Association between Age and Mortality in Pediatric and Adult Acute Respiratory Distress Syndrome.

Rationale: The epidemiology, management, and outcomes of acute respiratory distress syndrome (ARDS) differ between children and adults, with lower mortality rates in children despite comparable severity of hypoxemia. However, the relationship between age and mortality is unclear.Objective: We aimed to define the association between age and mortality in ARDS, hypothesizing that it would be nonlinear.Methods: We performed a retrospective cohort study using data from two pediatric ARDS observational cohorts (n = 1,236), multiple adult ARDS trials (n = 5,547), and an adult observational ARDS cohort (n = 1,079). We aligned all datasets to meet Berlin criteria. We performed unadjusted and adjusted logistic regression using fractional polynomials to assess the potentially nonlinear relationship between age and 90-day mortality, adjusting for sex, PaO2/FiO2, immunosuppressed status, year of study, and observational versus randomized controlled trial, treating each individual study as a fixed effect.Measurements and Main Results: There were 7,862 subjects with median ages of 4 years in the pediatric cohorts, 52 years in the adult trials, and 61 years in the adult observational cohort. Most subjects (43%) had moderate ARDS by Berlin criteria. Ninety-day mortality was 19% in the pediatric cohorts, 33% in the adult trials, and 67% in the adult observational cohort. We found a nonlinear relationship between age and mortality, with mortality risk increasing at an accelerating rate between 11 and 65 years of age, after which mortality risk increased more slowly.Conclusions: There was a nonlinear relationship between age and mortality in pediatric and adult ARDS.

Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.

Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a "multidimensional entity" characterized by four "domains" that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar-capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present "relevant measurements," defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as "experimental ALI." Finally, we propose that a time criterion defining "acute" in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. OBJECTIVE: To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery. DESIGN: Single-health system, multihospital retrospective cohort study. SETTING: 5 hospitals within the University of Pennsylvania Health System. PATIENTS: Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. MEASUREMENTS: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. RESULTS: Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. LIMITATIONS: Single-health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. CONCLUSION: Among patients with COVID-19-related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Erythrocytes identify complement activation in patients with COVID-19.

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

Plasma sRAGE Acts as a Genetically Regulated Causal Intermediate in Sepsis-associated Acute Respiratory Distress Syndrome.

Rationale: Acute respiratory distress syndrome (ARDS) lacks known causal biomarkers. Plasma concentrations of sRAGE (soluble receptor for advanced glycation end products) strongly associate with ARDS risk. However, whether plasma sRAGE contributes causally to ARDS remains unknown.Objectives: Evaluate plasma sRAGE as a causal intermediate in ARDS by Mendelian randomization (MR), a statistical method to infer causality using observational data.Methods: We measured early plasma sRAGE in two critically ill populations with sepsis. The cohorts were whole-genome genotyped and phenotyped for ARDS. To select validated genetic instruments for MR, we regressed plasma sRAGE on genome-wide genotypes in both cohorts. The causal effect of plasma sRAGE on ARDS was inferred using the top variants with significant associations in both populations (P < 0.01, R2 > 0.02). We applied the inverse variance-weighted method to obtain consistent estimates of the causal effect of plasma sRAGE on ARDS risk.Measurements and Main Results: There were 393 European and 266 African ancestry patients in the first cohort and 843 European ancestry patients in the second cohort. Plasma sRAGE was strongly associated with ARDS risk in both populations (odds ratio, 1.86; 95% confidence interval [1.54-2.25]; 2.56 [2.14-3.06] per log increase). Using genetic instruments common to both populations, plasma sRAGE had a consistent causal effect on ARDS risk with a ß estimate of 0.50 (95% confidence interval [0.09-0.91] per log increase).Conclusions: Plasma sRAGE is genetically regulated during sepsis, and MR analysis indicates that increased plasma sRAGE leads to increased ARDS risk, suggesting plasma sRAGE acts as a causal intermediate in sepsis-related ARDS.

Women with chronic kidney disease undergoing transcatheter aortic valve replacement: Caveat emptor.

Over 60% of women presenting for transcatheter aortic valve replacement (TAVR) have coexisting chronic kidney disease (CKD). In women undergoing TAVR, CKD was associated with significantly higher rates of adverse events, including a twofold higher rate of risk-adjusted mortality at 1 year. This study is an important step forward in our understanding of risk stratification in women with CKD undergoing TAVR and suggests that measures to optimize outcomes warrant further investigation in this high-risk group of patients.

Low to Moderate Air Pollutant Exposure and Acute Respiratory Distress Syndrome after Severe Trauma.

RATIONALE: Exposure to air pollution has molecular and physiologic effects on the lung that may increase the risk of acute respiratory distress syndrome (ARDS) after injury. OBJECTIVES: To determine the association of short- and long-term air pollutant exposures and ARDS risk after severe trauma. METHODS: We analyzed data from a prospective cohort of 996 critically ill patients presenting with acute trauma and an injury severity score greater than 15. Exposures to ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and particulate matter less than 2.5 µm were assessed by weighted averages of daily levels from all monitors within 50 km of the geocoded location of a patient's residence. Patients were followed for 6 days for the development of ARDS according to Berlin Criteria. The association between each exposure and ARDS was determined via multivariable logistic regression adjusting for potential confounders. MEASUREMENTS AND MAIN RESULTS: ARDS developed in 243 (24%) patients. None of the short-term exposures averaged over the 3 days before presentation was associated with ARDS, except sulfur dioxide, which demonstrated a nonlinear association. Nitrogen dioxide, sulfur dioxide, and particulate matter less than or equal to 2.5 µm in aerodynamic diameter exposure over the 6 weeks before presentation was significantly associated with ARDS (P < 0.05). All long-term exposures (3 yr) were associated with ARDS (P < 0.01) in adjusted models, despite exposure levels largely below U.S. and European Union air quality standards. CONCLUSIONS: Long-term low- to moderate-level air pollutant exposure is associated with a greater risk of developing ARDS after severe trauma and represents a novel and potentially modifiable environmental risk factor for ARDS.

Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation.

Acute kidney injury (AKI) is common after lung transplantation, but molecular markers remain poorly studied. The endothelial activation markers soluble thrombomodulin (sTM), protein C, and plasminogen activator inhibitor-1 (PAI-1) are implicated in kidney microcirculatory injury in animal models of AKI. We tested the association of 6-hour postreperfusion plasma levels of these markers with posttransplant AKI severity in patients enrolled in the Lung Transplant Outcomes Group prospective cohort study at the University of Pennsylvania during two eras: 2004-06 (n = 61) and 2013-15 (n = 67). We defined AKI stage through postoperative day 5 using Kidney Disease Improving Global Outcomes creatinine criteria. We used multivariable ordinal logistic regression to determine the association of each biomarker with AKI, adjusted for primary graft dysfunction and extracorporeal life support. AKI occurred in 57 (45%) patients across both eras: 28 (22%) stage 1, 29 (23%) stage 2-3. Higher sTM and lower protein C plasma levels were associated with AKI stage in each era and remained so in multivariable models utilizing both eras (sTM: OR 1.76 [95% CI 1.19-2.60] per standard deviation, P = .005; protein C: OR 0.54 [1.19-2.60], P = .003). We conclude that 6-hour postreperfusion plasma sTM and protein C levels are associated with early postlung transplant AKI severity.

Closing the gender gap (but not the generation gap) in acute coronary syndromes.

In patients with acute coronary syndromes (ACS) undergoing coronary angiography, elderly women have nearly 50% lower rates of adverse events compared to elderly men, primarily driven by lower cardiovascular mortality. Nonelderly men and women patients with ACS have similar risk-adjusted rates of adverse events. Elderly ACS patients have lower rates of and delays in coronary revascularization than younger patients.

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

BACKGROUND: Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation. METHODS: We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h. Patients were followed for 6 days for ARDS by the Berlin definition. We used multivariable logistic regression to determine the association of plasma RIPK3 with ARDS in each cohort, adjusting for confounders. In mice, we determined whether plasma and lung tissue RIPK3 levels rise concomitantly 4 h after injection with lipopolysaccharide and ZVAD-FMK, an apoptosis inhibitor. RESULTS: The change in plasma RIPK3 from presentation to 48 h (ΔRIPK3) was associated with ARDS in sepsis (OR 1.30, 95% CI 1.03-1.63, per ½ standard deviation) and trauma (OR 1.79, 95% CI 1.33-2.40). This association was not evident for presentation RIPK3 levels. Secondary analyses showed similar findings for the association of ΔRIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p < 0.001) and lung (p = 0.005) RIPK3 than control mice. CONCLUSIONS: The change in plasma RIPK3 from presentation to 48 h in both sepsis and trauma patients is independently associated with ARDS, and plasma RIPK3 may reflect RIPK3 activity in lung tissue.

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BACKGROUND: Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. METHODS: In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. MEASUREMENTS AND MAIN RESULTS: An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. CONCLUSIONS: Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.

Acute Respiratory Distress Syndrome Phenotypes.

The acute respiratory distress syndrome (ARDS) phenotype was first described over 50 years ago and since that time significant progress has been made in understanding the biologic processes underlying the syndrome. Despite this improved understanding, no pharmacologic therapies aimed at the underlying biology have been proven effective in ARDS. Increasingly, ARDS has been recognized as a heterogeneous syndrome characterized by subphenotypes with distinct clinical, radiographic, and biologic differences, distinct outcomes, and potentially distinct responses to therapy. The Berlin Definition of ARDS specifies three severity classifications: mild, moderate, and severe based on the PaO2 to FiO2 ratio. Two randomized controlled trials have demonstrated a potential benefit to prone positioning and neuromuscular blockade in moderate to severe phenotypes of ARDS only. Precipitating risk factor, direct versus indirect lung injury, and timing of ARDS onset can determine other clinical phenotypes of ARDS after admission. Radiographic phenotypes of ARDS have been described based on a diffuse versus focal pattern of infiltrates on chest imaging. Finally and most promisingly, biologic subphenotypes or endotypes have increasingly been identified using plasma biomarkers, genetics, and unbiased approaches such as latent class analysis. The potential of precision medicine lies in identifying novel therapeutics aimed at ARDS biology and the subpopulation within ARDS most likely to respond. In this review, we discuss the challenges and approaches to subphenotype ARDS into clinical, radiologic, severity, and biologic phenotypes with an eye toward the future of precision medicine in critical care.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

RATIONALE: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. OBJECTIVES: To identify genetic susceptibility targets for ARDS. METHODS: A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. MEASUREMENTS AND MAIN RESULTS: Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg-/- mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation. CONCLUSIONS: These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.

OBJECTIVE: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration. DESIGN: Retrospective subgroup analysis of randomized controlled trial. SETTING: Multicenter North American and European clinical trial. PATIENTS: Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population. INTERVENTIONS: Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours. MEASUREMENTS AND MAIN RESULTS: We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant. CONCLUSIONS: We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.

Why do we avoid radial procedures?

This meta-analysis of randomized trials demonstrated no statistically significant difference in the incidence of MACE between patients who underwent trans-ulnar or the trans-radial cardiac catheterization. No differences in arterial access time, fluoroscopy time, and contrast load between the two groups.

Fifty Years of Research in ARDS. Genomic Contributions and Opportunities.

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations. More recently, methodologies of causal inference are being applied to maximize the information gained from genetic associations. Although challenges of sample size, both recognized and unrecognized phenotypic heterogeneity, and the paucity of early ARDS lung tissue limit some applications of the rapidly evolving field of genomic investigation, ongoing genetic research offers unique contributions to elucidating ARDS pathogenesis and the paradigm of precision ARDS medicine.

Resistant hypertension in 2017.

PURPOSE OF REVIEW: Hypertension (HTN) is a ubiquitous condition and cause for significant morbidity and mortality. Over 400 000 deaths in the United States are related to HTN every year, more than all the Americans who died through all of World War II. As many as half the patients with HTN in the United States have resistant HTN, a blood pressure greater than 140/90 mmHg despite three medications including a diuretic. It appears that the prevalence of HTN and resistant HTN is increasing over time. There is a dire need for newer therapies that may reduce or eliminate the need for multiple pharmacologic agents, thus helping with compliance and reducing the possibility of their adverse events. RECENT FINDINGS: The current review summarizes the techniques and results reported in recent studies utilizing renal denervation technologies from the original Symplicity Trials to newer multipolar electrodes being used for optimal denervation. We also report the early experience with noninvasive renal denervation. Endovascular carotid body stimulation is also being investigated for resistant HTN. Renovascular HTN remains an underlying cause for resistant HTN, and revascularization may prove to be an effective treatment for many of these patients. SUMMARY: A multipronged approach utilizing lifestyle modification, pharmacologic therapy and tailored endovascular treatments may be the algorithm to treat the growing cohort of resistant HTN. However, most of the endovascular treatments remain to be validated, and renal revascularization for renovascular HTN has been set back by recent studies that did not appear to target the real renovascular cohort.