The Universal Vital Assessment (UVA) score at 6 hours post-resuscitation predicts mortality in hospitalized adults with severe sepsis in Mbarara, Uganda.

Sepsis is the leading cause of global death with the highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score is a validated resource-appropriate clinical tool to identify hospitalized patients in sSA who are at risk of in-hospital mortality. Whether a decrease in the UVA score over 6 hours of resuscitation from sepsis is associated with improved outcomes is unknown.

A randomized-controlled trial of parent-administered interventions to improve short-term motor outcomes in hospitalized very low birthweight infants.

Background: Premature infants are at increased risk for cerebral palsy (CP). Early interventions with a motor focus and administered by parents may improve motor outcomes.

Aims: Secondary study evaluating the short-term motor outcomes and risk for CP in very low birthweight (VLBW) infants randomized to multimodal interventions with a motor focus provided by parents versus usual care.

Measuring Disparities in the Impact of COVID-19 on Pediatric Mental Health in Primary Care Settings.

Objectives: To examine disparities in mental health diagnosis, depression screening, and depressive symptoms in pediatric primary care settings before and during the COVID-19 pandemic, and to evaluate the use of electronic health records to study temporal trends in pediatric mental and behavioral health (MBH).

Methods: This is an IRB-approved, retrospective study of pediatric patients (n=10,866) who visited three primary care sites at an academic medical center before (2017-2019) and during (2020-2022) the COVID-19 pandemic. We used logistic regression to compare rates of diagnoses, depression screening, and depression symptom scores among demographic groups.

Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis.

Background: Sleep disturbance in MS is common and can significantly impair overall quality of life. The ketogenic diet (KD) associates with improved sleep quality in people living with epilepsy and may have similar benefits when used within MS; however, the impact of a KD on sleep in this population remains poorly defined.

Methods: Forty-five patients with relapsing MS enrolled into a 6-month KD intervention trial and completed self-reported assessments of sleep quality and sleep disorder symptoms prior to diet initiation and while on diet, using the Epworth Sleepiness Scale (ESS) and Sleep Disorders Symptom Checklist-25 (SDS).

A model-assisted design for partially or completely ordered groups.

This paper proposes a trial design for locating group-specific doses when groups are partially or completely ordered by dose sensitivity. Previous trial designs for partially ordered groups are model-based, whereas the proposed method is model-assisted, providing clinicians with a design that is simpler. The proposed method performs similarly to model-based methods, providing simplicity without losing accuracy.

The Rise and Fall of Well-Controlled Blood Pressure: Labile Hypertension Following Repair of a Ruptured Abdominal Aortic Aneurysm.

Hypertension is a common pathology with several etiologies. If left uncontrolled, severe and even fatal complications can develop, including heart disease, vascular damage, and stroke. Primary hypertension is most commonly seen without an underlying etiology; however, several contributing factors can lead to the development of hypertension.

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

Background And Objectives: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH.

Measuring treatment adverse event burden in myasthenia gravis: Single-center prospective evaluation utilizing the Adverse Event Unit (AEU).

Introduction/aims: We developed a patient- and physician-weighted consensus unit called the adverse event unit (AEU) that quantifies and compares adverse event (AE) burden among any group of medications in neurological patients. In this study we evaluated preliminary validity and feasibility of measuring AE burden with the AEU in myasthenia gravis (MG).

Methods: This is a single-center, prospective, 1-year, observational study of adult MG patients presenting for routine care between April 1, 2021 and March 31, 2022.

Regadenoson for the treatment of COVID-19: A five case clinical series and mouse studies.

Background: Adenosine inhibits the activation of most immune cells and platelets. Selective adenosine A2A receptor (A2AR) agonists such as regadenoson (RA) reduce inflammation in most tissues, including lungs injured by hypoxia, ischemia, transplantation, or sickle cell anemia, principally by suppressing the activation of invariant natural killer T (iNKT) cells. The anti-inflammatory effects of RA are magnified in injured tissues due to induction in immune cells of A2ARs and ecto-enzymes CD39 and CD73 that convert ATP to adenosine in the extracellular space.

Ketogenic diet in relapsing multiple sclerosis: Patient perceptions, post-trial diet adherence & outcomes.

Background: Ketogenic diets (KDs) are safe and tolerable in people with multiple sclerosis (MS). While many patient-reported and clinical benefits are noted, the sustainability of these diets outside of a clinical trial is unknown.

Aims: Evaluate patient perceptions of the KD following intervention, determine the degree of adherence to KDs post-trial, and examine what factors increase the likelihood of KD continuation following the structured diet intervention trial.

Serum neurofilament light chain in relapsing multiple sclerosis patients on a ketogenic diet.

Background: Ketogenic diets have anti-inflammatory and neuroprotective properties which make these diets an attractive complimentary treatment approach for patients living with multiple sclerosis (MS). The objective of this study was to assess the impact of ketogenic diets on neurofilament light chain (NfL), a biomarker of neuroaxonal injury.

Methods: Thirty-nine subjects with relapsing MS completed a 6-month ketogenic diet intervention.

Regadenoson Reduces Soluble Receptor for Advanced Glycation End-Products in Lung Recipients.

Background: The selective adenosine A2A receptor (A2AR) agonist regadenoson reduces inflammation due to lung ischemia-reperfusion injury (IRI). The objective of this study was to investigate molecular and cellular mechanisms by which regadenoson reduces IRI in lung transplant recipients.

Methods: Fourteen human lung transplant recipients were infused for 12 hours with regadenoson and 7 more served as untreated controls.

Evidence That Binding of Cyclic GMP to the Extracellular Domain of NKA (Sodium-Potassium ATPase) Mediates Natriuresis.

Background: Extracellular renal interstitial guanosine cyclic 3',5'-monophosphate (cGMP) inhibits renal proximal tubule (RPT) sodium (Na) reabsorption via Src (Src family kinase) activation. Through which target extracellular cGMP acts to induce natriuresis is unknown. We hypothesized that cGMP binds to the extracellular α1-subunit of NKA (sodium-potassium ATPase) on RPT basolateral membranes to inhibit Na transport similar to ouabain-a cardiotonic steroid.

Isotonic design for phase I cancer clinical trials with late-onset toxicities.

This article addresses the problem of identifying the maximum tolerated dose (MTD) in Phase I dose-finding clinical trials with late-onset toxicities. The main design challenge is how best to adaptively allocate study participants to tolerable doses when the evaluation window for the toxicity endpoint is long relative to the accrual rate of new participants. We propose a new design framework based on order-restricted statistical inference that addresses this challenge in sequential dose assignments.

Standardizing Prostaglandin Initiation in Prenatally Diagnosed Ductal-Dependent Neonates; A Quality Initiative.

Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE.

Transcatheter Occlusion of Left-To-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia.

Introduction: Patent ductus arteriosus (PDA) and atrial septal defects (ASDs) cause pulmonary overcirculation, potentially worsening bronchopulmonary dysplasia (BPD) in premature infants. Transcatheter device occlusion of these defects is feasible and safe, though no case-controlled studies have assessed respiratory outcomes in infants with BPD. We hypothesized infants with BPD and ASDs or PDAs would experience improved respiratory outcomes following device occlusion of these lesions as compared to those who did not.

Collateral status, hyperglycemia, and functional outcome after acute ischemic stroke.

Background: Mixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial.

Methods: In this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment.

Gastrostomy tube placement in congenital cardiac surgery: a multi-institutional database study.

Introduction: Neonates and infants who undergo congenital cardiac surgery frequently have difficulty with feeding. The factors that predispose these patients to require a gastrostomy tube have not been well defined. We aimed to report the incidence and describe hospital outcomes and characteristics in neonates and infants undergoing congenital cardiac surgery who required gastrostomy tube placement.

Ceramide nanoliposomes augment the efficacy of venetoclax and cytarabine in models of acute myeloid leukemia.

Despite several new therapeutic options for acute myeloid leukemia (AML), disease relapse remains a significant challenge. We have previously demonstrated that augmenting ceramides can counter various drug-resistance mechanisms, leading to enhanced cell death in cancer cells and extended survival in animal models. Using a nanoscale delivery system for ceramide (ceramide nanoliposomes, CNL), we investigated the effect of CNL within a standard of care venetoclax/cytarabine (Ara-C) regimen.

Morphological integration of the hominoid postcranium.

Previous research has suggested that magnitudes of integration may be distinct in the postcranium of hominoids when compared to other primate species. To test this hypothesis, we estimated and compared magnitudes of integration of eight postcranial bones from three-dimensional surface scans for 57 Hylobates lar, 58 Gorilla gorilla, 60 Pan troglodytes, 60 Homo sapiens, 60 Chlorocebus pygerythrus, and 60 Macaca fascicularis. We tested the hypotheses that 1) magnitudes of integration would be distinct in the postcranium of hominoids compared to cercopithecoids, with the explicit prediction that magnitudes of integration would be lower in hominoids than in cercopithecoids, and 2) girdle elements (scapula, os coxa) would have lower magnitudes of integration across all taxa.

An effect size for comparing the strength of morphological integration across studies.

Understanding how and why phenotypic traits covary is a major interest in evolutionary biology. Biologists have long sought to characterize the extent of morphological integration in organisms, but comparing levels of integration for a set of traits across taxa has been hampered by the lack of a reliable summary measure and testing procedure. Here, we propose a standardized effect size for this purpose, calculated from the relative eigenvalue variance, .

Pharmacokinetic-Pharmacodynamic Determinants of Clinical Outcomes for Rifampin-Resistant Tuberculosis: A Multisite Prospective Cohort Study.

Background: Rifampin-resistant and/or multidrug-resistant tuberculosis (RR/MDR-TB) treatment requires multiple drugs, and outcomes remain suboptimal. Some drugs are associated with improved outcome. It is unknown whether particular pharmacokinetic-pharmacodynamic relationships predict outcome.