Primary Prevention of Bleeding from Oesophageal Varices

Variceal bleeding is the most serious complication of patients with cirrhosis and portal hypertension. Mortality related to variceal bleeding has been falling in recent years but is still considered among the leading causes of death in these patients. Therefore, the issue of primary prophylaxis of variceal bleeding is an important one. In the pre-primary prophylaxis setting (prevention of formation/growth of varices) all cirrhotics should be screened for varices at diagnosis although there is no currently indication for treating patients in order to prevent the formation of varices. Areas requiring further study include the natural history of low-risk varices and treatment possibilities for the decrease or the prevention of the development and/or the progression of varices. Patients with small varices could be treated with beta-blockers, which have been proved effective in reducing the risk of first variceal bleeding in patients with medium and large oesophageal varices. Endoscopic band ligation seems to be more effective in recent trials, but concerns have been raised regarding its safety. Further, studies are required to clarify whether the use of the combination of band ligation and beta-blockers is better than each treatment alone. The future aim is to improve current medical therapy taking into consideration the cost-effectiveness and the quality of life

The Impact of Host Metabolic Factors on Treatment Outcome in Chronic Hepatitis C

Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P = 0.003) and histological evidence of advanced fibrosis (P < 0.001). Older age (OR 2.51, P = 0.002), genotype (OR 3.28, P < 0.001), cirrhosis (OR 4.23, P = 0.005), and hepatic steatosis (OR 2.48, P = 0.001) were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related

The effect of critical incident debriefing in the emergency department

Session E presented Friday, September 28, 10:00-11:00 am Purpose: Emergency Department (ED) nurses and other staff can feel stressed after critical incidents such as the death of a patient, a violent event, or a medical error. This stress can lead to professional burnout and a decreased sense of personal well-being. Although debriefing sessions are widely recommended as a means of helping caregivers manage stress from critical incidents, there is very little evidence of the impact on job satisfaction and burnout. The objective of this study was to examine the effect of real-time critical incident debriefing on compassion satisfaction, burnout, and secondary traumatic stress in ED staff. Design: This project was an IRB-approved quasi-experimental research study. The Professional Quality of Life (ProQOL) scale was used to measure compassion satisfaction, burnout, and secondary traumatic stress. Setting: This study took place in an urban academic Emergency Department with 37,000 annual patient visits. Participants/Subjects: A convenience sample of ED nurses, patient care technicians, and providers was used. Key inclusion criteria included part-time or full-time employment at the ED in which the study was being performed. Per diem employees and those staff members who did not fall into the above job classifications were excluded. Study participants were provided a letter describing the study and the potential risks and benefits and written consent was obtained. To protect human subjects, study data was presented in aggregate and no individual responses or identifying information was recorded. Methods: Ten ED charge nurses were identified and specially trained to lead structured real-time debriefings using a critical incident debriefing tool after a predetermined critical incident occurred. All staff members who were directly involved in the incident and/or who self-identified as being emotionally affected by the incident were strongly encouraged to participate. Each debriefing followed a standardized format. The charge nurse led the debriefing within thirty minutes of the event, elicited input from the participants regarding emotion well-being, and provided support and resources in real-time. Study participants received an e-mail containing a link to complete the ProQOL Scale both pre- and post-intervention. Results/Outcomes: Pre and post-ProQOL survey responses were analyzed using a paired t-test. Preliminary analysis revealed no statistically significant effects on compassion satisfaction, burnout, or secondary traumatic stress, but anecdotal reports from participants were positive. Study limitations included a small sample size and an inconsistent dose of the intervention. Further data analysis is ongoing. Implications: Emergency Department caregivers are routinely exposed to potentially emotionally traumatic events, and leaders have the obligation to promote a healthy working environment that ensures the well-being of their teams. While there are many qualitative studies published on the effectiveness of debriefing on stress management, there is a scarcity of quantitative data that captures the value of debriefing after critical events. This study offered an opportunity to both track critical incidents and help caregivers manage stress from critical incidents in real time. Further data analysis will provide insight into the effect of debriefing on compassion satisfaction, burnout, and secondary traumatic stress. This study can easily be replicated in Emergency Departments nationwide to support ED staff after critical incidents have occurred

Exploring the role of IL-1β in inflammatory bowel disease pathogenesis

Interleukin 1β (IL-1β) is a significant mediator of inflammation and tissue damage in IBD. The balance between IL-1β and its endogenous inhibitor-IL-1Ra-, plays a critical role in both initiation and regulation of inflammation. However, the precise role of IL-1β as a causative factor in IBD or simply a consequence of inflammation remains unclear. This review summarizes current knowledge on the molecular and cellular characteristics of IL-1β, describes the existing evidence on the role of this cytokine as a modulator of intestinal homeostasis and an activator of inflammatory responses, and also discusses the role of microRNAs in the regulation of IL-1β-related inflammatory responses in IBD. Current evidence indicates that IL-1β is involved in several aspects during IBD as it greatly contributes to the induction of pro-inflammatory responses through the recruitment and activation of immune cells to the gut mucosa. In parallel, IL-1β is involved in the intestinal barrier disruption and modulates the differentiation and function of T helper (Th) cells by activating the Th17 cell differentiation, known to be involved in the pathogenesis of IBD. Dysbiosis in the gut can also stimulate immune cells to release IL-1β, which, in turn, promotes inflammation. Lastly, increasing evidence pinpoints the central role of miRNAs involvement in IL-1β-related signaling during IBD, particularly in the maintenance of homeostasis within the intestinal epithelium. In conclusion, given the crucial role of IL-1β in the promotion of inflammation and immune responses in IBD, the targeting of this cytokine or its receptors represents a promising therapeutic approach. Further research into the IL-1β-associated post-transcriptional modifications may elucidate the intricate role of this cytokine in immunomodulation

Spontaneous Cirrhosis Regression in an IFN-beta-induced AIH-like Syndrome Following Drug Withdrawal: Art of Facts or Artifacts?

Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) administration for multiple sclerosis (MS). Based on liver autoimmune serology, histology and appropriate exclusion of other liver diseases, a diagnosis of AIH-related cirrhosis was established. Following discontinuation of IFNβ-1b, a complete resolution of biochemical activity indices was observed and the patient remained untreated on her own decision. However, 3 years later, after a course of intravenous methylprednisolone for MS, a new acute transaminase flare was recorded which subsided again spontaneously after 3 weeks. Liver biopsy and elastography showed significant fibrosis regression (F2 fibrosis). To our knowledge, this is the first report showing spontaneous cirrhosis regression in an IFNβ-1b-induced AIH-like syndrome following drug withdrawal, suggesting that cirrhosis might be reversible if the offending fibrogenic stimulus is withdrawn

NAFLD and HBV interplay - related mechanisms underlying liver disease progression

Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets

Characterization of FGFR Alterations and Activation in Patients with High-Risk Non–Muscle-Invasive Bladder Cancer

Purpose:The Genomic Analysis of High-Risk Non–Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette–Guérin (BCG) treatment in high-risk non–muscle-invasive bladder cancer (HR-NMIBC). An FGFR predictive response signature (FGFR-PRS) was discovered that identifies patients with an activated FGFR pathway who could potentially benefit from FGFR-targeted therapy beyond those who are FGFR ALT (+).Experimental Design:Pretreatment tumor samples and clinical data were analyzed from 582 BCG-treated patients with HR-NMIBC. FGFR-PRS was discovered using a separate bladder cancer dataset and applied to the GARNER and other bladder cancer cohorts. FGFR-PRS was also applied to in vitro data from urothelial cancer cell lines treated with FGFR-active agents.Results:A total of 31% of pretreatment GARNER HR-NMIBC tumors were FGFR ALT (+), but this was not significantly associated with BCG response. For the subset of patients with paired pre- and post-BCG treatment samples, nearly one-third of pretreatment ALT (+) patients were ALT (−) posttreatment. FGFR-PRS identified patients with an activated FGFR pathway and identified approximately twofold additional patients compared with ALT status alone, and this increase was similar across tumor stage. A positive relationship between tumor growth inhibition and FGFR-PRS score was shown in bladder cancer in vitro models treated with FGFR-active agents.Conclusions:These data provide support for FGFR-targeted therapy use in FGFR ALT (+) HR-NMIBC and describe tumors with shared FGFR pathway–activated biology that is FGFR ALT (−) but FGFR-PRS (+). The latter suggests a broader potential patient population for FGFR-targeted therapy, which will require subsequent validation in patients treated with FGFR-targeted therapy.<p/