Citations

Abstract This real-world retrospective cohort study evaluated utilization and comparative effectiveness of covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapies in relapsed/refractory mantle cell lymphoma (R/R MCL) from electronic health records in the United States. Adults with R/R MCL who received second- or third-line (2L/3L) zanubrutinib, acalabrutinib, or ibrutinib monotherapy, on or after 1 January 2018, were included. Inverse probability of treatment weighting was used in adjusted Cox models to compare real-world time-to-next treatment (rwTTNT) and overall survival (rwOS). Among 698 patients who received 2L/3L cBTKi monotherapy, 49%, 32%, and 19% received acalabrutinib, ibrutinib, and zanubrutinib, respectively. Unadjusted analyses showed median rwTTNT for 2L zanubrutinib, acalabrutinib, and ibrutinib was 14.5 (95% confidence interval [CI], 11.0-23.2), 12.8 (95% CI, 10.5-15.6), and 10.3 (95% CI, 7.6-13.7) months, and median rwOS was 26.4 (95% CI, 23.2 to not reached [NR]), 29.2 (95% CI, 22.9-38.1), and 29.3 (95% CI, 21.8-41.6) months, respectively. Median rwTTNT for 3L zanubrutinib, acalabrutinib, and ibrutinib was 21.1 (95% CI, 3.9 to NR), 9.2 (95% CI, 6.8-14.7), and 9.6 (95% CI, 4.8-18.0) months, and median rwOS was NR (95% CI, 27.3 to NR), 27.4 (95% CI, 15.1-42.2), and 27.0 (95% CI, 15.6 to NR) months, respectively. Adjusted models in the 2L/3L cohorts combined showed numerically longer rwTTNT and statistically significantly longer rwOS for zanubrutinib vs ibrutinib (hazard ratio, 0.63; 95% CI, 0.42-0.96), and trends for improved rwTTNT and rwOS for zanubrutinib over acalabrutinib. Toxicity was a frequent reason for changing to another cBTKi. These findings suggest potential improvements in rwTTNT and rwOS with the use of second- and next-generation cBTKis for R/R MCL from 2018 and beyond.

Objective We examined the weight management practices of successful high school wrestlers to contribute meaningful data to the conversations that weight-certifying clinicians and athletic trainers have with athletes at the start of the wrestling season. Understanding how elite athletes navigate weight management can inform safer and more individualized guidance during preseason assessments. Specifically, we sought to determine the proportion of state-qualifying wrestlers who competed at or above their certified minimum weight class. We also quantified the magnitude of weight change from certification to state competition and analyzed seasonal trends in both body weight and body fat percentage over a 20-year period. Design Longitudinal retrospective review. Setting Four Minnesota high schools. Patients or Other Participants State-qualifying wrestlers from 2003 to 2023. Independent Variable State-qualifying weight class. Main Outcome Measure(s) Dependent variables are certification weight, measured body fat percent, and calculated minimum weight class. Results Only 48 wrestlers (52.7%; CI = 42.5%, 63.0%) competed at state in their minimum weight class, while the other 43 competed 1 to 2 weight classes above. Thirty-six wrestlers (39.6%) gained weight over the season. Conclusions Nearly half the successful wrestlers competed in weight classes above their minimum weight, while 5% lost 9% to 18% of their body mass over the wrestling season. This suggests factors other than maximizing individual athletic potential, such as team needs to fill a weight class, influence weight management decisions. Over the 20-year span of the study, trends toward lower measured body fat percentage and lower weight fluctuations suggest influences from sports specialization and year-round training and less emphasis on extreme leanness for competitive advantage. Athletes, in consultation with their coaches and clinicians, should select a competition weight class where they can adequately fuel, train, and recover. This may not be their minimum certified weight class.

Additive manufacturing (AM) of polyetheretherketone (PEEK) offers a promising route for producing lightweight, biocompatible, and patient-specific medical implants with complex geometries. This study investigates and optimizes fused deposition modeling (FDM) parameters for fabricating small-scale PEEK medical components with improved dimensional accuracy and surface quality. PEEK’s high processing temperature and thermal contraction make precision printing of fine features challenging. A Taguchi design of experiments (L9 orthogonal array) was employed to assess the effects of nozzle temperature, layer height, printing speed, and extrusion width on dimensional deviation and surface roughness using 5 × 5 × 5 mm cube specimens. Dimensional accuracy was quantified along the horizontal and vertical axes, and surface roughness was measured using a stylus profilometer. Statistical analysis showed layer height was the most significant factor affecting horizontal accuracy (p = 0.0225), while printing speed most strongly influenced vertical deviation. The optimal parameters, 450 °C nozzle temperature, 0.06 mm layer height, 7.5 mm/s printing speed, and 0.4 mm extrusion width, achieved mean deviations of 0.013 mm (horizontal) and 0.049 mm (vertical) with a surface roughness of 4.01 µm. Validation using a benchmark model and micro-computed tomography confirmed improved reproduction of small features under these conditions. The results demonstrate that precise control of FDM parameters enables accurate fabrication of sub-millimeter PEEK structures suitable for medical device applications.

Introduction Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities. Methods and analysis The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness. Ethics and dissemination Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments. Trial registration number ACTRN12625001050448.

Key Points Contemporary aspirin exacerbated respiratory disorder (AERD) therapy commonly includes aspirin desensitization (55%) and biologics (48%). Aspirin desensitization therapy has higher discontinuation rates than biologics. Patients receiving biologics are younger, and ∼25% of the patients switch to other agents.

ABSTRACT Objectives To review septal perforation management and outcomes in patients with hereditary hemorrhagic telangiectasia (HHT). Methods Collection and presentation of patient demographic, perforation size, and prior perforation and HHT treatment data over a 20‐year period. Symptom and quality of life treatment outcomes were determined using the Nasal Obstruction Symptom Evaluation (NOSE)‐Perf scale and the 5‐Factor Glasgow Inventory (GBI‐5F), respectively, in patients treated since 2017. Results Nine patients met study criteria. Mean (range) age was 64.4 (52–80) years and seven were biological males. Mean (range) perforation length and height were 1.9 (1.2–2.6) and 1.4 (1.0–1.8) cm. Four patients were treated with a customized septal button, one with posterior septal resection, and four with endonasal bilateral mucosal flap repair supported with an interposition graft. The button prostheses were well tolerated and the surgical closures successful at 8–60 months postoperatively. Subjective responses in the first three patients, and NOSE‐Perf with GBI‐5F scores in the latter six patients, demonstrated symptom and quality of life improvement for all patients. Perforation repair patients demonstrated substantial improvement in mean GBI‐5F subdomain scores for quality of life, self‐confidence, and social involvement and all have undergone sodium tetradecyl sclerotherapy injection postoperatively without re‐perforation. Conclusion Symptom and quality of life improvement can be achieved in HHT patients with a perforation using customized septal buttons, posterior septal resection, or bilateral flap surgical repair. Surgical closure combined with injection sclerotherapy is feasible with a low risk of re‐perforation and represents an effective treatment strategy in selected patients. Level of Evidence 4.

Constrictive pericarditis (CP) is characterized by stiff scarred pericardium as a result of repeated inflammatory insults. Patients with CP usually present with diastolic heart failure symptoms, including ascites, hepatomegaly, pedal edema, and potentially hepatic cirrhosis. This leads to delayed diagnosis. This review aims to fill the knowledge gaps in clinical presentation, pathophysiology, and diagnostic workup of CP. Furthermore, we highlight the key medical and surgical management aspects of CP.

Abstract INTRODUCTION Apolipoprotein E allele 4 (APOE ε4) is the main genetic risk factor for late‐onset Alzheimer's disease (AD), but most evidence comes from White populations in high‐income countries. We investigated APOE and AD pathology in an ethnically diverse Brazilian autopsy cohort. METHODS This cross‐sectional study used Biobank for Aging Studies (BAS) data. AD pathology was evaluated with Braak, Consortium to Establish a Registry for Alzheimer's Disease, and Thal criteria. APOE genotypes were obtained from blood or brain tissue. Regression models were adjusted for age, sex, race, and education; interaction with race was tested. RESULTS Among 1391 participants (mean age 75.1 ± 12.4 years, 50% women, 64% White), APOE ε4showed a dose response with greater AD pathological burden and higher odds of AD diagnosis, while APOE ε2/X was protective. APOE ε4/ε4 did not show full penetrance across age groups. Associations were similar in White and Black individuals. DISCUSSION APOE ε4was strongly associated with AD pathology, with consistent associations across racial groups. Highlights APOE ε4 increased AD neuropathological burden in Brazilians. APOE ε2/εX was protective against AD pathology. APOE ε4/ε4did not show full penetrance across age groups. Associations between APOE and AD pathology were similar by race. Large multiethnic autopsy study expands evidence beyond high‐income country studies.