Citations

CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10 −5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.

Introduction: This study evaluated the impact of parallel-level patient transfers on bed utilization efficiency within the Mayo Clinic Health System in Southern Minnesota, focusing on optimizing resources across tertiary and critical access hospitals. Methods: A retrospective analysis of 179,066 Emergency Department visits (2018–2022) was conducted, with ~2% involving parallel-level transfers for observation or admission. Machine learning was utilized to identify patients suitable for parallel transfers based on demographics, comorbidities, and clinical factors. A Random Forest model with an AUROC of 0.87 guided transfer decisions. Saved patient days were calculated as the difference between the actual LOS and the benchmark LOS based on Diagnosis-Related Groups (DRGs). Generalized estimating equations analyzed length of stay (LOS) differences, adjusted for confounders, with 95% confidence intervals (CI). Statistical analyses were conducted using SPSS (v.26). Results: The mean patient age was 56 years (SD = 17.2), with 51.4% being female. Saved patient days increased from ~600 to 5200 days over the study period. Transferred patients had a 5.7% longer unadjusted LOS compared to non-transferred patients (95% CI: 2.9–8.6%, p < 0.001). After adjustment for demographics and comorbidities, the LOS difference was not significant (adjusted mean difference: 0.4%, 95% CI: −1.7–2.5%, p = 0.51). Conclusions: Parallel-level transfers increased saved patient days, reflecting enhanced resource utilization. However, the adjusted LOS differences were not significant, highlighting the need for robust transfer protocols and controlled studies to confirm these findings.

Abstract Background: mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS. Methods: We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI. Results: Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity. Conclusions: Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36. Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Abstract We have previously reported the therapeutic effect of depletion and regeneration of endogenous microglia on autism spectrum disorder-like behaviors in offspring from the dams under maternal immune activation (MIA) by dampening their neuritogenic activation. Here we show a long-lasting pathological effect by MIA, leading to abnormal behaviors in offspring mice in a sex-specific manner at 3 months of age. MIA was induced by injecting Polyinosinic:polycytidylic acid [Poly(I:C)] at 10mg/kg at E9.5 with preselected dams based on the immunoreactivity to low-dose Poly(I:C) injection. MIA offspring show impairments in sociability, repetitive behavior, and spatial working and associative memories in both sexes, whereas only male offspring show social novelty deficit. MIA has no effect on anxiety-like behavior nor sensori-motor or locomotor activity. Administering colony stimulating factor receptor (CSF1R) inhibitor in young adult MIA offspring regenerates microglia and ameliorates sociability deficits in males and spatial working and associative memory impairments in both sexes without effect on social novelty impairments. Transcriptomic analysis of prefrontal cortex and hippocampal tissues reveals MIA and sex-specific pathways and highlights potential key genes involved in the corrective effect of microglial regeneration in MIA offspring. Our results underscore the potential of the sex-specific therapeutic applications of CSF1R inhibitor for MIA-related social and cognitive disorders.

ABSTRACTBarriers to pediatric palliative care (PPC) integration in pediatric oncology encompass resource availability, provider attitudes, patient/family hesitancy, and timing. We report on a unique multistep approach for the creation of a pediatric palliative oncology program that (1) optimizes PPC delivery for all resource‐typed settings, (2) offers continuity of care by spanning inpatient and outpatient clinical settings, (3) improves PPC equity through standardized referral practices, and (4) promotes collaborator buy‐in and partnership through the utilization of tools to introduce PPC to patients/families. Our model demonstrates success through objective increases in PPC consultation and reported satisfaction from patients, families, and oncologists.

Background: Breast reconstruction in de novo metastatic breast cancer (dnMBC) patients is a viable option. There remains no consensus on recommendations. We summarize postreconstruction clinical outcomes in dnMBC patients to identify surgical candidates. Methods: A systematic review was conducted across PubMed/MEDLINE, Scopus, and Web of Science from January 1, 1990, to November 1, 2024. The study methods were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on patient demographics, disease characteristics, oncological treatment, surgical details, and clinical outcomes were collected. Results: A total of 7 studies (2635 breast cancer survivors) were identified. The average (SD) age was 47.5 (2.35) years, and most participants were White (n = 2080, 79.3%). Across studies, 39.0% (n = 761) of patients underwent implant-based reconstruction, 38.8% (n = 757) autologous reconstruction, 5.99% (n = 117) combined reconstruction, and 16.4% (n = 320) were not specified. Most cancers were invasive ductal carcinoma (81.3%) with estrogen-positive (73.1%) or progesterone-positive (48.4%) receptors and human epidermal growth factor receptor 2–positive (33.7%) status. Primary tumors most often metastasized to bone (44.4%) or lymph nodes (38.5%). Overall survival and breast cancer–specific survival rates were prolonged among reconstructed patients without increased predilection for complications or delay in tumor treatment. Conclusions: Reconstruction in dnMBC patients is an appropriate option, especially among younger patients with oligometastatic disease. Future studies are encouraged to investigate the impact on well-being and prolonged survival rates, which primarily seem to be limited to those with low disease burden and hormone receptor–positive tumor subtypes.

Background: There has been minimal literature evaluating how a prior myocardial infraction (MI) influences outcomes after total knee arthroplasty (TKA). Thus, the purpose of this study was to evaluate how the timing, type, and treatment of MI prior to TKA affect postoperative cardiac complications, general medical complications, and surgical complications. Methods: A retrospective comparative study was conducted using a large insurance database. Patients undergoing primary TKA for osteoarthritis were included. Patients who had experienced MI within 2 years before TKA were identified and were matched 1:4 with patients who had not had such an MI on the basis of demographic variables and comorbidities. Patients who had a prior MI were stratified into 4 groups based on the timing of the MI: 0 to <6 months, 6 to <12 months, 12 to <18 months, and 18 to 24 months before TKA. The rates of postoperative cardiac, general medical, and surgical complications were compared between groups. Subanalyses on the prior MI type, treatment, and location were performed. Results: Prior MI was associated with increased risks of postoperative MI (odds ratio [OR], 3.97 [95% confidence interval (CI), 3.20 to 4.93]), heart failure (OR, 1.45 [95% CI, 1.24 to 1.75]), and 90-day mortality (OR, 2.15 [95% CI, 1.41 to 3.28]). The risk of postoperative MI was highest for those with MI within 6 months before TKA (OR, 6.86 [95% CI, 5.34 to 8.82]). Type-1 MI, ST-elevation MI (STEMI), non-ST-elevation MI (NSTEMI), and anterior and inferior MIs were linked to elevated postoperative MI and/or mortality risks, with timing closer to surgery further amplifying the risk. Percutaneous coronary intervention within 6 months before TKA also increased postoperative risks. Type-2 MI within 6 months before TKA was associated with an increased risk of periprosthetic joint infection compared with controls (OR, 4.23 [95% CI, 1.67 to 10.67]). Conclusions: Patients who had a prior MI, particularly within 6 months before TKA, had significantly elevated risks of postoperative MI, heart failure, and mortality. Outcomes varied by MI type, treatment, and location, with type-1 MIs and STEMIs increasing the postoperative mortality risk. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.