Citations

Objective Cervical artery dissection (CeAD) may be limited to the extracranial extradural space or extend to the intradural space. Intradural extension can potentially increase the risk of stroke and subarachnoid hemorrhage. However, the factors associated with intradural extension and its impact on clinical outcome remain unclear. Methods This was a secondary analysis of the STOP‐CAD observational, multi‐center study. Patients with CeAD and intradural extension (CeADid) were compared with those with pure CeAD extradural dissections (CeADed) using multiple regression analyses. Results Of 4,023 patients with CeAD, 534 (13.3%) had CeADid. In comparison to patients with CeADed, those with CeADid more often had clinical overt stroke or transient ischemic attack (TIA) at presentation, acute infarcts on imaging, a vertebral artery affected, and severe stenosis of the involved vessel ( p < 0.001 for all). In contrast, carotid involvement and complete occlusions were more frequent in patients with CeADed ( p < 0.001 for both). CeADid was associated with a shift in the distribution of scores on the modified Rankin Scale (mRS) toward worse functional outcome (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.62–0.92) but the odds for favorable outcomes (mRS = 0–2) did not differ between the groups after appropriate adjustments on multivariate analysis. CeADid was independently associated with higher mortality at 180 days on multivariate analysis (adjusted OR = 2.84, 95% CI = 1.50–5.38). Interpretation CeADid is associated with more severe clinical presentation, a shift toward less favorable outcomes, and higher mortality rates. These findings suggest that CeADid may represent a high‐risk type of CeAD. ANN NEUROL 2026;99:1189–1197

Abstract Background Liver surgery carries a high risk of complications due to the complex interplay of patient-related factors, disease characteristics, and liver function. Expertise is essential for healthcare professionals managing hepatobiliary patients. This European consensus provides evidence-based guidance on selected aspects of peri- and postoperative care. Methods A modified Delphi process was used to achieve consensus, with a 70% agreement threshold. The expert panel comprised hepatobiliary surgeons, anaesthetists, hepatologists, a specialist nurse, and a physiotherapist. A systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases. Six topics were addressed: thromboprophylaxis; perioperative antibiotics; prehabilitation/nutrition/mobilization; bile leak including bilioenteric anastomosis leaks; post-hepatectomy haemorrhage; and post-hepatectomy liver failure (PHLF). Evidence appraisal and statement development followed Scottish Intercollegiate Guidelines Network methodology. A patient representative reviewed the guideline. Results Searching the literature yielded 204 included publications from an initial 6514. Thirty-two statements were formulated with a median evidence level of 2. Evidence strength varied by topic with noticeably lower evidence levels in complex surgery settings and less prevalent conditions. In some topics, study heterogeneity and specific inclusion criteria resulted in conditional recommendations, despite high-level evidence. Notably, the weakest evidence was found for perioperative thromboprophylaxis and PHLF management. Strong recommendations were formulated for prehabilitation, early postoperative mobilization, and avoidance of routine drain use. Several evidence gaps warranting multicentre studies were identified. Conclusion Optimizing peri- and postoperative care after liver resection remains challenging. Standardizing key practices and addressing evidence gaps through collaborative research are vital to improve outcomes.

Abstract Rapid and profound reduction of free light chains (FLCs) improves outcomes in AL amyloidosis; however, early FLC kinetics with daratumumab‐based frontline therapy remain undefined. We retrospectively analyzed 315 patients treated with daratumumab–bortezomib–cyclophosphamide–dexamethasone (Dara–VCd) or Dara–Vd at eight centers. Involved FLC (iFLC), the difference between iFLC and uninvolved FLC (dFLC), and hematologic response (≥very good partial response [VGPR]) were assessed at baseline and at 1, 3, and 6 months, and correlated with light chain isotype, disease burden (bone‐marrow plasma‐cell percentage [%BMPC], baseline dFLC), and cytogenetics. Hematological ≥VGPR increased from 49.8% at 1 month to 66.0% at 3 months. The kappa isotype showed slower responses, with higher iFLC/dFLC and lower ≥VGPR at each time point compared to lambda. Higher %BMPC or baseline dFLC predicted persistently elevated iFLC/dFLC and reduced ≥VGPR. The t(11;14) translocation was associated with lower baseline FLC but similar subsequent kinetics. BMPC < 10% and dFLC < 18 mg/dL independently predicted early ≥VGPR (in ≤1 month). Early ≥VGPR conferred superior hematologic event‐free survival (heme‐EFS) and overall survival (OS) versus later responders (P < 0.001). At a 3‐month landmark, achieving dFLC < 1 mg/dL further stratified prognosis, conferring longer heme‐EFS and OS (P < 0.01). Frontline Dara‐based therapy elicits rapid, deep responses in AL amyloidosis; early ≥VGPR (within 1 month) and dFLC < 1 mg/dL by 3 months predict durable EFS and OS, whereas higher baseline disease burden delays hematologic response.

Abstract Background Apolipoprotein E (apoE) facilitates the fibrillization and deposition of amyloid β (Aβ) in Alzheimer's Disease (AD). Supported by robust literature from various groups, in our current study we have investigated the relative amyloidogenic properties of the three major human APOE alleles. Knowledge from such studies could provide insight into the role of ApoE protein in the deposition, evolution and maturation of parenchymal Aβ. Method We used hAbetaSAA (Jax Labs) mice crossed with human APOE targeted replacement mice to create hAbetaSAA mice homozygous for human APOE E2, E3 and E4 . Furthermore, APPsi mice (hAPPswe/indiana: Borchelt) expressing human APOE E3 or E4 were injected intracerebrally with AD brain lysates to examine the role of APOE genotype on Aβ seeding. Neuropathological examination was conducted via immunohistochemistry, immunofluorescence and immunoblotting. Result hAbetaSAA mice expressing human APOE E4 showed higher Aβ deposition relative to APOE E3 and APOE E2 by 5 months of age and progressing through 8 months and 13 months of age. In comparison, APP mice expressing humanized Aβ (Jax Labs) with human APOE E4 did not develop deposits in their lifetime. hAbetaSAA mice with endogenous mouse Apoe had the highest Aβ plaque deposition, with an approximately 60‐fold increase in Aβ burden compared to SAA APP mice expressing APOE E3 , especially in the earlier deposition phase. Removing mouse Apoe resulted in dose‐dependent reduction in Aβ deposition, consistent with previously published literature. Plaque morphology did not show any notable differences between APOE genotypes, and colocalization of apoE with Aβ were relatively equivalent across different APOE genotypes. Further, in the APPsi model seeded with AD‐derived seeds, we found that mice with APOE E4 or APOE E3 developed equal burdens of diffuse parenchymal Aβ, with no detectable changes in plaque morphology. Conclusion We conclude that apoE variants broadly influence the rate of amyloid deposition, but do not modify the morphology of the resulting deposits or colocalization with Aβ. Notably, when seeding with AD patient brain lysate, there was no significant difference in Aβ burden between APPsi mice expressing APOE E3 and E4 . Our study adds insights into the role of apoE isoforms in determining Aβ‐related phenotype.

ABSTRACT Background and Aims Chronic inflammatory demyelinating polyradiculoneuropathy ( CIDP ) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic ( EDX ) criteria required for diagnosis are challenging to apply in routine practice. This study evaluates the effectiveness of a machine‐assisted EDX tool in real‐time identification of demyelinating nerve conduction studies ( NCS ) stipulated by 2021‐ EAN / PNS CIDP criteria in conjunction with an online CIDP clinical probability calculator. Methods We prospectively evaluated 100 consecutive patients with referral or EDX diagnosis of polyradiculoneuropathy beginning January 1, 2024. Fifty patients were included, each from Jacksonville and Rochester Mayo Clinics. Routine electromyography ( EMG ) reports were compared to a machine‐assisted support tool applying 2021‐ EAN / PNS CIDP EDX criteria to NCS assessing demyelination. The EDX ‐assistant performance was compared to the final clinical diagnosis and our previously reported online CIDP clinical prediction tool ( https://news.mayocliniclabs.com/cidp‐calculator/ ). Results Among 100 patients (60% male; median age 64), 30 had a final clinical CIDP diagnosis with 29 having intravenous immunoglobulin follow‐up; 27 (93%) improved and 2 (7%) stabilized. Routine EMGs reported demyelination in 14 of 30 (47%), with 46% sensitivity and 79% specificity. The EDX ‐assistant identified CIDP demyelination in 28 of 30 (93%), with 93% sensitivity and 57% specificity. The clinical calculator detected CIDP in 30 of 30 (100%) with 86% specificity, increasing to 94% after excluding false positives lacking demyelinating features on the EDX tool. Interpretation A real‐time machine‐assisted EDX support tool, used with a clinical web‐based calculator, streamlines CIDP assessment by improving standardized identification of 2021‐EAN/PNS CIDP demyelinating NCS criteria and aiding clinical decisions.

Abstract Background Astroblastomas are rare brain tumors predominantly affecting children and young adults, for which molecular subtypes and clinical management remain undefined. Methods We analyzed tumor samples, molecular profiles, and clinical data from 200 patients, classified as “Astroblastoma, MN1-altered” under WHO criteria, using DNA methylation profiling, DNA/RNA profiling/sequencing, and survival analyses. Results DNA methylation analyses identified 3 groups: Group A (n = 143, characterized by MN1::BEND2 fusions, predominantly supratentorial location, with striking female predominance and favorable survival); Group B (n = 37, epigenetically and transcriptionally closely related to Group A, but characterized by EWSR1::BEND2 fusions, with spinal and infratentorial locations and poor prognosis); and Group C (n = 20, epigenetically and transcriptionally distinct, characterized by MN1::CXXC5 fusions, exclusively supratentorially located, with favorable survival). Progression-free and overall survival were significantly shorter in Group B (5-year PFS 14%; 10-year OS 54%) compared to A (5-year PFS 47%; 10-year OS 89%) and C (5-year PFS 75%; 10-year OS 89%). Radiotherapy improved PFS in Group B (hazard ratio 0.25), while no clear benefit was identified for Groups A and C. Conclusions Astroblastoma, MN1-altered, comprises 3 molecularly and clinically distinct groups, characterized by different fusion genes, including those without MN1. These new insights, including the identification of potential predictive biomarkers like 14q/16q loss, provide a framework for the development of risk-stratified therapeutic approaches. Importantly, we identified a molecularly defined high-risk group that benefits from radiation therapy. Our findings redefine Astroblastoma as a molecularly diverse tumor type, propose a refined classification, support the development of risk-adapted therapeutic strategies and provide a rational standard of care.

Abstract Background Small vessel vasculitides (SVV) comprise a heterogeneous group of cutaneous SVV (CSVV) that can be skin‐limited or systemic. Given their diverse forms and symptoms and the lack of a standardized diagnostic approach, it is crucial to establish clear and consensus‐driven recommendations for diagnosis. Objectives To standardize diagnosis for the detection of the type, extent, potential causes or underlying conditions of CSVV. Methods International experts comprised the panel. The Delphi panel data was collected through two rounds of questionnaires. Agreement was measured using an 11‐point Likert scale (0 = strongly disagree, 10 = strongly agree). A 7‐vote minimum was required for agreement on each statement. Delphi panel statements scoring 3–7 were discussed during the meeting. Results 20 experts participated in the first round of the Delphi panel, while 17 experts took part in the second. They agreed that the diagnosis of CSVV relies on a combination of clinical manifestations, laboratory findings and histopathology. Palpable purpura on the lower extremities is recognized as the most reliable hallmark for most SVV and a sign of immune complex vasculitis. When the latter is suspected, a skin biopsy for direct immunofluorescence (DIF) should be obtained from an early, partially blanchable macule because the type of perivascular immunoglobulin is important for further diagnosis. The proper selection of biopsy sites for routine HE biopsy depends on the morphology of lesions. A comprehensive medical history and selected laboratory testing should be conducted to investigate organ involvement, potential causes and associated conditions. The extent of diagnostic procedures should be based on the severity, duration, systemic symptoms and recurrence of SVV. Conclusions Experts reached a strong consensus on the management of CSVV patients, culminating in the first International Consensus Statement for adult CSVV. This statement proposes a practical management algorithm and underscores the importance of collaboration in rare diseases management.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P&lt; .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P&lt; .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P&lt; .001]; median OS, 136.1 vs 75.3 months [P&lt; .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.

Objectives: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists. Design: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as “advanced knowledge is essential,” “general, but not advanced, knowledge is essential,” or “knowledge is not essential.” Procedures were categorized as “intensivist performs routinely,” “intensivist only performs in an emergency,” or “intensivist knows” about the procedure. Setting: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors’ societies, were invited to participate. SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine. Interventions: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom’s polling feature. Measurements and Main Results: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as “intensivist performs.” Conclusions: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.