Citations

AbstractThumb carpometacarpal (CMC) arthritis is a common and sometimes debilitating condition with a variety of surgical treatments. Pyrocarbon thumb CMC hemiarthroplasty is one option, which has demonstrated promise; however, no long-term outcomes have been reported.We performed a retrospective institutional review of 106 primary thumb CMC pyrocarbon hemiarthroplasties with a minimum of 1 year, median 6.1-year follow-up. We analyzed rates of pain relief, reoperation, and implant failure as well as biomechanical, radiographic, and patient-reported outcomes.Pain was significantly decreased after surgery. Radial and palmar abduction were modestly improved postoperatively (increased from 40–50 degrees). Implants showed high rates of radiographic osteolysis (53%) and subsidence (44%). Two-, 5-, and 10-year rates of reoperation (18, 21, 21%) and implant removal (15, 19, and 19%), respectively.Pyrocarbon thumb CMC hemiarthroplasty provides high rates of pain relief and preservation of pinch and grip strength. Patients had modest improvement in radial and palmar abduction; however, hemiarthroplasty was associated with moderate rates of reoperation and implant revision.Therapy Level IV.

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 Diffuse large B-cell lymphoma (DLBCL) poses a challenge in hematology given its varied symptoms, and the complex interplay between disease and treatment effects on health-related quality of life (HRQoL). The phase 3 POLARIX study demonstrated superior progression-free survival and a similar safety profile with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with previously untreated DLBCL. Here, we evaluate HRQoL through patient-reported outcome (PRO) instruments to fully characterize the patient experience in the POLARIX study. Changes from baseline in HRQoL, lymphoma symptoms, and gastrointestinal (GI) symptoms were assessed, as well as incidence and severity of common symptoms by PROs vs clinician-reported adverse events (AEs). Baseline characteristics of PRO-evaluable patients (N = 874) were consistent. Comparison between PROs and clinician-reported AEs revealed a notable discordance; patients generally reported a higher incidence of symptoms than clinicians, emphasizing the need for patient-centric tools to accurately capture the patient experience. Both treatments exhibited rapid and sustained improvements in HRQoL and lymphoma symptoms, with the most substantial improvements seen in global health status/QoL, lymphoma symptoms, fatigue, role, emotional, and social functioning. GI symptoms (diarrhea, constipation, nausea, and vomiting) were generally similar between treatment arms and returned to baseline levels after treatment completion. These HRQoL data underscore the complementarity of PROs, as an adjunct to clinician-reported AEs, in evaluating the efficacy and tolerability of new treatments, including Pola-R-CHP, which may represent a new benchmark for patient-reported HRQoL in previously untreated DLBCL. This trial was registered at www.clinicaltrials.gov as NCT03274492.

The clinical benefit of blood transfusion is undeniable, and yet reliance on donated blood products has several shortcomings. These include risks of supply shortages due to reliance on volunteer donors, short storage life, and potential infectious disease transmission. Immune response complications to donated blood cannot be completely avoided, despite significant advances in testing. Many of these limitations are exacerbated in low-income countries. For decades, cell-free hemoglobin-based blood substitutes have been developed and tested as potential substitutes for red blood cell transfusions. Early studies found that purified, native hemoglobin exhibited significant safety risks, such as hypertension from excessive vasoconstriction and evidence of multiple organ toxicities. These effects are likely in part due to the reactive heme center, which will scavenge nitric oxide, generate reactive oxygen species, and may drive sterile inflammation. Numerous strategies have been explored to further modify hemoglobin in the hope of creating a safe and well-tolerated blood substitute. Despite some promising results in preliminary studies, large-scale clinical trials have continued to show elevated rates of adverse events and/or a failure to meet specified clinical endpoints. As a result, no hemoglobin-based oxygen carrier (HBOC) has obtained US Food and Drug Administration approval for clinical use. This review focuses on the history of HBOC development, the lessons that have been learned from prior failures of HBOC programs, and the status of ongoing artificial oxygen carrier development efforts.

PURPOSE Ziftomenib—a potent, highly selective, oral menin inhibitor—was well tolerated and demonstrated encouraging clinical activity as monotherapy for relapsed/refractory NPM1 -mutated ( NPM1 -m) and KMT2A -rearranged AML in the KOMET-001 phase I trial. METHODS In the registration-enabling phase II part of KOMET-001, patients with relapsed/refractory NPM1 -m AML received ziftomenib 600 mg once daily. The primary end point was the rate of complete remission with full hematologic recovery (CR)/CR with partial hematologic recovery (CRh). RESULTS From January 26, 2023, to May 13, 2024, 92 patients (median age, 69 years [range, 33-84]) were treated. The primary end point was met, with a CR/CRh rate of 22% (95% CI, 14 to 32; P = .0058); 61% were negative for measurable residual disease. Overall response rate was 33% (95% CI, 23 to 43), with a median duration of 4.6 months (95% CI, 2.8 to 7.4). Prespecified subgroup analyses showed comparable CR/CRh regardless of previous therapy, including venetoclax, or type of comutations. Median overall survival was 6.6 months (95% CI, 3.6 to 8.6). Common grade ≥3 treatment-emergent adverse events were febrile neutropenia (26%), anemia (20%), and thrombocytopenia (20%). Differentiation syndrome occurred in 25% of patients (15% grade 3; no grade 4-5) and was manageable with protocol-defined mitigation. Three patients (3%) discontinued treatment because of ziftomenib-related adverse events. CONCLUSION Ziftomenib demonstrated significant clinical benefit and deep responses in patients with heavily pretreated, relapsed/refractory NPM1 -m AML. Ziftomenib was well tolerated with a safety profile consistent with previous studies, including manageable differentiation syndrome, lack of clinically significant QTc prolongation, and low rates of myelosuppression.

When encountering diseases of the anterior vitreous and peripheral retina (ie, the “middle segment” of the eye), vitreoretinal (VR) surgeons are specifically trained in surgical techniques for managing the vitreous and visualizing the peripheral retina during anterior vitrectomy, and therefore, they are well equipped to address the complications of surgery involving the anterior vitreous space. This clinical update reviews and compares the current literature discussing techniques and patient outcomes related to complete pars plana vitrectomy versus incomplete, subtotal pars plana vitrectomy, and addresses the proposition of developing an abridged training curriculum for non-VR surgeons to acquire the knowledge and skills required to perform these procedures. Recent studies confirmed that operating in the anterior vitreous carries potential risk of retinal tear, retinal detachment, and other adverse events that may cause vision loss. To mitigate these risks, studies suggest that the use of dedicated visualization equipment and illumination instruments is necessary for surgeons to safely perform anterior vitrectomy and recognize complications, should any occur. Performing VR surgery in the absence of wide-angle viewing systems, endoillumination, careful peripheral examinations, modern vitrectomy platforms, and appropriate training may lead to outcomes that are detrimental to patient safety.

Background Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. Methods A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. Results Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high‐risk sources of embolism for the primary outcome in the unmatched and matched analyses. Conclusions Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.