Citations

Abstract INTRODUCTION Cognitive impairment in hospitalized older adults without delirium is often undiagnosed. We evaluated the diagnostic accuracy and prognostic value of two brief bedside screening tools—the 10‐point Cognitive Screener (10‐CS) and Short Portable Mental Status Questionnaire (SPMSQ). METHODS Multicenter prospective cohort of 2003 patients ≥65 years of age without delirium, admitted to 43 hospitals in five countries of the Creating a Hospital Assessment Network in Geriatrics (CHANGE) Study. Screening was completed within 48 h of admission. Dementia was defined as informant‐based Clinical Dementia Rating ≥1. RESULTS Dementia prevalence was 22%, with 35% undiagnosed. Both tools showed good accuracy for detecting dementia, with the 10‐CS slightly more accurate than SPMSQ (area under the curve [AUC] = 0.87 vs 0.85; p = 0.02). After adjustment, cognitive impairment detected by either tool was associated with increased risk of incident delirium, hospital‐associated disability in self‐care activities, and 90‐day mortality, but not prolonged stay. DISCUSSION Brief bedside screening identified dementia and predicted adverse outcomes, supporting its integration into routine hospital care.

Purpose To use publicly available injured list (IL) data to 1) describe Major League Baseball injury trends from 2010 to 2024; 2) analyze injury types and body regions affected to report the highest impact injuries; and 3) report the financial implications of time lost due to injury over this 15‐year period. Methods IL data for every Major League Baseball player (pitchers and position players) from the 2010 to 2024 regular seasons were collected using publicly available sources, including player demographics, IL placements, body part injured, and length of each IL stay. Player salaries were compiled to determine the “financial loss” per injury. Results Across 15 seasons, 8078 players were placed on the IL, totaling 478,085 days. The mean IL placements/year was 634, and the annual number increased by an additional 27 injuries/year ( P < .001). Mean total IL days/season was 31,872, and this increased year‐over‐year ( P = .008). Shoulder injuries represented the most IL placements (n = 1555), followed by elbow (n = 1344) and upper leg (n = 769). Elbow injuries averaged the most days missed/IL placement (mean: 93, median: 74) and the greatest total days missed (129,610), followed by shoulder (95,189). Pitchers comprised 55% of IL placements and most commonly injured their shoulder or elbow. Infielders and outfielders accounted for 21% and 16% of IL placements, respectively. A total financial loss of $9,636,753,291 was accumulated over 15 seasons. Financial loss increased season‐to‐season (+$32,309,178/year, P = .002). Elbow injuries accounted for the highest financial loss at $1,932,048,168 ($1,379,049 lost/injury). In 2024, $2,220,432 was lost/elbow injury, $1,110,573/shoulder injury, $1,397,322/any injury, and $952,973,760 total for the season. Conclusions This study observed that the number of players, IL placements, days spent on the IL, and financial loss due to injury increased steadily each year. Pitchers were the most frequently injured players with shoulder and elbow injuries being most common. Over the 15‐season study period, there was a total financial loss of nearly $9.7 billion due to salary paid to injured players, with elbow injuries contributing the highest loss at just under $2 billion. Clinical Relevance Injury trends and financial data from Major League Baseball highlight the growing burden of shoulder and elbow injuries, particularly in pitchers. These findings underscore the need for orthopaedic surgeons to focus on prevention, early intervention, and optimized surgical management of high‐impact injuries to reduce long‐term morbidity and associated financial costs at the elite level.

Abstract Background Surrogate endpoints are increasingly used as the basis of cancer drug approvals. A strong association between treatment effects on the surrogate and true endpoint is essential for their validation as reliable endpoints. We assess the current evidence of trial-level surrogacy for colorectal cancer (CRC) endpoints through a novel framework. Methods We developed a framework to grade the quality of oncology surrogate endpoints in 7 domains of the surrogate relationship: data source quality (A-B); disease setting homogeneity (0-3); uniformness of surrogate and true endpoint definitions (0-3); number of trials evaluated (0-4); and individual- (0-2) and trial-level associations (0-8). We screened PubMed using keywords and medical subject headings terms for meta-analyses published before July 6, 2024, validating surrogate endpoint associations across CRC trials. Two reviewers blindly assessed each article before reaching a consensus score. The main outcomes were framework-derived evidence scores and reported trial-level associations (R2) with overall survival. Results A total of 18 articles were identified, containing 39 evaluations of 12 unique surrogate endpoints for overall survival. Evidence scores ranged from B6 to A23. Only disease-free survival consistently demonstrated high-quality evidence of trial-level surrogacy (≥A18, median R2 = 0.92). Progression-free survival and objective response rate were low-quality surrogates in metastatic CRC (progression-free survival: B6-A15, median R2 = 0.55; objective response rate: B6-A13, median R2 = 0.33). Other evaluated endpoints were demonstrated to be unreliable surrogates. Conclusion Disease-free survival shows high-quality surrogacy in stage II-III colon cancer. Endpoints identified in the metastatic setting demonstrate inconsistent surrogacy evidence. Reassessment and identification of new endpoints are warranted, particularly with immunotherapy.

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Failed pediatric endotracheal intubation, prompting surgical airway management via emergency front of neck access (eFONA), is an intrinsically challenging topic. While rare, all emergency airway providers must be equipped to handle these complex clinical scenarios, both through initial training and maintenance of competency. Needle cricothyrotomy is a commonly taught method in cannot intubate cannot oxygenate (CICO) scenarios for children under age eight. However, needle cricothyrotomy is technically difficult, profoundly rare, and maintaining competency is a challenge. From a multidisciplinary perspective, we examine the utility of continuing to teach needle cricothyrotomy and explore alternatives. This project group suggests that pediatric eFONA training across disciplines should focus on surgical tracheotomy rather than needle cricothyrotomy, with consideration given to specialty-specific human performance factors.

Background Difficulty tolerating the uncertainty of ambiguous or unpredictable situations may influence how patients with functional motor disorder (FMD) respond to treatment. However, only one study has examined the role of intolerance of uncertainty (IU) in FMD treatment. Objectives This study sought to expand on prior findings in a larger sample of patients with FMD who completed an intensive motor-retraining programme. Methods A consecutive cohort of 109 patients with FMD completed a 1-week intensive outpatient motor-retraining programme. Patients rated their IU using the Intolerance of Uncertainty Scale-12 and functional motor outcomes using three empirical measures before and after treatment. Univariate and multivariable analyses were conducted to (1) characterise the rate of elevated IU, (2) evaluate potential changes in IU across the programme, (3) examine whether changes in IU predict improvements in motor functioning and (4) determine if IU incrementally predicts functional improvements in patients with clinically elevated IU. Results Findings revealed that clinically elevated IU was common (yielding a base rate of 44%) and that the ‘prospective’ subtype of IU significantly decreased with 1 week of FMD treatment. Change in IU was not significantly associated with improved functional outcomes across the sample. However, change in prospective IU did predict patient-specific functional outcomes among those with clinically elevated IU ( R 2 =11%). Conclusions Findings support prior work suggesting that certain subtypes of IU are common, modifiable and related to treatment outcomes in FMD. The ‘prospective’ subtype of IU may represent an operative factor that can enhance the efficacy of existing FMD rehabilitation programmes.

ABSTRACT Background Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk‐taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied. Methods An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP). Results The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback. Conclusion Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.

Abstract GPNMB (Glycoprotein non-metastatic melanoma protein B) is a canonical transcriptional target of MiT/TFE proteins (TFEB/TFE3/MITF), expressed at low levels in normal tissues but upregulated in numerous MiT/TFE-driven tumors such as translocation RCC, alveolar soft part sarcoma and MITF-driven melanoma, where it is associated with poor prognosis. CDX-011 (CR011-MMAE) is an anti-GPNMB ADC, with demonstrated efficacy in pre-clinical models of TFE3-fusion RCC. To further characterize GPNMB functionality and value as a cell-surface therapeutic target in tRCC, we engineered cell lines with genomic deletion of GPNMB via CRSIPR-Cas9 editing. Deletion of GPNMB in PRCC-TFE3 cell lines [UOK120/UOK124] significantly decreased clonogenic growth in 2D, spheroid size and viability and tumor xenograft growth in NSG mice and was associated with a decrease in phosphorylation of mTORC1 substrates [p-P70S6K, p-4EBP1]. We then examined expression of CD44, the primary receptor for GPNMB, and a tumor-associated antigen associated with poor prognosis in many cancers. Expression of CD44 and its ligand SPP1/OPN, was significantly increased in bulk RNA-Seq data from multiple transgenic models of SFPQ-TFE3, PRCC-TFE3 and ASPSCR1-TFE3, in human tRCC cases compared to normal kidney, and in SFPQ-TFE3/ PRCC-TFE3 transgenic kidney tumors and an ASPSCR-TFE3 PDX model, by immunoblotting and IHC, with increased membrane localization. shRNA-mediated depletion of CD44 profoundly and specifically decreased clonogenicity of multiple TFE3-fusion lines, with no effect seen in ccRCC lines. In conclusion, GPNMB regulates the growth of tRCC cells, potentially via an autocrine mechanism involving its receptor CD44, and targeting GPNMB-CD44 signaling may be of therapeutic benefit in tRCC. Citation Format: Kaushal Asrani, Juhyung Woo, Kewen Feng, Thiago Vidotto, Adrianna Amaral, Vikrant Palande, Jayaprakash Mandal, Eddie Imada, Christopher Thoburn, Sangeeta Ray, Huili Li, Yasser Ged, Nirmish Singla, John A. Copland, Laura Schmidt, W. Marston Linehan, Pedram Argani, Tamara Lotan. GPNMB:CD44 signaling drives tumor progression in translocation renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr B014.