Citations

ABSTRACT Pulmonary hypertension (PH) is a common complication in interstitial lung disease (ILD), but the additional burden it imposes on patients and healthcare systems is not well characterized. This retrospective analysis of claims data from the US Merative MarketScan database assessed hospitalization rates and costs over 2 years in patients with connective tissue disease‐related ILD (CTD‐ILD) and non‐CTD‐ILD with or without PH (between January 2017 and December 2019). Index was the date of first ILD claim; baseline was the 12‐month preindex period. In total, 16,129 patients with non‐CTD‐ILD (1502 [9%] with PH) and 4545 patients with CTD‐ILD (663 [15%] with PH) were identified. A higher proportion of patients with non‐CTD‐ILD with PH, compared with patients without PH, had all‐cause and heart failure (HF)‐related hospitalizations during baseline (all‐cause, 37.0% vs. 22.3%; HF‐related, 14.2% vs. 3.1%), 0–12 months (62.4% vs. 43.0%; 29.0% vs. 7.0%), and 13–24 months (44.7% vs. 18.3%; 21.5% vs. 3.2%) follow‐up ( p < 0.0001 for all). A significantly higher proportion of patients with CTD‐ILD with PH, compared with patients without PH, had all‐cause and HF‐related hospitalizations during baseline (all‐cause: 30.0% vs. 20.6%; HF‐related: 9.1% vs. 1.9%), 0–12 months (41.9% vs. 29.1%; 15.5% vs. 3.9%), and 13–24 months (37.9% vs. 18.9%; 13.9% vs. 2.5%) follow‐up ( p < 0.0001 for all). In both cohorts, total all‐cause and HF‐related costs were significantly higher in patients with PH at baseline, 0–12 months, and 13–24 months follow‐up ( p < 0.05 for all). PH substantially increased hospitalization risks and costs in both types of ILD, underscoring the importance of improving outcomes in patients with ILD‐PH.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

Abstract Background Adolescent and young adult (AYA) patients remain underrepresented in neuro-oncology research. Despite being the second most common primary brain tumor in this population, meningiomas have not been studied using age-specific molecular analyses. DNA methylation-based classification and prognostic tools have transformed meningioma care. This study aimed to evaluate the performance of these tools across age groups. Methods We analyzed 1,568 meningiomas with DNA methylation and clinical data, including 18 pediatric patients (&lt;15 years), 195 AYA patients (15-39 years), and 1,355 adult patients (&gt;39 years). Pediatric and AYA (P/AYA) tumors were combined and compared with adult tumors. The performance of established molecular classifiers and recurrence predictors, as well as differences in chromosomal copy number alterations were compared across age groups. Results While histologic grading was comparable between cohorts, P/AYA tumors displayed significantly fewer aggressive molecular groups and lower frequencies of chromosomal arm losses, including 1p, 6q, and 14q. The adult-trained recurrence predictor failed in the P/AYA population (AUC 0.57), despite similar score distributions. Retraining the model on an age-specific cohort using an identical analytic framework improved performance (AUC 0.79) and enabled effective stratification of progression-free survival (P = 0.00054). Importantly, 1p loss retained prognostic significance within the P/AYA group, supporting its clinical utility. Conclusions Molecular tools developed in adult-dominant cohorts do not generalize to younger patients due to both biological divergence and exclusion from model development. These findings underscore the need for age-specific molecular frameworks and highlight the imperative of including P/AYA populations in precision neuro-oncology research to ensure lifespan-equitable care.

Abstract Background and Aims Decrease in pulmonary vascular resistance (PVR) during exercise confers favourable prognosis in biventricular physiology, but its role in Fontan circulation remains unknown. This study aimed to evaluate the prognostic value of PVR index (PVRI) response to exercise in adults post-Fontan palliation. Methods Retrospective cohort of 88 adults (age ≥18 years) post-Fontan undergoing exercise (supine cycling) cardiac catheterization. Patients were categorized into absence (n = 23) or presence (n = 65) of exercise-induced reduction in PVRI. The clinical endpoint was a composite of death or transplantation. Results Age at catheterization was 32.2 ± 8.8 years, and 45.5% were female. Resting and exercise PVRI were 1.9 ± 0.9 and 1.2 (interquartile range [IQR] 0.8–2.1) WU·m2, respectively. Clinical, biochemical and echocardiographic parameters were not associated with PVRI response to exercise. During a follow-up of 2.2 ± 1.4 (IQR 1.2–2.6) years, resting PVRI was not associated with the clinical endpoint (hazard ratio [HR] 0.95 per WU·m2, 95% confidence interval [CI] 0.52–1.74; P = 0.86), whereas exercise PVRI was (HR 2.15 per WU·m2, 95% CI 1.24–3.73; P = .007). Exercise PVRI remained predictive of outcomes after adjusting for exercise pulmonary artery wedge pressure (HR 2.08 per WU·m2, 95% CI 1.19–3.62; P = .01) or clinical risk factors individually. Two-year event-free survival was lower in the no PVRI reduction than in the reduction group (67% vs 95%; P &lt; .001). Conclusions In adults post-Fontan, PVRI response to exercise is a robust predictor of clinical outcomes and offers additive prognostic information beyond resting invasive haemodynamic data and clinical risk factors, underscoring the importance of invasive exercise testing in this population.

BACKGROUND: The first total pancreatectomy (TP) resulting in survival past the immediate postoperative period was performed at Mayo Clinic in 1944. Although still uncommonly performed, indications have recently fluctuated. We aimed to evaluate trends in TP use and outcomes over four decades. STUDY DESIGN: Patients who underwent single-stage TP at Mayo Clinic Rochester from 1988 to 2024 were analyzed in two cohorts: early era (EE, 1988 to 2009) and modern era (ME, 2010 to 2024). RESULTS: In total, 437 patients were identified: 118 during EE (mean 8 per year) and 319 during ME (mean 21 per year). Primary indications were adenocarcinoma (42% EE vs 60% ME), intraductal papillary mucinous neoplasm (31% EE vs 17% ME), and chronic pancreatitis (11% EE vs 13% ME; p < 0.001). Concurrent vascular resection was performed in 9.3% (EE; all venous only) vs 53% (ME; venous alone in 20% and arterial with or without venous in 33%; p < 0.001). Multivisceral resection was performed in <1% (EE) vs 24% (ME; p < 0.001). Major complications occurred in 13% (EE) vs 27% (ME; p = 0.018), and 90-day mortality was 3.4% (EE) vs 6.3% (ME; p = 0.35). For adenocarcinoma, 5-year median overall survival from both surgery and diagnosis was significantly improved in ME (p = 0.009 and p < 0.001, respectively). Median last HbA1c was 7.7 (EE) vs 7.3 (ME; p < 0.001). Among patients surviving more than 1 year, insulin pumps were used in 12% (EE) vs 49% (ME; p < 0.001). Conclusions: The use of TP has dramatically increased in recent years, primarily for adenocarcinoma alongside increased use of neoadjuvant therapy and ever-expanding criteria for anatomic resectability. Operative complexity has significantly increased with resultant increased perioperative morbidity. TP remains a higher-risk procedure, specifically with en bloc vascular resections, emphasizing the importance of appropriate patient selection, preoperative patient education, and thoughtful postoperative and long-term management.

BACKGROUND: Early recognition of postoperative ileus remains difficult. OBJECTIVE: To determine whether myoelectric activity recorded by a noninvasive, wireless patch system correlated with the onset of postoperative ileus/bowel dysfunction. DESIGN: Single-arm, prospective study. The surgeon was blinded to myoelectric bowel activity until study completion. SETTINGS: Single surgeon, tertiary referral center. PATIENTS: Consecutive adult patients undergoing abdominal colorectal surgery. INTERVENTIONS: Three wireless patches acquiring myoelectrical GI activity were placed on the abdomen after surgery and removed before hospital discharge/reoperation. All patients followed an enterprise-specific enhanced recovery protocol. MAIN OUTCOME MEASURES: Ileus (nausea, vomiting, abdominal distention requiring nasogastric tube placement) or bowel dysfunction (similar symptoms without nasogastric tube needed) detected clinically within 30 postoperative days. Daily gut activity prints (histograms of the frequencies of all peaks detected in 10-minute time windows) were created for each patient for every 4-hour period after surgery, and activity was averaged and plotted for each group. Peaks in the 8 to 12 cycles per minute range were assigned to intestinal activity, and the energy under the peaks was summed through day 1, day 2, and day 3 and compared among patients. RESULTS: Patch application on 46 enrolled cases undergoing abdominal colorectal surgery (open in 17, robotic in 11, laparoscopic in 18) was not associated with any adverse events. Hyperactive intestinal activity was significantly higher in 12 patients who developed postoperative ileus/bowel dysfunction within 16 hours postoperatively ( p = 0.041), with a more pronounced difference at 20 and 24 hours ( p = 0.016 and p = 0.013, respectively). LIMITATIONS: Data were collected blindly during standard postoperative care; therefore, the integration of technology into clinical practice remains to be tested. CONCLUSIONS: Noninvasive measurement of intestinal myoelectrical activity allowed early identification of postoperative ileus/bowel dysfunction. Future studies will assess the possible advantages deriving from the integration of this system into clinical practice. See Video Abstract . LOS PICOS INTESTINALES HIPERACTIVOS OBSERVADOS POCAS HORAS DESPUÉS DE LA CIRUGÍA COLORRECTAL IDENTIFICAN A LOS PACIENTES QUE DESARROLLAN ÍLEO POSOPERATORIO ANTECEDENTES: El reconocimiento precoz del íleo posoperatorio sigue siendo difícil. OBJETIVO: Determinar si la actividad mioeléctrica registrada por un sistema de parches inalámbricos no invasivos se correlacionaba con la aparición de íleo posoperatorio/disfunción intestinal. DISEÑO: Estudio prospectivo de un solo grupo. El cirujano desconocía la actividad mioeléctrica intestinal hasta la finalización del estudio. ENTORNO: Un solo cirujano, centro de referencia terciario. PACIENTES: Pacientes adultos consecutivos sometidos a cirugía colorrectal abdominal. INTERVENCIONES: Se colocaron tres parches inalámbricos que registraban la actividad mioeléctrica gastrointestinal en el abdomen después de la cirugía y se retiraron antes del alta hospitalaria o la reintervención. Todos los pacientes siguieron un protocolo de recuperación mejorada específico de la empresa. PRINCIPALES MEDIDAS DE RESULTADO: Íleo (náuseas, vómitos, distensión abdominal que requiere la colocación de una sonda nasogástrica) o disfunción intestinal (síntomas similares sin necesidad de sonda nasogástrica) detectados clínicamente en los 30 días posteriores a la operación. Se crearon GutPrints (histogramas de frecuencias de todos los picos detectados en intervalos de 10 minutos) de la actividad intestinal diaria para cada periodo de 4 horas tras la cirugía, se promediaron y se representaron gráficamente para cada uno de los grupos. Los picos en el rango de 8 a 12 cpm (ciclos por minuto) se asignaron a la actividad intestinal y la energía bajo los picos se sumó a lo largo del día 1, el día 2 y el día 3 y se comparó entre los pacientes. RESULTADOS: La aplicación del parche en 46 casos inscritos sometidos a cirugía colorrectal abdominal (abierta en 17, robótica en 11 y laparoscópica en 18) no se asoció con ningún evento adverso. La actividad intestinal hiperactiva fue significativamente mayor en 12 pacientes que desarrollaron íleo postoperatorio/disfunción intestinal en las 16 horas posteriores a la operación ( p = 0,041), con una diferencia más pronunciada a las 20 y 24 horas ( p = 0,016 y p = 0,013, respectivamente). LIMITACIONES: Los datos se recopilaron de forma ciega durante la atención posoperatoria estándar, por lo que aún queda por comprobar la integración de la tecnología en la práctica clínica. CONCLUSIONES: La medición no invasiva de la actividad mioeléctrica intestinal permitió la identificación temprana del íleo/disfunción intestinal posoperatoria. En futuros estudios se evaluarán las posibles ventajas derivadas de la integración de este sistema en la práctica clínica. ( AI-generated translation )

Background Exercise cardiac catheterization is the gold standard for diagnosing diastolic dysfunction and impaired pulmonary reserve in patients with Fontan circulation. The diagnostic value of noninvasive parameters is unclear. Methods Patients who underwent simultaneous exercise hemodynamic evaluation and peripheral venous pressure (PVP) measurement were included. Echocardiographic surrogates for ventricular filling pressure were compared with invasive measures. Diastolic dysfunction was defined invasively as either resting pulmonary artery wedge pressure ≥12 mm Hg or exercise pulmonary artery wedge pressure >20 mm Hg. Results Twenty‐nine patients were included. Age at catheterization was 34±9 years. Atrioventricular valve systole‐to‐diastole duration ratio (S/D) and resting PVP were significant predictors of resting pulmonary artery wedge pressure (S/D: β=0.71 per 0.1 S/D [95% CI, 0.16–1.25]; P =0.01; PVP: β=0.68 per mm Hg [95% CI, 0.41–0.96]; P <0.001). By contrast, resting PVP was a predictor of diastolic dysfunction, whereas S/D was not. Based on these data, we proposed a 2‐tier assessment algorithm with the first tier considering resting PVP ≤15 mm Hg and S/D ≤1.1 and the second tier considering exercise PVP ≤25 mm Hg in those with 1 elevated resting parameter. This algorithm showed a positive predictive value of 88% (95% CI, 47%–100%), a negative predictive value of 90% (95% CI, 70%–99%), a sensitivity of 78% (95% CI, 40%–97%), and a specificity of 95% (95% CI, 75%–100%). Exercise PVP indexed to peak oxygen consumption also predicted invasively measured exercise pulmonary vascular resistance index (β=0.36 WU·m 2 per mm Hg/100 mL per min [95% CI, 0.08–0.64]; P =0.01). Conclusions This study presents a simple, noninvasive approach for evaluating diastolic function and pulmonary vascular reserve in patients with a Fontan circulation.

Background: Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. Objectives: To determine the correlation between DNAm and TL aging markers. Methods: We conducted a cross-sectional case–control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. Results: We analyzed biological ages in 270 participants (125 POMS, mean 15.7 years; 145 controls, mean 15.3 years). There were moderate correlations among the different DNAm clocks, but no correlations between DNAm clocks and TL in pooled analyses. In a stratified analysis, only the control group showed a modest correlation between TL and PhenoAge clock ( r = 0.2, p = 0.06). Conclusions: DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.

Objective To assess real‐world effectiveness of switching disease‐modifying therapy (DMT) in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS) initially treated with platform injectables on disease activity. Methods Of 2615 pediatric‐onset demyelinating disease patients at 12 clinics in the United States (US) Network of Pediatric MS Centers, those with MS/CIS on initial therapy with a platform injectable who switched to another class of platform injectable, oral or infusion DMT were analyzed. Relapse rate was modeled with negative binomial regression, adjusted for preidentified confounders. Results A total of 212 children switched DMT before age 18 (67% female, 95% MS). Ninety‐three switched from injectable to injectable, 76 injectable to oral, and 43 injectable to infusion. Switchers to oral or infusion were older at onset (injectable 12.3 years, oral 13.5 years, and infusion 14.2 years) and switch (injectable 14.6 years, oral 16.0 years, and infusion 15.7 years). Switchers to infusion DMT were more likely to have enhancing lesions (injectable 45%, oral 28%, and infusion 67%). Compared to injectable (annualized relapse rate [ARR] = 0.88, 95% confidence interval [CI] = 0.52–1.48), relapse rates were lower for injectable to oral (ARR = 0.34, 95% CI = 0.20–0.57; rate ratio: 0.38, 95% CI = 0.21–0.69) and injectable to infusion (ARR = 0.18, 95% CI = 0.09–0.37; rate ratio: 0.21, 95% CI = 0.10–0.44) ( p < 0.001). Adjusted number needed to treat in person‐years to prevent 1 relapse with oral over injectable was 1.84 (95% CI = 1.03–8.69) and infusion over injectable 1.43 (95% CI = 1.00–3.88). Interpretation Switching from platform injectable to oral or infusion compared to other platform injectable DMT led to better disease control in pediatric MS. Long‐term safety data are required. ANN NEUROL 2026;99:715–729

ABSTRACT Objective We sought to characterize the sixth most common finding in our neuroimmunological laboratory practice (tissue assay‐observed unclassified neural antibodies [UNAs]), combining protein microarray and phage immunoprecipitation sequencing (PhIP‐Seq). Methods Patient specimens (258; 133 serums; 125 CSF) meeting UNA criteria were profiled; October 2022–September 2023. Top‐ranking candidate antigens were validated in silico, by dual‐staining confocal microscopy, and ≥ 1 protein‐specific assay. Clinical data were reviewed. Results Among 21 patients, 11 autoantibodies were characterized (serum, 19; CSF, all 9 available). Autoantigens were CACNA1I, 1; CAMK2B, 2; CLIP2, 1; FMN2, 2; MAP1A, 2; MAP2, 5; NECAB1, 1; SNAP91, 3; SRCIN1, 1; SYNJ1, 1; SYT3, 2. Analytical validation was by confocal TIIFA (all), western blot (10/10 available), and cell‐based assay (5/5 performed). Clinical accompaniments were: encephalitis, 6; brainstem encephalitis, 2; encephalomyelitis, 2; cerebellar ataxia, 2; longitudinally extensive transverse myelitis (LETM), 2; sensory neuronopathy, 1; peripheral neuropathy, 4, and movement disorders, 2. Inflammatory MRI abnormalities were identified in 5/16 patients (31%) with CNS disorders: T2 signal change (2), LETM (2), leptomeningeal enhancement (1). Seven of 8 (88%) had inflammatory CSF (pleocytosis, 5 [median 25.5 cells, range 7–294]; elevated IgG index/synthesis rate, 4; CSF‐exclusive oligoclonal bands, 4). Six had paraneoplastic causation (lung cancer, 2; other, 4); 3 were postinfectious (1 each of COVID‐19, HSV‐1, and post‐Group A streptococcal infection). Of 9 immunotherapy‐treated patients, 5 improved. Interpretation UNAs are partly accounted for by a repertoire of diverse mostly intracellular synaptic antigens. Their characterization is expedited by protein arrays and PhIPSeq. Further individual studies are needed to assess them as disease biomarkers.