Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics.

Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19: mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols.

Heme Oxgenase-1, a Cardinal Modulator of Regulated Cell Death and Inflammation.

Heme oxygenase catalyzes the rate-limiting step in heme degradation in order to generate biliverdin, carbon monoxide (CO), and iron. The inducible form of the enzyme, heme oxygenase-1 (HO-1), exerts a central role in cellular protection. The substrate, heme, is a potent pro-oxidant that can accelerate inflammatory injury and promote cell death.

Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders.

Objective: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort.

Methods: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement.

Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial.

Background: Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients.

Methods: The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS.

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

Background And Purpose: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up.

Methods: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort.

Comorbid Conditions and Health-Related Quality of Life in Ambulatory Heart Failure Patients: REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life REVIVAL).

Background: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF.

Methods: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire).

Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow-Up of the PRECOMBAT Trial.

Background: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated.

Methods: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.

Prognostic Effects of Treatment Strategies for Left Main Versus Non-Left Main Bifurcation Percutaneous Coronary Intervention With Current-Generation Drug-Eluting Stent.

Background: Although 1-stent with provisional approach is the preferred strategy for the treatment of bifurcation lesions, the optimal treatment strategy according to lesion location is still debatable. This study aimed to identify whether clinical outcomes according to treatment strategy differed between left main (LM) and non-LM bifurcation lesions in the second-generation drug-eluting stent era.

Methods: The Coronary Bifurcation Stenting registry III is a retrospective multicenter registry of 2648 patients with bifurcation lesions who underwent percutaneous coronary intervention with second-generation drug-eluting stent.

CD8 T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome.

Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, we demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8 T cells (CTLs).

The spectrum of immune-mediated and inflammatory lesions of the brainstem: Clues to diagnosis.

The presentation of a patient with brainstem symptoms and signs invokes a number of common and less common differential diagnoses, and accurate diagnosis can be challenging. We review the major immune-mediated and inflammatory syndromes that can affect the brainstem including multiple sclerosis, neuromyelitis optica spectrum disorder, neuro-Behçet disease, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, neurosarcoidosis, Susac syndrome, and the histiocytic disorders. We focus on clinical features and MRI clues that help to distinguish among the different brainstem conditions.

Doxorubicin Activates Ryanodine Receptors in Rat Lymphatic Muscle Cells to Attenuate Rhythmic Contractions and Lymph Flow.

Doxorubicin is a risk factor for secondary lymphedema in cancer patients exposed to surgery or radiation. The risk is presumed to relate to its cytotoxicity. However, the present study provides initial evidence that doxorubicin directly inhibits lymph flow and this action appears distinct from its cytotoxic activity.

One-year mortality in geriatric trauma patients: Improving upon the geriatric trauma outcomes score utilizing the social security death index.

Background: Geriatric Trauma Outcomes Score (GTOS) predicts in-patient mortality in geriatric trauma patients and has been validated in a prospective multicenter trial and expanded to predict adverse discharge (GTOS II). We hypothesized that these formulations actually underestimate the downstream sequelae of injury and sought to predict longer-term mortality in geriatric trauma patients.

Methods: The Parkland Memorial Hospital Trauma registry was queried for patients 65 years or older from 2001 to 2013.

Impact of Bridge to Transplantation With Continuous-Flow Left Ventricular Assist Devices on Posttransplantation Mortality.

Background: Bridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT.

Randomized Trial Evaluating Percutaneous Coronary Intervention for the Treatment of Chronic Total Occlusion.

Background: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials.

Methods: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator.

ENSO Drives interannual variation of forest woody growth across the tropics.

Meteorological extreme events such as El Niño events are expected to affect tropical forest net primary production (NPP) and woody growth, but there has been no large-scale empirical validation of this expectation. We collected a large high-temporal resolution dataset (for 1-13 years depending upon location) of more than 172 000 stem growth measurements using dendrometer bands from across 14 regions spanning Amazonia, Africa and Borneo in order to test how much month-to-month variation in stand-level woody growth of adult tree stems (NPP) can be explained by seasonal variation and interannual meteorological anomalies. A key finding is that woody growth responds differently to meteorological variation between tropical forests with a dry season (where monthly rainfall is less than 100 mm), and aseasonal wet forests lacking a consistent dry season.

Effect of Lowering Diastolic Pressure in Patients With and Without Cardiovascular Disease: Analysis of the SPRINT (Systolic Blood Pressure Intervention Trial).

Systolic and diastolic blood pressure thresholds, below which cardiovascular events increase, are widely debated. Using data from the SPRINT (Systolic Blood Pressure Intervention Trial), we evaluated the relation between systolic and diastolic pressure and cardiovascular events among 1519 participants with or 7574 without prior cardiovascular disease. Using Cox regression, we examined the composite risk of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death, and follow-up systolic and diastolic pressure were analyzed as time-dependent covariates for a median of 3.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

Background: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD.

Methods: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort.

Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in Patients With ST-Segment-Elevation Myocardial Infarction: A Propensity Score-Matched Analysis.

Background: The Strategic Reperfusion Early After Myocardial Infarction trial and the French Registry of Acute ST-elevation or Non-ST-elevation Myocardial Infarction 2015 suggested that pharmacoinvasive strategy compares favorably with primary percutaneous coronary intervention (PPCI). We sought to assess the clinical impact of pharmacoinvasive strategy compared with PPCI in real-world patients with ST-segment-elevation myocardial infarction.

Methods And Results: We used the Korea Acute Myocardial Infarction Registry to identify ST-segment-elevation myocardial infarction patients receiving either pharmacoinvasive strategy defined as fibrinolysis followed by percutaneous coronary intervention (rescue/urgent or routine elective; n=708) or PPCI (n=8878).

Long-Term Clinical Outcomes of Fractional Flow Reserve-Guided Versus Routine Drug-Eluting Stent Implantation in Patients With Intermediate Coronary Stenosis: Five-Year Clinical Outcomes of DEFER-DES Trial.

Background: We aimed to compare the long-term clinical outcomes between fractional flow reserve (FFR)-guided and routine drug-eluting stent (DES) implantation in patients with an intermediate coronary stenosis.

Methods And Results: A total of 229 patients with an angiographically intermediate coronary stenosis were randomly assigned to FFR-guided or Routine-DES implantation group. For FFR-guided group (n=114), treatment strategy was determined according to the target vessel FFR (FFR<0.

Impact of common crystalloid solutions on resuscitation markers following Class I hemorrhage: A randomized control trial.

Background: Resuscitation after hemorrhage with crystalloid solutions can lead to marked acidosis and iatrogenically worsen the lethal triad. The effect of differing solutions on base deficit and lactate has been sparsely prospectively studied in humans. We sought to quantify the effect of normal saline (NS) and lactated Ringer's (LR) resuscitation in voluntary blood donors as a model for Class I hemorrhage.