A Novel Rat Model to Simulate Positive Margins in the Wound Bed of a Resected Sarcoma.

Background: One reason for local recurrence is the presence of positive surgical margins after tumor resection. An animal model accurately representing the microtumor burden will improve our understanding of these surgical margins. Using a rat model, we report a new methodology for creating microscopic tumors.

Editorial Commentary: Combined Anterior Cruciate Ligament/Medial Collateral Ligament Injuries: Surgeons Should Have a Low Threshold to Operate on the Medial Collateral Ligament.

Combined anterior cruciate ligament/medial collateral ligament (ACL/MCL) injuries are relatively common, and multiple factors are involved in surgical decision-making, particularly when it comes to the MCL. Historically, most surgeons treated the MCL conservatively and performed staged MCL reconstruction after MCL reconstruction only if there was persistent medial instability. This was followed by a nonoperative approach for the MCL (when reconstructing the ACL) unless there was evidence of extreme (grade III or >1 cm) valgus instability, valgus malalignment, or mid-substance or tibial-sided injury, avulsion, or Stener lesion.

Nine is the New Ten of Apgar Scores: An Observational Retrospective Cohort Study.

Apgar scores of 10 were once common but are now rare. We aggregated scores from US term infants from 1978 to 2021. We found that scores of 10 decreased by logarithmic decay independent of demographic changes.

The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease.

Objective: GREB1L has been linked prenatally to Potter's sequence, as well as less severe anomalies of the kidney, uterus, inner ear, and heart. The full phenotypic spectrum is unknown. The purpose of this study was to characterize known and novel pre- and postnatal phenotypes associated with GREB1L.

A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.

The utility of gene sequencing in identifying an underlying genetic disorder in prenatally suspected lower urinary tract obstruction.

Objective: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations.

Prevalence and Clinical Significance of Commonly Diagnosed Genetic Disorders in Preterm Infants.

Background And Objectives: Preterm infants (<34 weeks' gestation) experience high rates of morbidity and mortality before hospital discharge. Genetic disorders substantially contribute to morbidity and mortality in related populations. The prevalence and clinical impact of genetic disorders is unknown in this population.

The Contribution of Commonly Diagnosed Genetic Disorders to Small for Gestational Age Birth and Subsequent Morbidity and Mortality in Preterm Infants.

Objective: Preterm infants born small, vs. appropriate for gestational age (SGA, AGA) are at greater risk for morbidity and mortality. The contribution of genetic disorders to preterm SGA birth, morbidity, and mortality is unknown.

Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease.

Background: Rapid genome sequencing (rGS) has been shown to improve care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population.

Methods: We conducted a prospective evaluation of rGS to improve the care of infants with complex CHD in our cardiac neonatal intensive care unit.

Autologous Skin Grafts, versus Tissue-engineered Skin Constructs: A Systematic Review and Meta-analysis.

Unlabelled: For over 100 years, autologous skin grafts have remained the gold standard for the reconstruction of wounds but are limited in availability. Acellular tissue-engineered skin constructs (acellular TCs) and cellular tissue-engineered skin constructs (cellular TCs) may address these limitations. This systematic review and meta-analysis compare outcomes between them.

Virilization of a 46,XX Fetus Following Aromatase Inhibitor Treatment of Breast Cancer.

Virilization of the 46,XX infant may be attributed to maternal or fetoplacental origin. Maternal sources may be endogenous, as with an androgen-producing tumor, or drug-related. Iatrogenic virilization by maternal drug exposure is rarely reported, with individual case reports and case series demonstrating the effects of progesterone and other medications affecting the pituitary-ovarian axis.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.

Early-phase drug discovery of β-III-spectrin actin-binding modulators for treatment of spinocerebellar ataxia type 5.

β-III-Spectrin is a key cytoskeletal protein that localizes to the soma and dendrites of cerebellar Purkinje cells and is required for dendritic arborization and signaling. A spinocerebellar ataxia type 5 L253P mutation in the cytoskeletal protein β-III-spectrin causes high-affinity actin binding. Previously we reported a cell-based fluorescence assay for identification of small-molecule actin-binding modulators of the L253P mutant β-III-spectrin.

An induced pluripotent stem cell-derived NMJ platform for study of the NGLY1-Congenital Disorder of Deglycosylation.

There are many neurological rare diseases where animal models have proven inadequate or do not currently exist. NGLY1 Deficiency, a congenital disorder of deglycosylation, is a rare disease that predominantly affects motor control, especially control of neuromuscular action. In this study, NGLY1-deficient, patient-derived induced pluripotent stem cells (iPSCs) were differentiated into motoneurons (MNs) to identify disease phenotypes analogous to clinical disease pathology with significant deficits apparent in the NGLY1-deficient lines compared to the control.

Rapid joule heating improves vitrification based cryopreservation.

Cryopreservation by vitrification has far-reaching implications. However, rewarming techniques that are rapid and scalable (both in throughput and biosystem size) for low concentrations of cryoprotective agent (CPA) for reduced toxicity are lacking, limiting the potential for translation. Here, we introduce a joule heating-based platform technology, whereby biosystems are rapidly rewarmed by contact with an electrical conductor that is fed a voltage pulse.

The Prevalence and Clinical Significance of Congenital Anomalies of the Kidney and Urinary Tract in Preterm Infants.

Importance: The prevalence and importance of congenital anomalies of the kidney and urinary tract (CAKUT) in preterm infants is unknown.

Objective: To determine the prevalence of CAKUT in preterm infants and association with in-hospital morbidity and mortality.

Design, Setting, And Participants: This cohort study included infants cared for in neonatal intensive care units managed by a large US network of hospitals and doctors.

Negative-Pressure Wound Therapy versus Standard Surgical Dressings after Malignant Tumor Resection: A Systematic Review and Meta-Analysis.

Background: Negative-pressure wound therapy offers many advantages over standard surgical dressings in the treatment of open wounds, including accelerated wound healing, cost savings, and reduced complication rates. Although contraindicated by device manufacturers in malignancy-resected wounds because of hypothesized risk of tumor recurrence, negative-pressure wound therapy is still applied postoperatively because of limited clinical support. The authors performed a systematic review with meta-analysis to compare negative-pressure wound therapy outcomes with those of standard surgical dressings on open wounds, with their null hypothesis stating there would be no outcome differences.

Learning the Language of Medical Device Innovation: A Longitudinal Interdisciplinary Elective for Medical Students.

Problem: Physicians are playing a growing role as clinician-innovators. Academic physicians are well positioned to contribute to the medical device innovation process, yet few medical school curricula provide students opportunities to learn the conceptual framework for clinical needs finding, needs screening, concept generation and iterative prototyping, and intellectual property management. This framework supports innovation and encourages the development of valuable interdisciplinary communication skills and collaborative learning strategies.

Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study.

Background: The aim of the study was to determine the prevalence of congenital anomalies of the kidney and urinary tract (CAKUT) in the neonatal intensive care unit (NICU) and to evaluate risk factors associated with worse outcomes. We hypothesized that infants with CAKUT with extra-renal manifestations have higher mortality.

Methods: This is a cohort study of all inborn infants who were diagnosed with any form of CAKUT discharged from NICUs managed by the Pediatrix Medical Group from 1997 to 2018.

β-III-spectrin N-terminus is required for high-affinity actin binding and SCA5 neurotoxicity.

Recent structural studies of β-III-spectrin and related cytoskeletal proteins revealed N-terminal sequences that directly bind actin. These sequences are variable in structure, and immediately precede a conserved actin-binding domain composed of tandem calponin homology domains (CH1 and CH2). Here we investigated in Drosophila the significance of the β-spectrin N-terminus, and explored its functional interaction with a CH2-localized L253P mutation that underlies the neurodegenerative disease spinocerebellar ataxia type 5 (SCA5).

Outcomes of orthopaedic trauma surgery in COVID-19 positive patients.

Objectives: To investigate outcomes for operative orthopaedic trauma in patients who tested positive for coronavirus disease 2019 (COVID-19) during the height of the COVID-19 pandemic in New York.

Design: Retrospective case series.

Setting: Urban Level-1 academic trauma center.

Cryopreservation method for Drosophila melanogaster embryos.

The development of a widely adopted cryopreservation method remains a major challenge in Drosophila research. Here we report a robust and easily implemented cryopreservation protocol of Drosophila melanogaster embryos. We present innovations for embryo permeabilization, cryoprotectant agent loading, and rewarming.