Myasthenia gravis genome-wide association study implicates AGRN as a risk locus.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date. METHODS: We performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls). We carried out human leucocyte antigen (HLA) fine-mapping, gene-based and tissue enrichment analyses and investigated genetic correlation with 13 other autoimmune disorders as well as pleiotropy across MG and correlated disorders. RESULTS: We confirmed the previously reported MG association with TNFRSF11A (rs4369774; p=1.09×10-13, OR=1.4). Furthermore, gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent MG loci: HLA-DRB1 and HLA-B. MG onset-specific analysis reveals differences in the genetic architecture of early-onset MG (EOMG) versus late-onset MG (LOMG). Furthermore, we find MG to be genetically correlated with type 1 diabetes (T1D), rheumatoid arthritis (RA), late-onset vitiligo and autoimmune thyroid disease (ATD). Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders. DISCUSSION: Our gene-based analysis identifies AGRN as a novel MG susceptibility gene, implicating for the first time a locus encoding a protein (agrin) that is directly relevant to NMJ activation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Our results are also consistent with previous studies highlighting the role of HLA and TNFRSF11A in MG aetiology and the different risk genes in EOMG versus LOMG. Finally, we uncover the genetic correlation of MG with T1D, RA, ATD and late-onset vitiligo, pointing to shared underlying genetic mechanisms.

Earlier treatment initiation is associated with a decreased number of HIV-1 subtype A1 transmissions in Greece.

OBJECTIVES: Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. METHODS: Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. RESULTS: A significant decline was detected for the treatment window during 2014-2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. CONCLUSIONS: Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Hospital-wide antifungal prescription in Greek hospitals: a multicenter repeated point-prevalence study.

The aim of the study was to evaluate antifungal prescriptions among hospitalized adult patients in Greek hospitals. This multicenter two-times, 1-day, point-prevalence study was carried out in 2015 and 2017 in five and six hospitals, respectively. Among the 5812 patients screened in both periods, antifungals were prescribed in 129 patients (73 in 2015 and 56 in 2017); antifungals were used as prophylaxis in 31 patients (24%), pre-emptively in 32 (25%), empirically in 38 (30%), and as targeted therapy in 28 (22%). Triazoles were the class most commonly used (65 patients; 50%), followed by echinocandins (59; 46%) and liposomal amphotericin B (12; 9%). The use of echinocandins was higher (P 0.009) in the ICU (16 out of 22 patients), as compared with those in other departments (40%). Antifungal treatment was deemed inappropriate in 32/129 patients (25%) (16% in 2015 versus 36% in 2017; P 0.014). Inappropriate antifungal administration was more common if indicated by the primary physician, as compared with an infectious disease specialist (35% versus 5%; P < 0.001). Candidemia represented the majority of microbiologically documented infections (12 out of 28). Only two cases of proven pulmonary aspergillosis were diagnosed. Fluconazole and echinocandins were most frequently prescribed for identified or presumptive fungal infections, while fluconazole or posaconazole was given most frequently as prophylaxis. Antifungal treatment has been, ultimately, proven unnecessary in one-fourth of cases, underlining the need of a nationwide antifungal stewardship program.

Human visceral leishmaniasis in northern Greece: Seroepidemiology and risk factors in endemic region.

BACKGROUND & OBJECTIVES: Visceral leishmaniasis is endemic in Greece, with sporadic cases reported annually both in the mainland and in coastal areas. Seroepidemiological studies across Greece report seropositivity rates from 0.5 to 15%, in different parts of the country. The aim of the present study was to evaluate the Leishmania seropositivity rate of the general population of Drama prefecture, a rich in water supply region, in northern Greece. METHODS: Serum samples collected from 347 healthy individuals were tested for IgG Leishmania infantum antibodies. Furthermore, 132 domestic dogs, clinically suspected to suffer from canine leishmaniasis, from all across the prefecture, were also evaluated. RESULTS: Among 347 healthy individuals tested, 24 (6.9%) were positive for IgG L. infantum antibodies. Age, gender, occupational and leisure time activities didn't show significant relation to IgG seropositivity, whereas low altitude of place of residency and residency at places with surface water were significantly related to IgG seropositivity. All seropositive individuals follow a geographic pattern, gathering themselves in Drama basin (rich in surface and underground water bodies), whereas canine leishmaniasis cases show a wide distribution across the prefecture. INTERPRETATION & CONCLUSION: Evaluation of both human seroprevalence and high incidence of canine leishmaniasis, as well as favorable landscape and climatic conditions of the study area, indicates that high level of clinical awareness need to be employed by physicians, as human and canine visceral leishmaniasis constitutes a serious public health concern.

Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.

BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. METHODS: Adult patients with first-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.

Ghrelin Levels in Basal Conditions and During Glucose Tolerance Test in Prediabetic and Diabetic Patients.

Ghrelin is associated with glucose homeostasis but its' possible relevance with glucose levels in physiological and pathological conditions has so far been poorly investigated. The aim of the present study was to evaluate circulating ghrelin levels in prediabetic and diabetic patients in basal conditions and in response to oral glucose tolerance test (OGTT). A total of 90 male adults aged 40 - 73 years old were enrolled in our study. Fasting and postprandial plasma ghrelin, insulin and glucose levels were measured at 0, 60, 120 and 180 min following an OGTT in 40 patients with type 2 diabetes mellitus (T2DM), 20 with impaired glucose tolerance (IGT) and 30 controls. Incremental and total area under response curve were determined and calculated for glucose, insulin and ghrelin. Fasting plasma ghrelin concentrations were significantly lower in the T2DM group than IGT and control group patients (p<0.01) but not between healthy subjects and IGT group (p=0.746). In the diabetics' group ghrelin levels showed a statistically significant negative correlation with insulin and a positive correlation with HbA1c and glucose. At all time points after the OGTT ghrelin concentrations were significantly lower in the T2DM group compared to IGT group and controls. Plasma ghrelin concentrations are lower in male diabetic patients at the fasting state and remain lower at all time points after an OGTT while minor differences were found between normal and IGT subjects. Ghrelin might play a role in insulin and glucose metabolism in diabetic patients but not in patients with IGT.

Crimean-Congo haemorrhagic fever in a Greek worker returning from Bulgaria, June 2018.

We report a tick-borne case of severe Crimean-Congo haemorrhagic fever (CCHF) imported into Greece from Bulgaria. The patient presented severe thrombocytopenia, hemophagocytosis, haemodynamic instability, large haematomas and altered mental status. Supportive treatment and ribavirin were administered. Symptoms started one day after the tick was removed; the patient was discharged from the hospital 26 days after symptom onset. No secondary cases were observed. Phylogenetically the CCHF virus strain belongs to clade Europe 1.

A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.

BACKGROUND: Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. METHODS: We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks. RESULTS: A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events. CONCLUSIONS: Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

A fatty meal aggravates apnea and increases sleep in patients with obstructive sleep apnea.

PURPOSE: The purpose of this study was to investigate the role of a fatty meal before bedtime, on sleep characteristics and blood pressure in patients with obstructive sleep apnea (OSA). METHODS: Recently diagnosed, by full polysomnography (PSG), patients with OSA (n=19) were included. These underwent PSG for additional two consecutive nights. Two hours before the PSG examination, a ham and cheese sandwich of 360 kcal was served to all patients, at first night, while a fatty meal of 1,800 kcal was served before the second PSG examination. Comparisons were performed between the last two examinations in terms of PSG data and morning and night blood pressure measurements. RESULTS: After the fatty meal, a significant increase was observed in total sleep time (p=0.026) in the Apnea-Hypopnea Index (AHI) (p=0.015), as well as in the absolute number of obstructive and central apneas (p=0.032 and p=0.042, respectively) compared to the previous night. Conversely, distribution of sleep stages and indices of nocturnal hypoxia (average and minimum SpO2 and sleep time with SpO2<90 %) did not change significantly. Likewise, no significant change was observed in blood pressure measurements. CONCLUSIONS: Fatty meal intake before sleep can increase AHI in OSA patients, although it does not affect sleep architecture or indices of hypoxia.

Exploring genomic structure differences and similarities between the Greek and European HapMap populations: implications for association studies.

Studies of the genomic structure of the Greek population and Southeastern Europe are limited, despite the central position of the area as a gateway for human migrations into Europe. HapMap has provided a unique tool for the analysis of human genetic variation. Europe is represented by the CEU (Northwestern Europe) and the TSI populations (Tuscan Italians from Southern Europe), which serve as reference for the design of genetic association studies. Furthermore, genetic association findings are often transferred to unstudied populations. Although initial studies support the fact that the CEU can, in general, be used as reference for the selection of tagging SNPs in European populations, this has not been extensively studied across Europe. We set out to explore the genomic structure of the Greek population (56 individuals) and compare it to the HapMap TSI and CEU populations. We studied 1112 SNPs (27 regions, 13 chromosomes). Although the HapMap European populations are, in general, a good reference for the Greek population, regions of population differentiation do exist and results should not be light-heartedly generalized. We conclude that, perhaps due to the individual evolutionary history of each genomic region, geographic proximity is not always a perfect guide for selecting a reference population for an unstudied population.

Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study.

BACKGROUND: Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated. METHODS: Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated. RESULTS: Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 - 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 - 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 - 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028). CONCLUSIONS: We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.

Sleepiness as a marker of glucose deregulation in obstructive sleep apnea.

BACKGROUND: Excessive daytime sleepiness (EDS) is a major but not universally present feature of obstructive sleep apnea syndrome (OSAS). The latter has been associated with glucose dysmetabolism and insulin resistance. The aim of this study was to examine the role of EDS by investigating potential differences between somnolent and non-somnolent OSAS patients in glucose metabolism, insulin resistance, and levels of cardiovascular risk factors. METHODS: Included were 25 newly diagnosed otherwise healthy OSAS patients, reporting EDS (ESS ≥ 11) and 25 age- and BMI-matched, non-somnolent (ESS ≤ 10) OSAS patients, who served as controls. Fasting glucose and insulin levels, as well as homeostatic model assessment of insulin resistance (HOMA(IR)) index, levels of hs-CRP, and lipidemic profile were measured. RESULTS: The two groups did not differ in anthropometric or sleep characteristics. A significant correlation of ESS with glucose (p = 0.004), insulin (p = 0.011), and HOMA(IR) (p = 0.031) was observed. Somnolent patients had higher levels of glucose (p = 0.045), insulin (p = 0.012), and HOMA(IR) (p = 0.027). No difference was detected in other markers between the two groups. CONCLUSIONS: Daytime sleepiness in OSAS patients is associated with hyperglycemia and hyperinsulinemia. These results suggest its potential use as a surrogate marker of insulin resistance in such patients.

Liquid Biopsy in Type 2 Diabetes Mellitus Management: Building Specific Biosignatures via Machine Learning.

BACKGROUND: The need for minimally invasive biomarkers for the early diagnosis of type 2 diabetes (T2DM) prior to the clinical onset and monitoring of ß-pancreatic cell loss is emerging. Here, we focused on studying circulating cell-free DNA (ccfDNA) as a liquid biopsy biomaterial for accurate diagnosis/monitoring of T2DM. METHODS: ccfDNA levels were directly quantified in sera from 96 T2DM patients and 71 healthy individuals via fluorometry, and then fragment DNA size profiling was performed by capillary electrophoresis. Following this, ccfDNA methylation levels of five ß-cell-related genes were measured via qPCR. Data were analyzed by automated machine learning to build classifying predictive models. RESULTS: ccfDNA levels were found to be similar between groups but indicative of apoptosis in T2DM. INS (Insulin), IAPP (Islet Amyloid Polypeptide-Amylin), GCK (Glucokinase), and KCNJ11 (Potassium Inwardly Rectifying Channel Subfamily J member 11) levels differed significantly between groups. AutoML analysis delivered biosignatures including GCK, IAPP and KCNJ11 methylation, with the highest ever reported discriminating performance of T2DM from healthy individuals (AUC 0.927). CONCLUSIONS: Our data unravel the value of ccfDNA as a minimally invasive biomaterial carrying important clinical information for T2DM. Upon prospective clinical evaluation, the built biosignature can be disruptive for T2DM clinical management.

Dating the Origin and Estimating the Transmission Rates of the Major HIV-1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe.

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.

Long-term respiratory follow-up of H1N1 infection.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009. METHODS AND FINDINGS: Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the diagnosis. All patients were treated with oseltamivir from the first day of hospitalization. Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence. In total 44 patients were hospitalized 15/44 had asthma, 6/44 COPD, 5/44 leukemia. Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge. The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients. CONCLUSIONS: An improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract. This inflammation was not associated with the severity or clinical outcome of the patients. All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months. Early treatment with antiviral agents and vaccination represent the mainstay of management.

Alpha2B-adrenergic receptor insertion/deletion polymorphism in women with spontaneous recurrent abortions.

AIM: The aim of our study was to investigate the relationship between the alpha2B-adrenoreceptor insertion/deletion (I/D) polymorphism and recurrent spontaneous abortions (RSA). METHODS: Genotyping was performed in 48 women with a history of at least three consecutive spontaneous abortions and 96 women with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction and PCR were used for the research of DD, ID and II genotype characters. RESULTS: The distribution of DD, ID and II genotypes of the alpha2B-adrenoreceptor gene was 2 (4.2%), 19 (39.6%) and 27 (56.2%) in the study group and 6 (6.5%), 28 (30.4%) and 58 (63%) in the control group, respectively. There was no significant difference between the groups. The presence of the D allele was not associated with RSA (P = 0.78, odds ratio = 0.88, 95% CI = 0.47-1.65). CONCLUSION: Our data fall short of showing any association between the presence of the alpha2B D allele and the occurrence of spontaneous abortions in the examined population.

Evaluation of a new foam to increase skin hydration of the foot in type 2 diabetes: a pilot study.

The aim of the present study was to evaluate the efficacy of a new product (Neuropad repair foam(®)) in promoting skin hydration of the foot in type 2 diabetes. Included in this study were 20 type 2 diabetic patients (10 men, mean age 61·40 ± 2·44 years). Patients applied Neuropad repair foam(®) on the plantar aspect of the right foot twice daily. No agent was applied on the left foot. Patients were examined at baseline, after 7 treatment days and after 14 treatment days. Evaluation of skin dryness was performed by means of the Multi Skin test Corneometer MC 900. In the right foot, skin capacitance was 26·55 ± 4·14 arbitrary units (a.u.) at baseline, 28·90 ± 4·53 a.u. after 7 days of treatment and 32·05 ± 4·54 a.u. after 14 days of treatment. There was a significant increase in skin capacitance from baseline to 7 days of treatment (P < 0·001), from baseline to 14 treatment days (P < 0·001), as well as from 7 to 14 days of treatment (P < 0·001). The same significant (P < 0·001) increases were observed both in men and in women. No changes were noted in the left foot. At baseline, there was no difference in skin capacitance between right and left foot (P = 0·186). However, skin capacitance was significantly higher on the right versus left foot, both after 7 days (P < 0·001) and after 14 days of treatment (P < 0·001). In conclusion, results with the new foam appear encouraging in ameliorating skin dryness in the diabetic foot and further investigation is warranted.

Variants in clock genes could be associated with lower risk of type 2 diabetes in an elderly Greek population.

OBJECTIVES: Recent evidence has linked circadian rhythm dysregulation to an increased risk of metabolic disorders. This study explores a potential association between variation in genes regulating the endogenous circadian timing system (clock genes) and the risk of type 2 diabetes (T2D) in a sample of Greek elderly people. STUDY DESIGN: Variants within and upstream or downstream of PPARA, PPARD, CLOCK/TMEM165, PER1, PER2 and PER3 genes were genotyped in 716 individuals with T2D (A) and 569 normoglycemic controls (B), and allele frequencies were compared between the groups in a case control study design. MAIN OUTCOME MEASURES: Samples were genotyped on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. To avoid the possibility of subjects with prediabetes being included in the control group, people with HbA1c <5.7% and fasting glucose <100 mg/dl comprised group C (n = 393), for whom a separate analysis was performed (secondary analysis). RESULTS: A protective role against T2D was identified for 14 variants in the PPARA gene. The rs7291444, rs36125344, rs6008384 in PKDREJ, located upstream of PPARA, and rs2859389 in UTS2, located upstream of PER3, demonstrated a protective role against T2D in both analyses. In contrast, rs6744132, located between HES6 and PER2, was positively correlated with T2D risk. Only in the secondary analysis, rs2278637 in VAMP2, located downstream of PER1, and rs11943456 in CLOCK/TMEM165 were found to confer protection against T2D. In a recessive model analysis of all groups, PPARD variants exhibited a protective role against disease. CONCLUSIONS: Our findings suggest a possible implication of clock genes in T2D susceptibility. Further studies are needed to clarify the mechanisms that connect circadian rhythm dysfunction and T2D pathogenesis.

Evolution of epidemiological characteristics of infective endocarditis in Greece.

OBJECTIVE: The clinical profile, management and outcome of infective endocarditis (IE) may be influenced by socioeconomic issues. METHODS: A nationwide prospective study evaluated IE during the era of deep economic crisis in Greece. Epidemiological data and factors associated with 60-day mortality were analyzed through descriptive statistics, logistic and Cox-regression models. RESULTS: Among 224 patients (male 72.3%, mean age 62.4 years), Staphylococcus aureus (n = 62; methicillin-resistant S. aureus (MRSA) 33.8%) predominated in the young without impact on mortality (p = 0.593), whilst Enterococci (n = 36) predominated in the elderly. Complications of IE were associated with mortality: heart failure [OR 2.415 (95% CI: 1.159-5.029), p = 0.019], stroke [OR 3.206 (95% CI: 1.190-8.632), p = 0.018] and acute kidney injury [OR 2.283 (95% CI: 1.085-4.805), p = 0.029]. A 60-day survival benefit was solely related to cardiac surgery for IE during hospitalization [HR 0.386 (95% CI: 0.165-0.903), p = 0.028] and compliance with antimicrobial treatment guidelines [HR 0.487 (95% CI: 0.259-0.916), p = 0.026]. Compared with a previous country cohort study, history of rheumatic fever and native valve predisposition had declined, whilst underlying renal disease and right-sided IE had increased (p < 0.0001); HIV infection had emerged (p = 0.002). No difference in rates of surgery and outcome was assessed. CONCLUSIONS: A country-wide survey of IE highlighted emergence of HIV, right-sided IE and predominance of MRSA in the youth during a severe socioeconomic crisis. Compliance with treatment guidelines promoted survival.