Citations

Abstract The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation cohort. A risk prediction model for VTE at 30 days was derived using variables with P value < .05 in the multivariable model and was tested in the validation cohort. VTE risk factors on multivariable analysis in the derivation cohort included D-dimer ≥1 μg fibrinogen equivalent unit per mL (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.07-6.5) and hemoglobin (HR for each 1 g/dL increment, 1.19; 95% CI, 1.06-1.34) at ALL diagnosis. A VTE risk score based on these variables distinguished between a 4% (95% CI, 0.72-12) and 20% (95% CI, 14-27) 30-day cumulative incidence of VTE in the derivation cohort, with similar findings in the validation cohort (area under the curve, 0.56). The negative predictive value for VTE at 30 days was 96% and 93% in the derivation and validation cohorts, respectively, and the positive predictive value was 20% in both. We derived and validated a model using D-dimer and hemoglobin, which stratifies VTE risk in patients with ALL receiving asparaginase-based induction.

ABSTRACT The American Society for Apheresis (ASFA) Attending Physician Subcommittee of the Physicians' Committee performed an annual review of articles published in 2024 related to apheresis medicine. The 10 seminal apheresis articles selected by the subcommittee members are summarized in this review. PubMed was used to identify manuscripts published in 2024 in four areas of interest: donor apheresis, therapeutic apheresis, apheresis education, and apheresis for cellular therapy. Only full length, peer‐reviewed manuscripts in English with data from human subjects were included. Case reports, review articles, and meta‐analyses were excluded. Articles were considered seminal if they met at least one of the following previously established criteria: novel finding(s), practice‐altering outcomes, international in scope, randomized‐controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th special issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach.

Objective The primary lateral sclerosis ( PLS ) consensus diagnostic criteria and functional rating scale ( PLSFRS ) were recently established to facilitate and optimize future PLS clinical trials. We examined the trajectory of the PLSFRS and other functional outcome measures and biomarkers in the PLS Natural History Study ( PLS NHS ) to understand their performance in this prospective cohort. Methods The PLS NHS is a prospective, longitudinal, multicenter study of people living with PLS in different diagnostic categories: early (disease duration <2 years); probable (2–4 years); and definite PLS (4–15 years). PLSFRS scores and other functional outcome measures were collected at baseline, 3‐, 6‐, 9‐, and 12‐month follow‐up visits. Baseline characteristics were compared between the groups. The slopes of the PLSFRS and other functional outcome measures over 12 months were examined in the overall cohort and subgroups using linear mixed‐effect models. The associations between baseline characteristics and the rate of PLSFRS decline were analyzed with linear regression models. Results A total of 76 participants were included: early (n = 6); probable (n = 26); and definite (n = 44) PLS . Baseline PLSFRS total scores were highest in the early PLS group, followed by the probable and definite PLS groups. In the overall cohort, the PLSFRS total score declined by 0.33 points/month (95% confidence interval [0.27–0.39], adjusted p < 0.05). The rate of decline was steepest in the early PLS group, followed by the probable and definite PLS groups. Baseline neurofilament light chain level was associated with the rate of PLSFRS decline over 1 year ( p = 0.001). Interpretation In PLS, the rate of functional decline, as measured by the PLSFRS total score, is faster during the early phase of the disease. Neurofilament light might serve as a prognostic biomarker in PLS. ANN NEUROL 2026;99:418–428

Abstract Background The incidence, epidemiology, and clinical characteristics of enterococcal bloodstream infection (BSI) have not previously been studied on a population-based level in the United States. Methods We utilized the Expanded Rochester Epidemiology Project medical records linkage system to conduct a contemporary 5-year, retrospective, population-based study of monomicrobial enterococcal (ME) BSI among adult residents of 8 counties in southeast Minnesota from January 1, 2018 to December 31, 2022. Results A total of 109 cases of ME-BSI were identified. The overall age- and sex-adjusted incidence rate was 6.7 per 100 000 person-years (95% confidence interval, 5.4–7.9). Multivariable analysis revealed that male sex (P &lt; .001) and older age (P &lt; .001) were each independently associated with increased incidence, whereas no temporal association was demonstrated (year effect, P = .475). The median age of incident cases was 76.8 years (interquartile range, 65.0–83.3). Urinary tract source was the most common presumed source (42.2%), and Enterococcus faecalis was the predominant (83.5%) pathogen. Overall, 14.4% of patients met modified Duke criteria for definite infective endocarditis. Cumulative mortality was 28.4% at 12 weeks and 43.1% at 1 year. Conclusions In this population-based study, ME-BSI was significantly associated with older age and male sex. There was a high rate of mortality at 12 weeks and 1 year, with ∼1 out of 7 cases complicated by definite infective endocarditis. These findings underscore the importance of ongoing investigation of this syndrome.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive and chemo-resistant sarcomas with poor survival rates. Loss of CDKN2A or P53 following NF1 disruption is a key event in MPNST development. Here, we used CRISPR-Cas9 somatic tumorigenesis in mice to identify transcriptomic and metabolomic features distinguishing CDKN2A - versus P53 -deleted MPNSTs. Convergent, multiomic analyses revealed that CDKN2A -deleted MPNSTs are especially dependent on the pentose phosphate pathway (PPP) and NADPH metabolism for growth and viability. Disruption of glucose-6-phosphate dehydrogenase (G6PD), the PPP rate-limiting enzyme, slowed CDKN2A -deleted MPNST growth and sensitized MPNSTs to standard-of-care chemotherapy. Knockdown of the redox-regulated transcription factor NRF2 slowed MPNST growth and decreased G6PD transcription. Analysis of patient MPNSTs identified a NRF2 gene signature correlating with tumor transformation. Furthermore, G6PD and NRF2 expression in PanCancer TCGA samples correlates with patient survival. This work identifies NRF2-PPP dependency as a targetable vulnerability in these difficult-to-treat MPNSTs, particularly in the NF1/CDKN2A -deleted majority.