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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.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.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 HbA1c5.7% and fasting glucose100 mg/dl comprised group C (n = 393), for whom a separate analysis was performed (secondary analysis).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.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.

Introduction: The aim of this study was to estimate the prevalence of Type 2 Diabetes and related metabolic disorders in the Evros region. Material-Methods: A random sample of 541 people was studied using the Finnish Type 2 Diabetes Risk Score, and measurement of weight, height, waist and hip circumference, blood pressure, as well as Fasting Glucose and Postprandial Glucose with a reflectometer. The participants with a score of 15-20, score ≥20, FG ≥100 mg/dl and / or PG 140 mg/dl (n = 206) were subjected to a oral glucose tolerance test, according to WHO. Lipid profile, metabolic syndrome and cardiovascular risk were also assessed. Results: Prevalence of DM T2 in the study population was: 29.6%, and that of prediabetes was 10.9%. Obese (Body Mass Index ≥ 30 kg/m2) were: 52.5%, overweight (BMI 25-30kg/m2) were 33.2% and normal/low weight (BMI

BackgroundMyasthenia 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.MethodsWe 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.ResultsWe 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.DiscussionOur 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.

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.

A significant progress has been made over the years in the prognosis and treatment of patients with early diagnosis of HIV infection. However, late presentation of a large number of patients remains a serious public health problem. The aim of our study is to highlight the dimensions of the problem by evaluating the data from the HIV Unit of Alexandroupolis, a rural region with population heterogeneity and a strategic position between West and East, Europe, and Asia. This was a retrospective study, including 107 patients diagnosed with HIV infection in our unit from 2010 to 2018. Late presenters (LP) were defined as patients diagnosed with a CD4 cell count

ObjectivesSubtypes 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.MethodsOur 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.ResultsA 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.ConclusionsOur 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.

Introduction Assessment for cardiovascular autonomic neuropathy (CAN) remains difficult in everyday clinical practice. We sought to examine the diagnostic utility of various simple tools for diabetic peripheral neuropathy (DPN) in the detection of CAN in type 2 diabetes mellitus. Methods We examined 153 type 2 diabetes mellitus subjects by various DPN tools (vibration perception threshold, 10 g Semmes-Weinstein monofilament, Ipswich touch test, NC-stat®/DPNCheck, neuropathy disability score) for the detection of CAN. CAN was diagnosed by the standardised cardiovascular autonomic reflex function tests. Results For the diagnosis of CAN, assessment of small nerve fibre function (pinprick sensation, temperature perception) yielded a very high negative predictive value (97%), with high sensitivity (89%) and moderate specificity (73%). The vibration perception threshold was second in diagnostic utility (91% negative predictive value, 62% sensitivity and 75% specificity). Conclusions Based on their high negative predictive value, simple tools for DPN may prove useful to exclude CAN in type 2 diabetes mellitus. These encouraging results merit further evaluation to enable wider screening for CAN.

Background: The need for minimally invasive biomarkers for the early diagnosis of type 2 diabetes (T2DM) prior to the clinical onset and monitoring of β-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 β-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.

Background: Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM). Their simultaneous development remains disputable. The aim of the present study was to examine the correlation between CAN and the presence/severity of DSPN in DM. Methods: Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153; mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests. Results: In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients with mild and in those with moderate/severe DSPN compared with patients without DSPN in univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the 2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN. Conclusion: CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/ severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe DSPN and in patients without DSPN.

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger (p .001) and had lower median admission NIHSS-scores (p .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Background: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway. Methods: Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes. Results: Three common CARD8 variants confer decreased risk for DN, namely rs11665831 (OR = 0.62, p = 0.016), rs11083925 (OR = 0.65, p = 0.021), and rs2043211 (OR = 0.66, p = 0.026), independent of sex or co-inheritance with an IL-1B variant. Conclusion: CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common CARD8 variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups.

BackgroundMyasthenia Gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction. Here, we investigate the genetic architecture of MG performing a genomewide association study (GWAS) of the largest MG dataset analyzed to date.MethodsWe integrated GWAS from three different datasets (1,401 cases, 3,508 controls) and performed MG GWAS and onset-specific analyses. We also carried out HLA fine-mapping, gene-based, gene ontology and tissue enrichment analyses and investigated genetic correlation to other autoimmune disorders.FindingsWe observed the strongest MG association to TNFRSF11A (rs4369774, p=1.09×10−13; OR=1.4). Gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent loci significantly associated with MG: HLA-DRB1 (with a protective role) and HLA-B. MG onset-specific analysis, reveals differences in the genetic architecture of Early-Onset vs Late-Onset MG. Furthermore, we find MG to be genetically correlated with Type 1 Diabetes, Rheumatoid Arthritis and late-onset Vitiligo.InterpretationOverall, our results are consistent with previous studies highlighting the role of the HLA and TNFRSF11A in MG etiology and different risk genes in EOMG vs LOMG. Furthermore, our gene-based analysis implicates, for the first time, AGRN as a MG susceptibility locus. AGRN encodes agrin, which is involved in neuromuscular junction formation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Gene ontology analysis suggests an intriguing role for symbiotic processes in MG etiology. We also uncover genetic correlation of MG to Type 1 Diabetes, Rheumatoid Arthritis and late-onset Vitiligo, pointing to shared underlying genetic mechanisms.FundingThis work was supported by NSF award #1715202, the European Social Fund and Greek funds through the National Strategic Reference Framework (NSRF) THALES Programme 2012–2015 and the NSRF ARISTEIA II Programme 2007–2013 to PP, and grants from the Association Francaise contre les Myopathies (AFM, Grant No. 80077) to ST.Research in contextEvidence before this studyMyasthenia Gravis (MG) is a complex disease caused by the interaction of genetic and environmental factors that lead to autoimmune activation. Previous studies have shown that the human leukocyte antigen (HLA) displays the most robust genetic association signals to MG. Additional susceptibility genes that have emerged through genomewide association studies (GWAS), include CTLA4 and TNFRSF11A. Previous studies also support the hypothesis of distinct risk loci underlying Early-Onset versus Late-Onset MG subgroups (EOMG vs LOMG). For instance, PTPN22 and TNIP1 genes have been implicated in EOMG and ZBTB10 in LOMG. In the GWAS studies published so far, HLA and TNFRSF11A associations appear to be confirmed; however, the association of other implicated genes still requires replication.Added value of this studyWe present the largest GWAS for MG to date, integrating three different datasets. We identify AGRN as a novel MG risk locus and replicate previously reported susceptibility loci, including HLA, TNFRSF11A, and CTLA4. Our analysis also supports the existence of a different genetic architecture in EOMG vs LOMG and identifies a region between SRCAP and FBRS as a novel EOMG risk locus. Additionally, through HLA fine-mapping, we observe different HLA genes implicated in EOMG vs LOMG (HLA-B and HLA-DRB1 respectively). Finally, we detect positive genetic correlation of MG with other autoimmune disorders including Type 1 Diabetes, Rheumatoid Arthritis, and late-onset Vitiligo, suggesting a shared genetic basis across them.Implications of all the available evidenceOur study sheds light into the etiology of MG identifying AGRN as a novel risk locus. AGRN encodes agrin, a protein with a significant role in the formation of the neuromuscular junction and mutations in this gene have been associated with congenital myasthenic syndrome. Our findings hint to an intriguing hypothesis of symbiotic processes underlying MG pathogenesis and points to muscle growth and development in EOMG and steroid hormones synthesis in LOMG. The observed genetic correlations between MG and certain other autoimmune disorders could possibly underlie comorbidity patterns across this group of disorders.

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.

Greece had been a malaria-endemic country from prehistoric times to 1974, with northern Greece (Macedonia and Thrace)...

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

Diabetic foot infections are a common and serious problem for all health systems worldwide. The aim of this study was to examine the resistance to antibiotics of microorganisms isolated from infected soft tissues of diabetic foot ulcers, using tissue cultures. We included 113 consecutive patients (70 men, 43 women) with a mean age of 66.4 ± 11.2 years and a mean diabetes duration of 14.4 ± 7.6 years presenting with diabetic foot soft tissue infections. Generally, no high antibiotic resistance was observed. Piperacillin-tazobactam exhibited the lowest resistance in Pseudomonas, as well as in the other Gram-negative pathogens. In methicillin-resistant Staphylococcus aureus isolates, there was no resistance to anti-Staphylococcus agents. Of note, clindamycin, erythromycin, and amoxycillin/clavulanic acid exhibited high resistance in Gram-positive cocci. These results suggest that antibiotic resistance in infected diabetic foot ulcers in our area is not high and they are anticipated to prove potentially useful in the initial choice of antibiotic regimen.

Aim: To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population. Patients & methods: A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study. Results: CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001). Conclusion: Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.

Background: It is well established that there is an important genetic predisposition for type 2 diabetes mellitus (T2DM). Objective: To summarise available epidemiological data regarding T2DM transmission in various populations. Method: Narrative review. Results: The estimated risk for the diagnosis of T2DM increases approximately by 2-4 times, when father, mother or both have this condition. Conversely, many T2DM patients have family members with DM. Studies have suggested that the likelihood of T2DM in the next generation is higher in the event of a diabetic mother than father. Both genetic factors, such as mitochondrial DNA mutations, and environmental components, such as intra-uterine environment, have been implicated in the higher maternal transmission of T2DM. Despite the above findings, some studies in populations with high frequency of T2DM have not corroborated the predominantly maternal transmission. Such works have shown either an excess paternal or an equal transmission of T2DM. Conclusion: It appears that potential biases in reporting family history data, especially between the various racial groups, have contributed to the controversy over the existence of excess maternal transmission of DM.

Introduction The aim of this study was to assess the performance of VibraTip, a device used to test a person’s vibration perception during routine checks for peripheral neuropathy, against two thresholds of the Neuropathy Disability Score (NDS) for diagnosing distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM). Methods One hundred consecutive subjects with T2DM were enrolled in the study, of whom 54 were men. The mean age was 62.3 years, and the mean T2DM duration was 12.6 years. VibraTip was used at one foot site (on the pulp of the hallux; protocol A) and at three foot sites (pulp of the hallux and first and third metatarsal head; protocol B). NDS thresholds of ≥ 3 and ≥ 6 were used to establish the diagnosis of DSPN. Results Against the NDS ≥ 3 threshold, VibraTip showed a very high sensitivity (91.3%) and negative predictive value (NPV) (92%) and a high specificity (85.2%) with protocol A, and a very high sensitivity (95.6%) and NPV (96.1%) and a very high specificity (90.7%) with protocol B. Against the NDS ≥ 6 threshold, VibraTip showed a very high sensitivity (100%) and NPV (100%) and a very high specificity (95.2%) with protocol A, and very high sensitivity (100%) and NPV (100%) and very high specificity (96.8%) with protocol B. Conclusions The diagnostic performance of VibraTip is very high in patients with T2DM, rendering it a very useful device as a screening tool, particularly for the exclusion of DSPN. VibraTip performs very well at both NDS thresholds, but particularly well at the NDS ≥ 6 threshold. There appears to be no need to examine sites other than the hallux site with Vibratip.

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.

Posters are an established mode of disseminating scientific research. They require careful preparation and presentation. During the former, the authors need to pay attention to the following features: choice of text, fonts and colors, illustrations and graphics, adequate presentation of methods and results, as well as to-the-point discussion of key messages. The latter is regrettably slightly neglected but very important. Indeed, poster presenters need to give a brief talk highlighting the research question and communicating the findings of the study, their novelty, and the anticipated clinical implications. In conclusion, practice is needed to create successful posters, but the result may be useful and pleasing.

Introduction: Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Methods: Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. Results: We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger [median age 68 years (IQR:61-75) vs. 79 years (IQR:73-83); p Conclusions: ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Background: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway. Methods: Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes. Results: Three common CARD8 variants confer decreased risk for DN, namely rs11665831 (OR = 0.62, p = 0.016), rs11083925 (OR = 0.65, p = 0.021), and rs2043211 (OR = 0.66, p = 0.026), independent of sex or co-inheritance with an IL-1B variant. Conclusion: CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common CARD8 variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups.

Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p

Introduction New tests for improved diagnosis of diabetic peripheral neuropathy (DPN) are useful. Material and methods We evaluated the utility of automated nerve conduction study (NCS) of the sural nerve with a new portable device for the diagnosis of DPN in patients with type 2 diabetes mellitus (T2DM). This study included 114 T2DM patients (58 men) with mean age 64.60 ±8.61 years. Exclusion criteria were B12 depletion, alcohol abuse and other causes of peripheral neuropathy. The reference method was the Neuropathy Disability Score (NDS) with a threshold NDS ≥ 3. Sural nerve automated NCS was carried out with the portable NC-stat DPNCheck device. Sensory nerve conduction velocity and sensory nerve action potential amplitude were measured bilaterally. Automated NCS was considered abnormal when ≥ 1 of the two aforementioned neurophysiological parameters was abnormal in at least one leg. Results Examination with NC-stat DPNCheck exhibited 90.48% sensitivity, 86.11% specificity, 79.17% positive predictive value (PPV) and 93.94% negative predictive value (NPV). The positive likelihood ratio (LR+) was 6.51 and the negative likelihood ratio (LR-) was 0.11. Conclusions Sural nerve automated NCS with the NC-stat DPNCheck device exhibits high sensitivity and specificity for the diagnosis of DPN in T2DM.

Background and Aim:Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels.Materials and Methods:Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use.Results:At baseline, serum VEGF levels in OSA patients were higher compared with controls (pConclusion:In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.

Background: Nosocomial transmission is a major mode of infection of Crimean-Congo haemorrhagic fever (CCHF). In May 2018, a patient with CCHF was hospitalised in Greece. Objective: Our aim was to present the management of healthcare workers (HCWs) to the CCHF case. Methods: Contact tracing, risk assessment and follow-up of exposed HCWs were performed. Testing (RT-PCR and/or serology) was offered to contacts. Post-exposure prophylaxis (PEP) with ribavirin was considered for high-risk exposures. Results: Ninety-one HCWs were exposed to the case. Sixty-six HCWs were grouped as high-risk exposures. Ribavirin PEP was offered to 29 HCWs; seven agreed to receive prophylaxis. Forty-one HCWs were tested for CCHF infection; none was found positive. Gaps in infection control occurred. Discussion: CCHF should be considered in patients with compatible travel history and clinical and laboratory findings. Early clinical suspicion and laboratory confirmation are imperative for the implementation of appropriate infection control measures. Ribavirin should be considered for high-risk exposures. Infection control capacity for highly pathogenic agents should increase.

Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever stroke (FES). Adult patients with FES were registered during a 24-month period (2010–2012) and followed-up for 12 months. We calculated cumulative incidences of stroke mortality and recurrence. Univariable and multivariable Cox proportional hazards regression analyses were used to identify independent determinants of 1-year mortality and 1-year stroke recurrence. We prospectively documented 703 first ever stroke cases (mean age 75 ± 12 years; 52.8% males; 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 cumulative incidence rates of mortality of all FES patients at 28 days, 3 months and 1 year were 21.3% (95% CI 18.5–24.5%), 26% (95% CI 22.9–29.4%) and 34.7% (95% CI 31.3–38.3%), respectively. The risk of 1-year mortality was independently (p

Introduction: 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 perfecture, 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 (ESP) of 2013 and applied criteria of data quality, as proposed by the Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) project. Stroke diagnosis and classification was performed using WHO criteria on the basis of neuroimaging and/or autopsy data. Results: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% males; ischemic stroke (IS): 80.8%, intracerebral hemorrhage (ICH): 11.8%, subarachnoid hemorrhage (SAH): 4.4%, undefined: 3.0%) with a total follow-up time of 119,805 person-years. The unadjusted and ESP adjusted incidences of all strokes were 586.8 (95%CI: 543.4-630.2) and 534.3 (95%CI: 532.3-536.3) per 100,000 person-years, respectively. The unadjusted incidence rates for IS, ICH and SAH were 474.1 (95%CI: 435-513), 69.3 (95%CI: 54-84) and 25.8 (95%CI: 25.7-25.9) per 100,000 person-years, respectively. The corresponding ESP-adjusted incidence rates per 100,000 person-years were 425.9 (95%CI: 424-427), 63.3 (95%CI: 63-63.5) and 25.8 (95%CI: 25.7-25.9) for IS, ICH and SAH, respectively. The overall 30-day case fatality rate was 21.3% (95%: 18.3-24.4%) for all strokes, and was higher in hemorrhagic strokes than IS (40.4%, 95%CI: 31.3-49.4% vs 16.2%, 95%CI: 13.2%-19.2%). Conclusion: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences in South-Eastern Europe.

BACKGROUND We have earlier developed a pharmacogenomic algorithm for acenocoumarol dose prediction in Greek patients that included CYP2C9/VKORC1 genetic information. This study aims at analyzing the potential effect of CYP4F2, CYP2C19, and CYP1A2 gene polymorphisms on acenocoumarol dose requirements and at further improving the Greek-specific pharmacogenomic algorithm. METHODS A total of 205 Greek patients taking acenocoumarol (140 who reached and 65 who did not reach stable dose), participants of acenocoumarol EU-PACT trial, were included in the study. CYP4F2, CYP2C19, and CYP1A2 polymorphisms were genotyped by use of the PCR-RFLP method. All patients were previously genotyped for CYP2C9/VKORC1 polymorphisms. RESULTS In the pooled sample, CYP4F2, CYP2C19, and CYP1A2 polymorphisms do not affect independently acenocoumarol dose requirements. For CYP4F2, significant effects were found on patients' ability to reach stable dose and on acenocoumarol dose requirements when CYP2C9/VKORC1 sub-phenotypes were analyzed. Specifically, when the patients were stratified according to their CYP2C9/VKORC1 functional bins, in sensitive responders, CYP4F2*3 allele carriers (CYP4F2 *1/*3 and *3/*3 genotypes) were more frequent in the patient group who reached stable dose (p=0.049). Additionally, in CYP2C9 intermediate metabolizers (IMs), after adjusting for age, weight, and VKORC1 genotypes, CYP4F2 genotypes were significantly associated with acenocoumarol stable dose (β: 0.07; 95% CI: 0.006-0.134; p=0.033). CONCLUSIONS CYP4F2 gene shows a prominent weak association with acenocoumarol dose requirements. Sub-phenotype analysis is potentially important in determining additional gene polymorphisms that are associated with acenocoumarol dose requirements.

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health.

Platelet dysfunction plays a role in diabetic macrovascular complications. Several studies have assessed the effect of oral hypoglycemic agents (OHAs) on platelet function. Data from both in vivo and in vitro studies show a favorable effect for most of the traditional glucose-lowering therapies, while evidence is limited for the newer ones. Metformin, sulfonylureas, glitazones and acarbose exert a favorable effect on platelet function. Among incretin therapies, only sitagliptin has so far been demonstrated to have a beneficial effect on platelet aggregation. More in vivo and in vitro evidence is required to increase our knowledge on any potential beneficial effects of OHAs on platelet function. Any such effect may have implications for the reduction of cardiovascular risk in type 2 diabetes mellitus.

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.

In 2017, the management of type 1 diabetes mellitus (T1DM) remains intriguing for the clinician, who has to balance between adequate glycemic control and untoward events related to insulin up-titration. Thus, agents that will complement insulin actions and reduce adverse effects are highly welcome. Areas covered: In this review, the authors summarize results from studies on the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin in T1DM. Expert opinion: In T1DM, dapagliflozin is associated with significant antihyperglycemic and metabolic properties, which are achieved with reduction or stabilization of insulin dose and with a very low trend for hypoglycemia. However, there is a lot to learn with respect to diabetic ketoacidosis (DKA), bone fractures and lower limb ischemia.

Insulin is the cornerstone of type 1 diabetes mellitus (T1DM) therapy. However, it cannot achieve a delay in the onset or evolution of this condition, while cardiovascular morbidity remains an unquestionable threat.In this review, the authors discuss gevokizumab (XOMA 052), a recombinant monoclonal antibody that can neutralize human IL-1β by binding to it. This is relevant, because this IL has been associated with β-cell toxicity in both diabetes types. Moreover, gevokizumab presents two major advantages: it spares IL-1α and it exhibits favorable pharmacokinetic properties. Gevokizumab has already proven its safety and efficacy in improving glycemic control, β cell function and inflammation markers in clinical trials in diabetic patients.Despite the very promising characteristics of gevokizumab, important questions remain to be answered. One important question is what to expect from a combination of this agent with insulin and if there is a subset of patients that might respond more favorably to treatment. We also need to know at what stage in the natural history of T1DM could gevokizumab be most efficacious, as well as its potential effects on cardiovascular outcomes.

The present brief review looks at the evidence on the role of GLP-1 and its agonists in osteopenia and osteoporosis in type 2 diabetes (T2DM). There is accumulating data to suggest a favourable effect of GLP-1 on bone metabolism. However, most data is from experimental studies, while clinical confirmation is still inadequate. Moreover, little is known on the precise mechanisms underlying these effects. Therefore, we need randomised clinical trials in T2DM patients to learn more on the action of GLP-1 on bone metabolism and its potential clinical implications.

The prevalence of carbapenem-resistant pathogens (CRPs) has increased worldwide. Given the importance of CRPs for public health and the high rates of carbapenem resistance observed in Greece, the Hellenic Center for Disease Control and Prevention (HCDCP) under the auspices of the Ministry of Health has undertaken initiatives to develop an Action Plan (i) to estimate the burden of CRP infections in acute-care hospitals in Greece and (ii) to implement infection control measures to limit the intrahospital transmission of these organisms. Starting in November 2010, specific infections caused by CRPs were reported to the HCDCP weekly. Results showed that CRP infections constitute a significant public health problem in acute-care hospitals in this country, with a mean incidence of 0.48 per 1000 patient-days and a crude 28-day mortality rate of 34.4%. The second phase of the Action Plan consists of systemic evaluation for adherence to an infection control bundle including enhanced standard infection control practices, separation of carriers and infected patients from non-carriers, and strict implementation of contact precautions. Communication between hospitals and public health authorities has been established to facilitate rapid notification and feedback.

We evaluated olfactory dysfunction in 154 adults (74 men, mean age 60.9 ± 11.9 years), of whom 119 had type 2 diabetes mellitus (T2DM). Olfactory function was assessed with “Sniffin’ Sticks.” A total Threshold-Discrimination-Identification (TDI) score was calculated. Type 2 diabetes mellitus, hypertension, and hyperlipidemia were associated with lower olfactory scores (all TDI scores

Objective: The use of dipeptidyl-peptidase 4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) analogues for the treatment of diabetic mellitus (DM) type 2 is growing. Currently some of these agents have been approved in combination with insulin. Methods: We considered randomised controlled trials (RCTs) evaluating GLP1 analogues or DDP4 inhibitors combined with basal insulin in diabetic patients. We were limited to trials published in English language. Results: PubMed search retrieved 207 items. After excluding irrelevant items we ended with 7 eligible studies with 1808 participants. Mean baseline HbA 1c was 8.5% and median follow up was 24 weeks. Exenatide combined with insulin was used in 2 studies; DPP4 inhibitors were used in 5 studies (2 with sitagliptin, 1 with saxagliptin, 1 with vildagliptin and 1 with alogliptin). Conclusion: Incretin-based therapies combined with basal insulin are able to reduce HbA 1c by 0.5-0.7%. DPP4 inhibitors have no significant effect on weight, whereas GLP1 analogues reduced weight by 1-2 kg. Hypoglycaemia rates were generally comparable in all treatment groups. These are promising results, but the available evidence is limited. This is a poorly investigated field with few RCTs. New studies focusing on head-to-head comparisons with short-acting insulin on top of basal insulin are needed.

The objective of this study is to investigate antibiotic prescription practices among hospital-based physicians in Greece, using the 2007 national guidelines as the golden standard. A total of 168 physicians participated. Compliance rate with the first-line antibiotic treatment recommended by the national guidelines was 65·5% for acute bacterial sinusitis; 24% for acute uncomplicated cystitis; 36·4% for an acute febrile diarrheic syndrome; 38% for an afebrile adult with chronic obstructive pulmonary disease and non-productive cough of 7 days duration; 23·2% for streptococcal pharyngotonsillitis; 55·1% for a surgically sutured, dirty wound; and 48·2% for community-acquired pneumonia. The total mean rate of compliance with the first recommended antibiotic was 41·2%.

Elevated serum uric acid (SUA) levels (i.e. hyperuricaemia) have been associated with metabolic syndrome (MetS) and cardiovascular disease (CVD) morbidity and mortality. Elevated SUA levels predict the onset of type 2 diabetes (T2DM). SUA levels are increased during the early stages of impaired glucose metabolism. Furthermore, in diabetic patients, hyperuricaemia has been linked to both micro- and macrovascular complications. The present review considers: (1) SUA levels in patients with MetS, type 1 diabetes and T2DM; (2) the mechanisms that influence SUA levels in these patients; (3) the potential links between SUA and diabetic complications. The effect on SUA levels of drugs commonly prescribed for T2DM and the risk of uric acid nephrolithiasis in patients with MetS or DM are also briefly discussed.