191 research outputs found

    The hepatitis D virus in Italy. A vanishing infection, not yet a vanished disease

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    Introduction: Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. Objectives: To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. Methods: From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. Results: At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2–17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000–2009 to 50.2% (130/259) in 2010–2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. Conclusion: Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation

    A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals

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    Given q as the global frequency of the alleles causing a disease, any allele with a frequency higher than q minus the cumulative frequency of the previously known disease-causing mutations (threshold) cannot be the cause of that disease. This principle was applied to the analysis of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in order to decide whether they are the cause of cystic fibrosis. A total of 191 DNA samples fl-om random individuals from Italy, France, and Spain were investigated by DGGE (denaturing gradient gel electrophoresis) analysis of all the coding and proximal non-coding regions of the gene. The mutations detected by DGGE were identified by sequencing. The sample size was sufficient to select essentially all mutations with a frequency of at least 0.01. A total of 46 mutations was detected, 20 of which were missense mutations. Four new mutations were identified: 1341+28 C/T, 2082 C/T, L1096R, and I1131V. Thirteen mutations (125 G/C, 875+40 A/G, TTGAn, IVS8-6 5T, IVS8-6 9T, 1525-61 A/G, M470V, 2693 T/G, 3061-65 C/A, 4002 A/G, 4521 G/A, IVS8 TG10, IVS8 TG12) were classified as non-CF-causing alleles on the basis of their frequency. The remaining mutations have a cumulative frequency far exceeding q; therefore, most of them cannot be CF-causing mutations. This is the first random survey capable of detecting all the polymorphisms of the coding sequence of a gene

    Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection

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    Background: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking.Methods: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out.Results: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score >= 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE >= 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score >= 11 and SOFA score >= 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective.Conclusions: Both INCREMENT-SOT-CPE >= 11 and SOFA >= 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT
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