The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS.

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.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

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.

Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2.

OBJECTIVES: B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. METHODS: Serum and whole blood samples were collected from RTX-treated rheumatic patients 3-6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. RESULTS: Sixty patients were studied after a median (IQR) of 179 (117-221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4-10.75) vs 11 (6.75-14.75) grams, (P = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2-4) vs 6 (4-8), P = 0.002] and cumulative dose [4 (3-7) vs 10 (6.25-13) grams, P = 0.002] and had shorter time from last vaccination to sampling [140 (76-199) vs 192 (128-230) days, P = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P = 0.03). CONCLUSIONS: Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2.

The impact of frailty and illness perceptions on quality of life among people living with HIV in Greece: A network analysis.

OBJECTIVE: Despite the significant advances in healthcare, people living with HIV still face challenges that affect their quality of life (QoL), both in terms of their physical state as represented by frailty and of their illness perceptions (IP). The aim of this study was to unravel the associations between these constructs (QoL, frailty, IP). METHODS: This multicenter, cross-sectional study included 477 people living with HIV (93% male; median age = 43 years, IQR = 51.7) from six HIV clinics in Greece. Frailty phenotype, QoL and IP were assessed using Fried's criteria, EuroQoL (EQ-5D-5L) and Brief Illness Perception Questionnaire (BIPQ), respectively. Network analysis model was utilized. RESULTS: Among frailty criteria, exhaustion had the highest expected influence, while the strongest correlation concerns exhaustion and weak grip strength (pr = 0.14). Regarding the QoL items, usual activities displayed the highest expected influence. The correlations of pain/discomfort with mobility (pr = 0.31), and usual activities with self-care (pr = 0.34) were the strongest. For the BIPQ items, the strongest correlation was found between illness concern and emotional response (pr = 0.45), whereas the latter item was the one that displayed the highest expected influence. Three communities were formed: 1) personal control, treatment control and coherence, 2) the frailty items with mobility, self-care, usual activities, and pain/discomfort, and 3) the rest BIPQ items with anxiety/depression. Identity displayed the highest bridge strength, followed by pain/discomfort, usual activities and consequences. CONCLUSIONS: The interplay between QoL, frailty, and IP in people living with HIV requires clinical attention. Self-reported exhaustion, slow walking speed, and low physical activity affect the physical QoL dimensions, while anxiety/depression is strongly associated with illness-related concern and perceived emotional effects, leading to psychological distress. Symptom management can improve QoL, and information on the disease and treatment can enhance control over the disease. Developing interventions to address QoL, frailty, and IP is crucial.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk.

BACKGROUND: Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable. METHODS: The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy. RESULTS: Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence. CONCLUSIONS: Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations.

Remdesivir: Effectiveness and Safety in Hospitalized Patients with COVID-19 (ReEs-COVID-19)-Analysis of Data from Daily Practice.

Remdesivir was the first antiviral approved for treating COVID-19. We investigated its patterns of use, effectiveness and safety in clinical practice in Greece. This is a retrospective observational study of hospitalized adults who received remdesivir for COVID-19 in September 2020-February 2021. The main endpoints were the time to recovery (hospital discharge within 30 days from admission) and safety. The "early" (remdesivir initiation within 24 h since hospitalization) and "deferred" (remdesivir initiation later on) groups were compared. One thousand and four patients (60.6% male, mean age 61 years, 74.3% with severe disease, 70.9% with ≥1 comorbidities) were included, and 75.9% of them were on a 5-day regimen, and 86.8% were in the early group. Among those with a baseline mild/moderate disease, the median (95% CI) time to recovery was 8 (7-9) and 12 (11-14) days for the early and deferred groups, respectively (p < 0.001). The corresponding estimates for those with a severe disease were 10 (9-10) and 13 (11-15) days, respectively (p = 0.028). After remdesivir initiation, increased serum transaminases and an acute kidney injury were observed in 6.9% and 2.1%, respectively. Nine (0.9%) patients discontinued the treatment due to adverse events. The effectiveness of remdesivir was increased when it was taken within 24 h since admission regardless of the disease severity. Remdesivir's safety profile is similar to that described in clinical trials and other real-world cohorts.

Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) µm at baseline to 2.04 (0.26) µm (p = 0.019), and then to 1.93 (0.3) µm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study.

Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020-April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC50/90 values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Low pre-ART CD4 count is associated with increased risk of clinical progression or death even after reaching 500 CD4 cells/µL on ART.

INTRODUCTION: Clinical disadvantages of initiating ART at low CD4 counts have been clearly demonstrated but whether any excess risk remains even after reaching relatively high/safe CD4 levels remains unclear. We explore whether individuals starting ART with <500 CD4 cells/µL who increased their CD4 count above this level, have, from this point onwards, similar risk of clinical progression to serious AIDS/non-AIDS events or death with individuals starting ART with ≥500 CD4 cells/µL. METHODS: Data were derived from a multicenter cohort (AMACS). Adults, starting PI, NNRTI or INSTI based ART, in or after 2000 were eligible, provided they started ART with ≥500 ("High CD4") or started with CD4 <500 cells/µL but surpassed this threshold while on ART ("Low CD4"). Baseline was the date of ART initiation ("High CD4") or of first reaching 500 CD4 cells/µL ("Low CD4"). Survival analysis, allowing for competing risks, was used to explore the risk of progression to study's endpoints. RESULTS: The study included 694 persons in the "High CD4" and 3,306 in the "Low CD4" group. Median (IQR) follow-up was 66 (36, 106) months. In total, 257 events (40 AIDS related, 217 SNAEs) were observed. Rates of progression did not differ significantly between the two groups but the subgroup of those initiating ART with <200 CD4 cells/µL had significantly higher risk of progression after baseline, compared to those in the "High CD4" group. CONCLUSIONS: Individuals starting ART with <200 cells/µL remain on increased risk even after reaching 500 CD4 cells/µL. These patients should be closely followed.

Cardiovascular disease and risk assessment in people living with HIV: Current practices and novel perspectives.

Human immunodeficiency virus (HIV) infection represents a major cardiovascular risk factor, and the cumulative cardiovascular disease (CVD) burden among aging people living with HIV (PLWH) constitutes a leading cause of morbidity and mortality. To date, CVD risk assessment in PLWH remains challenging. Therefore, it is necessary to evaluate and stratify the cardiovascular risk in PLWH with appropriate screening and risk assessment tools and protocols to correctly identify which patients are at a higher risk for CVD and will benefit most from prevention measures and timely management. This review aims to accumulate the current evidence on the association between HIV infection and CVD, as well as the risk factors contributing to CVD in PLWH. Furthermore, considering the need for cardiovascular risk assessment in daily clinical practice, the purpose of this review is also to report the current practices and novel perspectives in cardiovascular risk assessment of PLWH and provide further insights into the development and implementation of appropriate CVD risk stratification and treatment strategies, particularly in countries with high HIV burden and limited resources.

Switching from Tenofovir Disoproxil to Tenofovir Alafenamide Fumarate: Impact on Cardiovascular Risk and Lipid Profile in People Living with HIV, an Observational Study.

In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with emtricitabine/elvitegravir/cobicistat (FTC/EVG/c), in patients with no exposure to other antiretrovirals. Routine laboratory measurements, somatometric characteristics, and smoking status were analyzed for the assessment of CVD risk changes, using D:A:D and ATP III scores pre- and postswitch. A total of 62 patients with a mean age of 32.9 years were included in this study. Sixty-one patients (98.4%) were men, 38 (61.3%) late presenters, and 39 (62.9%) active smokers. A year after the switch, there was a significant increase in total cholesterol (178 ± 38 to 194 ± 40 mg/dL, p < .001), high-density lipoprotein (45 ± 12 to 48 ± 13 mg/dL, p = .001), and low-density lipoprotein (117 ± 32 to 137 ± 36 mg/dL, p < .001). Mean increase of the 10-year D:A:D score was 1.13% (95% confidence interval, 1.05-1.22, p = .002). Changes were more prominent in nonsmokers. Body mass index and average weight showed an upward trend. Switching from TDF to TAF caused significant changes in lipid profile at 14 months of follow-up, in young, otherwise healthy PLHIV. CVD risk, as measured by D:A:D, showed a statistically significant increase, but more data are needed to determine clinical significance. These results point toward a patient-centered approach when selecting an ART regimen.

Mapping frailty in people living with HIV: A nationwide study in Greece.

OBJECTIVES: Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data. METHODS: Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored. RESULTS: The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/µl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty. CONCLUSIONS: Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.

Severe eosinophilic granulomatosis with polyangiitis responding to a combination of rituximab and mepolizumab.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is a multisystem antineutrophil cytoplasmic antibody (ANCA) positive vasculitis, characterized by the presence of chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Although the most commonly involved organ is the lung, followed by the skin, EGPA can affect any organ system. Herein, we present the complicated case of an 18-year-old male patient with severe life-threatening EGPA, with central nervous system, cardiac and gasterointestinal involvement, which was resistant to initial treatment with glucocorticoids and cyclophosphamide. The patient responded well, achieving complete remission after the addition of rituximab and mepolizumab to glucocorticoids and cyclophosphamide.

Insights into CD24 and Exosome Physiology and Potential Role in View of Recent Advances in COVID-19 Therapeutics: A Narrative Review.

Cluster of differentiation (CD) 24, a long-known protein with multifaceted functions, has gained attention as a possible treatment for Coronavirus Disease 19 (COVID-19) due to its known anti-inflammatory action. Extracellular vesicles (EVs), such as exosomes and microvesicles, may serve as candidate drug delivery platforms for novel therapeutic approaches in COVID-19 and various other diseases due to their unique characteristics. In the current review, we describe the physiology of CD24 and EVs and try to elucidate their role, both independently and as a combination, in COVID-19 therapeutics. CD24 may act as an important immune regulator in diseases with complex physiologies characterized by excessive inflammation. Very recent data outline a possible therapeutic role not only in COVID-19 but also in other similar disease states, e.g., acute respiratory distress syndrome (ARDS) and sepsis where immune dysregulation plays a key pathophysiologic role. On the other hand, CD24, as well as other therapeutic molecules, can be administered with the use of exosomes, exploiting their unique characteristics to create a novel drug delivery platform as outlined in recent clinical efforts. The implications for human therapeutics in general are huge with regard to pharmacodynamics, pharmacokinetics, safety, and efficacy that will be further elucidated in future randomized controlled trials (RCTs).

Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

OBJECTIVES: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis. METHODS: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B. RESULTS: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks. CONCLUSIONS: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations.

Filamentous Fungal Keratitis in Greece: A 16-Year Nationwide Multicenter Survey.

In a multicenter, prospective study of filamentous fungal keratitis in Greece, predisposing factors, etiology, treatment practices, and outcome, were determined. Corneal scrapings were collected from patients with clinical suspicion of fungal keratitis, and demographic and clinical data were recorded. Fungal identification was based on morphology, molecular methods, and matrix assisted laser desorption ionization time-of-flight mass-spectrometry. A total of 35 cases were identified in a 16-year study period. Female to male ratio was 1:1.7 and median age 48 years. Corneal injury by plant material, and soft contact lens use were the main risk factors (42.8% and 31.4%, respectively). Trauma was the leading risk factor for men (68.1%), contact lens use (61.5%) for women. Fusarium species were isolated more frequently (n = 21, 61.8%). F. solani was mostly associated with trauma, F. verticillioides and F. proliferatum with soft contact lens use. Other fungi were: Purpureocillium lilacinum (14.7%), Alternaria (11.8%), Aspergillus (8.8%), and Phoma foliaceiphila, Beauveria bassiana and Curvularia spicifera, one case each. Amphotericin B and voriconazole MIC50s against Fusarium were 2 mg/L and 4 mg/L respectively. Antifungal therapy consisted mainly of voriconazole locally or both locally and systemically, alone or in combination with liposomal AmB. Cure/improvement rate with antifungal therapy alone was 52%, keratoplasty was required in 40% of cases, and enucleation in 8%. In conclusion, filamentous fungal keratitis in Greece is rare, but with considerable morbidity. A large proportion of cases resulted in keratoplasty despite appropriate antifungal treatment.