Faculty Bibliography

INTRODUCTION/BACKGROUND:This review examines the role of urodynamics (UDS) in evaluating lower urinary tract symptoms (LUTS) following radical prostatectomy. We first present typical urodynamic findings in post-prostatectomy men, then discuss applications of UDS, and finally examine treatment pathways for post-prostatectomy LUTS beyond stress urinary incontinence (SUI) surgery. METHODS:A narrative review was performed focusing on the current primary literature and society guidelines on the role of UDS post-prostatectomy. RESULTS:LUTS after prostatectomy are common, most frequently storage LUTS, specifically SUI. For the index patient with clinically suspected SUI after prostate treatment, routine UDS before SUI surgery have not been shown to impact postsurgical continence outcomes. In cases where there is diagnostic uncertainty following noninvasive lower urinary tract evaluation, UDS plays an important role. UDS are highly beneficial in complex scenarios, such as severe mixed LUTS, prior radiation therapy, impaired bladder compliance, detrusor underactivity, and/or previous SUI surgery. Fluoroscopy during UDS and cystoscopy can provide additional clarity and confirmation of the diagnosis suggested by UDS. CONCLUSION/CONCLUSIONS:UDS are useful adjuncts in appropriately selected post-prostatectomy patients with LUTS, typically with complicating factors.

IMPORTANCE/UNASSIGNED:Insomnia and obstructive sleep apnea (OSA) are associated with pregnancy complications. OBJECTIVE/UNASSIGNED:To evaluate the association of insomnia and OSA during pregnancy with the risk of ischemic placental disease (IPD) and severe morbidity (SM) and to compare these risks between the 2 sleep disorders. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study included a statewide population-based sample of liveborn singleton births with linked birth certificates for birthing people and their infants in California from January 1, 2011, through December 31, 2020. The analysis was performed on July 22, 2024. EXPOSURES/UNASSIGNED:Insomnia and OSA. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes were IPD, defined as preeclampsia, placental abruption, and birth of a neonate small for gestational age (SGA), and SM, defined according to the Centers for Disease Control and Prevention definition. RESULTS/UNASSIGNED:During the study period, there were 4 145 096 singleton live births among birthing people aged 13 to 55 years; 4783 (0.1%) had insomnia, 5642 (0.1%) had OSA, and 4 134 671 (99.7%) had neither condition. The prevalence of insomnia and OSA was 116 and 136 cases per 1000 live births, respectively. Compared with patients without insomnia or OSA (738 660 [17.9%]), the adjusted relative risk (ARR) of any IPD was 1.42 (95% CI, 1.35-1.50) for those with insomnia (1406 patients [29.4%]) and 1.57 (95% CI, 1.50-1.64) for those with OSA (1848 [32.8%]). Compared with patients with neither disorder, the ARR of birth of an SGA neonate was higher for those with insomnia (1.23; 95% CI, 1.13-1.35) than for those with OSA. The ARR of preterm birth was 1.81 (95% CI, 1.68-1.95) for insomnia (711 patients [14.9%]) and 1.73 (95% CI, 1.62-1.85) for OSA (870 [15.4%]) vs neither disorder (279 364 [6.8%]). The ARR of SM was 2.26 (95% CI, 2.03-2.50) for insomnia (366 patients [7.7%]) and 2.81 (95% CI, 2.58-3.06) for OSA (545 [9.7%]) vs neither disorder (93 857 [2.3%]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study of singleton live births, pregnant individuals with insomnia or OSA were at increased risk for IPD, SM, and preterm birth compared with those without these sleep disorders. Further study is needed to determine the biological mechanisms for these risks and whether early identification and targeted preventive interventions may improve pregnancy outcomes.

Non-small cell lung cancer (NSCLC) patients with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti-PD-1. Here, we conducted an in vivo CRISPR screen that identified HDAC1 as a target to reverse anti-PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity exceeding previously generated inhibitors in this class in preclinical studies. Treatment with TNG260 led to increased expression of immunomodulatory genes in STK11-deficient cancer cells. When combined with anti-PD-1, TNG260 induced immune-mediated stasis and/or regression in STK11-deficient syngeneic tumor models and autochthonous NSCLC models. In the tumors of patients with STK11-deficient cancers on a clinical trial (NCT05887492), treatment with a combination of TNG260 and pembrolizumab increased intratumoral histone acetylation, PD-L1 tumor proportion scores, and T cell infiltration into the tumor microenvironment. This study illustrates a promising treatment strategy for addressing immune evasion in STK11-mutant NSCLC patients.

INTRODUCTION/BACKGROUND:AR selectivity and enhances detrusor relaxation without compromising voiding function. This review summarises the clinical and real-world evidence supporting the efficacy, safety and patient-reported benefits of vibegron in OAB. METHODS:A comprehensive search of the PubMed database was conducted in December 2024 using the keyword "vibegron". This search yielded 123 entries, which were subsequently screened by title for relevance to the objectives of this narrative review. All relevant articles identified through this process were included. RESULTS:AR selectivity and lack of cytochrome P450 interactions offer advantages in specific patient groups. Ongoing research, including real-world phase IV studies, aims to further define the long-term effectiveness and safety of vibegron in clinical practice. CONCLUSION/CONCLUSIONS:Vibegron represents an important advance in the pharmacologic management of OAB, providing a well-tolerated and effective alternative to existing therapies.

OBJECTIVE:To evaluate the prevalence and risk factors for severe perioperative surgical morbidity among patients undergoing cesarean delivery. METHODS:This was a retrospective cross-sectional study of patients who underwent cesarean delivery in any California hospital between 2016 and 2021. Linked birth certificate and maternal discharge data identified cesarean delivery hospitalizations. We constructed a composite index for severe perioperative surgical morbidity, including intra-abdominal or pelvic visceral and vascular injuries, hysterectomy, pelvic or retroperitoneal hematoma, wound complications, ileus or bowel obstruction, acute peritonitis, and shock. Severe perioperative surgical morbidity prevalence was quantified overall and stratified by prelabor and intrapartum cesarean deliveries. We developed a multivariable Poisson log-linear regression model to identify independent risk factors for severe perioperative surgical morbidity. In secondary analyses, severe perioperative surgical morbidity prevalence and risk factors were assessed separately by prelabor and intrapartum cesarean delivery. RESULTS:Among 594,655 cesarean deliveries, 10,182 (171/10,000, 95% CI, 168-175) had severe perioperative surgical morbidity. The most common categorized morbidities were wound complications (59/10,000, 95% CI, 57-61); bladder, genitourinary, or pelvic injury (45/10,000, 95% CI, 43-47); ileus or bowel obstruction (33/10,000, 95% CI, 32-35); shock (15/10,000, 95% CI, 14-16); and intraoperative bowel injury (14/10,000, 95% CI, 13-15). Severe perioperative surgical morbidity prevalence was higher among patients undergoing intrapartum compared with prelabor cesarean delivery (203/10,000, 95% CI, 198-209 vs 146/10,000, 95% CI, 142-150). Patients with placenta accreta spectrum disorder had the highest severe perioperative surgical morbidity risk (adjusted risk ratio 15.3, 95% CI, 14.0-16.7). CONCLUSION/CONCLUSIONS:Nearly 1 in 60 patients who undergo cesarean delivery in California experienced severe perioperative surgical morbidity, with a higher prevalence occurring among intrapartum compared with prelabor cesarean deliveries. These findings underscore the need for systematic measurement and evaluation of surgical quality of care among patients undergoing cesarean delivery to identify opportunities for morbidity reduction.

OBJECTIVE:KEYNOTE-775 defined lenvatinib/pembrolizumab as the new standard-of-care for patients with proficient mismatch repair (pMMR) recurrent EC. However, the regimen required dose reductions in 66.5 % of participants and the generalizability of these results was uncertain. We conducted an observational study to determine the prescribing patterns, outcomes and side effects in a real-world setting. METHODS:A national multidisciplinary consortium was utilized to study treatment patterns of patients with advanced/recurrent EC treated with lenvatinib/pembrolizumab from 2019 through 2022. Treatment decisions were based on the physician's recommendation. RESULTS:188 patients across 14 institutions were included. Histologic subtypes were 33 % endometrioid, 41 % serous, 9.6 % mixed, 10.1 % carcinosarcoma, and 2.1 % clear cell. 85.6 % were pMMR and 5.3 % were dMMR. Lenvatinib starting dose was 20 mg in 19.7 %, 18 mg in 14.9 %, 14 mg in 47.3 %, and 10 mg in 18.1 %. Median dose intensity of lenvatinib was 14 mg. Pembrolizumab dosing was 200 mg Q3W in 94.1 %. Grade ≥ 3 adverse events (AE) rates related to lenvatinib were similar across starting doses: 20 mg (13.5 %), 18 mg (17.9 %), 14 mg (7.9 %), 10 mg (17.6 %) (p = 0.31). Response rates in relation to lenvatinib starting dose were 20 mg (27 %), 18 mg (35.7 %), 14 mg (39.3 %), 10 mg (44.1 %) (p = 0.50). In relation to lenvatinib starting dose, PFS, OS and duration of therapy were not statistically different. Response rates (p = 0.24), PFS (p = 0.66) & OS (p = 0.22) were similar in White and Black patients. CONCLUSIONS:In a real-world analysis, the predominant starting dose was 14 mg lenvatinib and 200 mg pembrolizumab. Starting at varying doses does not appear to compromise response rates or survival and no new severe adverse events emerged.

Adolescents and young adults with a cancer diagnosis face unique challenges during treatment and into survivorship related to fertility and family building. This review provides an updated overview of the impact of cancer and its associated treatments, including novel treatments in male and female fertility. An overview of fertility preservation and family building options, including experimental options, is also provided.

A clinical trial of a multi-strain vaginal synbiotic (NCT05659745, registered 12/19/2022 at clinicaltrials.gov) led to an optimal vaginal microbiome dominated by L. crispatus (CST I). The synbiotic led to a significant increase in L. crispatus compared to placebo (p < 0.05), and conversion to CST I was significantly higher with the vaginal synbiotic than with placebo (90 vs 11%; p < 0.002). Mechanistically, the synbiotic reduced Gardnerella vaginalis and Candida, clinically important microbes.

OBJECTIVE:To propose a model of international meetings of minimally invasive gynecologic surgery to decrease the carbon footprint while preserving personal interactions and the financial stability of meetings and of medical societies. WHAT WE KNOW/UNASSIGNED:International medical society meetings create a substantial carbon footprint, with 95% generated by air travel. Meetings may be organized virtually or in-person with distinct benefits and drawbacks of each format. In-person meetings encourage personal interactions, sensitive discussions, and social exchanges which are important for learning and mental well-being. WHAT WE PROPOSE/UNASSIGNED:A collaborative effort of international societies to organize annual scientific meetings at one main venue per continent and regional hubs where participants, can come together in person. Presentations and session moderations will be possible from main venues and distant hubs. Carbon footprint from air travel would decrease, while the scientific contents would be improved by the collaboration between the societies. We theorize that local hubs, easier and less expensive to reach, will increase the number of participants who face economic, geopolitical, ecological and familial barriers to travel. Regional and time differences would allow each society to preserve the specific characteristics and sessions of its conference. The preservation of one main venue on each continent, will enable a gradual transition, allowing medical societies and corporate sponsors to take advantage of the enlarged audience, while measuring the desired outcomes and being able to adjust their management. Hubs participants will be actively involved reducing the burden of travel, transitioning to a preference of joining the main venue only every second or third year. CONCLUSION/CONCLUSIONS:An economically sustainable approach towards low carbon footprint, scientifically improved and more accessible meetings needs to be considered.