Citations

Abstract The diagnosis of predementia stages indicates an increased risk of progression to dementia. The Amyloid, Tau, and Neurodegeneration AT(N) classification considers measurements of altered proteins and the presence of neurodegeneration to classify the risk groups regarding the pathophysiology of Alzheimer's disease (AD). The cognitive and anatomical characteristics of the patients in the predementia stage according to the AT(N) classification are not fully understood. To investigate whether there are differences in the clinical and anatomical profiles among older adults in the predementia stage according to the ATN classification, and to investigate the associations involving cognition and cortical thickness and subcortical volume in the AT(N) groups. In total, 72 older adults with subjective cognitive decline and mild cognitive impairment were allocated to groups according to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging scans, and cerebrospinal fluid analyses. We used multivariate and univariate analyses with post-hoc testing to verify differences among groups. In addition, linear regressions were performed to verify the interactions involving cognition and gray matter metrics. The suspected non-AD pathophysiology group showed worse performance in attention/executive function than the AD continuum and normal biomarkers groups (p = 0.04). However, the ATN classification groups did not differ in terms of cortical thickness (p > 0.05). In addition, in the AD continuum group, memory was associated with left fusiform gyrus thickness (p = 0.000 uncorrected; r = 0.238). Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).

ABSTRACT Background: Obesity is considered a global epidemic and has shown a progressive increase in recent decades. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), is the most effective sustainable weight loss option. However, weight regain is one of the challenges facing patients and is attributed to several factors, including dilatation of the gastrojejunal anastomosis (GJA). Objectives: The central objective of this study is to correlate the influence of time on GJA widening in patients undergoing RYGB over a 7-year period. Methods: Prospective and longitudinal study conducted over 7 years in patients undergoing RYGB. Surgical and endoscopic procedures were performed in a medium hospital in the same city. Weight, body mass index (BMI) and GJA size were assessed at intervals of 2, 6, 12, 24, 30, 48, 60, and 72 months after the surgical procedure. Results: The highest mean value in the distribution of anastomosis diameter was 20±2.27 mm at 72 months after surgery. The lowest mean value was 10.2±1.70 mm at 2 months after surgery. The analysis showed that there is a significant effect of time on anastomosis diameter, with statistically significant differences in the mean value between 2, 6, 12, 24, 60, and 72 months after surgery (F(1,724,5,172)=9.555, P<0.05). Conclusion: Multiple comparative analysis showed that there are statistically significant differences between the mean lengths of anastomosis across the times studied, with a greater influence of the time factor 24 months after surgery.

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

Importance Total thyroidectomy is the established surgical standard for hereditary and sporadic medullary thyroid cancer (sMTC). However, for unilateral sporadic tumors, its benefit over lobectomy remains uncertain. Objective To compare oncologic outcomes between total thyroidectomy and lobectomy in patients with sMTC. Data Sources and Study Selection MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception to December 2025 to identify comparative studies on patients with sMTC who underwent total thyroidectomy or lobectomy. Data Extraction and Synthesis Reviewers working independently and in duplicate screened titles, abstracts, and full-text articles for eligibility using standardized instructions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) and Meta-Analysis of Observational Studies in Epidemiology ( MOOSE ) guidelines were used for reporting. Main Outcomes and Measures Primary outcomes were mortality, overall survival, structural recurrence, biochemical cure, and distant metastasis development. The secondary outcome was postoperative complications. Effect measures were calculated as odds ratios (ORs) or relative risks (RRs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results Nine retrospective studies met inclusion criteria and comprised 1371 patients (295 of 397 patients [74.3%] with documented sex were female, and median age ranged from 45.0 to 58.2 years). A total of 531 patients (38.7%) underwent lobectomy and 840 (61.3%) underwent total thyroidectomy. Of 341 tumors, 280 (82.1%) lacked extrathyroidal extension, 284 of 401 tumors (70.8%) measured smaller than 2 cm (70.8%), and 197 of 343 tumors (57.4%) were node negative; central neck dissection was performed in 445 of 492 patients (90.4%). Multifocal disease was uncommon and reported in 30 of 330 patients (9.1%). Mortality did not differ at 5 years (RR, 0.30; 95% CI, 0.07-1.35) or beyond (RR, 1.00; 95% CI, 0.40-2.47). Overall survival at 5 years was similar (RR, 1.02; 95% CI, 0.94-1.11). Total thyroidectomy was not associated with lower structural recurrence rates at 5 years (OR, 0.45; 95% CI, 0.14-1.49), but it was associated beyond 5 years (OR, 7.26; 95% CI, 1.07-49.21). No differences were observed for biochemical cure at 5 years (OR, 0.86; 95% CI, 0.47-1.56) or beyond 5 years (OR, 0.87; 95% CI, 0.26-2.89). Distant metastasis development did not differ at 5 years (OR, 1.64; 95% CI, 0.09-31.52). Sensitivity analyses revealed no differences across any outcomes. Postoperative complications were more common in total thyroidectomy. Risk of bias was high in 4 studies, moderate in 4, and low in 1. Conclusions and Relevance Findings in this systematic review and meta-analysis, based on data from retrospective studies, suggest that thyroid lobectomy may be associated with oncologic outcomes comparable to total thyroidectomy in selected patients with sMTC.

ABSTRACT Autoantibody internalization has been implicated in autoimmune disease pathogenesis, yet its mechanisms, and generality across different diseases, cell types, and affected tissues remain poorly defined. Using bulk RNA sequencing, we identified reproducible, autoantibody-specific transcriptomic signatures consistent with autoantigen dysfunction in muscle biopsies from patients with anti-Mi2 dermatomyositis and anti-PM/Scl scleromyositis across independent cohorts. Electroporation of purified patient IgG into primary cultures of healthy cells was sufficient to induce the corresponding transcriptomic programs in vitro . Direct immunofluorescence demonstrated immunoglobulin internalization into subcellular compartments matching the localization of the autoantigen in different affected tissues. Spatial transcriptomic analyses revealed that antibody-secreting cells translocated cytoplasmic material (i.e., immunoglobulin RNA) into adjacent affected cells expressing autoantibody-specific transcripts. The disease-specific transcripts were present not only in muscle fibers, but also in other cells, including macrophages, endothelial cells, and fibroblasts. Autoantibody-induced transcriptomic programs were associated with cell damage and autoantibody-specific reactive inflammatory programs, including activation of type I interferon and TGF-ß1 signaling in anti-Mi2 dermatomyositis and activation of type II interferon in anti-PM/Scl scleromyositis. Antibody internalization was also observed in different tissues from patients with other autoimmune diseases, including anti-U1RNP mixed connective tissue disease, anti-Ku overlap syndrome, and anti-Scl70 systemic sclerosis. Together, these findings establish autoantibody internalization as a shared pathogenic mechanism across diverse autoimmune diseases, providing a unifying framework for conditions driven by autoantibodies against intracellular antigens.

Purpose: Familial history of aortic disease has been associated with increased risk of aneurysm-related complications after standard endovascular aortic repair. The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) for complex aortic aneurysms in patients with or without familial aortic aneurysms (FAAs). Materials and Methods: We reviewed the clinical data of consecutive patients enrolled in a prospective non-randomized study to investigate outcomes after FB-EVAR for treatment of complex aortic aneurysms between 2013 and 2022. Familial aortic aneurysm was defined as occurrence of an aortic aneurysm or dissections in a first- or second-degree relative and compared with patients with sporadic aortic aneurysms (SAAs). Endpoints included procedural metrics, 30-day mortality and major adverse events (MAEs), mid-term patient survival, freedom from reintervention and endoleak, and aneurysm sac shrinkage. Results: There were 499 patients treated with FB-EVAR (70% males, mean age was 74±7.7 years) including 66 (13%) patients with FAAs and 434 (87%) with SAAs. Both groups had similar demographics, clinical characteristics, aneurysm extent, and prior history of aortic dissection or aortic repair. Patients with FAAs had longer fluoroscopy time (82 vs 71 minutes) and radiation exposure (1856 vs 1213 mGy; each p<0.05), with no difference in technical success (FAA, 94% vs SAA, 97%; p=0.51). There was no difference in 30-day mortality (1.5% vs 0.9%; p=1.00) and MAEs (23% vs 18%; p=0.44) among patients with FAA and SAA, respectively. Median follow-up was 28 months. At 3 years, patient survival, freedom from secondary interventions, and cumulative incidence of sac shrinkage were 76±2.5%, 74±2.5%, and 32±2.6% for all patients, respectively, with no difference between FAA and SAA groups. Conclusion: Fenestrated-branched endovascular aortic repair was performed with high technical success, low mortality, and low incidence of MAEs regardless of the presence of FAA. There was no difference in mid-term patient survival, secondary interventions, and sac changes among patients with or without family history of aortic disease. Clinical Impact This study demonstrates that fenestrated-branched endovascular aortic repair (FB-EVAR) can be performed with high technical success and comparable early and mid-term outcomes in patients with or without a familial history of aortic aneurysm, after exclusion of genetically triggered aortic diseases. These findings challenge the assumption that family history alone should preclude complex endovascular repair. Clinically, this supports broader use of FB-EVAR in carefully selected patients with familial aortic disease, emphasizing anatomical suitability rather than pedigree alone. The innovation lies in validating FB-EVAR as a safe alternative to open repair for this understudied population, informing patient selection, counseling, and surveillance strategies.

Importance A greater proportion of older patients (age ≥65 years) are undergoing thyroidectomy amidst an aging population. Given the elusive results in the literature, clarifying whether older patients face different thyroidectomy safety profiles is crucial for optimizing risk assessment and patient counseling. Objective To evaluate the association between older age (age ≥65 years) and thyroidectomy safety by comparing endocrine-related complications, including recurrent laryngeal nerve injury, hypocalcemia, hematoma, and mortality in older compared with younger patients. Data Sources Ovid MEDLINE, CINAHL, Ovid Embase, and the Cochrane Library were systematically searched from inception to May 29, 2025; only English-language studies were included. Study Selection Cohort studies comparing thyroidectomy outcomes between older and younger patients and reporting endocrine-related complications were included. Two independent reviewers screened abstracts and full texts. Of 3192 studies identified, 11 met inclusion criteria. Data Extraction and Synthesis Two independent reviewers extracted data following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias across studies was evaluated using the ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) tool. Random-effects models were used to pool data. Main Outcomes and Measures Incidence of recurrent laryngeal nerve injury, hypocalcemia, and hematoma; odds ratios (ORs) with 95% CIs were calculated. Results The analysis included 11 studies with a total of 427 886 patients of whom 104 232 (24.4%) were older adults (≥65 years). Older adults had greater odds of overall recurrent laryngeal nerve injury (2.3% vs 1.0%; OR, 1.58; 95% CI, 1.15-2.16; I 2 = 76%), hematoma (2.4% vs 1.0%; OR, 2.32; 95% CI, 1.70-3.16; I 2 = 0%), and mortality at last follow-up (0.3% vs 0.01%; OR, 11.09; 95% CI, 1.77-69.52; I 2 = 90%) compared with younger patients. However, rates of overall hypocalcemia (OR, 0.80; 95% CI, 0.61-1.05; I 2 = 71%) and wound complications (OR, 1.38; 95% CI, 0.92-2.06; I 2 = 0%) were similar. Conclusions and Relevance This systematic review and meta-analysis found that thyroidectomy is safe in older patients, with only small absolute increases in recurrent laryngeal nerve injury, hematoma, and mortality despite statistical significance. These findings support individualized counseling and perioperative planning while acknowledging the overall safety of thyroidectomy in this population.

Background Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion. Methods Patients undergoing 4‐vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy‐matched patent controls. Patient‐specific pulsatile rigid‐wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time‐averaged wall shear stress (TAWSS) was defined as <10 or >70 dynes/cm 2 . Results Nine patients (36 target vessels) experienced 10 branch occlusions. Postoperative pressure and flow did not differ significantly between occluded and patent renal or mesenteric branches. However, occluded renal and mesenteric branches demonstrated significantly larger postoperative areas of abnormal TAWSS compared with controls (renal: 14.5% versus 5.9%, P =0.003; mesenteric: 17.7% versus 9.9%, P =0.035). Logistic generalized estimating equation modeling showed abnormal TAWSS to be a significant predictor of renal branch occlusion ( P =0.0085). Model estimates suggested occlusion probabilities of 1.1%, 31%, and 94% at 0%, 10%, and 20% abnormal TAWSS surface area, respectively. A cluster‐bootstrapped receiver operating characteristic curve (area under the curve, 0.876) identified a >10.2% threshold that correctly classified 92% of renal occlusions. Abnormal TAWSS frequently localized to distal stent–artery interfaces. Conclusions Elevated abnormal TAWSS within stented renal branches is associated with subsequent branch occlusion after fenestrated and branched endovascular aneurysm repair. Computational flow simulation‐derived TAWSS thresholds may help identify high‐risk branches before failure, warranting prospective validation.

Accurate assessment of distal tibiofibular syndesmotic injuries is essential to prevent chronic instability and poor functional outcomes, and conventional radiography, CT, and MRI play complementary and critical roles in the imaging of these injuries.

Abstract Background The quantification of Neurofilament Light chain (NfL) in blood and cerebrospinal fluid (CSF) has proven valuable for diagnosing and prognosing various neurological disorders, including Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, parkinsonism, multiple sclerosis, and ischemic damage. However, there is considerable variability in clinical and laboratory practices between centers, primarily due to different contexts of use (COU), analytical methods, and the application of cutoffs or scales. Additionally, for the same biochemical profile, the interpretation and reporting of results may vary from one center to another, raising concerns about the commutability of the tests. To date, no consensus has been reached among laboratories to define the most appropriate use of cutoffs or conclusions/comments based on NfL profiles. Method This international project involves 38 laboratories across 18 countries, all specialized in the biochemical diagnosis of neurological disorders. Using a questionnaire, we obtained descriptions from each center regarding their COU, pre‐analytical and analytical protocols (including the biological fluid and methods used to quantify NfL). Through a consensus approach, we developed a harmonized strategy for the use and reporting of NfL results across different centres according to their respective COU. Results Among the centers, 63% quantified NfL in the CSF, 87% in blood and 53% in both fluids. COU were as follow: frontotemporal dementia (71%), Alzheimer disease (71%), multiple sclerosis (61%), amyotrophic lateral sclerosis (61%), psychiatric syndrome (45%), Creutzfeldt‐Jakob disease (32%), Parkinson disease (39%), peripheral neuropathy (29%), traumatic brain injury (21%), Huntington's disease (13%), amyloid transthyretin related (11%) and cardiac arrest (8%). Most of the centers define pathological cutoffs based on publications (50%) and take age into account for this purpose (42%). Reporting is mostly transmitted through numeric results (95%). Conclusion Harmonizing cutoffs, reporting, and interpretation across various clinical contexts will facilitate the incorporation of this biomarker into routine clinical practice.