Kidney Blood Flow and Renin-Angiotensin-Aldosterone System Measurements Associated With Kidney and Cardiovascular Dysfunction in Pediatric Shock.

Importance: Pediatric acute kidney injury (AKI) is a prevalent and morbid complication of shock. Its pathogenesis and early identification remain elusive.

Objectives: We aim to determine whether renal blood flow (RBF) measurements by point-of-care ultrasound (POCUS) and renin-angiotensin-aldosterone system (RAAS) hormones in pediatric shock associate with vasoactive requirements and AKI.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

Background: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock.

Methods: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB.

Dysfunction of the renin-angiotensin-aldosterone system in human septic shock.

Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management.

Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock.

Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS.

Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial.

Effect of Automated Real-Time Feedback on Early-Sepsis Care: A Pragmatic Clinical Trial.

Objectives: To determine if a real-time monitoring system with automated clinician alerts improves 3-hour sepsis bundle adherence.

Design: Prospective, pragmatic clinical trial. Allocation alternated every 7 days.

Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model.

Sepsis, defined as organ dysfunction caused by a dysregulated host-response to infection, is characterized by immunosuppression. The vasopressor norepinephrine is widely used to treat low blood pressure in sepsis but exacerbates immunosuppression. An alternative vasopressor is angiotensin-II, a peptide hormone of the renin-angiotensin system (RAS), which displays complex immunomodulatory properties that remain unexplored in severe infection.

T cell activation and IFNγ modulate organ dysfunction in LPS-mediated inflammation.

LPS challenge is used to model inflammation-induced organ dysfunction. The effects of T cell activation on LPS-mediated organ dysfunction and immune responses are unknown. We studied these interactions through in vivo administration of anti-CD3ε (CD3) T cell activating antibody and LPS.

Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.

Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation.

Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes.

The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded.

Physiologic Response to Angiotensin II Treatment for Coronavirus Disease 2019-Induced Vasodilatory Shock: A Retrospective Matched Cohort Study.

Objectives: To assess the early physiologic response to angiotensin-II treatment in patients with coronavirus disease 2019-induced respiratory failure and distributive shock.

Design: Retrospective consecutive-sample cohort study.

Setting: Three medical ICUs in New York during the coronavirus disease 2019 outbreak.

Inhibition of Angiotensin Converting Enzyme Impairs Anti-staphylococcal Immune Function in a Preclinical Model of Implant Infection.

Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery.

General and Intensive Care Outcomes for Hospitalized Patients With Solid Organ Transplants With COVID-19.

Purpose: COVID-19 has been associated with a dysregulated inflammatory response. Patients who have received solid-organ transplants are more susceptible to infections in general due to the use of immunosuppressants. We investigated factors associated with mechanical ventilation and outcomes in solid-organ transplant recipients with COVID-19.

Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury.

In sepsis-induced acute kidney injury, kidney blood flow may increase despite decreased glomerular filtration. Normally, angiotensin-II reduces kidney blood flow to maintain filtration. We hypothesized that sepsis reduces angiotensin type-1 receptor (AT1R) expression to account for this observation and tested this hypothesis in a patient case-control study and studies in mice.

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference.

Use of Organ Dysfunction as a Primary Outcome Variable Following Cecal Ligation and Puncture: Recommendations for Future Studies.

Outcomes variables for research on sepsis have centered on mortality and changes in the host immune response. However, a recent task force (Sepsis-3) revised the definition of sepsis to "life-threatening organ dysfunction caused by a dysregulated host response to infection." This new definition suggests that human studies should focus on organ dysfunction.

Sepsis Presenting in Hospitals versus Emergency Departments: Demographic, Resuscitation, and Outcome Patterns in a Multicenter Retrospective Cohort.

Background: Differences between hospital-presenting sepsis (HPS) and emergency department-presenting sepsis (EDPS) are not well described.

Objectives: We aimed to (1) quantify the prevalence of HPS versus EDPS cases and outcomes; (2) compare HPS versus EDPS characteristics at presentation; (3) compare HPS versus EDPS in process and patient outcomes; and (4) estimate risk differences in patient outcomes attributable to initial resuscitation disparities.

Design: Retrospective consecutive-sample cohort.