scholarly journals Delta-Like Canonical Notch Ligand 1 in Patients Following Liver Transplantation—A Secondary Analysis of a Prospective Cohort Study

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 894
Author(s):  
Sebastian O. Decker ◽  
Dagmar Hildebrand ◽  
Thomas Bruckner ◽  
Christoph Lichtenstern ◽  
Klaus Heeg ◽  
...  

Opportunistic bacterial infections are dreaded risks in patients following liver transplantation (LTX), even though patients receive an antibiotic prophylaxis. The timely recognition of such an infection may be delayed, as culture-based diagnostic methods are linked with a relevant gap in performance. We measured plasma concentrations of Delta-like canonical Notch ligand 1 (DLL1) in 93 adult patients at seven consecutive time points after liver transplantation and correlated the results to the occurrence of culture-proven bacterial infection or a complicated clinical course (composite endpoint of two or more complications: graft rejection or failure, acute kidney failure, acute lung injury, or 90-day mortality). Patients exhibited elevated plasma concentrations after liver transplantation over the whole 28 d observation time. Patients with bacterial infection showed increased DLL1 levels compared to patients without infection. Persistent elevated levels of DLL1 on day 7 and afterward following LTX were able to indicate patients at risk for a complicated course. Plasma levels of DLL1 following LTX may be useful to support an earlier detection of bacterial infections in combination with C-reactive protein (CRP) and procalcitonin (PCT), or they may lead to risk stratification of patients as a single marker for post-operative complications. (Clinical Trial Notation. German Clinical Trials Register: DRKS00005480).

2018 ◽  
Author(s):  
Andres Cardenas ◽  
Isabel Graupera ◽  
Elsa Sola ◽  
Pere Ginès

Cirrhosis is the most advanced stage of all the different types of chronic liver diseases. It is defined as a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Hepatic fibrosis is potentially reversible if the causative agent is removed. However, advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible. Cirrhosis is a progressive and severe clinical condition associated with considerable morbidity and high mortality. It leads to a wide spectrum of characteristic clinical manifestations, mainly attributable to hepatic insufficiency and portal hypertension. Major complications of portal hypertension include ascites, gastrointestinal (GI) variceal bleeding, hepatic encephalopathy (HE), renal failure, and bacterial infections. In recent years, major advances in the understanding of the natural history and pathophysiology of cirrhosis and the treatment of its complications have led to improved management, quality of life, and life expectancy of patients with this disease. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (HCC). Decompensated cirrhosis carries a poor short-term prognosis; thus, orthotopic liver transplantation (OLT) should always be considered in suitable candidates. This chapter describes the epidemiology, etiology and genetic factors, pathogenesis, diagnosis, general management, and treatment of cirrhosis. Complications of cirrhosis are discussed, including ascites, spontaneous bacterial peritonitis, dilutional hyponatremia, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome and postpulmonary hypertension, HE, and HCC. Indications and contraindications for liver transplantation are described. Figures show liver biopsy results and ultrasound images in cirrhosis from hepatitis C, a patient with tense ascites, transjugular intrahepatic portosystemic shunting (TIPS), large esophageal varices with red spots, and HCC. Tables outline the main causes of cirrhosis and the diagnostic methods for identifying them, the Child-Pugh score, diagnostic criteria for hepatorenal syndrome, grades of HE, and indications for liver transplantation.This chapter contains 6 highly rendered figures, 8 tables, 73 references.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1195
Author(s):  
Jiong Yu ◽  
Xiaowei Shi ◽  
Jing Ma ◽  
Ronggao Chen ◽  
Siyi Dong ◽  
...  

The relationship between aseptic systemic inflammation and postoperative bacterial infection is unclear. We investigated the correlation of systemic inflammation biomarkers with 30-day clinically significant bacterial infections (CSI) after liver transplantation (LT). This retrospective study enrolled 940 patients who received LT and were followed for 30 days. The primary end point was 30-day CSI events. The cohort was divided into exploratory (n = 508) and validation (n = 432) sets according to different centers. Area under the receiver operated characteristic (AUROC) and Cox regression models were fitted to study the association between baseline systemic inflammation levels and CSI after LT. A total of 255 bacterial infectious events in 209 recipients occurred. Among systemic inflammation parameters, baseline C-reactive protein (CRP) was independently associated with 30-day CSI in the exploratory group. The combination of CRP and organ failure number showed a good discrimination for 30-day CSI (AUROC = 0.80, 95% CI, 0.76–0.84) and the results were confirmed in an external verification group. Additionally, CRP levels were correlated with bacterial product lipopolysaccharide. In conclusion, our study suggests that pre-transplantation CRP is independent of other prognostic factors for 30-day CSI post-LT, and can be integrated into tools for assessing the risk of bacterial infection post-LT or as a component of prognostic models.


2017 ◽  
Author(s):  
Andres Cardenas ◽  
Isabel Graupera ◽  
Elsa Sola ◽  
Pere Ginès

Cirrhosis is the most advanced stage of all the different types of chronic liver diseases. It is defined as a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Hepatic fibrosis is potentially reversible if the causative agent is removed. However, advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible. Cirrhosis is a progressive and severe clinical condition associated with considerable morbidity and high mortality. It leads to a wide spectrum of characteristic clinical manifestations, mainly attributable to hepatic insufficiency and portal hypertension. Major complications of portal hypertension include ascites, gastrointestinal (GI) variceal bleeding, hepatic encephalopathy (HE), renal failure, and bacterial infections. In recent years, major advances in the understanding of the natural history and pathophysiology of cirrhosis and the treatment of its complications have led to improved management, quality of life, and life expectancy of patients with this disease. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (HCC). Decompensated cirrhosis carries a poor short-term prognosis; thus, orthotopic liver transplantation (OLT) should always be considered in suitable candidates. This chapter describes the epidemiology, etiology and genetic factors, pathogenesis, diagnosis, general management, and treatment of cirrhosis. Complications of cirrhosis are discussed, including ascites, spontaneous bacterial peritonitis, dilutional hyponatremia, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome and postpulmonary hypertension, HE, and HCC. Indications and contraindications for liver transplantation are described. Figures show liver biopsy results and ultrasound images in cirrhosis from hepatitis C, a patient with tense ascites, transjugular intrahepatic portosystemic shunting (TIPS), large esophageal varices with red spots, and HCC. Tables outline the main causes of cirrhosis and the diagnostic methods for identifying them, the Child-Pugh score, diagnostic criteria for hepatorenal syndrome, grades of HE, and indications for liver transplantation.This chapter contains 6 highly rendered figures, 8 tables, 73 references.


2017 ◽  
Author(s):  
Andres Cardenas ◽  
Isabel Graupera ◽  
Elsa Sola ◽  
Pere Ginès

Cirrhosis is the most advanced stage of all the different types of chronic liver diseases. It is defined as a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Hepatic fibrosis is potentially reversible if the causative agent is removed. However, advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible. Cirrhosis is a progressive and severe clinical condition associated with considerable morbidity and high mortality. It leads to a wide spectrum of characteristic clinical manifestations, mainly attributable to hepatic insufficiency and portal hypertension. Major complications of portal hypertension include ascites, gastrointestinal (GI) variceal bleeding, hepatic encephalopathy (HE), renal failure, and bacterial infections. In recent years, major advances in the understanding of the natural history and pathophysiology of cirrhosis and the treatment of its complications have led to improved management, quality of life, and life expectancy of patients with this disease. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (HCC). Decompensated cirrhosis carries a poor short-term prognosis; thus, orthotopic liver transplantation (OLT) should always be considered in suitable candidates. This chapter describes the epidemiology, etiology and genetic factors, pathogenesis, diagnosis, general management, and treatment of cirrhosis. Complications of cirrhosis are discussed, including ascites, spontaneous bacterial peritonitis, dilutional hyponatremia, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome and postpulmonary hypertension, HE, and HCC. Indications and contraindications for liver transplantation are described. Figures show liver biopsy results and ultrasound images in cirrhosis from hepatitis C, a patient with tense ascites, transjugular intrahepatic portosystemic shunting (TIPS), large esophageal varices with red spots, and HCC. Tables outline the main causes of cirrhosis and the diagnostic methods for identifying them, the Child-Pugh score, diagnostic criteria for hepatorenal syndrome, grades of HE, and indications for liver transplantation.This chapter contains 6 highly rendered figures, 8 tables, 73 references.


2017 ◽  
pp. E176-E187 ◽  
Author(s):  
Bao-Jie Shi ◽  
Xiao-Yu Yu ◽  
Hao Li ◽  
Tong-Hai Xing ◽  
Jun-Wei Fan ◽  
...  

Purpose: The purpose of this study was to retrospectively evaluate the association between Interleukin-18 (IL-18) gene polymorphisms of the donor and recipient in liver transplant patients with bacterial infections. Methods: Five single nucleotide polymorphisms (SNPs) (rs7106524, rs5744247, rs1946518, rs549908 and rs187238) of the IL-18 gene from the donors were genotyped and their association with post-operative bacterial infections was evaluated in liver transplant patients (N=113). A second independent group of liver transplant patients from a different organ transplant centre was also recruited for validation purposes (N=44). Results: IL-18 mRNA mean expression levels and protein levels were significantly lower in liver transplant patients with bacterial infections. For the donor SNP rs1946518, more recipients carried the A allele in the bacterial-infected group than the uninfected group (61.4% vs 39.7%; P ≤0.002). The mean IL-18 mRNA expression and protein levels were significantly lower in the transplanted livers of recipients carrying the rs1946518 AA genotype compared with those from recipients with CC genotype (3.64, 3.33 vs. 2.75, P≤0.048). The A allele of rs1946518 also resulted in lower luciferase activity than the C allele in a reporter assay. The area under ROC curve indicated that the rs1946518 SNP genotype in the donor liver predicted an increased risk of bacterial infection after liver transplantation (AUROC>0.82). Conclusions: These findings indicate that the IL-18 rs1946518 SNP in the donor liver is a risk factor for developing bacterial infection after liver transplantation.


Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1027
Author(s):  
Ana de Lucio Delgado ◽  
Jose Antonio Villegas Rubio ◽  
Corsino Rey Galan ◽  
Belen Prieto García ◽  
Maria de los Reyes González Expósito ◽  
...  

We investigated the kinetics of CRP, PCT, IL-6 and MR-proADM in a cohort of consecutive febrile patients with cancer in order to test the hypothesis that higher plasma concentrations and the absence of a rapid decrease in peak values would be associated with disease severity. (1) Method: A prospective descriptive and analytical study of patients with cancer and fever (≤18 years of age) at a University Hospital was carried out between January 2018 and December 2019. Information collected: sex, age, diagnosis, date and symptoms at diagnosis and medical history. The episodes were classified into three groups: bacterial infection, non-bacterial infection and systemic inflammatory response syndrome (SIRS). (2) Results: One hundred and thirty-four episodes were included. Bacterial infection criteria were met in 38 episodes. Biomarkers were measured at four different points: baseline, at 12–24 h, at 25–48 h and at 49–72 h. All the biomarkers evaluated decreased after the peak level was reached. IL-6 and MR-proADM showed a trend towards higher levels in the SIRS group although this rise was statistically significant only for IL-6 (p < 0.005). Bacterial infections more frequently presented values of PCT above the cut-off point (>0.5 ng/mL) at 12–24 h. (3) Conclusion: In our experience, IL-6 kinetics is faster than PCT kinetics and both are faster than CRP in patients with fever and cancer who present a good outcome. Patients with a good evolution show a rapid increase and decrease of PCT and particularly of IL-6 levels.


2020 ◽  
Author(s):  
Mojtaba Shafiekhani ◽  
Reza Shahriarirad ◽  
Nahid parandvar ◽  
Kourosh Kazemi ◽  
Afsaneh Vazin

Abstract Background: Liver transplantation (LT) is the only curative therapy for acute and chronic end-stage liver disease in pediatrics. Nevertheless, bacterial infection post-transplant account for one of the most significant causes of mortality which requires attention, along with appropriate antibacterial treatment. Therefor this study was designed to provide a multifaceted overview of bacterial infections during a one-year experience in the biggest pediatrics LT center in Iran.Methods: In this retrospective cohort study, records from all liver transplant pediatrics in Abu-Ali Sina hospital, Shiraz, Fars, Iran from April 2019 to February 2020 were assessed. Demographic, laboratory, and clinical data were extracted along with the administered therapeutic approach for the patient.Results: an incidence of 67.9% bacterial infection rate was observed, in which more than 64.06% of isolated pathogens were Gram-negative and 35.93% were gram-positive. The most isolated pathogens were E. coli sp. and pseudomonas sp. for gram negative, and enterococci and staph sp. for gram positive. Our study demonstrated that Intra-abdominal Surgical Site Infections (24.24%) was the most common site of infections in post LT pediatrics. According to the results of the sensitivity-resistance pattern of isolated pathogens, 24.39% of isolated gram-negative bacteria were Extensively drug resistant (XDR). Also, 30.43% of gram-positive bacteria were Vancomycin-resistant enterococci (VRE) and 8.69% of them were methicillin-resistant staphylococcus aureus (MRSA). Furthermore, multivariate regression analysis showed that the only risk factor for bacterial infections after LT is the length of stay in the ICU. The mortality rate in our study was 22%, which was significantly higher among the infection group (P = 0.008). Also, it was found that patients receiving colistin had a significantly shorter in length of stay in the ICU and hospital than those who did not receive colistin. There is no any significant difference between piperacillin-tazobactm versus meropenem as empirical treatment regarding clinical outcomes.Conclusion: a high rate of bacterial infection was detected among hospitalized pediatrics in the early period after LT. High antibacterial resistance of bacteria isolated from LT pediatrics is alarming. Furthermore, Replacement of piperacillin-tazobactam instead of carbapenems in empirical treatment should be considered.


2021 ◽  
Vol 22 (6) ◽  
pp. 3148
Author(s):  
Alberto Gómez-Carballa ◽  
Ruth Barral-Arca ◽  
Miriam Cebey-López ◽  
Xabier Bello ◽  
Jacobo Pardo-Seco ◽  
...  

The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (n = 695) and bacteria- (n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT, ISG15 and DNMT1, that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81; specificity: 0.87); testing set: AUC 0.87 (sensitivity: 0.82; specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.


2019 ◽  
Vol 2 (1) ◽  
pp. 1-3
Author(s):  
Attabak Toofani Milani ◽  
Mahshid Mohammadian ◽  
Sadegh Rostaminasab ◽  
Roghayeh Paribananaem ◽  
Zohre Ahmadi ◽  
...  

Conventional diagnostic test have limitations to deferential diagnosis in clinical suspicion ofbacterial infection cases, that in some cases lead to inappropriate antibiotic therapy and increases antibiotic resistance. A new diagnostic insight is procalcitonin (PCT) test to improve diagnosis of bacterial infections and to guide antibiotic therapy. Serum PCT levels are of useful test as a biomarker in patients with bacterial infections for several reasons. Initial rise of PCT levels due to bacterial infection, subsequent sequential PCT levels can be used to assess the effectiveness and duration of antibiotic therapy. Based on clinical researches results, in bacterial infections, promising good results obtained when use of PCT used as differential diagnostic test. But further intervention studies are needed before use of PCT in clinical routine tests. The goal of this review is to study the PCT reliability as infections diagnostic biomarker.


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