Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function.

Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 ± 35.8 vs. 115.6 ± 79.3 pg/ml P < 0.0001) and controls (pre 29.9 ± 14.5 vs. 116.0 ± 74.0 pg/ml, P = 0.001). A significant microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P < 0.0001). Relative Streptococcaceae abundance, normally abundant in saliva, significantly increased postomeprazole in controls (1 vs. 5%) and cirrhosis (0 vs. 9%) and was correlated with serum gastrin levels (r = 0.4, P = 0.005). We found significantly reduced hippurate in cirrhosis vs. controls both pre- and postomeprazole and increased lactate in both groups post vs. preomeprazole, whereas dimethylamine (DMA) decreased in cirrhosis only. On correlation network analysis, significant changes in linkages of bacteria with metabolites (hippurate/DMA/lactate) were found postomeprazole, compared with pre-PPI in cirrhosis patients. In conclusion, omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth.

Use of point-of-care ultrasound in the management of patients presenting with shock: the treatment implications of an early bedside diagnosis of pulmonary embolism.

Point-of-care ultrasound has been used to identify real-time indicators of acute obstruction to right ventricular outflow and aid appropriate diagnosis and management of patients presenting with extensive pulmonary embolism in whom haemodynamic instability permits only bedside investigation. We present the case of a 70-year-old woman who presented with shock. A focused bedside echocardiography was performed and showed left ventricular septal wall flattening and a severely dilated right ventricle with impaired systolic function. The right atrium was dilated with a floating thrombus visible on the sub-xiphoid view. The patient was treated with intravenous systemic thrombolysis (alteplase) prior to undergoing CT pulmonary angiogram. This showed saddle pulmonary embolus, with extensive thrombus in the main and all lobar pulmonary arteries bilaterally, with evidence of right heart strain.