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Background: There are limited data on outcomes of older patients with chronic diseases. Skeletal muscle loss of aging (primary sarcopenia) has been extensively studied but the impact of secondary sarcopenia of chronic disease is not as well evaluated. Older patients with chronic diseases have both primary and secondary sarcopenia that we term compound sarcopenia. We evaluated the clinical impact of compound sarcopenia in hospitalized patients with cirrhosis given the increasing number of patients and high prevalence of sarcopenia in these patients. Design: The Nationwide Inpatients Sample (NIS) database (years 2010–2014) was analyzed to study older patients with cirrhosis. Since there is no universal hospital diagnosis code for “muscle loss”, we used a comprehensive array of codes for “muscle loss phenotype” in the international classification of diseases-9 (ICD-9). A randomly selected 2% sample of hospitalized general medical population (GMP) and inpatients with cirrhosis were stratified into 3 age groups based on age-related changes in muscle mass. In-hospital mortality, length of stay (LoS), cost of hospitalization (CoH), comorbidities and discharge disposition were analyzed. Results. Of 517,605 hospitalizations for GMP and 106,835 hospitalizations for treatment of cirrhosis or a cirrhosis-related complication, 207,266 (40.4%) GMP and 29,018 (27.7%) patients with cirrhosis were >65 years old, respectively. Muscle loss phenotype in both GMP and inpatients with cirrhosis 51–65 years old and >65 years old was significantly (p < 0.001 for all) associated with higher mortality, LoS, and CoH compared to those ≤50 years old. Patients >65 years old with cirrhosis and muscle loss phenotype had higher mortality (adjusted OR: 1.06, 95% CI [1.04, 1.08] and CoH (adjusted odds ratio (OR): 1.10, 95% confidence interval (CI) [1.04, 1.08])) when compared to >65 years old GMP with muscle loss phenotype. Muscle loss in younger patients with cirrhosis (≤50 years old) was associated with worse outcomes compared to GMP >65 years old. Non-home discharges (nursing, skilled, long-term care) were more frequent with increasing age to a greater extent in patients with cirrhosis with muscle loss phenotype for each age stratum. Conclusion: Muscle loss is more frequent in older patients with cirrhosis than younger patients with cirrhosis and older GMP. Younger patients with cirrhosis had clinical outcomes similar to those of older GMP, suggesting an accelerated senescence in cirrhosis. Compound sarcopenia in older patients with cirrhosis is associated with higher inpatient mortality, increased LoS, and CoH compared to GMP with sarcopenia.

Background. Hyaluronan (HA) is a naturally occurring glycosaminoglycan polymer produced in all vertebrates, and usually present at the high molecular weight (>106 Da). Low molecular weight HA has signaling properties, and fragments ~35 kDa size (HA35) have biological activity in eliciting epithelial β-defensins and tight junction proteins, notably ZO1, important components of innate host defense arsenal of the gut barrier in preclinical models. Safety, tolerability, impact on metabolism, gut permeability, and microbiome composition in healthy human subjects were all evaluated prospectively. Methods. Pharmaceutical grade HA35 (140 mg in water once daily for seven days), was administered orally to 20 healthy subjects (30.7 ± 5.6 years). Demographical, clinical, biochemical laboratory tests, metabolic function and stool microbiome composition were measured on Day 0, 8 and 28. Results. HA35 was tolerated well in all subjects with no serious adverse events in any subjects. No statistical differences in any of the measurements were seen among the study group over the course of the trial. In aggregate there were no changes in demographical, clinical, biochemical laboratory tests, and metabolic function or microbiome composition during the 28-day study. Conclusion. Oral HA35 administration (140 mg/day) is a safe treatment in healthy individuals and does not affect metabolic, inflammatory or microbiome parameters.