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 Background Emerging evidence suggests irreversible electroporation (IRE) with standard-of-care (SOC) chemotherapy may improve survival in patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) when compared to SOC alone. This study evaluates the overall survival (OS) and progression-free survival (PFS) of Stage 3 PDAC patients treated with SOC plus IRE with the NanoKnife System versus SOC alone. Methods This prospective, multicenter study included two cohorts from the DIRECT registry: an IRE cohort from sites offering IRE as part of clinical care, and a comparator SOC cohort of prospectively enrolled and contemporaneous retrospective patients. Enrollment spanned 08/05/2019 to 02/05/2023, with follow-up through at least 24 months, death, or loss to follow-up. Included were 137 patients (99 IRE; 38 SOC), aged ≥18 years with Stage 3 PDAC and no progression after three months of SOC therapy. Results Median (interquartile range) time from diagnosis to enrollment was 8 (6-10) months for IRE and 4 (3-6) for SOC (p<0.0001). Median OS and PSF from enrollment were 18 (95% confidence interval [CI]: 15-24) months and 9 (95% CI: 7-12) months for IRE, and 10 (95% CI: 8-14) months and 6 (5-8) months for SOC, respectively (p<0.0001 and p=0.009). Adverse events occurred in 80% (79/99) of IRE patients and 95% (36/38) of SOC patients; 29% (29/99) of the IRE cohort experiencing an IRE-related adverse event. Conclusions IRE was associated with improved OS versus SOC alone and may be an effective consolidative treatment for Stage 3 PDAC after three months of induction chemotherapy.

ABSTRACT Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) and by broth microdilution for imipenem-relebactam (I/R). Characteristics and outcomes, including desirability of outcome rankings (DOOR), were compared between patients infected with isolates not susceptible vs susceptible to each agent. Of 800 CRPA isolates, susceptibility to C/T, CZA, and I/R was 69%, 67%, and 33%, respectively. USA isolates ( n = 526) were more frequently susceptible to these agents than isolates from other countries ( n = 274; C/T: 83% vs 42%; CZA: 77% vs 47%; I/R: 37% vs 23%; P < 0.001 for each comparison) and isolates with carbapenemases ( n = 157) were less frequently susceptible than isolates without carbapenemases ( n = 643; C/T: 7% vs 84%; CZA: 24% vs 77%; I/R: 6% vs 39%; P < 0.001 for each comparison). Thirty-day mortality and DOOR were similar overall in patients infected with isolates not susceptible vs susceptible to each βL/βLI. However, the adjusted probability of a better DOOR outcome for a randomly selected patient with bacteremia due to a C/T-not susceptible vs -susceptible isolate was 38.2% (95% confidence interval, 25.6%–52.7%). Resistance to novel βL/βLIs, especially I/R, is common in CRPA, particularly outside the USA and in carbapenemase-producing isolates. Additional treatment options are needed for CRPA infections.

Abstract Rationale Dyspnea is a prominent symptom of fibrotic hypersensitivity pneumonitis (fHP), limiting patients’ activity and impairing their quality of life. The University of California San Diego Shortness of Breath questionnaire (UCSD-SOBQ) is a 24-item instrument used to assess dyspnea severity in patients with various respiratory conditions. Objectives This study aimed to examine the reliability and responsiveness of the UCSD-SOBQ score, its validity as a measure of dyspnea severity, and its prognostic value in a prospective cohort with fHP. Methods We conducted psychometric analyses on UCSD-SOBQ response data and assessed the association between score changes and survival in patients with fHP who completed the UCSD-SOBQ and other HP severity metrics at baseline, 6 and 12 months. We introduce the reliable change index (RCI) and the likely change index (LCI) to assess the statistical significance of within-individual change in UCSD scores. Results At baseline, internal consistency was high (Cronbach’s alpha = 0.97). Significant moderately strong correlations were observed between UCSD-SOBQ scores and percent predicted forced vital capacity (FVC%), r = -0.46, percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%), r = -0.32, and Borg dyspnea scores r = 0.56. UCSD-SOBQ scores were significantly different between the lowest and highest strata of FVC% (64.9 ± 18.9 vs. 36.2 ± 22.9), DLCO% and Borg scores. The threshold for worsening within-individual change in the UCSD-SOBQ score at 95% confidence was 12 points. A 1-point higher baseline UCSD-SOBQ score was associated with a 2% increase in the risk of death or transplant (HR 1.02, 95% CI 1.00, 1.04). Conclusions In fHP, the UCSD-SOBQ score is a reliable and valid measure of dyspnea severity, is responsive to change, discriminates patients with differing severities, and is associated with transplant free survival. Additional qualitative data and psychometric analyses could tailor the UCSD-SOBQ to fHP and may further improve its measurement properties.

Abstract Rationale Quantitative CT using multiple instance learning (MIL)-usual interstitial pneumonia (UIP) classifier and data-driven textural analysis (DTA) provides objective and reproducible measurements of disease pattern and extent, respectively. However, the understanding of their individual or combined relationships with outcomes in fibrotic hypersensitivity pneumonitis (fHP) remains limited. Objectives To determine whether visual CT patterns of fHP or UIP, a MIL-UIP classifier, baseline and changes in DTA over 12-months and DTA at 12 months are associated with progression-free survival (PFS) in fHP. Methods The primary cohort included 134 participants with fHP. Associations between CT variables and subsequent lung function change, and PFS were assessed using linear mixed models and Cox hazards models. Results were validated in a combined dataset from three independent populations (N = 216). Results Visual patterns of fHP or UIP were not associated with PFS. A baseline MIL-UIP classification and DTA were significantly associated with 24-month PFS. However, the MIL-UIP did not predict PFS after adjusting for DTA fibrosis extent. Over 12 months, a 1-point increase in DTA across and within patients resulted in a significant decline in FVC% and DLCO%. A 12-month change in DTA (HR = 1.07, 95%CI 1.01-1.13) and DTA at 12-months (HR = 1.03, 95%CI 1.01-1.05) were associated with subsequent 12-month PFS. Similar estimates were observed in the validation cohort. Conclusions In fHP, the objectively measured extent of lung fibrosis is more prognostic than either a UIP classifier or visual CT patterns of fHP or UIP. Baseline DTA, DTA at 12 months, and its change over 12-months are associated with PFS.

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.

OBJECTIVE Adamantinomatous craniopharyngioma (ACP) is a rare type of brain tumor that affects a wide age range, from children to older adults. Due to the rarity of the disease, existing studies are predominantly limited to single-center or single-surgeon experiences, often lacking statistical power and generalizability. The aim of this study was to address this gap by providing a comprehensive analysis of ACP outcomes based on a large multicenter cohort from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). METHODS This multicenter retrospective cohort study was conducted via the RAPID consortium and assessed patients with histologically confirmed ACP treated surgically between August 2000 and November 2024 at high-volume pituitary centers across the United States. RESULTS Among the 359 patients (206 male, median age at primary surgery of 47 years) included in the analysis, 76% underwent endoscopic transsphenoidal surgery and 22% underwent craniotomy. Gross-total resection was achieved in 45% and subtotal resection in 47%. Notably, 120 of 311 patients (39%) presented with preoperative hypothalamic-pituitary axis dysfunction. Following all treatments, permanent hypothyroidism was reported in 40% of patients, adrenal insufficiency in 33%, and arginine vasopressin deficiency in 19%. Of 263 patients who underwent primary surgery, radiation therapy was administered in 84 (32%). Progression-free survival (PFS) declined from 66% at 1 year to 31% at 6 years. In the multivariable analysis, independent predictors of worse PFS included subtotal resection (HR 0.22, 95% CI 0.11–0.42; p = 0.001), partial resection (HR 0.11, 95% CI 0.04–0.28, p = 0.001), larger tumor size (HR 0.77, 95% CI 0.64–0.94; p = 0.009), and tumor extension beyond the sella and suprasellar regions (HR 0.21, 95% CI 0.06–0.74; p = 0.016). Primary surgery and salvage surgery groups showed comparable PFS. CONCLUSIONS In this large multicenter cohort study, gross-total resection was achieved in fewer than half of patients and was independently associated with improved PFS. Approximately one-third of patients underwent radiation therapy after primary surgery. These findings provide robust evidence supporting the prognostic value of extent of resection and inform contemporary treatment algorithms for ACP. The high incidence of postoperative endocrinopathy underscores the need for individualized multidisciplinary long-term care. While the retrospective design is a limitation, the multicenter approach enhances the generalizability of these results.

ABSTRACT Our study aimed to develop a novel, reproducible, minimally invasive turkey knee osteoarthritis (OA) model and evaluate whether intra‐articular hyaluronan (HA) alone or combined with purified exosome product (PEP) attenuates OA‐related functional and structural deterioration. OA was induced arthroscopically by transection of the anterior and posterior cruciate ligaments with resection of the anterior horn of the medial meniscus. Animals received intra‐articular injections of saline, HA, or PEP + HA at postoperative 2–5 weeks. Gait was assessed at 4, 8, and 12 weeks, and cartilage degeneration, subchondral bone sclerosis, osteophyte formation, synovial fibrosis, heterotopic ossification, and meniscal integrity were evaluated by quantitative CT and histology at week 12. Compared with saline, HA improved lameness, preserved cartilage glycosaminoglycan content, and reduced meniscal rupture, subchondral bone sclerosis, and periarticular heterotopic ossification. PEP + HA provided additional benefits, including prolonged stance phase, reduced synovial fibrosis, and greater chondroprotection than HA alone, while plantar pressure variables, subchondral bone remodeling, and patellar osteophytes did not differ between HA and PEP + HA. This turkey model reliably produces human‐like OA changes and enables longitudinal functional and structural assessment. Intra‐articular HA mitigated OA progression, and the addition of PEP conferred incremental joint protection.