Liver fibrosis staging with combination of APRI and FIB-4 scoring systems in chronic hepatitis C as an alternative to transient elastography.

BACKGROUND: Liver disease severity must be determined before treatment of chronic hepatitis C (CHC). We evaluated the diagnostic performance of the APRI and FIB-4 scores compared to transient elastography liver stiffness (TE-LS) in detecting significant fibrosis (F3) or cirrhosis (F4). METHODS: We retrospectively enrolled 575 patients with CHC who underwent TE-LS between May 2014 and September 2018: 365 (63.5%) male, mean age 51.54±12.4 years. APRI and FIB-4 scores were compared to TE-LS. RESULTS: One hundred patients (17.5%) had TE-LS values between 9 and 11.9 kPa, and were classified as F3, while 265 (46%) were classified as F4 (TE-LS ≥12 kPa). APRI and FIB-4 scores predicted F4 patients adequately using cutoff values of 0.65 (sensitivity 85.5%, specificity 77%) and 1.63 (sensitivity 91%, specificity 77%), respectively. Cutoff values of 0.64 for APRI and 1.46 for FIB-4 predicted F3/F4 patients (sensitivity 72% and 81.5%; specificity 83% and 79%, respectively). The use of these cutoff values with APRI and FIB-4 in combination adequately predicted patients with significant fibrosis or cirrhosis (positive predictive value 91.5%), while cutoff values of 0.3 and 0.98, respectively, predicted F1/F2 patients with specificity 94.5% and sensitivity 26.5%, suggesting that in 58.5% of patients TE-LS could possibly be avoided. CONCLUSIONS: The APRI/FIB-4 combination performed well in predicting significant fibrosis, while FIB-4 performed well in predicting cirrhosis. These noninvasive biochemical markers could be used as screening tools instead of LS measurement, which is not widely available. Further prospective validation studies are required to confirm this finding.

Association between genotypes of rs34436714 of NLRP12 and serum tumor necrosis factor-alpha in inflammatory bowel disease: A case-control study.

We aimed to investigate the impact of the single nucleotide polymorphisms of rs34436714 of the NOD-like receptor protein 12 gene on the production of tumor necrosis factor-alpha (TNFα) in patients with inflammatory bowel disease (IBD)In a matched case-control study 90 patients with IBD, 56 with Crohn disease (CD) and 34 with ulcerative colitis, were genotyped and compared to 98 healthy comparators matched for age and gender. Expression level of TNFα, interleukin (IL)-6, IL-12, and soluble triggering receptor expressed on myeloid cells were measured in patients' sera. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated for TNFα production.Serum TNFα was greater among carriers of GT/TT genotypes than GG genotypes of rs34436714. Stimulated TNFα production was also higher in carriers of GT/TT genotypes. The frequency of CD with fistulizing behavior and with CD involving the small intestine was greater among carriers of GT/TT genotypes than of the GG genotype. Distribution of the GG, GT, and TT genotypes of rs34436714 were in Hardy-Weinberg equilibrium in both groups. The genotype distribution was the same in both groups.Carriage of minor frequency alleles of rs34436714 was accompanied by greater circulating levels of TNFα and by greater capacity for stimulated TNFα production by PBMCs. These alleles had an impact on the phenotype of patients with CD.

Update on ischemic colitis: from etiopathology to treatment including patients of intensive care unit.

Ischemic colitis is the result of colonic hypoperfusion and is regarded as a relatively rare condition. It can be roughly classified as occlusive and non-occlusive. Pathogenesis includes a usually transient compromise in the colonic vasculature, with a parallel activation of an inflammatory cascade caused primarily by reperfusion. Diagnosis of ischemic colitis remains often difficult and requires a combination of diagnostic techniques, whereas clinical signs are occasionally only seen late as complications. Gold standard is considered to be colonoscopy. Clinical presentation and treatment of ischemic colitis vary widely depending on the degree of ischemia. Patients of intensive care unit (ICU) with ischemic colitis are often under-diagnosed, since the parallel co-morbidities and the nonspecific nature of symptoms that mimic almost any abdominal pathology, can mislead the doctor. Moreover, sedated or ventilated patients can mask many of the characteristic features of ischemic colitis and make the diagnosis challenging. Bedside colonoscopy and diagnostic laparoscopy in ICUs are two options, which seem lately to be reliable and promising in diagnosing ischemic colitis in critically ill patients.

Immunomodulatory Role of Clarithromycin in Acinetobacter baumannii Infection via Formation of Neutrophil Extracellular Traps.

Macrolide antibiotics have been shown to act as immunomodulatory molecules in various immune cells. However, their effect on neutrophils has not been extensively investigated. In this study, we investigated the role of macrolide antibiotics in the generation of neutrophil extracellular traps (NETs). By assessing ex vivo and in vivo NET formation, we demonstrated that clarithromycin is able to induce NET generation both in vitro and in vivo. Clarithromycin utilizes autophagy in order to form NETs, and these NETs are decorated with antimicrobial peptide LL-37. Clarithromycin-induced NETs are able to inhibit Acinetobacter baumannii growth and biofilm formation in an LL-37-dependent manner. Additionally, LL-37 antimicrobial function depends on NET scaffold integrity. Collectively, these data expand the knowledge on the immunomodulatory role of macrolide antibiotics via the generation of LL-37-bearing NETs, which demonstrate LL-37-dependent antimicrobial activity and biofilm inhibition against A. baumannii.