Binary Toxin and Death after Clostridium difficile Infection

TOC Summary: Strains with these genes in addition to toxins A and B were associated with the highest case-fatality rates

The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus

The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79–1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83–1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85–1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus

Case report of an atypical early onset X-linked retinoschisis in monozygotic twins

BACKGROUND: X-linked Retinoschisis (XLRS) is one of the most common macular degenerations in young males, with a worldwide prevalence ranging from 1:5000 to 1:20000. Clinical diagnosis of XLRS can be challenging due to the highly variable phenotypic presentation and limited correlation has been identified between mutation type and disease severity or progression. CASE PRESENTATION: We report the atypical early onset of XLRS in 3-month-old monozygotic twins. Fundus examination was characterized by severe bullous retinal schisis with pre-retinal and intraretinal haemorrhages. Molecular genetic analysis of the RS1 was performed and the c.288G > A (p. Trp96Ter) mutation was detected in both patients. CONCLUSIONS: Early onset XLRS is associated with a more progressive form of the disease, characterized by large bullous peripheral schisis involving the posterior pole, vascular abnormalities and haemorrhages. The availability of specific technology permitted detailed imaging of the clinical picture of unusual cases of XLRS. The possible relevance of modifying genes should be taken into consideration for the future development of XLRS gene therapy

Measles among migrants in the European Union and the European Economic Area

Aims: Progress towards meeting the goal of measles elimination in the EU and the European Economic Area (EEA) by 2015 is being obstructed, as some children are either not immunized on time or never immunized. One group thought to be at increased risk of measles is migrants; however, the extent to which this is the case is poorly understood, due to a lack of data. This paper addresses this evidence gap by providing an overview of the burden of measles in migrant populations in the EU/EEA. Methods: Data were collected through a comprehensive literature review, a country survey of EU/EEA member states and information from measles experts gathered at an infectious disease workshop. Results: Our results showed incomplete data on measles in migrant populations, as national surveillance systems do not systematically record migration-specific information; however, evidence from the literature review and country survey suggested that some measles outbreaks in the EU/EEA were due to sub-optimal vaccination coverage in migrant populations. Conclusions: We conclude that it is essential that routine surveillance of measles cases and measles, mumps and rubella (MMR) vaccination coverage become strengthened, to capture migrant-specific data. These data can help to inform the provision of preventive services, which may need to reach out to vulnerable migrant populations that currently face barriers in accessing routine immunization and health services

High heterogeneity in methods used for the laboratory confirmation of pertussis diagnosis among European countries, 2010 : integration of epidemiological and laboratory surveillance must include standardisation of methodologies and quality assurance

Despite extensive childhood immunisation, pertussis remains one of the world's leading causes of vaccinepreventable deaths. The current methods used for laboratory diagnosis of pertussis include bacterial culture, polymerase chain reaction (PCR) and enzymelinked immunosorbent assay (ELISA) serology. We conducted a questionnaire survey to identify variations in the laboratory methods and protocols used among participating countries included in the European surveillance network for vaccine-preventable diseases (EUVAC.NET). In February 2010, we performed the survey using a web-based questionnaire and sent it to the country experts of 25 European Union countries, and two European Economic Area (EEA) countries, Norway and Iceland. The questionnaire consisted of 37 questions which covered both general information on surveillance methods and detailed laboratory methods used. A descriptive analysis was performed. Questionnaires were answered by all 27 contacted countries. Nineteen countries had pertussis reference laboratories at the national level; their functions varied from performing diagnosis to providing technical advice for routine microbiology laboratories. Culture, PCR and serology were used in 17, 18 and 20 countries, respectively. For PCR, nine laboratories used insertion sequence IS481 as the target gene, which is present in multiple copies in the Bordetella pertussis genome and thus has a greater sensitivity over single copy targets, but has been proved not to be specific for B. pertussis. Antibodies directed against pertussis toxin (PT) are specific for B. pertussis infections. For ELISA serology, only 13 countries' laboratories used purified PT as coating antigen and 10 included World Health Organization (WHO) or Food and Drug Administration (FDA) reference sera in their tests. This present survey shows that methods used for laboratory confirmation of pertussis differ widely among European countries and that there is a great heterogeneity of the reference laboratories and functions. To evaluate the effects of different pertussis immunisation programmes in Europe, standardisation and harmonisation of the laboratory methods are needed.peer-reviewe

Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes

Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. Results: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10–1.64) and 1.99 (1.55–2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10–1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06–1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). Conclusions: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry

Monitoring COVID‐19 vaccine effectiveness against COVID‐19 hospitalisation and death using electronic health registries in ≥65 years old population in six European countries, October 2021 to November 2022

Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65-79 and ≥80 years in six European countries. Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome, VE was estimated monthly over 8-week follow-up periods, allowing 1 month-lag for data consolidation. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and VE = (1 - aHR) × 100%. Site-specific estimates were pooled using random-effects meta-analysis. Results: For ≥80 years, considering unvaccinated as the reference, VE against COVID-19 hospitalisation decreased from 66.9% (95% CI: 60.1; 72.6) to 36.1% (95% CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95% CI: 88.0; 98.4) to 67.7% (95% CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79 years. The second booster VE against hospitalisation ranged between 82.0% (95% CI: 75.9; 87.0) and 83.9% (95% CI: 77.7; 88.4) for the ≥80 years and between 39.3% (95% CI: -3.9; 64.5) and 80.6% (95% CI: 67.2; 88.5) for 65-79 years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80 years. Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multicountry data from EHR facilitate robust near-real-time VE monitoring in the EU/EEA and support public health decision-making.European Centre for Disease Prevention and Control, Grant/Award Numbers ECDC/2021/018, RS/2022/DTS/24104.info:eu-repo/semantics/publishedVersio

The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities