Abstract

Antineutrophil cytoplasmic antibody-associated vasculitis has associations with both thrombosis and diffuse alveolar hemorrhage (DAH). Management of patients having coexistence of both thrombotic and hemorrhagic manifestations is challenging. Thrombotic conditions require anticoagulation, which can theoretically increase the risk of bleeding and thereby worsen DAH. In this review, we highlight the management of a patient of granulomatosis with polyangiitis with DAH who developed deep vein thrombosis. A systematic review of the literature was also performed summarizing and discussing the issues pertaining to the management of such patients.

Abstract

BACKGROUND Therapeutic apheresis has been used in treating hematological and non-hematological diseases. For a successful procedure, efficient vascular access is required. Presently, peripheral venous access (PVA), central venous catheterization (CVC), implantable ports, and arteriovenous fistulas (AVFs) are used. This review aims to evaluate different type of access and their pros and cons to help physicians determine the best venous access. METHODS The electronic search included PubMed and Google Scholar up to Nov. 2020. The Mesh terms were apheresis, peripheral catheterization, central catheterization, and arteriovenous fistula. RESULTS A total of 228 studies were found through database searching. Two independent authors reviewed the articles using their titles and abstracts; 88 articles were selected and the full text was reviewed. Finally, 25 were included. The inclusion criteria were studies incorporating patients with any indication for apheresis. CONCLUSION PVA has been promoted in recent years in many centers across the United States to lower the rate of complications associated with vascular access and to make this procedure more accessible. Several factors are involved in selecting appropriate venous access, such as the procedure's duration and frequency, patient's vascular anatomy, and staff's experience. In short-term procedures, temporary vascular access like PVA or CVC is preferred. Permanent vascular access such as AVF, tunneled cuffed central lines, and implantable ports are more beneficial in prolonged treatment period but each patient has to be evaluated individually by apheresis team for the most appropriate method.

Abstract

OBJECTIVE To assess the effects of plasma exchange on important outcomes in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). DESIGN Systematic review and meta-analysis of randomised controlled trials. ELIGIBILITY CRITERIA Randomised controlled trials investigating effects of plasma exchange in patients with AAV or pauci-immune rapidly progressive glomerulonephritis and at least 12 months' follow-up. INFORMATION SOURCES Prior systematic reviews, updated by searching Medline, Embase, and CENTRAL to July 2020. RISK OF BIAS Reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. SYNTHESIS OF RESULTS Meta-analyses were conducted using random effects models to calculate risk ratios and 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methods. Outcomes were assessed after at least12 months of follow-up and included all-cause mortality, end stage kidney disease (ESKD), serious infections, disease relapse, serious adverse events, and quality of life. RESULTS Nine trials including 1060 participants met eligibility criteria. There were no important effects of plasma exchange on all-cause mortality (relative risk 0.90 (95% CI 0.64 to 1.27), moderate certainty). Data from seven trials including 999 participants that reported ESKD demonstrated that plasma exchange reduced the risk of ESKD at 12 months (relative risk 0.62 (0.39 to 0.98), moderate certainty) with no evidence of subgroup effects. Data from four trials including 908 participants showed that plasma exchange increased the risk of serious infections at 12 months (relative risk 1.27 (1.08 to 1.49), moderate certainty). The effects of plasma exchange on other outcomes were uncertain or considered unimportant to patients. LIMITATIONS OF EVIDENCE There is a relative sparsity of events, and treatment effect estimates are therefore imprecise. Subgroup effects at the participant level could not be evaluated. INTERPRETATION For the treatment of AAV, plasma exchange has no important effect on mortality, reduces the 12 month risk of ESKD, but increases the risk of serious infections. FUNDING No funding was received. REGISTRATION This is an update of a previously unregistered systematic review and meta-analysis published in 2014.

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare multisystem autoimmune condition that causes inflammation of small and medium-sized blood vessels and is more commonly seen in the geriatric population. ANCA-associated vasculitis (AAV) is typically characterized as necrotizing vasculitis and includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The mortality rate remains high, with especially cardiovascular disease, infections, and malignancies being the leading causes of death. Existing treatment options depend heavily on the use of glucocorticoids (GCs), often in combination with cyclophosphamide (CYC); however, as the multitude of adverse effects associated with these agents has increased, numerous studies are being conducted to reduce not only these harmful effects but also improve remission rates. Rituximab, avacopan, corticosteroids, including intravenous pulse methylprednisolone, plasma exchange, and immunological targeting are among the emerging treatments. The purpose of this review is to emphasize the pathogenesis and traditional treatment modalities and give insights into the recent advances in managing this disorder in an attempt to spare the adverse effects of conventional therapies while achieving better remission rates with combination therapies as well. The authors explored multiple databases, employing appropriate keywords, satisfying the quality appraisal, after which a total of 14 reports were included in this review. Upon overall analysis, it can be concluded that rituximab and CYC, when used in combination, provided a safer alternative to GCs while exhibiting equal, if not superior, effectiveness and results, thus, paving the way for additional in-depth research in a larger population of interest.

Abstract

BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. METHODS Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. RESULTS Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I(2) = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I(2) = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I(2) = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I(2) = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I(2) = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I(2) = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I(2) = 75.5%). CONCLUSIONS Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.

Abstract

OBJECTIVE The aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines. METHODS A systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference. RESULTS A total of 729 full-text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow-up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse-free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer-term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events. CONCLUSION This comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.

Abstract

Nephrotic syndrome (NS) affects 115-169 children per 100,000, with rates varying by ethnicity and location. Immune dysregulation, systemic circulating substances, or hereditary structural abnormalities of the podocyte are considered to have a role in the etiology of idiopathic NS. Following daily therapy with corticosteroids, more than 85% of children and adolescents (often aged 1 to 12 years) with idiopathic nephrotic syndrome have full proteinuria remission. Patients with steroid-resistant nephrotic syndrome (SRNS) do not demonstrate remission after four weeks of daily prednisolone therapy. The incidence of steroid-resistant nephrotic syndrome in children varies between 35 and 92 percent. A third of SRNS patients have mutations in one of the important podocyte genes. An unidentified circulating factor is most likely to blame for the remaining instances of SRNS. The aim of this article is to explore and review the genetic factors and management of steroid-resistant nephrotic syndrome. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till September 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Steroid resistance", "nephrotic syndrome", "nephrosis" and "hypoalbuminemia". We comprehensively reviewed the literature on the epidemiology, genetics, current treatment protocols, and management of steroid-resistant nephrotic syndrome. We found that for individuals with non-genetic SRNS, calcineurin inhibitors (cyclosporine and tacrolimus) constitute the current mainstay of treatment, with around 70% of patients achieving full or partial remission and an acceptable long-term prognosis. Patients with SRNS who do not react to calcineurin inhibitors or other immunosuppressive medications may have deterioration in kidney function and may develop end-stage renal failure. Nonspecific renal protective medicines, such as angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid medications, slow the course of the illness. Recurrent focal segmental glomerulosclerosis in the allograft affects around a third of individuals who get a kidney transplant, and it frequently responds to a combination of plasma exchange, rituximab, and increased immunosuppression. Despite the fact that these results show a considerable improvement in outcome, further multicenter controlled studies are required to determine the optimum drugs and regimens to be used.

Abstract

OBJECTIVE The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy. DESIGN Systematic review and meta-analysis. METHODS We searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses. RESULTS A total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I(2)=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I(2)=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I(2)=84.2%). CONCLUSION GMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone. PROSPERO REGISTRATION NUMBER CRD42019134050.

Abstract

OBJECTIVES To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.

Abstract

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.