The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes.

The biological mechanisms through which most nonprotein-coding genetic variants affect disease risk are unknown. To investigate gene-regulatory mechanisms, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA sequencing in 4,732 participants and integrated protein, metabolite and lipid data from the same individuals. We identified cis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes).

Quality of Care and Long-term Survival After ST-elevation Myocardial Infarction in Adults with Cancer.

Background: While current evidence suggests that the clinical outcomes of ST-elevation myocardial infarction (STEMI) are worse among patients with cancer, it is unknown what role the quality of care received during admission plays. We aimed to evaluate the association between care quality and patient survival after discharge.

Methods: A nationally-linked cohort of STEMI patients (January 2005-March 2019) were obtained from the UK Myocardial Infarction National Audit Project (MINAP) and UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registries.

Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial.

Background: COVID-19 convalescent plasma (CCP) is a treatment option for COVID-19. This study investigated the safety and efficacy of early, very high-titre CCP in immunocompromised individuals with mild COVID-19.

Methods: This randomised, controlled, open-label trial assessed CCP in immunocompromised patients (n = 120) with mild COVID-19 in 10 clinical trial centres across Germany, France, and the Netherlands.

Expected outcomes of stratified post-donation testing in whole blood donation in England: A discrete event simulation modeling study.

Background: In England, blood donors with low hemoglobin concentration are deferred following on-session testing to prevent donations below regulatory thresholds, thereby protecting donors' health and blood supply quality. However, deferrals are costly, time-consuming and may discourage donors. Post-donation testing (PDT), where hemoglobin levels are measured after donation, offer potential alternatives as used in some European countries.

The United Kingdom Infected Blood Inquiry: Its findings and lessons for the future of transfusion.

The UK Infected Blood Inquiry report was published in May 2024 after 6 years of taking oral and written evidence from patients, clinicians, blood services, government officials and politicians about the transmission of infection by blood transfusion to thousands of patients in the 1970s through to the 1990s. The same problems with transfusion-transmitted infection occurred in many other countries in the same period but their reviews, inquiries and decisions about compensation occurred many years earlier than in the UK. The publication of the report has been welcomed but begs two important questions.

Evaluation of gestational nonpersistent pesticide exposure with newborn size and gestational length in rural Ghana using a novel time-varying extension of multiple informant models.

Background: Gestational pesticide exposure may negatively affect newborn outcomes. Prior results evaluating nonpersistent pesticides are inconsistent.

Objective: To examine associations between gestational exposure to nonpersistent pesticides and newborn outcomes and identify critical windows of susceptibility.

Strategies to Improve Health Care Provider Prescription of and Patient Adherence to Guideline-Recommended Cardiovascular Medications for Atherosclerotic Occlusive Disease: Protocol for Two Systematic Reviews and Meta-Analyses of Randomized Controlled Trials.

Background: In patients with atherosclerotic occlusive diseases, systematic reviews and meta-analyses of randomized controlled trials (RCTs) report that antiplatelets, statins, and antihypertensives reduce the risk of major adverse cardiac events, need for revascularization procedures, mortality, and health care resource use. However, evidence suggests that these patients are not prescribed these medications adequately or do not adhere to them once prescribed.

Objective: We aim to systematically review and meta-analyze RCTs examining the effectiveness of implementation or adherence-supporting strategies for improving health care provider prescription of, or patient adherence to, guideline-recommended cardiovascular medications in patients with atherosclerotic occlusive disease.

Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial.

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Cross-modal contrastive learning for unified placenta analysis using photographs.

The placenta is vital to maternal and child health but often overlooked in pregnancy studies. Addressing the need for a more accessible and cost-effective method of placental assessment, our study introduces a computational tool designed for the analysis of placental photographs. Leveraging images and pathology reports collected from sites in the United States and Uganda over a 12-year period, we developed a cross-modal contrastive learning algorithm consisting of pre-alignment, distillation, and retrieval modules.

Transfusion-specific alloimmune responses following blood transfusion pre-kidney transplantation.

It is widely accepted that blood transfusions can cause allosensitization, but it is often reported that new human leukocyte antigen (HLA) antibodies are nonspecific and transient. This study explores the effect of blood transfusion on allosensitization in waitlisted transplant patients including the development of transfusion-specific antibodies (TSAs), both while they remain on the waiting list, and following subsequent transplantation. A total of 105 blood donors of transfusions received by 50 patients on the transplant waiting list were HLA typed.

Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood.

Background: Metrics evaluating the functional quality of red blood cells (RBCs) must consider their role in oxygen delivery. Whereas oxygen-carrying capacity is routinely reported using haemoglobin assays, the rate of oxygen exchange is not measured, yet also important for tissue oxygenation. Since oxygen-unloading depends on the diffusion pathlength inside RBCs, cell geometry offers a plausible surrogate.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

International cross-sectional survey on current and updated definitions of intra-abdominal hypertension and abdominal compartment syndrome.

Background: The Abdominal Compartment Society (WSACS) established consensus definitions and recommendations for the management of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in 2006, and they were last updated in 2013. The WSACS conducted an international survey between 2022 and 2023 to seek the agreement of healthcare practitioners (HCPs) worldwide on current and new candidate statements that may be used for future guidelines.

Methods: A self-administered, online cross-sectional survey was conducted under the auspices of the WSACS to assess the level of agreement among HCPs over current and new candidate statements.

Receptor activity-modifying protein modulation of parathyroid hormone-1 receptor function and signaling.

Introduction: Receptor activity-modifying proteins (RAMPs) are known to modulate the pharmacology and function of several G-protein-coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R). However, the precise effects of different RAMPs on PTH1R signalling and trafficking remain poorly understood. This study investigated the impact of RAMP2 and RAMP3 on PTH1R function using a range of PTH and PTH-related protein (PTHrP)-derived ligands.

A systematic review and meta-analysis of outcomes associated with development of surgical site infection after lower-limb revascularization surgery.

Objectives: Although surgical site infection (SSI) is a commonly used quality metric after lower-limb revascularization surgery, outcomes associated with development of this complication are poorly characterized. We conducted a systematic review and meta-analysis of studies reporting associations between development of an SSI after these procedures and clinical outcomes and healthcare resource use.

Methods: We searched MEDLINE, Embase, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies examining adjusted associations between development of an SSI after lower-limb revascularization surgery and clinical outcomes and healthcare resource use.

Transfusion-induced HLA sensitization in wait-list patients and kidney transplant recipients.

Human leukocyte antigen (HLA) sensitization remains an impediment to successful solid organ transplantation, whether it be chances of receiving a transplant offer or subsequent transplant longevity. Current treatments targeting HLA antibodies lack long-term effectiveness; therefore, preventing HLA sensitization should remain a priority in all potential wait-list candidates and transplant recipients. Recent advances in the management of anemia in patients with chronic kidney disease may reduce the need for red cell transfusions.

Misexpression of inactive genes in whole blood is associated with nearby rare structural variants.

Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors.

Clinical impact of early post-transplant red cell transfusions in kidney transplantation: a systematic review and meta-analysis.

Introduction: Red blood cell transfusions (RBCT) represent a potentially modifiable risk factor for HLA sensitisation and adverse outcomes post transplantation. Evidence of the clinical impact of post-transplant RBCT has been infrequently reported. Herein, we performed a systematic review of available literature to assess the prevalence of RBCT post kidney transplant, and the effect of transfusion on transplant outcomes.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis.

Introduction: International guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs, which characteristics predict clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications, and whether underprescription and non-adherence are associated with adverse health and health system outcomes.

Methods And Analysis: We will search MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 2006 onwards.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

Background: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures.

Methods: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery.

In vivo genotoxicity testing strategies: Report from the 8th International Workshop on Genotoxicity Testing (IWGT).

The in vivo working group (WG) considered three topics: acceptable maximum doses for negative erythrocyte micronucleus (MN) tests, validation status of MN assays in non-hematopoietic tissues, and nuisance factors in the comet assay. The WG reached agreement on many issues, including: negative erythrocyte MN studies should be acceptable if dosing is conducted to Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 474 recommendations and if sufficient bone marrow exposure is demonstrated; consensus on the evidence required to demonstrate "sufficient" exposure was not reached. The liver MN test using six-week-old rats is sufficiently validated to develop an OECD TG, but the impact of animal age warrants additional study.