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Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1β and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1β levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis. © 2018, The Author(s).

Background: Two models are mostly used to predict survival in cirrhosis: the Child–Pugh score (CP score) and the model for end-stage liver disease score (MELD score). Aims: The aim of this study is to evaluate the CP score and the MELD score for short- and long-term prognosis in cirrhosis, as well as CP-creatinine score, MELD-Na score, and UKELD score. Methods: One thousand and forty-seven patients from five referral centers were included: men/women: 620/427, median age: 58 years (IQR 48–66), median follow-up: 33 months (IQR 12–74), CP (A/B/C): 493/357/147, CP score: 7 (IQR 5–9), MELD score: 12 (IQR 9–16). The performance of each score was evaluated by the Cox hazard model in terms of their: discrimination ability (C-index and Somer’s D) and calibration (3, 12 months). Internal validation was done with bootstrapping (100 samples). Results: Three hundred and fifty-two patients (33.6%) died. All scores were significantly associated with overall mortality, when assessed by univariate Cox analysis. CP-creatinine score performed significantly better than all other scores [bootstrap C-index 0.672, 95% CI 0.642–0.703, bootstrap Somer’s D 0.344 (0.285–0.401)], apart from CP score, which showed similar performance. Inclusion in the multivariable Cox model of age together with CP-creatinine score improved the discriminative ability of the model [bootstrap C-index (95% CI) 0.700 (0.661–0.740)]. In terms of calibration, CP-creatinine score was the best for both 3- and 12-month survival in the total population. Conclusions: CP score and CP-creatinine score have better prognostic value compared to MELD score, MELD-Na score, and UKELD score for predicting short- and long-term mortality in patients with stable cirrhosis. © 2017, Springer Science+Business Media New York.

The normal esophageal mucosa creates a protective epithelial barrier that constrains the acidic reflux in the esophageal lumen. Microscopic findings and functional studies indicate that this barrier might be impaired in patients with non erosive reflux disease (NERD) but not in patients with functional heartburn (FH). Whereas endoscopy and pH monitoring are the most important diagnostic tools in the diagnosis of NERD, recent studies suggest that esophageal biopsies might have a complementary role. Particularly in the differential diagnosis between NERD and FH, the application of histological severity scores showed very promising results. Further evaluation of the scores could lead to routine application of histology in specific NERD populations. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.

From January 1988 through October 1997, 167 cardiac transplants were performed. 1246 endomyocardial biopsies (EMBs) from 138 cardiac allograft recipients were investigated and graded according to the Working Formulation (WF) criteria. The specimens were inadequate in 44 EMBs (3.5%), while 598 (48%) showed no rejection. The grade of rejection was: mild (grade 1A and 1B) in 531 EMBs (42.6%), mild/moderate (grade 2) in 38 (3.1%), and moderate (grade 3A and 3B) in 35 (2.8%). The indications for transplantation were: dilated cardiomyopathy (46.1%); ischemic disease (37.1%); valvular disease (12%); hypertrophic cardiomyopathy (1.8%); myocarditis (1.2%); congenital cardiopathy (0.6%), restrictive cardiomyopathy (0.6%) and chronic rejection (0.6%). The most reliable histologic feature of acute rejection was the myocyte necrosis or damage in presence of pironinophilic mononuclear cell infiltrate, so our protocol requires multifocal or diffuse myocyte damage (rejection grade 3A and 3B) to perform an additional treatment, which was required in 35 cases (2.8%). An intermediate grade mild/moderate 2, was introduced from the WF to classify the EMBs in which the myocyte necrosis was scant or not clear; this grade in our series generally resolves without any additional treatment; in order to monitor the rejection another EMB was performed 5 days after in these patients. The EMBs showed also the following lesions other than acute rejection: Quilty A (79 patients; 57.25%), Quilty B (24 pts; 17.39%), early ischemic necrosis (43 pts; 31.15%) and late ischemic necrosis (5 pz; 3.62%). Quilty B and late ischemic necrosis were correlated with acute rejection (grade 2), furthermore the patients with graft vascular disease showed 3 or more episodes of acute rejection. These findings confirm the relationship between acute and chronic rejection. Furthermore, a relationship between chronic rejection (4 pts) and infection from hepatitis C (antibodies positive 3 pts/4) and cytomegalovirus (antibodies positive 4 pts/4) was found in our series. In the follow-up period (117 months), a 30.72% death rate was recorded; the main causes of death were: early failure of the transplanted heart (30 pts) in 4 of them associated with pulmonary hypertension, infections (6 pts), sudden death (4 pts), graft's vasculopathy (4 pts), acute pancreatitis (1 pts) pulmonary embolism (1 pts), lung (1 pts) and ovary (1 pts) carcinoma, acute rejection (1 pts), others (2 pts). In the early period (1 month), the most frequent cause of death was the early failure of the transplanted heart, while in the late period (1 year) the chronic rejection following by sudden death and tumours. The actuarial survival curve drops to 83.13% after the first post-operative month, abates to 75.30 at the end of the first year, and progressively decreases to 70.48% at the end of the fifth follow-up year. The mortality rate was 38.7% in pts transplanted for ischemic disease and 24.7% for dilated cardiomyopathy. Cardioplegia seems to play an important role in the success of the heart transplant.

OBJECTIVE: Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness. METHODS: Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I-II essential hypertension suffering from OSAS (35 men, aged 49 ± 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid-femoral pulse wave velocity (c-fPWV) measurements. RESULTS: Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI) < 5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 ± 4 versus 29.3 ± 4 kg/m, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 ± 0.06 versus 0.42 ± 0.07, P = 0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c-fPWV by 9% (8.56 ± 0.49 versus 7.85 ± 0.93 m/s, P = 0.001) and this difference remained significant even after adjustment for confounders (P = 0.04). In the total study population, c-fPWV was correlated with age (r = 0.35, P = 0.015), office systolic blood pressure (r = 0.30, P = 0.007), RWT (r = 0.30, P = 0.03), logAHI (r = 0.389, P = 0.0001) and minimum oxygen saturation (r = -0.418, P = 0.0001). CONCLUSIONS: OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk. © 2007 Lippincott Williams & Wilkins, Inc.

The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1 beta, and activation of the NF-kappa B pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFVmutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFVmutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings.

A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.