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June 2025: Region 10 Emerging Special Pathogen Treatment Center (RESPTC) at Providence Sacred Heart Medical Center & Children’s Hospital
No full textREGION 10 SPECIAL PATHOGENS NEWSLETTERhttps://digitalcommons.providence.org/special_pathogens_newsletters/1008/thumbnail.jp
The Western Aortic Collaborative: Multi-institutional Aortic Surgery, Education, and Research.
No full textThe Western Aortic Collaborative (WAC) is a new, hybrid, multi-institutional academic model that seeks to perform aortic surgery research and education.The WAC has three fundamental thoracic aortic surgery goals: (1) advancing surgical techniques, (2) furthering education and development of aortic surgeons, and (3) performing multi-institutional clinical research. The WAC utilizes a hybrid model of annual in-person meetings at the Western Thoracic Surgical Association (WTSA) combined with videoconferencing platforms that regularly connect surgeons dispersed throughout the Western region. The structure of WAC is intentionally horizontal. The goal is to promote cross-pollination of ideas, techniques, and experiences between surgeons at different institutions.For its research goals, the WAC first identified the principal areas of aortic surgery with the greatest knowledge gaps and which of those knowledge gaps could best be addressed by institutional practice differences within WAC. Using this natural experiment design, five high-priority research topics from the aortic root to the left subclavian artery were created. In order to perform this subspecialized, multi-institutional research, the WAC created a novel, cloud-based database that piggybacks on the Society for Thoracic Surgeon database. The combined database also preserves the ability to generate subspecialized variables and to link with each institution\u27s medical record system for semi-automated functionality.In its inaugural year, the WAC succeeded in its primary goals of utilizing remote technology platforms and the annual WTSA meeting to create a regional community of aortic surgeons with shared research and educational goals
Outcome metrics for primary endoscopic endonasal surgery for low-risk patients with Cushing\u27s disease: an evidence-based position statement from the Registry of Adenomas of the Pituitary and Related Disorders consortium.
No full textOBJECTIVE: Reports of surgical outcomes for Cushing\u27s disease are mostly limited to single-center experiences by expert surgeons. Therefore, no generalizable surgical outcome metrics for endoscopic endonasal Cushing\u27s disease surgery are available for practitioners to guide quality-improvement efforts. This is potentially problematic, given the high morbidity and excess mortality observed in patients who do not achieve remission. This study proposes a bundle of evidence-based metrics for low-risk patients with Cushing\u27s disease, for whom optimal outcomes would be expected, that focus on the cost efficiency of care and surgical outcomes from multicenter collaboration of US pituitary centers.
METHODS: The steering committee of the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) consortium proposed the metrics based on available data from 12 US pituitary centers. A benchmarking population of low-risk patients undergoing first-time surgery was identified. Patient characteristics and outcomes were aggregated and analyzed by a data coordinating center. Metrics were reported using 2 approaches.
RESULTS: A total of 431 patients from 12 centers who underwent primary endoscopic transsphenoidal surgery from January 1, 2006, to December 31, 2022, were included. There were 227 patients in the low-risk cohort (age \u3c 70 years, BMI \u3c 50, microadenoma, and Knosp grade 0-2). For the cost-efficiency metrics, the mean (SD) length of stay was 3.8 (4.8) midnights, and the percentage of patients readmitted was 11.1%. The rate of disposition to a skilled nursing facility was 2.2%. For surgical outcomes, the rate of postoperative CSF leakage was 1.3%, and the rate of 1-year sustained surgical remission was 81.2%. The rates of permanent and temporary arginine vasopressin deficiencies were 1.8% and 11.9%, respectively. The 75th percentile performance by center was 3.0 midnights for length of stay, 6.3% for 90-day unplanned readmission, \u3c 1% for disposition to a skilled nursing facility, \u3c 1% for CSF leakage, and 92.2% for 1-year sustained remission. The 75th percentile was \u3c 1% for both permanent and temporary arginine vasopressin deficiencies.
CONCLUSIONS: An evidence-based bundle of metrics in a Cushing\u27s disease patient population at low risk who underwent first-time endoscopic pituitary surgery is proposed. Surgeons can use these metrics to assess and improve the quality of their clinical pathways
Biomarker-guided dose selection in the iintune-1 study of dazostinag,a STING agonist, alone and in combination with pembrolizumab for patients with metastatic solid tumors
No full textINBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering.
No full textBackground: Immunotherapies targeting immune checkpoint inhibitors have revolutionized cancer treatment but are limited by incomplete patient responses. Costimulatory agonists like OX40 (CD134), a tumor necrosis factor receptor family member critical for T-cell survival and differentiation, have shown preclinical promise but limited clinical success due to suboptimal receptor activation. Conventional bivalent OX40 agonists fail to induce the trimeric engagement required for optimal downstream signaling. To address this, we developed INBRX-106, a hexavalent OX40 agonist designed to enhance receptor clustering independently of Fc-mediated crosslinking and boost antitumor T-cell responses.
Methods: We assessed INBRX-106\u27s effects on receptor clustering, signal transduction, and T-cell activation using NF-kß reporter assays, confocal microscopy, flow cytometry, and single-cell RNA sequencing. Therapeutic efficacy was evaluated in murine tumor models and ex vivo human samples. Clinical samples from a phase I/II trial (NCT04198766) were also analyzed for immune activation.
Results: INBRX-106 demonstrated superior receptor clustering and downstream signaling compared with bivalent agonists, leading to robust T-cell activation and proliferation. In murine models, hexavalent OX40 agonism resulted in significant tumor regression, enhanced survival, and increased CD8+ T-cell effector function. Clinical pharmacodynamic analysis in blood samples from patients treated with INBRX-106 showed heightened T-cell activation and proliferation, particularly in central and effector memory subsets, validating our preclinical findings.
Conclusions: Our data establish hexavalent INBRX-106 as a differentiated and more potent OX40 agonist, showcasing its ability to overcome the limitations of conventional bivalent therapies by inducing superior receptor clustering and multimeric engagement. This unique clustering mechanism amplifies OX40 signaling, driving robust T-cell activation, proliferation, and effector function in preclinical and clinical settings. These findings highlight the therapeutic potential of INBRX-106 and its capacity to redefine OX40-targeted immunotherapy, providing a compelling rationale for its further clinical development in combination with checkpoint inhibitors
Outcomes With Femoral IABP in Heart Failure and Acute Myocardial Infarction-Related Cardiogenic Shock.
No full textBACKGROUND: Intra-aortic balloon pump (IABP) insertion has not been shown to improve mortality rates in acute myocardial infarction-related cardiogenic shock (AMI-CS) but is increasingly used in heart failure-related cardiogenic shock (HF-CS).
OBJECTIVE: We sought to compare IABP-related outcomes in patients with HF-CS and AMI-CS.
METHODS: The Cardiogenic Shock Working Group registry was queried for patients with CS receiving femoral IABPs as the first temporary mechanical circulatory support (tMCS) device. Patients were divided into those with AMI-CS or HF-CS and were excluded if they received the IABP in conjunction with venoarterial extracorporeal membrane oxygenation (VA-ECMO) or another device concomitantly. Outcomes, including rates of native heart survival (NHS) (ie, weaned from IABP and discharged), heart replacement therapy (HRT) (ie, bridge to durable left ventricular assist device or heart transplant), need for another tMCS device, and death, were recorded and compared between the 2 cohorts.
RESULTS: In total, 886 patients were supported by IABPs as the first tMCS device; of these, 407 (45.6%) had HF-CS and 384 (43.3%) had AMI-CS. Those with HF-CS were younger but had higher burdens of cardiovascular comorbidities than those with AMI-CS. Among the HF-CS cohort, 33.2% had NHS, and 26.7% were bridged to HRT without another tMCS device. In the AMI-CS cohort, 43.4% had NHS and 2.1% were bridged to HRT without another tMCS device. Mortality rates were higher in AMI-CS group (36.4% vs 20.6%; P \u3c 0.001). Complication rates were higher in those with AMI-CS and in those needing another tMCS device.
CONCLUSION: Patients with HF-CS were more likely to have a favorable outcome with IABPs than those with AMI-CS
Accuracy of Falls Screening Tools in Adult Patients With Cancer: A Systematic Review.
No full textIMPORTANCE: Patients with cancer experience increased falls risk secondary to oncological treatment and cancer-related sequelae.
OBJECTIVE: Identifying diagnostically and prognostically accurate screening tool(s) for falls risk in populations with cancer is an important issue.
DATA SOURCES: Screening tests were identified in PubMed and CINAHL.
STUDY SELECTION: Two independent reviewers screened citations for inclusion.
DATA EXTRACTION AND SYNTHESIS: Data extraction was performed by 1 reviewer and verified by a second. Tests were investigated for clinical utility, validity, diagnostic accuracy, and predictive capacity. Recommendations for screening measures were formulated using predetermined criteria.
MEASURES: Falls risk screening tools were identified for populations with cancer.
RESULTS: Of 532 articles screened, 24 articles were included. Fifty-five variations of screening measures were identified, of which 47 had sufficient clinical utility. Twenty measures contained data on diagnostic accuracy or predictive capacity. No screening measure met all criteria to be highly recommended for both ruling in and ruling out falls risk currently (diagnostic accuracy) or in the future (predictive capacity). History of falls demonstrated good diagnostic accuracy for ruling in immediate falls risk (specificity 98.9%, positive predictive value 84.6%). A negative falls history was highly indicative of lower future falls risk status (negative predictive value 82.5% to 90.1%). Fear of falling demonstrated accuracy for ruling out immediate risk for falls (negative predictive value 87.0%, sensitivity 88.7%). Strong predictive capacity was demonstrated with the Timed Up & Go (TUG) Standard (sensitivity 93% at ≤7.8 s, specificity 95% at ≥11.35 s).
CONCLUSIONS: Based on these results, a history of falls plus either the TUG Standard for those with a history of falls or subjective report of fear of falling for those without a history of falls is recommended for risk screening in populations with cancer.
RELEVANCE: Different screening tools are required for immediate versus future falls risk and are setting dependent