Citations

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.

OBJECTIVE The minimal important difference (MID) and minimal important change (MIC) are two metrics that bridge the gap between statistical significance and clinical relevance and are critical to managing clinical decisions and conducting clinical research. The objective of this study was to define MIDs to evaluate cross-sectional differences among groups and to define MICs to evaluate longitudinal within-patient changes for the Mayo Clinic Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS Anchor-based methods were used to define MIDs and MICs for the VSQOL Index domain scores, which range from 0 to 100 points, for a national cohort of 1050 patients with sporadic vestibular schwannoma, 644 of whom completed the VSQOL Index twice approximately 1 year apart. RESULTS The median of the MID estimates for the VSQOL Index domains were: hearing problems (17, IQR 12.5–21); dizziness and imbalance (21, IQR 18–23); pain, discomfort, and tinnitus (19.5, IQR 15–23.5); problems with face or eyes (18, IQR 17–28); impact on physical, emotional, and social well-being (19.5, IQR 14.5–23.5); difficulty with thinking and memory (23.5, IQR 18.5–28.5); global quality of life (12, IQR 8–16); and satisfaction or regret (13.5, IQR 7–17). MIC estimates for the hearing problems and satisfaction and regret domains were not obtained because the correlations between these domain scores and their associated anchors were not sufficiently strong. The MIC estimates (minimum and maximum) for the remaining domains were: dizziness and imbalance (7.2 and 8.3); pain, discomfort, and tinnitus (8.3 and 8.5); problems with face or eyes (7.0 and 7.4); impact on physical, emotional, and social well-being (2.1 and 8.0); and difficulty with thinking and memory (12.9 and 15.0). The median of the MIC estimates for global quality of life was 5.2 (IQR 3.7–5.6). CONCLUSIONS The MIDs and MICs reported herein provide a framework to interpret quality-of-life benefit or harm cross-sectionally among groups and longitudinally within patients. Moving forward, these values should be considered when interpreting studies using the VSQOL Index to assess disease-specific quality of life in patients with sporadic vestibular schwannoma.

ABSTRACT The limited efficacy of current therapies against cholangiocarcinoma (CCA) necessitates the development of novel treatment strategies. Src family kinases (SFKs) contribute significantly to tumor progression and resistance in CCA. Therefore, we investigated the novel, first-in-class SFK ‘OFF’ inhibitor NXP900 in diverse preclinical CCA models, including those with acquired resistance. This study evaluated the therapeutic effects of NXP900 and detailed adaptive molecular responses to SFK inhibitor therapy. We also aimed to identify biomarkers predictive of drug sensitivity using integrated multiomic profiling and develop strategies to overcome resistance. NXP900 inhibited YAP activity through direct inhibition of tyrosine phosphorylation and indirect activation of the Hippo pathway via LATS. These effects were associated with decreased tumor cell viability in CCA cell lines and several in vivo models. Notably, IDH -mutant patient-derived xenograft CCA models were particularly sensitive to NXP900. NXP900 also synergized with gemcitabine/cisplatin chemotherapy, enhancing antitumor efficacy in both in vitro and in vivo models. Multiomic analyses combining transcriptomics, global proteomics, and phosphoproteomics identified molecular features associated with primary response and acquired resistance. IL13RA-AKT signaling was upregulated in resistant models; NXP900 sensitivity could be restored with AKT or IL13RA2 inhibition. Together, these findings demonstrate the therapeutic potential of NXP900 as a novel YAP inhibitor in CCA and support further investigation in a clinical trial. Graphical Abstract

Abstract Despite advances in endoscopic techniques, many colorectal surgeries in the United States are still performed for non-malignant colorectal polyps (NMCRPs). This study evaluated trends, demographic variations, and outcomes of surgeries for NMCRPs among all colorectal surgeries over the past decade. Using the TriNetX nationwide database, we identified adults (≥ 18 years of age) who underwent colectomy or proctectomy for NMCRPs or colorectal cancer between 2013 and 2023. We evaluated the proportion of surgeries performed for NMCRPs, stratified by demographic factors, and compared postoperative adverse events (AEs) between NMCRP and colorectal cancer surgeries. Among 136,721 surgeries, 52,480 (38.4%) were for NMCRPs. The proportion of NMCRP surgeries decreased from 59% in 2013 to 33% in 2023, with the most significant decline between 2013 and 2016. Black individuals showed the highest decrease. Compared with colorectal cancer surgeries, NMCRP surgeries were associated with significantly lower risks of wound, infectious, urinary, pulmonary, gastrointestinal, and cardiac AEs. Although the proportion of NMCRP surgeries has declined, ongoing efforts in education and training are needed to further reduce unnecessary surgeries and improve patient outcomes.

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.

What was done? A review of artificial intelligence (AI) applications for the imaging of uterine fibroids, endometriosis, and adenomyosis. What was found? AI models can assist with the recognition, segmentation, and localization of uterine fibroids, and the differentiation of benign fibroids and sarcomas. Models can aid in the diagnosis of adenomyosis and endometriosis, and the prediction of the impact of endometriosis on fertility. What the findings mean? Deployed thoughtfully, AI tools could reduce variability, shorten read times, and add objective measurements to routine care. Studies evaluating these models are limited by single-institution designs and continued reliance on expert sonologists and radiologists.