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.

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.

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.

Treatment of splenic marginal zone lymphoma with rituximab monotherapy: progress report and comparison with splenectomy.

BACKGROUND: Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy. AIM: To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results. METHODS: The studied population included 85 patients. Fifty-eight received rituximab at a dose of 375 mg/m2 per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1-2 years, whereas 27 patients were treated using splenectomy only. RESULTS: The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were 2 weeks and 3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression-free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p = .09) and 73% and 58% (p = .06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p <.0001). CONCLUSIONS: Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first-line treatment of choice for patients with SMZL.

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.

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.

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.

Early-stage gastric MALT lymphoma: is it a truly localized disease?

Early-stage gastric mucosa-associated lymphoid tissue lymphoma (GML) is considered a localized disease with an indolent course. Circulating malignant cells have been detected in other early-stage indolent lymphomas by molecular methods. We investigated the incidence of occult blood disease in early-stage GML patients, its impact on clinical outcome, and the similarity between blood and gastric lymphocytic clones. Sixty-two patients with localized GML were included in the study; 51 of them had Helicobacter pylori infection. Monoclonality was investigated by leader polymerase chain reaction. Sequencing was performed for the immunoglobulin variable gene (VH) analysis. Blood involvement was absent in all patients by conventional staging methods. In the whole group of 62 patients, the incidence of blood IgH rearrangement was 45%, and this did not correlate with baseline patient characteristics. The monoclonal blood and gastric products of five patients were sequenced and compared with each other. Clonal identity was evident in four of five patients. The VH3 gene was the most frequently used, both in the blood and in the stomach. Early-stage GML is not a truly localized disease because half the patients had a circulating clone, probably identical to the gastric one. The clinical significance of occult blood disease and the potential appropriate intervention need to be further investigated.

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.

Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital.

BACKGROUND: The dissemination of acquired metallo-beta-lactamases (MBLs) in members of the family Enterobacteriaceae is regarded as an emerging clinical threat. The clinical characteristics and outcomes of 17 cases of infection due to MBL-producing isolates were analyzed. METHODS: During a 3-year period, medical records for all patients with confirmed infection due to an MBL-producing strain belonging to the Enterobacteriaceae family were retrospectively analyzed. We screened for MBL production with the imipenem-ethylenediaminetetraacetic acid disk synergy test, and results were confirmed by polymerase chain reaction. Genetic relatedness between isolates was evaluated by repetitive extragenic palindromic polymerase chain reaction. RESULTS: Fourteen cases of bacteremia and 3 cases of ventilator-associated pneumonia due to an MBL-producing isolate were studied. Most of the patients had previously been colonized with an MBL-producing organism, and almost 60% had been exposed to carbapenems before infection. The isolated pathogens (Klebsiella pneumoniae, 14 cases; and Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes, 1 case each) exhibited variable minimum inhibitor concentrations of carbapenems (1 to >32 microg/mL) and resistance to most other beta-lactams. Tigecycline was active against all isolates, whereas colistin and gentamicin were active against 88% of them. Molecular studies confirmed the presence of a gene belonging to bla(VIM-1) cluster in all isolates. Among the 12 K. pneumoniae isolates, which were subjected to molecular typing, 11 distinct clones were identified. Five cases ( approximately 30%) occurred in patients who were already receiving carbapenem-containing treatment, and carbapenem treatment was considered to have failed. Twelve cases were treated with a colistin-containing regimen. The attributable mortality rate was 18.8%. CONCLUSIONS: MBL-producing Enterobacteriaceae can cause severe, often fatal infection in severely ill patients, irrespective of the MIC of carbapenems. Colonization with an MBL-producer is a preceding event, highlighting the importance of surveillance. Both infection control practices and antibiotic policies should be intensified to contain the spread of these problematic bacteria.

Screening for resistant gram-negative microorganisms to guide empiric therapy of subsequent infection.

OBJECTIVE: To define the potential of resistant gram-negative colonization surveillance to predict etiology of subsequent infection and improve adequacy of empiric antimicrobial treatment. DESIGN: Retrospective cohort study. SETTING: A mixed medical-surgical six-bed intensive care unit (ICU), from November 2003 to December 2006. PATIENTS: All patients having at least one episode of ventilator-associated pneumonia (VAP) or bloodstream infection (BSI) caused by a resistant gram-negative pathogen during the study period. INTERVENTIONS: Colonization surveillance of the respiratory tract and gastrointestinal tract was systematically performed in all ICU patients. Tracheal aspirates were obtained twice weekly and rectal swabs once weekly. Both tracheal and rectal samples were cultured in antibiotic-enriched media (containing ceftazidime, ciprofloxacin, imipenem or piperacillin/tazobactam), to focus on resistant gram-negative pathogen isolation. MEASUREMENTS AND RESULTS: Colonization concordance between resistant, gram-negative pathogens of infectious episodes and previous, recent (

Colistin susceptibility testing by Etest and disk diffusion methods.

The accuracy of disk susceptibility methods for colistin against 778 bacterial pathogens was evaluated in comparison with Etest using interpretive criteria available from the Clinical and Laboratory Standards Institute (CLSI). Colistin exhibited excellent activity against Acinetobacter baumannii and Escherichia coli isolates (minimum inhibitory concentration for 90% of the organisms (MIC(90))=0.5 mg/L), whilst it was less active both against Enterobacter spp. and Klebsiella pneumoniae (MIC for 50% of the organisms (MIC(50))=0.5 mg/L, MIC(90)=16 mg/L). Colistin also showed good activity against Pseudomonas aeruginosa (MIC(90)=2 mg/L, MIC(50)=1 mg/L) but poor activity against Stenotrophomonas maltophilia (MIC(50)=8 mg/L, MIC(90)=128 mg/L). Only 0.8% of minor errors were observed between the studied methods for P. aeruginosa isolates when the CLSI criteria were applied. All A. baumannii isolates with a zone diameter < or =12 mm were resistant and those with a zone diameter > or =14 mm were susceptible according to MIC breakpoints established by the CLSI. Among nine isolates exhibiting a zone diameter of 13 mm, one was resistant to colistin (MIC=8 mg/L) and eight isolates were susceptible (MIC=0.5 mg/L). Applying a MIC breakpoint of < or =2 mg/L for susceptibility in Enterobacteriaceae, all isolates with a zone diameter > or =14 mm were susceptible, whilst all isolates with a zone diameter < or =11 mm were resistant. Among isolates with zone diameters of 12-13 mm, 59% were characterised as susceptible. Major errors were observed only in K. pneumoniae isolates at a rate of 0.8%. The poor agar diffusion characteristics of colistin limit the predictive accuracy of the disk diffusion test and consequently values of 12-13 mm should be confirmed with MIC determination by Etest or broth dilution method.

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.