Search

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published

Wolfgang Domej,1 Karl Oettl,2 Wilfried Renner31Division of Pulmonology, Department of Internal Medicine, 2Institute of Physiological Chemistry, 3Clinical Institute of Medical and Chemical Diagnostics, Medical University of Graz, Graz, AustriaAbstract: Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.Keywords: reactive oxygen species, reactive nitrogen species, chronic obstructive pulmonary disease, antioxidants

[for full text, please go to the a.m. URL], 17. Grazer Konferenz – Qualität der Lehre 2013: Teaching medical skills

Question: The question how much and what kind of chemistry is necessary and good for a medical curriculum is a matter of controversy and depends on the premedical education [ref:1], [ref:2], [ref:3]. A problem in the first year of education is the low acceptance of basi[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

[for full text, please go to the a.m. URL], 14. Grazer Konferenz – Qualität der Lehre: New Horizons in Teaching and Learning

The objective of this thesis is to provide a comprehensive analysis of the issues surrounding the use of performance-based payments as a form of contract financing and to determine the major reasons why PBP have not been readily adopted in Department of Defense (DoD) contracts. In order to fully research, analyze, and evaluate the issues surrounding PBP and the reasons why they have not been readily adopted, two separate online surveys were developed and distributed. One survey was disseminated to DoD acquisition workforce personnel such as contracting officers and program managers. The second survey was distributed to contracting, program management, and acquisition personnel within the defense industrial base. Additionally, interviews were conducted with DoD personnel and defense contractors involved with PBP. Analysis led to concluding: training in PBP is inadequate, a lack of coordination exists between the Procuring Contracting Officer (PCO) and Administrative Contracting Officer (ACO) in establishing PBP terms, the PBP payment process needs immediate improvement, and a culture change is still needed with DoD. Recommendations to expand the use of PBP are: develop a comprehensive training program on PBP, encourage the use of Integrated Product Teams (IPTs) in the PBP process, improve the payment process for PBP, and continue the strong push for the expansion of PBP usage. http://archive.org/details/performancebased109455880 US Navy (USN) author

Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine, SCOPUS: ar.j, info:eu-repo/semantics/published

UNLABELLED: Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD.CONCLUSION: These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).