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Reducing Surgical Site Infections Post Cesarean Section through Multi-Modal Standardized Education
No full textLinavonkibart and pembrolizumab in immune checkpoint blockade-resistant advanced solid tumors: a phase 1 trial.
No full textAlthough immune checkpoint inhibitor therapies have revolutionized oncology, many cancers are unresponsive or develop resistance that involves transforming growth factor-β1 (TGFβ1). This multicenter, open-label, phase 1 study (DRAGON trial, SRK-181-001) evaluated safety, pharmacokinetics, pharmacodynamics, predictive biomarkers and efficacy of linavonkibart, a first-in-class fully human selective anti-latent TGFβ1 antibody with anti-programmed cell death protein 1 (PD-1) therapy. The DRAGON trial was divided into three treatment parts: part A1 (dose-escalation cohorts with single-agent linavonkibart), part A2 (dose-escalation cohorts with the combination treatment of linavonkibart and pembrolizumab) and part B (dose-expansion cohorts with the combination treatment). The primary objective of the study was to determine the safety and tolerability of linavonkibart alone and in combination with pembrolizumab. Secondary objectives included evaluation of linavonkibart pharmacokinetics for each treatment paradigm, assessment of anti-linavonkibart antibody development (parts A and B) and measurement of antitumor activity (part B) after treatment. All primary and secondary objectives were met in the study. Overall, linavonkibart had a manageable safety profile, and combined therapy with pembrolizumab was generally consistent with that of pembrolizumab monotherapy. Dermatological reactions were the only additional risk identified. Neither cytokine release syndrome nor infusion interruption was observed in any patient enrolled in DRAGON. In part A (n = 34), no dose-limiting toxicities or grade 4 or 5 treatment-related adverse events occurred (linavonkibart; ≤3,000 mg once every 3 weeks (Q3W) and 2,000 mg once every 2 weeks (Q2W)). In part B (n = 78), patients progressing on prior anti-PD-1 therapy received linavonkibart (1,500 mg Q3W/1,000 mg Q2W) with pembrolizumab (200 mg Q3W). This combination demonstrated confirmed objective response rates of 20.0%, 18.2%, 9.1% and 9.1% in anti-PD-1-resistant patients with clear cell renal cell cancer (ccRCC), melanoma, head and neck squamous cell cancer and urothelial cancer, respectively. Biomarker data provide proof of mechanism and a potential ccRCC patient selection strategy. ClinicalTrials.gov identifier: NCT04291079
Per oral endoscopic myotomy and laparoscopic Heller myotomy show similar outcomes in type III achalasia.
No full textBACKGROUND: Achalasia is classified into 3 manometric subtypes with variable treatment response. Guidelines recommend per oral endoscopic myotomy (POEM) over laparoscopic Heller myotomy (LHM) for the treatment of achalasia type III. However, there is limited evidence directly comparing these operations. We aimed to compare the treatment response to POEM vs LHM in type III achalasia.
METHODS: We conducted a retrospective, case-control review of patients undergoing primary myotomy for type III achalasia or achalasia variants with type III features. The primary outcome was symptomatic response assessed using the Eckardt score (ES) with a score of ≤3 classified as success. The secondary outcome was the need for reintervention(s) within 3 years.
RESULTS: There were 46 patients, of whom 16 underwent POEM, and 30 underwent LHM. The groups were similar in demographics, preoperative ESs, and rates of preoperative endoscopic interventions. Both groups had median myotomy lengths of 6 cm (4 cm esophageal and 2 cm gastric). After myotomy, both groups had similar rates of success (14/16 POEM vs 26/30 LHM, P =.94). The primary persisting symptom was dysphagia in both groups. Reinterventions occurred in 4/16 (25%) of POEM patients who underwent 9 reinterventions compared with 5/30 (16.7%) LHM patients who underwent 6 reinterventions (P =.49). Most patients in both groups had symptomatic improvement after their last reintervention.
CONCLUSION: Patients with type III achalasia had similar improvements after undergoing POEM or LHM. There was no difference in reintervention rates between the groups. Patients undergoing reintervention after POEM were more likely to undergo multiple reinterventions
Reducing Hospital-Acquired Infections: Implementing Dual registered Nurse Verification for Foley Catheter and Central Line Indications
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Middle Meningeal Artery Embolization for Subdural Hematoma: CT/MRI End Points of the EMBOLISE Trial.
No full textBackground Chronic subdural hematomas (cSDHs) are associated with high recurrence risks following surgical evacuation. The EMBOLISE trial demonstrated that, compared with surgery alone, adjunctive middle meningeal artery embolization (MMAE) significantly reduced reoperation rates. However, given the limitations of the clinical end points of the trial, which may be subject to interrater variability and certain biases, the quantitative imaging metrics need to be evaluated. Purpose To evaluate the prespecified imaging end points of the EMBOLISE trial and assess the long-term resolution of cSDH through quantitative imaging analyses. Materials and Methods EMBOLISE was a multicenter, randomized, interventional trial conducted across 39 U.S. sites between December 2020 and August 2023. Prespecified secondary imaging end points included changes in hematoma volume and thickness and midline shifts from 24 hours to 90 days after the procedure at CT and MRI. The post hoc analyses performed herein extended the assessment to 180 days and included absolute hematoma metrics. Mixed-effects modeling was employed to adjust for confounders. Results Four hundred patients were enrolled in the EMBOLISE study, among whom 352 were included (mean age, 72 years ± 10.4 [SD]; 256 men). The mean cSDH volume was 126 mL at screening, with no intergroup differences. At 90 and 180 days, the MMAE plus surgery group had lower cSDH volumes (20.6 mL vs 28.9 mL [P = .03] and 19.4 mL vs 31.5 mL [P = .04], respectively). Mixed-effects models revealed a 6.9 mL (95% CI: -13.5, -0.40; approximately 25%) greater volume reduction and an 8.4 mL (95% CI: -15.2, -1.6; approximately 30%) lower absolute volume at 90 days in the MMAE group There was no evidence of a difference in the prespecified secondary imaging end points between the groups. Conclusion While the prespecified secondary imaging end points did not significantly differ, the absolute 90- and 180-day hematoma volumes were significantly lower in patients who received MMAE and surgery. Confounder-adjusted mixed-effects analysis indicated a greater reduction in hematoma volume with adjunctive MMAE. ClinicalTrials.gov identifier NCT04402632 © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Ramasamy and Baker in this issue
Early Detection of Wellness-to-Disease Transitions in the AI Era: Implications for Pharmacology and Toxicology.
No full textPrecision medicine demands a shift from static, single-analyte diagnostics toward dynamic, systems-level understanding of health and disease. This review explores how the convergence of systems biology, multiomics, and artificial intelligence (AI) redefines biomarker discovery to drive early disease detection and personalized intervention. We highlight pioneering efforts that use longitudinal, multimodal data to map individual health trajectories and uncover early disease signals. Advances in AI, including machine learning and contextualization using knowledge graphs and digital twins, are accelerating clinical translation by enabling predictive, context-aware analyses. Real-world applications, including omics-informed diagnostics and digital health monitoring, demonstrate the potential of this approach to transform health care from reactive treatment to proactive wellness. These technologies also inform the development of targeted therapeutics that intervene earlier, personalize treatment, and potentially halt or reverse disease progression. We outline challenges, emerging solutions, and future directions that position AI-driven systems biology at the center of next-generation precision health
IL-12 and the Antitumor Response: The Good, the Bad, and the Unknown.
No full textIL-12 is a proinflammatory cytokine secreted by antigen-presenting cells. It promotes the differentiation of cytotoxic T cells, which makes it a strong candidate to boost the antitumor immune response in cancer patients. While its first use in humans faced severe toxicity, more recent approaches have been taken to limit toxicity while retaining its biologic function. These strategies, summarized in this review, include systemic and local delivery of IL-12 and demonstrated promising results in murine tumor models. However, their translation in cancer patients was met with limited efficacy. Recent evidence indicates that exposure to IL-12 results in the expression of immunoregulatory molecules by T cells, suggesting the existence of a negative feedback loop that might impair the antitumor immune response. Therefore, a more thorough understanding of the biology of IL-12 in the context of cancer is crucial to advance the design of novel clinical trials. This approach can lead to improved therapy regimens and promising results in the future
The Impact of a Remote Patient Care Program on Health Care Costs and Utilization Among Medicare Patients With Chronic Disease.
No full textRemote patient monitoring coupled with technology-enabled, guideline-directed clinical care-or remote patient care (RPC)-has consistently led to improved outcomes for Medicare patients with chronic diseases. However, the ability for RPC to drive reductions in total cost of care and health care utilization is limited. We sought to determine whether an RPC program can reduce health care costs and utilization. Using patient-level Medicare claims data, a difference in difference analysis was conducted to assess the impact of an RPC program compared with a propensity score-matched control group on total health care costs and resource utilization over a 12-month period following program activation. The retrospective analysis included patients enrolled into an RPC program from July 1, 2022 to October 31, 2023 from primary care and cardiology clinics across 15 states. The RPC program included a group of clinicians who monitored and triaged vitals and conducted clinical visits using standardized clinical protocols to facilitate guideline-directed clinical interventions. We compared 5872 patients enrolled in an RPC program to 11,449 eligible propensity score-matched control patients. RPC resulted in a statistically significant reduction in total cost of care (-1428 per patient per year; P\u3c .01). Patients enrolled in the RPC program also had a lower rate of hospitalizations (-23 vs +41/1000 patients/y; 27% reduction; P\u3c .01). These data highlight the potential for a nationwide RPC program to lead to significant cost savings and a reduction in health care utilization among Medicare patients at scale