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Abstract: Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, aggressive salvage therapy was the predominant second-line choice (38%). Overall response rate to therapy after POD24 was 64% (95% confidence interval [CI], 56-70); complete response rate was 39% (95% CI, 32-46). The median event-free survival for therapy after POD24 was 9.8 months (95% CI, 7.3-12.1); 5-year overall survival (OS) was 71% (95% CI, 65-78). OS was inferior for patients aged >70 years (hazard ratio [HR], 2.31; 95% CI, 1.27-4.20) and those with high-risk FL International Prognostic Index scores at diagnosis (HR, 2.10; 95% CI, 1.23-3.60). No treatment category stood out with more favorable results. Cause of death was predominantly lymphoma related. Patients with follicular histology at their POD24 event had a low cumulative incidence of transformation (1.1% at 5 years). Our study is among the largest cohorts describing contemporary patterns of care for patients with POD24, providing a focused data set useful for interpreting and designing prospective clinical trials in this population., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Hypertension in pregnancy contributes substantially to maternal morbidity and mortality, persistent hypertension, and rehospitalization. Hypertensive disorders of pregnancy are also associated with a heightened risk of cardiovascular disease, and timely recognition and modification of associated risk factors is crucial in optimizing long-term maternal health. During pregnancy, there are expected physiologic alterations in blood pressure (BP); however, pathophysiologic alterations may also occur, leading to preeclampsia and gestational hypertension. The diagnosis and effective management of hypertension during pregnancy is essential to mitigate maternal risks, such as acute kidney injury, stroke, and heart failure, while balancing potential fetal risks, such as growth restriction and preterm birth due to altered uteroplacental perfusion. In the postpartum period, innovative and multidisciplinary care solutions that include postpartum maternal health clinics can help optimize short- and long-term care through enhanced BP management, screening of cardiovascular risk factors, and discussion of lifestyle modifications for cardiovascular disease prevention. As an adjunct to or distinct from postpartum clinics, home BP monitoring programs have been shown to improve BP ascertainment across diverse populations and to lower BP in the months after delivery. Because of concerns about pregnant patients being a vulnerable population for research, there is little evidence from trials examining the diagnosis and treatment of hypertension in pregnant and postpartum individuals. As a result, national and international guidelines differ in their recommendations, and more studies are needed to bolster future guidelines and establish best practices to achieve optimal cardiovascular health during and after pregnancy. Future research should focus on refining treatment thresholds and optimal BP range peripartum and postpartum and evaluating interventions to improve postpartum and long-term maternal cardiovascular outcomes that would advance evidence-based care and improve outcomes worldwide for people with hypertensive disorders of pregnancy., Competing Interests: Dr Sarma is a consultant for Pfizer. Dr Honigberg reports consulting fees from Comanche Biopharma, advisory board service for Miga Health, site principal investigator work for Novartis, and research support from Genentech. Dr Yang is an advisory board member for Idorsia, Mineralys, Qure.ai, and Sky Labs; consults for Genentech; and receives honoraria from the American College of Cardiology and research grants from Microsoft Research. Dr Harrington is a consultant for Pfizer and Always. Dr Sachdev is an employee of the American Medical Association. The views expressed in the article are those of the authors and may not necessarily reflect the official position of the American Medical Association. The other authors report no disclosures or conflicts of interest.

Background: Whether the differing mechanistic effects between angiotensin-2 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on the renin-angiotensin system translate to differential effects on clinical cognitive outcomes is unclear., Methods: We employed an active comparator, new-user cohort study to emulate a target trial evaluating the per-protocol effect of initiating and continuously adhering to an ARB vs. ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial. Inverse probability of treatment and censoring weighted cumulative incidence functions accounted for confounding, the competing risk of death, adherence, and loss to follow-up., Results: Of 9,361 SPRINT participants (mean age 67.1±9.5 years, 36.7% female, 58.7% non-Hispanic White), 710 and 1,289 were new users of an ARB or ACEI. Overall, 291 (41.0%) ARB initiators and 854 (66.3%) ACEI initiators were non-adherent during follow-up. The IP-weighted 4-year probabilities of full adherence and being alive among ARB was 56.0% (95% CI: 52.2%-59.9%) and 30.5% (95% CI: 28.0%-33.1%) for ACEI. The 4-year weighted risk ratios (RR) for amnestic MCI/PD and for amnestic MCI/PD/death with initiation and full adherence to ARB vs. ACEI were 0.94 (95% CI: 0.66-1.29) and 0.79 (95% CI: 0.58-1.06). ARB vs. ACEI initiation and adherence was associated with a weighted RR of 0.36 (95% CI: 0.14-0.76)., Conclusions: In this target trial emulation of older adults at high risk for cardiovascular disease, there was insufficient evidence to conclude a beneficial effect of initiating and continuously adhering to an ARB vs. ACEI on adjudicated clinical cognitive outcomes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America.)

Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but there are limited real-world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high-grade B cell lymphoma treated with R-GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy (n = 100), those utilizing R-GemOx as a bridge to ASCT or CAR T (n = 83), and those aged 70 and older (n = 71). Overall response rates (ORRs) for all patients treated with R-GemOx were 45% with a complete response (CR) rate of 29%. The median event-free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R-GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R-GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R-GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R-GemOx in the rapidly evolving landscape of R/R DLBCL therapies., (© 2025 Wiley Periodicals LLC.)

Background: Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages., Methods: We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting., Results: Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71-79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model., Conclusions: Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe (1) PA screening practices in a large, diverse health system, (2) the development of a computable phenotype for PA screening, and (3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening., Study Design: A multidisciplinary team developed a multipronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across 2 primary care practices for 7 months. Screening frequencies were compared with clinics not receiving the intervention., Results: The baseline frequency of screening of eligible patients within 1 year was 1.4%. Higher mean systolic blood pressure (odds ratio [OR] 1.4; p < 0.001), more antihypertensive medications (OR 1.3; p = 0.002), lower minimum serum potassium (OR 2.0; p = 0.001), specialist care (OR 3.0; p < 0.001), and Black race (OR 1.5; p = 0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% vs 4.1%; p = 0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the nonintervention clinics (1.8%; p < 0.001)., Conclusions: PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase I/II BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with relapsed / refractory B-cell malignancies (clinicaltrials.gov 03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (N=40, 31.5%), specifically atrial fibrillation (N=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common reasons for pirtobrutinib discontinuation were progressive disease (26.8%), AE (10.2%) or death (5.5%). The most frequent treatment-emergent AE were fatigue (39.4%) and neutropenia (37.0%). Among patients who discontinued a prior BTKi for a cardiac issue, 75% had no recurrence of their cardiac AE. No patient discontinued pirtobrutinib for the same AE that led to discontinuation of the prior BTKi. In 78 chronic lymphocytic / small lymphocytic lymphoma (CLL/SLL) and 21 mantle cell lymphoma (MCL) patients intolerant to prior BTKi, overall response rate to pirtobrutinib was 76.9% and 81.0%, respectively. Median progression-free survival for CLL/SLL was 28.4 months but was not estimable for MCL. These results suggest that pirtobrutinib was safe, well-tolerated, and an efficacious option in patients with prior BTKi-intolerance.

Competing Interests: None.

Importance: Nitric oxide deficiency may contribute to exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Prior pilot studies have shown improvements in exercise tolerance with single-dose and short-term inorganic nitrate administration., Objective: To assess the impact of chronic inorganic nitrate administration on exercise tolerance in a larger trial of participants with HFpEF., Design, Setting, and Participants: This multicenter randomized double-blinded crossover trial was conducted at the University of Pennsylvania, the Philadelphia Veterans Affairs Medical Center, and Northwestern University between October 2016 and July 2022. Participants included patients with symptomatic (New York Heart Association class II/III) HFpEF who had objective signs of elevated left ventricular filling pressures. Image quantification, physiological data modeling and biochemical measurements, unblinding, and statistical analyses were completed in 2024., Intervention: Potassium nitrate (KNO3) (6 mmol 3 times daily) vs equimolar doses of potassium chloride (KCl) for 6 weeks, each with a 1-week washout in between., Main Outcomes and Measures: The coprimary end points included peak oxygen uptake and total work performed during a maximal effort incremental cardiopulmonary exercise test. Secondary end points included the exercise systemic vasodilatory reserve (ie, reduction in systemic vascular resistance with exercise) and quality of life assessed using the Kansas City Cardiomyopathy Questionnaire., Results: Eighty-four participants were enrolled. Median age was 68 years and 58 participants were women (69.0%). Most participants had NYHA class II disease (69%) with a mean 6-minute walk distance of 335.5 (SD, 97.3) m. Seventy-seven participants received the KNO3 intervention and 74 received the KCl intervention. KNO3 increased trough levels of serum nitric oxide metabolites after 6 weeks (KNO3, 418.4 [SD, 26.9] uM vs KCl, 40.1 [SD, 28.3] uM; P < .001). KNO3 did not improve peak oxygen uptake (KNO3, 10.23 [SD, 0.43] mL/min/kg vs KCl, 10.17 [SD, 0.43] mL/min/kg; P = .73) or total work performed (KNO3, 25.9 [SD, 3.65] kilojoules vs KCl, 23.63 [SD, 3.63] kilojoules; P = .29). KNO3 nitrate did not improve the vasodilatory reserve or quality of life, though it was well-tolerated., Conclusions and Relevance: In this study, potassium nitrate did not improve aerobic capacity, total work, or quality of life in participants with HFpEF., Trial Registration: ClinicalTrials.gov Identifier: NCT02840799.

Introduction: Clinical trials provide meaningful data regarding the safety and efficacy of novel therapies but there is often a lag between the time of new drug approval and information on posttreatment clinical outcomes in real-world practice. This study evaluated clinical outcomes in a large real-world population of patients with relapsed and/or refractory large B-cell lymphoma (r/r LBCL) treated with chemoimmunotherapy or novel therapies in second or later lines of therapy (2L+)., Materials and Methods: Data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) cohort (1/1/2015-2/15/2023) were analyzed. Patients' demographic and clinical characteristics were described and response rates, duration of response, progression-free survival, and overall survival were evaluated. Multivariable Cox proportional hazards regression models were used to assess associations between patient clinical characteristics and outcomes., Results: The 2L+ cohort included patients treated with chemoimmunotherapy (N = 593), lenalidomide-based therapy (n = 60), polatuzumab vedotin-based therapy (N = 116), tafasitamab-based therapy (N = 55), and loncastuximab tesirine (N = 42). Most patients who received prior chimeric antigen receptor T-cell therapy (CAR-T) were refractory to the treatment. Across all patients, overall response rates were <50%, with one-quarter achieving complete response and median duration of response and overall survival were short (<6 and <10 months, respectively) among patients treated with chemoimmunotherapy or novel therapies. The prognosis was worse for patients who had previously received CAR-T. Primary refractory status, high-risk disease, and failing 3 or more lines of therapy were significantly associated with worse outcomes., Conclusion: Patients with r/r LBCL have unfavorable outcomes and need more effective treatment alternatives., Competing Interests: Disclosure LJN has received honoraria for participating in the advisory boards of AbbVie, AstraZeneca, BMS, Genentech, Genmab, Gilead/Kite, Incyte, Ipsen, Janssen, Merck, Novartis, Regeneron, and Takeda; and research support from BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, IGM Biosciences, Janssen, Merck, Novartis, and Takeda. YW has received research funding (to his institution) from AbbVie, Eli Lilly, Genentech, Genmab, Incyte, InnoCare, LOXO Oncology, MorphoSys, and Novartis; compensation (to his institution) for serving on the advisory boards of AstraZeneca, BeiGene, Eli Lilly, Genmab, Incyte, InnoCare, Jansen, Kite, LOXO Oncology, and TG Therapeutics; compensation (to his institution) for providing consultancy services to AbbVie and Innocare; and honoraria (to his institution) from Kite. TMH is on the Data Monitoring Committees of Eli Lilly & Company and Seagen; and has received research funding (to his institution) from Genentech/Roche, Genmab, and Sorrento. DC has received honoraria from Beigene and Ono, and research funding from BMS, Genmab, Ipsen, Morphosys, and Ono. BSK has served as a consultant for ADC Therapeutics, Celgene/BMS, and Genentech/Roche. BKL has received compensation from Genentech/Roche and MEI Inc. for Data Safety Monitoring Board participation, and for participating in the advisory board of Genentech/Roche; and has received research funding from AstraZenenca, Genentech/Roche, and Genmab. JLK has received honoraria for providing consultancy services to or compensation for participating in the advisory boards of AbbVie and Beigene; and research support from Viracta Therapeutics. JBC has served as an advisor to ADCT, AstraZeneca, Beigene, Janssen, Kite/Gilead, and Loxo/Lilly; and has received research funding from AstraZeneca, BMS/Celgene, Genentech, Loxo/Lilly, Novartis, and Takeda. PM has served as a consultant for AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, Epizyme, Genentech, Janssen, and Merck. ISL is a current employee of the University of Miami; has received honoraria from Adaptive; has served in a consulting or advisory role for Lymphoma Research Foundation; has received research funding from the National Cancer Institute; and has received compensation for teaching from Kyowa Kirin. CC has served as consultant for and has received honoraria from AbbVie, BMS, Genentech, and Mashup Media; has received research funding from Genentech, Genmab, and Gilead; and has had leadership roles in Follicular Lymphoma Cures Foundation and American Society of Hematology. SA has received research funding (to his instituition) from AstraZeneca, Beigene, Genentech, Genmab, and Regeneron; has served on the Speakers Bureau for Genentech and Total CME; and has acted as a consultant/advisor for Abbvie, ADC Therapeutics, Beigene, Fate Therapeutics, Genentech, and Seattle Genetics. MAL has received compensation from Genmab and GNE. MJM has received research funding from BMS, Genmab, and Roche/Genentech; is on the advisory board of AstraZeneca; and has received compensation (to his institution) for providing consultancy services to BMS. LH, CG, RR, and MSD are employees of Analysis Group Inc., which provided paid consultancy services to Genmab, the study sponsor. AM, TW, MJ, and AK are current employees of Genmab and hold stock options. AW and RK are current employees of AbbVie and hold stock options. CRF has served as a consultant for AbbVie, Bayer, BeiGene, Celgene, Denovo Biopharma, Foresight Diagnostics, Genentech/Roche, Genmab, Gilead, Karyopharm, N-Power Medicine, Pharmacyclics/Janssen, SeaGen, and Spectrum; holds stock or stock options for Foresight Diagnostics and N-Power Medicine; and has received research funding from 4D, AbbVie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, BostonGene, Celgene, Cellectis EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, Morphosys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, and Ziopharm as well as Burroughs Wellcome Fund, Cancer Prevention and Research Institute of Texas RR190079: CPRIT Scholar in Cancer Research; Eastern Cooperative Oncology Group, National Cancer Institute, and V Foundation. All the other authors declared that they have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationales: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C)., Primary Hypothesis: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention., Design: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team., Sites: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas., Primary Outcomes: Improvement in systolic blood pressure and LDL-C., Secondary Outcomes: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention., Estimated Enrollment: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits., Enrollment Dates: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist., Current Status: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394., Competing Interests: Conflict of interest Dr. Volpp is a Scientific Board member of THRIVE Global and a part owner of VALHealth, a behavioral economics consulting firm and has received research funding and consulting support from the American Heart Association. Dr. Asch is also a part owner of VALHealth and a Scientific Board member of THRIVE Global., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale & Objective: The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD., Study Design: Prospective cohort study., Setting & Participants: 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study., Exposure: Albuminuria stage at study entry., Outcome: Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death., Analytical Approach: Linear mixed effects and Cox proportional hazards regression analyses., Results: Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m 2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m 2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m 2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively)., Limitations: Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding., Conclusions: Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria., Plain-Language Summary: Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: We briefly review the concept of psychological safety and discuss the actions that can create it in the anesthesiologist's work environment., Recent Findings: The interest in psychological safety has grown in popularity since the publication of Amy Edmondson's book The Fearless Organization in 2018. While the concept and its benefits are described in the healthcare literature, the specific actions necessary to create it are often not., Summary: To ensure patient safety, we want members of the teams we lead to be comfortable sharing emerging problems that they see before we become aware of them. As educators, we want trainees to approach us when they do not understand something and openly participate and contribute without the fear of how others will perceive them. These scenarios require an environment of psychological safety - the ability to ask for help, admit mistakes, and be respectfully forthright with unpopular beliefs without the fear of being ostracized or ignored. Methods for creating an environment of psychological safety will be discussed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D 3 vs. placebo., Methods: In this phase 3, randomized, double-blind, placebo-controlled trial, patients with low tumor burden follicular, marginal zone or small lymphocytic lymphoma, age 18 or older, with stage two or greater disease and no prior systemic treatment were enrolled at 7 academic cancer centers. Patients were stratified by histology and FLIPI (Follicular Lymphoma International Prognostic Index) score and randomized 2:1 to receive 2000 IU vitamin D 3 or placebo daily beginning on day one with rituximab 375 mg/m 2 administered weekly times four. 257 patients were assessed for participation: 24 were not eligible and 22 refused. Patients with stable disease or disease progression at week 13 counted as events; responding patients continued treatment with vitamin D or placebo until progression for up to three years. The primary endpoint was EFS, defined as the time from randomization to lack of response at week 13, initiation of a new treatment, disease progression or death. Secondary endpoints included week 13 response and OS. This trial is registered at clinicaltrials.gov, NCT03078855., Findings: 206 evaluable patients (135 on vitamin D and 71 on placebo) were enrolled between September 2017 and March 2022 with a median EFS follow-up of 19.6 months (IQR, 9.3-33.5). The median age was 62 years (IQR, 54-70); 118 (57%) female; 182 (89%) white. At week 13 the mean vitamin D level increased to 41.6 ng/mL (SD 10.1) in the vitamin D arm vs. remaining stable (31.3 ng/mL, SD 11.2) in the placebo arm. There was insufficient evidence of a difference in EFS between the two arms (P = 0.26): three-year EFS in the vitamin D arm was 47.7% (95% CI, 39.0-58.4) compared to 49.5% (95% CI, 37.6-65.0) in the placebo arm. There was no difference in week 13 response between the arms (both 84%). Adverse events associated with vitamin D supplementation were rare. The median OS follow-up was 35.1 months (IQR, 22.9-45.1), overall survival was 96.6% (95% CI, 93.1-98.6) and there was no significant difference between the vitamin D and placebo arms (P = 0.47)., Interpretation: As tested in this study, there is no benefit to routine vitamin D supplementation in patients with indolent lymphoma treated with rituximab. These results have implications for ongoing and planned studies of vitamin D supplementation in other malignancies., Funding: This study was funded by the National Institutes of Health, National Cancer Institute grant R01CA214890., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Abstract: There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or stable disease (SD) by imaging after completion of frontline treatment (PR/SD); (3) progression of disease by imaging (and confirmed by biopsy) within 12 months of frontline therapy completion after prior documentation of complete response (CR; early relapse [ER]). A total of 478 patients were included in the analysis. Among these, 217 (45%) were PP, 86 (18%) were PR/SD, and 175 (37%) were ER. The 6-month and 1-year cumulative incidence of nonrelapse mortality after auto-HCT were 0.9% and 1.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) after auto-HCT were 4.33 and 10.09 years, respectively. Although those not in CR at the time of auto-HCT were associated with inferior PFS and OS, advanced age and diagnosis before 2011 were associated with inferior OS. This study showcases the safety and long-term efficacy of auto-HCT, even in patients with high-risk disease who are traditionally considered chemotherapy refractory, and will serve as a benchmark for the ongoing transplant vs no transplant trials., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect <1% of non-Hodgkin lymphomas., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Resistant and uncontrolled hypertension are common presentations to the nephrology clinic. Many of these patients benefit from evaluation for secondary hypertension in order to optimize antihypertensive therapy and reduce the risks of target organ damage from uncontrolled hypertension. The purpose of this review is to present several cases of difficult-to-control and/or secondary hypertension and to identify optimal approaches to evaluating and managing hypertension in these high-risk patients., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first-line β-blocker use without a compelling condition has fallen out of favor in US guidelines., Methods and Results: This serial cross-sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (<140, 140 to <160, and ≥160 mm Hg), as well as trends in subgroups (age, sex, race and ethnicity, and comorbidities warranting β-blocker use). Among 2 832 684 eligible Veterans (average age 61 years, 95% men, 65% non-Hispanic White, and 8% with cardiovascular disease), from 2000-2004 to 2015-2019, initial monotherapy increased across all pretreatment systolic BP levels (<140 mm Hg: 62.1% to 66.4%; 140 to <160 mm Hg: 70.7% to 76.8%; ≥160 mm Hg: 64.2% to 69.7%). Initiation of dual therapy decreased across all pretreatment systolic BP levels (<140 mm Hg: 25.0% to 24.2%; 140 to <160 mm Hg: 20.4% to 17.6%; ≥160 mm Hg: 22.7% to 22.0%). Among 2 521 696 Veterans (89% of overall) without a β-blocker-indicated condition in 2015 to 2019, 20% initiated a β-blocker, most commonly as monotherapy., Conclusions: More than half of US Veterans diagnosed with hypertension with a pretreatment systolic BP ≥160 mm Hg were started on antihypertensive monotherapy. There are disparities between guideline-recommended first-line treatments and the actual regimens initiated for newly diagnosed Veterans with hypertension.

Background: In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications., Methods: Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up., Results: A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86])., Conclusions: Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management., Competing Interests: None.

Purpose of Review: This review aims to inform the reader of the complexity of blood pressure responses when comparing blood pressure measured in the medical environment to that outside the medical environment. In addition, we summarize what is known about current predictors of white coat hypertension, reevaluate the relationship of white coat hypertension to cardiovascular outcomes, and provide some clinical guidance on management., Recent Findings: Differences in outcomes exist when white coat effect occurs in unmedicated people versus the white coat effects in those on antihypertensive therapy. White coat hypertension is relatively common, carries a small but definite increase in cardiovascular risk, and is prone to conversion to sustained hypertension. Future research will hopefully tease out the roles of ancillary findings that characterize a white coat hypertensive (like modest elevations in creatinine, glucose and triglycerides) in the elevated cardiovascular risk, and test the effectiveness of mitigation strategies in these patients., (© 2024. The Author(s).)

Clinical bleeding events are reported here from 773 patients with B-cell malignancies receiving pirtobrutinib monotherapy from the phase 1/2 BRUIN study (ClinicalTrials.gov identifier: NCT03740529), either in the presence or absence of antithrombotic therapy (antithrombotic exposed [AT-E], n  = 216; antithrombotic nonexposed [AT-NE], n  = 557). Among the AT-E cohort, 51.9% received platelet aggregation inhibitors, 36.6% received direct factor Xa inhibitors, 18.5% received heparins, 5.6% received salicylic acid for indications other than platelet aggregation inhibition, and 2.3% received thrombolytics. Warfarin was not permitted. Any-grade bleeding/bruising events occurred in 97 patients (44.9%; 95% confidence interval [CI], 38.3-51.5) in the AT-E cohort and 181 patients (32.5%; 95% CI, 28.6-36.4) in the AT-NE cohort. Most bleeding/bruising events in both cohorts began within the first 6 months of treatment (AT-E: 65.4%; AT-NE: 72.5%). Contusion was the most common bleeding/bruising event in both cohorts (AT-E: 22.7%; AT-NE: 18.1%). Grade ≥3 bleeding/bruising events were reported in six patients (2.8%) in the AT-E cohort and 11 patients (2.0%) in the AT-NE cohort. Bleeding/bruising events requiring or prolonging hospitalization were reported in 2.3% and 1.6% of patients in the AT-E and AT-NE cohorts, respectively. No bleeding/bruising events led to pirtobrutinib dose reduction or permanent discontinuation in the AT-E cohort, and one patient (0.2%) in the AT-NE cohort experienced an event requiring dose reduction. These data support the safety of pirtobrutinib in patients requiring antithrombotic therapies., Competing Interests: NL reports research funding from Genentech, TG Therapeutics, BeiGene, AstraZeneca, AbbVie, MingSight, Eli Lilly and Company/Loxo@Lilly, Oncternal Therapeutics, and Octapharma, and consulting fees/honoraria from Genentech, Pharmacyclics, BeiGene, AstraZeneca, AbbVie, Adaptive Biotechnologies, Eli Lilly and Company/Loxo@Lilly, and Janssen. CST reports honoraria from Loxo@Lilly. JAW reports grants from the National Cancer Institute, Leukemia and Lymphoma Society, and CLL Global Society; consulting fees from AbbVie, AstraZeneca, BeiGene, Genentech, Janssen, Loxo@Lilly, Merck, Newave, and Pharmacyclics; and is on the advisory board of Gilead. AJA reports honoraria from Dr. Reddy's; is on advisory boards for Genentech, Eli Lilly and Company, Amgen, TG Therapeutics, Incyte, BeiGene, Janssen, Epizyme, and SeaGen; and reports research funding from Eli Lilly and Company, Incyte, and BeiGene. MLP reports participation on a data safety monitoring board or advisory board at Bristol‐Myers Squibb, Cellectar Biosciences, MustangBio, and Synthekine. PLZ reports membership on an entity's board of directors or advisory committee at AstraZeneca, Sandoz, Celltrion Healthcare, MSD, Secura Bio, Gilead, Janssen‐Cilag, Bristol‐Myers Squibb, Takeda, Roche, Servier Pharma, Kyowa Kirin, EUSA Pharma, Novartis, ADC Therapeutics, Incyte, and BeiGene; is on the speakers bureau of AstraZeneca, Celltrion Healthcare, MSD, Gilead, Janssen‐Cilag, Bristol‐Myers Squibb, Takeda, Roche, Servier Pharma, Kyowa Kirin, EUSA Pharma, Novartis, Incyte, and BeiGene; and has consultancy roles at MSD, EUSA Pharma, and Novartis. IWF reports consultancy roles at Genmab, BeiGene, Genentech, Secura Bio, Hutchison MediPharma, Kite Pharma, InnoCare Pharma, AbbVie, Novartis, Myeloid Therapeutics, Servier Pharma, Century Therapeutics, TG Therapeutics, and Vincerx Pharma. BF reports consultancy roles and membership on an entity's board of directors or advisory committee at BeiGene, AstraZeneca, ADC Therapeutics, AbbVie, Bristol‐Myers Squibb/Juno, Genentech, Genmab/AbbVie, Loxo@Lilly, and Pharmacyclics; and research funding from Genentech, Genmab/AbbVie, Loxo@Lilly, and Pharmacyclics. JBC reports research funding from Bristol‐Myers Squibb/Celgene, Novartis, Genentech, BioInvent, LAM Therapeutics, Takeda, ADC Therapeutics, AbbVie, and Loxo/Lilly; and consultancy roles at AstraZeneca, Janssen, BeiGene, and Loxo/Lilly. WJ reports research funding from Eli Lilly and Company; grants from AstraZeneca and BeiGene; and is on the advisory board for Eli Lilly and Company, AstraZeneca, and BeiGene. AK, HK, AC, and DET report full‐time employment with Loxo Oncology during the conduct of the study. ASR, RS, and LC report full‐time employment with Eli Lilly and Company during the conduct of the study., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear., Methods and Results: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort., Conclusions: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Introduction: Following an index femoral fragility fracture, patients are at risk of a subsequent peri-implant fracture. Management of these injuries are further complicated by patient factors and multi-institutional care. This study quantifies such events and compare rate of identification between in-system and out-of-system patients., Methods: A retrospective chart review of index operative femoral fragility fractures at a level I trauma center from January 1, 2005 to January 1, 2018 identified 840 patients with twenty-two subsequent peri-implant fractures. Kaplan Meier survival analyses assessed associations between patient and injury characteristics with the subsequent fracture while accounting for differential follow-up. Cumulative incidence curves were reported, and Cox regression analyses estimated hazard ratios for statistically significant associations. In-system and out-of-system patients were compared with absolute rate of identifying subsequent fracture and follow-up time., Results: Cumulative incidence of subsequent fracture was 2.1 % at 2 years, 3.4 % at 4 years, and 4.6 % at 6 years. The index fracture pattern (intertrochanteric vs other) was associated with a cumulative incidence of subsequent peri-implant fracture (0.8 % at 2 years, 1.4 % at 4 years, and 2.7 % at 6 years for intertrochanteric fractures vs 3.4 % at 2 years, 5.3 % at 4 years, and 6.4 % at 6 years for non-intertrochanteric fractures), p = 0.029. Follow-up was shorter for out-of-system patients (median 6 versus 28 months, p < 0.001), and only 1 of 348 out-of-system patients (0.3 %) vs. 21 of 492 in-system patients (4.3 %) were diagnosed with a subsequent peri-implant fracture (p < 0.001). There was no association of subsequent peri-implant fracture with patient demographics or comorbidity burden., Conclusion: Cumulative incidence of subsequent peri-implant fracture was higher for non-intertrochanteric (femoral neck, shaft and distal femur) fractures than intertrochanteric fractures. Out-of-system patients had shorter follow-up and were less likely to be diagnosed with a subsequent peri-implant fracture, indicating ascertainment bias and underscoring the importance of accounting for loss to follow-up., Level of Evidence: Therapeutic Level III., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Delhi Orthopedic Association. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Metabolic and bariatric surgery (MBS) is the most effective and durable treatment for obesity. We aimed to compare the trajectories of antihypertensive medication (AHM) use among obese individuals treated and not treated with MBS., Methods: Adults with a body mass index of ≥35 kg/m 2 were identified in the Merative Database (US employer-based claims database). Individuals treated with versus without MBS were matched 1:1 using baseline demographic and clinical characteristics as well as AHM utilization. Monthly AHM use was examined in the 3 years after the index date using generalized estimating equations. Subanalyses investigated rates of AHM discontinuation, AHM initiation, and apparent treatment-resistant hypertension., Results: The primary cohort included 43 206 adults who underwent MBS matched with 43 206 who did not. Compared with no MBS, those treated with MBS had sustained, markedly lower rates of AHM use (31% versus 15% at 12 months; 32% versus 17% at 36 months). Among patients on AHM at baseline, 42% of patients treated with MBS versus 7% treated medically discontinued AHM use ( P <0.01). The risk of apparent treatment-resistant hypertension was 3.41× higher (95% CI, 2.91-4.01; P <0.01) 2 years after the index date in patients who did not undergo MBS. Among those without hypertension treated with MBS versus no MBS, 7% versus 21% required AHM at 2 years., Conclusions: MBS is associated with lower rates of AHM use, higher rates of AHM discontinuation, and lower rates of AHM initiation among patients not taking AHM. These findings suggest that MBS is both an effective treatment and a preventative measure for hypertension., Competing Interests: E. Wall-Wieler, Y. Liu, and F. Zheng are employed by Intuitive. The other authors report no conflicts.

Abstract: Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological Resource cohort (MER; N = 949) or the Lymphoma Epidemiology of Outcomes cohort (LEO; N = 2755) from September 2002 to May 2021. Primary refractory LBCL was defined as no response (stable disease [SD]) or progressive disease (PD) during, or by the end of, frontline (1L) IC (primary PD; PPD); partial response at end of treatment (EOT PR); or relapse within 3 to 12 months after achieving CR at EOT to 1L IC (early relapse). In the MER cohort, patients with PPD had inferior overall survival (OS; 2-year OS rate: 15% MER, 31% LEO) when compared with other subgroups considered in defining primary refractory disease, EOT PR (2-year OS rate: 38% MER, 50% LEO) and early relapse (2-year OS rate: 44% MER, 58% LEO). Among patients receiving 1L IC with curative intent, we identified that patients with PPD are the key subgroup with poor outcomes. We propose a definition of primary refractory LBCL as SD or PD during, or by the end of, 1L treatment., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with R/R FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized matching- adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. ORR (73%, 95% CI: 65-80%) and CR rates (53%, 95% CI: 45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI: 70-88%; CR=60%, 95% CI: 49-70%, respectively). PFS at 12 months was similar in the weighted LEO CReWE (60%, 95% CI: 51-69%) and the mosunetuzumab (58%, 95% CI: 47-68%) trial. Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria provide context for best practices in this setting.

Background: Deep inferior epigastric perforator (DIEP) flap breast reconstruction is among the higher-risk patient groups for venous thromboembolism (VTE) in plastic surgery. Surgeons often opt for a patient-specific approach to postoperative anticoagulation, and the field has yet to come to a consensus on VTE chemoprophylaxis regimens., Methods: A new chemoprophylaxis protocol was introduced starting in March of 2019 that involved 2 weeks of treatment with enoxaparin, regardless of patient risk factors. A retrospective chart review was conducted on all patients who underwent DIEP flap breast reconstruction at the authors' institution between January of 2014 and March of 2020. Patients were grouped based on whether they enrolled in the new VTE protocol in the postoperative period or not. Patient demographics, prophylaxis type, and outcomes data were recorded, retrospectively. The primary outcome measure was postoperative VTE incidence., Results: Risk of VTE was significantly higher in patients discharged without VTE prophylaxis compared with patients discharged with prophylaxis (3.7% versus 0%; P = 0.03). Notably, zero patients in the VTE prophylaxis group developed a deep venous thrombosis or pulmonary embolism. In addition, the risk of a VTE event was 25 times greater in patients with a Caprini score greater than or equal to 6 ( P = 0.0002)., Conclusion: The authors demonstrate the successful implementation of a 2-week VTE chemoprophylaxis protocol in DIEP flap breast reconstruction patients that significantly reduces the rate of VTE while not affecting the rate of hematoma complications., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Purpose: Animal studies have suggested that Erythropoiesis-Stimulating Agents (ESAs) may increase vascular endothelial growth factor (VEGF)-related retinopathies, but this effect is unclear in humans. This study evaluates the risk of vision-threatening diabetic retinopathy (VTDR), defined as either diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), in patients exposed to an ESA., Methods: Two analyses were performed. First, a retrospective matched-cohort study was designed using a de-identified commercial and Medicare Advantage medical claims database. The ESA cohort of non-proliferative diabetic retinopathy patients who were new users of an ESA from 2000 to 2022 was matched to controls up to a 3:1 ratio. Exclusion criteria included less than 2 years in the plan, history of VTDR or history of other retinopathy. Multivariable Cox proportional hazards regression with inverse proportional treatment weighting (IPTW) was used to assess the hazard of developing VTDR, DME, and PDR. The second analysis was a self-controlled case series (SCCS) evaluating the incidence rate ratios (IRR) of VTDR during 30-day periods before and after initiating an ESA., Results: After inclusion of 1502 ESA-exposed patients compared with 2656 controls, IPTW-adjusted hazard ratios found the ESA cohort had an increased hazard of progressing to VTDR (HR = 3.0 95%CI:2.3-3.8; p  < .001) and DME (HR = 3.4,95%CI:2.6-4.4, p  < .001), but not PDR (HR = 1.0,95%CI:0.5-2.3, p  = .95). Similar results were found within the SCCS which demonstrated higher IRRs for VTDR (IRRs = 1.09-1.18; p  < .001) and DME (IRRs = 1.16-1.18; p  < .001), but not increased IRRs in PDR (IRR = 0.92-0.97, p  = .02-0.39)., Conclusion: ESAs are associated with higher risks for VTDR and DME, but not PDR. Those studying ESAs as adjunctive therapy for DR should be cautious of possible unintended effects.

Abstract: Chimeric antigen receptor (CAR) T-cell (CAR-T) immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care use and outcomes in patients treated with CAR-T therapy for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-Ts were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic, and clinical data were collected and analyzed. In total, 466 adult patients were included in our analysis. Median follow-up after CAR-T therapy was 12.7 months. Median progression-free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months; hazard ratio [HR], 1.56 [1.03-2.4]; P = .04) or Asians (2.7 months; HR, 1.7 [1.02-2.67]; P = .04). Differences in median overall survival (mOS) were not significant. For Medicare (n = 206) vs Medicaid (n = 33) vs private insurance (n = 219) vs self-pay (n = 7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (P < .001), respectively; and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (P < .001), respectively. Our multicenter retrospective analysis showed that race and insurance status can affect outcomes for patients treated with CAR-T therapy., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction., Methods and Results: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin-like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47-0.7]; P =3.13E-05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44-0.69]; P =0.0001), and DNASE1 (deoxyribonuclease-1) (HR, 0.5704 [95% CI, 0.46-0.71]; P =0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α-1, collagen XV α-1), metabolism (pancreatic α-amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission., Conclusions: Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.