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Project #108: Fall Reduction in the Emergency Room Setting
No full texthttps://scholarlycommons.henryford.com/qualityexpo2025/1018/thumbnail.jp
Project #083: Using a Multi-Prong Approach to Reduce Colon Surgical Site Infections (SSI)
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Project #120: Preventing Workplace Violence: Implement a Behavioral Emergency Response Team Leveraging Existing Resources
No full texthttps://scholarlycommons.henryford.com/qualityexpo2025/1023/thumbnail.jp
Project #128: Sepsis ED Triage Processes
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Time-to-event prediction in ALS using a landmark modeling approach, using the ALS Natural History Consortium dataset.
No full textBACKGROUND AND OBJECTIVES: Times to clinically relevant events are a valuable outcome in observational and interventional studies, complementing linear outcomes such as functional rating scales and biomarkers. In ALS, there are several clinically relevant events. We developed dynamic prediction models for several of these times to events that can be used for clinical trial modeling and personal planning.
METHODS: Landmark time-to-event analysis was implemented to determine the effect of patient characteristics on disease progression. Longitudinal data from 1557 participants in the ALS Natural History Consortium dataset were used. Five outcomes in the ALS disease progression were considered: loss of ambulation, loss of speech, gastrostomy, noninvasive ventilation (NIV) use, and continuous NIV use. Covariates in our models include age at diagnosis, sex, onset location, riluzole use, diagnostic delay, ALSFRS-R scores at the landmark time, and ALSFRS-R rates of change from baseline. Internal and external validation techniques were used.
RESULTS: For each of our models and landmark times, we present risk prediction intervals for random sets of patient characteristics. We demonstrate our models\u27 application for an individual\u27s personal predicted time-to-event. Our internal and external validation metrics indicate good concordance and overall performance. The time to loss of speech models perform the best for each metric in terms of both internal and external validation.
DISCUSSION: Landmarking is an efficient, individualized risk prediction model that is intuitive for both clinicians and patients. Importantly, landmarking can be used for clinical trial modeling, personal planning, and development of real-world evidence of the impacts of treatment interventions
Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets
No full textCancer progression and therapeutic resistance are closely linked to a stemness phenotype. Here, we introduce a protein-expression-based stemness index (PROTsi) to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes. Utilizing datasets from the Clinical Proteomic Tumor Analysis Consortium across 11 tumor types, we validate PROTsi\u27s effectiveness in accurately quantifying stem-like features. Through integration of PROTsi with multi-omics, including protein post-translational modifications, we identify molecular features associated with stemness and proteins that act as active nodes within transcriptional networks, driving tumor aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets, both shared and tumor specific. These stemness-associated proteins demonstrate predictive value for clinical outcomes, as confirmed by immunohistochemistry in multiple samples. The findings emphasize PROTsi\u27s efficacy as a valuable tool for selecting predictive protein targets, a crucial step in customizing anti-cancer therapy and advancing the clinical development of cures for cancer patients
Establishment of a patient-derived 3D in vitro meningioma model in xeno-free hydrogel for clinical applications
No full textBACKGROUND: Meningiomas exhibit a complex biology that, despite notable successes in preclinical studies, contributes to the failures of pharmaceutical clinical trials. Animal models using patient tumor cells closely mimic in vivo conditions but are labor-intensive, costly, and unsuitable for high-throughput pharmaceutical testing. In comparison, monolayer cell models (two-dimensional, 2D) are cost-efficient but lack primary tumor cell-cell interactions, potentially overestimating treatment effects. Three-dimensional (3D) models offer an alternative through more precise mimicking of tumor morphology and physiology than 2D models and are less costly than in vivo methods. Here, we aimed to establish a 3D cell model in a solid xeno-free medium using patient-derived tumors, thus creating a bench-to-clinic pathway for personalized pharmaceutical testing.
METHODS: Four WHO grade 1 and one WHO grade 2 (third-passage, fresh) and 12 WHO grade 1 patient-derived meningioma cells (sixth-passage, frozen) and the malignant IOMM-Lee cell line were used to establish 2D and 3D models. The 3D model was developed using a solid xeno-free medium. After 3 months for the primary tumor and 13 days for the IOMM-Lee cell line, the 3D models were extracted and assessed using histology, immunohistochemistry, and epigenetic analyses (EPICv2 array) on five pairs to evaluate their structural fidelity, cellular composition, and epigenetic landscape compared to the original tumor.
RESULTS: None of the frozen samples successfully generated 3D models. Models from fresh meningioma samples were more immunohistochemically similar to the primary tumors compared to 2D models, particularly regarding proliferation. 3D models displayed loss of fibrous tissue. All 3D models had similar copy number variation profiles, visually. Genome-wide DNA methylation level patterns were similar between pairs of 3D models and primary tumors. Correlation plots between CpG methylation levels showed high congruency between primary meningiomas and their corresponding 3D models for all samples (R \u3e 0.95).
CONCLUSIONS: Our patient-derived 3D meningioma models closely mimicked primary tumors in terms of cell morphology, immunohistochemical markers and genome-wide DNA methylation patterns, providing a cost-effective and accessible alternative to in vivo models. This approach has the potential to facilitate personalized treatment strategies for patients requiring additional therapy beyond surgery
Impact of Gastroparesis on Outcomes After Pancreas Transplantation
No full textBACKGROUND: Gastroparesis (GP) is a chronic disorder of the stomach characterized by delayed gastric emptying and frequently associated with longstanding diabetes. This is a single-center retrospective analysis designed to establish the prevalence and assess the impact on posttransplant outcomes of GP among pancreas transplant recipients.
METHODS: Medical records for all recipients of pancreas transplants performed between January 2003 and December 2023 were reviewed. GP was defined by abnormal gastric-emptying scintigraphy or other motility study or a history of symptoms. Primary outcomes included graft loss and patient death. Clinical outcomes included length of stay after transplant and readmissions, including specifically for GP symptoms.
RESULTS: Of 731 recipients, 156 (21%) were diagnosed with GP before transplant. Patients with GP were younger and more likely to be female individuals. Posttransplant, there was no difference in length of stay, graft survival, or patient survival. Patients with GP were more likely to be readmitted and to be specifically admitted for GP symptoms. Requirement for interventions was more common in patients with GP.
CONCLUSIONS: GP is identified with increased frequency among the specific patient population referred for pancreas transplant, and although it does not seem to affect allograft or patient survival, it does seem to have an impact on readmissions and the need for interventions
Impact of Rural Status on Lower Extremity Bypass Outcomes for Patients With Chronic Limb Threatening Ischemia
No full textBACKGROUND: Previous studies noted that the rural population experienced higher peripheral artery disease related mortality than their urban counterparts. Our study aimed to assess the impact of rural status on lower extremity bypass (LEB) outcomes for patients with chronic limb threatening ischemia.
METHODS: We analyzed data from the Blue Cross Blue Shield Michigan Cardiovascular Consortium registry data from 2016 to 2022. Primary exposure included patient\u27s residence based on rural-urban commuting area codes. Primary outcome was major adverse cardiovascular events. Secondary outcomes include 30-day and 1-year mortality, hospital readmission, bypass revision, wound complications, amputations, and 30-day renal failure requiring dialysis. We conducted univariate and multivariate analysis to evaluate association between rural status and LEB outcomes.
RESULTS: Rural patients tended to be White (P \u3c 0.001), had insurance (P \u3c 0.001), were current smokers (P \u3c 0.001), had hyperlipidemia (P \u3c 0.001), prior congestive heart failure (P = 0.031), chronic obstructive pulmonary disease (P \u3c 0.001), prior cerebrovascular disease or transient ischemic attack (P = 0.005), take preprocedure aspirin (P = 0.011) and statin (P = 0.007), and were less likely to live in a distressed community (P \u3c 0.001). They were not at increased risks of 30-day and 1-year major adverse cardiovascular events. They had higher odds of bypass revision (P = 0.028) at 1 year. However, they did not have higher odds of amputation at 30 days and 1 year.
CONCLUSION: Rural status does not impact LEB outcomes. Rural patients achieve comparable outcomes compared with their urban counterparts due to overwhelmingly White rural demographics, optimal medical therapy, socioeconomic status, and increased health-care utilization
Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES): protocol for a pragmatic, international multicentre randomised trial
No full textINTRODUCTION: Acute pain is commonly experienced by millions of patients who undergo outpatient surgical procedures. Moreover, an increasing number of procedures are performed on an outpatient basis, requiring greater postoperative planning to ensure effective pain management. Analgesic approaches commonly involve prescription opioids and non-steroidal anti-inflammatory drugs (NSAIDs), but an optimal regimen that balances pain and adverse effects has not been identified. In addition, critical gaps in evidence exist regarding how opioids and NSAIDs compare as analgesic regimens after surgery.
METHODS AND ANALYSIS: The Comparing Analgesic Regimen Effectiveness and Safety after Surgery (CARES) trial is a pragmatic, international, multicentre randomised trial that enrols adults undergoing three elective surgical procedures (laparoscopic cholecystectomy, breast lumpectomy, hernia repair). Participants are randomised to receive discharge analgesic prescriptions that consist of either NSAIDs or low-dose opioids (ie, 10 pills of oxycodone 5 mg or equivalent), with both groups prescribed acetaminophen around-the-clock. The primary effectiveness outcome is patient-reported worst daily pain intensity over the first 7 days after surgery. The primary safety outcome is the occurrence of opioid and/or NSAID side effects over the first 7 days after surgery. Secondary outcomes are assessed by patient report and medical record review at 1 week, 1 month, 3 months and 6 months after surgery and include sleep disturbance, patient perception of improvement/change after treatment, pain interference, anxiety, depression, health-related quality of life, clinically important adverse events, substance use, opioid misuse, chronic pain, healthcare utilisation related to pain and quality of recovery.
ETHICS AND DISSEMINATION: Investigational review boards at the University of Michigan and other sites have approved the CARES trial. The first patient enrolled in CARES in February 2023, with recruitment anticipated through 2026. Dissemination builds on the input of patient partners and other members of an engaged Stakeholder Advisory Board, with activities spanning co-production of summaries to share results with study participants, publications in biomedical journals and lay press, presentations to scientific and community organisations, and other multimedia communication materials.
TRIAL REGISTRATION NUMBER: NCT05722002