BACKGROUND:Rectal carriage of multidrug-resistant organisms (MDROs) and Clostridioides difficile contributes to hospital transmission, yet data from high-endemic settings remain limited. METHODS:We conducted a point-prevalence survey in October 2024 among 424 adult inpatients at a Greek university hospital. Rectal swabs were screened for carbapenem-resistant organisms (CROs), vancomycin-resistant enterococci (VRE), and C. difficile using molecular and culture methods. Participants were followed until discharge or death to assess clinical outcomes. Associations were evaluated using multivariable regression. RESULTS:Prevalence was 19.8% for CROs, 35.6% for VRE, and 9.9% for asymptomatic C. difficile. Among CRO carriers, Enterobacterales predominated (13.4%), followed by Pseudomonas aeruginosa (6.1%) and Acinetobacter baumannii (5.4%), with KPC- and NDM-type carbapenemases most frequently detected. Twenty patients carried multiple carbapenemase genes. VRE isolates were almost exclusively Enterococcus faecium with VanA phenotype. CRO and VRE carriage were associated with prolonged hospitalization (CRO: β-coef: 21.52 days, 95% CI: 8.82-34.22; VRE: β-coef: 21.37, 95% CI: 10.57-32.18). CRO carriage was associated with higher in-hospital mortality (OR: 2.50, 95% CI: 1.22-5.11) and CRO bloodstream infection (OR: 9.77, 95% CI: 1.60-58.03). Asymptomatic C. difficile carriage was linked to higher in-hospital mortality (OR: 3.77, 95% CI: 1.40-10.17). CONCLUSIONS:Rectal MDRO and C. difficile carriage is common in high-endemic hospital settings and associated with adverse clinical outcomes, highlighting the need for targeted surveillance, infection control, and antimicrobial stewardship.

Bacterial infections, especially bloodstream infections (BSIs), compromise the overall survival of patients with hematological malignancies undergoing cellular therapies. The interplay between rectal colonization by different types of multidrug-resistant organisms (MDRO) and subsequent BSIs is not fully determined. We aimed to describe the natural history and risk factors for colonization by MDRO, as well as its impact on subsequent BSIs in patients treated with cellular therapies in an environment of antimicrobial resistance. Retrospective, single-center cohort study of consecutive adult hematological malignancies patients treated with allogeneic or autologous hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell therapy between 2021 and 2024 in Attikon University Hospital (Greece), with ≥1 available rectal screening test for carbapenem-resistant gram-negative bacilli (CR-GNB) and vancomycin-resistant Enterococcus faecium (VRE). Univariate and multivariate Cox regression were implemented for identifying predictors of CR-GNB and VRE colonization. We also studied the concordance between rectal colonization and subsequent BSIs. One hundred eighty-two patients were included (male: 64%, mean age: 50.2 ± 13 yr, acute myeloid leukemia/myelodysplastic syndrome diagnosis: 55%, relapsing/refractory disease: 58%, allogeneic HCT: 85%). Median duration of hospitalization and neutropenia was 35 and 15 d, respectively. At baseline, 95% of patients were negative on rectal screening for both CR-GNB and VRE, and of those, 8.4% and 23% were colonized with CR-GNB and VRE during follow-up, respectively. Prior colonization with the same pathogen was independently associated with subsequent CR-GNB (HR: 13.0, 95% CI: 2.83 to 59.3) and VRE (HR: 4.83, 95% CI: 2.28 to 10.2) colonization. Seventy-nine patients had ≥1 BSIs (gram-positive: 60%, gram-negative: 38%), with three concordant CR-GNB BSIs among 16 colonized patients (18.7%) and two CR-GNB BSIs among 153 noncolonized patients (1.3%). Regarding VRE, we identified two concordant BSIs among 45 colonized patients (4.4%). Despite the high MDRO prevalence, we observed low rates of CR-GNB colonization in neutropenic patients treated with cellular therapies, with one patient out of five experiencing a concordant CR-GNB BSI. VRE colonization was more frequent, but it rarely resulted in a concordant BSI. These findings highlight the importance of infection control strategies and support de-escalation approaches in empirical antibacterial treatment of febrile neutropenia in this vulnerable population.

Remdesivir is recommended for hospitalized patients with severe COVID-19 and for those at high risk of progression. Real-world Omicron-era data on incidental COVID-19 and high-risk outpatients remain limited. We conducted a multicenter retrospective cohort study (ReEs-COVID19) in Greece (June-December 2022) including adults with PCR-confirmed SARS-CoV-2 infection who received remdesivir. Hospitalized patients with incidental COVID-19 (Group A, n = 138) and high-risk outpatients (Group B, n = 312) were analysed. Outcomes included clinical deterioration, mortality, and adverse events. Group A patients were older with more comorbidities. Remdesivir was initiated earlier in Group A (median 1 vs. 2 days) but with a more heterogeneous duration (48.9% vs. 97.8% in Group B, which received the standard 3-day regimen). Clinical deterioration due to COVID-19 occurred in 5.8% vs. 0.6%, and 30-day mortality was 18.1% (25/138) in Group A, including 10 COVID-19-related deaths (7.2%). Group B had two deaths (0.6%), none COVID-19-related. Adverse events were uncommon, with mild kidney injury in 3.6% of Group A and hepatotoxicity in 2.2% vs. 0.3%. In high-risk outpatients, the ReEs-COVID19 study confirmed the effectiveness and safety of remdesivir's profile. Among incidental cases, two distinct disease patterns were identified, associated with different remdesivir regimens and highlighting the importance of comorbidities and the need for tailored clinical interventions.

BACKGROUND:HIV-related stigma in healthcare settings remains a barrier to equitable care for people living with HIV. Data on HIV-related knowledge and stigmatizing attitudes among healthcare workers (HCWs) in Greece are limited. This study aimed to describe HIV-related knowledge, stigmatizing attitudes and discriminatory practices among HCWs in Greece and to identify factors associated with higher knowledge and stigma. METHODS:We conducted a secondary analysis of the Greek subset of the 2023 ECDC/EACS survey on HIV-related knowledge and stigma among HCWs. HIV knowledge was assessed using three items on undetectable equals untransmittable ('U=U'), post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), combined into a four-level ordinal variable. Stigmatizing attitudes were assessed using an eight-item mean score. Associations with knowledge were examined using proportional-odds ordinal logistic regression, and associations with stigma were assessed using a multivariable linear model. RESULTS:Among 826 respondents, correct knowledge was reported by 57.9% for 'U=U', 59.4% for PEP and 39.0% for PrEP. Nearly half answered no more than one item correctly. Higher knowledge was independently associated with younger age, male gender, doctor role, hospital-based practice and greater occupational contact with people living with HIV. The mean stigma score was 2.1 on a 1-5 scale. Higher stigma scores were independently associated with older age, lower HIV knowledge and absence of prior HIV stigma/discrimination training. Doctors had lower adjusted stigma scores than nurses in pairwise comparisons. CONCLUSIONS:Important gaps in HIV prevention knowledge and persistent stigmatizing attitudes were observed among HCWs in Greece. Findings support structured, decentralized educational and stigma-reduction interventions across healthcare settings.

Introduction:Paradoxical reactions during anti-tuberculosis treatment are immune-mediated reactions that complicate treatment even in immunocompetent patients. Case description:We present the case of a previously healthy 24-year-old man with disseminated tuberculosis, who experienced persistent fever, weight loss, and radiological deterioration despite appropriate treatment. These findings were consistent with a paradoxical reaction to treatment, after extensive work-up excluded treatment failure, co-infections, and systemic inflammatory conditions. However, high-dose corticosteroids failed to achieve improvement. Ultimately, an interleukin-1 receptor antagonist (anakinra) was initiated as a salvage therapy for this corticosteroid-refractory paradoxical reaction, resulting in rapid defervescence, normalization of inflammatory markers, and radiological improvement. Conclusion:This case underscores the diagnostic and therapeutic challenges when managing severe reactions in tuberculosis patients, while highlighting the importance of biologics like anakinra in corticosteroid-refractory paradoxical reactions. LEARNING POINTS:Paradoxical reactions to anti-tuberculosis treatment remain an overlooked cause of non-resolving fever in immunocompetent and immunocompromised patients with tuberculosis and should be considered after ruling out treatment-refractory or complicated infection in persistently febrile patients.Prompt treatment of severe reactions prevents major complications and improves clinical outcomes.Corticosteroid-refractory paradoxical reactions illustrate the potential role of biologics, such as tumour necrosis factor inhibitors and, in our case, interleukin-1 receptor antagonists, in controlling excessive inflammation in tuberculosis.

Abstract Background/Aim HIV infection is related with cardiovascular adverse events. We investigated the effects of antiretroviral treatment in myocardial and vascular function of newly diagnosed patients with HIV. Patients and methods: A total of 70 newly diagnosed HIV patients were enrolled. Patients were randomized to 4 different treatments which were descovy plus resolsta (emtricitabine/ tenofovir alafenamide), tivicay plus descovy (tenofovir alafenamide/ emtricitabine), genvoya (elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide) and descovy plus isentress (raltegravir). We measured at baseline and 12 months posttreatment: (a) Left Ventricular (LV) Global Longitudinal Strain (GLS), (b) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE). At baseline, we compared the HIV patients with 35 healthy matched controls. Results At baseline patients with HIV had devastated myocardial function, endothelial function and endothelial glycocalyx compared with healthy controls. Twelve months after intervention HIV patients improved myocardial function, as assessed by GLS, GWI and GCW as well as endothelial function as evaluated by decrease of PBR5-25. Nevertheless, in HIV patients 12 months post treatment myocardial and endothelial function and endothelial glycocaylyx was impaired in comparison with healthy controls. Conclusions Treatment with antiretroviral therapy partially improves myocardial and arterial function 12 months post treatment.

Background: Immunomodulators tocilizumab and baricitinib have been used for the treatment of severe COVID-19, however, there are only few published studies comparing their efficacy. Research design and methods: All consecutive non-ICU hospitalized severe COVID-19 patients who received baricitinib or tocilizumab, were included retrospectively. Primary outcomes were mortality or intubation on day 14, time to oxygen therapy weaning and duration of hospitalization. Safety was measured as treatment-related adverse events. Results: 321 hospitalized patients with severe COVID-19 were included (mean age 62.4 years +/- 14.7); 241 (75.1%) received baricitinib (mean age 64.2 years +/- 15.2) and 80 (24.9%) tocilizumab (mean age 57.3 +/- 11.7). Patients who received baricitinib presented significantly lower risk of mortality or intubation on day 14, compared to the tocilizumab group after adjusting for age, sex, vaccination, Charlson comorbidity index, body mass index, remdesivir administration and WHO ordinal scale at enrollment (OR: 0.42, 95% CI: 0.20-0.86). In the augmented inverse-probability weighting regression, the protective role of baricitinib remained statistically significant (OR: 0.76, 95% CI: 0.66-0.88). No difference in secondary bacterial infections was detected, but tocilizumab was associated with significant higher rate of liver injury (Odds Ratio, 95%CI, p < 0.001). Conclusions: Our study suggests survival and safety are significantly better for baricitinib compared to tocilizumab in severe COVID-19. Clinical randomized trials are needed for confirmation.

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive impairment (NCI) remains a concern despite combination antiretroviral therapy (cART), with cognitive problems often persisting even after viral suppression. The mechanisms underlying neurocognitive deterioration in people living with HIV (PLWH) and the role of plasma biomarkers remain unclear. This study aims to evaluate neurocognitive trajectories and biomarker changes in a real-world cohort of newly diagnosed PLWH initiating cART in Greece. Methods: This prospective, single-center study assessed neuropsychological performance and plasma biomarkers in treatment-naïve PLWH at baseline and 18 months after cART initiation. HIV-associated neurocognitive disorder (HAND) was classified using the Frascati criteria, and plasma biomarkers of inflammation and monocyte activation were measured. Correlations between biomarkers and cognitive performance were analyzed. Results: A total of 39 treatment-naïve PLWH were enrolled in this study. At baseline, 45.7% of participants met criteria for HAND, predominantly, asymptomatic neurocognitive impairment (ANI). Over 18 months, neurocognitive function improved, particularly in speed of information processing, executive function, and visuospatial ability, while verbal fluency, fine motor dexterity, and attention/working memory remained unchanged. Biomarkers of inflammation and monocyte activation decreased following cART, except for neopterin, which increased (10.6 vs. 13 ng/mL, p = 0.002), and plasma NFL (7.5 vs. 7.2 pg/mL, p = 0.54), which remained stable. A negative correlation between monocyte activation markers and cognitive performance was observed only at follow-up, suggesting that systemic inflammation may mask these associations in untreated PLWH. Conclusions: Early cART initiation supports neurocognitive recovery and reduces immune activation in PLWH. The observed correlation between cognitive performance and monocyte activation markers after viral suppression highlights the potential utility of plasma biomarkers in predicting cognitive impairment.

During the coronavirus disease-19 (COVID-19) pandemic, there was an unprecedented requirement for hospital bed availability. The present study aimed to examine the characteristics and outcomes of patients hospitalized in a COVID-19 unit that operated as a novel middle-step unit in Greece. The present study aimed to determine whether the middle-step unit supported the central general hospitals; thus, highlighting the potential of these models in future pandemics. During the 9-month period of operation, a total of 631 patients were admitted. In addition, 539 (85.4%) patients were discharged, 57 (9%) patients were referred to surrounding hospitals for further management and 35 (5.6%) patients succumbed. Based on the results of the present study, an algorithm for patient referral to middle-step units was outlined for future pandemics.

Introduction: Long-term lung sequelae in severe COVID-19 survivors, as well as their treatment, are poorly described in the current literature. Objective: To investigate lung fibrotic sequelae in survivors of severe/critical COVID-19 pneumonia and their fate according to a "non-interventional" approach. Methods: Prospective study of the above COVID-19 survivors after hospital discharge from March 2020 to October 2022. Re-evaluation lasted 3-12 months and included chest HRCT, PFTs, dyspnea, and overall health evaluation by modified Medical Research Council (mMRC) and St. George's Respiratory Questionnaire (SGRQ), respectively. Results: In this study, 198 patients (61.1% male) with a median age of 57 years (IQR 49-66). After 3 months, 187 (94.4%) patients were assessed; after 6 months, 82 (41.1%) patients were assessed; and after 12 months, 16 (8%) patients were assessed. At each time point, a significant reduction was observed in the extent of COVID-19-associated opacities (p < 0.001 and p = 0.002) and of parenchymal bands (p = 0.014 and p = 0.025). Persisting fibrotic-like changes were observed in 18 (9%) patients (apical findings in 2 patients, fibrotic non-specific interstitial pneumonia-like changes in 14 patients, minimal fibrotic changes in 2 patients). At 3 months, the predicted median FVC% was 93% (80-100%) and the predicted DLCO% was 65% (58-78%) with a statistically significant improvement at 6 months in both (p = 0.001). Moreover, 81.1% had mMRC ≤ 1 and the median SGRQ was 11.65 [0-24.3] with a significant reduction at 6 months in both dyspnea (p < 0.001) and SGRQ (p = 0.027) persisting at 12 months. Conclusions: This prospective study, including only survivors of severe/critical COVID-19 pneumonia, documented the significant improvement in all imaging, functional, and clinical parameters by applying the "non-interventional" approach. These data do not indicate any post-COVID-19 severe/critical pneumonia and "epidemic of widespread pulmonary fibrosis".

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has impacted global health. Remdesivir was approved based on clinical trials demonstrating improved outcomes in hospitalized patients. The ReEs-COVID19 study provides real-world evidence on its effectiveness and safety across two periods: Pre-Omicron and Omicron. This retrospective, observational cohort study included 1610 patients hospitalized with COVID-19, treated with remdesivir during Pre-Omicron (September 2020–February 2021; n = 606) and Omicron (June 2022–March 2023; n = 1004) periods. Primary endpoint: time to discharge; Hepatic/renal function abnormalities were also investigated. In the Omicron period patients were older and had more comorbidities but remdesivir was initiated earlier (median: 2 days from symptom onset) compared to the Pre-Omicron period (8 days). ICU admissions rates and direct COVID-19-related deaths were significantly lower, but overall 30-day mortality was higher during the Omicron period. Earlier remdesivir administration was associated with faster discharge. Abnormal liver tests and acute kidney injury were rare across both periods. ReEs-COVID19 confirmed remdesivir’s effectiveness and safety in real-world clinical settings during both periods, underscoring its importance in treatment of hospitalized COVID-19 patients, especially when initiated earlier in the disease course. Further research is needed to evaluate its utility in specific subgroups (e.g., immuno-compromised) and in combination with other treatments.

Abstract Background/Aim HIV infection is related with cardiovascular adverse events. We investigated the effects of antiretroviral treatment in myocardial and vascular function of newly diagnosed patients with HIV. Patients and methods A total of 70 newly diagnosed HIV patients (41.2±8.7 years old, 87 % male) were enrolled. Patients were randomized to the newer integrase inhibitor Dolutegravir or to the older protease inhibitor Darunavir/Cobicistat. We measured at baseline and 12 months posttreatment: (a) Left Ventricular (LV) Global Longitudinal Strain (GLS), (b) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE), (c) Coronary Flow Reserve (CFR) of Left Anterior Descending Artery. At baseline, we compared the HIV patients with 35 healthy matched controls. Results At baseline patients with HIV had impaired myocardial function, endothelial function and endothelial glycocalyx compared with healthy controls. Twelve months after intervention HIV patients improved myocardial function, as assessed by GLS, GWI, GCW, GWW and GWE (p<0.05). Moreover, twelve months after intervention HIV patients improved endothelial function, as evaluated by an increase in CFR and a decrease in PBR5-25 (p<0.05). Response to therapy was similar between the two groups of treatment. Nevertheless, in HIV patients 12 months post treatment myocardial, endothelial function and endothelial glycocaylyx was impaired in comparison with healthy controls. Conclusions Treatment with antiretroviral therapy partially improves myocardial and arterial function 12 months post treatment.

Abstract Introduction EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. Conclusions EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.

Introduction: Currently approved SARS-CoV-2 vaccines have been proven effective in protecting against severe COVID-19; however, they show variable efficacy against symptomatic infection and disease transmission. We studied the breakthrough COVID-19 infection (BTI) after booster vaccination against SARS-CoV-2 in people living with HIV (PWH). Methods: This was a retrospective, single-center, descriptive cohort study involving PWH, who were followed in the HIV Clinic of “Attikon” University Hospital in Athens, Greece. A BTI was defined as a case of laboratory-confirmed COVID-19 occurring at least 14 days after the third (booster) vaccine dose. Results: We studied 733 PWH [males: 89%, mean age: 45.2 ± 11.3 years, mean BMI: 26.1 ± 4.1, HIV stage at diagnosis (CDC classification): A/B/C = 80/9/11%, MSM: 72.6%] with well-controlled HIV infection. At least one comorbidity was recorded in 54% of cases. A history of ≥1 vaccination was reported by 90%, with 75% having been vaccinated with ≥3 vaccines. Four hundred and two (55%) PWH had a history of COVID-19 and 302 (41.2%) had a BTI, with only 15 (3.7%) needing hospitalization. Only one patient was admitted to the ICU, and no death was reported. Regarding BTI after booster dose, increased age (OR = 0.97, 95% CI: 0.96–0.99, per 1-year increase), and COVID-19 infection prior to booster dose (OR = 0.38, 95% CI: 0.21–0.68) were associated with a lower likelihood for BTI, whereas higher BMI (OR = 1.04, 95% CI: 1.01–1.08) and MSM as a mode of HIV transmission were associated with increased risk (OR = 2.59, 95% CI: 1.47–4.56). The incidence rate of total COVID-19 and BTI followed the epidemic curve of the general population, with the highest incidence recorded in June 2022. Conclusions: A significant proportion of PWH with well-controlled HIV infection experienced a BTI, with the majority of them having mild infection. These data, which include the period of Omicron variant predominance, confirm the importance of vaccination in the protection against severe COVID-19.

Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55–13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.