Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries.

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

First Tarsometatarsal Alignment May Self-Correct After Triple Arthrodesis in Progressive Collapsing Foot Deformity.

Background: Triple arthrodesis is commonly used to correct rigid progressive collapsing foot deformity (PCFD). These patients often have associated first tarsometatarsal (TMT) instability on lateral weightbearing radiographs. It has not been well established if it is necessary to add first TMT arthrodesis to adequately correct the overall deformity.

Impact of a care bundle on short peripheral catheter-associated complications in a resource-limited neonatal unit.

Background: Short peripheral catheter (SPC)-associated complications occur frequently in hospitalised neonates. Few studies have reported the use of SPC care bundles in resource-limited neonatal units.

Objective: To evaluate the impact of a SPC care bundle on SPC associated complications (infiltration, dislodgement, phlebitis) and catheter dwell time.

RELATIONSHIP BETWEEN TRPM4 RS8104571 GENOTYPE, CIRCULATING TRPM4 AND SUR1, AND CLINICAL OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY.

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients.

Navigating the disappointment of manuscript rejection: An author's dialogue with a reviewer and editor of tropical doctor (TD).

With the majority of medical journals having a rejection rate of >80% of submitted manuscripts, it does come as a shock and as grief to the author who great expectations before submission. Though the majority of literature available does mention how to overcome the lacunae in the manuscript before considering resubmission in another journal, none addresses the mental agony and setback the author faces and the way to overcome this setback. Every author should develop immunity and also be adequately mentally prepared to overcome this misery.

Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study.

Objectives: To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation.

Methods: Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression.

Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium.

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted.

Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living with HIV-1 Treated with Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit.

An in vitro platform for quantifying cell cycle phase lengths in primary human intestinal epithelial cells.

The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human intestinal epithelial cells (IECs). Here, we present two reporters and a complete platform for analyzing cell cycle phases in live primary human IECs. We interrogate the transcriptional identity of IECs grown on soft collagen, develop two fluorescent cell cycle reporter IEC lines, design and 3D print a collagen press to make chamber slides for optimal imaging while supporting primary human IEC growth, live image cell cycle dynamics, then assemble a computational pipeline building upon free-to-use programs for semi-automated analysis of cell cycle phases.

Projecting the Potential Clinical and Economic Impact of HIV Prevention Resource Reallocation in Tennessee.

Background: In 2023, Tennessee replaced $6.2 M in US Centers for Disease Control and Prevention (CDC) human immunodeficiency virus (HIV) prevention funding with state funds to redirect support away from men who have sex with men (MSM), transgender women (TGW), and heterosexual Black women (HSBW) and to prioritize instead first responders (FR), pregnant people (PP), and survivors of sex trafficking (SST).

Methods: We used a simulation model of HIV disease to compare the clinical impact of Current, the present allocation of condoms, preexposure prophylaxis (PrEP), and HIV testing to CDC priority risk groups (MSM/TGW/HSBW); with Reallocation, funding instead increased HIV testing and linkage of Tennessee-determined priority populations (FR/PP/SST).

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

Background: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg.

Methods: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA.

Cardiometabolic Risk Profiles of Adolescents Living With Perinatally Acquired HIV in South Africa.

Background: We assessed the Pathological Determinants of Atherosclerosis in Youth (PDAY) score and other potential cardiovascular disease risk factors in adolescents previously enrolled in the Children with HIV Early antiRetroviral (CHER) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 clinical trials.

Methods: Coronary artery and abdominal aorta (AA) PDAY scores were calculated for 56 participants over 15 years of age using a weighted combination of dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. A PDAY score ≥1 is associated with early atherosclerosis.

Impact of COVID status and blood group on complications in patients in hemorrhagic shock.

Objective: Among critically injured patients of various blood groups, we sought to compare survival and complication rates between COVID-19-positive and COVID-19-negative cohorts.

Background: SARS-CoV-2 infections have been shown to cause endothelial injury and dysfunctional coagulation. We hypothesized that, among patients with trauma in hemorrhagic shock, COVID-19-positive status would be associated with increased mortality and inpatient complications.

Paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates exposed to HIV (PETITE study): an open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial.

Background: Existing solid antiretroviral fixed-dose combination formulations are preferred over liquid formulations in children, but their suitability for neonates is unknown. We evaluated the pharmacokinetics and safety of paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates.

Methods: In this open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial, generic abacavir- lamivudine (120:60 mg) double-scored dispersible tablets and lopinavir boosted with ritonavir (40:10 mg) granules were studied.

Preventing severe hypoglycemia in adults with type 2 diabetes (PHT2): Design, delivery and evaluation framework for a randomized controlled trial.

Background: Severe hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia.

KLRG1 Cell Depletion as a Novel Therapeutic Strategy in Patients with Mature T-Cell Lymphoma Subtypes.

Purpose: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms.

Experimental Design: Primary specimens, cell lines, patient-derived xenograft models, commercially available, and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation.

Results: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), and gamma/delta T-cell lymphoma (G/D TCL).