Bibert S.,University of Lausanne |
Wojtowicz A.,University of Lausanne |
Taffe P.,University of Lausanne |
Manuel O.,University of Lausanne |
And 8 more authors.
AIDS | Year: 2014
Background: Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. Objectives: To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. Design and methods: This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4+ nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. Results: A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (logrank test P=0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P=0.03), after adjustment for CD4+ nadir and slope, HAART and HIV-risk groups. Conclusion: We reported for the first time an association between an IFNL3/4 polymorphismand susceptibility to AIDS-relatedCMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source
Casini A.,University of Geneva |
Lukowski S.,University of Geneva |
Quintard V.L.,The Surgical Center |
Crutu A.,The Surgical Center |
And 4 more authors.
Thrombosis Research | Year: 2014
Introduction Causative mutations leading to congenital quantitative fibrinogen are frequently clustered in FGA encoding the fibrinogen Aα-chain. Mutations of FGB encoding the Bβ-chain are less common and of interest since the Bβ-chain is considered the rate-limiting factor in the hepatic production of the fibrinogen hexamer. Method Four novel FGB mutations were identified in two afibrinogenemic (one new-born and one 30 years old male) and hypofibrinogenemic (a 49 years old female) patient, with heterogeneous thrombotic and bleeding phenotype. The human fibrinogen beta chain precursor protein sequence (P02675) was obtained from the UniProt database. The resulting models were analysed in SwissPdbViewer 4.1 and POV-Ray 3.7. Results The FGB c.895 T>C p.Y299H (numbering from the initiator Met) and the FGB c.1415G>T p.G472V were predicted to be deleterious by SIFT analysis. The first replaces an uncharged aromatic amino acid side chain by a positively charged side chain modifying the balance in the distribution of hydrophobic and hydrophilic of the 10 Å neighbourhood residues. The second replaces one non-charged aliphatic side chain by another without any changes for the 10 Å surrounding region. The FGB c.352C>T p.Q118X leads to a severe premature termination codon and the FGB intron 4: IVS4-1G>C (c719-1G>C) leads to skipping of exon 5 or usage of a cryptic acceptor site located upstream or downstream of the normal site. Conclusions The continuous characterization of novel molecular defects responsible for fibrinogen deficiency combined with modelling of mutant proteins will continue to provide a better comprehension of the complexity of fibrinogen synthesis and physiology. © 2014 Elsevier Ltd. All rights reserved. Source
Sax H.,University of Geneva |
Uckay I.,University of Geneva |
Balmelli C.,Regional Hospital of Lugano |
Bernasconi E.,Regional Hospital of Lugano |
And 7 more authors.
Annals of Surgery | Year: 2011
Objective: To assess the overall burden of healthcare-associated infections (HAIs) in patients exposed and nonexposed to surgery. Background: Targeted HAI surveillance is common in healthcare institutions, but may underestimate the overall burden of disease. Methods: Prevalence study among patients hospitalized in 50 acute care hospitals participating in the Swiss Nosocomial Infection Prevalence surveillance program. Results: Of 8273 patients, 3377 (40.8%) had recent surgery. Overall, HAI was present in 358 (10.6%) patients exposed to surgery, but only in 206 (4.2%) of 4896 nonexposed (P < 0.001). Prevalence of surgical site infection (SSI) was 5.4%. Healthcare-associated infections prevalence excluding SSI was 6.5% in patients with surgery and 4.7% in those without (P < 0.0001). Patients exposed to surgery carried less intrinsic risk factors for infection (age >60 years, 55.6% vs 63.0%; American Society of Anesthesiologists score >3, 5.9% vs 9.3%; McCabe for rapidly fatal disease, 3.9% vs 6.6%; Charlson comorbidity index >2, 12.3% vs 20.9%, respectively; all P < 0.001) than those nonexposed, but more extrinsic risk factors (urinary catheters, 39.6% vs 14.1%; central venous catheters, 17.8% vs 7.1%; mechanical ventilation, 4.7% vs 1.3%; intensive care stay, 18.3% vs 8.8%, respectively; all P<0.001). Exposure to surgery independently predicted an increased risk of HAI (odds ratio 2.43; 95% CI 2.0-3.0). Conclusions: Despite a lower intrinsic risk, patients exposed to surgery carried more than twice the overall HAI burden than those nonexposed; almost half was accountable to SSI. Extending infection control efforts beyond SSI prevention in these patients might be rewarding, especially because of the extrinsic nature of risk factors. Copyright © 2011 by Lippincott Williams & Wilkins. Source
Bucher H.C.,University of Basel |
Richter W.,Institute for Lipid Metabolism |
Glass T.R.,University of Basel |
Magenta L.,Regional Hospital of Lugano |
And 8 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012
Objectives: HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy. Methods: We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation. Results: In models including cholesterol, triglycerides, highdensity lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events. Conclusions: HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression. Copyright © 2012 by Lippincott Williams & Wilkins. Source
Young J.,University of Basel |
Xiao Y.,Analysis Group Inc. |
Xiao Y.,McGill University |
Moodie E.E.M.,McGill University |
And 9 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015
Background: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channeling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. Methods: We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. Results: A total of 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patientyears). In a conventional Cox model, recent\-but not cumulative\- exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 months caused the greatest increase in risk. Conclusions: Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source