Characterizing hospital pathways for the care of acquired hemophilia in France using comprehensive national health data

PurposeAcquired hemophilia (AH) is a rare, serious bleeding disorder most often associated with older age and life-threatening complications. The patient care pathway for AH is complex because of the different types of bleeding, the presence of comorbidities, and the heterogeneity of medical specialists who care for these patients.MethodsThis observational study used the French national PMSI (Programme de médicalisation des systèmes d’information) database to characterize patients with AH in real-life practice and analyze their hospital pathway. In total, 180 patients with AH were identified over a 5-year study period (January 2010 to December 2014), based on three criteria: bypassing agent use, International Classification of Diseases, 10th revision code allocation, and aged over 65 years. Comparison of the incidence rate of AH versus registry data validated the PMSI as an epidemiological database.ResultsRituximab was prescribed more often (60/180; 33.3%) than expected following guidelines and was associated in half of cases to early infections (32/60; 53.3%), surgery procedures were frequently performed during the year before AH onset (29/159; 18.2%), which may suggest a triggering effect, extended hospital stays (median: 20 days) and mortality remaining high (66/180; 36.7%) that occurred mainly during the first month after AH diagnosis. Median costs and number of injections were comparable between recombinant activated factor VII and plasma-derived activated prothrombin complex concentrate.ConclusionThese findings could inform future medico-economic approaches in this AH population (duration of stays, bypassing agents, rituximab use, comorbidities, hospitalizations with infections).     

A prospective,double-blind,randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Background and aimsPatients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).MethodsRecords of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.ResultsThirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA_1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).ConclusionsCOVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.     

白细胞介素17A在银屑病发病及治疗中的研究进展

【摘要】 近十余年来的基础和临床研究发现并确立了Th17/白细胞介素17A（IL-17A）在银屑病发病中的核心地位。IL-17A不仅能影响角质形成细胞的增殖活性和细胞功能，对银屑病免疫病理环境中的免疫细胞和相关细胞因子也有很重要的调控作用。近年来针对IL-17A通路的单抗如司库奇尤单抗、ixekizumab、brodalumab等在国内外陆续上市，在临床应用中展现出了显著的疗效。本文介绍IL-17A在银屑病发病机制中的作用以及靶向IL-17A及其受体IL-17RA生物治疗的最新进展。     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

Immunization with BLS-Stx2B chimera totally protects dams from early pregnancy loss induced by Shiga toxin type 2 (Stx2) and confers anti-Stx2 immunity to the offspring

Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved in food-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC and is responsible for systemic complications including Hemolytic Uremic Syndrome (HUS). It has been previously demonstrated that Shiga toxin type 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. The main purpose of this study was to determine if an active immunization prevents Stx2 mediated pregnancy loss and confers passive protective immunity to the offspring. For that purpose Sprague Dawley female rats were immunized with the chimera based on the enzyme lumazine synthase from Brucella spp. (BLS) and the B subunit of Shiga toxin 2 (Stx2B) named BLS-Stx2B. After immunization females were mated with males. At day 8 of gestation, dams were challenged intraperitoneally with a sublethal and abortifacient dose of Stx2. The immunization induced high anti-Stx2B-specific antibody titers in sera and most important, prevented pregnancy loss. Pups born and breastfeed by immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fostering experiments indicated that passive protective immunity against Stx2 was transmitted through lactation. These results indicate that immunization of adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss and confers anti Stx2 protective immunity to the offspring.     

Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women

BackgroundGroup B Streptococcus (GBS) is the leading cause of life-threatening infections in new-borns and may cause invasive disease, stillbirth and preterm delivery during pregnancy. While no licensed vaccine exists, maternal immunization might protect against neonatal disease and adverse pregnancy outcomes. We assessed the safety and immunogenicity of a prototype vaccine consisting of the fused N-terminal domains of the AlphaC and Rib surface proteins of GBS (GBS-NN).MethodsGBS-NN was tested in a randomised, double-blind, placebo-controlled, parallel group, phase I study, in healthy non-pregnant women. A dose-escalation phase, with two doses, four weeks apart, of 10, 50 or 250 µg, administered with or without aluminium hydroxide, was initially assessed (n = 60). This was followed by a dose-confirmation study, where one dose of 100 µg adjuvanted GBS-NN was compared with two doses of either 50 or 100 µg adjuvanted GBS-NN, again administered with four weeks interval between the doses (n = 180). Safety and immunogenicity were monitored for one year.ResultsGBS-NN was well tolerated with some, mostly mild, injection site reactions observed. Adjuvant significantly increased antibody concentrations and the response was boosted by a second dose. The IgG GMCs remained strongly elevated during the whole one-year duration of the study. Maximal responses occurred after two 50 µg doses, resulting in IgG GMC of 16.9 µg/ml at the primary immunological endpoint, twelve weeks after the first dose. For this regimen, 100% and 89% of the subjects achieved antibody levels above the arbitrary thresholds of 1 and 4 µg/ml, respectively. The added beneficial effect of a second dose was most pronounced for subjects with pre-existing IgG levels below the median of the entire cohort.ConclusionThe prototype GBS-NN vaccine was found to be well tolerated and highly immunogenic with an optimal regimen of two doses of 50 µg in the presence of adjuvant. Further development of a maternal vaccine based on the N-terminal domains of the alpha-like protein family of GBS is warranted (NCT02459262).