Citations

Purpose Outcomes with bispecific T-cell engagers (TCEs) in relapsed/refractory multiple myeloma (RRMM) are heterogeneous. A practical tool to guide prognosis is needed. We developed a model integrating clinical, biological, and treatment-related variables to predict progression-free survival (PFS) in patients receiving B-cell maturation antigen (BCMA)- or G-protein–coupled receptor class 5 member D-directed TCEs. Methods We evaluated outcomes of 577 BCMA-directed and 366 talquetamab treatments across 15 US Multiple Myeloma Immunotherapy Consortium centers. Variables significantly associated with inferior PFS in a multivariate Cox model were incorporated into a prognostic score and validated in an independent multicenter International Myeloma Foundation cohort. Results With a median follow-up of 8.4 months, the median PFS was 6.4 months (7.0 months for BCMA TCE; 6.1 months for talquetamab); 92% of patients were triple-class-refractory. Six variables significantly associated with inferior PFS—high-risk cytogenetic abnormalities (HRCAs) [del(17p) or ≥2 HRCAs], hyperferritinemia (≥600 ng/mL), anemia (hemoglobin <9 g/dL), early relapse (<18 months from frontline therapy), general performance status (Eastern Cooperative Oncology Group Performance Status ≥2), and exposure to prior BCMA-directed therapy—were combined to form the CHARGE index, stratifying patients into three risk groups. The median PFS was 21.8 months (95% CI, 11.7 to not reached), 7.1 months (95% CI, 6.1 to 10.1), and 1.6 months (95% CI, 1.2 to 2.5) in the low-, intermediate-, and high-risk groups, respectively; hazard ratios (HRs) were 2.0 (95% CI, 1.5 to 2.7) and 4.8 (95% CI, 3.5 to 6.7) for intermediate- and high-risk versus low-risk groups. External validation (n = 173) showed that the median PFS was not reached, 7.0 months, and 3.0 months, with corresponding HRs of 2.9 (95% CI, 1.7 to 4.9) and 4.8 (95% CI, 2.6 to 8.7). Conclusion The CHARGE index provides a simplified and externally validated framework for predicting treatment outcomes in patients with RRMM receiving TCEs.

ABSTRACT The optimal phage susceptibility testing (PST) method is unclear. Here, two PST methods were compared using Pseudomonas aeruginosa isolates recovered from patients with cystic fibrosis enrolled in a placebo-controlled clinical trial of a single intravenous dose of a four-phage cocktail (WRAIR-PAM-CF1). In total, 508 P. aeruginosa sputum isolates were evaluated, including isolates collected before or after phage or placebo treatment, isolates from the same trial participants over time, and isolates of different colony morphologies from the same participants at the same time point. Susceptibility to phages PaWRA01Φ11, PaWRA01Φ39, PaWRA02Φ83, and PaWRA02Φ87 and a cocktail of all four phages was assessed using a plaque assay (PA) and a Biolog Omnilog-based liquid assay (LA) with the same bacterial inoculum. A total of 170/508 isolates (33%) and 195/508 isolates (38%) were identified as susceptible to the cocktail by PA and LA, respectively. Among the susceptible isolates, 169/170 (99%; PA) and 187/195 (96%; LA) also tested susceptible to at least one of the four phages in the cocktail. Susceptible percent agreement between the PA and LA ranged from 76% to 100% and non-susceptible percent agreement ranged from 89% to 100% for all phages studied and the cocktail. Phage PaWRA02Φ83 demonstrated the greatest individual activity, with 164/508 (32%) and 188/508 (37%) isolates testing susceptible by PA and LA, respectively. The four-phage cocktail provided numerically broader coverage of P. aeruginosa (i.e., had the highest susceptibility rate) than did any single phage. There was high concordance between PST results by PA and LA. IMPORTANCE Standardization of phage susceptibility testing (PST) methods is essential to support phage therapy trials and any future clinical implementation. There are no standardized PST methods or interpretive criteria for PST. In this study, PST was performed by a plaque assay and a Biolog Omnilog-based liquid assay on Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients enrolled in a clinical trial. Susceptibility of 508 isolates to four phages and a cocktail of all four was evaluated. There was high concordance between susceptibility assessed by plaque and liquid assays and numerically broader coverage of P. aeruginosa by the cocktail compared to any single phage. This manuscript should be of interest to those performing PST.

Background Nonobstructive hypertrophic cardiomyopathy (HCM) affects approximately one‐third of all patients with HCM and carries substantial morbidity, yet no approved disease‐modifying therapies exist. We conducted a systematic review of prospective interventional studies evaluating pharmacologic therapies in adults with nonobstructive HCM. Methods A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov was performed through September 2025. Eligible studies included randomized and nonrandomized prospective interventional trials. A narrative synthesis was performed by pharmacologic class and outcome domain. Results Twenty‐nine clinical trials evaluating 9 pharmacologic classes were identified: cardiac myosin inhibitors, cardiac sarcomere modulators, metabolic modulators, angiotensin II receptor blockers, angiotensin receptor‐neprilysin inhibitors, mineralocorticoid receptor antagonists, SGLT2 (sodium‐glucose cotransporter 2) inhibitors, beta blockers, and calcium channel blockers. Cardiac myosin inhibitors demonstrated reductions in left ventricular hypertrophy, improvements in diastolic function, and marked reductions in cardiac biomarkers, although improvements in exercise capacity and symptoms were variable. SGLT2 inhibition showed concordant improvements in diastolic function, atrial remodeling, biomarkers, and functional status in patients with symptomatic nonobstructive HCM and comorbid type 2 diabetes. Angiotensin receptor blockade showed signals of structural remodeling with valsartan and candesartan without consistent functional benefit. Mineralocorticoid receptor antagonism and angiotensin receptor‐neprilysin inhibition demonstrated largely neutral effects. Among metabolic modulators, ninerafaxstat improved ventilatory efficiency and quality of life in patients with greater baseline symptom burden. Conclusions Pharmacologic responsiveness in nonobstructive HCM is variable and appears to be mechanism‐ and disease stage‐dependent. Ongoing trials evaluating cardiac myosin inhibitors, SGLT inhibitors, and novel therapeutic agents including ninerafaxstat and EDG‐7500 will be critical in further defining the therapeutic landscape.

ABSTRACT Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty that can be challenging to diagnose and treat. Neutrophils are a prominent feature in PJI, with neutrophil extracellular traps (NETs) known to be present; little is known, however, about the physiology of PJI-associated NETs. Here, the proteomes of PJI and non-infectious arthroplasty failure (NIAF), analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) and proximity extension assay (PEA)-based profiling of fluids derived from sonication of arthroplasty components removed from patients who had undergone revision arthroplasty, were compared, with a focus on NET formation. In addition, in vitro effects of synovial fluid components on Staphylococcus aureus- induced NET formation were characterized. LC-MS/MS (PJI n = 85, NIAF n = 26) and PEA (PJI n = 95, NIAF n = 39) showed NET formation and neutrophil degranulation to be associated with PJI, with the complement cascade and platelet activation pathways identified as potential contributors. In vitro studies showed delayed NET formation in artificial synovial fluid compared to standard cell culture media conventionally used to evaluate NETs. Together, these results demonstrate the presence of NETs in PJI, identify potential pathways involved in PJI-associated NETosis, and point to an influence of synovial components on NET formation during PJI. IMPORTANCE Periprosthetic joint infection (PJI) is a major complication of joint replacement, placing a significant burden on patients and the healthcare system. Our research reveals that neutrophils and their antimicrobial “traps” are dominant features of the immune response at the infection joint site. Importantly, we found that the unique environment of the joint delays the formation of these traps, potentially contributing to the pathogenesis of PJI. By establishing a new experimental platform tailored for the infected joint, this work provides a foundational platform for probing these mechanisms and supports the development of improved diagnostic and therapeutic strategies.

ABSTRACT Objective To estimate the pooled prevalence of lymphedema among adults with mucosal head and neck cancer treated with radiation therapy. Data Sources PubMed, Embase, Scopus, and Cochrane Library. Review Methods A comprehensive literature search of PubMed, Embase, Scopus, and Cochrane Library (2000–2025) identified cohort, case series, cross‐sectional, and clinical trial studies reporting lymphedema after radiotherapy for head and neck cancer. Logit‐transformed lymphedema prevalence was pooled using a DerSimonian‐Laird random‐effects model with Hartung‐Knapp‐Sidik‐Jonkman variance correction; statistical heterogeneity was evaluated using I 2 . This review was not prospectively registered. Results A total of 26 studies ( n = 3133 patients) met inclusion criteria. The pooled prevalence of lymphedema was 49% (95% CI, 36%–62%), with considerable heterogeneity (I 2 = 94%). Subgroup analyses yielded a pooled prevalence of 37% (12%–71%) for external and 45% (31%–60%) for internal lymphedema. Among studies reporting severity‐graded data, the pooled prevalence of clinically significant (grade ≥ 2) lymphedema was 32% (14%–59%). Lymphedema definitions and assessment methods varied across the included studies, most commonly employing clinical grading. Methodological quality was mixed, reflecting the predominantly retrospective, single‐arm nature of the available evidence. Overall certainty of evidence was very low. Funnel plot inspection and Egger's test suggested small‐study effects ( p = 0.06). Conclusion Lymphedema affects nearly half of patients following radiation for head and neck cancer. These findings may support routine surveillance, early identification, and timely referral for lymphedema management within survivorship care pathways. Future prospective studies should adopt standardized definitions and outcome measures to refine risk estimates and guide prevention strategies. Level of Evidence N/A.

Serrated polyposis syndrome (SPS) is the most common polyposis syndrome, yet SPS often goes unrecognized. SPS diagnosis is based on clinical criteria established by the World Health Organization and includes the size, cumulative lifetime number, and location of serrated polyps throughout the colon. Individuals with SPS have an increased risk of prevalent and incident colorectal cancer (CRC). Meticulous inspection, clearing of the colon and frequent surveillance colonoscopy is recommended to decrease incident CRC. Colorectal surgery is indicated for individuals diagnosed with cancer or whose polyp burden cannot be managed endoscopically by expert endoscopists. There is no common germline pathogenic variant associated with SPS. Germline genetic testing is indicated only in individuals who meet criteria for a known hereditary syndrome in the appropriate clinical setting. First-degree relatives of patients with SPS are at heightened risk of CRC and should undergo colonoscopic screening.

Abstract Context. Thyroid nodule ultrasound findings are crucial in guiding management decisions for patients with thyroid nodules. However, the frequency with which ultrasound images are discussed and reviewed with patients during clinical visits is not well understood. Objective. To assess how often thyroid ultrasound images are shown and discussed with patients during consultations, and to identify predictors of image review during clinical visits. Design and setting. Secondary analysis of a multicenter pilot randomized clinical trial conducted at two academic medical centers in the United States. Participants. Adults undergoing evaluation for thyroid nodules. Intervention. Participants were randomized to receive either usual care or care enhanced with a conversation aid. Main Outcome Measures. The primary outcome was the frequency of thyroid nodule imaging review evaluated as a binary outcome. Secondary outcomes included evaluation of predictors of image discussion. Results. Eighty-five patients were evaluated. Most participants were women (80%), mean age (60 years, SD 16), and White (86%), undergoing new patient visits (84%). Thyroid nodule ultrasound images were reviewed with patients in 53% of visits (45/85), and in all cases, clinicians initiated the imaging discussion. Predictors of image review included type of consultation (new patient visit) (OR 10.6, 95% CI: 1.79, 62.3). Age, sex, study arm, thyroid nodule size or cancer risk and plan of care (e.g., completing a biopsy) were not statistically associated with review of clinical images. Conclusions. Review of thyroid ultrasound images during clinical visits is relatively common, with consultation type serving as significant predictor.

Abstract Background: Sexual and gender minority (SGM) representation is growing in the United States. This study estimated the future SGM cancer burden amidst shifting cancer patterns. Methods: Age-specific incidence data for breast, prostate, colorectal, lung, and melanoma were obtained from the Surveillance, Epidemiology, and End Results Program’s 12-registry database. Nordpred age-period-cohort models projected incidence through 2040 to 2044. Rates were applied to US Census population estimates and generation- and sex-specific SGM identification proportions from Gallup’s 2023 to 2024 surveys. Prophet was used for sensitivity analysis. Results: At ages 55 to 59, breast cancer cases among Millennial SGMs were 3,672% higher than among Silent Generation SGMs (34,850 vs. 924 cases), melanoma cases were 1,061% higher (5,526 vs. 476 cases), and colorectal cancer cases were 2,206% higher (23,594 vs. 1,023 cases). Compared with Generation X, Millennial prostate cancer cases were 142% higher (8,100 vs. 3,344 cases), and lung cancer cases were 169% higher (5,451 vs. 2,029 cases). By 2040 to 2044, Millennials were projected to account for 68.4% of breast cancer cases and 59.7% of colorectal cancer cases among SGMs. Conclusions: At ages 55 to 59, the 5-year cancer burden was projected to be 15 times higher among Millennials than Silent Generation SGMs (77,521 vs. 5,134 cases), driven primarily by the larger SGM population in younger generations. Oncology systems will need to prepare for the increase in cancer care demand. Impact: These findings identify a substantial generational shift in the SGM cancer burden and may inform oncology workforce capacity, culturally responsive cancer care, and healthcare system preparation for this growing population.