Candida auris in Greek healthcare facilities: Active surveillance results on first cases and outbreaks from eleven hospitals within Attica region.

BACKGROUND: Candida auris was sporadically detected in Greece until 2019. Thereupon, there has been an increase in isolations among inpatients of healthcare facilities. AIM: We aim to report active surveillance data on MALDI-TOF confirmed Candida auris cases and outbreaks, from November 2019 to September 2021. METHODS: A retrospective study on hospital-based Candida auris data, over a 23-month period was conducted, involving 11 hospitals within Attica region. Antifungal susceptibility testing and genotyping were conducted. Case mortality and fatality rates were calculated and p-values less than 0.05 were considered statistically significant. Infection control measures were enforced and enhanced. RESULTS: Twenty cases with invasive infection and 25 colonized were identified (median age: 72 years), all admitted to hospitals for reasons other than fungal infections. Median hospitalisation time until diagnosis was 26 days. Common risk factors among cases were the presence of indwelling devices (91.1 %), concurrent bacterial infections during hospitalisation (60.0 %), multiple antimicrobial drug treatment courses prior to hospitalisation (57.8 %), and admission in the ICU (44.4 %). Overall mortality rate was 53 %, after a median of 41.5 hospitalisation days. Resistance to fluconazole and amphotericin B was identified in 100 % and 3 % of tested clinical isolates, respectively. All isolates belonged to South Asian clade I. Outbreaks were identified in six hospitals, while remaining hospitals detected sporadic C. auris cases. CONCLUSION: Candida auris has proven its ability to rapidly spread and persist among inpatients and environment of healthcare facilities. Surveillance focused on the presence of risk factors and local epidemiology, and implementation of strict infection control measures remain the most useful interventions.

Prognostic Impact of Serum ß2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients.

The significance of serum beta-2 microglobulin (sß2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sß2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sß2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sß2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sß2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sß2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sß2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sß2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.

Population-based study of influenza and invasive meningococcal disease among Greek children during the COVID-19 pandemic.

BACKGROUND: Aiming to the containment of the coronavirus disease 2019 (COVID-19) pandemic, governments worldwide have implemented a series of non-pharmaceutical interventions. Many of them and especially school closures have impacted the circulation of multiple airborne pathogens among children and adolescents. This study investigates the incidence of influenza and invasive meningococcal disease among children aged 0-14 years in Greece during the COVID-19 pandemic. METHODS: Data regarding the number of influenza-like illness cases, influenza-related paediatric intensive care unit (PICU) admissions and invasive meningococcal disease cases among children 0-14 years old were obtained from the National Public Health Organization. The incidence of the two diseases during the COVID-19 pandemic period (2020/2021) was compared with that of the six preceding seasons (2014-2019). RESULTS: A notable decrease was observed in both influenza and invasive meningococcal disease cases during the period 2020/2021 compared with the years 2014-2019. The mean annual rate of influenza-like illness cases and influenza-related PICU admissions in children 0-14 years old has reduced by 66.9% and 100%, respectively, while the mean annual invasive meningococcal disease rate has declined by 70%. Both weekly influenza-like illness and monthly invasive meningococcal disease rates were significantly decreased. CONCLUSIONS: The activity of influenza and invasive meningococcal disease in the children and adolescents of Greece has decreased during the COVID-19 pandemic period. Reduced transmission is likely related to the public health measures that were implemented to control the pandemic. The value of these measures may have relevance to the future management of influenza or invasive meningococcal disease epidemics.

Comparative effectiveness and durability of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign.

As national coronavirus disease 2019 (COVID-19) mass vaccination campaigns are rolled out, monitoring real-world Vaccine Effectiveness (VE) and its durability is essential. We aimed to estimate COVID-19 VE against severe disease and death in the Greek population, for all vaccines currently in use. Nationwide active surveillance and vaccination registry data during January-December 2021 were used to estimate VE via quasi-Poisson regression, adjusted for age and calendar time. Interaction terms were included to assess VE by age group, against the "delta" severe acute respiratory syndrome coronavirus 2 variant and waning of VE over time. Two doses of BNT162b2, mRNA-1273, or ChAdOx1 nCov-19 vaccines offered very high (>90%) VE against both intubation and death across all age groups, similar against both "delta" and previous variants, with one-dose Ad26.COV2.S slightly lower. VE waned over time but remained >80% at 6 months, and three doses increased VE again to near 100%. Vaccination prevented an estimated 19 691 COVID-19 deaths (95% confidence interval: 18 890-20 788) over the study period. All approved vaccines offer strong and also durable protection against COVID-19 severe disease and death. Every effort should be made to vaccinate the population with at least two doses, to reduce the mortality and morbidity impact of the pandemic.

Human Brucellosis in Greece, 2005-2020: A Persistent Public Health Problem.

Brucellosis remains an important zoonosis in various parts of the world. In Greece, brucellosis is endemic in sheep and goats. Since 1998, animal control measures include vaccination of sheep and goats older than 3 months of age in the mainland (vaccination zone) and slaughtering of infected livestock on the islands (eradication zone). We retrieved data from the mandatory notification system for 2005-2020 to describe the epidemiology in humans and assess current public health measures. Overall, 1786 notifications and an additional 111 cases related to an outbreak in 2008 (eradication zone) were recorded. The mean annual notification rate was 0.9/100,000 population (standard deviation [SD]: 0.35). A substantial mean annual decline in notification rate was reported in 2019 and 2020. A statistically significant decreasing trend of brucellosis notification rate was observed over the whole 16-year period (p < 0.001). The mean annual notification rate was significantly higher in the vaccination zone (1.2/100,000) (SD: 036) compared with the eradication zone (0.2/100,000) (SD: 0.14) (p < 0.001). Seventy percent of cases was male (n = 1175) and the highest mean notification rate was recorded in the 45-64 age group (1.3/100,000). The majority of cases (71%) reported animal contact and almost half of the cases (49%) were stockbreeders by occupation. Consumption of unpasteurized dairy products, mainly of their own production, was reported by 57% of cases; for 115 (6.5%) cases, animal exposure or consumption of unpasteurized dairy products were not recorded. Despite animal control measures, brucellosis remains endemic in Greece with cases in the vaccination zone, as well as the eradication zone. We recommend re-evaluation and strengthening of animal control programs and training of people working in stock breeding regarding disease transmission in co-operation with local farmers' associations.

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021.

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.

Hypertensive crisis and pulmonary edema following rituximab-induced anaphylaxis.

Rituximab is a monoclonal antibody against the protein CD20. Various lymphomas as well as non-malignant immune disorders are treated with this antibody. Hypersensitivity reactions associated with the use of rituximab include urticaria, hypotension, chest tightness, vomiting, oxygen desaturation and bronchospasm. A very uncommon case of hypertensive crisis and pulmonary edema following rituximab-induced hypersensitivity reaction in an 80-year-old man receiving rituximab for non-Hodgkin lymphoma is reported. Anaphylaxis manifesting as coronary vasospasm following drug treatment, including rituximab, could be proved a serious condition in patients who need specific treatment. In these patients desensitization protocols seem to be mandatory.

Successful treatment of noncirrhotic portal hypertension with eculizumab in paroxysmal nocturnal hemoglobinuria: A case report.

BACKGROUND: Idiopathic non-cirrhotic portal hypertension (INCPH) is mainly associated with thrombophilia in Western countries. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. Portal and hepatic venous thrombosis were reported in PNH. A rare case of INCPH complicating PNH is described. CASE SUMMARY: A 63-year old woman with a 2-year past medical history of PNH without treatment was admitted because of jaundice and refractory ascites requiring large volume paracentesis. Liver histology revealed portal venopathy with portal fibrosis and sclerosis, nodular regenerative hyperplasia, parenchymal ischemic changes, and focal sinusoidal and perivenular fibrosis without bridging fibrosis or cirrhosis, all indicative of INCPH. The flow cytometry confirmed PNH diagnosis and eculizumab treatment was initiated. Her condition was improved gradually, bilirubin was normalized 6 months following initiation of eculizumab, and 1 year later diuretics were stopped. CONCLUSION: Eculizumab improved intravascular hemolysis and reversed clinical manifestations of INCPH in a patient with paroxysmal nocturnal hemoglobinuria.

The prognostic significance of chromosome 17 abnormalities in patients with myelodysplastic syndrome treated with 5-azacytidine: Results from the Hellenic 5-azacytidine registry.

In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS-R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5-azacytidine through the Hellenic 5-azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with -17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS-R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan-Meier, Log Rank P < 0.00001), but these results were confounded by the fact that most (92.3%) of the cases with a chromosome 17 abnormality (with the exception of i(17q) that was found in all cases as an isolated abnormality) were found in the context of a complex karyotype. Nevertheless, one should not ignore the contribution of chromosome 17 abnormalities to the prognostic significance of a complex karyotype since 33.8% of complex karyotypes encompassed a chromosome 17 abnormality.

Prevalence, incidence burden, and clinical impact of healthcare-associated infections and antimicrobial resistance: a national prevalent cohort study in acute care hospitals in Greece.

BACKGROUND: Assessing the overall burden of healthcare-associated infections (HAIs) is challenging, but imperative in evaluating the cost-effectiveness of infection control programs. This study aimed to estimate the point prevalence and annual incidence of HAIs in Greece and assess the excess length of stay (LOS) and mortality attributable to HAIs, overall and for main infection sites and tracer antimicrobial resistance (AMR) phenotypes and pathogens. PATIENTS AND METHODS: This prevalent cohort study used a nationally representative cross-section of 8,247 inpatients in 37 acute care hospitals to record active HAIs of all types at baseline and overall LOS and in-hospital mortality up to 90 days following hospital admission. HAI incidence was estimated using prevalence-to-incidence conversion methods. Excess mortality and LOS were assessed by Cox regression and multistate models correcting for confounding and time-dependent biases. RESULTS: HAIs were encountered with daily prevalence of 9.1% (95% confidence interval [CI] 7.8%-10.6%). The estimated annual HAI incidence was 5.2% (95% CI 4.4%-5.3%), corresponding to approximately 121,000 (95% CI 103,500-123,700) affected patients each year in the country. Ninety-day mortality risk was increased by 80% in patients with HAI compared to those without HAI (adjusted hazard ratio 1.8; 95% CI 1.3-2.6). Lower respiratory tract infections, bloodstream infections, and multiple concurrent HAIs doubled the risk of death, whereas surgical site and urinary tract infections were not associated with increased mortality. AMR had significant impact on the daily risk of 90-day mortality, which was increased by 90%-110% in patients infected by carbapenem-resistant gram-negative pathogens. HAIs increased LOS for an average of 4.3 (95% CI 2.4-6.2) additional days. Mean excess LOS exceeded 20 days in infections caused by major carbapenem-resistant gram-negative pathogens. CONCLUSION: HAIs, alongside with increasing AMR, pose significant burden to the hospital system. Burden estimates obtained in this study will be valuable in future evaluations of infection prevention programs.

The significance of platelet microparticles in patients with chronic hepatitis C and their association with antiviral treatment and smoking.

BACKGROUND: Platelet microparticles (PMPs) are platelet-derived membrane vesicles involved in cardiovascular diseases and atherosclerosis. Chronic hepatitis C (CHC) is associated with increased atherosclerosis, but the effect of therapy on its atherogenic potential has not been adequately studied. METHODS: We evaluated PMP levels before and after treatment with pegylated-interferon-alfa and ribavirin in 28 CHC patients compared with 20 non-alcoholic fatty liver disease (NAFLD) patients and 20 healthy volunteers (HV). RESULTS: Twenty-four (86%) CHC patients achieved sustained virological response (SVR). PMP levels were determined at baseline in CHC, NAFLD patients, and HV, and at end-of-treatment (EOT) and 24 weeks post-treatment (SVR24) in CHC patients. PMP levels at baseline were higher in CHC than NAFLD patients (P<0.001) and HV (P=0.007). Higher PMPs at baseline were observed in smokers than non-smokers with CHC (P=0.006). Among smokers from all groups, PMPs at baseline were higher in CHC than NAFLD patients (P=0.001) and HV (P=0.024). In CHC patients, PMPs declined from baseline to both EOT (P=0.035) and SVR24 (P=0.006). Only CHC patients with SVR had a significant decline in PMPs from baseline to SVR24 (P=0.018). PMPs at ΕΟΤ and SVR24 in all CHC patients were similar to PMPs in NAFLD patients and HV. CONCLUSIONS: PMP levels are increased in CHC patients, particularly smokers, which further supports the atherosclerotic potential of CHC and suggests a potentially synergistic effect of smoking and CHC on the atherosclerotic process. Since PMP levels in CHC patients with SVR were similar to NAFLD patients and HV, the atherosclerotic potential of CHC seems to be abolished by effective antiviral treatment.

Immunohistochemical analysis of IL-6, IL-8/CXCR2 axis, Tyr p-STAT-3, and SOCS-3 in lymph nodes from patients with chronic lymphocytic leukemia: correlation between microvascular characteristics and prognostic significance.

A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼ 40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereas IL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.

Action Plan to combat infections due to carbapenem-resistant, Gram-negative pathogens in acute-care hospitals in Greece.

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.

Apoptotic and proliferative characteristics of proliferation centers in lymph node sections of patients with chronic lymphocytic leukemia.

We have analyzed the immunohistochemical expression of a wide range of molecules along with the proliferation rate separately in the proliferation centers (PCs) and in the rest of the tumor area, in lymph node or spleen sections of patients with chronic lymphocytic leukemia (CLL). Fas, FasL and c-FLIP were observed both within and outside the PCs in all cases. However, only the difference in FasL expression between the PCs and the non-PC areas attained statistical significance. Median survivin expression in the PCs was higher compared to the non-PC areas. Cleaved caspase 3 was expressed at very low levels both within and outside PCs, while BCL-2 protein was expressed at high levels in all cases in both tumor compartments. Multivariate analysis demonstrated that concurrent overexpression of Fas/FasL/c-FLIP in the PCs was correlated with worse outcome for progression-free survival as well as for overall survival.