CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells

BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells.     

Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis

BackgroundThe proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance.ObjectiveThe aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19.Data SourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020.Study Eligibility CriteriaWe included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing.ParticipantsThe study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult).MethodsThe main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis.ResultsWe screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3–80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03–0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18–1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15–1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7–15.2%) from 31 studies.ConclusionsThree-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.     

Perineal wound management after abdominoperineal rectal excision for carcinoma with unsatisfactory hemostasis or gross septic contamination: Primary closure vs. packing

PURPOSE: This study was designed to compare the results of two methods on the rate of postoperative perineum healing. PATIENTS AND METHODS: In this prospective, randomized, multicenter trial of 234 consecutive patients undergoing abdominoperineal rectal excision for carcinoma, 48 had unsatisfactory hemostasis or intraoperative gross septic contamination. Three patients were withdrawn because of protocol violation. Of the 45 remaining patients, 21 were randomized to undergo primary closure of the perineum with drainage while 24 underwent packing. Preoperative factors (sex, age, degree of obesity, weight loss, anemia, or presence of ascites), intraoperative findings (Dukes stage, degree of hemostasis, gross septic contamination), and postoperative oncologic courses (recurrence, mortality rate) were similar in both groups. All patients were followed for at least 12 months or until their demise. RESULTS: There was no significant difference in the number of early (one vs. zero) or late (five vs. four) deaths between primary closure and packing groups, respectively. Median duration of hospital stay was 25 and 27 days, respectively. Primary closure was associated with a significantly higher rate of healed perineums at one month (30 percent vs. 0 percent) (P = 0.01) and a shorter delay to complete cicatrization (median, 47 vs. 69 days) (P < 0.01). From three months onward, there was no difference in healing between the two groups, but two patients in the packing group had not healed at one year. Conversely, hematoma, perineal abscess, and reoperations were significantly more frequent (P < 0.01) in the primary closure group. CONCLUSION: Primary closure associated with drainage after abdominoperineal resection for carcinoma expedites perineal healing but morbidity is higher.     

Validation of Prosthetic Mitral Regurgitation Quantification Using Novel Angiographic Platform by Mock Circulation

ObjectivesThis study aimed to validate a dedicated software for quantitative videodensitometric angiographic assessment of mitral regurgitation (QMR).BackgroundQuantitative videodensitometric aortography of aortic regurgitation using the time-density principle is a well-documented technique, but the angiographic assessment of mitral regurgitation (MR) remains at best semi-quantitative and operator dependent.MethodsFourteen sheep underwent surgical mitral valve replacement using 2 different prostheses. Pre-sacrifice left ventriculograms were used to assess MR fraction (MRF) using QMR and MR volume (MRV). In an independent core lab, the CAAS QMR 0.1 was used for QMR analysis. In vitro MRF and MRV were assessed in a mock circulation at a comparable cardiac output to the in vivo one by thermodilution. The correlations and agreements of in vitro and in vivo MRF, MRV, and interobserver reproducibility for QMR analysis were assessed using the averaged cardiac cycles (CCs).ResultsIn vivo derived MRF by QMR strongly correlated with in vitro derived MRF, regardless of the number of the CCs analyzed (best correlation: 3 CCs y = 0.446 + 0.994x; R = 0.784; p =0.002). The mean absolute difference between in vitro derived MRF and in vivo derived MRF from 3 CCs was 0.01 ± 4.2% on Bland-Altman analysis. In vitro MRV and in vivo MRV from 3 CCs were very strongly correlated (y = 0.196 + 1.255x; R = 0.839; p < 0.001). The mean absolute difference between in vitro MRV and in vivo MRV from 3 CCs was –1.4 ± 1.9 ml. There were very strong correlations of in vivo MRF between 2 independent analysts, regardless of the number of the CCs.ConclusionsIn vivo MRF using the novel software is feasible, accurate, and highly reproducible. These promising results have led us to initiate the first human feasibility study comprising patients undergoing percutaneous mitral valve edge-to-edge repair.     

Contact tracing for tuberculosis and treatment for latent infection in a low incidence country

OBJECTIVE: To determine the yield of contact tracing after exposure to active tuberculosis (TB) cases in a low incidence area for TB as well as completion rate and tolerance to treatment for latent TB infection (LTBI). METHODS: Retrospective study based on a database including all patients evaluated in Geneva during contact tracing procedures; review of medical records of contacts for whom treatment of LTBI was indicated. RESULTS: 3582 subjects were screened over 10 years (on average 4.3 contacts per index case); 8 (0.2%) had active TB. LTBI was detected in 28% of subjects screened. Foreign origin, exposure and contagiousness of index case were predictive of LTBI. Of the 996 subjects with LTBI, files of 705 subjects followed at our centre were reviewed: treatment was indicated in 571 (81%). Side-effects led to interruption of treatment for LTBI in 32 cases (6.9% of subjects treated); 227 subjects eligible for treatment (40%) either refused or stopped treatment, or were lost to follow-up. Completion rate was 67%. CONCLUSIONS: In a low-incidence environment for TB, contact tracing procedures had a very low yield for detection of active TB cases; acceptance and completion rates for LTBI therapy were in agreement with recent studies..