Intermountain Medical Center is the flagship hospital of Intermountain Healthcare. Located in Murray, Utah on a 100-acre (0.40 km2) site at the center of the Salt Lake Valley, Intermountain Medical Center serves as a major adult referral center for six surrounding states and more than 75 regional health care institutions. The hospital is also a Level I trauma center, accredited by the American College of Surgeons. It has 452 beds and is accredited by the Commission on Accreditation of Rehabilitation Facilities. Intermountain Medical Center opened in October 2007, and several premature babies were transferred by Intermountain Healthcare's Life Flight to the hospital on the first day for better treatment and care.The hospital, the nearby parking lots, and the nearby UTA rail station were built on the site of the former Asarco Murray lead smelter, which was reclaimed as part of an EPA Superfund program.Intermountain Medical Center and University of Utah Hospital were tied for #1 atop rankings nearly 60 hospitals statewide, according to U.S. News & World Report's 2015-2016 "Best Hospitals" rankings..
BACKGROUND AND AIMS:The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS:The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS:One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (-11.6, 11.9), massive/torrential -5.8% (-17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (-3.0, 22.7), massive/torrential -15.2% (-28.9, -1.5)]. CONCLUSIONS:Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.
Importance:As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies. Objective:To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion. Design, Setting, and Participants:This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, at 26 hospitals in 20 US states. Case patients presented with COVID-19-like illness and positive SARS-CoV-2 nucleic acid or antigen test results; control patients had COVID-19-like illness but tested negative for SARS-CoV-2. Exposure:Receipt of a 2024-2025 COVID-19 vaccine at least 7 days before illness onset. Main Outcomes and Measures:Main outcomes were COVID-19-associated hospitalization and severe in-hospital outcomes (supplemental oxygen therapy, acute respiratory failure, intensive care unit admission, and invasive mechanical ventilation or death). Logistic regression was used to estimate the odds of vaccination in case and control patients, adjusting for demographics, clinical characteristics, and enrollment region. The VE was estimated as (1 - adjusted odds ratio) × 100%. Results:A total of 8493 patients (median [IQR] age, 66 [54-76] years; 4338 female [51.1%]), including 1888 case patients with COVID-19 (among whom 951 [50.4%] had successful whole-genome sequencing, including 348 [36.6%] with KP.3.1.1, 218 [22.9%] with XEC, and 134 [14.1%] with LP.8.1 infections) and 6605 control patients were enrolled. Vaccine effectiveness against COVID-19-associated hospitalization was 40% (95% CI, 27%-51%), and protection was sustained through 90 to 179 days after vaccination. Vaccine effectiveness was higher against the most severe outcome of invasive mechanical ventilation or death at 79% (95% CI, 55%-92%). It was 49% (95% CI, 25%-67%) against hospitalization with KP.3.1.1, 34% (95% CI, 4%-56%) against XEC, and 24% (95% CI, -19% to 53%) against LP.8.1, with increasing median time since dose receipt among vaccinated case patients due to sequential circulation patterns (60, 89, and 141 days, respectively). The VE was similar against lineages with spike protein S31 deletion (41% [95% CI, 22%-56%]) and T22N and F59S substitutions (37% [95% CI, 9%-57%]). Conclusions and Relevance:In this multicenter, case-control analysis of VE, 2024-2025 COVID-19 vaccines may have provided protection against hospitalizations and severe in-hospital outcomes as multiple JN.1 descendant lineages circulated. Monitoring COVID-19 VE, including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.
Viral myocarditis is a major cause of sudden cardiac death and can lead to dilated cardiomyopathy in adults. However, effective treatments remain elusive due to an incomplete understanding of its molecular drivers. Here, we investigate the role of β-arrestins (βarrs), scaffolding proteins that regulate GPCR signaling, in acute viral myocarditis. Using global βarr1 and βarr2 knockout (KO) mice, we assessed immune cell infiltration and apoptosis as markers of cardiac inflammation under Coxsackievirus (CVB3) infection. CVB3-infected βarr1 and 2 KO mice exhibited suppressed recruitment of NK cells, monocytes, macrophages, dendritic cells, and T cells over a broad range of viral titers at 7 days postinfection along with reduced cardiac apoptosis. At 4 days postinfection, immune cell expansion in secondary lymphoid organs, including B cells, CD8+ T cells, CD64+ myeloid progenitors, and monocyte/macrophages was also impaired in βarr KO mice. Importantly, cardiomyocyte-specific βarr1 and 2 dual deletion mirrored the attenuated inflammatory response and apoptosis observed in global βarr KO mice. Mechanistically, cardiomyocytes lacking βarr1 or βarr2 displayed defective cGAS-STING pathway activation, with impaired STING, TBK1, and IRF3 phosphorylation and inhibited IFNβ production at 24 h post-CVB3 infection. These data highlight βarrs as critical mediators of the inflammatory response in the heart and secondary lymphoid organs during viral myocarditis and demonstrate that cardiomyocyte βarrs plays a fundamental role in the inflammatory response to CVB3 viral myocarditis.NEW & NOTEWORTHY Viral myocarditis can lead to dilated cardiomyopathy in adults, yet the molecular mechanisms that induce cardiac inflammation in viral myocarditis remain unclear. β-Arrestins are scaffolding proteins that mediate intracellular signaling during viral infection. We demonstrated that cardiomyocyte β-arrestins are necessary for immune cell recruitment, induction of cardiac apoptosis, and cGAS-STING pathway activation during acute coxsackievirus B3 infection. Targeting β-arrestins appears to decrease the inflammatory response in acute viral myocarditis.
BACKGROUND:Cardiogenic shock (CS) remains highly morbid despite significant advancements in management. A cornerstone of this management is Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO). However, consensus surrounding the management of VA ECMO for CS, including the use of concomitant Left Ventricular Mechanical Unloading (LVMU), remains limited. METHODS:We thus conducted a national survey of practice patterns in the treatment of CS to characterize such variability. Surveys were distributed to physicians involved in management of VA ECMO across a variety of center types. RESULTS:Responses representing 67 institutions were analyzed. VA ECMO was used for a median of 10% of CS patients at each institution. Formal shock teams were present at 64.1% of centers and were associated with both higher annual VA ECMO volume (P⟨0.01) and greater intra-aortic balloon pump use prior to VA ECMO (p = 0.03). LVMU was employed by 63.4% of centers, most commonly using Impella (93.3%), with unloading initiated at ECMO cannulation in a median of 30% of cases. Triggers and targets for LVMU varied widely, though pulmonary capillary wedge pressure was the most common endpoint. CONCLUSIONS:These findings highlight substantial heterogeneity in CS diagnosis, VA ECMO initiation, and LVMU strategies, underscoring the need for prospective studies to define optimal care.
