Transamniotic Delivery of Coagulation Factor VIII mRNA: A Step Toward a Potential Novel Strategy for the Perinatal Management of Hemophilia A.

Hemophilia A is an X-linked monogenic disease resulting in insufficient pro-coagulant factor VIII (FVIII) levels. Hemophiliac infants are at risk for life-threatening hemorrhage, especially during birth. No perinatal treatment for Hemophilia A is currently available.

Sustained early postnatal humoral and cellular immunity against human cytomegalovirus after transamniotic fetal mRNA vaccination in a rodent model.

Purpose: We sought to examine the humoral and cellular immune responses to transamniotic fetal mRNA vaccination against a human cytomegalovirus (hCMV) antigen over time in early postnatal life in a rodent model.

Methods: Seven pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 82) of a custom-made mRNA encoding for hCMV envelope glycoprotein-B (hCMV-gB) antigen encapsulated by a lipid-polymer composite on gestational day 17 (E17; term = E21-22). At three time points between 1 and 3 months after birth, serum levels of antigen-specific hCMV-gB IgG antibodies were measured by ELISA.

Transamniotic fetal delivery of recombinant human immunoglobulin monoclonal antibodies: A potential novel strategy for prevention of neonatal respiratory syncytial virus (RSV) disease.

Purpose: Modified monoclonal class-G immunoglobulins (IgG) have been shown to protect infants from respiratory syncytial virus (RSV), a prevalent disease with particularly high morbidity in newborns. We sought to determine whether a clinically relevant monoclonal IgG against RSV could be delivered to the fetus via transammiotic fetal immunotherapy (TRAFIT) and remain bioavailable after birth.

Methods: Fetuses (n = 75) from five pregnant dams received volume-matched intra-amniotic injections on gestational day 17-18 (E17-18, term = E21-22) of either an FDA approved and commercially available recombinant human immunoglobulin-G1-kappa (IgG1κ) monoclonal antibody against RSV (Nirsevimab®) (n = 30) or of saline (n = 45), the latter to control for possible IgG1κ interspecies homology.

Peripapillary hyperreflective ovoid mass-like structures before and after intracranial decompression: a longitudinal cohort study.

Purpose: To appraise the association of peripapillary hyperreflective ovoid mass-like structures (PHOMS) with the need for intracranial pressure (ICP) decompression surgery, and to study the impact of decompression surgery on the persistence of PHOMS.

Design: Retrospective longitudinal cohort study.

Subjects: Patients with syndromic craniosynostosis evaluated at Boston Children's Hospital (2010 - 2023) who had a minimum of two consecutive optic nerve volume scans.

Atrioventricular Inflow and Subsequent Ventricular Growth After Staged Ventricular Recruitment for Unbalanced Atrioventricular Canal Defect.

Background: In patients with unbalanced atrioventricular canal (uAVC) defect, the hypoplastic ventricle grows variably after staged ventricular recruitment, which involves atrial septation without ventricular septal defect closure. We hypothesized that the atrioventricular inflow size into the hypoplastic ventricle after recruitment correlates with ventricular growth.

Methods: This single-institution retrospective review included 53 patients who underwent staged ventricular recruitment for uAVC between 2011 and 2024.

Neo-aortic valve regurgitation and root dilation after arterial switch operation in patients with native left ventricular outflow tract obstruction.

Objective: To assess risk factors for neo-aortic insufficiency (AI) after the arterial switch operation (ASO) or double-switch operation (DSO) for transposition of the great arteries (TGA) beyond the neonatal period. We hypothesized that native left ventricular outflow tract obstruction (nLVOTO) without prior pulmonary artery banding (PAB) increases the risk of neo-AI-related reoperation.

Methods: This retrospective review included 157 patients (excluding neonates) with D- or L-TGA who underwent ASO (n = 47) or DSO (n = 110) between 2011 and 2024.

Overactive Bladder Symptoms in Cancer Patients Undergoing Chemotherapy.

Objectives: To determine if chemotherapy contributes to the development of overactive bladder (OAB) in female cancer patients.

Methods: A prospective, longitudinal study was conducted from 2017 to 2023 at Mount Auburn Hospital to assess the effects of chemotherapy on the development of OAB. Sixty-five female patients diagnosed with nonmetastatic breast cancer, lung cancer, or lymphoma were asked to complete 5 validated questionnaires regarding bladder symptoms just before starting chemotherapy and again at 6 weeks, 3 months, 6 months, and 12 months.

Tailored preoperative assessment in neonatal cardiac surgery: a European Congenital Heart Surgeons Association study†.

Objectives: Current preoperative counselling in neonatal cardiac surgery is mainly focused on the primary procedure. However, other factors must be considered when evaluating the surgical risk of a neonate. We aimed to develop a risk adjustment model to personalize preoperative counselling using data from the European Congenital Heart Surgeons Association Congenital Database (ECHSA-CD).

Eliminating left ventricular outlet stenosis lowers the risk for endocardial fibroelastosis recurrence†.

Objectives: Patients with endocardial fibroelastosis (EFE) in the setting of congenital critical aortic valve (AoV) stenosis and left ventricular outflow tract obstruction (LVOTO) are at risk for diastolic dysfunction, limiting biventricular circulation. EFE resection is the only available treatment option, but frequently recurs requiring re-resections. We aimed to investigate whether augmentation of a left ventricular outlet stenosis (AoV stenosis ± LVOTO) with a Ross/Ross-Konno procedure prevents EFE recurrence.

Microstructural alterations of the trigeminal ganglion in chronic ocular surface pain patients: A diffusion MRI study.

Noxious stimuli to the ocular surface are encoded by sensory axons of trigeminal ganglion (TG) neurons and conveyed through the ophthalmic branch of the trigeminal nerve (CN V1). We hypothesized that chronic ocular surface pain (COSP) may be associated with microstructural alterations of the trigeminal nerve structures. Our objective was to demonstrate the feasibility of using diffusion tractography to identify and analyze diffusion properties to assess TG microstructure in individuals with and without COSP.

Heightened visual light sensitivity discomfort measured by the ocular photosensitivity analyzer is associated with chronic ocular pain.

Purpose: To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.

Methods: Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.

Clinical Efficacy of Ex Vivo Cross-Linking on Neovascularization of the Donor Cornea Carrier Tissue for the Boston Type I Keratoprosthesis.

Purpose: To evaluate the effect of corneal cross-linking (CXL) on corneal neovascularization (CNV) between eyes that were randomized to receive either CXL or non-CXL donor corneas as the carrier tissue for Boston keratoprosthesis surgery.

Design: A retrospective masked analysis of CNV from slit lamp photographs taken at postoperative weeks 16, 24, 36, and 52.

Subjects: Sixty-eight donor corneas were prospectively randomized 1:1 to receive either donor corneas that underwent ex vivo CXL or were non-CXL.

An endothelial specific mouse model for the capillary malformation mutation Gnaq p.R183Q.

Capillary malformation (CM) is a congenital, non-hereditary lesion composed of enlarged and tortuous blood vessels. CM is associated with a somatic p.R183Q activating mutation in the Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene in endothelial cells (EC).

Identification of vitronectin as a potential non-invasive biomarker of metastatic breast cancer using a label-free LC-MS/MS approach.

Background: Breast cancer (BC) is a complex heterogenous disease that is a leading cause of death in women. For patients with early stage disease following primary BC therapy, approximately 30% will develop metastatic BC (MBC). The median survival of MBC patients is ~ 2-3 yr.

Novel Mammillary Body Manual Segmentation: Application for Quantitative MRI Analysis of Critically Ill Infants.

Background And Purpose: Previous qualitative studies have shown that mammillary body (MB) assessment can serve as an early marker of poor long-term neurodevelopmental outcomes. This study aims to establish a reliable quantitative method for analyzing the surface area, volume, and signal intensity of MB in infancy.

Methods: A novel methodology was retrospectively tested in a cohort of critically ill preterm and term-born patients following esophageal atresia (EA) repair, and healthy term-born controls ( = 13/group) using non-sedated brain MRI on a 3T Siemens scanner.

A Basic Machine Learning Primer for Surgical Research in Congenital Heart Disease.

Artificial intelligence and machine learning are rapidly transforming medicine, healthcare, and surgery. Machine learning is a valuable tool for surgeons and researchers in pediatric cardiovascular and thoracic surgery, with innovative applications constantly evolving and expanding. Utilizing machine learning in addition to traditional statistical methods can gain insights into the data and develop more powerful prediction models for improving surgical management and patient outcomes.

Transamniotic Fetal Delivery of Human Alpha-1 Antitrypsin mRNA in a Healthy Rodent Model.

Alpha-1 antitrypsin deficiency (AATD) can manifest at any age, including the perinatal period. Its manifestations include obstructive lung disease, which can be severe and for which current therapies are of limited benefit. We sought to determine whether the transamniotic route could be a viable alternative for administering AAT mRNA to the fetus.

An endothelial specific mouse model for the capillary malformation mutation Gnaq p.R183Q.

Capillary malformation (CM) is a congenital, non-hereditary lesion composed of enlarged and tortuous blood vessels. CM is associated with a somatic GNAQ p.R183Q activating mutation in endothelial cells (EC).

Combination Automated Microfluidics Measurement of Urine C-C Motif Ligand 2, CXC-Motif Chemokine 9, CXC-Motif Chemokine 10, and Vascular Endothelial Growth Factor A for Monitoring Patients with a Kidney Transplant.

Key Points: Combining urine C-C motif ligand 2, CXC-motif chemokine 9, CXC-motif chemokine 10, and vascular endothelial growth factor A identifies stable transplant recipients without biopsy-proven acute rejection with >75% specificity and 94% negative predictive value. Measuring four urine analytes in combination using an automated platform is highly efficient (<70 minutes) and reproducible across three independent sites. Automated urine analyte measurement provides critical decision support and outperforms eGFR measurements alone for post-transplantation monitoring.

The Natural History of Congenital Hepatic Hemangiomas.

Objective: To characterize the clinical presentation, radiologic and histologic findings, and management options for congenital hepatic hemangioma (HH) with a focus on describing its natural history and rate of involution.

Study Design: Retrospective review of patients in our HH registry with a congenital HH born between 2004 and 2022 was performed. HH volumes were calculated using the formula for an ellipsoid.

Characteristics of two subtypes of nonacute acquired comitant esotropia with distance diplopia.

Purpose: To determine demographic and sensorimotor characteristics of patients with nonacute acquired comitant esotropia with distance diplopia (NACEDD).

Methods: History, demographic, and sensorimotor characteristics of all patients ≥10 years of age presenting with esotropia and gradual-onset distance diplopia at Boston Children's Hospital (2017-2022) were collected. Definition of NACEDD required absence of inflammatory, autoimmune, mechanical, or neurologic causes of strabismus.

Prevalence and Clinical Associations of Peripapillary Hyperreflective Ovoid Mass-like Structures in Craniosynostosis.

Background: Patients with craniosynostosis are at high risk of developing elevated intracranial pressure (ICP) causing papilledema and secondary optic atrophy. Diagnosing and monitoring optic neuropathy is challenging because of multiple causes of vision loss including exposure keratopathy, amblyopia, and cognitive delays that limit examination. Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are an optical coherence tomography (OCT) finding reported in association with papilledema and optic neuropathy.

Transamniotic Delivery of Hematopoietic Stem Cells Genetically Modified to Carry a Human Hemoglobin Subunit Beta Gene (HBB) in a Healthy Rodent Model.

Background: We sought to determine whether transamniotic stem cell therapy (TRASCET) could be a viable alternative for the fetal administration of genetically modified hematopoietic stem cells (HSCs) carrying a human hemoglobin subunit beta gene (hHBB) in a healthy syngeneic rat model.

Methods: Time-dated pregnant Lewis dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 61) of a suspension of donor HSCs genetically modified with either both a hHBB gene and a firefly luciferase reporter gene (n = 42) or the firefly luciferase reporter gene alone to control for HBB-derived protein interspecies homology (n = 19) on gestational day 17 (E17; term = E21). Donor HSCs consisted of syngeneic cells phenotyped by flow cytometry with successful hHBB transduction confirmed by ELISA prior to administration in vivo.

Multicentre analysis of severe perioperative adverse events in children undergoing surgery who were infected with SARS-CoV-2: a propensity score-adjusted analysis.

Background: The incidence of severe adverse events in children with SARS-CoV-2 undergoing anaesthesia has not been well established. We examined the relationship between SARS-CoV-2 infection and severe perioperative adverse events in children.

Methods: This multicentre (21 North American institutions), retrospective cohort study included children <18 years old, with American Society of Anesthesiologists physical status (ASA PS) of 1-4 and non-severe SARS-CoV-2, who underwent general anaesthesia between April 1, 2020, and March 31, 2021.