Faculty Bibliography

OBJECTIVE/UNASSIGNED:Prior clinical findings have demonstrated that maternal laparotomy with trans-amniotic trans-uterine suturing of the fetoscopic port site during in utero myelomeningocele repair reduces the risk of membrane rupture. However, due to laparotomy-associated morbidity, we aimed to explore the feasibility of using a vascular closure device for percutaneous trans-amniotic trans-uterine suturing. METHODS/UNASSIGNED:cannula over the same guidewire. Samples of the sutured uterine wall were sent to pathology and H&E staining was performed to assess uterine hole closure and amnion-to-uterus fixation. RESULTS/UNASSIGNED:device effectively sutured the amnion to the uterus in both the pre- and post-close approach. The pre-close technique achieved better amnion-to-uterus approximation and more appropriate uterine hole closure. H&E staining revealed that without suturing, amnion separation from the chorion layer occurred, and the uterine hole persisted. The post-close technique showed partial connection between the amnion and chorion, but inadequate uterine hole closure with amnion shift into the defect. Optimal closure, with secure amnion-to-chorion fixation and uterine closure, was achieved through the pre-close technique. CONCLUSION/UNASSIGNED:Device seems to be a feasible device for use of uterine port closure in maternal-fetal surgery, larger animal studies with mid-pregnancy application are needed to further validate or refute these findings.

Aqueductal stenosis is a specific type of non- communicating hydrocephalus, which is characterized by narrowing or constriction of the cerebral aqueduct, also known as the aqueduct of Sylvius. Due to the blockage, the flow of cerebrospinal fluid (CSF) through the aqueduct becomes restricted or obstructed, leading to an abnormal accumulation of CSF within the ventricles and increased intracranial pressure. Progressive expansion of the ventricles leads to increasing cerebral mantle compression during fetal brain development, which can lead to irreversible damage with deleterious consequences. Early intervention could be crucial to mitigate the risk of subsequent cerebral injury. However, diagnostic challenges, unclear efficacy and frequent complications have hindered the integration of treatment for prenatal hydrocephalus into standard practice. Factors including improper patient selection, inadequate CSF diversion or fetal access techniques and suboptimal timing of intervention have been shown to impede success. To address these limitations and advance patient care, an evidence-based update of prenatal hydrocephalus interventions is warranted. This review aims to comprehensively explore the approaches to prenatal treatment of hydrocephalus from both a neurosurgical and fetal surgical perspective, integrating the latest advancements in prenatal diagnosis and fetal intervention. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVE:Fetal surgery (FS) for spina bifida (SB) repair improves infant outcomes; however, spontaneous preterm birth (sPTB) is common. We aimed to evaluate maternal and fetal immune responses following FS for SB repair. METHOD:Pregnant participants undergoing fetoscopic SB repair at 24-26 weeks of gestational age (GA) were prospectively recruited and compared to GA matched low-risk controls. Blood samples were collected at baseline, 2-week post-surgery (POD14), and delivery. Cytokine analysis, flow cytometry, and T cell receptor (TCR) sequencing were performed. RESULTS:sPTB occurred in 5/6 of the FS group (0/6 of controls). Maternal blood in the FS group demonstrated increased alpha-fetoprotein (AFP) and anti-inflammatory IL-1RA at baseline and POD14, increased pro-inflammatory IL-8 only post-operatively, and elevated growth factors throughout. T cell phenotypes following FS revealed reduced TH17 frequency but increased activation receptors on cytotoxic T cells. At delivery, the FS cohort had reduced Th2 and Th17 helper T cells and CD4+ memory T cells, but CD8 T cells still showed increased activation. No TCR expansion was detected post-surgery, suggesting antigen-independent activation. Cord blood in FS repaired neonates had increased AFP, IL-8, IL-1RA. CONCLUSION:Systemic immune changes following FS, particularly T cell maturation and activation, were observed. Further characterization of these mechanisms may help predict and prevent surgery-induced PTB, improving outcomes.

Cerebrovascular dysfunction is associated with risk and progression of Alzheimer's disease, but the extent to which it promotes Alzheimer's pathophysiology is unclear. Understanding the relationship between cerebrovascular dysfunction and Alzheimer's disease markers in midlife is critical to inform our understanding of the earliest manifestations of the disease and prevention strategies. We examined the association of cerebral blood flow with two biomarkers of tau pathophysiology, plasma phosphorylated tau 181 (p-tau181) concentrations and tau PET MK6240 standard uptake value ratio. This was a cross-sectional study of participants in the Offspring Study in upper Manhattan. Analyses included arterial spin labelling MRI, plasma p-tau181 concentration and 18F-MK-6240 tau PET data in the entorhinal cortex. Four hundred and fifty-nine participants (54.8 ± 10.8 years old, 63.3% women) had available MRI and plasma p-tau181 data, and 98 (60.4 ± 5.8 years old, 61.2% women) had additional tau PET data. Lower cerebral blood flow was associated with both higher plasma p-tau181 concentration and entorhinal cortex tau standard uptake value ratio. Higher plasma p-tau181 levels were associated with small clusters of lower regional cerebral blood flow, primarily in regions that correspond to sites of early Alzheimer's disease pathology. Higher tau PET levels were associated with lower cerebral blood flow throughout the brain. These findings suggest that there is relationship between cerebral blood flow and indicators of tau pathophysiology in middle age that is likely bidirectional.

Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. Although the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model, and a nitrofen rat model, we investigated whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing. We showed that CDH in humans and lambs caused defective alveolar epithelial differentiation manifested by more alveolar epithelial type II (ATII) cells, fewer ATI cells, and the emergence of cells coexpressing ATI and ATII markers. Associated with these alveolar epithelial defects, we found a decrease in the level and nuclear localization of YAP. Reduced YAP and abnormal distal lung development were evident as early as 21 weeks of gestation in human CDH. In addition, rat fetuses with CDH also showed diminished nuclear YAP and more abundant ATII cells. In contrast, the littermates without the hernia had no such alveolar phenotypes. Furthermore, fetal tracheal occlusion in the surgical lamb model of CDH fully normalized nuclear YAP and rescued alveolar epithelial defects in a gestational age-dependent manner. Taken together, our findings across species indicate that lung compression in CDH is sufficient to disrupt alveolar epithelial differentiation and impair YAP signaling. Tracheal occlusion can restore nuclear YAP and rescue the alveolar defects in CDH, depending on the timing and the duration of this prenatal surgical intervention.

OBJECTIVE:Membrane damage at or near the uterine entry site is a prevalent complication of fetal surgery and may result in chorioamniotic separation (CAS), preterm prelabor rupture of membranes (PPROM) and preterm birth. Transamniotic transuterine suturing approaches offer the potential to reduce the prevalence of CAS and PPROM accompanying fetoscopy, with the overarching aim of reducing preterm birth. This study aimed to explore the feasibility and potential efficacy of employing a novel vascular closure device for transamniotic transuterine suturing in a sheep model of fetoscopic surgery. METHODS:This study employed a pregnant sheep model to simulate fetal surgery and was conducted between December 2023 and February 2025. We used multiple methodologies to evaluate the Abbott Perclose™ vascular closure device for suturing membranes at the uterine entry site before or after the insertion of a 12-French outer diameter cannula. Feasibility was defined as successful suture placement by two independent surgical teams at two different gestational ages. Potential efficacy was demonstrated by the watertight closure of the entry site during in-vivo gross examination, along with organizing fibrosis and healing of membranes and myometrium, as assessed by postdelivery histopathological evaluation. The procedures were conducted in two phases during the sheep's gestation. Three approaches were used for abdominal entry to access the uterus: midline laparotomy and direct uterine entry; 2-cm mini laparotomy allowing access to the uterus; and a percutaneous approach. Histopathological examination of samples from the entry sites was conducted using routine microscopy, trichrome staining and immunohistochemistry for Connexin 43 (Cx43). This study was approved by the Institutional Animal Care and Use Committee (AN-2010). RESULTS:Ten pregnant sheep were included in this study, four of which had a twin pregnancy. The median gestational age at the occurrence of the first and second rounds of intervention was 85.5 and 104 days, respectively. Overall, 32 Perclose devices were used, and 75% (24/32) were placed successfully. Watertight closure of all sutures was observed during the first and second rounds of intervention, at Cesarean delivery and in situ. Histopathological examination confirmed organizing fibrosis surrounding the device entry site, in addition to overexpression of Cx43. CONCLUSIONS:Employing multiple orthogonal approaches, we have shown for the first time that the Perclose device is both feasible and potentially efficacious as a novel means of uterine port closure in our preclinical sheep model of fetoscopic surgery. Inspired by our success in this preclinical model, we anticipate that clinical validation studies will provide translational data and a direct means of measuring efficacy in the reduction of CAS, PPROM and preterm birth. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Although guidelines exist for the evaluation of serious bacterial infections in febrile young infants, these infections are less likely to be considered in those who are afebrile. We discuss the case of an afebrile, well-appearing, previously healthy 5-week-old girl who presented with left knee swelling and was found to have an Escherichia coli urinary tract infection complicated by E coli septic arthritis. This case underscores the importance of considering serious bacterial infections in afebrile, well-appearing infants less than 2 months old and maintaining a low threshold for diagnostic testing. Furthermore, this case highlights a unique pathophysiology of septic arthritis from a urinary source, emphasizing the need for providers to consider urine testing in cases of young infants with septic arthritis.

OBJECTIVE:The objective of this study was to describe the technical aspects and postnatal neurosurgical outcomes of a prenatal, 3-miniport fetoscopic myelomeningocele (MMC) repair technique providing a multilayered closure using cryopreserved decellularized human umbilical cord (HUC) matrix allograft for duraplasty. METHODS:The authors conducted a subanalysis of an ongoing prospective cohort study analyzing the neurosurgical outcomes of 57 of 92 consecutive patients who underwent multilayered fetoscopic surgical MMC repair using HUC matrix allograft for duraplasty at their institution from December 2016 to March 2022, including more than 24 months of postnatal follow-up. RESULTS:Of 92 patients who underwent fetoscopic MMC repair, 88 had duraplasty using cryopreserved HUC matrix allograft. Fifty-seven patients had at least 24 months of follow-up data. The mean gestational age at the time of surgical repair was 24.8 ± 0.7 weeks. The average operative time from skin incision to closure was 260 ± 43.4 minutes, in which 79% of this time was used for the fetoscopic portion. No patient required intraoperative emergency delivery. At birth, there were no cases of CSF leak or complete wound dehiscence. Six (11.5%) of 52 patients experienced superficial wound dehiscence, and only 2 (3.5%) required surgical revision. At 30 months, 54.8% of patients were noted to be independent ambulators, 35.5% were therapeutic ambulators, and 9.7% remained wheelchair users in this subset of patients. The rate of hydrocephalus requiring CSF diversion was 35.3%, and 84.3% of patients had complete reversal of hindbrain herniation at birth. Eight (15.7%) of 51 patients had spinal inclusion cysts noted on routine follow-up spinal imaging, but only 2 (3.9%) required surgical intervention due to radiological progression without neurological symptoms. CONCLUSIONS:A laparotomy-assisted, 3-miniport fetoscopic approach for prenatal MMC multilayered repair offers excellent access and visualization for an effective watertight closure. The use of HUC matrix allograft as a dural substitute was shown to be effective with a low rate of neurosurgical postnatal complications.