Candida auris: Outbreak, surveillance and epidemiological monitoring in Northern Greece.

Candida auris is an emerging fungal pathogen associated with multi-drug resistance rates and widespread outbreaks in hospitals and health care units worldwide. Sequencing studies have revealed that different clonal lineages of the fungus seem to be prevalent among distinct geographical sites. The first case of C. auris in Northern Greece was reported in Thessaloniki in October 2022, almost two years after the first isolation in Greece (Athens 2019). The Mycology Laboratory of the Medical School of Aristotle University of Thessaloniki stands as the reference laboratory for fungal diseases in Northern Greece and a meticulous search for the yeast, in plenty of suspicious samples, has been run since 2019 in the Lab as well as a retrospective analysis of all its yeasts' collection, back to 2008, with negative results for the presence of C. auris. Here, are presented the findings concerning the outbreak and surveillance of C. auris in Northern Greece, mainly the region of Thessaloniki and the broader area of Macedonia, from October 2022 until August 2023. The isolates from Northern Greece continue to fall in Clade I and present with an almost equal and stable sensitivity profile until now.

The study concerns the outbreak of Candida auris in Northern Greece since October 2022 and the effort for surveillance and epidemiological monitoring. All isolates continue to fall in Clade I and present with an almost equal and stable sensitivity profile till now.

Coinheritance of Triplicated Alpha-Globin Gene and Beta-Thalassemia Mutations in Adulthood: Ten Years of Referrals in Northern Greece.

Greece is a country of ~11 million people, where hemoglobinopathies are the most common genetic diseases. The reported data describe the clinical phenotype of cases with coinheritance of triplicated α-globin (anti-α3.7 kb) and ß-globin gene mutations in Northern Greece, that were referred within the last 10 years, in The Adult Thalassemia Unit of "Hippokration" Hospital, Thessaloniki, Northern Greece. The description of specific genotypes of the ß-globin gene mutations in coinheritance with the triplicated α-globin gene (anti-α3.7 kb) and correlation with the hematologic and clinical data in adulthood may be useful in the evaluation of pediatric patients' prognosis and in genetic counseling of couples at risk.

First Report of a Coincidental Discovery of Hb Antibes-Juan-Les-Pins (HBB: c.349_350insGTGTGCTGGCCC) in a Greek Woman.

The rare Hb Antibes-Juan-Les-Pins (HBB: c.349_350insGTGTGCTGGCCC) was first reported in France. Hb Antibes-Juan-Les-Pins seems to be an innocuous variant and few published data are available. Heterozygous carriers have mild clinical or hematological findings. The abnormal hemoglobin (Hb) is detected by high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CZE), but confirmation of the variant requires molecular analysis. This is the first description of Hb Antibes-Juan-Les-Pins heterozygosity in a woman of Greek origin.

Aspergillus galactomannan detection: Trichoderma as a cause of positive results.

Aspergillus galactomannan immunoassay is a main diagnostic and monitoring tool in medical mycology. However, the specificity of the method can be skewered by the presence of several other fungi. Trying to diagnose a possible fungal infection of the lower respiratory tract in a haematology patient, it appeared that the fungus Trichoderma longibrachiatum is an additional probable cause of positive galactomannan results. Although, that Trichoderma is a rare but emerging pathogen in immunocompromised patients, the above information could be a caution point in the clinical evaluation of diagnostic results.

Vaginal yeast colonisation: From a potential harmless condition to clinical implications and management approaches-A literature review.

Vaginal yeast colonisation is a common clinical condition in premenopausal women. The potential pathogenicity and the circumstances under which it could evolve into infection are not fully clarified. Extensive review the literature regarding the definition of the vaginal yeast colonisation, its demographic features and causes as well as the risk factors favouring infection along with the necessity of treatment. Databases, namely PubMed-MEDLINE, Google Scholar, the University College London databases, e-journals, e-books and official Health Organisations websites were extensively searched in English, French, German and Greek language with no restriction in the type of publications during the last thirty years. In healthy women, vaginal yeast colonisation is an asymptomatic state with Candida albicans being the most prevalent species. Pregnant, HIV-positive and diabetic hosts are at higher risk. Other risk factors include oral contraceptives, hormonal replacement therapy and previous antibiotic use. Colonisation does not necessitate therapeutic intervention when asymptomatic. Prophylactic therapy during the third trimester of pregnancy is often recommended for reducing the risk of neonatal candidiasis. The distinction between commensalism and vaginitis is often complicated. Clinicians should be aware of the clinical context in order to decide the indicated therapeutic approach.

Effects of major adipokines and the -420 C > G resistin gene polymorphism on the long-term outcome of patients with acute ischemic stroke.

Aim: The association between adiponectin, leptin, and resistin and the long-term outcome of ischemic stroke are controversial. We aimed to evaluate this relationship. Methods: We prospectively studied 83 patients consecutively hospitalized for acute ischemic stroke (38.6% males, age 79.7 ± 6.3 years). Serum adiponectin, leptin, and resistin levels and the -420C > G polymorphism of the resistin gene were determined at admission. Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS). Results: Patients with the G allele had lower mRS (p < .05) and patients with adverse outcome had higher serum resistin levels (p < .05). The only independent predictor of adverse outcome was mRS at discharge (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.54-5.00; p < .001). Higher adiponectin levels were an independent predictor of cardiovascular morbidity (RR 1.07, 95% CI 1.01-1.14; p < .05). Patients who died had higher serum adiponectin levels than those who survived (p < .05). The only independent predictor of all-cause mortality was NIHSS at admission (RR 1.19, 95% CI 1.04-1.35; p < .01). Conclusions: In patients with acute ischemic stroke, the G allele of the -420C > G polymorphism of the resistin gene promoter is more frequent in those with a more favorable functional outcome at one year after discharge. Patients with higher serum resistin levels appear to have worse long-term functional outcome, while higher serum adiponectin levels are associated with higher incidence of cardiovascular events.

Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) (HBB: c.118C>T) and the Presence of αααanti-3.7/αα in Greece. A Case Presentation.

The rare point mutation Cap +1570 (T>C) (HBB: c*96T>C) has been reported in families of Czech, Greek, Turkish and Italian origin. The mutation contributes to a reduction of the ß-globin chain synthesis, and in heterozygous carriers, it causes a silent phenotype, while in compound heterozygosity with severe ß-thalassemia (ß-thal) mutations, it leads to a non transfusion dependent ß-thal intermedia (ß-TI) state. We report a case of compound heterozygosity for codon 39 (C>T) (HBB: c.118C>T) and Cap +1570, in addition to the presence of αααanti-3.7/αα.

Compound Heterozygosity for Hb Adana (HBA2: c.179G>A) and the -α3.7/αα Thalassemia Deletion in Greece: Clinical Phenotype and Genetic Counseling.

Hb Adana (HBA2: c.179G>A) is found worldwide but is extremely rare and carriers are asymptomatic, with red cell indices similar to α+-thalassemia (α+-thal) carriers. First line screening tests are unable to detect the unstable hemoglobin (Hb). Coinheritance with the α-thal (-α3.7) deletion is herein presented and the challenges involving genetic counseling of couples carrying the mutations are discussed.

First Report of a Coincidental Discovery of Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] in a Greek Family.

The rare Hb Shimonoseki [α54(E3)Gln→Arg, HBA2: c.164A > G (or HBA1)] has been reported in Western Japan. Hb Shimonoseki seems to be an innocuous variant and few published data are available. Heterozygous carriers have no clinical or hematological findings. The abnormal hemoglobin (Hb) was detected by high performance liquid chromatography (HPLC) and classic electrophoresis or capillary electrophoresis (CE), but confirmation of the variant is based on molecular studies. This is the first description of Hb Shimonoseki heterozygosity in a Greek family.

Efficacy of the National Thalassaemia and Sickle Cell Disease Prevention Programme in Northern Greece: 15-Year Experience, Practice and Policy Gaps for Natives and Migrants.

Hemoglobinopathies constitute the most frequent monogenic disorders worldwide and in Greece. In Greece, carrier frequency is estimated at about 8.0%, resulting in a heavy disease burden in the past. Therefore, the implementation of a national prevention program of the disease was an urgent necessity. Moreover, due to migration flow from different geographic areas in the last two decades, the observed spectrum of underlying mutations was expanded, leading to the adaptation of diagnostic approaches. We report the results of the National Thalassaemia Prevention Programme in Northern Greece, over a 15-year period (2001-2015). In total 33,837 healthy at-risk individuals (individuals or couples, 91.0% Greeks) were screened. We have screened 1598 pregnancies in 371 (23.0%) (10.0% non Greeks), of whom both parents carried gene defects and were offered genetic counseling. Seventy-six fetuses (23.0%) were predicted to be affected by severe forms of the disease. Following informed parental choices, 73 of the above pregnancies were terminated. Meanwhile, within the study period, 58 new thalassemic babies (five non Greeks) were referred to the Thalassaemia and Sickle Cell Disease Care Unit of Northern Greece, reflecting mostly parental unawareness, choice or the program failure. Based on the region's population, the birth rate and the prevalence of the disease, the anticipated number of new cases is about 45 annually. According to our data, four thalassemic newborns were registered annually at a stable rate in the last 15 years, reaching a reduction of 90.0% of new affected births. Overall, the National Thalassaemia Prevention Programme effectively decreased the incidence of affected newborns in our region.

Major Adipokines and the -420C>G Resistin Gene Polymorphism as Predictors of Acute Ischemic Stroke Severity and In-Hospital Outcome.

BACKGROUND: The role of adiponectin, leptin, and resistin and the -420C>G polymorphism of the resistin gene promoter in the pathogenesis of ischemic stroke are controversial. We aimed to evaluate whether serum levels of these adipokines and the -420C>G polymorphism are associated with ischemic stroke severity and in-hospital outcome. METHODS: We prospectively studied 93 patients who were consecutively hospitalized for acute ischemic stroke (39.8% males, age 79.7 ± 6.3 years). Stroke severity was evaluated at admission by the National Institutes of Health Stroke Scale (NIHSS). In-hospital outcome was evaluated by dependency rates at discharge and in-hospital mortality. RESULTS: The G allele was more prevalent in patients with severe stroke (P < .05). Independent predictors of severe stroke were high-sensitivity C-reactive protein levels (relative risk [RR] 1.43, 95% confidence interval [CI] 1.08-1.91, P < .05). Patients with dependency at discharge had lower serum leptin levels (P < .05). Independent predictors of functional dependence were prior ischemic stroke (RR 7.55, 95% CI 1.69-33.58, P < .01), serum triglyceride levels (RR .98, 95% CI .96-0.99, P < .05), and NIHSS at admission (RR 1.47, 95% CI 1.17-1.84, P < .001). The G allele was more prevalent in patients who died (P < .05). Independent predictors of in-hospital mortality were systolic blood pressure (RR 1.09, 95% CI 1.01-1.19, P < .05) and NIHSS at admission (RR 1.26, 95% CI 1.08-1.48, P < .005). CONCLUSIONS: The G allele of the -420C>G polymorphism of the resistin gene promoter appears to be associated with more severe stroke and higher in-hospital mortality in patients with acute ischemic stroke. Higher leptin levels appear to be related to favorable functional outcome.

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence.

Extramedullary hematopoiesis (EMH) results from the extension of hematopoietic tissue beyond the confines of the bones. Since the initiation of regular transfusion programs from an early age for all thalassemia major (ΤΜ) patients, EMH has not been considered a clinical issue anymore. The present study aims to record the prevalence of EMH in chronically transfused ΤΜ patients followed at our institution and to investigate possible risk factors associated with its occurrence. The project was designed as a retrospective, nonexperimental, descriptive, exploratory study. In total, the study enrolled 104 patients. EMH was revealed in 15/104 (14%) patients. The presence of intravening sequence (IVS)-I-6 was significantly related with the development of EMH (p < 0.05). No other demographic or biological factor studied was found to be related with the presence of EMH. The study stresses a profound incidence of asymptomatic EMH in a solid group of well-transfused ΤΜ patients. Given the high incidence of the IVS-I-6 allele in the Mediterranean and Middle Eastern region, high-quality, prospective, multicenter studies could confirm the association of EMH occurrence with the presence of the IVS-I-6 mutation and further evaluate the exact role of this mutation in the EMH process.

Prevalence of onychomycosis among patients with nail psoriasis who are not receiving immunosuppressive agents: Results of a pilot study.

Nail psoriasis and onychomycosis can often be hard to differentiate clinically and may coexist, complicating each other's course. The aim of this study was to determine the prevalence of onychomycosis among patients with nail psoriasis not being treated with immunosuppressive agents, which constitute an independent risk factor for fungal infections. A cross-sectional study was performed. All adult patients with nail psoriasis who were not receiving antifungal and/or immunosuppressive treatment were recruited at the 2nd University Dermatology Department of Aristotle University of Thessaloniki from 10/2016 till 02/2017. If onychomycosis was clinically suspected, nail samples were collected and direct microscopy with 15% KOH solution and culture were performed. Target-NAPSI and DLQI score were also calculated. Of the 23 patients recruited, 20 were men and 3 were women, with a mean age of 53.43 years (48.25, 58.62), a mean target-NAPSI score of 10.72 (9.62, 11.77) and a mean DLQI score of 10.17 (7.46, 12.89). A total of 34.78% of patients tested positive for onychomycosis. Yeast were isolated in 37.50% of cases, non-dermatophyte filamentous fungi in 37.50% and T. rubrum in 12.50%. The prevalence of onychomycosis among nail psoriasis patients is higher than that among the general population of Greece (15%-20%). Yeast and moulds predominate in infection cases of nail psoriasis patients.

Pulmonary co-infections by Pneumocystis jirovecii and Aspergillus fumigatus in non-HIV patients: A report of two cases and literature review.

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life-threatening opportunistic infection in HIV-infected patients. However, non-HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co-infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non-HIV patients. Two cases of pulmonary co-infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non-HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non-Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co-infection by P. jirovecii and other fungi in non-HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.

Serum levels of leptin and IP-10 in preeclampsia compared to controls.

PURPOSE: Preeclampsia (PE) is a pregnancy-specific syndrome with a complex, yet elusive, etiology. The production of a variety of factors probably implicated in diverse pathways may trigger endothelial dysfunction leading to PE pathogenesis. The aim of the present study was to investigate and compare the concentrations of leptin and interferon-gamma-inducible protein-10 (IP-10), factors characterized by inflammatory, immunomodulatory and angiogenic activities, and to evaluate their possible interaction in women with normotensive pregnancy and PE. METHODS: The study was carried out on a total of 58 pregnant women, 29 women with PE and 29 controls. Serum leptin and IP-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum leptin levels were significantly increased in women with PE compared to controls and this difference was stronger in women with severe PE (p < 0.001). Although IP-10 serum concentrations were elevated in our preeclamptic women, this difference was not statistically significant. No correlation was found between leptin and IP-10. CONCLUSIONS: The results of the present study support a significant role of leptin in PE; however, this association was independent from serum IP-10 levels, suggesting that there is no crucial interplay between these two proteins in PE.

Serum levels of TNF- α , IL-12/23 p40, and IL-17 in psoriatic patients with and without nail psoriasis: a cross-sectional study.

Nail involvement has started playing a major role in the overall assessment and management of psoriatic disease. Biologics indicated for moderate to severe chronic plaque psoriasis are shown to be beneficial in nail disease. This study aimed to assess and compare the serum levels of TNF-α, IL-12/23 p40, and IL-17 in psoriatic patients with and without nail involvement. 52 consecutively selected patients with chronic plaque psoriasis were included in this cross-sectional study. Patients were studied and analyzed after they had been divided into 2 groups regarding the presence (n = 24) or not (n = 28) of nail psoriasis. The mean serum levels of TNF-α were significantly higher in the group of psoriatic patients with nail lesions compared to those without (t-test; 5.40 ± 1.17 versus 3.80 ± 1.63, P = 0.026). However, the median serum levels of both IL-12/23 p40 (Mann-Whitney; 92.52 (34.35-126.87) versus 150.68 (35.18-185.86), P = 0.297) and IL-17 (Mann-Whitney; 28.49 (0.00-28.49) versus 8.59 (0.00-8.59), P = 0.714) did not significantly differ between the 2 groups. These results confirm the important role of TNF-α in the pathogenesis of nail psoriasis and may suggest that anti-TNF agents could be more beneficial in psoriatic nail disease than agents targeting IL-12/23 p40 or IL-17 and its receptors.

Dermatophytic Biofilms: Characteristics, Significance and Treatment Approaches.

Microbes are found in the environment, possibly more often as biofilms than in planktonic forms. Biofilm formation has been described for several important fungal species. The presence of a dermatophytoma in a dermatophytic nail infection was the basis for the proposal that dermatophytes form biofilms as well. This could explain treatment failure and recurrent dermatophytic infections. Several investigators have performed in vitro and ex vivo experiments to study the formation of biofilms by dermatophytes and their properties. The nature of the biofilm structure itself contributes to fungal protection mechanisms against many harmful external agents, including antifungals. Thus, a different approach should be carried out regarding susceptibility testing and treatment. Concerning susceptibility testing, methods to evaluate either the inhibition of biofilm formation, or the ability to eradicate it, have been introduced. As for treatment, in addition to classical antifungal agents, some natural formulations, such as plant extracts or biosurfactants, and alternative approaches, such as photodynamic therapy, have been proposed. Studies that connect the results of the in vitro and ex vivo experimentation with clinical outcomes are required in order to verify the efficacy of these approaches in clinical practice.

Comparison of Equiosmolar Doses of 7.5% Hypertonic Saline and 20% Mannitol on Cerebral Oxygenation Status and Release of Brain Injury Markers During Supratentorial Craniotomy: A Randomized Controlled Trial.

BACKGROUND: Hyperosmolar therapy is the mainstay of treatment to reduce brain bulk and optimize surgical exposure during craniotomy. This study investigated the effect of equiosmolar doses of 7.5% hypertonic saline (HTS) and 20% mannitol on intraoperative cerebral oxygenation and metabolic status, systemic hemodynamics, brain relaxation, markers of cerebral injury, and perioperative craniotomy outcomes. METHODS: A total of 51 patients undergoing elective supratentorial craniotomy were randomly assigned to receive 7.5% HTS (2 mL/kg) or 20% mannitol (4.6 mL/kg) at scalp incision. Intraoperative arterial and jugular bulb blood samples were collected at predefined time intervals for assessment of various indices of cerebral oxygenation; multiple hemodynamic variables were concomitantly recorded. S100B protein and neuron-specific enolase levels were determined at baseline, and at 6 and 12 hours after surgery for assessment of neuronal injury. Brain relaxation and perioperative outcomes were also assessed. RESULTS: Demographic and intraoperative data, brain relaxation score, and perioperative outcomes were comparable between groups. Jugular bulb oxygen saturation and partial pressure of oxygen, arterial-jugular oxygen and carbon dioxide differences, and brain oxygen extraction ratio were favorably affected by 7.5% HTS up to 240 minutes postinfusion ( P <0.05), whereas mannitol was associated with only a short-lived (up to 15 min) improvement of these indices ( P <0.05). The changes in cerebral oxygenation corresponded to transient expansion of intravascular volume and improvements of cardiovascular performance. Increases in S100B and neuron-specific enolase levels at 6 and 12 hours after surgery ( P <0.0001) were comparable between groups. CONCLUSIONS: The conclusion is that 7.5% HTS has a more beneficial effect on cerebral oxygenation than an equiosmolar dose of 20% mannitol during supratentorial craniotomy, yet no clear-cut clinical superiority of either solution could be demonstrated.

Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Markers of Vascular Damage.

BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular morbidity and delay the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms underpinning these benefits are not entirely clear. More specifically, it is uncertain whether these agents exert cardiorenal protective effects through a direct action on the vascular wall. The aim of the present study was to evaluate the effects of SGLT2 inhibitors on markers of subclinical vascular damage. METHODS: In total, 40 adult patients with T2DM and glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 and age- and gender-matched patients with T2DM and GFR > 60 mL/min/1.73 m2 were consecutively enrolled. Indices of arterial stiffness (pulse wave velocity, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (Alx@75) and central systolic, diastolic, pulse and mean pressure), carotid atherosclerosis (stenosis, intima-media thickness (cIMT) and maximal plaque thickness) and peripheral arterial disease (ankle brachial index (ABI)) were determined. The chi-squared and Mann-Whitney U-test were used to detect differences in categorical and continuous variables between groups, respectively. RESULTS: In total, 15 patients were treated with SGLT2 inhibitors and 25 patients were not receiving these agents. Serum low-density lipoprotein cholesterol levels were lower in the former whereas other cardiovascular risk factors, the prevalence of established cardiovascular disease, anthropometric and demographic characteristics, and vital signs did not differ between the 2 groups. The AIx was lower in patients treated with SGLT2 inhibitors (21.9 ± 11.3 vs. 29.7 ± 12% in patients not treated with SGLT2 inhibitors; p < 0.05). The AIx@75 was also lower in the former (21.3 ± 10.9 and 32.6 ± 11.3%, respectively, p < 0.005). Other markers of arterial stiffness were similar in the 2 groups. In addition, markers of carotid atherosclerosis and the ABI did not differ between patients treated and not treated with SGLT2 inhibitors. CONCLUSIONS: Treatment with SGLT2 inhibitors appears to reduce arterial stiffness. Accordingly, these agents might improve cardiovascular outcomes not only in patients with T2DM and established cardiorenal disease but also in lower-risk patients.