Controversy and progress for treatment of acute cholangitis after Tokyo Guidelines (TG13)

Sun, Zhipeng; Zhu, Yubing; Zhu, Bin; Xu, Guangzhong; Zhang, Nengwei

doi:10.5582/bst.2016.01033

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…Current guidelines recommend treatment with third-generation cephalosporins (3GC) or a penicillin/beta-lactamase inhibitor-based agent as first-line options for empiric therapy [15,16], initiated as an intravenous infusion. An early switch to oral therapy was found to be non-inferior compared with continuing intravenous infusion [17].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis

et al. 2017

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BackgroundAcute cholangitis (AC) requires the immediate initiation of antibiotic therapy in addition to treatment for biliary obstruction. Against a background of an increasing prevalence of multi-drug resistant (MDR) bacteria, the risk factors for the failure of empiric therapy must be defined.MethodsUsing a pathogen-based approach, 1764 isolates from positive bile duct cultures were retrospectively analyzed to characterize the respective pathogen spectra in two German tertiary centers. Using a patient-based approach, the clinical and laboratory data for 83 patients with AC were assessed to identify risk factors for AC with pathogens resistant to the applied empiric therapy.ResultsBile cultures were predominantly polymicrobial, and empiric antibiotic therapies did not cover the full biliary pathogen spectrum in 78% of cases. MDR bacteria were isolated from the bile of 24/83 (29%) patients. The univariate risk factors for biliary MDR bacteria were male sex, nosocomial AC, prior antibiotic exposure and prior biliary stenting, of which biliary stenting was the only independent risk factor according to multivariate analysis (OR = 3.8; 95% CI 1.3–11.0, P = 0.013). Although there were no significant differences in survival or hospital stay in AC patients with and without detected biliary MDR pathogens, the former more often had a concomitant bloodstream infection (58% vs. 24%; P = 0.019), including those involving MDR pathogens or fungi (21% vs. 2%; P = 0.007).ConclusionPatients with biliary stents who develop AC should receive empiric therapy covering enterococci and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. These patients are at an increased risk for bloodstream infections by MDR pathogens or fungi.

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Section: Introductionmentioning

confidence: 99%

Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis

et al. 2017

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“…A well-known challenge to studying protein ubiquitination is its heterogeneous nature; when a major ubiquitination site (lysine) is mutated, it is common for nearby lysines to be alternatively targeted (Xu & Jaffrey 2013). In practice, this means that mutating single lysines does not alter ubiquitination, even if the major site is mutated, as alternative sites are targeted.…”

Section: Resultsmentioning

confidence: 99%

MuRF1 mono-ubiquitinates TRα to inhibit T3-induced cardiac hypertrophy in vivo

Wadosky

Berthiaume

Tang

et al. 2016

Journal of Molecular Endocrinology

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Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth and participates in homeostasis of the heart. T3 activates pro-survival pathways including Akt and mTOR. Treatment with T3 after myocardial infarction is cardioprotective and promotes elements of physiological hypertrophic response after cardiac injury. Although T3 is known to benefit the heart, very little about its regulation at the molecular level has been described to date. The ubiquitin proteasome system (UPS) regulates nuclear hormone receptors such as estrogen, progesterone, androgen, and glucocorticoid receptors by both degradatory and non-degradatory mechanisms. However, how the UPS regulates T3-mediated activity is not well understood. In this study, we aim to determine the role of the muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) in regulating T3-induced cardiomyocyte growth. An increase in MuRF1 expression inhibits T3-induced physiological cardiac hypertrophy, whereas a decrease in MuRF1 expression enhances T3’s activity both in vitro and in cardiomyocytes in vivo. MuRF1 interacts directly with TRα to inhibit its activity by posttranslational ubiquitination in a non-canonical manner. We then demonstrated that a nuclear localization apparatus that regulates/inhibits nuclear receptors by sequestering them within a subcompartment of the nucleus was necessary for MuRF1 to inhibit T3 activity. This work implicates a novel mechanism that enhances the beneficial T3 activity specifically within the heart, thereby offering a potential target to enhance cardiac T3 activity in an organ-specific manner.

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“…While not immediately useful in the initial evaluation, blood cultures are positive in up to 70% of patients with cholangitis and may help in severe disease to guide antibiotic therapy once sensitivities are available (2). There is some disagreement concerning the utility of routinely obtaining blood cultures in patients with suspected cholangitis (20,22,23). The Infectious Disease Society of America (IDSA) does not recommend routine collection of blood cultures in mild, community-acquired intra-abdominal infection, but specifies that cultures may be helpful if obtained in septic or toxic-appearing patients (23).…”

Section: Diagnosismentioning

confidence: 99%