Idiopathic cholangiopathy in a biliary cast syndrome necessitating liver transplantation following head trauma

The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.     

Association of hepatitis C infection and acute coronary syndrome: A case-control study

Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45–1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies.     

Tuning the endothelial response: differential release of exocytic cargos from Weibel‐Palade bodies

Essentials

• Endothelial activation initiates multiple processes, including hemostasis and inflammation.
• The molecules that contribute to these processes are co‐stored in secretory granules.
• How can the cells control release of granule content to allow differentiated responses?
• Selected agonists recruit an exocytosis‐linked actin ring to boost release of a subset of cargo.

Summary

Background

Endothelial cells harbor specialized storage organelles, Weibel‐Palade bodies (WPBs). Exocytosis of WPB content into the vascular lumen initiates primary hemostasis, mediated by von Willebrand factor (VWF), and inflammation, mediated by several proteins including P‐selectin. During full fusion, secretion of this large hemostatic protein and smaller pro‐inflammatory proteins are thought to be inextricably linked.

Objective

To determine if secretagogue‐dependent differential release of WPB cargo occurs, and whether this is mediated by the formation of an actomyosin ring during exocytosis.

Methods

We used VWF string analysis, leukocyte rolling assays, ELISA, spinning disk confocal microscopy, high‐throughput confocal microscopy and inhibitor and siRNA treatments to demonstrate the existence of cellular machinery that allows differential release of WPB cargo proteins.

Results

Inhibition of the actomyosin ring differentially effects two processes regulated by WPB exocytosis; it perturbs VWF string formation but has no effect on leukocyte rolling. The efficiency of ring recruitment correlates with VWF release; the ratio of release of VWF to small cargoes decreases when ring recruitment is inhibited. The recruitment of the actin ring is time dependent (fusion events occurring directly after stimulation are less likely to initiate hemostasis than later events) and is activated by protein kinase C (PKC) isoforms.

Conclusions

Secretagogues differentially recruit the actomyosin ring, thus demonstrating one mechanism by which the prothrombotic effect of endothelial activation can be modulated. This potentially limits thrombosis whilst permitting a normal inflammatory response. These results have implications for the assessment of WPB fusion, cargo‐content release and the treatment of patients with von Willebrand disease.

     

Drivers of Inpatient Hospital Experience Using the HCAHPS Survey in a Canadian Setting

ObjectiveTo identify factors associated with patients’ overall rating of inpatient hospital care.ConclusionsOur results are novel in the Canadian population. Several questions for future research have been generated, in addition to opportunities for quality improvement within our own organization.     

Macrolides in cystic fibrosis

Macrolide antibiotics have been licensed since the 1950s and have an important role in the treatment of a diverse range of infectious diseases. Macrolide antibiotics have antibacterial activity against gram-positive bacteria, some gram-negative bacteria and intracellular pathogens. The spectrum of antibacterial activity combined with excellent intracellular and tissue penetration has led to the extensive use of this class of drugs in respiratory disease. Macrolide antibiotics also have demonstrated anti-inflammatory properties in various in vitro and in vivo model systems. Novel antimicrobial and anti-inflammatory properties of macrolide may result in clinical benefits, particularly in conditions where the infectious agent is inherently resistant to macrolides. Three randomized control trials have demonstrated improved lung function in patients treated with the macrolide antibiotic, azithromycin. Azithromycin was generally well tolerated and resulted in reduction in the inflammatory response which may be due to an immunomodulatory role. Short term studies (three to six months) have not demonstrated the development of increased bacterial resistance or the emergence of new pathogens following azithromycin.