The role of endothelial shear stress on haemodynamics, inflammation, coagulation and glycocalyx during sepsis.

Sepsis is a multifactorial syndrome primarily determined by the host response to an invading pathogen. It is common, with over 48 million cases worldwide in 2017, and often lethal. The sequence of events in sepsis begins with the damage of endothelium within the microvasculature, as a consequence of the inflammatory and coagulopathic responses to the pathogen that can progress to multiple organ failure and death.

Fluid management in Acute Respiratory Distress Syndrome: A narrative review.

Acute Respiratory Distress Syndrome remains a major source of morbidity and mortality in the modern intensive care unit (ICU). Major advances in the understanding and management of this condition were made in the last two decades. The use of low tidal ventilation is a well-established therapy.

Supportive management strategies for disseminated intravascular coagulation. An international consensus.

The cornerstone of the management of disseminated intravascular coagulation (DIC) is the treatment of the underlying condition triggering the coagulopathy. However, a number of uncertainties remain over the optimal supportive treatment. The aim of this study was to provide evidence and expert-based recommendations on the optimal supportive haemostatic and antithrombotic treatment strategies for patients with DIC.

Complement inhibition decreases early fibrogenic events in the lung of septic baboons.

Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents.

Anticoagulant modulation of inflammation in severe sepsis.

Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed.

Acute lung injury and fibrosis in a baboon model of Escherichia coli sepsis.

Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS.

Bronchial responsiveness in patients with restrictive spirometry.

Background: Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect.

Iloprost improves gas exchange in patients with pulmonary hypertension and ARDS.

Objective: We hypothesized that nebulized iloprost would improve ventilation-perfusion matching in patients with pulmonary hypertension and ARDS as reflected by an improved Pao2/Fio2 ratio and Pao2 without adversely affecting lung mechanics or systemic hemodynamics.

Methods: Patients with ARDS and pulmonary hypertension were enrolled. With constant ventilator settings, hemodynamics, airway pressures, and gas exchange measured at baseline were compared with values 30 min after administration of 10 μg nebulized iloprost, and again 30 min after a second, larger, 20 μg dose of iloprost, and then a final measurement 2 h after the second dose.

Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients.

Background: Despite the lack of randomized trials, nebulized Dornase alpha and hypertonic saline are used empirically to treat atelectasis in mechanically ventilated patients. Our objective was to determine the clinical and radiological efficacy of these medications as an adjunct to standard therapy in critically ill patients.

Methods: Mechanically ventilated patients with new onset (<48 h) lobar or multilobar atelectasis were randomized into three groups: nebulized Dornase alpha, hypertonic (7%) saline or normal saline every 12 h.

Pathophysiology, staging and therapy of severe sepsis in baboon models.

We review our baboon models of Escherichia coli sepsis that mimic, respectively, the shock/disseminated intravascular coagulation (DIC) and organ failure variants of severe sepsis, and analyse the pathophysiologic processes that are unique to each. The multi-stage, multi-factorial characteristics of severe sepsis develop as a result of the initial insult, which - depending on its intensity - activates components of the intravascular compartment leading to overwhelming shock/DIC; or initiates a sequence of events involving both the intra- and extravascular (tissues) compartments that lead to organ failure. In the latter case, the disorder passes through two stages: an initial inflammatory/coagulopathic intravascular first stage triggered by E.

Early anion gap metabolic acidosis in acetaminophen overdose.

Purpose: The study aimed to determine the incidence and clinical significance of early high (>15 mEq/L) anion gap metabolic acidosis in acetaminophen (APAP) overdose.

Methods: A retrospective review of a cohort of 74 patients presenting within 24 hours of APAP overdose was conducted.

Results: Early high anion gap metabolic acidosis was present in 41% of patients on admission and persisted for 1.

Optical coherence tomography as an adjunct to flexible bronchoscopy in the diagnosis of lung cancer: a pilot study.

Unlabelled: Lung cancer is the leading cause of cancer-related deaths in the United States and the second most common type of cancer in both men and women. Optical coherence tomography (OCT) scanning can generate high-resolution cross-sectional images of complex, living tissues in real time. The objectives of this study were to determine the feasibility of using OCT imaging during flexible bronchoscopy and to preliminarily assess the ability of OCT imaging to distinguish an endobronchial malignancy from normal endobronchial mucosa.

Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis.

Severe sepsis leads to massive activation of coagulation and complement cascades that could contribute to multiple organ failure and death. To investigate the role of the complement and its crosstalk with the hemostatic system in the pathophysiology and therapeutics of sepsis, we have used a potent inhibitor (compstatin) administered early or late after Escherichia coli challenge in a baboon model of sepsis-induced multiple organ failure. Compstatin infusion inhibited sepsis-induced blood and tissue biomarkers of complement activation, reduced leucopenia and thrombocytopenia, and lowered the accumulation of macrophages and platelets in organs.

Troponin-I as a prognosticator of mortality in severe sepsis patients.

Purpose: The purpose of this retrospective study was to evaluate cardiac troponin-I (cTnI) as a 28-day mortality prognosticator and predictor for a drotrecogin alfa (activated) (DrotAA) survival benefit in recombinant human activated Protein C Worldwide Evaluation in Severe Sepsis patients.

Methods: Cardiac troponin-I was measured using the Access AccuTnI Troponin I assay (Beckman Coulter, Fullerton, CA). There were 598 patients (305 DrotAA, 293 placebo) with baseline cTnI data (cTnI negative [<0.

Tracheal and endobronchial involvement in disseminated histoplasmosis: a case report.

Histoplasmosis is an endemic fungal infection that can involve any organ when disseminated. Although oral, pharyngeal, laryngeal, and endobronchial involvement have been described, direct tracheal involvement has not been reported. We describe the first case of disseminated histoplasmosis with direct involvement of the trachea.

Effects of nocturnal continuous positive airway pressure therapy in patients with resistant hypertension and obstructive sleep apnea.

Study Objective: To examine the long-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) in patients with obstructive sleep apnea and resistant hypertension.

Methods: Study subjects were 98 patients with obstructive sleep apnea syndrome and hypertension who had 3 or more documented daytime BP measurements taken within 3 months of enrollment and every 3 months after CPAP initiation for 1 year. Resistant hypertension was defined as daytime BP of at least 140 mm Hg systolic or 90 mm Hg diastolic, despite the use of 3 or more antihypertensive medications.

Prosthetic valve endocarditis caused by Candida lusitaniae, an uncommon pathogen: a case report.

Introduction: Candida lusitaniae was originally described as a human pathogen in 1979 and typically affects immunocompromised patients.

Case Presentation: We describe a case of prosthetic valve endocarditis with Candida lusitaniae in an immunocompetent 62-year-old woman following aortic valve replacement. In vitro testing demonstrated that our isolate was sensitive to amphotericin B, caspofungin and fluconazole.

Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease.

Background: Nonselective systemic vasodilators worsen ventilation perfusion (V/Q) matching and gas exchange in patients with chronic obstructive pulmonary disease (COPD). Inhaled iloprost has the potential to act preferentially in ventilated regions of the lung, thereby reducing pulmonary hypertension (PH) while alveolar ventilation is still maintained.

Objectives: To investigate the acute effects of inhaled iloprost on V/Q matching in patients with COPD and PH.

Early administration of high-dose antithrombin in severe sepsis: single center results from the KyberSept-trial.

Background: The overall finding in the KyberSept trial of no treatment effect of high-dose antithrombin (AT) in severe sepsis was inconsistent for the primary outcome, 28-day mortality, possibly because of patient heterogeneity. No data have been reported on the effects of AT therapy administered early in severe sepsis when microcirculation is disturbed but irreversible organ damage has not yet developed.

Objective: We report the post hoc results of the KyberSept trial in patients with severe sepsis treated at a single center early after new onset organ failure.

Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock.

Objective: To assess the safety and efficacy of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene (PHP), in patients with distributive shock.

Design: Phase II multicenter, randomized (1:1), placebo-controlled study.

Setting: Fifteen intensive care units in North America.