H epatitis C viral infection is a common cause of chronic liver disease, with a worldwide prevalence of 3%. About 140 million people worldwide and 4 million in the United States are infected with HCV. An estimated 65% to 80% of the individuals infected with HCV develop persistent infection. As many as 20% to 50% of these individuals develop cirrhosis and 5% develop hepatocellular carcinoma. 1,2 The rate of disease progression varies widely, and unknown factors other than alcohol use, obesity, and age may influence the longterm clinical outcome of the disease. In recent years many efforts have been made to identify receptors involved in viral entry into host cells. Two molecules are proposed to function as HCV receptors, namely, the low-density lipoprotein receptor (LDLR) and CD81. [3][4][5] Experiments in vitro showed competitive inhibition of binding between HCV and LDLR by purified LDL. 3 If similar inhibition occurs in vivo, the serum concentration of beta-lipoproteins may influence HCV proliferation because cell infection is required for replication of the virus. 6 Serum HCVAg levels negatively correlated with serum beta-lipoproteins, supporting the concept that LDLR is the HCV receptor and that beta-lipoproteins competitively inhibit infection of hepatocytes with HCV. 6 Additional in vivo evidence has been reported by in situ hybridization studies on keratinocytes obtained from vasculitic lesions of patients with type II cryoglobulinemia. 3 These keratinocytes with upregulation of LDL receptors were found to have the positive HCV RNA strand compared to keratinocytes obtained from normal skin of the same person with low levels of LDL receptors. In those with chronic HCV infection, polymorphisms of the LDLR can influence the severity of fibrosis (single-nucleotide polymorphism [SNP] in exon 8), clearance of virus (SNP in exon 10), Abbreviations: LDLR, low-density lipoprotein receptor; VLDL, very-low-density lipoprotein; HDL, high-density lipoprotein; EVR, early viral response; ETR, endof-treatment response.

ObjectivesAcute kidney injury (AKI) affects up to one-quarter of hospitalised patients and 60% of patients in the intensive care unit (ICU). We aim to understand the baseline characteristics of patients who will develop distinct AKI trajectories, determine the impact of persistent AKI and renal non-recovery on clinical outcomes, resource use, and assess the relative importance of AKI severity, duration and recovery on survival.MethodsIn this retrospective, longitudinal cohort study, 156 699 patients admitted to a quaternary care hospital between January 2012 and August 2019 were staged and classified (no AKI, rapidly reversed AKI, persistent AKI with and without renal recovery). Clinical outcomes, resource use and short-term and long-term survival adjusting for AKI severity were compared among AKI trajectories in all cohort and subcohorts with and without ICU admission.ResultsFifty-eight per cent (31 500/54 212) had AKI that rapidly reversed within 48 hours; among patients with persistent AKI, two-thirds (14 122/22 712) did not have renal recovery by discharge. One-year mortality was significantly higher among patients with persistent AKI (35%, 7856/22 712) than patients with rapidly reversed AKI (15%, 4714/31 500) and no AKI (7%, 22 117/301 466). Persistent AKI without renal recovery was associated with approximately fivefold increased hazard rates compared with no AKI in all cohort and ICU and non-ICU subcohorts, independent of AKI severity.DiscussionAmong hospitalised, ICU and non-ICU patients, persistent AKI and the absence of renal recovery are associated with reduced long-term survival, independent of AKI severity.ConclusionsIt is essential to identify patients at risk of developing persistent AKI and no renal recovery to guide treatment-related decisions.

Background and objectivesIn 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing.Design, setting, participants, & measurementsThis retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration–recommended erythropoietin-stimulating agent labeling for Medicare-insured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006–2010) and postpolicy (2012–2016) implementation using interrupted time series and Cox proportional hazards regression models.ResultsOf 481,564 patients, erythropoietin-stimulating agent use immediately decreased by 84.8 per 1000 persons (P<0.001), with a significant decrease in the slope of the trend line (both P=0.001). Blood transfusion use rapidly increased by 8.34 per 1000 persons in April 2012 and then gradually decreased (both P=0.001). The percentage of patients with hemoglobin >11 g/dl decreased from 68% in January 2006 to 28% in December 2016, whereas those with hemoglobin <9 g/dl increased from 5% to 9%. Overall major adverse cardiovascular event (adjusted hazard ratio, 0.95; 95% confidence interval, 0.94 to 0.96), stroke (adjusted hazard ratio, 0.83; 95% confidence interval, 0.80 to 0.86), all-cause mortality (adjusted hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89), cardiovascular mortality (adjusted hazard ratio, 0.81; 95% confidence interval, 0.79 to 0.83), and heart failure (adjusted hazard ratio, 0.86; 95% confidence interval, 0.84 to 0.88) risks were lower. Acute myocardial infarction risk (adjusted hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.06) was higher after policies changed.ConclusionsThe Medicare reimbursement policy and Food and Drug Administration–recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis.

Introduction: Recurrent Aphthous Stomatitis (RAS) is a common oral mucosal disorder that affects 20% of the population worldwide. Factors such as trauma, stress, genetic, hypersensitivity, nutrition, immune disturbance and hormonal imbalance may disturb the oxidant and antioxidant balance of an organism and precipitate RAS, but the relationships are poorly understood.