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.

Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep-wake cycles, hormone secretion, and metabolism. These rhythms are controlled by the brain's suprachiasmatic nucleus, which synchronizes with environmental signals, such as light and temperature, and consequently maintains alignment with the day-night cycle. Molecular feedback loops, driven by core circadian "clock genes", such as Clock, Bmal1, Per, and Cry, are essential for rhythmic gene expression; disruptions in these feedback loops are associated with various health issues. Dysregulated lipid metabolism in the brain has been implicated in the pathogenesis of neurological disorders by contributing to oxidative stress, neuroinflammation, and synaptic dysfunction, as observed in conditions such as Alzheimer's and Parkinson's diseases. Disruptions in circadian gene expression have been shown to perturb lipid regulatory mechanisms in the brain, thereby triggering neuroinflammatory responses and oxidative damage. This review synthesizes current insights into the interconnections between circadian rhythms and lipid metabolism, with a focus on their roles in neurological health and disease. It further examines how the desynchronization of circadian genes affects lipid metabolism and explores the potential mechanisms through which disrupted circadian signaling might contribute to the pathophysiology of neurodegenerative disorders.

PURPOSE/OBJECTIVE:Financial toxicity (FT) is increasingly recognized as a major issue in cancer care. We evaluated the prevalence and risk factors for FT in patients with pancreatic ductal adenocarcinoma (PDAC) and FT associations with treatment adherence and quality of life (QOL). METHODS:A screening questionnaire based on the Comprehensive Score for Financial Toxicity (COST) was implemented at our National Cancer Institute-designated comprehensive cancer center. Respondents with pathologic diagnosis of PDAC who completed >50% of prompts between June 2022 and June 2023 were analyzed. COST ≤16 was categorized as FT. Associations between FT and demographic and clinical factors were assessed using logistic regression, and QOL was assessed using linear regression. RESULTS:= .049). Patients experiencing FT reported worse QOL, with a median score of 5 (IQR, 4-7) versus 8 (IQR, 6-9) without FT. This relationship persisted after adjusting for demographic and clinical factors; the effect size of FT (β = -1.5; 95% CI, -1.1 to -1.9) was nearly double that of poor performance status (β = -.8; 95% CI, -1.3 to -0.4). CONCLUSION/CONCLUSIONS:FT affected nearly one in four patients with PDAC at a high-volume cancer center and was associated with worse QOL and medication nonadherence. Universal screening and interventions to reduce FT are warranted. Clinical trials investigating QOL as an end point must account for potential confounding due to FT.

PURPOSE OF REVIEW/OBJECTIVE:Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM). The purpose of this review is to summarize existing and emerging knowledge around the intersection of statins and these two important clinical problems. RECENT FINDINGS/RESULTS:Since initial reporting of statin-induced hyperglycemia and NODM, the totality of available data corroborates an association between incident diabetes and statin use. A consensus that high-intensity statin and individuals with obesity or glycemic parameters approximating diabetes thresholds constitute the majority of risk exists. Alterations in insulin signaling, glucose transport and gastrointestinal microbiota are leading hypotheses underlying the mechanisms of statin-induced hyperglycemia. The probability of NODM based on an individual's risk factors and statin specific properties can be anticipated. This risk needs to be contextualized with the risk of ASCVD. In order to effectively adjudicate the risk of NODM, improvement in formulating and ultimately conveying a comprehensive ASCVD risk assessment to patients is necessary.

OBJECTIVES/OBJECTIVE:Investigate trends in where patients died of anal cancer in the USA. METHODS:Retrospective cohort study using the US National Center for Health Statistics Wide-Ranging ONline Data for Epidemiologic Research platform from 2003 to 2020; all patients with death certificates listing anal cancer as the underlying cause of death in the USA. Main outcome measure of location of patient death: inpatient facility, home, hospice, nursing home/long-term care facility and other. RESULTS:There were a total of 16 296 deaths with anal cancer as the underlying diagnosis during the study period. The crude rate increased from 0.191 per 100 000 deaths in 2003 to 0.453 per 100 000 deaths in 2020. Over the study period, 22.4% of patient deaths occurred in inpatient facilities, 44.9% at home, 12.2% at hospice facilities and 13.1% at nursing homes/long-term care facilities. The percentage of deaths occurring in hospice facilities increased from 1.0% to 13.3% during the study period. Deaths at home also increased from 42.7% in 2003 to 55.8% in 2020. Meanwhile, inpatient deaths decreased from 33.5% in 2003 to 14.4% in 2020. CONCLUSIONS:There has been a significant increase in the proportion of patients with anal cancer dying at home or hospice from 2003 to 2020.

INTRODUCTION/UNASSIGNED:Balancing surgical margins and functional outcomes is crucial during radical prostatectomy for prostate cancer. Stimulated Raman Histology (SRH) is a novel, real-time imaging technique that provides histologic images of fresh, unprocessed, and unstained tissue within minutes, which can be interpreted by either humans or artificial intelligence. METHODS/UNASSIGNED:Twenty-two participants underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with intraoperative SRH surgical bed assessment. Surgeons resected and imaged surgical bed tissue using SRH and adjusted treatment accordingly. An SRH convolutional neural network (CNN) was developed and tested on 10 consecutive participants. The accuracy, sensitivity, and specificity of the surgical team's interpretation were compared to final histopathological assessment. RESULTS/UNASSIGNED:A total of 121 SRH periprostatic surgical bed tissue (PSBT) assessments were conducted, an average of 5.5 per participant. The accuracy of the surgical team's SRH interpretation of resected PSBT samples was 98%, with 83% sensitivity, and 99% specificity. Intraoperative SRH assessment identified 43% of participants with a pathologic positive surgical margin intraoperatively. PSBT assessment using the CNN demonstrated no overlap in tumor probability prediction between benign and tumor infiltrated samples, mean 0.30% (IQR 0.10-0.43%) and 26% (IQR 18-34%, p<0.005), respectively. CONCLUSION/UNASSIGNED:SRH demonstrates potential as a valuable tool for real-time intraoperative assessment of surgical margins during RALP. This technique may improve nerve-sparing surgery and facilitate decision-making for further resection, reducing the risk of positive surgical margins and minimizing the risk of recurrence. Further studies with larger cohorts and longer follow-up periods are warranted to confirm the benefits of SRH in RALP.

OBJECTIVE:We examined if thyroid autoimmunity is relevant to the relationship between maternal TSH levels and pregnancy outcomes. DESIGN/METHODS:Retrospective cohort analysis of data from two randomized controlled trials (RCTs). SUBJECTS/METHODS:Participants of the Pregnancy in Polycystic Ovary Syndrome (PPCOS II, n = 746) and the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS, n = 832 with unexplained infertility) RCTs. EXPOSURE/METHODS:Pre-trial intervention levels of thyroid stimulating hormone (TSH) at threshold of ≥2.0 mU/L and thyroid peroxidase antibody (TPO-Ab) at titer threshold of ≥30 U/mL. MAIN OUTCOME/RESULTS:Live birth (primary outcome), pregnancy loss and preterm birth (secondary outcomes). Generalized linear model (GLM) analyses examined the relationship between exposure to TSH and TPO-Ab at specified thresholds with the specified outcomes; covariates adjusted for included age, body mass index, race, ethnicity, education, smoking, duration of infertility, PCOS (versus unexplained infertility) and randomized intervention arm in the respective RCTs. RESULTS:On adjusted analyses, live birth was significantly reduced in the exposed population (those with TSH ≥2.0 mU/L and TPO-Ab ≥30 U/mL, n= 117/1578, 7.4%, adjusted risk ratio [ARR] 0.55, 95% CI 0.35- 0.87) compared to the unexposed (those with TSH <2.0 mU/L and TPO-Ab <30 U/mL, n=865/1578, 54.8%). Furthermore, the risk of pregnancy loss and of early preterm birth (<32 weeks) was significantly higher in the exposed compared to the unexposed (ARR for pregnancy loss was 1.66, 95% CI 1.14- 2.42, and ARR for early preterm birth was 4. 82 (95% CI 1.53- 15.19). CONCLUSIONS:In women with TPO-Ab titers ≥30 U/mL, pregnancy outcomes may be compromised at TSH threshold of ≥2 mU/L. These findings of an interaction between TSH and TPO for pregnancy outcomes merit further investigation in prospective studies.

BACKGROUND:General surgery has changed significantly over the last decades, with the need for advanced training and expertise. The Fellowship Council (FC) accredits fellowships that train approximately 200 fellows annually. This study aimed to analyze FC graduates' perceptions of training, current practices, and the job market. METHODS:Data were collected between May 2022 and June 2022 via a survey (SurveyMonkey; Momentive Inc) distributed via email to 2119 previous FC graduates from 2012 to 2021. RESULTS:There were 257 respondents. However, less than half of the respondents (47%) came from surgeons within the first 3 years after training. Of the respondents, 38% had advanced gastrointestinal (GI) minimally invasive surgery (MIS) training, 26% had bariatric surgery training, 14% had foregut surgery training, and the remaining 22% had hepatobiliary, advanced/complex GI, advanced endoscopy, and colorectal surgery training. Most respondents performed acute care surgery (ACS) as part of their training. Of note, 75% of respondents take ACS call, and 55% of respondents do not perform some operations that they trained in during their fellowship. More than 60% of surgeons had difficulty securing employment. CONCLUSION/CONCLUSIONS:Despite niche training, there exists a demand for ACS care. There may be an underutilization of advanced training, or this may reflect how surgeons enter practice and gain experience. The challenge in obtaining employment may be due to the saturation of the market, selectivity of the applicants, or hiring challenges during the COVID-19 pandemic. Most surgeons who undertook FC training practice surgery within their domains of training and with some components of ACS. Despite the desire to hire fellowship-trained surgeons, most FC graduates experience difficulty securing employment.

Microsomal triglyceride transfer protein (MTP) plays crucial roles in the assembly and secretion of apolipoprotein B-containing lipoproteins and loss of function MTP variants are associated with abetalipoproteinemia, a disease characterized by the absence of these lipoproteins. MTP is a heterodimeric protein of two subunits, MTP and protein disulfide isomerase (PDI). In this study, we report a proband with abetalipoproteinemia who was monitored annually over a period of ten years in her third decade and had very low plasma lipids and undetectable apoB-containing lipoproteins. Genetic testing revealed biallelic variants in the MTTP gene. She has a well-documented nonsense mutation Gly865* that does not interact with the PDI subunit. She also has a novel missense MTP mutation, Ile344Asn. We show that this mutation abrogates lipid transfer activity in MTP and does not support apolipoprotein B secretion. This residue is present in the central α-helical domain of MTP and the substitution of Ile with Asn at this position disrupts interactions between MTP and PDI subunits. Ile344 is away from the known MTP:PDI interacting sites identified in the crystal structure of MTP suggesting that MTP:PDI interactions are more dynamic than previously envisioned. Identification of more missense mutations will enhance our understanding about the structure-function of MTP and the role of critical residues in these interactions between the two subunits. This knowledge may guide us in developing novel treatment modalities to reduce plasma lipids and atherosclerosis.

OBJECTIVE: This study aimed to investigate if retroverted (RV) uterus noted on nuchal translucency (NT) ultrasound is associated with second-trimester pregnancy loss and other adverse pregnancy outcomes. STUDY DESIGN/METHODS:-value <0.05 denoting significance. Multivariable logistic regression was used to adjust for possible confounding variables. RESULTS: = 0.0056). No other differences in adverse outcomes were observed. CONCLUSION/CONCLUSIONS: Persistent RV uterus in the first trimester is associated with increased risk of first-trimester vaginal bleeding. However, rates of pregnancy loss were similar between groups, providing valuable information for patient counseling. Significantly more RV subjects conceived by IVF, highlighting the need for further study in this population. KEY POINTS/CONCLUSIONS:· Pregnancy outcomes of patients with retroverted uterus have not been widely studied.. · Significantly more patients with a retroverted uterus conceived by in vitro fertilization.. · Patients with retroverted uterus were four times more likely to have first-trimester bleeding.. · Despite increased rates of vaginal bleeding, there was no increased rate of pregnancy loss..