Genomewide scans of inbred strains of mice have linked the genes encoding the hepatocanalicular cholesterol transporter ABCG5/G8 to gallstone formation. Five nonsynonymous coding single-nucleotide polymorphisms (SNPs) in the orthologous human genes are associated with differences in serum cholesterol and plant sterol levels. We now tested these ABCG5/G8 SNPs for linkage and association with gallstone susceptibility in humans. Prospectively, we collected data from 178 white individuals with gallbladder stones or history of cholecystectomy in 84 families and from 70 stone-free controls, as confirmed by abdominal ultrasound. We performed nonparametric linkage (NPL) analysis of affected sib pairs (ASPs) and association tests of cases and controls. In ASPs, gallstones were strongly linked to the D19H variant of the ABCG8 gene (NPL score ‫؍‬ 7.1; P ‫؍‬ 4.6 ؋ 10 ؊13 ). The risk of gallstones in carriers of the 19H allele was significantly increased in randomly selected cases from the ASP cohort compared to the stone-free controls (OR ‫؍‬ 3.018; P ‫؍‬ 0.017). Consistent with the mouse model, heterozygosity for the lithogenic ABCG8 allele was associated with gallstones in humans; 21.4% of gallstone patients carried the heterozygous D19H genotype, compared with 8.6% of controls (OR ‫؍‬ 2.954; P ‫؍‬ 0.026). Conclusion: The linkage and association studies identified the cholesterol transporter ABCG5/G8 as a genetic determinant of gallstone formation, or LITH gene, in humans. The function of this transporter and the results of the genetic study taken together indicate that in gallstone-susceptible carriers of the ABCG8 19H allele, cholesterol cholelithiasis is secondary to increased hepatobiliary cholesterol secretion. (HEPATOLOGY 2007;46:793-801.)

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Background: Systemic inflammatory status is known as an important factor of colorectal cancer prognosis. Our study aimed to evaluate the performances of inflammation biomarker ratios as classification models of seven outcomes in patients with colorectal cancer. Methods: A retrospective cohort study was conducted on subjects with colorectal cancer over five years at a single center in Transylvania, Romania. Seven derived ratios were calculated based on laboratory data: neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and albumin-to-globulin (AGR) ratios, Systemic Immune Inflammation Index (SII) and Prognostic Nutritional Index (PNI). The utility of these ratios as predictors for seven outcomes was further evaluated in multivariable regression models. Results: Our study shows that the evaluated ratios exhibit specific performances for individual outcomes, proving a fair ability as screening tools (NLR and dNLR for survival, T stage and M stage; NLR and SII for T stage; and PLR for M stage). A dNLR over 3.1 (OR = 2.48, 95% CI (1.421 to 4.331)) shows predictive value for survival. A value of NLR over 3.10 (OR = 1.389, 95% CI (1.061 to 1.817)) is positively associated with an advanced T stage, while LMR is negatively related to the T stage (OR = 0.919, 95% CI (0.867 to 0.975)). NLR over 4.25 (OR = 2.647, 95% CI (2.128 to 3.360)) is positively associated with, while PNI is negatively related (OR = 0.970, 95% CI (0.947 to 0.993)) to, the M stage. Conclusion: Each of the evaluated ratios possesses prognostic value for certain outcomes considered, but the reported models need external validation to recommend their clinical practice utilization.

Aim: The present study aimed at identifying the pattern of patients with critical limb ischemia (CLI) compared with those with peripheral arterial occlusive disease (PAOD). Materials and methods: A four-year retrospective study was conducted with patients hospitalized in the Second Surgical Clinic at the Emergency County Hospital Cluj-Napoca. The medical charts of patients with PAOD (n=466) and CLI (n=223) were reviewed and data were collected. Results: The study included 689 patients; mean age 67 years for PAOD patients and 65 years for CLI patients. A significantly higher percentage of patients were male in both groups (79.25%, P < 0.0001). Most of the patients in both groups had received at least a secondary education (P < 0.0001). Most of the subjects in both groups were smokers (>71.30%) with no difference between groups (P = 0.566). No significant differences were found between the groups in comorbidities (diabetes, arterial blood hypertension, cardiac ischemia, rhythm disorders, P > 0.05). There were more CLI patients that were overweight than overweight patients with PAOD (P = 0.0004). High serum cholesterol (>200 mg/dL) and triglycerides (>150 mg/dL) levels were found in the CLI group (P < 0.05). Age was identified as a risk factors for amputation (OR = 1.03, 95%Cl [1.01−1.05], P = 0.0012). Conclusions: The profile of a patient with critical limb ischemia and peripheral arterial occlusive disease is a 65-67-year-old male smoker with at least a secondary education. The CLI patient is overweight with pathological serum levels of cholesterol and triglycerides.