Comparable cellular and humoral immunity upon homologous and heterologous COVID-19 vaccination regimens in kidney transplant recipients

BackgroundKidney transplant recipients (KTRs) are at high risk for a severe course of coronavirus disease 2019 (COVID-19); thus, effective vaccination is critical. However, the achievement of protective immunogenicity is hampered by immunosuppressive therapies. We assessed cellular and humoral immunity and breakthrough infection rates in KTRs vaccinated with homologous and heterologous COVID-19 vaccination regimens.MethodWe performed a comparative in-depth analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific T-cell responses using multiplex Fluorospot assays and SARS-CoV-2-specific neutralizing antibodies (NAbs) between three-times homologously (n = 18) and heterologously (n = 8) vaccinated KTRs.ResultsWe detected SARS-CoV-2-reactive T cells in 100% of KTRs upon third vaccination, with comparable frequencies, T-cell expression profiles, and relative interferon γ and interleukin 2 production per single cell between homologously and heterologously vaccinated KTRs. SARS-CoV-2-specific NAb positivity rates were significantly higher in heterologously (87.5%) compared to homologously vaccinated (50.0%) KTRs (P < 0.0001), whereas the magnitudes of NAb titers were comparable between both subcohorts after third vaccination. SARS-CoV-2 breakthrough infections occurred in equal numbers in homologously (38.9%) and heterologously (37.5%) vaccinated KTRs with mild-to-moderate courses of COVID-19.ConclusionOur data support a more comprehensive assessment of not only humoral but also cellular SARS-CoV-2-specific immunity in KTRs to provide an in-depth understanding about the COVID-19 vaccine–induced immune response in a transplant setting

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Model vir onderrig van neonatale verpleegkundiges as reflektiewe praktisyns

A model is developed for the education of neonatal nurses as reflective practitioners in a South African context to prepare them for their demanding role in neonatal nursing practice. An exploratory and descriptive design was used, which was in essence qualitative and contextual in nature. Neonatal nursing practice related to education of reflective neonatal nurses was explored and verified to synthesise competences and professional characteristics expected of reflective neonatal nurses and to deduce the content outline of an educational programme. The model was constructed, described and evaluated by experts in model development, higher education, nursing education and/or neonatal nursing practice.’n Model is ontwikkel vir onderrig van neonatale verpleegkundiges as reflektiewe praktisyns in ’n Suid-Afrikaanse konteks. ’n Ondersoekende en beskrywende ontwerp is gebruik wat in wese ’n kwalitatiewe en kontekstuele aard het. Neonatale verpleegpraktyk rakende onderrig van reflektiewe neonatale verpleegkundiges is ondersoek en gevalideer om die verwagte bevoegdhede en professionele eienskappe van reflektiewe neonatale verpleegkundiges te sintetiseer, en ’n oorsig van die inhoud van so ’n program af te lei. Eksperts in modelontwikkeling, hoëronderwys, verpleegonderwys en/of neonatale verpleegpraktyk het die model gevalideer

The “religiosity gap” in a clinical setting: experiences of mental health care consumers and professionals

In Western countries, professionals in mental health care (“professionals”) tend to be less religious than “consumers”. This qualitative study explores the meaning of this “religiosity gap” for professionals and consumers in mental health care. Both a regular, secular and a Christian clinic in the Netherlands participated in this study. Content analysis was applied to 35 consumer interviews and 18 interviews with professionals. Consumers reported negative experiences (e.g., perceived disrespect and a lack of confidence) and/or negative expectations (e.g., misunderstanding and misinterpretation) related to a religiosity gap. They also mentioned advantages of a “religiosity match”, like safety and confidence and appreciated professionals’ religious/spiritual self-disclosure. Professionals in secular care setting tended to avoid religion and spirituality. In both clinics, they tended to neutralise religious/spiritual differences and be reticent in self-disclosure. Professionals are recommended to recognise the relevance of a religiosity gap and to consider different strategies in approaching religion/spirituality

Regionalization of federal health reporting using the example of diabetes surveillance

Unzureichend behandelt kann die Stoffwechselerkrankung Diabetes mellitus zu schwerwiegenden Folgeerkrankungen führen. Nationale und internationale Analysen zeigen einen kontinuierlichen Anstieg der Diabetesprävalenz über die letzten Jahre. Am Robert Koch-Institut (RKI) wird derzeit eine Nationale Diabetes-Surveillance aufgebaut, die das Diabetesgeschehen indikatorenbasiert unter Nutzung von Primär- und Sekundärdaten kontinuierlich abbilden soll. Ziel des Bund-Länder-Gesprächs war es, die Bundesländer frühzeitig in die Konzeption der Diabetes-Surveillance einzubinden und die Bedarfe der Gesundheitsberichterstattung (GBE) der Länder zu berücksichtigen. Das RKI lud alle Vertreter der Länder-GBE zu einem Gespräch nach Berlin ein. Dies war bereits das zweite Bund-Länder-Gespräch im Rahmen der Diabetes-Surveillance. Ein kontinuierlicher Austausch in Form regelmäßiger Bund-Länder-Gespräche wird angestrebt.Insufficiently treated diabetes mellitus can lead to severe comorbidities. National and international analyses show a continuous increase in diabetes prevalence over the last decades. Currently, an indicator-based national diabetes surveillance system is implemented at the Robert Koch Institute (RKI) to monitor and report on diabetes development on the basis of available primary and secondary data. The aim of the meeting was to go into deeper discussions and to integrate expectations and expertise of the federal states into the design of the national surveillance system. A close collaboration between the RKI and the federal states is intended.Peer Reviewe

Improved SARS-CoV-2 Neutralization of Delta and Omicron BA.1 Variants of Concern after Fourth Vaccination in Hemodialysis Patients

Hemodialysis patients are exposed to a markedly increased risk when infected with SARS-CoV-2. To date, it is unclear if hemodialysis patients benefit from four vaccinations. A total of 142 hemodialysis patients received four COVID-19 vaccinations until March 2022. RDB binding antibody titers were determined in a competitive surrogate neutralization assay. Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Delta (B.1.617.2), or Omicron (B.1.1.529, sub-lineage BA.1) to determine serum infection neutralization capacity. Four weeks after the fourth vaccination, serum infection neutralization capacity significantly increased from a 50% inhibitory concentration (IC50, serum dilution factor 1:x) of 247.0 (46.3–1560.8) to 2560.0 (1174.0–2560.0) for the Delta VoC, and from 37.5 (20.0–198.8) to 668.5 (182.2–2560.0) for the Omicron VoC (each p p p = 0.051). Our findings suggest that hemodialysis patients benefit from a fourth vaccination in particular in the light of the highly infectious SARS-CoV-2 Omicron-variants. A routinely applied four-time vaccination seems to broaden immunity against variants and would be recommended in hemodialysis patients