Citations

OBJECTIVE Maximal safe resection of intra-axial brain tumors near the motor cortex is aided by intraoperative motor mapping. Here, the authors compared outcomes in patients undergoing either low-frequency bipolar stimulation (LFBS) or high-frequency monopolar stimulation (HFMS) for cortical and/or subcortical motor mapping during brain tumor resection. METHODS A retrospective analysis of patients undergoing an asleep craniotomy with motor mapping or an awake craniotomy with motor and speech mapping with a single surgeon was performed. Three cohorts were compared: 1) asleep LFBS (AsLFBS), 2) awake LFBS (AwLFBS; motor + speech mapping), and 3) asleep HFMS. HFMS mapping was not used for awake craniotomies. RESULTS A total of 284 patients who underwent 300 craniotomies with motor mapping were identified. No significant differences in permanent neurological deficits (p = 0.377) or extent of resection (EOR) of nonenhancing tumors (p = 0.453) were identified between LFBS or HFMS motor mapping cases. Both EOR (92.7% vs 83.5%, p = 0.035) and permanent neurological deficits (7.6% vs 3.3%) occurred more frequently in enhancing tumors with LFBS, although the latter was not statistically significant. HFMS was associated with higher rates of subcortical motor pathway identification (p = 0.001) and fewer total intraoperative seizures (p = 0.003) compared with LFBS. Previous resection (HR 0.46, p = 0.003) and a higher cortical threshold (HR 0.95, p = 0.023) were significantly associated with longer survival, while preoperative aphasia (HR 2.24, p = 0.022), hospital length of stay (HR 1.1, p = 0.005), an insular-based tumor (HR 3.5, p = 0.021), and a histological diagnosis of glioblastoma (HR 2.9, p = 0.001) were negative predictors. Interestingly, overall FLAIR EOR was significantly associated with a marginally decreased overall survival (HR 1.01, p = 0.011). CONCLUSIONS No significant differences in postoperative neurological deficits were found between LFBS and HFMS paradigms. HFMS may identify subcortical motor fibers more reliably while resulting in significantly fewer intraoperative seizures. Although LFBS was associated with greater EOR of contrast-enhancing tumors, it may also be associated with higher rates of postoperative deficits, perhaps reflecting less reliable identification of subcortical motor fibers.

Importance TMEM106B is a frontotemporal lobar degeneration (FTLD) genetic susceptibility factor, and TMEM106B protein aggregates are a feature of aging and neurodegeneration. Whether TMEM106B protein levels are associated with clinical features is unknown. Objective To investigate the clinical associations of cerebrospinal fluid (CSF) TMEM106B in FTLD. Design, Setting, and Participants This cross-sectional study was conducted in 2 independent frontotemporal dementia (FTD) cohorts (recruitment from April 2009 through July 2023, with analyses from January 2025 through April 2026), with a 2-year follow up. This multicenter clinical study integrated clinical, genetic, biomarker, and neuroimaging data. Individuals were recruited through the University of California, San Francisco (n = 3733), or ALLFTD (n = 2343). Participants with available CSF were included. A discovery cohort (n = 271) included participants with sporadic neuropathology-confirmed FTLD; presymptomatic or symptomatic carriers of pathogenic variants in C9orf72 , GRN , or MAPT ; or controls. An independent validation cohort (n = 383) included participants with clinically diagnosed sporadic FTD, Alzheimer disease (AD), and controls. Exposures CSF samples for TMEM106B quantification with aptamer proteomics (SomaScan version 3.0 [discovery cohort] and SomaScan version 4.1 [validation cohort]). Main Outcomes and Measures Parametric tests compared the primary outcome, CSF TMEM106B, by disease severity, TMEM106B rs1990622 genotype, sex, clinical syndrome, pathological diagnosis, and pathogenic variant and determined associations with brain volume. Results In the discovery (n = 271; 136 women [51%]; median [IQR] age, 59 [38-80] years) and validation (n = 383; 183 women [48%]; median [IQR] age, 64 [50-78] years) cohorts, lower CSF TMEM106B was associated with more severe disease (β, −0.15; 95% CI, −0.24 to −0.04; P = .003), lower frontotemporal brain volumes (β, 0.42; 95% CI, 0.24-0.61; P < .001), and faster clinical progression (β, −2.21; 95% CI, −3.70 to −0.72; P = .001). Associations of TMEM106B with clinical disease severity were independent of those with neurofilament light chain. TMEM106B levels were influenced by TMEM106B rs1990622 genotype, where individuals with the protective G/G genotype had lower levels than the risk A/A genotype. CSF TMEM106B levels did not differentiate between FTLD subtypes or between FTLD and AD. Conclusions and Relevance Per the results of this cross-sectional study, TMEM106B is detectable in CSF and levels reflect disease severity in sporadic and genetic FTLD and AD, but levels are also influenced by the TMEM106B rs1990622 genotype. CSF TMEM106B could support further studies to understand the mechanisms of disease and develop clinical tools in FTLD and other neurodegenerative diseases.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

BACKGROUND: Surgical management of Crohn’s disease of the colon and rectum frequently requires total proctocolectomy with end ileostomy. There are limited data on the need for Crohn’s disease–directed therapy and the prevalence of recurrence after surgery. OBJECTIVE: To determine the risk of small-bowel Crohn’s disease recurrence and evaluate risk factors for postoperative recurrence after total proctocolectomy with end ileostomy. DESIGN: Retrospective cohort study. SETTINGS: Multistate tertiary health care system. PATIENTS: Adult patients with Crohn’s disease undergoing total proctocolectomy with end ileostomy between 2014 and 2023. MAIN OUTCOME MEASURES: The primary outcome was small-bowel Crohn’s disease recurrence. RESULTS: A total of 193 patients with a median age of 45 years (interquartile range, 34–61) were included. More than half of the patients (n = 102; 52.9%) had a history of small-bowel Crohn’s disease, and the majority (n = 134; 69.4%) received biologic therapy before surgery. The median follow-up time was 4.8 years (interquartile range, 2.0–7.6). Postoperatively, 30.6% of patients (n = 59) received biologic therapy. Thirty-five patients (18.1%) had small-bowel Crohn’s disease recurrence for an estimated 5-year recurrence-free rate of 80.2% (95% CI, 73.0–85.7). Seven patients (3.6%) developed small-bowel Crohn’s disease recurrence requiring surgery for an estimated 5-year surgical recurrence-free rate of 94.7% (95% CI, 89.0–97.5). On multivariable analysis, history of small-bowel Crohn’s disease (HR 2.17; 95% CI‚ 1.04–4.54) and diagnosis at age younger than 18 years (HR 2.31; 95% CI‚1.1–4.86) were associated with small-bowel Crohn’s disease recurrence. LIMITATIONS: Retrospective design and nonstandardized follow-up. CONCLUSIONS: Patients undergoing total proctocolectomy with end ileostomy for Crohn’s disease have approximately a 20% risk of small-bowel recurrence at 5 years but a low risk of requiring surgical intervention. Patients with a history of small-bowel Crohn’s disease and younger age at diagnosis have a higher risk of recurrence and may warrant consideration of more frequent surveillance and medical prophylaxis. See Video Abstract . FACTORES DE RIESGO DE RECURRENCIA DE LA ENFERMEDAD DE CROHN DEL INTESTINO DELGADO DESPUÉS DE UNA PROCTOCOLECTOMÍA TOTAL ANTECEDENTES: El tratamiento quirúrgico de la enfermedad de Crohn del colon y el recto frecuentemente requiere proctocolectomía total con ileostomía terminal. Existe información limitada sobre la necesidad de terapia dirigida a la enfermedad de Crohn y la prevalencia de recurrencia tras la cirugía. OBJETIVO: Determinar el riesgo de recurrencia de la enfermedad de Crohn del intestino delgado y evaluar los factores de riesgo de recurrencia posoperatoria tras proctocolectomía total con ileostomía terminal. DISEÑO: Estudio de cohorte retrospectivo. ÁMBITO: Sistema de atención médica terciaria multiestatal. PACIENTES: Pacientes adultos con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2014 y 2023. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la recurrencia de la enfermedad de Crohn del intestino delgado. RESULTADOS: Se incluyeron un total de 193 pacientes con una mediana de edad de 45 años (RIC, 34-61). Más de la mitad de los pacientes (n = 102, 52,9 %) tenían antecedentes de enfermedad de Crohn del intestino delgado y la mayoría (n = 134, 69,4 %) recibieron terapia biológica antes de la cirugía. El tiempo medio de seguimiento fue de 4,8 años (RIC, 2,0-7,6). Después de la cirugía, el 30,6 % de los pacientes (n = 59) recibieron terapia biológica. Treinta y cinco pacientes (18,1 %) tuvieron recurrencia de la enfermedad de Crohn del intestino delgado para una tasa estimada libre de recurrencia a 5 años del 80,2 % (IC del 95 %, 73,0-85,7). Siete pacientes (3,6 %) desarrollaron recurrencia de la enfermedad de Crohn del intestino delgado que requirió cirugía para una tasa estimada libre de recurrencia quirúrgica a 5 años del 94,7 % (IC del 95 %, 89,0-97,5). En el análisis multivariable, los antecedentes de enfermedad de Crohn del intestino delgado (HR 2,17; IC del 95%: 1,04-4,54) y el diagnóstico antes de los 18 años (HR 2,31; IC del 95%: 1,1-4,86) se asociaron con la recurrencia de la enfermedad de Crohn del intestino delgado. LIMITACIONES: Diseño retrospectivo y seguimiento no estandarizado. CONCLUSIONES: Los pacientes sometidos a proctocolectomía total con ileostomía terminal por enfermedad de Crohn tienen aproximadamente un 20% de riesgo de recurrencia en el intestino delgado a los 5 años, pero un bajo riesgo de requerir intervención quirúrgica. Los pacientes con antecedentes de enfermedad de Crohn del intestino delgado y menor edad al diagnóstico tienen un mayor riesgo de recurrencia y podrían requerir una vigilancia más frecuente y profilaxis médica. (AI-generated translation )

Background. The adoption of technical variant grafts has expanded the donor pool for pediatric liver transplantation, but it also poses a risk of portal vein thrombosis (PVT). This study evaluated risk and prognostic factors of PVT in children undergoing liver transplantation with technical variant grafts. Methods. A total of 3137 pediatric patients from 19 centers were included: 470 received split/reduced deceased donor grafts and 2667 received living donor grafts. Multivariable logistic regression was used to identify risk factors, whereas time-dependent Cox models were used to assess the impact on survival. Results. PVT occurred in 102 patients (3.3%) and was associated with increased mortality (adjusted hazard ratio, 2.86; 95% confidence interval [CI], 1.13-7.25; P = 0.027) and graft loss (adjusted hazard ratio, 9.97; 95% CI, 4.90-20.3; P < 0.001). Risk factors included younger age, lower weight, higher Pediatric End-Stage Liver Disease score, longer cold ischemia and operation times, higher graft-to-recipient weight ratio, increased red blood cell transfusions, and biliary atresia. After adjusting for center, lower weight (odds ratio, 0.84 per kg; 95% CI, 0.71-1.00; P = 0.047) and biliary atresia (odds ratio, 2.34; 95% CI, 1.10-5.00; P = 0.027) remained predictors. Five-year patient (88.4% versus 93.1%) and graft survival (82.7% versus 96.3%) were significantly inferior in patients with PVT. Conclusions. Low-weight children with biliary atresia constituted a high-risk group, highlighting the necessity for early detection and management.

Abstract Metabolic vulnerabilities in cancer have been targeted primarily to suppress tumor growth, but less is known about the metabolic requirements for tumor cell invasion. Here we report that lipid catabolism by cytosolic and lysosomal lipases supports pancreatic cancer cell invasion through both overlapping and distinct functional and metabolic mechanisms. Lysosomal acid lipase (LAL)-dependent lipid droplet catabolism promotes invadopodia formation and stabilization, enabling extracellular matrix degradation. In addition to modulating cellular energetics, lipidomics revealed that lipid droplet catabolism regulates cholesterol and membrane phospholipid levels. Using spatially resolved biosensors and cholesterol imaging, we found that lysosomal lipid catabolism occurs at invadopodia and sustains local ATP and membrane cholesterol. These findings identify spatially organized lipid catabolism as a mechanism that couples local energetics and membrane remodeling during the earliest steps of pancreatic cancer cell invasion.