Citations

Background: A summary of pharmacist-based practices and preferences regarding the prevention and management of high-dose methotrexate (HDMTX) toxicity in patients with lymphoma does not exist. The objective of the study was to describe current practices surrounding management of HDMTX therapy. This was done through a self-administered, web-based, cross-sectional survey of hematology/oncology pharmacists to ascertain practices and individual attitudes about HDMTX therapy management. Responses were summarized with descriptive statistics. Response comparisons were made using Chi-square or Fisher’s exact test for categorical data, and Kruskal-Wallis test for variables on the Likert scale. A total of 175 pharmacists provided 116 eligible surveys [68 (59%) complete responses and 48 (41%) partial responses] for analysis. The Cockcroft-Gault estimated creatinine clearance formula was the most preferred method (61%) to estimate kidney function and determine HDMTX dosing. Respondents would proceed with HDMTX therapy until the predicted risk of AKI, or AKI stage 2 or 3, exceeded 50% and 20%, respectively. Preferred treatment modifications for a high predicted AKI risk after HDMTX exposure included additional prehydration, HDMTX dose reduction, and increased kidney function monitoring, although levels and degrees of agreement varied. Respondents indicated that serum cystatin C-based GFR estimates lacked evidence, accuracy, and practicality in HDMTX therapy management. There was limited familiarity with cell cycle arrest biomarker use during HDMTX therapy. Glucarpidase was considered time-sensitive and highly effective; however, acquisition cost represented a barrier to use, and the optimal dose was felt to be unknown. In conclusion, there is significant heterogeneity in supportive practices and beliefs about the optimal management for patients with lymphoma receiving HDMTX therapy.

Importance Brain metastases are common in patients with cancer, and radiation is often used for management. Among patients with more than 4 brain metastases, the effects of stereotactic radiation targeting only individual tumors, compared with whole brain radiation with hippocampal avoidance, which radiates both tumors and normal brain, remain unknown. Objective To determine whether stereotactic radiation improves symptom severity and interference with daily functioning, compared with whole brain radiation with hippocampal avoidance. Design, Setting, and Participants Phase 3, open-label, randomized clinical trial conducted at 4 United States–based centers. Eligible patients had 5 to 20 brain metastases and no prior brain-directed radiation. Enrollment occurred between April 11, 2017, and May 17, 2024 (final follow-up, March 18, 2025). Intervention Stereotactic radiation, compared with whole brain radiation with hippocampal avoidance. Main Outcomes and Measures Mean weighted patient-reported symptom severity and interference score change over 6 months postbaseline relative to baseline using the MD Anderson Symptom Inventory–Brain Tumor instrument (scale, 0-10; score change range, −10 to 10; −10 = best). A clinically meaningful Δ was defined as 0.98. Results Of 196 randomized patients (mean age, 61 years; 129 [66%] female; 176 [90%] White; median number of brain metastases, 14 [IQR, 11-18]; 49 [25%] with prior neurosurgical resection), 83 (42%) completed the 6-month assessment. For the primary outcome, between baseline and postbaseline assessments through the 6-month follow-up, stereotactic radiation changed the weighted composite MD Anderson Symptom Inventory–Brain Tumor score from 2.69 to 2.37 (mean change, −0.32) and hippocampal-avoidance whole brain radiation changed the score from 2.29 to 3.03 (mean change, 0.74) (mean difference, −1.06 [95% CI, −1.54 to −0.58]; P < .001). Related grade 3-5 adverse events occurred in 12 patients (12%) in the stereotactic radiation group and 13 patients (13%) in the hippocampal-avoidance whole brain radiation group; grade 1-3 fatigue was most frequent (27 [28%] vs 43 [44%], respectively). Conclusions and Relevance In patients with 5 to 20 brain metastases, these findings support stereotactic radiation over hippocampal-avoidance whole brain radiation to improve symptoms and interference with daily functioning, key components of quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT03075072

Abstract Background Computational modeling is a tool being deployed for orthopaedic solutions but its use in the hand and wrist remains limited. This work used a model to simulate a clinically relevant provocative scaphoid shift maneuver (SSM) with different levels of scapholunate interosseous ligament (SLIL) injuries to observe the effect on different metrics. Methods A personalized model simulated the full SSM motion cycle from ulnar deviation with extension to radial deviation with flexion informed by the participant’s motion obtained from dynamic computed tomography. Models repeated the SSM under different levels of SLIL injury and reported changes in joint kinematics, contact mechanics, and ligament forces. Results The fully injured model increased scaphoid dorsal translation, flexion, and radial deviation compared to the intact condition and caused a subluxation of the scaphoid. Radioscaphoid contact areas were approximately 200% greater in the fully injured model compared with all others and the fully injured model was the only condition where contact force decreased across the motion cycle. Ligament forces in the intact condition were on average 33.0 N and 54.2 N for the volar and dorsal SLIL, respectively. Lastly, the long radiolunate, an extrinsic stabilizer, had forces that increased following SLIL injury. Conclusions Computational models can successfully recreate clinically observed behaviors of an SSM, including scaphoid subluxation, while providing new insights via quantification of contact mechanics and ligament forces. Contact mechanics metrics may be important for understanding the long-term progression of untreated SLIL injuries to osteoarthritis. Additionally, ligament force metrics may explain the progression of SLIL injuries from volar SLIL to dorsal SLIL and highlight the importance of repairing extrinsic stabilizers of the joint, due to increased force sharing following SLIL injury. This work provides a pathway to future studies investigating the effects of SLIL injury and repair, both acutely and chronically.

Abstract Background Follow-up blood cultures (FUBCs) for streptococcal bacteremia are infrequently positive and may not provide sufficient clinical impact to justify the time and resources expended for their routine use. We aimed to evaluate the frequency of and risk factors for positive FUBCs in patients with streptococcal bacteremia and to compare clinical outcomes among patients with or without positive FUBCs. Methods We retrospectively reviewed hospitalized patients with streptococcal bacteremia from September 2023 to June 2024 within a multisite health system. Patients ≥18 years old with ≥1 positive blood culture for a Streptococcus species were included. Patients with polymicrobial bacteremia, those who died or were discharged to hospice within 48 hours of their index culture, and Minnesota residents who declined research authorization were excluded. Results We included 454 patients, with 48 (10.6%) having positive FUBCs. The rate of positivity ranged from 0% for Streptococcus pyogenes to 18.5% for Streptococcus anginosus. Endocarditis and osteomyelitis were more common in the positive than in the negative FUBC group (22.9% vs 12.1%, respectively, for endocarditis [P = .04] and 16.7% vs 5.4% [P = .005] for osteomyelitis). Positive FUBCs were associated with a higher incidence of infection relapse (8.5% vs 2.7%; P = .047) and longer duration of antibiotics (30 vs 16 days; P = .01), but no differences in mortality rate, length of stay, or infection-related readmission were observed. Conclusions Positive FUBCs were infrequent for S pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, and group C and G streptococci. It may be reasonable to forego FUBC for these streptococcal species if endocarditis or osteomyelitis are not clinically suspected.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

Abstract In a real-world analysis of brexucabtagene autoleucel recipients with relapsed/refractory B-cell acute lymphoblastic leukemia (N = 278), lack of response to prior blinatumomab correlates with significantly worse following chimeric antigen receptor T-cell therapy outcomes.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.