Citations

This joint Clinical Consensus Statement on the safety and feasibility of concomitant urogynecologic and gynecologic oncology surgical procedures reflects statements drafted by content experts from the American Urogynecologic Society and the Society of Gynecologic Oncology. The writing group used a Delphi process to evaluate statements developed from a structured literature search and assessed consensus. A total of 35 statements were assessed in the following categories: (1) background, (2) treatment options, (3) timing of concurrent surgery, (4) risk factors, and (5) value-based care. Of the 35 statements, 28 reached consensus on initial review. Three statements were omitted, and 4 statements were revised and reached consensus following second review utilizing the Delphi process.

Background While delivery of supplemental oxygen is a life-saving therapy, exposure to high oxygen, called hyperoxia, leads to increased intensive care unit mortality. Hyperoxia induces oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic ALI (HALI). Elucidating molecular mechanisms in HALI could identify therapeutic targets in ALI. Methods In the current study, we examined in vivo effects of HALI on Beclin-1 (BCN1), which regulates autophagy, and modulation of BCN1 by epidermal growth factor receptor (EGFR). Effects of HALI on BCN1 and autophagy were examined in mice with genetically decreased EGFR (EGFR Wa5/+ ). Wildtype (WT) and EGFR Wa5/+ mice were exposed to 100% oxygen for 24–72 hours along with normoxia controls (eight groups; n=4–6/group), and analysis of pulmonary BCN1 and autophagy was completed. Results In WT, HALI led to increased BCN1 (59% increased total BCN1/β-Actin; p<0.01) in lung and alveolar epithelium (484% increased H-score; p<0.001). HALI led to decreased microtubule-associated protein 1B-light chain (LC3B)-II/-I ratios (43% decrease; p<0.05) and increased p62 (93% increase; p<0.05), suggesting reduced autophagic flux. In human alveolar type-II cells derived from induced pluripotent stem cells (AT2s iPSC ), HALI caused increased LDH release (130% increase; p<0.0001) and decreased LC3B-II/-I ratios (32% decrease; p<0.05). We previously showed that EGFR Wa5/+ mice are protected in HALI. In the current study, EGFR Wa5/+ mice showed increased pulmonary BCN1 (122% increase; p<0.05), reduced phosphorylated-(p-)/total BCN1 (47% decrease; p<0.05) and decreased LC3B-II/-I ratios (70% decrease; p<0.01) in HALI compared with WT. In addition, wortmannin (1 mg/kg), which decreases BCN1-mediated autophagy, increased mortality in HALI compared with vehicle control (n=10/group; 18% decreased hours survived; p<0.001). Conclusions These data delineate a novel cell death pathway in HALI involving BCN1 and EGFR with therapeutic potential.

INTRODUCTION: To perform a proof-of-concept study to evaluate the performance of individual and combined anorectal manometry and balloon expulsion testing (BET) parameters for diagnosing dyssynergic defecation (DD) using machine learning (ML). METHODS: A single gastrointestinal motility specialist assessed (2008–2018) 307 patients. A ML model was constructed on anorectal manometry/BET data. BET was weight-based in 235 patients and time-based in 72 patients. Missing data were imputed. Data were split 75% train/25% test with preprocessing performed. Five common ML models were trained, and performance was compared using receiver operating characteristic (ROC) area under the curve and accuracy based on 100 bootstrapped samples. The most accurate models were fine-tuned and evaluated on the test set. RESULTS: The median age was 40 years, body mass index 22.2 kg/m 2 , and 81% were women. Two-hundred and 22 (72.3%) patients had a clinical diagnosis of DD. Compared with patients without clinical diagnosis of DD, patients with DD had significantly lower rectoanal pressure gradient (RAG) (median −34.7 [IQR −57.1, −13.0] vs −24.6 [IQR −44.5, −2.4] mm Hg, P = 0.009) and more abnormal BET (59.5% vs 11.8%, P < 0.001). Four features were retained in the optimized model as predictors of DD: abnormal BET, greater resting anal pressure (RAP), and more negative RAG. The optimal parameter was abnormal BET ( P = 0.003), but combinations of 2 manometry results (RAP and RAG) yielded positive predictive values (PPVs) >80%. The optimized logistic regression model had an area under the curve of 0.878, with a sensitivity of 75.0% and specificity of 81.8% at a probability threshold of 0.704. DISCUSSION: Abnormal BET, or a combination of 2 manometric parameters (RAP and RAG), provides >80% positive predictive value for diagnosing DD in patients with chronic constipation.

Purpose: To quantify the prevalence of neural axial abnormalities in congenital early-onset scoliosis (C-EOS) patients stratified by age group, correlate prevalence of treatment, and determine if a delay in MRIs affects outcomes. Methods: A multicenter registry with data on 751 C-EOS patients was retrospectively reviewed, of which 659 patients were included. Data included demographics, pre-index major coronal curve, age at first MRI, intraspinal MRI findings, neurosurgical interventions and scoliosis fixation performed, intraoperative and postoperative complications, and unplanned return to the operating room (UPROR) for orthopaedic complications. Patients were divided into 2 cohorts utilizing age 3 as a cutoff. This age cutoff was selected based on an FDA warning of the potential neurocognitive effects of anesthesia used for MRIs in patients younger than 3 years. Spearman Rho correlations, independent t tests, and χ 2 tests were used for statistical analysis. Results: Patients were divided into 2 groups: first MRI younger than or equal to 3 years of age (n=277) and older than 3 years of age (n=382). One hundred thirty-three abnormal MRIs were identified (20%). There was no significant correlation between age at MRI and abnormal intraspinal findings (rs= −0.018, P =0.64). Among patients with abnormal MRIs, no correlation existed between age at MRI and UPROR. In this cohort, 23 neurosurgical procedures were performed and no significant difference was found in UPROR between groups ( P =0.54). There were 3 neurologic complications in the younger than or equal to 3-year group and 0 in the older than 3-year group ( P =0.07). No significant difference was found in mean pre-index major coronal curve ( P =0.25). Conclusions: The prevalence of neural axis abnormalities in C-EOS was 20%. There was no significant correlation between age at first MRI and the chance of an abnormal MRI. There were no significant differences in neurological complications and UPROR between the younger than or equal to 3-year and older than 3-year groups. Thus, in C-EOS, MRI may be cautiously deferred until after the age of 3 in patients with normal neurological examinations and radiological findings.

Abstract Background Polycystic ovary syndrome (PCOS) affects 10% to 13% of individuals assigned female at birth (AFAB), although a greater prevalence is reported in transgender/gender diverse individuals (TGD) (23.8-38.8%). Testosterone therapy (TT) in TGD individuals is linked to worsening cardiovascular risk factors (CVRFs). Whether TT induces more adverse cardiometabolic changes in TGD with PCOS than TGD without PCOS remains uncertain. Objective To compare the effects of TT on CVRF in TGD with and without PCOS. Methods We retrospectively reviewed 373 records to identify 62 TGD with PCOS (withestablished guideline criteria) and 132 age-matched TGD without PCOS. Data included longitudinal anthropometric measurements, hormone and metabolic parameters, and CVRF before and after TT. Group comparison of PCOS vs without PCOS before and after TT was conducted via independent t-tests, Mann–Whitney-U, and Chi-square. Results At baseline, TGD with PCOS had significantly greater body mass index (BMI), obesity prevalence, and, after controlling for BMI, baseline metformin use. There were no significant differences between TGD with and without PCOS when comparing intra-participant changes after TT. Controlling for BMI, TGD with PCOS on TT exhibited significantly greater hyperlipidemia prevalence, alanine transaminase (ALT) levels, and bioavailable testosterone concentrations than TGD without PCOS on TT. Conclusion Greater baseline cardiometabolic risk was largely BMI-related in TGD with PCOS compared to TGD without PCOS. Only hyperlipidemia and elevated ALT were more prevalent during TT after adjusting for BMI. These findings support cardiometabolic monitoring during TT in all TGD individuals without significant increased risk with PCOS history.

OBJECTIVE Epilepsy affects nearly 50 million individuals worldwide, with one-third of cases resistant to antiseizure medications. For these patients, surgical intervention offers a potential path to seizure freedom. While resective surgery has been the gold standard, laser interstitial thermal therapy (LITT) has emerged as a minimally invasive alternative. The aim of this study was to evaluate the efficacy and safety of LITT versus resective surgery in patients with nontumoral epilepsy. METHODS A systematic review and meta-analysis were conducted using PubMed, Embase, and Scopus, including studies comparing seizure freedom rates, complications, and procedural outcomes between LITT and open surgery in nontumoral epilepsy. Eleven studies met the inclusion criteria, comprising 389 LITT and 557 open surgery patients with varying epilepsy etiologies, including temporal lobe epilepsy, focal cortical dysplasia, and tuberous sclerosis. Statistical analysis was performed using a random-effects model to assess seizure freedom, complications, and reoperation rates. RESULTS Open surgery demonstrated higher rates of complete seizure freedom, although not reaching significance (68.1% vs 53.7%, RR 0.81, p = 0.07). This outcome was sensitive to influential analysis and reached significance in the epileptogenic zone–directed resection subgroup analysis. Although adequate seizure freedom was comparable between the groups (LITT: 63.0% vs open: 74.0%, RR 0.90, p = 0.11), the open surgery group had higher rates of control in the pediatric and non–temporal lobe epilepsy subgroups. Complication rates were significantly higher in the open surgery group (30.0% vs 18.3%, RR 0.55, p < 0.01). LITT patients had significantly shorter hospital stays (3.4 vs 6.8 days, standardized mean difference −0.93, p < 0.01). Reoperation rates were comparable between groups (13.1% for LITT vs 13.4%, RR 1.59, p = 0.26). CONCLUSIONS While LITT offers a less invasive approach with reduced hospitalization and morbidity, open surgery remains slightly superior in achieving long-term seizure freedom. Patient selection remains critical, and further studies are needed to refine decision-making criteria based on epilepsy subtype and lesion characteristics.

OBJECTIVE Early discharge following uncomplicated endonasal resection of pituitary adenoma has been described as safe and feasible. Discharge on postoperative day (POD) 1 is not a widely implemented practice in the United States. This study aimed to evaluate the safety of routine POD1 discharges by assessing postoperative unplanned medical care rates compared with those of patients discharged on POD 2 or later (POD2+). The secondary endpoint was to identify predictors of delayed discharge in the POD2+ cohort. METHODS A retrospective database review of the medical records of 534 patients who underwent endonasal resection of pituitary adenoma at the Mayo Clinic was performed. Relevant demographics, tumor characteristics, and perioperative metrics were abstracted from the medical record, including intraoperative CSF leakage, postoperative complications, emergency department visits, or inpatient readmissions within 30 days. Descriptive, univariate, and multivariate analyses were performed. RESULTS In comparison to 422 (79%) patients discharged on POD1, 112 (21%) patients discharged on POD2+ had a higher unplanned medical care rate (13% vs 5.5%, p = 0.019). There were significantly more men in the POD1 group (48%) than in the POD2+ group (37%) (p < 0.04). The most common reasons for POD1 unplanned care were endocrine dysfunction (2.4%), split evenly between syndrome of inappropriate antidiuretic hormone and adrenal insufficiency, whereas the most frequent reason in the POD2+ cohort was medical (0.06%). Univariate analyses indicated that female sex, higher BMI, intensive care unit (ICU) admission, obstructive sleep apnea, continuous positive airway pressure dependence, intraoperative CSF leakage, and diabetes insipidus (DI) increased the likelihood of POD2+ discharge. The reduced logistic regression model demonstrated a higher likelihood of POD2+ discharge with older age, ICU admission, intraoperative CSF leakage, and DI (p < 0.001). Common factors contributing to discharge after POD1 included endocrine (n = 66, 35%) and/or medical (n = 65, 34%) reasons. CONCLUSIONS Routine patient discharge on POD1 following uncomplicated endonasal resection of pituitary adenoma is a safe practice, as evidenced by the significantly lower rates of unplanned medical care and complications compared with those of patients discharged on POD2 or later. Delayed discharge was associated with older age, ICU admission, intraoperative CSF leakage, and DI. The most frequent reasons for POD1 readmission were endocrine versus medical reasons for POD2+. Preoperative identification of risk factors for delayed discharge and preemptive management of endocrine and medical complications may reduce the length of stay and return to medical care.

PURPOSE There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs. METHODS Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion. RESULTS Consensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies. CONCLUSION This foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation—ultimately contributing to the development of safer, more effective therapies.

Background: Running often elicits stress urinary incontinence (SUI) in parous athletes. While cadence retraining improves running biomechanics, its impact on incontinence is unclear. This feasibility study assessed the implementation and preliminary effects of a 6-week cadence retraining program in parous female runners with SUI. Methods: A total of 8 participants with self-reported SUI and a preferred running cadence ≤ 170 steps/minute underwent treadmill testing before and after the intervention. The program involved a 6-week cadence retraining program using a Garmin Forerunner 55 watch. Feasibility was assessed across 6 domains. Running outcome measures included cadence and vertical oscillation. SUI outcome measures included the Questionnaire for Urinary Incontinence Diagnosis and Urinary Distress Inventory-6 scores. Paired t-tests were conducted (α = .05). Results: Following the 6-week program, feasibility outcomes supported the viability of study procedures and high adherence. Statistically significant increases in cadence ( P = .016) and decreases in vertical oscillation ( P = .019) and concomitant decreases in Questionnaire for Urinary Incontinence Diagnosis ( P = .013) and Urinary Distress Inventory-6 ( P = .042) scores were observed. Discussion: This study demonstrated the feasibility and acceptability of a 6-week cadence retraining program for parous runners with SUI. Given the growing movement to foster athleticism after pregnancy, these findings will appeal to physical therapists searching for acceptable treatment options for SUI in parous runners. Preliminary running mechanics and SUI symptoms warrant a larger randomized controlled trial. A power analysis estimated a sample size of 66 participants for a future full-scale efficacy study.

BACKGROUND & OBJECTIVE Sleep-disordered breathing (SDB) may be a remediable contributor to abnormal cognitive outcomes for children with myelomeningocele. We investigated the frequency of SDB among neonates with fetal vs postnatal myelomeningocele repair. METHODS In this nine-center, prospective, observational study, neonates with myelomeningocele born at more than 30 weeks gestational age underwent a 10-hour bedside polysomnogram at at least 35 weeks postmenstrual age, before hospital discharge. The primary outcome was SDB severity, reflected by the apnea-hypopnea index (AHI; number of respiratory events per hour of sleep). Decisions regarding surgical timing (fetal vs postnatal), technique (open fetal vs fetoscopic approach), and SDB treatment were made by the clinical teams. RESULTS Among 173 infants, 92/173 (53%) had SDB (median AHI 22.5, IQR 12.2–44.2). In unadjusted analysis, AHI was higher among the 90 neonates with fetal repair vs 83 with postnatal surgery (median 29, IQR 14–49, vs 19, IQR 10–36, P = .008). In propensity-adjusted multivariable models, prematurity was independently associated with AHI, whereas surgical timing (fetal vs postnatal) was not. Hindbrain herniation, myelomeningocele level, and clinical need for ventriculoperitoneal shunt did not predict AHI in adjusted models. Supplemental oxygen was commonly prescribed, for 44% of fetal vs 39% of postnatal myelomeningocele repair infants (P = .5). CONCLUSIONS SDB affects more than half of neonates with myelomeningocele. The higher AHI after fetal surgery could stem from the elevated incidence of prematurity in this group. As SDB is treatable and has a potential impact on neurodevelopment, routine screening could become an integral part of a strategy to optimize long-term medical and neurodevelopmental outcomes.