Citations

ABSTRACT Central venous catheters (CVCs) are a cornerstone of hematopoietic stem cell transplantation (HSCT), facilitating the delivery of chemotherapy, parenteral nutrition, medications, and blood products. Despite CVCs’ essential role, prolonged use can lead to complications such as increased risk of infection, thrombosis, mechanical issues, and psychosocial burden. However, the timing of CVC removal remains highly variable across institutions. Additionally, there are no standardized guidelines to balance the benefits of extended access against the risks of prolonged use. This narrative review examines the existing literature on CVC management post‐HSCT, highlighting key factors influencing the removal timing, such as patient characteristics, disease‐specific considerations, and institutional practices. The review emphasizes the urgent need for multi‐institutional research and standardized protocols to improve outcomes, reduce complications, and enhance the quality of care for HSCT patients.

Abstract Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by drug‐resistant seizures and developmental slowing. Although cognitive and executive function deficits have been described, their early trajectory is not well understood. Methods The prospective ENVISION natural history study (NCT04537832) assessed cognitive, executive, and adaptive function in children younger than 5 years of age with SCN1A + DS every 6 months for up to 2 years using Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID‐III), Wechsler Preschool & Primary Scale of Intelligence, 4th Edition (WPPSI‐IV), Vineland Adaptive Behavior Scales, 3rd Edition (VABS‐3), Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF‐P), and Pediatric Evaluation of Disability Inventory (PEDI). Results Fifty‐eight children were enrolled, with 47% younger than age 2 years. At least 80% of children did not achieve age‐appropriate milestones. Mean BSID‐III Cognitive raw scores increased minimally, with age‐equivalent gains of only 3 months over 1.5 years. Mean Cognitive Composite scores declined significantly by Month 12 (from 81.6 to 72.2; change: –11.0, 95% confidence interval [CI]: −15.3 to −6.8), signaling a widening gap compared with neurotypical development. Executive function worsened, with mean BRIEF‐P Global Executive Composite T‐scores increasing by 3.2 points/year. For some participants, scores were 5 standard deviations (SD) above the normative mean, reflecting abilities profoundly below age expectations (bottom .00003% of the population). Adaptive functioning worsened, with mean VABS‐3 Adaptive Behavior Composite decreasing from 78.7 to 68.1 over 1.5 years (change: –9.0, 95% CI: −11.9 to −6.1) and greater decline among children <2 years at enrollment, with scores decreasing by ~15 points (1 SD). Over half of children >3 years could not remove clothing independently; and when placed on a toilet, 48% could not use it. Significance Infants and young children with SCN1A + DS show significant and progressive developmental slowing across several domains, highlighting urgent need for therapies to mitigate the devastating impact on individuals and families.

ABSTRACT Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder causing hypogammaglobulinemia. Although rare, nodular regenerative hyperplasia is the most common liver complication in CVID, which can progress to noncirrhotic portal hypertension. We report a case of a young male with CVID presenting with recurrent parastomal bleeding secondary to noncirrhotic portal hypertension from CVID-associated nodular regenerative hyperplasia.

Background: Acquired and congenital limb length discrepancies often coexist with deformities of the distal femur. Lengthening of the femur along its anatomic axis changes the limb's mechanical alignment. Angular correction and lengthening can be achieved at the same site if a retrograde lengthening nail is used with a specific preoperative planning method (“reverse planning”) which permits patient-specific selection of the final mechanical axis. Methods: A consecutive cohort series of children, adolescents, and young adults (mean 15.6 ± 4.8 years) undergoing retrograde implantable femoral lengthening between the years 2011 and 2024 were analyzed. Surgical details, lengthening parameters, Limb Lengthening and Reconstruction Society (LLRS)–AIM index, accuracy of final correction, and complications were reviewed and classified. Patients were eligible only if the distal femoral physis was closed. Results: Seventy-three lengthening were eligible in the study period. Average lengthening was 4.2 ± 1.4 cm (range 2.0-8.0 cm), and consolidation index was 39.4 ± 21.9 days/cm. Deformities and length discrepancies were moderately complex, with a mean LLRS AIM score of 6 (range 1-13). Complication rates were similar to previous reports of intramedullary femoral lengthening, comparable between congenital (12 of 31, 39%) and acquired etiologies (16 of 42, 38%). Preoperative coronal alignment ranged from 14° varus to 20° valgus, while final coronal alignment was 0.4° ± 3.4° of neutral (range 7° valgus to 13° varus). Coronal deformities up to 20° and sagittal deformities up to 23° were corrected acutely at the lengthening site. Conclusions: Retrograde intramedullary femoral lengthening with acute deformity correction at the same site is an alternative to antegrade lengthening with separate osteotomy of the distal femur in children and adolescents. The reverse planning method allows reproducible length and deformity correction at the same location. Specific intraoperative technical adjuncts are used to achieve and maintain the desired alignment. Level of Evidence: Diagnostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

ABSTRACT Background Chronic myelomonocytic leukemia (CMML) is largely a disease of individuals older than 50 years; its occurrence in patients aged 50 years and younger is rare. The authors sought to characterize the clinicopathologic features and genetic profile of young‐onset (age 50 years and younger) CMML (y‐CMML) compared with older onset (older than 50 years) CMML (o‐CMML). Methods The authors conducted a multi‐institutional study of 32 patients with y‐CMML and 119 patients with o‐CMML, analyzing clinical, morphologic, cytogenetic, and molecular data. Results Patients who had y‐CMML frequently presented with splenomegaly (59% vs. 11%; p < .001) and hepatomegaly (25% vs. 2%; p < .001) compared with those who had o‐CMML. Although the overall incidence of cytogenetic abnormalities was similar, patients who had y‐CMML exhibited distinct mutational patterns. PTPN11 mutations were significantly more common in y‐CMML (13% vs. 3%; p = .034) than in o‐CMML, whereas TET2 (6% vs. 57%; p < .001) and SRSF2 (16% vs. 46%; p = .002) mutations were significantly less frequent. In addition, multi‐hit TET2 (6% vs. 34%; p = .002) and TET2‐SRSF2 (3% vs. 29%; p = .003) co‐mutations were rare in y‐CMML. However, the molecular differences did not affect the CMML‐specific risk‐stratification categories because the clinical outcomes, including overall survival and leukemia‐free survival, did not differ between the two groups. Conclusions CMML in patients aged 50 years and younger is rare and presents with unique clinical and mutational features, suggesting a distinct pathogenesis.

Background The association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood. Objective The aim of this study was to assess the association of alcohol consumption, smoking behavior, sleep quality and physical, cognitive, and social activity with cerebral amyloid pathology. Methods For this cross-sectional study, we selected participants from the Amyloid Biomarker Study data pooling initiative. We used generalized estimating equations to assess associations of dichotomized lifestyle measures with amyloid pathology. Results We included 9171 participants with normal cognition (NC) and 2555 participants with mild cognitive impairment (MCI) from the Amyloid Biomarker Study. Of participants with NC, 58% were women, 34% were APOE ε4 carrier, and 27% had amyloid pathology. Of participants with MCI, 48% were women, 47% were APOE ε4 carrier, and 57% had amyloid pathology. In NC, cognitively active participants were less likely to have amyloid pathology (OR = 0.77, 95%CI 0.66–0.89, p < 0.001). In MCI, participants who had ever smoked or had sleep problems were less likely to have amyloid pathology (OR = 0.85, 95%CI 0.73–0.99, p = 0.029; OR = 0.62, 95%CI 0.45–0.86, p = 0.004). Conclusions In NC, cognitive activity was associated with a lower frequency of amyloid pathology. In MCI, favorable lifestyle behaviors were not associated with a lower frequency of amyloid pathology. The results of the current study contribute to the broader evidence base on lifestyle and AD by further characterizing the role of lifestyle behaviors in AD pathology across different clinical stages.

Abstract Pediatric, adolescent and young adult patients (Ped/AYA; 0–39 years) with meningiomas are underrepresented in neuro-oncology research, despite meningiomas being the second most common primary brain tumor in this age group. While DNA methylation-based models have advanced classification and prognostication in adults, their utility in younger populations remains uncertain. To address this gap, we aimed to evaluate the performance of current DNA methylation-based classification and recurrence prediction models in Ped/AYA patients with meningiomas and identify age-associated molecular differences. As part of this study, we analyzed 1,568 meningioma samples with DNA methylation and clinical data, including subsets with whole-exome and RNA sequencing. Patients were grouped into Ped/AYA (≤39 years, n = 213) and adult (&gt;39 years, n = 1,355) cohorts. We assessed classifier performance, performed subgroup-specific model retraining, and compared molecular profiles across age groups. Our results showed that molecular classification differed significantly between age groups, with Ped/AYA tumors less frequently belonging to the most aggressive Proliferative Molecular Group. The DNA methylation-based recurrence model performed well in adults (AUC = 0.83) but poorly in the Ped/AYA cohort (AUC = 0.57). However, retraining the model on only younger patients improved performance (AUC = 0.75). In addition, Ped/AYA tumors exhibited significantly fewer chromosomal alterations, including lower frequencies of 1p, 6q, and 14q loss (p&lt;0.05). Taken together, these findings indicate that predominantly adult-trained methylation models underperform in younger meningioma patients due to both biological divergence and exclusion from training datasets. Our findings underscore the need for age-specific molecular tools to improve prognostication and support personalized care across the lifespan in neuro-oncology.

Abstract IDH-wildtype diffuse astrocytic gliomas with lower-grade histological features alongside specific genomic alterations (e.g., TERT promoter mutation, EGFR amplification, gain Chr7/loss Chr10) are presently diagnosed as glioblastoma, IDH-wildtype (GBM) under WHO 2021 criteria. Previous analyses categorized these into “early/evolving” or “surgically undersampled” GBMs. However, it remains unclear whether these tumors share identical clinical and prognostic features with histologic GBM. Data from IDH-wt molecular GBMs across six institutions were aggregated. Astrocytic IDH-wt tumors of any grade that lacked necrosis or microvascular proliferation on initial histopathology yet exhibited molecular alterations consistent with WHO 2021 GBM diagnosis, were included. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups based on overall survival (OS). Among the 264 patients included, the median age was 60 years (IQR: 51-67), with 162 (61%) being male. Additionally, 210 (80%) were diagnosed since 2016, and 216 (82%) received chemoradiation plus adjuvant temozolomide (GBM-SOC). The median follow-up period was 3.9 years (95% CI: 3.4, 4.6). Identified univariate risk factors for worse survival included older age, biopsy-only status, EGFR amplification, absence of initial adjuvant treatment, low post-operative KPS, and tumor histologic grade of 3. RPA divided patients into four distinct survival groups (p&lt;0.0001). The “best” risk group comprised lower grade (&lt;=2) tumors (n=58, median OS (mOS): 40 months (95% CI: 33, NA)). The “second best” group included Grade 3 patients receiving GBM-SOC without steroids during initial RT (n=139, mOS: 25 months (95% CI: 22, 28)). The “second worst” group encompassed Grade 3 patients who were on steroids during initial RT while receiving GBM-SOC (n=38, mOS: 15 months (95% CI: 13, 20)). The “worst” group contained Grade 3 tumors that had not undergone SOC (n=29, mOS: 9 months (95% CI: 4, 26)). These data show that histologic features and treatment are strong indicators of patient outcomes.