Faculty Bibliography

INTRODUCTION/BACKGROUND:Parental refusal of intramuscular (IM) vitamin K in newborns poses challenges, particularly for pediatric urologists assessing the safety of neonatal circumcision. Vitamin K deficiency bleeding (VKDB) is a known risk, with lack of prophylaxis increasing bleeding complications. This study evaluates the safety of neonatal circumcision without IM vitamin K, reviews guidelines, and explores alternative prophylaxis options. OBJECTIVE:To assess if neonatal circumcision can be safely performed on infants lacking IM vitamin K and to identify both optimal timing and alternative prophylactic approaches. METHODS:We conducted a literature review using PubMed and Google Scholar to gather data on neonatal circumcision and VKDB in the context of IM vitamin K refusal. Additionally, we searched for relevant guidelines from the American Urological Association (AUA), American Academy of Pediatrics (AAP), and other organizations. Our study included analysis of ten recent cases of neonatal circumcision without IM vitamin K, focusing on safety outcomes and timing. RESULTS:IM vitamin K is the most effective prophylaxis against VKDB, significantly reducing bleeding risk up to sixfold in neonatal circumcision. Oral vitamin K, sometimes used as an alternative in Europe, shows variable effectiveness and lacks standardization in the U.S. Newborn prothrombin (PT) levels fluctuate significantly in the first week: PT levels are high at birth, drop within 24 h, reach a nadir at 24-72 h, then rebound. Circumcisions performed at 14 days on ten patients without IM vitamin K showed no bleeding complications, suggesting that timing circumcisions after PT stabilization may be safer. CONCLUSIONS:IM vitamin K prophylaxis should remain standard care. In cases of refusal, alternative prophylaxis and timing circumcision after the PT nadir may improve safety. This study underscores the need for updated guidelines from professional organizations, including the AUA, to address the growing trend of IM vitamin K refusal and its implications for neonatal circumcision.

BACKGROUND/UNASSIGNED:Glenoid component positioning is an important and challenging aspect of total shoulder arthroplasty. The use of freehand technique with standard instrumentation or preoperative planning based on 2-dimensional computed tomography (CT) scans provides an opportunity for improvement in terms of component accuracy, precision, and deformity correction. These techniques have produced varying outcomes. METHODS/UNASSIGNED:Preoperative planning software (PPS), patient specific instrumentation (PSI), and intraoperative navigation (NAV) have been developed to improve the accuracy of implant placement and deformity correction with the ultimate goals of improved patient outcomes and implant longevity. Literature search was conducted on published and available studies comparing the accuracy of glenoid component placement and improvements in surgical and patient outcomes amongst the aforementioned techniques. RESULTS/UNASSIGNED:PPS, PSI, and NAV have demonstrated improved accuracy over freehand techniques with standard instrumentation. However, data demonstrating the clinical benefit and cost effectiveness of these new technologies are lacking. DISCUSSION/UNASSIGNED:In this paper, we reviewed the evidence available to answer the question of whether or not advanced shoulder arthroplasty technologies have been beneficial and reviewed future technologies in development such as virtual/mixed-reality and robotic assisted shoulder surgery. LEVEL OF EVIDENCE/UNASSIGNED:4.

BACKGROUND/UNASSIGNED:Spinopelvic mechanics are critical in total hip arthroplasty; however, there is no established consensus for adjusting acetabular component positioning based on spinopelvic parameters. This study aimed to (1) validate a recently developed Patient-Specific acetabular safe-zone calculator that factors in spinopelvic parameters and (2) compare differences with hip-spine classification targets. METHODS/UNASSIGNED:A total of 3750 patients underwent primary total hip arthroplasty across 3 academic referral centers, with 33 (0.88%) requiring revision for instability. Spinopelvic parameters were measured before initial total hip arthroplasty, and acetabular component position was measured following the index and revision procedures. Most operations employed either computer navigation or robotic assistance (94%). Surgical approaches included both anterior and posterior techniques. Utilizing our recently developed patient-specific safe-zone calculator, theoretical intraoperative positions were calculated and compared to true component positions before and after revision. RESULTS/UNASSIGNED:< .001). CONCLUSIONS/UNASSIGNED:A patient-specific approach improved acetabular component positioning accuracy within 6° of version and 4° of inclination of stable, revised hips. Patient-specific safe zones provide quantitative targets for nuanced spinopelvic preoperative planning that may mitigate risk of instability and may indicate use of assisted technologies.

BACKGROUND:The anti-inflammatory and antimicrobial benefits of prebiotics may present an affordable and cost-effective strategy for not only the prevention but also treatment of malnutrition. Therefore, the present trial has been designed with the aim to evaluate the role of prebiotics on the gut microbiome of severe acute malnourished (SAM) children. METHODS:The study is designed as a prospective, double-blinded, triple-armed, multi-centered randomized controlled trial, with 6-59 months old uncomplicated SAM children recruited to the experimental group receiving ready-to-use therapeutic food (RUTF) plus prebiotics and the active comparator group receiving RUTF plus starch for 2 months duration (8 weeks). Healthy children with matching age and gender will be recruited to placebo comparator group and will receive starch as a placebo during the study period. A total of 58 participants will be recruited to each arm with 1:1:1 allocation ratio following a pre-defined inclusion and exclusion criteria. The results of the gut microbiome diversity will serve as the primary outcome, while weight-for-height/length z-score, mid-upper-arm circumference, neurodevelopment assessment, and body mass accumulation will serve as the secondary outcome. Data collection and evaluations will be conducted at baseline and at the end of the trial (week 8), while the safety monitoring will be conducted at every second week. For analysis, the principles of intention-to-treat will be followed. CONCLUSIONS:Conclusively, the results of the present trial would provide useful insights and high-quality data for the treatment and management of SAM children by evaluating the effect of RUTF plus prebiotic on the gut microbiome diversity of children, leading to medical evidence for designing the large-scale studies. TRIAL REGISTRATION/BACKGROUND:The present trial is registered at ClinicalTrials.gov with identifier No: NCT06155474 and registration date 4 December 2023.

Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)-a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited. Here, we performed a neuropathological study examining the colocalization between hnRNP A1, hnRNP A2B1, hnRNP K, and phosphorylated tau in two brain regions (hippocampus and frontal cortex) in six disease groups (Alzheimer's disease, mild cognitive impairment, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and controls). Contrary to expectations, hnRNP A1, hnRNP A2B1, and hnRNP K did not colocalize with AT8-immunoreactive phosphorylated tau pathology in any of the tauopathies examined. However, we did observe significant cellular mislocalization of hnRNP A1, hnRNP A2B1 and hnRNP K in tauopathies, with unique patterns of mislocalization observed for each hnRNP. These data point to broad dysregulation of hnRNP A1, A2B1 and K across tauopathies with implications for disease processes and RNA regulation.

IMPORTANCE/UNASSIGNED:Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). OBJECTIVE/UNASSIGNED:To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. INTERVENTIONS/UNASSIGNED:EVT vs MM. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. RESULTS/UNASSIGNED:A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03876457.

Universal in the United States (US) since 2006, newborn screening (NBS) programs for sickle cell disease (SCD) allow for early identification of the disease and, as an unintentional byproduct, identification of sickle cell trait (SCT). Unlike other carrier states, SCT is highly prevalent and is found in nearly 3 million Americans, which results in important reproductive implications. Currently, all NBS programs in the US are responsible for their own policies regarding SCT notification, and little is known about how SCT notification practices are performed and how these practices vary across NBS programs. We surveyed NBS programs personnel in all 50 states, the District of Columbia, and the US' territories of Puerto Rico and Guam (n = 53) using an electronic survey. There was a 100% response rate. All NBS programs (100%) provide notification of SCT status to either a pediatrician or parent: 49% notify the pediatrician only, 45% notify both the pediatrician and parent, and 6% notify the parent only. A total of 98% of NBS programs retain electronic records of SCT status, but only 38% can be directly accessed by pediatricians/primary care doctors. No state operates a publicly available database that allows individuals to access their own records. Only one state provides renotification at reproductive age. In conclusion, there is wide variability in NBS practices for SCT notification. This study demonstrates a need for national guidelines to standardize SCT notification across the US to ensure effective notification and counseling for SCT.