Citations

ABSTRACT Objective This study aimed to evaluate relationships between delayed gastric emptying and appetite suppression during treatment with liraglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA). Methods We conducted a secondary data analysis from a 16‐week randomized, placebo‐controlled liraglutide trial in patients with obesity. We examined correlations between solid food gastric emptying and measurements of satiation and energy intake in the entire cohorts at baseline and end of treatment and separately in placebo‐ and liraglutide‐treated patients who completed the trial. We also compared appetitive measures among liraglutide‐treated participants who displayed either normal, persistently delayed, or transiently delayed emptying during treatment. Results In the entire cohorts at baseline and completion, gastric emptying correlated significantly with energy intake and, at baseline, with one parameter of satiation. Gastric emptying accounted for only 4%–6% of the variance in these appetitive measures. No such correlations were found in the placebo‐ or liraglutide‐treated groups alone. There were no differences in appetitive measures among the subgroups that displayed different gastric emptying patterns during liraglutide treatment. Conclusions Delayed gastric emptying appears to play little direct role in appetite suppression induced by liraglutide. Further research should explore whether delayed emptying or other gastrointestinal effects of other GLP‐1RAs affect appetite directly or indirectly. Trial Registration: ClinicalTrials.gov identifier: NCT02647944

BACKGROUND: Aortic enlargement is a powerful predictor of dissection and rupture, yet it is rarely evaluated during routine myocardial perfusion imaging, despite the widespread availability of computed tomography (CT) attenuation correction scans. The aim of this study was to determine whether fully automated, opportunistically derived, artificial intelligence-based aortic measurements from myocardial perfusion imaging CT attenuation correction scans are associated with adverse outcomes in a large multicenter cohort. METHODS: CT attenuation correction scans from patients undergoing positron emission tomography/CT and single-photon emission CT/CT myocardial perfusion imaging across 10 centers were included. A deep learning model automatically segmented the thoracic aorta, and a postprocessing algorithm extracted maximum ascending and descending diameters. The aortic size index was calculated by indexing the diameter to body surface area. RESULTS: A total of 29 339 patients (56% men; median age, 66 years [interquartile range, 58–75 years]) were included. Over a median follow-up of 3.5 years (interquartile range, 1.9–5.0 years), 5083 (17.3%) patients died. Median ascending and descending aortic size index values were 1.8 cm/m 2 (interquartile range, 1.6–2.0) and 1.5 cm/m 2 (interquartile range, 1.4–1.6), respectively, with an increase with age and higher values in females. Elevated aortic size index thresholds (ascending >2.2 cm/m 2 ; descending >1.6 cm/m 2 ) were significantly associated with increased all-cause mortality (ascending: adjusted hazard ratio, 1.16 [95% CI, 1.07–1.26], P <0.001; descending: adjusted hazard ratio, 1.23 [95% CI, 1.14–1.31]; P <0.001). Notably, the prognostic value of an abnormal aortic size index persisted independent of age, sex, and perfusion abnormalities. CONCLUSIONS: Artificial intelligence can unlock previously unused information within routine myocardial perfusion imaging CT attenuation correction scans by rapidly and automatically quantifying aortic size at scale. Opportunistic aortic measurements derived from CT attenuation correction may serve as an adjunctive risk biomarker and could add prognostic value to standard myocardial perfusion imaging without additional imaging or radiation.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Abstract Background Spinocerebellar ataxia type 3 (SCA3), the most common autosomal dominant ataxia, is driven by the accumulation of polyglutamine‐expanded (polyQ) ATXN3 proteins. While promising as biomarkers, their longitudinal trajectories across multiple biofluids remain poorly defined. Objectives To quantify polyQ ATXN3 levels in cerebrospinal fluid (CSF), plasma, and urine within a comprehensive cohort, utilizing serial measurements to map protein dynamics. Methods We employed a validated immunoassay to quantify polyQ ATXN3 in 97 symptomatic and 13 presymptomatic SCA3 patients, correlating levels with clinical features, ancestry, disease status, and longitudinal progression. Results Asian participants exhibited lower plasma but elevated urinary polyQ ATXN3 levels relative to other ancestries. While CSF levels were higher in symptomatic patients at baseline, they showed a significant longitudinal decline. Conclusions PolyQ ATXN3 is a viable multi‐biofluid biomarker. Declining CSF levels likely reflect neurodegeneration, supporting its role in tracking progression and emphasizing the need for ancestry‐based adjustment in trials. © 2026 International Parkinson and Movement Disorder Society.

Abstract Carcinoid heart disease (CHD) is associated with advanced neuroendocrine tumor liver metastases (NETLM) and may preclude surgical cytoreduction. We assessed perioperative and long‐term outcomes of hepatectomy in patients with CHD. We retrospectively analyzed 311 patients undergoing cytoreductive hepatectomy for intestinal NETLM: non‐functional ( n = 163), carcinoid syndrome (CS) without CHD ( n = 110), and CHD ( n = 38), including patients undergoing pre‐hepatectomy valve replacement. CHD patients more frequently had >10 liver metastases (78%) and larger lesions (median 9.5 cm) and required major hepatectomy more often (58%). Major morbidity was higher in CHD (up to 47%), yet 90‐day mortality remained low (≤4%). Median overall survival after hepatectomy was comparable across groups (12.5 vs. 9.1 vs. 11.4 years; p = .19), including matched analyses. With optimal cardiac management, cytoreductive hepatectomy in CHD is feasible and provides long‐term survival comparable to patients without CHD.

Abstract Purpose: The addition of MEK inhibition (MEKi) to programmed cell death ligand 1 (PD-L1) blockade improves progression-free survival (PFS) in patients with advanced biliary tract cancer. Although MEK inhibitors may increase tumor cell immunogenicity, they can impair T-cell priming/effector function, limiting combination efficacy. We hypothesized that the addition of a CD27 agonist could restore T-cell function and enhance antitumor immunity in this combination. Patients and Methods: We conducted a randomized, phase II trial evaluating atezolizumab (840 mg, intravenously, days 1 and 15) in combination with the CD27 costimulatory monoclonal antibody [CDX-1127/varlilumab (3 mg/kg, intravenously, days 1 and 15)], with/without the addition of an MEK inhibitor [cobimetinib (60 mg, orally, daily, days 1–21, off days 22–28)] in unresectable biliary tract cancer following at least one metastatic therapy. Overall response rate (ORR) and PFS were coprimary endpoints. Treatment-related changes in CD8+ tumor-infiltrating lymphocytes (TIL) were the primary correlative outcomes. Results: The trial was closed early following interim preplanned ORR analysis. At closure, 57 patients had been enrolled [n = 29 in the cobimetinib + atezolizumab + varlilumab (CAV) arm; n = 28 in the atezolizumab + varlilumab (AV) arm]. A majority (67%) had intrahepatic cholangiocarcinoma, and 32% were immunotherapy experienced. Both regimens were well tolerated without new safety signals. Objective responses were rare [0% (CAV); 3.8% (AV)]. The median PFS (mPFS) was 2.40 (CAV) and 1.84 (AV) months [hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.38–1.18]. Among immunotherapy-experienced patients, the mPFS was 3.62 (CAV) and 1.84 (AV) months (HR, 0.54; 95% CI, 0.18–1.62). Treatment with CAV increased intratumoral CD8+ T-cell density compared with treatment with AV. Conclusions: The combinations of atezolizumab and varlilumab with/without cobimetinib were safe, but neither meaningfully improved outcomes in biliary tract cancer treated in the later lines. Correlative tissue studies validated preclinical work that MEKi increases CD8+ TILs.

This review aims to evaluate the treatment and outcomes of femur fractures in children with cerebral palsy (CP). Femur fractures are common in this population because of physiological and mechanical factors. Treatment approaches vary based on functional status and fracture characteristics. Medline, Embase, Central, and Scopus databases were systematically searched for studies investigating outcomes following femur fractures in children aged 0–18 with CP who received surgical or nonsurgical treatment. Primary outcomes were fracture location, ambulatory status, treatment types, and complications. A meta-analysis was conducted when data homogeneity permitted, using mean differences for continuous outcomes and risk ratios for dichotomous outcomes. Of 213 screened articles, seven were included, reporting 335 femur fractures in 258 patients. Most fractures occurred in the distal femur (52%) followed by mid-diaphyseal fractures (32%). Treatment varied by ambulatory status and fracture location, with 60% managed nonoperatively, typically in nonambulatory patients and for distal fractures. Nonoperative treatment, mainly spica casting, showed higher malunion rates (29%) and complications like pressure sores (11%). In contrast, operative treatment, preferred for proximal and mid-diaphyseal fractures, resulted in lower malunion rates in nonambulatory children (7%; P = 0.02) but had risks of postoperative pneumonia (6%) and surgical site infection (13%). Outcomes indicated improved healing and function with operative treatments in ambulatory children. Femur fractures in children with CP require individualized treatments based on the patient’s fracture type and ambulatory status. Future studies should incorporate fracture mitigation metrics, functional outcomes, and caregiver impact to inform optimal patient-centered care.

Abstract Introduction Bipolar disorder (BD) has been associated with increased medical burden and accelerated biological aging. Long non-coding RNAs (lncRNAs) regulate molecular pathways related to cellular senescence, inflammation, and telomere maintenance, which are implicated in both BD and aging. This study examined whether aging-related lncRNA expression reflects familial vulnerability or illness-specific effects, and whether childhood trauma and lifestyle factors modulate these signatures within a gene–environment framework. Methods In this cross-sectional study, expression levels of aging-related lncRNAs, including Antisense Non-coding RNA in the INK4 Locus (ANRIL), HOX Transcript Antisense Intergenic RNA (HOTAIR), Nuclear Enriched Abundant Transcript 1 (NEAT1), Taurine Upregulated Gene 1 (TUG1), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), Growth Arrest-Specific 5 (GAS5), and Telomerase RNA Component (TERC), were measured in peripheral blood mononuclear cells (PBMCs) from individuals with bipolar disorder (BD) (n=68), siblings without BD diagnosis (SIB) (n=54), and healthy controls (HC) (n=70) using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Childhood trauma and lifestyle were assessed using the Childhood Trauma Questionnaire (CTQ) and the Healthy Lifestyle Profile II (HPLP-II). Principal component analysis generated a composite aging-related lncRNA factor. Results At the individual transcript level, NEAT1 and TERC were elevated, whereas GAS5 was reduced, in both BD and SIB relative to HC. The aging-related lncRNA composite score was higher in BD and SIB than in HC (F = 7.315, p = 0.001). Familial liability to BD (presence vs. absence of familial liability ) showed a significant main effect on the composite score (F(1,182)=8.18, p=0.005) and interacted with childhood trauma (F(1,182)=10.14, p=0.002). In multivariable models, total CTQ and physical neglect were independently associated with lower composite scores, while familial liability remained a positive predictor (all p<0.001). Conclusions Aging-related lncRNA alterations mark familial vulnerability to BD and are shaped by childhood trauma within a gene–environment interaction framework.

Abstract Objective This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). Methods Multicenter inpatient and follow‐up clinical and EEG data were analyzed using International League Against Epilepsy definitions and American Clinical Neurophysiology Society (ACNS) EEG terminology. Results Forty‐four patients were included from the Yale NORSE/FIRES Biorepository (median age = 29 years, 33 female, 38 cryptogenic). Nine hundred twenty inpatient EEG days were reviewed (median = 13.5 days/patient). Presenting status epilepticus (SE) types included 24 convulsive SE (CSE), five focal–motor (FMSE), and 15 nonconvulsive (NCSE). Of 39 patients with post discharge follow‐up (median = 14.7 months), 61.5% ( n = 24) had seizures and required more antiseizure medications than seizure‐free patients (median = 4 vs. 1, p < .001). Inpatient EEG captured epileptiform discharges in all and periodic discharges in 38 patients. Seizures were captured in 38 patients: 33 electrographic (11 only electrographic) and 27 electroclinical. Total seizure burden ranged 6.5–29 615.0 min (median = 50.7). Seizures fulfilling ACNS EEG criteria for SE were captured in 20 patients; two had CSE and the remainder NCSE with coma, nine of whom also had FMSE. Inpatient seizure days (median = 50.0 vs. 15.5%, p = .004) and seizure burden (median = 42.9 vs. 0 min, p = .009) were higher in the first half of monitored days. Interictal findings were equally present and did not predict postdischarge seizures, whereas electroclinical seizures (90.9% vs. 45.5%, p = .037), seizure burden (median = 116.8 vs. 32.5 min, p = .045), and proportion of seizure days (36.3% vs. 20.0%, p = .037) did. Among 12 patients with follow‐up EEGs (median = 19.6 months post onset), posterior‐dominant rhythm (PDR) returned in nine; five had periodic discharges, and three had seizure captured. Significance Seizures are most commonly convulsive upon presentation and nonconvulsive or clinically subtle throughout the inpatient course in NORSE. Inpatient seizures, but not interictal abnormalities, occur earlier in the inpatient course and presence of electroclinical seizures, seizure burden, and proportion of seizure days but not interictal findings are associated with postdischarge seizures. Although return of PDR reflects neurological recovery, seizure persistence and EEG abnormalities post‐NORSE are common.