Clinical and Demographic Factors Linked to Low-Value Emergency Department Visits in Pediatric Patients With Spina Bifida.

Purpose: Identifying factors associated with emergency visits that could be delivered at lower cost sites may help guide population health strategies for pediatric patients with spina bifida.

Materials And Methods: Emergency department encounters (2016-2023) by patients with spina bifida (younger than 18 years) in the Pediatric Health Information System were identified. Absence of clinical and imaging charges was defined as low-value emergency visit.

A Bispecific Modeling Framework Enables the Prediction of Efficacy, Toxicity, and Optimal Molecular Design of Bispecific Antibodies Targeting MerTK.

Inhibiting MerTK on macrophages is a promising therapeutic strategy for augmenting anti-tumor immunity. However, blocking MerTK on retinal pigment epithelial cells (RPEs) results in retinal toxicity. Bispecific antibodies (bsAbs) containing an anti-MerTK therapeutic and anti-PD-L1 targeting arm were developed to reduce drug binding to MerTK on RPEs, since PD-L1 is overexpressed on macrophages but not RPEs.

PEGylation of anti-MerTK Antibody Modulates Ocular Biodistribution.

Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers.

Congenital Anomalies of the Kidneys and Urinary Tract.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are some of the most common abnormalities detected on prenatal imaging assessment. It is estimated that CAKUT comprises 20% to 30% of all major birth defects. More than 200 clinical syndromes currently include CAKUT as a component of the phenotype.

Primary and secondary vaginal reconstruction with autologous buccal mucosa and intravaginal wound vacuum therapy.

Background: Vaginal reconstruction with autologous buccal mucosa graft offers a promising alternative to the use of skin grafts and vascularized intestinal segments. Given the novelty of this procedure, the optimal approach to postoperative wound management remains unclear with current practices often requiring many months of vaginal stents/molds. This study aims to evaluate a newly developed negative pressure intravaginal wound vacuum placed at the conclusion of the vaginoplasty with the goals of facilitating graft take and healing.

Technical Considerations in Primary Repair of a Congenital Prostatic Rectourethral Fistula in an Adult-Sized Patient.

Congenital anorectal malformations are generally diagnosed and repaired as a neonate or infant, but repair is sometimes delayed. Considerations for operative repair change as the patient approaches full stature. We recently encountered a 17-year-old male with an unrepaired congenital rectourethral fistula and detail our experience with his repair.

Structure-Based Design of Potent, Selective, and Orally Bioavailable VPS34 Kinase Inhibitors.

VPS34 is a class III phosphoinositide 3-kinase involved in endosomal trafficking and autophagosome formation. Inhibitors of VPS34 were believed to have value as anticancer agents, but genetic and pharmacological data suggest that sustained inhibition of VPS34 kinase activity may not be well tolerated. Here we disclose the identification of a novel series of dihydropyrazolopyrazinone compounds represented by compound as potent, selective, and orally bioavailable VPS34 inhibitors through a structure-based design strategy.

Reoperative surgery in anorectal malformation patients.

Currently accepted primary repair of congenital anorectal malformations (ARMs) includes a posterior sagittal incision, which allows for optimal visualization and identification of important pelvic structures and anatomical features. Reconstructive surgery involves meticulous dissection and separation of pelvic structures, and careful reconstruction can result in good functional outcomes for many patients, who live without ongoing sequelae from their malformation. However, some patients may require reoperative procedures for anatomic or functional reasons.

Timing and outcomes of testicular torsion during the COVID-19 crisis.

Background: During the COVID-19 crisis, there has been widespread reporting that non-COVID-19-related medical care has been delayed, even for emergent conditions. Testicular torsion is an emergent condition with higher risk of testicular loss with longer ischemic times. We sought to investigate whether patients with testicular torsion had longer time from symptom onset to initial presentation, longer total ischemic time, and higher rate of orchiectomy during the pandemic.

A New Approach to Cloaca: Laparoscopic Separation of the Urogenital Sinus.

Cloaca malformation repair strategy is strongly dictated by common channel and urethral lengths. Mid to long common channel cloacas are challenging and often require laparotomy for dissection of pelvic structures. The balance of common channel and urethral lengths often dictates the approach for reconstruction.

Contrast enhanced colostography: New applications in preoperative evaluation of anorectal malformations.

Introduction: Understanding details of anatomic relationships between the colon and surrounding structures is a critical piece of preoperative planning prior to surgical repair of anorectal malformations (ARMs). Traditional imaging techniques involve ionizing radiation, distention of the rectum with supraphysiologic intraluminal pressures, and sometimes require sedation. Recent developments in the field of contrast agents have allowed the emergence of an ultrasound-based technique that can avoid these requirements while continuing to provide high resolution structural information in three dimensions.

MAP4K4 negatively regulates CD8 T cell-mediated antitumor and antiviral immunity.

During cytotoxic T cell activation, lymphocyte function-associated antigen-1 (LFA-1) engages its ligands on antigen-presenting cells (APCs) or target cells to enhance T cell priming or lytic activity. Inhibiting LFA-1 dampens T cell-dependent symptoms in inflammation, autoimmune diseases, and graft-versus-host disease. However, the therapeutic potential of augmenting LFA-1 function is less explored.

Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP.

Clearance of apoptotic cells by macrophages prevents excessive inflammation and supports immune tolerance. Here, we examined the effect of blocking apoptotic cell clearance on anti-tumor immune response. We generated an antibody that selectively inhibited efferocytosis by phagocytic receptor MerTK.

Case series: Comparison of contrast-enhanced genitosonography (ceGS) to fluoroscopy and cone-beam computed tomography in patients with urogenital sinus and the cloacal malformation.

In this case series, contrast enhanced genitosonography is compared to genitography performed using fluoroscopy and cone-beam computed tomography in patients with urogenital sinus and the cloacal malformation. The method of contrast enhanced genitosonography is described, including contrast preparation, contrast administration, ultrasound imaging approaches, as well as the benefits and potential pitfalls of this technique compared to fluoroscopy and computed tomography.

Expanding the phenotypic spectrum of Mabry Syndrome with novel PIGO gene variants associated with hyperphosphatasia, intractable epilepsy, and complex gastrointestinal and urogenital malformations.

Mabry syndrome is a glycophosphatidylinositol (GPI) deficiency characterized by intellectual disability, distinctive facial features, intractable seizures, and hyperphosphatasia. We expand the phenotypic spectrum of inherited GPI deficiencies with novel bi-allelic phosphatidylinositol glycan anchor biosynthesis class O (PIGO) variants in a neonate who presented with intractable epilepsy and complex gastrointestinal and urogenital malformations.

Further Delineation of Liver Involvement in Girls and Women with Turner Syndrome: Case Report of a 2-Year-Old with Liver Dysfunction and Review of Patients Followed in the MassGeneral Hospital Turner Syndrome Clinic.

Background: Liver function test (LFT) abnormalities, which may reflect underlying pathophysiology, are a well-known feature of Turner syndrome. Less frequently, liver findings may include vascular changes and, rarely, severe liver disease. Although previous studies on children and adolescents suggest a frequency of LFT abnormalities of up to 60%, less is known about the age at onset and natural history.

Autophagy Regulation of Metabolism Is Required for CD8 T Cell Anti-tumor Immunity.

Autophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8 T-cell-mediated control of tumors.

Contrast-Enhanced Colosonography for the Evaluation of Children With an Imperforate Anus.

This case series describes a novel method for showing the preoperative anatomy of children with anorectal malformations using ultrasound contrast, which we have termed "contrast-enhanced colosonography (ceCS)." Six patients with anorectal malformations without a perineal fistula were studied both by fluoroscopic distal colostography and ceCS, and their results were confirmed surgically. Contrast-enhanced CS precisely showed the complex anatomic relationships in all cases.

Chemotherapy Combines Effectively with Anti-PD-L1 Treatment and Can Augment Antitumor Responses.

Immunotherapy with checkpoint inhibitors has proved to be highly effective, with durable responses in a subset of patients. Given their encouraging clinical activity, checkpoint inhibitors are increasingly being tested in clinical trials in combination with chemotherapy. In many instances, there is little understanding of how chemotherapy might influence the quality of the immune response generated by checkpoint inhibitors.

Dual diagnoses in 152 patients with Turner syndrome: Knowledge of the second condition may lead to modification of treatment and/or surveillance.

Turner syndrome is a sex chromosome abnormality in which a female has a single X chromosome or structurally deficient second sex chromosome. The phenotypic spectrum is broad, and atypical features prompt discussion of whether the known features of Turner syndrome should be further expanded. With the advent of clinical whole exome sequencing, there has been increased realization that some patients with genetic disorders carry a second genetic disorder, leading us to hypothesize that a "dual diagnosis" may be more common than suspected for Turner syndrome.