A Multi-Institutional Study of Magnetic Resonance/Ultrasound Fusion-Guided Nanoparticle-Directed Focal Therapy for Prostate Ablation.

Purpose: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa.

Elevating Lower Extremity Reconstruction: An Algorithmic Approach to Free Flap Re-elevation.

Background:  Free flap (FF) reconstruction is frequently required for soft-tissue coverage after significant orthopaedic trauma of the lower extremity (LE). While usually the final step in limb salvage, re-elevation of the previously inset FF may be necessary to restore a functional limb. In this study, we present our algorithm for LE FF re-elevation and review our experience to identify factors associated with successful limb salvage and return to ambulation.

Principles and Practice in Pediatric Vascular Trauma: Part 1: Scope of Problem, Team Structure, Multidisciplinary Dynamics, and Solutions.

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For the patients who initially survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and additionally trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells.

Principles and Practice in Pediatric Vascular Trauma: Part 2: Fundamental Vascular Principles, Pediatric Nuance, and Follow-up Strategies.

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For those patients who survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly.

Causes of Death and Mortality Trends in Individuals with Thalassemia in the United States, 1999-2020.

Purpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US).

Patients And Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level.

Use and utility of C-reactive protein (CRP) in neonatal early-onset sepsis: a secondary analysis of a prospective surveillance study.

Objective: Characterize C-reactive protein (CRP) within 72 postnatal hours in early-onset sepsis (EOS).

Study Design: Secondary analysis of a prospective surveillance study of neonates with EOS 2015-2017. We examined CRP use by center and neonatal characteristics, and CRP levels by time, neonatal characteristics, clinical signs, and pathogen.

Real-time performance improvement optimizes damage control resuscitation best practice adherence: Results of a pilot prospective observational study.

Background: Maintaining balanced blood product ratios during damage control resuscitation (DCR) is independently associated with improved survival. We hypothesized that real-time performance improvement (RT-PI) would increase adherence to DCR best practice.

Study Design And Methods: From December 2020-August 2021, we prospectively used a bedside RT-PI tool to guide DCR in severely injured patients surviving at least 30 min.

Designing Prefaculty Competencies for Diverse Learners Through a Modified Delphi Process.

Importance: Faculty diversity in academic medicine may better prepare the next generation of equity-minded health care practitioners and leaders. Prefaculty development is an emerging concept to support trainees in achieving key knowledge, skills, and experiences to become successful faculty.

Objective: To outline competencies, with corresponding milestones, to support the academic career development of learners, inclusive of racial, ethnic, sexual, and gender identities minoritized in medicine.

Fetal biophysical predictors of pulmonary hypertension severity, management, and treatment in infants born with congenital diaphragmatic hernia.

Background: Pulmonary hypertension (PHTN) causes significant morbidity and mortality in patients with congenital diaphragmatic hernia (CDH). Currently, there is no routinely obtained prenatal prognostic marker to reliably predict postnatal CDH-associated PHTN severity.

Methods: The CDH Study Group (CDHSG) registry was queried for infants born from 2015 to 2021 with a graded (1-4) PHTN diagnosis.

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is characterized by a developmental insult which compromises cardiopulmonary embryology and results in a diaphragmatic defect, allowing abdominal organs to herniate into the hemithorax. Among the significant pathophysiologic components of this condition is pulmonary hypertension (PH), alongside pulmonary hypoplasia and cardiac dysfunction. Fetal pulmonary vascular development coincides with lung development, with the pulmonary vasculature evolving alongside lung maturation.

Natural history study of Pseudoachondroplasia: A focus on oral health.

Background: Pseudoachondroplasia (PSACH) is a rare dwarfing condition characterized by short limbs and fingers, and multiple skeletal abnormalities/complications. There are few natural history studies delineating the medical problems in PSACH leaving a gap in many areas, especially oral health. Our study aimed to obtain information pertaining to oral health and other health-related problems (pregnancy and childbirth, skeletal health, joint pain) in patients with PSACH.

Alcohol and Atrial Fibrillation: An Update and New Perspectives.

In the Western world, sales of alcoholic beverages are skyrocketing. Alcohol (ethanol) is consumed for its transient euphoric effects but is a risk factor for the development of heart disease. Here, we review the possible association between alcohol consumption and atrial fibrillation.

Efficacy of letrozole for the treatment of tubal ectopic pregnancy: A meta-analysis.

Background: Tubal ectopic pregnancy (EP) is a life-threatening condition, especially if undiagnosed or misdiagnosed, tipically in low income countries and/or where women have limited access to health care. The current management protocol of tubal EP consists of either surgical management, or medical management with methotrexate. Recent studies, while few, have suggested that letrozole, an aromatase inhibitor, may play a role in the medical treatment of tubal EP.

Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes.

This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores.

Identification of Hypoxia-ALCAM Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance.

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM macrophages, and exhausted CD8 T cells around the tumor boundary.