Citations

Abstract Frailty influences treatment outcomes in older patients with multiple myeloma (MM), yet existing frailty tools capture limited geriatric domains and are incompletely studied in the context of contemporary therapies. We prospectively evaluated patient-reported comprehensive geriatric assessment (CGA) domains and their associations with treatment toxicity and patient-reported outcomes (PRO) in older adults with MM. Patients aged ≥60 years with newly diagnosed or relapsed/refractory MM initiating a new therapy completed electronic CGA and PRO questionnaires at baseline and 4 months. Outcomes included clinician- and patient-reported treatment toxicity, treatment adaptations, health care use, and health-related quality of life (HRQOL). A cumulative deficit frailty index (FI) was derived from CGA and HRQOL domains. Among 90 patients (mean age, 72 years), geriatric impairments were common, particularly physical function domains. High-grade nonhematologic toxicities were significantly associated with older age, comorbidities, patient-reported functional limitations, and anxiety. Toxicity rates on the PRO version of the Common Terminology Criteria for Adverse Events (CTCAE) were higher than on CTCAE, highlighting a discordance between physician- and patient-reported treatment toxicity. Frailty was present in 22% and associated with worse baseline HRQOL and increased high-grade nonhematologic toxicity but not treatment adaptations or health care use. Average CGA and HRQOL scores remained stable over 4 months, although individual trajectories varied. Patient-reported geriatric impairments are prevalent in older adults with MM and strongly associated with nonhematologic toxicities even in the contemporary treatment era. Physician-reported CTCAE may not fully reflect patients' symptom burden. Heterogeneity in individual geriatric trajectories during treatment emphasize the need for longitudinal assessment. This study was registered at www.clinicaltrials.gov as NCT05918185.

Abstract Background There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

An accurate differential diagnosis for diffuse lung disease can be confidently established by using a systematic approach to identify the predominant radiographic pattern, determine the distribution of disease, and assess for architectural or volume change.

Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

Abstract Early-phase clinical trials of Bruton’s tyrosine kinase (BTK) degraders have demonstrated efficacy in patients with BTK inhibitor-resistant chronic lymphocytic leukemia (CLL). How clinical resistance to BTK degraders arises is unknown. Here we sequenced serial CLL samples from patients enrolled in the phase I trials of zelebrudomide and bexobrutideg and observed recurrent expansion of preexisting BTK A428D mutations at relapse. Unlike previously studied BTK inhibitor resistance mutations, BTK A428D conferred pan-resistance to BTK inhibitors and degraders. In the absence of BTK-directed therapies, however, cells bearing BTK A428D exhibited a competitive disadvantage. A crystal structure of BTK A428D revealed that the mutant aspartate clashes with the adenine ring of ATP and the adenine-mimetic moiety of BTK inhibitors and degraders. Combining BTK degraders with venetoclax mitigated the expansion of BTK A428D. These results provide the molecular basis for clinical resistance to BTK degraders and will inform the development of next-generation BTK degrader therapies.

Background: Although skin cancer survivors have an increased risk of future malignancies, many are unaware of this and may not undergo preventative screening. Objective: To evaluate skin cancer survivors’ prevalence of breast, colorectal, cervical, and lung cancer screening. Methods: This is a retrospective cross-sectional analysis of The Behavioral Risk Factor Surveillance System database from 2017 to 2021 comparing skin cancer, other cancer, and non-cancer controls. Multivariate analysis compared screening rates, controlled for socioeconomic, chronic disease, and behavioral factors. Results: Compared to non-cancer controls, skin cancer survivors had higher odds of undergoing screening for breast (odds ratios [OR]: 1.35, 95% confidence interval [CI] 1.20–1.51), colorectal (OR 1.53, 95% CI 1.40–1.66), and cervical cancer (OR 1.32, 95% CI 1.12–1.56). Lung cancer screening rates were low and similar between skin cancer survivors and non-cancer individuals (OR 1.21, 95% CI 0.84–1.74). In a subset analysis of skin cancer survivors, those who had melanoma were less likely to be screened for breast and colorectal cancer. Limitations: This study is based on anonymous, national survey data, relying on patient recall of their health information. Conclusion: Skin cancer survivors undergo cancer screenings for breast, colorectal, and cervical cancer at higher rates compared to non-cancer controls. Melanoma survivors have lower rates of breast and colorectal screening compared to non-melanoma skin cancer survivors. Skin cancer survivors should be reminded of preventive cancer screening, particularly for lung cancer.

Purpose of review Hepatorenal syndrome (HRS) is the extreme manifestation of acute renal dysfunction in patients with cirrhosis, resulting from systemic vasodilation and renal vasoconstriction, leading to a reduction in the glomerular filtration rate. Recent findings The diagnostic criteria redefined diagnostic criteria for HRS-AKI (Hepatorenal syndrome -Acute kidney injury) as our understanding of disease progression has improved. This understanding of the HRS disease process guides current management, with the combination of intravascular volume expansion and vasoconstrictor therapy being the cornerstone of treatment. In addition to treatment selection, timing of treatment initiation, duration, dosage, and monitoring during treatment are decisive factors in HRS outcomes. Pathogenesis of HRS-AKI may be different in patients with acute-on-chronic liver failure (ACLF) in comparison to decompensated cirrhosis. Unfortunately, outcomes remain poor with medical therapies alone and a high risk of disease recurrence exists for HRS-AKI with persistence of the cirrhotic milieu. Liver transplantation remains the only definitive treatment of HRS-AKI. Given the critical nature of HRS-AKI, a multidisciplinary approach involving hepatologists, nephrologists, and intensive care physicians is essential for optimal clinical management. Summary Patients with HRS-AKI should be managed ideally in tertiary care centers and referred for liver transplantation promptly when eligible.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Background: We describe an investigation of a cluster of eight Corynebacterium amycolatum sternal surgical site infections (SSIs) that occurred among cardiac surgery patients from February to October 2025. Although C. amycolatum is a member of the skin microbiota, clinically significant infections caused by this organism may occur in cardiac surgery patients. Methods: The investigation included retrospective reviews of SSIs, clinical cultures and medical records, surgical observations, and operating room (OR) assessment. Line lists of surgical case criteria and infection prevention practices were created to assess common factors among cases (e.g., staffing, instrumentation, equipment, skin preparation and antisepsis, nasal decolonization, antibiotic protocols, and closure). Whole genome sequencing of isolates was performed and analyzed using SNIPPY for single-nucleotide polymorphism (SNP)-based phylogenetic analysis. Results: Phylogenetic analysis indicated isolates from five of eight case patients who had cardiac surgeries occurring over a six-week period from February to April 2025 were genetically related (?7 SNPs across the genome), suggesting a common source of infection. These five isolates were ceftriaxone, meropenem, and penicillin resistant. The other three case patient isolates were unrelated (<3181 to <15,000 SNPs); two were ceftriaxone, meropenem and penicillin resistant (one also doxycycline intermediate resistant), and the third penicillin resistant. Use of sternal tape for closure was identified as a recent practice change. Four of five genetically related cases involved the same surgeons and suture tape for sternal closure (wire for all other cases). Sternal tape was discontinued with three cases occurring afterwards. Seven patients completed chlorhexidine gluconate bathing and nasal decolonization. Hair was removed in the OR with reusable surgical clippers. All received the same skin antiseptic, and antibiotic prophylaxis was appropriate. No trends were identified in instrument or equipment use. Broad infection control measures were implemented, including surgical clipper replacement, OR cleaning and ultraviolet light disinfection, headlamp cleaning, and environmental repairs. Leadership was engaged through frequent meetings and audits. Infection control practices such as minimizing OR traffic, double gloving, glove changes, and strict adherence to hand hygiene and attire were reinforced. Two of eight cases occurred after these recommendations were completed but were not genetically related to the primary cluster. Conclusion: We describe a cluster of invasive C. amycolatum sternotomy SSIs. Only two genetically unrelated cases of C. amycolatum occurred following infection control investigation and interventions, underscoring the effectiveness of a comprehensive, multidisciplinary approach. This organism has rarely been reported as a cause of SSIs and may be an emerging pathogen.