Evaluation of tripartite motif 59 and its diagnostic utility in benign bowel diseases and colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in developing countries. Tripartite motif-59 (TRIM59) a member of the TRIM ubiquitin ligase family, is a surface molecule that regulates biological processes such as cell proliferation, apoptosis, and tumorigenesis. Previous studies reported that TRIM59 expression was upregulated in human CRC, however, the expression pattern and role of TRIM59 in benign colorectal lesions remain unclear. Sixty patients diagnosed with CRC and 60 patients with benign lesions (Crohn's disease, ulcerative colitis, adenoma, and familial adenomatous polyposis) were recruited to the present study. TRIM59 gene expression was assessed by real-time quantitative polymerase chain reaction. Expression of TRIM59 protein and p-AKT were determined using, enzyme-linked immunoassay while p53 expression was detected by immunohistochemistry. Antioxidant/oxidant role of glutathione (GSH)/malondialdehyde (MDA) were evaluated by colorimetric methods in all of the studied groups. Our results showed upregulated expressions of TRIM59 gene and protein levels in CRC tissues and benign colonic lesions compared to nontumor tissues. Their levels were higher in inflammatory compared to noninflammatory bowel lesions. There were significant interrelations among TRIM59 gene expression, protein levels, tumor, node, metastasis staging, and the presence of metastasis (p < 0.0001). Receiver-operator characteristic curve analyses showed that at the cutoff point of 2.5 TRIM59 mRNA expression can discriminate between CRC cases and benign bowel group (area under the curve [AUC]: 0.639, sensitivity: 86.7%, specificity: 41.7%), and between CRC and controls (AUC: 0.962, sensitivity: 90%, specificity: 91.7%). TRIM59 could be a potential biomarker in the early detection, diagnosis, and treatment of benign colonic lesions and CRC.

Health care-associated infections in pre-transplant liver intensive care unit: Perspectives and challenges.

BACKGROUND: Health care-associated infections (HAIs) threaten patient's safety worldwide especially in the intensive care units (ICU). In end-stage liver disease (ESLD), the condition is much more complicated. Data regarding HAIs among ESLD patients is lacking. We aimed to assess the incidence of HAIs, risk factors, causative micro-organisms, antimicrobial susceptibilities and mortality rates among patients with end-stage liver disease (ESLD) admitted to pre-transplant liver intensive care unit (LICU). METHOD: This prospective observational study included 337 ESLD patients admitted to LICU, Al-Rajhi liver center, Assiut University Hospital, Assiut, Egypt between January 2016 and June 2016 and they were followed up for the development of HAI manifestations. The medical history, physical examination and severity of underlying disease were determined. Clinical samples were taken from patients who developed HAIs for microbiological diagnosis and antimicrobial susceptibility testing. RESULTS: A total of 57 (16.9%) ESLD patients developed HAIs with the incidence density of 26.8 per 1000 patient-days. Blood stream infection was the most common (49.1%). Escherichia coli (21.1%) followed by methicillin-resistant Staphylococcus aureus (MRSA) (15.8%) were the commonest bacteria. Multidrug resistant organisms were reported in 52.6% of the isolates. Fungal causes were 15.8% with Candida species dominance. Sphingomonas paucimobilis and Achromobacter dentrificans were reported for the first time as pathogens for HAIs in LICU. Prolonged hospital stay, intravenous line duration, prolonged use of proton pump inhibitors and paracentesis were predictors for HAIs. No significant difference between ESLD patients with and without HAIs regarding mortality (36.8% vs. 48.6%, P=0.2). CONCLUSION: High HAI rate among ESLD patients is a matter of worry. Effective surveillance program, active infection control measures and national antibiotic policies are necessary to reduce the burden of HAIs.

Minimal hepatic encephalopathy in patients with liver cirrhosis: magnetic resonance spectroscopic brain findings versus neuropsychological changes.

BACKGROUND AND STUDY AIM: Minimal hepatic encephalopathy (MHE) is a subtle complication of cirrhosis that may have a detrimental effect on daily functioning and may progress to overt hepatic encephalopathy (HE). The aims of this study were to identify MHE and assess neuropsychological changes in those patients. PATIENTS AND METHODS: A case-control study was conducted in 35 cirrhotic patients. MHE was identified by brain (hydrogen-1) magnetic resonance spectroscopy ((1)H-MRS). Neuropsychological changes were evaluated using cognitive abilities screening instrument (CASI) test, Hamilton depression scale, and soft neurological sign assessment. RESULTS: Of the patients, 16 (45.7%) had significant brain (1)H-MRS findings suggesting MHE in the form of decreased myo-Inositol/creatine (mI/Cr) and choline/creatine (Cho/Cr) ratios and increased glutamine-glutamate/creatine (Glx/Cr) ratios in white and grey matters compared to patients without MHE and healthy controls. Patients with MHE had significantly lower abstract thinking subset and total CASI score in comparison to patients without MHE (p=0.03 and p=0.05, respectively) and controls (p=0.003 and p=0.02, respectively). No statistically significant differences were observed amongst different groups regarding other CASI subsets, depression, and soft neurological assessment in spite of a tendency towards increased values in patients with MHE. CONCLUSION: MHE associated with neurophysiological changes demonstrated by (1)H-MRS preceded neuropsychological changes. Thus, (1)H-MRS may be considered as a potential tool for diagnosis of cirrhosis-associated cerebral dysfunction and a promising method for prioritisation of subjects awaiting liver transplantation.

Fungal infection in patients with end-stage liver disease: low frequency or low index of suspicion.

BACKGROUND: End-stage liver disease (ESLD) is associated with dysregulation of the immune system and increased susceptibility to infections. Although invasive fungal infection (IFI) is a growing public health problem, studies of IFI in ESLD are lacking. The aims of this study were to screen for IFI in ESLD and to assess risk factors and serum interleukin 17 (IL-17) as a marker of the cellular immune response. METHODS: Both blood and ascitic fluid samples were collected from 46 patients with ESLD for fungal culture and PCR. Serum IL-17 levels were determined. RESULTS: Seven patients had isolated IFI (four had spontaneous fungal peritonitis, two had fungemia, and one had a disseminated fungal infection) and five cases had combined fungal and bacterial infections. Spontaneous fungal peritonitis was attributed to Candida species, while fungemia was caused by Aspergillus species. Patients with IFI had higher serum IL-17 levels and increased mortality compared to patients without IFI. A history of antibiotic use (p = 0.002), higher model for end-stage liver disease (MELD) scores (p = 0.04), and hepatorenal syndrome (p = 0.006) were risk factors for IFI. CONCLUSIONS: Patients with ESLD had a low frequency of IFI; however, in patients with these infections, delayed diagnosis and treatment may contribute to a high fatality rate. Thus, clinicians should have a high index of suspicion for this unusual but lethal entity, as prompt detection and appropriate treatment can improve the outcome.