Citations

Abstract The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently celebrated its 20th anniversary, reflecting two decades of major contributions to Alzheimer's research through open data sharing and longitudinal multimodal assessments. This review synthesizes 122 high‐impact studies using ADNI data or biospecimens from 2023 to mid‐2025 to clarify mechanisms of Alzheimer's disease (AD) progression. Studies describe impairment of glymphatic clearance and the impact of cerebral small vessel disease, trajectories of amyloid beta and tau deposition, inflammation, metabolic disturbances, synaptic dysfunction, and neurodegeneration, leading to cognitive impairment and neuropsychiatric symptoms. Multifactorial contributions from genetic and epigenetic influences, co‐pathologies and comorbidities, and mechanisms of resilience modulate disease progression. Finally, heterogeneity of clinical presentation and disease course is described in the context of multiple contributing factors, highlighting the complexity of AD. By integrating imaging, fluid biomarkers, genetics, and clinical measures, ADNI provides a comprehensive research dataset for unraveling mechanisms underlying AD progression.

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using FFPE tissues from 159 patients with DLBCL, and identified 746 cancer genes at or proximal to the rearrangement breakpoints with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis for genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

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.

Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation, yet its long-term impact remains understudied. Heterogeneous populations, short follow-up, and inadequate control of donor-related factors have limited prior studies. Using the Scientific Registry of Transplant Recipients (2005–2024), we evaluated the association between DGF and long-term graft outcomes, including a mate-kidney (same donor, discordant DGF status) analysis to isolate its independent effect. We identified 103,678 dialysis-dependent deceased donor kidney recipients maintained on tacrolimus and mycophenolate. Mixed-effects Cox models, adjusted for donor, recipient, immunologic, and procurement factors. DGF occurred in 30.1% of recipients and was associated with increased death-censored graft failure (HR 1.40; 95% CI 1.33–1.47) and overall graft failure (HR 1.27; 95% CI 1.23–1.31). DGF recipients had higher rejection rates at 6 (6.0% vs. 4.7%) and 12 months (8.9% vs. 7.3%), longer hospital stay, and higher 1-year rehospitalization. In the mate-kidney analysis (6,818 donors), DGF remained strongly associated with death-censored graft failure (HR 1.58; 95% CI 1.39–1.80) and overall graft failure (HR 1.35; 95% CI 1.25–1.46), confirming the independent effect of DGF. DGF is a strong predictor of adverse long-term outcomes irrespective of rejection and warrants targeted prevention strategies and intensified follow-up.

Abstract Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts. One sentence summary A combination of four mitochondrial functional tests to identify or confirm suspected primary mitochondrial disease in fibroblasts had good sensitivity and excellent specificity, well beyond what was perceived using enzyme assays only.

Introduction The introduction of the purpose‐built single‐port (SP) robotic platform has allowed for the advent of regionalized minimally invasive surgical approaches for robotic radical prostatectomy (RARP), including the extraperitoneal and transvesical techniques. This study sought to develop a best practice consensus on the key principles, patient selection, surgical techniques, expected clinical outcomes, and learning curves pertaining to SP‐RARP. Methods A modified Delphi consensus was developed by a panel of experts, consisting of a 33‐item questionnaire, with each statement rated using a binary Likert scale (‘agree’ or ‘disagree’). The survey was distributed via email to all practicing SP‐RARP surgeons across the USA and Europe. Consensus was defined as ≥75% agreement on a given statement. Results A total of 53 surgeons participated in the Delphi Consensus across the two rounds. Of 33 statements, 28 (84.8%) reached agreement in the first round. The remaining consensus was achieved in the second round, involving 35 surgeons, and with one additional statement. The panel agreed that, although are no absolute contraindications to SP‐RARP, the preference towards specific SP‐RARP techniques should remain guided by the individual patients and surgical expertise. Although the SP extraperitoneal technique is recommended to pursue pelvic lymph node dissections, the panel agreed that transvesical SP‐RARP showed promise in promoting shorter hospital stay, faster recovery of urinary continence, and utility in patients with extensive prior abdominal surgery. Consensus was also reached on the need for a structured training pathway, with most recommending beginning with extraperitoneal SP‐RARP before advancing to the transvesical approach. Conclusion This Delphi consensus demonstrates broad agreement among experienced SP surgeons in the USA and Europe, forming the foundation for future research on the clinical utility and necessary training pathways for SP‐RARP. Nevertheless, empirical validation based on clinical data from large cohort studies remains important.

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 )

Abstract Objective Invasive presurgical evaluation plays a key role in pediatric epilepsy surgery, particularly in magnetic resonance imaging (MRI)‐negative cases, by guiding resective, disconnective, or ablative procedures. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Taskforce study provides an updated global overview of current invasive evaluation practices. Methods Group‐level data were collected from 61 epilepsy surgery programs (49 pediatric‐only) in 29 countries across six continents. Included were children and adolescents who underwent presurgical evaluation and epilepsy surgery in 2023. The study was designed to enable comparison with the similar ILAE survey conducted in 2004. Results A total of 2427 patients were included. Invasive evaluations were performed in 21.1% of cases, most frequently in North America (33.7%, higher than Europe: 18.0%, p = .003). Among invasive cases, 32.3% had no detectable MRI abnormalities. The main indication for invasive evaluation was seizure onset localization (88.1%), followed by motor or sensory mapping (17.2%) and language mapping (14.2%). Stereoelectroencephalography (SEEG) was the predominant technique (19.8% overall, 93.6% of invasive cases), more common in North America (30.0%, p = .021) and less common in South America (7.4%, p < .001). Subdural electrodes were used in only 3.2% of invasive cases, and combined depth and subdural approaches in 3.2%. SEEG‐guided radiofrequency thermocoagulation (RF‐TC) was performed in 40.9% of SEEG cases, most commonly in Asia (63.8%). In 16.2% of invasive evaluations, patients did not proceed to resection, disconnection, or ablation, with the highest rate in Europe (28.5%). Significance This global survey provides the first broad overview of invasive evaluation practices in pediatric epilepsy surgery across participating centers worldwide. It highlights the widespread adoption of SEEG, declining use of subdural electrodes, and increasing application of SEEG‐guided RF‐TC. The high proportion of MRI‐negative cases and the considerable proportion of patients not proceeding to resection, disconnection, or ablation underscore the complexity of contemporary surgical candidates and the need for further refinement of selection strategies.