Omer S. Ashruf

Background: Patients with cancer have elevated cardiovascular risk but have been underrepresented in cardiovascular outcome trials of incretin-based therapies. We compared cardiovascular outcomes associated with tirzepatide and semaglutide in adults with cancer and type 2 diabetes or overweight/obesity.Methods: We conducted an active-comparator, new-user cohort study emulating a target trial using deidentified electronic health record data from 61 US healthcare organizations. Adults initiating tirzepatide or semaglutide between May 1, 2022, and March 1, 2024, were eligible. Tirzepatide initiators were propensity score matched 1:1 to semaglutide initiators on 76 baseline covariates. The primary outcome was three-point major adverse cardiovascular events (MACE): myocardial infarction, stroke, or cardiovascular death. Cox models estimated hazard ratios (HRs) with 95% CIs over follow-up of up to 30 months.Findings: The matched cohort included 23,536 patients, with 11,768 in each treatment group. Mean age was 59.5 years, 62.9% were female, and mean follow-up was 569 days. MACE occurred in 651 tirzepatide initiators and 842 semaglutide initiators. Tirzepatide initiation was associated with a lower risk of MACE than semaglutide initiation (HR 0.80, 95% CI 0.73–0.89), including lower risks of myocardial infarction (HR 0.79, 95% CI 0.68–0.92) and stroke (HR 0.86, 95% CI 0.75–0.99). Cardiovascular death did not differ significantly between groups. Tirzepatide was also associated with lower risks of heart failure exacerbation, all-cause hospitalization, and all-cause mortality.Interpretation: Tirzepatide initiation was associated with lower cardiovascular risk than semaglutide initiation in adults with cancer and cardiometabolic conditions. Prospective confirmation is warranted before these findings inform treatment selection.

AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible—for the first time—to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.

Key Points: The cumulative incidence of AKI diagnosis post–hematopoietic stem cell transplantation was 12.9%. Calcineurin inhibitor use was associated with the highest cumulative incidence, 21.6%, after hematopoietic stem cell transplantation. Patients with AKI with hypertension/hypertensive disease had a 30-day survival probability of 63.9% (hazard ratio, 4.86, 95% confidence interval, 3.58 to 6.60). Patients with AKI were 2.5 times more likely to experience composite hospitalization and/or mortality at 30 days. Of patients who developed AKI, dialysis dependence has nearly tripled since 2014. Background: AKI is a common complication in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), with a reported prevalence ranging from 68% to 84%. Few multicenter pediatric studies comprehensively assess the epidemiologic associations and clinical outcomes associated with AKI development. Methods: An observational, retrospective analysis was conducted using an aggregated electronic health record data platform. The study population consisted of pediatric patients (age n=713) and those without AKI (n=4455). Both groups were propensity matched for age, sex, race, prior cancer diagnosis, and other comorbidities. End points were incidence, mortality risk, clinical outcomes, and prevalence of dialysis dependence. Competing risks analysis, Cox proportional hazard analyses, Kaplan–Meier survival curves, and incidence/prevalence rates were calculated. Results: After matching, 688 patients were identified. Cumulative incidence of AKI diagnosis post-HSCT was 13.7%. Hypertensive disease, calcineurin inhibitors, and vancomycin were the most prevalent risk factors for AKI, with calcineurin inhibitors showing the highest cumulative incidence (21.6%). Patients with AKI with hypertensive disease had a survival probability of 63.9% at 30 days, followed by calcineurin inhibitors (64.4%) and vancomycin (65.9%). Patients with AKI were 1.7 times more likely to experience composite hospitalization and/or mortality at 30 days. At 365 days post-HSCT, patients with AKI had higher rates of all-cause emergency department visits, intensive care unit admissions, and mechanical ventilation compared with non-AKI. Of patients who developed AKI, the prevalence of dialysis dependence has nearly tripled since 2014. Conclusions: The findings highlight a strong association between specific risk factors, such as hypertension, calcineurin inhibitor use, and vancomycin use, with increased mortality and adverse clinical outcomes in patients with AKI after HSCT. These results emphasize the need for preventative actions such as 24-hour BP monitoring and discontinuation of potential nephrotoxic medications.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium’s evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19–63%, and VGPR in 21–65%. The common adverse events were cytokine release syndrome (17–82%), anemia (5–52%), neutropenia (12–75%), and thrombocytopenia (14–42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.

Immunoglobulin M monoclonal gammopathy is detected in Waldenström macroglobulinemia (WM), a rare lymphoplasmacytic lymphoma with serum immunoglobulin M. We report three rare presentations with focu... Plain language summary Lymphoplasmacytic lymphoma (LPL) is an aberrant proliferation of plasma cells which may present as Waldenström macroglobulinemia, a disease characterized by high levels of im... Tweetable abstract Case series showcases diagnostic and management criteria of three diverse presentations of IgM gammopathy: type I cryoglobulinemia, type II cryoglobulinemia, and Bing–Neel syndrome.

Osteoarthritis (OA) is the most common degenerative joint disease characterized by enzymatic degradation of the cartilage extracellular matrix (ECM) causing joint pain and disability. There is no disease-modifying drug available for the treatment of OA. An ideal drug is expected to stop cartilage ECM degradation and restore the degenerated ECM. The ECM primarily contains type II collagen and aggrecan but also has minor quantities of other collagen fibers and proteoglycans. In OA joints, the components of the cartilage ECM are degraded by matrix-degrading proteases and hydrolases which are produced by chondrocytes and synoviocytes. Matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS5) are the major collagenase and aggrecanase, respectively, which are highly expressed in OA cartilage and promote cartilage ECM degradation. Current studies using various in vitro and in vivo approaches show that natural compounds inhibit the expression and activity of MMP-13, ADAMTS4, and ADAMTS5 and increase the expression of ECM components. In this review, we have summarized recent advancements in OA research with a focus on natural compounds as potential therapeutics for the treatment of OA with emphasis on the prevention of cartilage ECM degradation and improvement of joint health.