Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial.

OBJECTIVE: To compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis. METHODS: We conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing at least 2 years of fixed-schedule rituximab. In the B cell arm, rituximab was reinfused upon B cell repopulation; in the ANCA arm, rituximab was reinfused upon significant rise in ANCA level. Evaluations were conducted every 3 months. The primary endpoint was clinical relapse, defined as a modified BVAS/WG >0 by 36 months. Secondary endpoints included serious adverse events (SAEs) and rituximab exposure. RESULTS: 115 patients were enrolled. Median follow-up time was 4.1 years (IQR 2.5-5.0). By Kaplan-Meier analysis, 4.1% (95% CI 1.0 to 15.6) of patients had a clinical relapse in the B cell arm, compared with 20.5% (95% CI 11.9 to 34.1) in the ANCA arm, at 3 years after study entry (log-rank p=0.045). Total SAEs, including infectious SAEs, and deaths did not differ. The number of SAEs due to COVID-19 was higher in the B cell arm (p=0.049). In the B cell arm, patients received a mean of 3.6 (SD 2.4) infusions (3.6 g) per person over the median study follow-up time of 4.1 years, compared with 0.5 (SD 1.4) infusions (0.5 g) per patient in the ANCA arm (p<0.001). CONCLUSIONS: Rituximab dosed for B cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level in maintenance of remission for ANCA vasculitis. Overall safety was equivalent; SAEs due to COVID-19 and rituximab exposure were higher with the B cell strategy. TRIAL REGISTRATION NUMBER: NCT02749292.

Increased Risk of Postoperative Complications in Patients Who Have Obstructive Sleep Apnea Undergoing Total Joint Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to multiple adverse health outcomes and postoperative complications. Despite the high prevalence of OSA in patients undergoing total joint arthroplasty (TJA), few studies have evaluated the postoperative course of OSA patients after joint arthroplasty surgery. METHODS: PubMed (MEDLINE) and Scopus (EMBASE, MEDLINE, and COMPENDEX) were used to conduct a systematic review of articles from inception to July 2023. Primary studies comparing postoperative outcomes following TJA between patients who had and did not have OSA were included. Postoperative medical complications, utilization of critical care, hospital stay, and mortality data were extracted. Descriptive statistics and random-effects meta-analysis models were used to analyze the available data. Included studies were evaluated for methodological risks of bias using the risk of bias in non-randomized studies of interventions. This review was registered on the International Prospective Register of Systematic Reviews (ID: CRD42023447610). RESULTS: There were 7 studies with a total of 20,977 patients (9,425 hip; 11,137 knee; 415 hip or knee) that were included. Pulmonary complications were most frequently studied, followed by thromboembolic events. Cardiac, gastrointestinal, hematologic, genitourinary, and delirium events were also reported across studies. Meta-analysis revealed that OSA patients had 4-fold increased odds of overall medical complications (OR [odds ratio], 4.23; 95% confidence interval (CI), 2.97 to 6.04; P < .001; I2 = 0%), 4-fold increased odds of pulmonary complications (OR, 4.31; 95% CI, 2.82 to 6.60; P < .001; I2 = 0%), 2-fold increased odds of thromboembolic complications (OR, 1.92; 95% CI, 1.22 to 3.03; P = .005; I2 = 9%), and 4-fold increased odds of delirium (OR, 3.94; 95% CI, 1.72 to 9.04; P = .001; I2 = 0%). CONCLUSIONS: A significant association was found between OSA and overall medical, pulmonary, and thromboembolic complications. These patients also had a higher incidence of postoperative delirium. The present findings underscore the need for comprehensive perioperative strategies to mitigate these risks in OSA patients who elect to undergo TJA.

How Do We Improve Sleep Quality After Total Joint Arthroplasty? A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite the importance of sleep for physiological function, rehabilitation, and recovery, sleep quality after total joint arthroplasty (TJA) remains poor. The objective of this systematic review was to identify, summarize, and evaluate postoperative interventions aimed at improving sleep quality after TJA. METHODS: A systematic review of PubMed (MEDLINE) and Scopus (Embase, MEDLINE, COMPENDEX) from inception to April 2024 was conducted (PROSPERO ID: CRD42023447317). Randomized controlled trials on interventions to improve sleep quality were included. Sleep outcomes, including the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Patient-Reported Outcome Measurement Information System-Sleep Disturbance, Numeric Rating Scale sleep scores,l9 were extracted. Descriptive statistics were used to analyze the available data. RESULTS: Of the 1,549 articles identified, seven randomized trials with a total of 840 patients were included (394 total hip arthroplasties [THA], 446 total knee arthroplasties [TKA]). Pittsburgh Sleep Quality Index was the most commonly used outcome for assessing sleep quality. Among THA studies, zolpidem, combined fascia iliaca compartment block (FICB) and dexmedetomidine (DEX), and perioperative methylprednisolone were shown to markedly improve postoperative sleep quality. Neither topical cannabidiol nor topical essential oil was found to improve postoperative sleep quality after TKA. Melatonin had no effect on sleep outcomes after TJA. CONCLUSION: Zolpidem, FICB + DEX, and perioperative methylprednisolone are effective interventions to improve sleep quality after THA. Topical cannabis, topical essential oil, and melatonin did not improve sleep quality. No effective sleep interventions for TKA patients were identified. Improving sleep quality remains a potential therapeutic goal to improve patient satisfaction after TJA. Continued investigation on this topic is therefore necessary.

T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19.

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4+ and CD8+ T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell-deficient individuals, particularly within the CD8+ T cell compartment, in comparison with healthy controls. Evaluation of clinical outcomes demonstrates that vaccination of RTX-treated individuals was associated with about 4.8-fold reduced odds of moderate or severe COVID-19 in the absence of vaccine-induced antibodies. Analysis of T cell differentiation demonstrates that RTX administration increases the relative frequency of naïve CD8+ T cells, potentially by depletion of CD8+CD20dim T cells, which are primarily of an effector memory or terminal effector memory (TEMRA) phenotype. However, this also leads to a reduction in preexisting antiviral T cell immunity. Collectively, these data indicate that individuals with B cell deficiencies have enhanced T cell immunity after both SARS-CoV-2 infection and vaccination that potentially accounts for reduced hospitalization and severe disease from subsequent SARS-CoV-2 infection.