Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial.

Introduction: Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes.

Improving 1-year liver allograft survival hazard ratios.

Background: The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme.

Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness.

Background: Attending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.

Method: From June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease.

Evolution and effectiveness of bilateral and multilateral development assistance for health: a mixed-methods review of trends and strategic shifts (1990-2022).

Background: Development assistance for health (DAH) plays a vital role in supporting health programmes in low- and middle-income countries. While DAH has historically focused on infectious diseases and maternal and child health, there is a lack of comprehensive analysis of DAH trends, strategic shifts and their impact on health systems and outcomes. This study aims to provide a comprehensive review of DAH from 1990 to 2022, examining its evolution and funding allocation shifts.

Health and economic impact of oral PrEP provision across subgroups in western Kenya: a modelling analysis.

Introduction: Oral pre-exposure prophylaxis (PrEP) is a priority intervention for scale-up in countries with high HIV prevalence. Policymakers must decide how to optimise PrEP allocation to maximise health benefits within limited budgets. We assessed the health and economic impact of PrEP scale-up among different subgroups and regions in western Kenya.

Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction.

Background: The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.

Utilization of primary tumor samples for cancer neoantigen discovery.

Background: The use of tumor-infiltrating T lymphocytes (TIL) that recognize cancer neoantigens has led to lasting remissions in metastatic melanoma and certain cases of metastatic epithelial cancer. For the treatment of the latter, selecting cells for therapy typically involves laborious screening of TIL for recognition of autologous tumor-specific mutations, detected through next-generation sequencing of freshly resected metastatic tumors. Our study explored the feasibility of using archived formalin-fixed, paraffin-embedded (FFPE) primary tumor samples for cancer neoantigen discovery, to potentially expedite this process and reduce the need for resections normally required for tumor sequencing.

Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15.

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15).

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer.

Background: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

Predicting Elevated Postvoid Residual Urine Volume Following OnabotulinumtoxinA Treatment for Overactive Bladder: A Pilot Study.

Objectives: To evaluate possible predictors of elevated postvoid residual volume (PVR) following onabotulinumtoxinA administration in patients with idiopathic overactive bladder (OAB), a condition that may include urinary urgency, frequency, and nocturia, without any identifiable cause or underlying neurological or metabolic condition.

Methods: Adults who had been treated with 100-200 U onabotulinumtoxinA for OAB and had previous failure of other OAB treatments were identified by retrospective review of medical chart data from three urology clinics in the United States treating patients with a variety of urological conditions. A total of 211 patients were allocated to cohorts based on posttreatment PVR < 200 mL (n = 173) and ≥ 200 mL (n = 38).

Expanding access to maggot containment dressings through redesign and innovation.

There are two major styles of maggot debridement dressings: (1) confinement dressings that form a cage around the wound, and (2) containment dressings that completely surround the maggots within a sealed porous bag. For producers and clinicians wanting to prepare containment dressings using readily available polyester bags, it is currently difficult to seal these bags without expensive high-temperature plastic welders. This study aimed to identify simple and affordable methods for sealing maggots within polyester net bags.

Comparison of Clinical and Radiological Outcomes of Three-Column Lumbar Osteotomies with and without Interbody Cages for Adult Spinal Deformity.

Background Context: Correcting sagittal malalignment in adult spinal deformity (ASD) is a challenging task, often requiring complex surgical interventions like pedicle subtraction osteotomies (PSOs). Different types of three-column osteotomies (3COs), including Schwab 3, Schwab 4, Schwab 4 with interbody cages, and the "sandwich" technique, aim to optimize alignment and fusion outcomes. The role of interbody cages in enhancing fusion and segmental correction remains unclear.

In-depth Computational Analysis Reveals The Significant Dysregulation of Key Gap Junction Proteins (GJPs) Driving Thoracic Aortic Aneurysm Development.

Objective: Thoracic Aortic Aneurysm (TAA) represents an aortic pathology that is caused by the deranged integrity of the three layers of the aortic wall, and is related to severe morbidity and mortality. Consequently, it is crucial to identify the biomarkers implicated in the pathogenesis and biology of TAA. The aim of the current computational study was to assess the differential gene expression profile of the gap junction proteins (GJPs) in patients with TAA in order to identify novel potential biomarkers for the diagnosis and treatment of this disease.

Association of Sugar sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption with Chronic Liver Disease and Liver Related Events: A Large Prospective Cohort Study.

Background: Previous observational studies haven't reached an agreement on the association between coffee consumption and risk of liver diseases. Also, none of these studies took sweetener added in coffee into consideration.

Objective: We aim to explore the associations of consumption of sweetened and unsweetened coffee with chronic liver disease (CLD) and liver-related events (LREs), and evaluate the degree to which sweetener added counteracted the effect of coffee.

Valve Sparing Aortic Root Replacement in the Resternotomy Setting.

Objectives: While valve-sparing aortic root replacement (VSRR) has demonstrated satisfactory outcomes, its utility in a reoperative sternotomy setting remains uncertain. This study evaluates the perioperative safety and long-term durability of reoperative sternotomy VSRR.

Methods: All consecutive VSRR at two centers from 2005-2020 were included.

The Effect of Blood Pressure on Rates of Progression in Focal Ischemic versus Generalized Cup Enlargement Glaucoma Phenotypes.

Purpose: To investigate the impact of blood pressure (BP) on rates of retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes with focal ischemic (FI) versus generalized enlargement (GE) optic disc phenotypes.

Design: Prospective cohort study.

Participants: The study included 122 eyes from 101 patients diagnosed with primary open-angle glaucoma.

Evaluating student understanding of core pharmacokinetic concepts.

Both educators and graduates have expressed concern about a perceived pharmacology knowledge gap that includes difficulty applying fundamental principles to clinical and research problems. Consequently, we sought to determine the extent to which current students can explain the meaning of, and appropriately apply, a subset of core concepts, and to identify any misconceptions arising from the responses. Of the twenty-four pharmacology core concepts arising from the recent international collaboration, four pharmacokinetic concepts were chosen, namely drug bioavailability, drug clearance, volume of distribution, and steady-state concentration.

The Effects of Socioeconomic Position on Endogenous Pain Modulation: A Quasi-Experimental Approach.

Socioeconomic Position (SEP) is a multidimensional construct encompassing education, income, occupation, and neighborhood distress, influencing chronic pain severity, interference, and duration. However, its impact on placebo analgesia, where reduced pain perception occurs due to treatment belief, remains understudied. Using a quasi-experimental approach, we investigated SEP's influence on placebo analgesia in 401 participants with temporomandibular disorder (TMD) and 400 pain-free individuals.

Prevalence and Patterns of Social Media Use in Early Adolescents.

Objective: To describe patterns of social media use, including underage (under 13 years) use and sex differences, in a diverse, national sample of early adolescents in the U.S.

Methods: We analyzed the social media use data in the Adolescent Brain Cognitive Development Study (2019-2021, Year 3), which includes a national sample of early adolescents in the U.

Personalized theta-burst stimulation enhances social skills in young minimally verbal children with autism: a double-blind randomized controlled trial.

Background: Minimally verbal children with autism are understudied and lack effective treatment options. Personalized continuous theta-burst stimulation (cTBS) targeting the amygdala and its circuitry may be a potential therapeutic approach for this population.

Methods: In a double-blind randomized controlled trial, minimally verbal children with autism (ages 2-8 years) received 4 weeks of cTBS.

Phase 3, Randomized, Comparison Study of Intracameral Bimatoprost Implant 10 µg and Selective Laser Trabeculoplasty.

Purpose: To evaluate the intraocular pressure (IOP)-lowering effect and safety of up to two bimatoprost implant administrations versus selective laser trabeculoplasty (SLT).

Design: Phase 3 (Stage 2), randomized, 24-month, multicenter, patient- and efficacy evaluator-masked, paired-eye clinical trial (NCT02507687).

Participants: Patients (n=183) with open-angle glaucoma or ocular hypertension inadequately managed with topical IOP-lowering medication for reasons other than efficacy.

Non-colorectal Cancer Screening and Vaccinations in Patients with Inflammatory Bowel Disease: Expert Review.

Description: The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice (BPA) statements for gastroenterologists and other health care providers who provide care to patients with inflammatory bowel disease (IBD). The focus is on IBD-specific screenings (excluding colorectal cancer screening, which is discussed separately) and vaccinations. We provide guidance to ensure that patients are up to date with the disease-specific cancer screenings, vaccinations, as well as advice for mental health and general wellbeing.

Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.

Background: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Fecal microbiota transplantation (FMT) is beneficial in phase-1 studies, but route and dose-related questions remain.

Methods: We performed a phase-2 randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in cirrhosis and HE on lactulose and rifaximin.

Effects of periodontal disease on the proteomic profile of the periodontal ligament.

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into the control and experimental periodontitis groups.