Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Counting the cost of major infection and sepsis in New Zealand: an exploratory study using the National Minimum Data Set.

AIM: To explore the population-at-risk and potential cost of a sepsis episode in New Zealand. METHOD: Retrospective analysis of the National Minimum Data Set using two code-based algorithms selecting (i) an inclusive cohort of hospitalised patients diagnosed with a 'major infection' with the potential to cause sepsis and (ii) a restricted subset of these patients with a high likelihood of clinical sepsis based on the presence of both a primary admission diagnosis of infection and at least one sepsis-associated organ failure. RESULTS: In 2016, 24% of all inpatient episodes were associated with diagnosis of a major infection. The sepsis coding algorithm identified a subset of 1,868 discharges. The median (IQR) reimbursement associated with these episodes was $10,381 ($6,093-$10,964). In both groups, 30-day readmission was common (26.7% and 11% respectively). CONCLUSIONS: Infectious diseases with the potential to cause sepsis are common among hospital inpatients. Direct treatment costs are high for those who present with or progress to sepsis due to these infections

Magnetic resonance imaging: The underlying principles

The creation of a magnetic resonance image (MRI) and its inherent contrast are controlled by a variety of anatomical structure- and sequence-dependent parameters. While these may seem confusing to the uninitiated, they provide MRI with great flexibility and make it a powerful clinical tool. This article describes the principles of basic physics behind magnetic resonance spectroscopy (MRS) and imaging, including a basic description of the properties of magnetic resonance compatible nuclei, how a radiofrequency (RE) pulse produces a signal, and how this signal can be spatially encoded to produce an image. The relaxation properties of the MRI signal depend on biological tissue type and can provide information on tissue composition, environment, and pathological changes. The contrast properties within an image can be manipulated based on the relaxation properties of the anatomical sample and the nature of the imaging sequence. The benefits of T1- and T2-weighted images in musculoskeletal imaging and the common sequences used (including turbo spin echo [TSE], fat suppression sequences such as STIR, and rapid breath-hold sequences such as HASTE and FISP) are discussed. The principles behind contrast agents and diffusion-weighted imaging and how they can be applied in the body are considered. J Orthop Sports Phys Ther 2011;41(11):806-819, Epub 7 June 2011. doi:10.2519/jospt.2011.357

Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used massively parallel exome sequencing coupled with Sanger re-sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 ( BAP1 ) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination, and six affecting its ubiquitin carboxy-terminal hydrolase (UCH) domains. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest the BAP1 pathway as a therapeutic target

A half century of Romance linguistics: Selected proceedings of the 50th Linguistic Symposium on Romance Languages

The present volume presents a selection of the revised and peer-reviewed proceedings articles of the 50th Linguistic Symposium on Romance Languages (LSRL 50) which was hosted virtually by the faculty and students from the University of Texas at Austin. With contributions from rising and senior scholars from Europe and the Americas, the volume demonstrates the breadth of research in contemporary Romance linguistics with articles that apply corpus-based and laboratory methods, as well as theory, to explore the structure, use, and development of the Romance languages. The articles cover a wide range of fields including morphosyntax, semantics, language variation and change, sociophonetics, historical linguistics, language acquisition, and computational linguistics. In an introductory article, the editors document the sudden transition of LSRL 50 to a virtual format and acknowledge those who helped them to ensure the continuity of this annual scholarly meeting

A half century of Romance linguistics: Selected proceedings of the 50th Linguistic Symposium on Romance Languages

The present volume presents a selection of the revised and peer-reviewed proceedings articles of the 50th Linguistic Symposium on Romance Languages (LSRL 50) which was hosted virtually by the faculty and students from the University of Texas at Austin. With contributions from rising and senior scholars from Europe and the Americas, the volume demonstrates the breadth of research in contemporary Romance linguistics with articles that apply corpus-based and laboratory methods, as well as theory, to explore the structure, use, and development of the Romance languages. The articles cover a wide range of fields including morphosyntax, semantics, language variation and change, sociophonetics, historical linguistics, language acquisition, and computational linguistics. In an introductory article, the editors document the sudden transition of LSRL 50 to a virtual format and acknowledge those who helped them to ensure the continuity of this annual scholarly meeting

A half century of Romance linguistics: Selected proceedings of the 50th Linguistic Symposium on Romance Languages

The present volume presents a selection of the revised and peer-reviewed proceedings articles of the 50th Linguistic Symposium on Romance Languages (LSRL 50) which was hosted virtually by the faculty and students from the University of Texas at Austin. With contributions from rising and senior scholars from Europe and the Americas, the volume demonstrates the breadth of research in contemporary Romance linguistics with articles that apply corpus-based and laboratory methods, as well as theory, to explore the structure, use, and development of the Romance languages. The articles cover a wide range of fields including morphosyntax, semantics, language variation and change, sociophonetics, historical linguistics, language acquisition, and computational linguistics. In an introductory article, the editors document the sudden transition of LSRL 50 to a virtual format and acknowledge those who helped them to ensure the continuity of this annual scholarly meeting

A half century of Romance linguistics: Selected proceedings of the 50th Linguistic Symposium on Romance Languages

The present volume presents a selection of the revised and peer-reviewed proceedings articles of the 50th Linguistic Symposium on Romance Languages (LSRL 50) which was hosted virtually by the faculty and students from the University of Texas at Austin. With contributions from rising and senior scholars from Europe and the Americas, the volume demonstrates the breadth of research in contemporary Romance linguistics with articles that apply corpus-based and laboratory methods, as well as theory, to explore the structure, use, and development of the Romance languages. The articles cover a wide range of fields including morphosyntax, semantics, language variation and change, sociophonetics, historical linguistics, language acquisition, and computational linguistics. In an introductory article, the editors document the sudden transition of LSRL 50 to a virtual format and acknowledge those who helped them to ensure the continuity of this annual scholarly meeting