Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Eating disorders can profoundly impact reproductive health in females, spanning from the onset of puberty through menopause. The impact is due to a variety of factors, including nutritional status, body fat percentage, and hormone regulation. Notably, fertility and pregnancy are particularly vulnerable to undernutrition and disordered eating. This narrative review provides a comprehensive summary and discussion of available literature from the past 5 years exploring the impact of eating disorders on fertility, obstetric outcomes, and fetal outcomes. RECENT FINDINGS/RESULTS:Current literature demonstrates that EDs can have a negative impact on fertility, obstetric outcomes, and fetal outcomes. Primary research and systematic reviews support associations including increased use of assisted reproductive treatment for infertility, anemia and hyperemesis during pregnancy, and preterm delivery. Associated fetal outcomes include infant low birth weight, small for gestational age, and microcephaly. EDs, when unrecognized and left untreated, can negatively impact fertility, obstetric outcomes, and fetal outcomes. It is important for providers to be aware of these associations and implement screening to identify at-risk patients, as appropriate treatment can improve reproductive outcomes.

BACKGROUND/UNASSIGNED:For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide the use of AAT augmentation therapy post-LT. METHODS/UNASSIGNED:We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher's exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. RESULTS/UNASSIGNED: = 0.02, log-rank test). CONCLUSIONS/UNASSIGNED:In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.

BACKGROUND:Four-dimensional computed tomography is routinely used to localize parathyroid disease, with consistently excellent parathyroid gland localization rates reported. This study evaluated whether pairing 4-dimensional computed tomography results with preoperative clinical variables can accurately predict single-gland disease in primary hyperparathyroidism. METHODS:Patients with primary hyperparathyroidism who underwent both 4-dimensional computed tomography imaging and parathyroidectomy between January 2019 and September 2021 at a large academic health system were included. Patient demographics, preoperative characteristics, and peri- and postoperative data were collected. The accuracy of 4-dimensional computed tomography in correctly identifying patients with single-gland disease with and without preoperative calcium and parathyroid hormone levels was calculated. Single-gland disease was defined by intraoperative parathyroid hormone decrease >50% and a hypercellular gland on pathology. RESULTS:One hundred seventy-five patients had 4-dimensional computed tomography results suggestive of single gland disease. One hundred fifty-two patients (87%) were predicted correctly to have single-gland disease. The predictive accuracy increased when stratifying by preoperative calcium (≥10.5 mg/dL, ≥11 mg/dL, and ≥12 mg/dL) and parathyroid hormone levels (≥65 pg/mL, ≥100 pg/mL, and ≥200 pg/dL). The accuracy further increased when stratifying by age (≤50 years). Accuracy for single gland disease was 100% when combined with any of the following: (1) calcium ≥12 mg/dL, (2) parathyroid hormone ≥200 pg/dL, or (3) calcium ≥11 mg/dL in patients ≤50 years. CONCLUSION/CONCLUSIONS:Four-dimensional computed tomography alone accurately predicted single gland disease in 87% of patients with primary hyperparathyroidism. When combined with preoperative calcium, parathyroid hormone and age thresholds, predictive accuracy for single-gland disease approached 100%. Given the high likelihood of single-gland disease in these scenarios, clinicians may consider offering focused unilateral parathyroidectomy without intraoperative parathyroid hormone monitoring in selected patients.

BACKGROUND:Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data. METHODS:Safety outcomes within 30 days of histotripsy were collected after obtaining Food and Drug Administration clearance (December 22, 2023 to July 26, 2024). All centers that performed histotripsy were invited to participate in this study. Complications requiring treatment were graded using the Clavien-Dindo classification and Comprehensive Complication Index (CCI). RESULTS:A total of 295 patients underwent histotripsy for 510 tumors at 18 centers. The treated liver tumor types included colorectal metastases (n = 140), neuroendocrine tumors (n = 46), hepatocellular carcinomas (n = 31), pancreatic tumors (n = 30), and breast metastases (n = 26). The most common numbers of tumors treated per procedure were 1 (n = 170), 2 (n = 69), and 3 (n = 37). All 8 liver segments were treated for tumors. Safety data were available for 230 patients from 9 centers. Of note, 12 of 230 patients (5.2%) experienced complications of any grade. Most patients (9 [75%]) had minor cases (Clavien-Dindo grade ≤ II). The median and mean CCIs were 0.00 (IQR, 0.00-0.00) and 0.00 (95% CI, 0.00-0.75). All 3 major complications (Clavien-Dindo grade > II [1.3%]) were death due to disease progression. All 3 patients underwent histotripsy with palliative intent for known advanced intra- and extrahepatic diseases. CONCLUSION/CONCLUSIONS:To the best of our knowledge, this is the first study to report on the real-world therapeutic use of histotripsy for liver tumors. Histotripsy was well tolerated, with few overall complications and rare serious complications, indicating a safety profile that compares favorably with that of other liver-directed and surgical therapies for the treatment of liver tumors. Long-term follow-up data, including oncologic outcomes, were collected.

Pregnancy of unknown location is a condition in which a pregnancy test is positive, but no intrauterine or extrauterine pregnancy is visualized using transvaginal ultrasonography. We recommend using standardized nomenclature and definitions to describe intrauterine pregnancy (IUP), probable IUP, pregnancy of unknown location (PUL), probable ectopic pregnancy (probable EP), and ectopic pregnancy (EP) (Best Practice). Among abortion-seeking patients found to have a PUL, the incidence of ectopic pregnancy (EP) is 4-8%. We recommend clinical judgment in assessing the risk for EP in the setting of PUL; the absence of an intrauterine gestational sac (GS) or yolk sac should not delay care (GRADE 1B). In asymptomatic individuals with an undesired PUL who prefer to proceed with immediate treatment (medication or procedural management without delay) and have a low risk of EP, as determined by the clinician based on history, symptoms, and all other available data, we recommend medication management with mifepristone and misoprostol or procedural management via uterine aspiration and clear plans for ensuring pregnancy resolution in a timely fashion (GRADE 1B). While both medication and procedural management of undesired PUL are associated with earlier pregnancy resolution and identification of EP, the two main risks of inadequate follow-up include ongoing pregnancy and missing or delaying a subsequent diagnosis of EP. For individuals with PUL choosing immediate treatment with medication management, we recommend clinicians obtain a baseline serum quantitative hCG at the time of medication provision to aid in diagnosis and follow-up (GRADE 1A). Following medication management of PUL with mifepristone and misoprostol, we suggest a repeat serum quantitative hCG level, with pregnancy resolution defined as either a 50% decline or greater at 48-72 hours after misoprostol or an 80% decline or greater at seven days after mifepristone or 5-10 days after misoprostol (GRADE 2B). We recommend against direct extrapolation of follow-up recommendations from no-test abortion clinical protocols to individuals with a documented PUL treated with mifepristone and misoprostol, given the higher risk of EP among individuals with a known PUL (GRADE 1C). When uterine aspiration is performed at less than 42 days of gestation, including for individuals with PUL or probable IUP, and both chorionic villi and GS are not visualized, we recommend repeat ultrasonography (if an IUP or probable IUP was seen initially), serum quantitative hCG follow-up, or both (GRADE 1B). When both chorionic villi and GS are not visualized after uterine aspiration and serial serum hCG follow-up is warranted, we recommend testing on the day of the procedure and 24-72 hours later, with pregnancy resolution defined as greater than 50% decline 24 hours after aspiration, greater than 70% by 48 hours, or greater than 80% by approximately 72 hours (GRADE 1B).

» Multifactorial Pathogenesis: Legg-Calvé-Perthes disease (LCPD) may result from a complex interplay of genetic, epigenetic, and environmental factors, culminating in avascular necrosis of the femoral head in children aged 4 to 10 years.» Genetic Contributions: Mutations in COL2A1 weaken cartilage integrity, and polymorphisms in IL6 drive inflammatory responses, exacerbating bone resorption and necrosis.» Role of Epigenetics: Epigenetic mechanisms, such as altered DNA methylation and miRNA dysregulation, may modulate disease progression by linking genetic susceptibility to environmental influences.» Environmental Amplifiers: Key environmental risk factors, including maternal smoking, low birth weight, and socioeconomic deprivation, may exacerbate the genetic and epigenetic predisposition to LCPD.» Future Directions: Advancements in genetic screening and epigenetic therapies, such as miRNA modulators and DNA methylation inhibitors, combined with preventive measures like improved prenatal care and reduced smoke exposure, may offer promising avenues for optimizing outcomes in LCPD.

Endometriosis is a common disease, affecting approximately 10% of women of reproductive age. Several intersecting guidelines and consensus statements provide information on imaging diagnosis and surveillance strategies for endometriomas. SRU consensus panel recommendations provide information on initial detection of endometriosis on routine pelvic imaging. Revised American Society of Reproductive Medicine (rASRM) classification, the #ENZIAN classification, and the deep pelvic endometriosis index (dPEI) aim to assess the overall extent of disease and assist in presurgical planning. The Ovarian-Adnexal Reporting and Data System (O-RADS) aims to risk stratify lesions evaluated with US or MR based on their imaging morphology, from typical benign lesions to atypical presentations and malignant transformation. Emerging data shows increased risk of ovarian cancer in patients with endometriosis, especially following menopause and in those patients with long standing endometriosis. (Chen et al. in Front Oncol. 14:1329133, 2024;Streuli et al. in Climacteric. 20:138-143, 2017;Secosan et al. in Diagnostics (Basel). 10:134, 2020;Inceboz in Womens Health (Lond Engl). 11:711-715, 2015;Cassani et al. in Maturitas. 190, 2024;Gemmell et al. in Hum Reprod Update. 23:481-500, 2017;Giannella et al. in Cancers (Basel). 13:4026, 2021;) Current O-RADS guidelines mandate follow-up of endometriomas up to 2 years with further follow-up based on clinical factors. No consensus guidelines exist for imaging surveillance of patients with deep endometriosis from a malignancy standpoint. This review explores the imaging appearance of endometriomas, imaging features of malignant transformation, surveillance strategies and gaps in current literature, and attempts to better understand the risk of malignancy and to encourage further research for long-term imaging surveillance of endometriosis patients.

BACKGROUND:The US Food and Drug Administration approved satralizumab for use in adult patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) in 2020, but real-world data are limited. The objective of this case series is to describe the experience with satralizumab in adult patients with AQP4-IgG+ NMOSD who previously received rituximab. METHODS:Case information for patients with AQP4-IgG+ NMOSD who had received satralizumab for ≥6 months was obtained from US healthcare providers from April 1, 2022, to September 30, 2023. Patient characteristics, examination findings, diagnostic tests, treatment response and adverse events were recorded. Patients who received satralizumab after discontinuing treatment with rituximab were included in this case series. RESULTS:Twenty patients were included, and their ages ranged from 19 to 70 years. Overall, 45 % of patients self-identified as Black/African American, 40 % as White, 10 % as Asian and 5 % as multiracial. Time since confirmed NMOSD diagnosis ranged from 4 to 17 years. Median (range) duration of rituximab treatment was 50 (12-162) months. The main reasons for switching to satralizumab were intolerance (60 %) to and inadequate disease control (25 %) with rituximab. The majority of patients (70 %) received satralizumab for ≥24 months and as monotherapy (90 %). All 20 patients were free from radiographically confirmed relapses with satralizumab. Overall, patients maintained disease control with satralizumab, and adverse events primarily included asymptomatic laboratory abnormalities. Two patients permanently discontinued satralizumab due to adverse events. CONCLUSIONS:In this retrospective case series, satralizumab was effective and well tolerated in patients with NMOSD who switched due to ineffectiveness and/or poor tolerability of rituximab. These outcomes align with the long-term efficacy and safety outcomes with satralizumab in the Phase III SAkura clinical trials.