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Project #151: Mobility Matters: Let’s Keep Moving Interprofessional Collaboration
No full texthttps://scholarlycommons.henryford.com/qualityexpo2025/1029/thumbnail.jp
Cumulative smoking exposure impacts oncologic outcomes of upper tract urothelial carcinoma
No full textBACKGROUND: The impact of cumulative smoking exposure (CSE) on oncologic outcomes for upper tract urothelial carcinoma (UTUC) remains understudied. We examined the effect of this factor on oncologic outcomes in UTUC patients undergoing radical nephroureterectomy utilizing a large contemporary multicenter, multinational cohort.
METHODS: Multicenter review of 1,730 patients across 17 institutions. A total of 1,041 patients met selection criteria: nephroureterectomy for urothelial carcinoma without variant histology and complete pathologic and smoking data. Smoking exposure was stratified as light, moderate, or heavy by cigarettes per day and years smoking based on prior studies. Cancer-specific (CSS) and overall survival (OS) were assessed using Kaplan-Meier and multivariable hazards models. A sub-analysis examined the effect of smoking cessation on survival stratified by CSE.
RESULTS: Median follow-up (IQR) was 24 (10-48) months. Light CSE was equal to a median of 2.0 pack years smoked, moderate CSE was equivalent to 13.0 pack years, and heavy CSE was equivalent to 40 pack-years. Five-year CSS and OS were 97% and 91% in nonsmokers, 96% and 89% with light exposure, 85% and 66% with moderate exposure, and 75% and 60% with heavy exposure. On multivariable hazards models, both moderate and heavy smoking exposure were associated with worse CSS and OS compared to nonsmokers. Smoking cessation was not associated with improved survival outcomes among patients with moderate or heavy CSE.
CONCLUSIONS: Increasing CSE was associated with worse general health and oncologic outcomes in this UTUC cohort. Smoking cessation can modulate cancer outcomes up to certain thresholds of smoking exposure, emphasizing the need for both early smoking cessation and continued aggressive cancer treatment in patients with UTUC
Use of Cardiac Rehabilitation in Older Patients With Myocardial Infarction Complicated by Cardiogenic Shock
No full textHarnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations
No full textBACKGROUND: We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year.
METHODS: Plasma samples from individuals with HF with reduced ejection fraction (HFrEF; ejection fraction \u3c 40%; training/validation n=1247/762) and preserved ejection fraction (HFpEF; ejection fraction ≥ 50%; training/validation n=725/785) from 3 independent studies were run on the SomaScan Assay measuring ≈5000 proteins. Machine learning techniques resulted in unique 17- and 14-protein models for HFrEF and HFpEF that predict 1-year mortality. Discrimination was assessed via C-index and 1-year area under the curve (AUC), and survival curves were visualized. PRSs were also compared with Meta-Analysis Global Group in Chronic HF (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements and further assessed for sensitivity to disease progression in longitudinal samples (HFrEF: n=396; 1107 samples; HFpEF: n=175; 350 samples).
RESULTS: In validation, the HFpEF PRS performed significantly better (P≤0.1) for mortality prediction (C-index, 0.79; AUC, 0.82) than MAGGIC (C-index, 0.71; AUC, 0.74) and NT-proBNP (PRS C-index, 0.76 and AUC, 0.81 versus NT-proBNP C-index, 0.72 and AUC, 0.76). The HFrEF PRS performed comparably to MAGGIC (PRS C-index, 0.76 and AUC, 0.83 versus MAGGIC C-index, 0.75 and AUC, 0.84) but had a significantly better C-Index (P=0.026) than NT-proBNP (PRS C-index, 0.75 and AUC, 0.78 versus NT-proBNP C-index, 0.73 and AUC, 0.77). PRS included known HF pathophysiology biomarkers (93%) and novel proteins (7%). Longitudinal assessment revealed that HFrEF and HFpEF PRSs were higher and increased more over time in individuals who experienced a fatal event during follow-up.
CONCLUSIONS: PRSs can provide valid, accurate, and dynamic prognostic estimates for patients with HF. This approach has the potential to improve longitudinal monitoring of patients and facilitate personalized care
ALADDIN: A Machine Learning Approach to Enhance the Prediction of Significant Fibrosis or Higher in Metabolic Dysfunction-Associated Steatotic Liver Disease
No full textINTRODUCTION: The recent US Food and Drug Administration approval of resmetirom for treating metabolic dysfunction-associated steatohepatitis in patients necessitates patient selection for significant fibrosis or higher (≥ F2). No existing vibration-controlled transient elastography (VCTE) algorithm targets ≥ F2.
METHODS: The mAchine Learning ADvanceD fibrosis and rIsk metabolic dysfunction-associated steatohepatitis Novel predictor (ALADDIN) study addressed this gap by introducing a machine-learning-based web calculator that estimates the likelihood of significant fibrosis using routine laboratory parameters with and without VCTE. Our study included a training set of 827 patients, a testing set of 504 patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease from 6 centers, and an external validation set of 1,299 patients from 9 centers. Five algorithms were compared using area under the curve (AUC) in the test set: ElasticNet, random forest, gradient boosting machines, XGBoost, and neural networks. The top 3 (random forest, gradient boosting machines, and XGBoost) formed an ensemble model.
RESULTS: In the external validation set, the ALADDIN-F2-VCTE model, using routine laboratory parameters with VCTE (AUC 0.791, 95% confidence interval [CI]: 0.764-0.819), outperformed VCTE alone (0.745, 95% CI 0.717-0.772, P \u3c 0.0001), FibroScan-aspartate aminotransferase (0.710, 0.679-0.748, P \u3c 0.0001), and Agile-3 model (0.740, 0.710-0.770, P \u3c 0.0001) regarding the AUC, decision curve analysis, and calibration. The ALADDIN-F2-Lab model, using routine laboratory parameters without VCTE, achieved an AUC of 0.706 (95% CI: 0.668-0.749) and outperformed Fibrosis-4, steatosis-associated fibrosis estimator, and LiverRisk scores.
DISCUSSION: Along with the steatosis-associated fibrosis estimator model developed to target significant fibrosis or higher, ALADDIN-F2-VCTE ( https://aihepatology.shinyapps.io/ALADDIN1 ) uniquely supports a refined noninvasive approach to patient selection for resmetirom without the need for liver biopsy. In addition, ALADDIN-F2-Lab ( https://aihepatology.shinyapps.io/ALADDIN2 ) offers an effective alternative when VCTE is unavailable
IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Phthalate exposure and reproductive effects in rodents: a model for approaches on the protective role of natural products
No full textIN BRIEF: Exposure to phthalates, alone or in mixtures, at different periods of development alters the reproductive function of males and females, especially in rodents, where they have been most studied. This review addressed the most recent data (last 10 years) on exposure to phthalates in different scenarios and how the use of natural products could mitigate the harmful effects caused by exposure at different stages of development.
ABSTRACT: This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review because most studies that have focused on developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of endocrine-disrupting chemicals in humans and animals at different developmental periods. Various food bioactive compounds (FBCs), such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs), present antioxidant, anti-inflammatory, antitumor, and other biological properties with the potential to reduce deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies carried out in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). In addition, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction because there is a lack of studies with females
XL888 and pembrolizumab modulate the immune landscape of colorectal tumors in a phase Ib/II clinical trial
No full textWe conducted a phase Ib/II clinical trial to evaluate the safety, feasibility, and clinical activity of combining pembrolizumab (anti-PD-1) with XL888 (Hsp90 inhibitor) in patients with advanced colorectal cancer (CRC). We hypothesized that this regimen would modulate soluble and cellular immune mediators and enhance clinical outcomes. The trial employed a 3 + 3 open-label design, with an expansion cohort at the recommended phase II dose (RP2D) in treatment-refractory, mismatch repair-proficient CRC patients. Comprehensive analyses of plasma cytokines, peripheral blood mononuclear cells (PBMCs), and spatial immune cell patterns in liver biopsies were performed to identify unique immune signatures resulting from the combined therapy. The combination of pembrolizumab and XL888 proved to be safe and feasible, with a subset of patients achieving stable disease, although no objective responses were observed in this heavily pre-treated population. Correlative studies revealed immunomodulatory effects in tumors and circulation, including a reduction in IL6(+) cells and macrophages (CD68(+)) within metastatic liver tissue, alterations in blood CD3(+) cells, and upregulation of numerous inflammatory plasma cytokines. These findings suggest local and systemic immune activation by the combination of pembrolizumab and XL888. While clinical activity was modest in treatment-refractory CRC patients, there were notable effects on the tumor immune environment and systemic immune modulation
Associations of COVID-19 vaccination with risks for post-infectious cardiovascular complications: an international cohort study in cancer patients with SARS-CoV-2 infection
No full textBACKGROUND: Whether COVID-19 vaccination is associated with risks for cardiovascular complications after SARS-CoV-2 infection in patients with cancer is unknown. The objective of this study was to investigate the associations between the two.
METHODS: This registry (COVID-19 and Cancer Consortium)-based retrospective cohort study included patients with laboratory-confirmed SARS-CoV-2 infection from the United States, Canada, and Mexico between April 2021 and December 2022. Patients without COVID-19 vaccination were assigned to the unvaccinated group and patients with ≥ 2 doses of COVID-19 vaccination were assigned to the fully-vaccinated group. The primary outcome was a composite of post-infectious cardiac complications, including acute myocardial infarction, other ischemic heart disease, atrial fibrillation, ventricular fibrillation, other arrhythmias, cardiomyopathy, and congestive heart failure. The secondary outcome was a composite measure of post-infectious cardiovascular events, comprising of the cardiac complications along with pulmonary embolism, deep vein thrombosis, superficial vein thrombosis, other thrombosis, and cerebrovascular stroke. Multivariable logistic regression was used for data analysis.
FINDINGS: A total of 2729 patients were included for analyses, with 1382 in the unvaccinated group and 1347 in the fully-vaccinated group. The median age of the study population was 65 (interquartile range (IQR), 55-74) years. Overall, 1534 (56.0%) were women; 1272 (47%) were never smokers; 1639 (60%) were not obese; 2043 (75%) had stable cancer, and 446 (16%) took anticoagulants at baseline. The primary and secondary analyses showed lower risks of cardiac complications and cardiovascular events in the fully-vaccinated group, with adjusted odds ratios (aOR) of 0.66 (95% confidence interval (CI), 0.48-0.89) and 0.76 (95% CI, 0.59-0.99), respectively. The protective trend with COVID-19 vaccination was observed across infections with different dominant SARS-CoV-2 strains and in patients with or without anticoagulant use.
INTERPRETATION: COVID-19 vaccination was associated with a reduced risk of cardiac complications and cardiovascular events by 34% and 24%, respectively, after SARS-CoV-2 infection in patients with cancer.
FUNDING: National Institutes of Health USA; National Science and Technology Council of Taiwan
