OBJECTIVES:Exercise has been scarcely studied in patients with cirrhosis, and prior evidence showed hepatic venous pressure gradient (HVPG) to be increased in response to exercise. The aim of this study was to investigate the effects of a supervised physical exercise program (PEP) in patients with cirrhosis.METHODS:In an open-label, pilot clinical trial, patients with cirrhosis were randomized to PEP (cycloergometry/kinesiotherapy plus nutritional therapy, n=14) or control (nutritional therapy, n=15); for 14 weeks. Primary outcomes were: the effect of PEP in HVPG, and quality of life (chronic liver disease questionnaire, CLDQ). As secondary outcomes we investigated changes in physical fitness (cardiopulmonary exercise testing), nutritional status (phase angle—bioelectrical impedance), ammonia levels, and safety.RESULTS:Twenty-two patients completed the study (11 each). HVPG decreased in subjects allocated to PEP (−2.5 mm Hg (interquartile range: −5.25 to 2); P=0.05), and increased in controls (4 mm Hg (0–5); P=0.039), with a significant between-groups difference (P=0.009). No major changes were noted in CLDQ in both groups. There was significant improvement in ventilatory efficiency (VE/VCO2) in PEP group (−1.9 (−3.12 to −0.1); P=0.033), but not in controls (−0.4 (−5.7 to 1.4); P=0.467). Phase angle improvement and a less-pronounced exercise-induced hyperammonemia were noted only in PEP group. No episodes of variceal bleeding or hepatic encephalopathy were observed.CONCLUSIONS:A supervised PEP in patients with cirrhosis decreases the HVPG and improves nutritional status with no changes in quality of life. Further studies evaluating physical training in cirrhosis are eagerly awaited in order to better define the benefits of sustained exercise. ClinicalTrials.gov:NCT00517738.

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Background: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. Methods: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. Results: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44–64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24–0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). Conclusion: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Primary PTCA has been shown to be superior to any thrombolytic regimen and offers higher reperfusion rates and better coronary flow grades. Its limitations include recurrent ischemia (10%-15%), infarct-related artery reocclusion (5%-10%), angiographic restenosis (35%-50%), and need to perform repeat PTCA or CABG at 6-month follow-up (20%). Thus, the current role of coronary stenting for acute myocardial infarction (AMI) is very promising. From December 1995 through January 1997, 335 patients underwent primary angioplasty during the first 12 hr from symptom onset at our institution. We performed a retrospective study comparing the in-hospital and 6-month follow-up outcome of 61 patients who underwent coronary stenting (stent group) against 61 patients with optimal (residual lesion stenosis < 30%) balloon-only primary angioplasty (stent-like group). Patients were routinely treated with aspirin, and ticlopidine was given only to the stent group. In-hospital major adverse cardiac events (MACE) rate was 11.5% without statistical differences between the groups. Cardiac death rate was similar in both groups (4.9 vs. 6.6%; P = 1.0) and only two (3.3%) patients from the stent group and none from the PTCA group had nonfatal myocardial reinfarction. At 6-month follow-up, the rate of recurrent angina was higher in the stent-like group (30.9 vs. 7.1%; P < 0.001). Multivariate analysis showed that only stenting of the infarct-related artery was a borderline independent predictor for MACE (OR = 0; 95% CI = 0-1; P = 0.057). Primary stenting for AMI reduces the rate of recurrent angina or symptoms and MACE at 6-month follow-up.