High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

BACKGROUND: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Phlegmasia cerulea dolens superimposed on disseminated intravascular coagulation in COVID-19.

COVID-19 infection has several cardiovascular implications, and coagulopathy is a common abnormality in these patients, often coupled with elevated plasma fibrinogen and D-dimer levels, contributing to adverse outcomes. Phlegmasia cerulea dolens (PCD) is a rare manifestation of deep vein thrombosis. It is life-threatening and can rapidly lead to venous gangrene of the extremity. Only a few cases of COVID-19 associated with PCD are reported in the literature, despite thromboembolism being the common paradigm between the two diseases. We present the case of a 64-year-old adult with acute severe COVID-19 pneumonia who developed PCD despite constantly elevated activated partial thromboplastin time and international normalized ratio.

Thoracic ultrasound evaluation and B-type natriuretic peptide value in elective cesarean section under spinal anesthesia.

BACKGROUND: Pregnancy-induced changes in cardiovascular status make women more susceptible to pulmonary edema. During cesarean section, to counterbalance the effect of hypotension caused by spinal anesthesia, anesthesiologists must choose between two fundamental approaches to maintain the hemodynamic state-intravenous fluids or vasopressors-and this choice will depend upon their particular opinions and experience. We aim to assess for any correlations between thoracic ultrasound A- and B-line artifacts, brain natriuretic peptide (BNP) levels, and the amount of intraoperative fluids administered. RESULTS: From December 2016 to August 2018, at the University-Hospital of Udine, we enrolled 80 consecutive pregnant women undergoing cesarean section. We observed a statistically significant difference in the volume of fluids administered in the first 24 h (p = 0.035) between the patients presenting B-lines in at least one basal area of their thoracic ultrasound and patients with no evident B-lines (AUC 66.4%; IC 0.49-0.83). Dividing the population on whether their BNP levels were higher or less than 20 pg/mL, no statistically significant difference was revealed with regard to fluids administered in the first 24 h (p = 0.537). CONCLUSIONS: Thoracic ultrasound is a non-invasive and easy-to-use tool for detecting fluid intolerance in pregnant women undergoing cesarean section. BNP levels were slow to rise following the cesarean section and did not show any clear correlation with fluid volumes administered.

Comparison of Patient Characteristics and Course of Hypertensive Hypokinetic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy.

Hypertensive hypokinetic cardiomyopathy (HHC) is defined by left ventricular (LV) systolic dysfunction with a history of systemic hypertension as the only possible cause. Although commonly encountered in clinical practice, its characterization and differences with true idiopathic dilated cardiomyopathy (IDC) are lacking. The aim of this study was to characterize the clinical instrumental features and the natural history of HHC. We analyzed the data of 4,191 patients referred to our center for newly diagnosed LV systolic dysfunction from 2005 to 2010. Of them, 310 presented idiopathic LV systolic dysfunction (LV ejection fraction <50%): 136 (44%) had a history of systemic hypertension and were defined HHC. The remaining 174 patients were considered IDC. Compared with patients with IDC, those with HHC were older (63 ± 11 vs 47 ± 14 years, p <0.001), with worse comorbidity profile, higher blood pressure, and increased LV mass. During follow-up, patients with HHC showed earlier and higher proportion of LV reverse remodeling (46% vs 21% at 6 months' follow-up). Moreover, they had a better long-term survival free from cardiovascular death/ventricular assist device/heart transplant/malignant ventricular arrhythmias (5.1 vs 12.6 in HHC and IDC, p = 0.03). Indeed, their mortality was mainly driven by noncardiovascular causes (at 10 years 9.6% vs 1.7% in HHC and IDC, p <0.001). In conclusion, HHC has a high prevalence among patients with "idiopathic" LV dysfunction. The natural history of patients with HHC is characterized by a rapid response to optimal therapy for heart failure, a favorable cardiovascular outcome, and a relevant incidence of noncardiovascular events.

U-shaped relationship between vitamin D levels and long-term outcome in large cohort of survivors of acute myocardial infarction.

BACKGROUND: Previous studies in the setting of patients with acute myocardial infarction (AMI) have demonstrated that hypovitaminosis D is associated with increased mortality risk during a follow-up whose median did not exceed two years. OBJECTIVE: To evaluate the impact of vitamin D levels on long-term mortality in patients with AMI. RESULTS: In our study 477 patients with AMI were included. During a median follow-up period of 57 (IQR 53-64) months, 93 patients (20%) died. A non-linear U-shaped relationship between 25(OH)D levels and long-term mortality was observed; patients with vitamin D<10ng/mL and >30ng/mL had higher mortality rate than those with intermediate values. After adjustment for differences in baseline features and treatment, it was confirmed that extreme values of vitamin D (<10 or >30ng/mL) are independent predictors of mortality with HR of 3.02 (95% CI 1.78-5.11). Other independent predictors of outcome were age, NYHA class at discharge, treatment with ACE inhibitors and statins. The estimated time-dependent ROC curve of the multivariable model including vitamin D showed an AUC significantly higher than the model without vitamin D: AUC 0.82 (95% CI 0.76-0.87) vs. 0.77 (95% CI 0.71-0.83), p=0.005. Addition of vitamin D to the model that included all significant factors for mortality improved the prognostic accuracy as showed by the metrics of reclassification (NRI 0.34 (95% CI 0.14-0.48), p=0.003 and IDI 0.06 (95% CI 0.01-0.12, p=0.005 p=0.03). CONCLUSIONS: We report a U-shaped relationship between vitamin D levels and long-term outcome of patients surviving AMI.