Vancomycin-Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention.

Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed.

Evolutionary Perspectives on the Developing Skeleton and Implications for Lifelong Health.

Osteoporosis is a significant cause of morbidity and mortality in contemporary populations. This common disease of aging results from a state of bone fragility that occurs with low bone mass and loss of bone quality. Osteoporosis is thought to have origins in childhood.

Impact of flow disruptions in the delivery room.

Aim: Flow disruptions (FDs) are deviations from the progression of care that compromise safety and efficiency of a specific process. The study aim was to identify the impact of FDs during neonatal resuscitation and determine their association with key process and outcome measures.

Methods: Prospective observational study of video recorded delivery room resuscitations of neonates <32 weeks gestational age.

Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model.

Background: Vancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases.

Objectives: To clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies.

Author Correction: Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Integrative analysis reveals RNA G-quadruplexes in UTRs are selectively constrained and enriched for functional associations.

G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. By integrating multiple sources of genetic and genomic data, we show that putative G-quadruplex forming sequences (pG4) in 5' and 3' UTRs are selectively constrained, and enriched for cis-eQTLs and RNA-binding protein (RBP) interactions. Using over 15,000 whole-genome sequences, we find that negative selection acting on central guanines of UTR pG4s is comparable to that of missense variation in protein-coding sequences.

Efficacy of a Mobile Behavioral Intervention for Workers With Insomnia.

Objective: Insomnia is often unrecognized in the workplace despite a 10% prevalence. Cognitive behavioral therapy for insomnia (CBTi) is efficacious but often not available. This study assessed the efficacy of the self-guided CBTi Coach mobile app.

A Contemporary View of the Definition and Diagnosis of Osteoporosis in Children and Adolescents.

The last 2 decades have seen growing recognition of the need to appropriately identify and treat children with osteoporotic fractures. This focus stems from important advances in our understanding of the genetic basis of bone fragility, the natural history and predictors of fractures in chronic conditions, the use of bone-active medications in children, and the inclusion of bone health screening into clinical guidelines for high-risk populations. Given the historic focus on bone densitometry in this setting, the International Society for Clinical Densitometry published revised criteria in 2013 to define osteoporosis in the young, oriented towards prevention of overdiagnosis given the high frequency of extremity fractures during the growing years.

Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver.

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. Mouse studies performed on the Space Shuttle showed disruption of lipid metabolism in liver. However, given that these animals were not sacrificed on-orbit and instead returned live to earth, it is unclear if these disruptions were solely induced by space stressors (e.

Mitochondrial deficits in human iPSC-derived neurons from patients with 22q11.2 deletion syndrome and schizophrenia.

Schizophrenia (SZ) is a highly heterogeneous disorder in both its symptoms and risk factors. One of the most prevalent genetic risk factors for SZ is the hemizygous microdeletion at chromosome 22q11.2 (22q11DS) that confers a 25-fold increased risk.

Chimeric Antigen Receptor T-Cell Therapy Clinical Results in Pediatric and Young Adult B-ALL.

Chimeric antigen receptor (CAR)-modified T-cell therapy has revolutionized the care of patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Results from clinical trials across multiple institutions report remarkable remission rates with CD19-directed CAR-modified T-cell therapy. These remissions are also proving to be durable in many patients with a relapse-free survival (RFS) of approximately 50% to 60% at 1 year across several trials and institutions in this population that has been historically very difficult to treat.

Comparing Outcomes and Costs of Medical Patients Treated at Major Teaching and Non-teaching Hospitals: A National Matched Analysis.

Background: Teaching hospitals typically pioneer investment in new technology and cultivate workforce characteristics generally associated with better quality, but the value of this extra investment is unclear.

Objective: Compare outcomes and costs between major teaching and non-teaching hospitals by closely matching on patient characteristics.

Design: Medicare patients at 339 major teaching hospitals (resident-to-bed (RTB) ratios ≥ 0.

Individualising care in severe bronchopulmonary dysplasia: a series of N-of-1 trials comparing transpyloric and gastric feeding.

Objective: Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia.

Design: N-of-1 multiple crossover trials with individual patient and pooled data analyses.

Setting: Level IV intensive care nursery.

Changes In Physician Consolidation With The Spread Of Accountable Care Organizations.

While early evidence suggests that accountable care organizations (ACOs) are associated with higher quality and lower costs, there have been simultaneous concerns that ACOs may incentivize consolidation of physician groups. This is particularly concerning as previous research has shown that consolidation is associated with lower quality and higher prices. Using a difference-in-differences strategy and data from the Medicare Shared Savings Program, which began in 2012, we examined whether physician practices consolidated after ACOs entered health care markets.

Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines?

Background: Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations.

Comparing Outcomes and Costs of Surgical Patients Treated at Major Teaching and Nonteaching Hospitals: A National Matched Analysis.

Objective: To compare outcomes and costs between major teaching and nonteaching hospitals on a national scale by closely matching on patient procedures and characteristics.

Background: Teaching hospitals have been shown to often have better quality than nonteaching hospitals, but cost and value associated with teaching hospitals remains unclear.

Methods: A study of Medicare patients at 340 teaching hospitals (resident-to-bed ratios ≥ 0.

Comparison of Neonatal Intubation Practice and Outcomes between the Neonatal Intensive Care Unit and Delivery Room.

Background: Characteristics of neonatal tracheal intubations (TI) may vary between the neonatal intensive care unit (NICU) and delivery room (DR). The impact of the setting on TI outcomes is not well characterized.

Objective: The aim of this study was to define variation in neonatal TI practice between settings, and identify the association between setting and TI success and safety outcomes.

How Should Schools Respond to Learners' Demands for Global Health Training?

In the past decade, more students than ever entered medical school with the desire, if not the expectation, of participating in meaningful global health experiences. Schools must now weigh benefits to students of global experiences against burdens of students' learning experiences on institutions and individuals with whom schools partner. Most often, global health training is done as offsite immersion rotations in research or clinical settings.

A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction.

Background: Phenotypic heterogeneity and complicated gene–environment interplay in etiology are among the primary factors that hinder the identification of genetic variants associated with cocaine use disorder.

Methods: To detect novel genetic variants associated with cocaine use disorder, we derived disease traits with reduced phenotypic heterogeneity using cluster analysis of a study sample (n = 9965). We then used these traits in genome-wide association tests, performed separately for 2070 African Americans and 1570 European Americans, using a new mixed model that accounted for the moderating effects of 5 childhood environmental factors.

Excessive daytime sleepiness and topographic expansion of Lewy pathology.

Objective: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up.

Methods: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men.

The Utility of DXA Assessment at the Forearm, Proximal Femur, and Lateral Distal Femur, and Vertebral Fracture Assessment in the Pediatric Population: 2019 ISCD Official Position.

Dual-energy X-ray absorptiometry (DXA) is widely used in the evaluation of bone fragility in children. Previous recommendations emphasized total body less head and lumbar spine DXA scans for clinical bone health assessment. However, these scan sites may not be possible or optimal for all groups of children with conditions that threaten bone health.

Prevalence of Left Ventricular Systolic Dysfunction in Myotonic Dystrophy Type 1: A Systematic Review.

Cardiac involvement is recorded in about 80% of patients affected by myotonic dystrophy type 1 (DM1). The prevalence of cardiac conduction abnormalities and arrhythmias has been well described. Data regarding the prevalence of left ventricle systolic dysfunction (LVSD) and heart failure (HF) are still conflicting.

A single-center SCN8A-related epilepsy cohort: clinical, genetic, and physiologic characterization.

Objective: Pathogenic variants in SCN8A, encoding the voltage-gated sodium (Na+) channel α subunit Nav1.6, is a known cause of epilepsy. Here, we describe clinical and genetic features of all patients with SCN8A epilepsy evaluated at a single-tertiary care center, with biophysical data on identified Nav1.