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Response to comment on: Associations between donor-derived cell-free DNA dynamics and clinical outcomes after kidney allograft rejection: A prospective, multicenter study.
No full textEfficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer.
No full textBACKGROUND: Garsorasib (D-1553), a highly selective, oral KRAS
METHODS: Pancreatic cancer patients with KRAS G12C mutation were enroled and received garsorasib 600 mg twice daily treatment in two international, multicenter, open-label phase 1/2 trials (NCT04585035 and NCT05383898) with similar eligibility criteria. Their data were pooled for analyses of efficacy and safety endpoints.
RESULTS: As of April 30, 2024, 24 KRAS G12C-mutated pancreatic cancer patients were enroled with a median follow-up of 8.9 months (range 1.1-22.9). Among 22 evaluable patients, the confirmed objective response rate (ORR) was 45.5% (95% CI, 24.4 to 67.8) with a median duration of response (DOR) of 6.4 months (95% CI, 4.2 to 16.4). The median progression-free survival (PFS) was 7.6 months (95% CI, 3.3 to 8.5) and the 6-month OS rate was 79.2% (95% CI, 57.0, 90.8). Treatment-related adverse events (TRAEs) occurred in 18 (75.0%) patients, including 6 (25.0%) with grade ≥3 events. No TRAEs led to treatment discontinuation. The safety profile was consistent with previous reports of garsorasib.
CONCLUSION: Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer
Discrimination of normal from slow-aging mice by plasma metabolomic and proteomic features.
No full textTests that can predict whether a drug is likely to extend mouse lifespan could speed up the search for anti-aging drugs. We have applied a machine learning algorithm, XGBoost regression, to seek sets of plasma metabolites (n = 12,000) and peptides (n = 17,000) that can discriminate control mice from mice treated with one of five anti-aging interventions (n = 278 mice). When the model is trained on any four of these five interventions, it predicts significantly higher lifespan extension in mice exposed to the intervention which was not included in the training set. Plasma peptide data sets also succeed at this task. Models trained on drug-treated normal mice also discriminate long-lived mutant mice from their respective controls, and models trained on males can discriminate drug-treated from control females. Triglycerides are over-represented among the most influential features in the regression models. Triglycerides with longer fatty acid chains tend to be higher in the slow-aging mice, while triglycerides with shorter fatty acid chains tend to decrease. Plasma metabolite patterns may help to select the most promising anti-aging drugs in mice or in humans and may give new leads into physiological and enzymatic targets relevant to the discovery of new anti-aging drugs
Elevated creatinine-to-hemoglobin ratio is a novel preoperative marker for worsened survival outcomes in upper tract urothelial carcinoma: analysis from the ROBUUST registry.
No full textBACKGROUND: To determine the utility of creatinine-to-hemoglobin (Cr:Hgb) ratio, as a predictor of survival outcomes in upper tract urothelial carcinoma (UTUC).
METHODS: We performed a multi-institutional retrospective analysis of UTUC-patients who underwent robotic radical nephrouretectomy utilizing the ROBUUST (ROBotic surgery for Upper Tract Urothelial Cancer Study) registry. Patients were divided into elevated Cr:Hgb ratio (\u3e0.15, based on upper-limit of normal for creatinine and lower-limit of normal for hemoglobin) vs. non-elevated Cr:Hgb ratio (≤0.15). Primary outcome was all cause mortality (ACM)/overall survival (OS). Secondary outcomes were cancer-specific mortality (CSM) / survival (CSS) and recurrence-free survival (RFS). Cox proportional hazards (MVA) was used to elucidate predictive factors for ACM, CSM, and RFS. Kaplan-Meier analysis (KMA) was performed to analyze 5-year OS, CSS, and RFS.
RESULTS: Overall, 829 patients were analyzed (744 non-elevated / 85 elevated Cr:Hgb). Elevated Cr:Hgb patients had more frequently advanced-stage (P=0.016) and high-grade tumors (P\u3c 0.001) at time of surgery. MVA demonstrated increasing-age (HR=1.04, P=0.002), elevated Cr:Hgb (HR=2.49, P=0.003), lympho-vascular invasion (HR=4.61, P\u3c 0.001), and higher-stage (HR=3.82, P\u3c 0.001) to be associated with worsened ACM. Increasing-age (HR=1.04, P=0.030), elevated Cr:Hgb (HR=3.64, P\u3c 0.001), and lympho-vascular invasion (HR=4.52, P\u3c 0.001) were independently associated with worsened CSM. Elevated Cr:Hgb (HR=1.27, P=0.001) was independently associated with worsened recurrence. For elevated vs. non-elevated Cr:Hgb patients, KMA revealed significantly worse 5-year OS (78% vs. 65%, P=0.002), CSS (86% vs. 74%, P\u3c 0.001), and RFS (53% vs. 22%, P=0.004).
CONCLUSIONS: Baseline elevated Cr:Hgb predicted worsened survival outcomes in UTUC patients and may serve a pre-operative marker to stratify oncologic risk and guide counseling and management
GLP-1 Receptor Agonists vs Alternatives for Alcohol Use Disorder: A Multi-Target Trial Emulation
No full textSex Disparities in Cardiac Rehabilitation: Referral, Enrollment, and Completion among STEMI Patients
No full textInitiation of Guideline Directed Medical Therapy while on Microaxial Flow Pump Is Associated with Reduced In-Hospital Mortality
No full textMaternal rest improves growth in small-for-gestational-age fetuses (\u3c10th percentile).
No full textBACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of \u3c 10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question.
OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus.
STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of \u3c 10th percentile for gestational age. The mothers were asked to rest in the left lateral recumbent position. Fetal biometry was performed 2 weeks after the diagnosis. All fetuses before entry into the study had a previous ultrasound that demonstrated an estimated fetal weight of \u3e10th percentile. To assess the response to bed rest, the change in fetal biometric parameters (estimated fetal weight, head circumference, abdominal circumference, and femur length) after the recommendation of bed rest was computed for 2 periods: (1) before the diagnosis of a weight of \u3c 10th percentile vs at the time of diagnosis of a weight of \u3c 10th percentile and (2) at the time of diagnosis of a weight of \u3c 10th percentile vs 2 weeks after maternal bed rest. For repeated measures, proportions were compared using the McNemar test, and percentile values were compared using the Bonferroni Multiple Comparison Test. A P value of \u3c .05 was considered significant. To describe changes in the estimated fetal weight without bed rest, 2 control groups in which the mothers were not placed on bed rest after the diagnosis of a small-for-gestational-age fetus were included.
RESULTS: A total of 265 fetuses were observed before and after maternal bed rest. The following were observed in this study: (1) after 2 weeks of maternal rest, 199 of 265 fetuses (75%) had a fetal weight of \u3e10th percentile; (2) the median fetal weight percentile increased from 6.8 (interquartile range, 4.4-8.4) to 18.0 (interquartile range, 9.5-29.5) after 2 weeks of bed rest; (3) similar trends were noted for the head circumference, abdominal circumference, and femur length. In the groups of patients who were not asked to be on bed rest, a reassignment to a weight of \u3e10th percentile at a follow-up examination only occurred in 7 of 37 patients (19%) in the Texas-Michigan group and 13 of 111 patients (12%) in the Colorado group compared with the bed rest group (199/265 [75%]) (P\u3c .001).
CONCLUSION: Patients who were prescribed 2 weeks of bed rest after the diagnosis of a fetal weight of \u3c 10th percentile had an increase in weight of \u3e10th percentile in 199 of 265 fetuses (75%). This increase in fetal weight was significantly higher than that in the 2 control groups in which bed rest was not prescribed. This observation suggests that bed rest improves fetal growth in a subset of patients
Participant Needs, Service Utilization, and Costs in a Medicaid Housing Pilot Program.
No full textIMPORTANCE: Housing instability and homelessness have wide-ranging health and social effects. Health systems increasingly recognize the importance of addressing these needs to make progress toward health equity goals and reduce health care costs. State Medicaid programs are uniquely positioned to support the housing needs of their members but are relatively new to the housing space and need to understand how to most effectively partner with the housing sector to improve health outcomes.
OBJECTIVE: To evaluate the implementation and initial outcomes of a housing benefit pilot program, including participant characteristics, needs, and service utilization.
DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study involving a pilot program that provided temporary rental assistance, housing navigation, and additional supports to Medicaid members between May 2022 and October 2024. The pilot took place in the Portland, Oregon, metropolitan area involving Medicaid members of Health Share of Oregon, a large coordinated care organization. Individuals were referred to the program primarily from foster care, substance use disorder residential programs, and corrections facilities. Data were analyzed from October 2024 to March 2025.
EXPOSURE: Enrolled participants received services, including temporary rental assistance, housing navigation, and other supports, for up to 12 months, with modifications made mid-pilot due to capacity challenges.
MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, baseline needs, service utilization, and costs associated with the housing benefit program.
RESULTS: Of 716 referrals, 517 individuals (mean [SD] age, 37.8 [11.1] years; 295 [57.1%] male) enrolled; including 14 American Indian or Alaskan Native individuals (2.7%), 7 Asian individuals (1.4%), 67 Black individuals (13.0%), 22 Hispanic individuals (4.3%), 6 Native Hawaiian or Pacific Islander individuals (1.2%), and 308 White individuals (59.6%); 513 individuals (99.2%) spoke English. Participants had substantial housing needs, with rent (383 individuals [74.1%]) and utility (282 individuals [54.5%]) support being the most frequently reported needs and used services. The mean (SD) cost per member per month was 1586). Frequently reported nonhousing needs included employment (154 individuals [42.3%]), food (152 individuals [41.8%]), mental health (94 individuals [25.8%]), and transportation (86 individuals [23.6%]).
CONCLUSIONS AND RELEVANCE: The findings of this cohort study provide critical insights into the types of services needed and associated costs for supporting housing as a Medicaid benefit. Significant needs were observed, emphasizing the necessity of cross-sector collaboration and clear role definitions between health care and housing organizations. The findings offer valuable lessons for the design and implementation of housing support programs under Medicaid; these insights are crucial as Oregon and other states consider similar initiatives to address housing as a health-related social need
