory Agents; Granulomatosis with Polyangiitis; Humans
PubMed: 16827598
DOI: 10.2165/00003495-200666090-00004 -
World Journal of Gastroenterology Apr 2008Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. Some UC patients remain refractory to conventional... (Review)
Review
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. Some UC patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side-effects. Recently, cyclosporine and leukocyte removal therapy have been used for refractory UC patients. To predict the efficacy of these therapies is important for appropriate selection of treatment options and for preparation for colectomy. Endoscopy is the cornerstone for diagnosis and evaluation of UC. Endoscopic parameters in patients with severe or refractory UC may predict a clinical response to therapies, such as cyclosporine or leukocyte removal therapy. As for the patients with quiescent UC, relapse of UC is difficult to predict by routine colonoscopy. Even when routine colonoscopy suggests remission and a normal mucosal appearance, microscopic abnormalities may persist and relapse may occur later. To more accurately identify disease activity and to predict exacerbations in UC patients with clinically inactive disease is important for deciding whether medical treatment should be maintained. Magnifying colonoscopy is useful for the evaluation of disease activity and for predicting relapse in patients with UC.
Topics: Colitis, Ulcerative; Colonoscopy; Cyclosporine; Endoscopy; Gastroenterology; Humans; Leukocytes; Microscopy, Confocal; Prognosis; Recurrence; Time Factors; Treatment Outcome
PubMed: 18407585
DOI: 10.3748/wjg.14.2133