Abstract

INTRODUCTION Intravenous immunoglobulin (IVIG) was reported to be the third most used monotherapy in livedoid vasculopathy (LV). There is currently a lack of randomized controlled clinical trials and no standardized therapeutic regimen for IVIG therapy in LV. METHODS We performed a systematic review of the efficacy and safety of IVIG in treating patients with LV using PubMed, Cochrane, and Embase databases. RESULTS Eighty LV patients from 17 articles were included, receiving IVIG therapy at a dose of 1-2.1 g/kg body weight every 4 weeks. The effective rate of IVIG therapy in LV patients was 95% (76/80) in published studies, showing a good clinical response for resolution of pain, skin ulcerations, and neurological symptoms, and reducing the dependence on glucocorticoids and immunosuppressive agents. IVIG therapy was well tolerated, and no severe adverse events were observed. CONCLUSION Overall, to a certain degree, IVIG is probably a safe and effective treatment alternative for refractory LV patients, which still need to be confirmed by large-scale randomized controlled clinical trials.

Abstract

OBJECTIVE We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Abstract

BACKGROUND Anemia is a known risk factor for ischemic heart disease and serves as an independent predictor of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This meta-analysis pools data from randomized controlled trials (RCTs) to better define hemoglobin (Hb) thresholds for transfusion in this setting. RESULTS MEDLINE, EMBASE, and Cochrane databases were searched using the terms "Acute Coronary Syndrome" AND "Blood Transfusion" including their synonyms. A total of three randomized controlled trials were included. Restrictive transfusion strategy (RTS) was defined as transfusing for Hb ≤ 8 g/dl with a post-transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb ≤ 10 g/dl and post-transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and major adverse cardiac events (MACE). The primary analytic method used was random effects model. Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 years in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS [odds ratio (OR) 1.69; 95% CI 0.35 to 8.05]. Similarly, there was no difference in MACE (OR 0.74; 95% CI 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), or the incidence of recurrent ACS (OR 1.21; 95% CI 0.49 to 2.95). CONCLUSIONS In the setting of ACS, there is no difference between LTS and RTS for the outcomes of mortality, MACE, recurrent ACS, or CHF at 30 days. Further evidence in the form of high-quality RCTs are needed to compare RTS and LTS.

Abstract

BACKGROUND AND OBJECTIVES There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I(2) = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I(2) = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I(2) = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

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

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

Acute idiopathic pericarditis (AIP) is a benign inflammatory condition associated with high recurrence rates. Non-steroidal anti-inflammatory drug (NSAIDs) and colchicine are the recommended therapies. Our objective was to systematically assess effects of pharmacological therapies on recurrences or treatment failure in patients with first and subsequent AIP episodes. PubMed, BioMedCentral, Cochrane, Clinicaltrials.gov, Google Scholar and EMBASE (Ovid) were searched up to April 2020 for randomized controlled trials (RCT) evaluating NSAIDs, indomethacin, colchicine, steroids, intravenous immunoglobulins, immunomodulators, or interleukin receptor antagonists in adult patients with acute episode of idiopathic pericarditis. Mantel-Haenzel random effects models were used for meta-analyses, and effects were reported as odds ratios (ORs) and their 95% confidence intervals (CI). Six RCTs of colchicine plus NSAIDs (n=914 patients) and one RCT of anakinra (n=21) were found. No RCTs testing NSAIDs or corticosteroids were identified. Colchicine plus NSAIDs and anakinra significantly reduced recurrence (OR 0.37; 95%CI 0.27-0.51; and OR 0.02; 95%CI, 0.00-0.32, respectively). Colchicine plus NSAIDs also reduced treatment failure (OR 0.29; 95%CI 0.21-0.41). No differences in adverse events between colchicine and placebo were found (OR 1.16; 95%CI 0.72 to 1.86). In conclusion, Colchicine plus NSAIDS and anakinra are efficacious for preventing AIP recurrences. Colchicine reduces treatment failure as well. Although its use is supported by clinical experience, no solid evidence is currently available for the role of NSAIDs or steroids in the treatment of AIP.

Abstract

INTRODUCTION The optimal therapy for bleeding-related gastric varices is still a controversial topic. There is a paucity of literature that comprehensively summarizes the available literature regarding safety and efficacy of thrombin in bleeding gastric varices. METHODS Four independent reviewers performed a comprehensive review of all original articles published from inception to October 2020, describing the use of thrombin for management of bleeding gastric varices. Primary outcomes were (1) pooled early and late rebleeding rate, (2) pooled gastric variceal related mortality rate, (3) pooled rescue therapy rate, and (4) pooled adverse event rate with the use of thrombin in bleeding gastric varices. The meta-analysis was performed and the statistics were two-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger's test. RESULTS Eleven studies were included in the analysis after comprehensive search. This yielded a pooled early rebleeding rate of 9.3% (95% CI 4.9-17) and late rebleeding rate 13.8% (95% CI 9-20.4). Pooled rescue therapy rate after injecting thrombin in bleeding gastric varices was 10.1% (95% CI 6.1-16.3). The pooled 6-week gastric variceal-related mortality rate after injecting thrombin in bleeding gastric varices was 7.6% (95% CI 4.5-12.5). There were a total of four adverse events out of a total of 222 patients with pooled adverse event rate after injecting thrombin in bleeding gastric varices was 5.6% (95% CI 2.9-10.6). CONCLUSION In summary, the systematic review and meta-analysis on the use of thrombin for bleeding gastric varices suggest low rates of rebleeding and minimal rates of adverse events. While, early and late rebleeding rate and rescue therapy rate are similar to cyanoacrylate-based therapy, the minimal rates of adverse events are perhaps the most important benefit of thrombin. Thus, the current data suggest that thrombin is a very promising therapeutic alternative with low risk of adverse events for bleeding gastric varices.

Abstract

INTRODUCTION Nasal packing is the mainstay of epistaxis management; however, packs cause patient discomfort and can lead to hospital admission. Absorbable haemostats provide clotting factors or act as a substrate to stimulate clotting and represent a potential treatment alternative. A systematic review was performed to evaluate the efficacy of topical haemostats in the management of epistaxis. METHODS A systematic literature search of 7 databases was performed. Only eligible randomised controlled-trials (RCTs) and observational studies were included. The primary outcome was short-term haemostatic success (<7 days). Secondary outcomes included long-term haemostatic control (no re-bleeding 7-30 days), patient discomfort and adverse effects. Meta-analysis was performed where possible. RESULTS Of 2,249 records identified, 12 were included in the qualitative synthesis and 4 RCTs were included in meta-analysis. The following haemostats were reported: gelatin-thrombin matrix (n=8), aerosolised/gel tranexamic acid (n=1), cellulose agents (n=2), and fibrin sealants (n=1). Studies involving tranexamic acid on removable delivery devices (e.g. pledgets) were excluded. There was heterogeneity in outcome measures and inclusion criteria (coagulopathies/anticoagulants were excluded in 3 RCTs and 2 observational studies). The short-term haemostatic success varied between studies (13.9% to 100%). No significant post-procedural complications were reported. The meta-analysis favoured absorbable haemostatic agent versus packing (risk ratio 1.20; 95% confidence interval 1.05 to 1.37; p=0.007). The risk of bias across all studies was moderate to high. CONCLUSIONS The evidence suggests haemostatic agents are effective at managing acute epistaxis when compared with nasal packing. More data are required before recommendations can be made regarding management in patients on anticoagulants.