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Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus‐8 (HHV‐8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single‐gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV‐8.

Background Despite their central role in the global response to the COVID-19 pandemic and previous infectious disease outbreaks, factors influencing the acceptability and implementation of social distancing measures are poorly understood. This systematic review aims to identify such factors drawing on qualitative literature. Methods A systematic search was carried out in eleven databases. Papers were included in the review if they reported on qualitative studies of factors influencing the implementation of social distancing measures in potentially epidemic infectious diseases. An adapted meta-ethnographical approach was used for synthesis. Review findings were assessed for strength and reliability using GRADE-CERQual. Results Twenty-nine papers were included from the systematic search that yielded 5620 results, and supplementary methods. The review identifies two broad categories of barriers to social distancing measures: individual- or community-level psychosocial phenomena, and shortcomings in governmental action or communication. Based on this, 25 themes are identified that can be addressed to improve the implementation of social distancing. Conclusion Among other findings, the review identifies the need for good communication as well as the need for authorities to provide comprehensive support as two key opportunities to increase acceptability and adherence. Further important enablers of adherence are adequate preparedness and appropriate legislation, the presence of community involvement, solidarity within communities and trust in governments and authorities.

Health-Promoting School (HPS) interventions aim to reduce bullying and violence via curriculum, environmental and family/community-engagement components. Despite evidence of their effectiveness, factors influencing the implementation of such interventions are poorly understood. This systematic review aims to examine such factors by assessing qualitative process evaluations of HPS interventions aiming to reduce bullying, aggression or violence. A comprehensive systematic search of 12 databases was carried out, and 20 reports from 17 studies were included. Thematic synthesis was used to identify factors affecting implementation. Factors that enable implementation were related to programme characteristics and stakeholder buy-in, including support from leadership, teachers, students and parents. Good communication and staff climate were important. Interventions were better implemented when they framed health promotion as a core school business, were supported by a national policy, used local data to show need and effectiveness and provided high-quality, pragmatic and accessible staff training. The results of this review can serve to guide and facilitate the design and implementation of future bullying and violence prevention programmes. Since there is significant overlap in terms of the important pillars and guiding principles for all interventions guided by the HPS framework, the findings may apply to outcomes beyond bullying and violence.

Aim: To systematically review qualitative literature on social distancing in order to identify and describe factors that enable or prevent its implementation. Methods: A rapid systematic qualitative review was conducted in accordance with PRISMA and ENTREQ guidelines. A comprehensive systematic search was carried out in MEDLINE, EMBASE, PsychINFO, Global Health, CINAHL and Web of Science. Included papers (i) report on primary qualitative studies (ii) of the barriers and facilitators to the implementation of social distancing measures (iii) in potentially epidemic infectious diseases. After critical appraisal and standardised data extraction, a meta-ethnographical approach was used for synthesis. Review findings were assessed for strength and reliability using CerQUAL. Results: 28 papers were included from the systematic search that yielded 5620 results. One additional paper was found by searching references. The review identifies two broad categories of barriers to social distancing measures: individual- or community-level psychological or sociological phenomena, and perceived shortcomings in governmental action. Based on this, 25 themes are identified that can be addressed to improve the implementation of social distancing. Conclusion: There are many barriers, on different levels, to the implementation of social distancing measures. Among other findings, the review identifies the need for good communication as well as the need for authorities to provide comprehensive support as two key opportunities to increase acceptability and adherence. High-quality research is needed during the COVID-19 pandemic to better describe mechanisms by which implementation of social distancing can be improved, and, more importantly, what is already known has to be put into practice.

Introduction Recent evidence suggests an association of plasma Proenkephalin A 119–159 (penKid) with early and successful liberation from continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury. However, these exploratory results are derived from a monocentric trial and therefore require external validation in a multicenter cohort. Methods Data and plasma samples from the “Effect of Regional Citrate Anticoagulation versus Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury—A Randomized Clinical Trial” (RICH Trial) were used for this validation study. PenKid was measured in all plasma samples available at CRRT initiation and at day 3 of CRRT. Patients were categorized into low and high penKid groups with a cutoff at 100 pmol/l. Competing-risk time-to-event analyses were performed. Competing risk endpoints were successful and unsuccessful liberation from CRRT, the latter meaning death or initiation of a new RRT within one week of discontinuation of primary CRRT. Then penKid was compared to urinary output. Results Low pre-CRRT penKid levels at CRRT initiation were not associated with early and successful liberation from CRRT compared to patients with high pre-CRRT penKid levels [subdistribution hazard ratio (sHR) 1.01, 95% CI 0.73–1.40, p = 0.945]. However, the landmark analysis on day 3 of ongoing CRRT demonstrated an association between low penKid levels and successful liberation from CRRT (sHR 2.35, 95% CI 1.45–3.81, p < 0.001) and an association between high penKid levels and unsuccessful liberation (sHR 0.46, 95% CI 0.26–0.80, p = 0.007). High daily urinary output (> 436 ml/d) was even stronger associated with successful liberation (sHR 2.91, 95% CI 1.80–4.73, p < 0.001) compared to penKid. Discussion This study suggests that penKid may be a competent biomarker to monitor the recovery of kidney function during CRRT. This is in line with previous findings and investigated this concept in a multicenter cohort. Again, low penKid was associated with early and successful CRRT liberation, but was outperformed by high daily urinary output. The findings of this study now warrant further evaluation in prospective studies or a randomized controlled trial. Trial registration The RICH Trial was registered at clinicaltrials.gov: NCT02669589. Registered 01 February 2016.

Background Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes. Methods This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7–1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months. Discussion This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. Trial registration ClinicalTrials.gov NCT05726825, Registered on 14 February 2023.