Citations

OBJECTIVE Historically, craniopharyngioma (CP) was divided into adamantinomatous CP (ACP) and papillary CP (PCP) subtypes based on histopathological features. However, each harbors a unique genetic profile and progressively differing treatment paradigms, leading to their reclassification by the WHO in 2016 as two distinct entities. Descriptive in nature, this large multi-institutional study aimed to establish current differences between the presentation, treatment patterns, and clinical course of these pathologies to serve as a baseline for future studies as new treatment paradigms emerge. METHODS The authors queried the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) database, which encompassed patients from 14 participating institutions across the United States between 2000 and 2024. The database was screened for adult patients who underwent initial CP treatment with a confirmed histopathological diagnosis of ACP or PCP. Patient demographic characteristics, clinical course, tumor treatment, and outcomes data were collected and compared by CP type. RESULTS The final analysis included 273 ACP and 99 PCP adult patients who underwent initial surgical treatment. ACP patients presented younger on average (mean 48.3 vs 52.8 years, p = 0.034). PCP patients were more likely to present with hypothyroidism (33.3% vs 20.5%, p = 0.010), hyperlipidemia (25.3% vs 15.8%, p = 0.036), fatigue (28.3% vs 17.6%, p = 0.024), temperature intolerance (9.1% vs 1.5%, p < 0.001), and cardiac arrhythmia (6.1% vs 1.1%, p = 0.006). The groups demonstrated similar postsurgical and neuroendocrinological outcomes. Postoperative median (IQR) progression-free survival did not significantly differ between groups (19.0 [7.0–37.0] for ACP vs 5.0 [3.5–7.5] months for PCP, p = 0.972). ACP patients were more likely to receive radiation after surgery (27.8% vs 15.2%, p = 0.012). CONCLUSIONS This large multicenter descriptive study aimed to characterize similarities and differences between the clinical courses of molecularly distinct ACP and PCP, which has not previously been described. The findings should serve as a baseline to inform future studies, particularly with the recent introduction of targeted therapy for PCP.

OBJECTIVE Frailty is a known predictor of adverse outcomes in pituitary surgery, yet its impact regarding craniopharyngioma remains unclear. The authors assessed preoperative frailty, measured by the 11-factor modified frailty index (mFI-11), and its association with perioperative morbidity among adult patients undergoing craniopharyngioma surgery. METHODS Using the Registry for Adenomas of the Pituitary and Related Disorders (RAPID) database, the authors performed a retrospective cohort study of the records of patients ≥ 18 years of age who underwent craniopharyngioma surgery between June 2007 and November 2024. Patients were stratified into the following categories according to their numeric mFI-11 score: fit (scores 0 and 1), managing well (scores 2 and 3), and mildly frail (scores 4–6). Primary outcomes included hospital length of stay (LOS) and discharge disposition. Secondary outcomes included 90-day readmission, surgical outcomes, and complications. Multivariable analyses were performed to identify independent predictors of hospital LOS and non-home discharge, adjusting for age, surgeon experience, American Society of Anesthesiologists class, complications, and surgical approach. RESULTS Among 278 patients (221 fit, 43 managing well, 14 mildly frail), higher-frailty patients were older (mean age 47.8 ± 16.1 years in fit vs 60.1 ± 12.5 years in managing well vs 67.6 ± 8 years in mildly frail, p < 0.001) and more likely to present urgently (24.2% vs 36.4% vs 78.6%, p = 0.001). Gross-total resection was achieved less frequently in frail patients (44.8% vs 24.3% vs 23.1%, p = 0.030). Overall complication rates were similar; however, increasing frailty was associated with higher rates of postoperative mortality (0% vs 2.8% [1/36] vs 7.7% [1/13], p = 0.018), pneumonia (0.5% [1/195] vs 2.8% [1/36] vs 15.4% [2/13], p = 0.006), and reintubation (2.6% [5/195] vs 2.8% [1/36] vs 30.8% [4/13], p = 0.002). Higher frailty was associated with a stepwise rise in median [IQR] LOS (5 [3–8] days vs 7 [4–12] days vs 13 [6.5–21.8] days, p < 0.001) and remained an independent predictor of extended LOS on multivariable analysis (β = 1.729 per point, p = 0.006). Rates of non-home discharge showed a similar pattern (9.2% vs 30.0% vs 64.3%, p < 0.001), with frailty independently predicting non-home discharge (OR 2.352, 95% CI 1.527–3.822). Unplanned 90-day readmission rates were significantly higher in the mildly frail cohorts (22.5% vs 45.7% vs 53.8%, p = 0.002). CONCLUSIONS The mFI-11 scores independently predicted perioperative morbidity following craniopharyngioma resection. Incorporating frailty screening into preoperative screening may improve risk stratification, family and patient counseling, and discharge planning.

OBJECTIVE Craniopharyngiomas are benign intracranial tumors that can be difficult to manage operatively and often result in postoperative complications and prolonged recovery. Understanding the factors that influence length of stay (LOS), discharge disposition, and readmission can guide perioperative planning and patient counseling. The authors examined the clinical, radiographic, and surgical predictors of extended LOS (eLOS), nonhome discharge, 90-day readmission, and hospitalization ratio (HR) after craniopharyngioma resection using a large, multicenter cohort. METHODS A retrospective analysis was conducted using the Registry of Adenomas of the Pituitary and Related Disorders database, encompassing 469 patients who underwent craniopharyngioma resection at 14 US academic centers from 2011 to 2025. Patients were stratified by 4 outcomes: eLOS (> 75th percentile), discharge to home versus skilled nursing facility/rehabilitation, 90-day hospital readmission, and hospitalization ratio (i.e., integration of initial and readmission LOS). Multivariable logistic regression models identified independent predictors for each outcome among patient and surgical variables. RESULTS An eLOS (> 10 days) was independently associated with preoperative memory loss (OR 3.75, 95% CI 1.95–7.21), gait imbalance (OR 5.90, 95% CI 1.53–22.70), and postoperative complications (OR 4.07, 95% CI 2.34–7.06). The use of a nasoseptal flap was protective against an eLOS (OR 0.52, 95% CI 0.28–0.93). Discharge to home was predicted by an endoscopic approach (OR 3.87, 95% CI 1.78–8.44) and postoperative intact thirst (OR 2.22, 95% CI 1.05–4.66) and negatively predicted by preoperative diabetes mellitus (OR 0.21, 95% CI 0.09–0.50), LOS (OR 0.87, 95% CI 0.84–0.91), and postoperative cognitive dysfunction (OR 0.30, 95% CI 0.13–0.72). Among 385 patients with follow-up data, a 90-day readmission was independently associated with postoperative complications (OR 5.62, 95% CI 3.12–10.13), preexisting coronary artery disease (OR 4.30, 95% CI 1.46–12.69), and postoperative cognitive dysfunction (OR 3.33, 95% CI 1.76–6.44). A higher HR was associated with diabetes mellitus (unstandardized B 0.059, 95% CI 0.010–0.108, p = 0.02), postoperative complications (unstandardized B 0.054, 95% CI 0.021–0.086, p = 0.001), and postoperative cognitive dysfunction (unstandardized B 0.049, 95% CI 0.006–0.092, p = 0.02). Tumor pathologic subtype and size, prior treatment, extent of resection, and surgeon experience were not directly predictive of outcomes. CONCLUSIONS Cognitive and functional status, systemic comorbidities, and postoperative complications, in addition to surgical approach, are important predictors of the early clinical course after craniopharyngioma surgery. Early identification of high-risk patients may help to guide treatment decisions, improve discharge planning, and reduce healthcare utilization.

Abstract Introduction Custom stents are a fast-evolving and revolutionary therapy for use in patients who require therapeutic stenting options due to a variety of tracheal, bronchial, and parenchymal diseases. The combination of increasing high-resolution CT imaging with 3-D printing technology has allowed for even greater flexibility in therapeutic treatment. Returned mesh is a well-described phenomenon in the medical literature and can create a wide variety of difficult to manage complications. Description The patient is a 64-year-old male with a past medical history of tracheobronchomalacia status post tracheoplasty with prolene mesh placement in April 2011 which was complicated by erosion of mesh through the membranous airway in April 2017. He subsequently underwent a right thoracotomy with a muscle flap reconstruction of the membranous trachea in May 2017. This was then complicated by a diverticulum of the distal trachea that was non-communicative with the esophagus and chronic stenosis of the left mainstem bronchus with residual mesh retained in the posterior membranous left mainstem bronchus. He had a custom Y-stent placed for the first time in February 2022 due to persistent sensation of shortness of breath along with productive cough. He experienced immediate relief after placement of his custom stent and has since demonstrated remarkable stability, rarely requiring unscheduled bronchoscopy for mucous clearance. He has nonetheless derived immense benefit from stenting from a symptomatic standpoint since initial placement in 2022. Discussion Customized stents utilizing 3-D printing technology have allowed far more flexibility to the clinical approach of patients with complex airway pathology. As tracheal and bronchial reconstruction surgeries continue to involve more complicated management modalities, including the use of mesh, complications will continue to arise. Mesh erosion is a potentially devastating complication from tracheobronchoplasty. It will, therefore, be important to facilitate treatment of complications from these and other modalities. Therapeutic bronchoscopy with custom stent placement will almost certainly continue to evolve as an effective tool in the management of patients such as these. This abstract is funded by: None

Abstract Introduction Nuclear protein in testis (NUT) carcinoma, formerly known as NUT midline carcinoma, is a rare and highly aggressive subtype of squamous cell carcinoma characterized by NUTM1 gene rearrangements. It typically affects children and young adults and shows a predilection for midline structures of the head, neck, and thorax. We describe a rare case of NUT carcinoma in an elderly patient presenting with central airway obstruction treated with tumor debulking, devascularization, and pulsed electric field (PEF) ablation. Case An 89-year-old woman on chronic anticoagulation for atrial fibrillation presented with respiratory distress and hemoptysis requiring intubation and mechanical ventilation. Chest CT revealed a developing right lower lobe infiltrate and bronchoscopy demonstrated a non-obstructing right lower lobe endobronchial lesion. Pathology of the lesion confirmed NUT carcinoma but the patient was lost to follow-up. Two months later, she presented with altered mental status and respiratory failure. Imaging revealed a 4.6 x 2.6 cm mass at the level of the cricoid cartilage causing approximately 75% tracheal obstruction with tracheal wall invasion. She underwent rigid bronchoscopy with tumor debulking and devascularization, achieving &gt;80% tracheal patency post-procedure. EBUS-guided PEF ablation was then performed to target residual bulky tumor found in the paratracheal area. Given her age, comorbidities, and poor performance status, palliative chemotherapy was deferred and palliative radiotherapy was offered to limit tumor progression. Discussion NUT carcinoma is a rare and aggressive malignancy with a poor prognosis. This case demonstrates rapid tumor progression leading to respiratory failure within two months of initial diagnosis. Management options for malignant central airway obstruction in non-surgical candidates may include endobronchial debulking and ablative therapies. In this case, EBUS-guided PEF ablation, a non-thermal technique that delivers brief electric pulses to induce tumor apoptosis while sparing adjacent structures, was successfully used to treat residual disease with the goal of reducing marginal regrowth and maintain airway patency. PEF ablation has been described in percutaneous and bronchoscopic management of early stage non-small cell lung cancer; however, its application in central airway obstruction represents an innovative therapeutic approach. Although chemoradiation may be considered when feasible, no standard regimen exists for NUT carcinoma. It typically responds poorly to conventional therapies, underscoring the importance of complementary local treatment strategies in select patients. This case highlights the rapidly progressive course of NUT carcinoma and demonstrates the potential role of PEF ablation as a novel adjunct in the palliative management of malignant central airway obstruction. This abstract is funded by: None

Abstract Rationale The United States has the highest per capita incarceration rate of any developed democracy. As the incarcerated population ages, medically complex and frail patients are increasingly hospitalized in the community, often arriving without decisional capacity and with limited family involvement. This is the first analysis of state laws and policies governing decision-making for incapacitated incarcerated patients. Methods Two team members independently conducted Westlaw and Internet searches for statutes, regulations and department of corrections (DOC) policies from 50 states and the District of Columbia, identifying language about medical decision-making for incapacitated incarcerated patients. These parallel searches were merged into a single database and reviewed by the analytic team, who created a codebook of inductively and deductively derived themes, guided by principles of grounded theory. The codebook was then systematically applied to the database by 2 independent coders; all data were double-coded. Disputes were resolved by consensus with the entire analytic team, in consultation with a legal scholar. Results Thirty-four of 51 jurisdictions have language addressing decision-making for incapacitated incarcerated patients. Data collected include the definition and determination of incapacity, language affirming incarcerated persons’ right to autonomy in medical decision-making, approaches to decision-making for patients with and without surrogate decision-makers, and whether treatment over patient/surrogate objection is authorized. Assertions about the importance of advance care planning (n = 25) are often undercut by procedural hurdles (n = 20), such as complex witnessing requirements for advance directive completion. Many jurisdictions (n = 26) allow family or friends to serve as legally recognized decision-makers. Thirteen jurisdictions exclude an incarcerated person from serving as decision-maker for another incarcerated person. Fourteen jurisdictions have provisions allowing for treatment over the objection of a patient or their surrogate. While approaches to unrepresented patients differ widely (Figure), 5 jurisdictions grant narrow decisional authority to treating physicians and 4 jurisdictions authorize correctional employees to make medical decisions. Conclusion A heterogeneous assortment of laws, policies and regulations govern the care of incapacitated incarcerated patients, with wide variation observed from jurisdiction to jurisdiction. One-third of jurisdictions lack policies or language regarding decision-making processes for incapacitated incarcerated patients. Even more troubling, 14 jurisdictions allow treatment over a patient or surrogate’s objection and 4 jurisdictions delegate authority over decisions for unrepresented patients to correctional employees, such as the prison medical director or the warden. These findings raise serious concerns about autonomy, beneficence and justice. National reform is needed to align correctional policies with established ethical standards for surrogate decision-making. This abstract is funded by: National Institute on Aging

OBJECTIVE The aim of this study was to evaluate freedom from tumor progression and clinical outcomes in older adults with small- to medium-sized vestibular schwannoma (VS) managed by observation versus stereotactic radiosurgery (SRS) to better inform optimal management in this patient population. METHODS In this international multicenter study, patients aged ≥ 60 years with Koos grade I or II VS managed by observation or SRS were retrospectively reviewed. Propensity score matching was conducted using patient characteristics, tumor size, and hearing assessments. Outcome measures of freedom from tumor progression, serviceable hearing preservation (SHP), and neurological function (tinnitus, vestibulopathy, House-Brackmann grade, and trigeminal nerve function) were assessed for both groups. RESULTS The observation and SRS groups each comprised 51 matched patients (median age 68 years for both). Ipsilateral serviceable hearing was observed at presentation for 35 patients in each group. The median follow-up duration was 39 months in the observation group versus 27 months in the SRS group (p = 0.5). Tumor progression was significantly lower with SRS than with observation (2% vs 52.9%, p < 0.001). The rate of 5-year freedom from tumor progression was 100% in the SRS group versus 43% (95% CI 29%–64%) in the observation group. The rate of 10-year freedom from tumor progression was 90% (95% CI 73%–100%) in the SRS group versus 20% (95% CI 8.5%–49%) in the observation group. At the last follow-up, hearing loss occurred in 42.9% of the observation group and 51.4% of those who underwent SRS (p = 0.5). The 3-year SHP rate was 68% (95% CI 53%–88%) versus 65% (95% CI 49%–85%) (p = 0.8), and the 5-year SHP rate was 53% in both groups (95% CI 36%–78% in the observation group and 95% CI 35%–79% in the SRS group, p = 0.8). The composite endpoint of tumor progression and/or worsened neurological outcome, including hearing loss, tinnitus, vestibulopathy, facial nerve dysfunction (House-Brackmann grade), or trigeminal dysfunction, demonstrated a significantly lower rate in the SRS group (17.6%) compared with the observation group (66.7%) (p < 0.001). CONCLUSIONS SRS in older patients for management of Koos grade I or II VS resulted in significantly superior rates of freedom from tumor progression, comparable hearing preservation rates, and significantly higher rates of favorable overall radiographic and neurological outcomes than observation alone. Compared with observation, SRS might be the preferred management option in this patient population.

BACKGROUND AND OBJECTIVES: Craniopharyngiomas are complex intracranial tumors that pose significant challenges in surgical management. We aimed to develop risk-stratified surgical outcome benchmarks for adult patients undergoing endoscopic craniopharyngioma resection by using the Registry of Adenomas of the Pituitary and Related Disorders database to facilitate comparisons across institutions and guide clinical decision-making. METHODS: A retrospective cohort of adult patients (18 years and older) with craniopharyngioma undergoing a first-time endoscopic transnasal surgery across 14 academic centers in the United States was analyzed using data collected from 2011 to 2024. Patients were stratified into low-risk and high-risk cohorts based on criteria including age, body mass index, selected tumor characteristics (size, infundibular relationship, intraventricular extension), and previous radiation. Surgical outcomes were analyzed, and benchmarking ranges were defined using the established methodology. RESULTS: The overall cohort included 318 patients with a mean age of 50 years. Upon benchmarking analysis (50th-75th percentile performance), low-risk patients (n = 136) had a median length of stay of 4.0 to 6.0 days, 90-day readmission rates of 15.5% to 22.2%, skilled nursing facility discharge rates of <1.0%, postoperative cerebrospinal fluid leak incidence of <1.0% to 14.3%, gross total resection rates of 50.0% to 60.8%, new postoperative arginine vasopressin deficiency rates of 33.3% to 50.0%, and tumor progression/recurrence rates of <1.0% to 18.3% over a median follow-up period of 27.0 (IQR 10.5-56.5) months. Benchmarking ranges were proposed for each outcome to facilitate cross-institutional comparisons. CONCLUSION: Establishing surgical outcome benchmarks for adult patients undergoing craniopharyngioma resection using data from the Registry of Adenomas of the Pituitary and Related Disorders provides a framework for assessing surgical performance and guiding clinical decision-making. Benchmark ranges can inform institutional quality improvement efforts, perioperative risk stratification, and patient counseling regarding expected postoperative outcomes.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.