Creating a plasma coordination center to support COVID-19 outpatient trials across a national network of hospital blood banks.

Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

A novel digital health approach to improving global pediatric sepsis care in Bangladesh using wearable technology and machine learning.

Sepsis is the leading cause of child death globally with low- and middle-income countries (LMICs) bearing a disproportionate burden of pediatric sepsis deaths. Limited diagnostic and critical care capacity and health worker shortages contribute to delayed recognition of advanced sepsis (severe sepsis, septic shock, and/or multiple organ dysfunction) in LMICs. The aims of this study were to 1) assess the feasibility of a wearable device for physiologic monitoring of septic children in a LMIC setting and 2) develop machine learning models that utilize readily available wearable and clinical data to predict advanced sepsis in children.

Quantifying variant contributions in cystic kidney disease using national-scale whole-genome sequencing.

BACKGROUNDCystic kidney disease (CyKD) is a predominantly familial disease in which gene discovery has been led by family-based and candidate gene studies, an approach that is susceptible to ascertainment and other biases.METHODSUsing whole-genome sequencing data from 1,209 cases and 26,096 ancestry-matched controls participating in the 100,000 Genomes Project, we adopted hypothesis-free approaches to generate quantitative estimates of disease risk for each genetic contributor to CyKD, across genes, variant types and allelic frequencies.RESULTSIn 82.

Modelling climate impacts on paediatric sepsis incidence and severity in Bangladesh.

Background: Sepsis is a leading cause of paediatric mortality worldwide, disproportionately affecting children in low- and middle-income countries. The impacts of climate change on the burden and outcomes of sepsis in low- and middle-income countries, particularly in paediatric populations, remain poorly understood. We aimed to assess the associations between climate variables (temperature and precipitation) and paediatric sepsis incidence and mortality in Bangladesh, one of the countries most affected by climate change.

Self-supervised learning for characterising histomorphological diversity and spatial RNA expression prediction across 23 human tissue types.

As vast histological archives are digitised, there is a pressing need to be able to associate specific tissue substructures and incident pathology to disease outcomes without arduous annotation. Here, we learn self-supervised representations using a Vision Transformer, trained on 1.7 M histology images across 23 healthy tissues in 838 donors from the Genotype Tissue Expression consortium (GTEx).

Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design.

Background: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials.

Armed actor interventions in humanitarian and public health crises: examining perspectives of crisis-affected community members.

Background: Despite frequently providing non-military services in times of crisis, little systematic research has examined the perspectives of crisis-affected community members on the role of armed actors responding to humanitarian crises and public health emergencies.

Methods: To address this research gap, 175 interviews were conducted (2020-2021) amongst humanitarian and public health practitioners; armed actors; and crisis-affected community members across three country and four crisis contexts. Specifically, this effort included an Ebola outbreak in the Democratic Republic of the Congo; a refugee crisis on the Jordanian-Syrian border; and a volcanic eruption and COVID-19 outbreak in the Philippines.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

Derivation and Internal Validation of a Mortality Prognostication Machine Learning Model in Ebola Virus Disease Based on Iterative Point-of-Care Biomarkers.

Background: Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care.

Methods: This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care.

Perceptions toward Ebola vaccination and correlates of vaccine uptake among high-risk community members in North Kivu, Democratic Republic of the Congo.

The tenth Ebola Virus Disease (EVD) outbreak (2018-2020, North Kivu, Ituri, South Kivu) in the Democratic Republic of the Congo (DRC) was the second-largest EVD outbreak in history. During this outbreak, Ebola vaccination was an integral part of the EVD response. We evaluated community perceptions toward Ebola vaccination and identified correlates of Ebola vaccine uptake among high-risk community members in North Kivu, DRC.

Human dissection for anesthesiology resident training augments anatomical knowledge and clinical skills.

Anatomy is an essential component of clinical anesthesiology. The use of simulated patients and alternative materials, including embalmed human bodies, have become increasingly common during resident physician training due to the deemphasis on anatomical education during undergraduate medical training. In this report, the need for a more extensive review of relevant anatomy for the practice of anesthesiology was addressed by the design, evaluation, and dissemination of a human dissection course for procedural training of anesthesiology residents.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.

COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect.

A comparison of the NIRUDAK models and WHO algorithm for dehydration assessment in older children and adults with acute diarrhoea: a prospective, observational study.

Background: Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines.

Methods: A random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study.

Early antibody treatment, inflammation, and risk of post-COVID conditions.

Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC.

The role of civil society organizations (CSOs) in the COVID-19 response across the Global South: A multinational, qualitative study.

Despite receiving less attention than high-income countries, low- and middle-income countries (LMICs) experienced more than 85% of global excess deaths during the first two years of the COVID-19 pandemic. Due to the unprecedented speed and scale of the COVID-19 pandemic, which placed large demands on government capacity, many LMICs relied on civil society organizations (CSOs) to assist in implementing COVID-19 response programs. Yet few studies have examined the critical role CSOs played in mitigating the effects of the COVID-19 pandemic in low resource settings.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

Background: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

Methods: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19.

Ebola vaccine uptake and attitudes among healthcare workers in North Kivu, Democratic Republic of the Congo, 2021.

Introduction: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs.

Methods: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC.

Common Risk Variants in Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.

Introduction: Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at and have identified several non- loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

Study Design And Methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.