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.

Effectiveness of full (booster) COVID-19 vaccination against severe outcomes and work absenteeism in hospitalized patients with COVID-19 during the Delta and Omicron waves in Greece.

AIM: We estimated vaccine effectiveness (VE) of full (booster) vaccination against severe outcomes in hospitalized COVID-19 patients during the Delta and Omicron waves. METHODS: The study extended from November 15, 2021 to April 17, 2022. Full vaccination was defined as a primary vaccination plus a booster ≥ 6 months later. RESULTS: We studied 1138 patients (mean age: 66.6 years), of whom 826 (72.6 %) had ≥ 1 comorbidity. Of the 1138 patients, 75 (6.6 %) were admitted to intensive care unit (ICU), 64 (5.6 %) received mechanical ventilation, and 172 (15.1 %) died. There were 386 (33.9 %) fully vaccinated, 172 (15.1 %) partially vaccinated, and 580 (51 %) unvaccinated patients. Unvaccinated patients were absent from work for longer periods compared to partially or fully vaccinated patients (mean absence of 20.1 days versus 12.3 and 17.3 days, respectively; p-value = 0.03). Compared to unvaccinated patients, fully vaccinated patients were less likely to be admitted to ICU [adjusted relative risk (ARR: 0.49; 95 % CI: 0.29-0.84)], mechanically ventilated (ARR: 0.43; 95 % CI: 0.23-0.80), and die (ARR: 0.57; 95 % CI: 0.42-0.78), while they were hospitalized for significantly shorter periods (ARR: 0.79; 95 % CI: 0.70-0.89). The adjusted full VE was 48.8 % (95 % CI: 42.7 %-54.9 %) against ICU admission, 55.4 % (95 % CI: 52.0 %-56.2 %) against mechanical ventilation, and 22.6 % (95 % CI: 7.4 %-34.8 %) against death. For patients with ≥ 3 comorbidities, VE was 56.2 % (95 % CI: 43.9 %-67.1 %) against ICU admission, 60.2 % (95 % CI: 53.7 %-65.4 %) against mechanical ventilation, and 43.9 % (95 % CI: 19.9 %-59.7 %) against death. CONCLUSIONS: Full (booster) COVID-19 vaccination conferred protection against severe outcomes, prolonged hospitalization, and prolonged work absenteeism.

A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis.

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004-0.36), p: 0.005], significantly better overall survival by Kaplan-Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64-348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).

Reliability, Validity and Psychometric Properties of the Greek Translation of the Posttraumatic Stress Disorder Scale.

The Greek version of the Davidson Trauma Scale (DTS) was developed to respond to the need of Greek-speaking individuals. The translated questionnaire was administered to 128 HIV outpatients (aged 37.1±9.1) and 166 control patients (aged 32.4±13.4). In addition to the DTS Greek scale, subjects were assessed with two other scales useful for assessing validity. For each factor analyses two components were extracted, based on Cattell's scree test. The two components solution accounted for 55.34% of the total variation in case of frequency variables and 61.45% in case of severity variables. The Cronbach's alpha coefficient and Guttman split-half coefficient of the DTS scale were 0.93 and 0.88 respectively. The test-retest reliability of the Greek version of DTS scale proved to be satisfactory. Individual items had good intra-class correlation coefficients higher than 0.5, which means that all questions have high levels of external validity. The psychometric strength of interview for posttraumatic stress disorder-Greek version it's reliable for its future use, particularly for screening subjects with possible diagnosis of posttraumatic stress disorder.

RELIABILITY, VALIDITY, AND PSYCHOMETRIC PROPERTIES OF THE GREEK TRANSLATION OF THE CAMBRIDGE DEPERSONALIZATION SCALE (CDS).

INTRODUCTION: The Cambridge Depersonalisation Scale is meant to capture the frequency and duration of depersonalisation symptoms over the 'last 6 months'. METHODS: In order to develop a Greek version of CDS scale, the CDS scale was translated in Greek by 2 psychiatrists. Then, the Greek version of CDS scale was back-translated by a person who did not knew the original English version. The back-translated version was reviewed in order to establish whether is consistent with the original English version. After this procedure we administered the Greek version of CDS scale to a sample of 294 Greeks in order to assess the reliability and the validity of the Greek version of scale. RESULTS: The five components solution accounted for 58.204% of the total variation. Initial eigenvalues of the five components were: factor 1=11.555, factor 2=1.564, factor 3=1.356, factor 4=1.247 and factor 5=1.157. Six items did not load on any factor. Correlations between factors were low ranged from 0.134 to 0.314 and no complex variables were found. Cronbach's alpha and Guttman split-half coefficient were used to evaluate interval consistency of CDS scale in 294 individuals. The alpha coefficients and Guttman split-half coefficient of the CDS scale were 0.938 and 0.921, respectively. The test-retest reliability proved to be satisfactory. The intraclass correlation coefficients for the total CDS score was very good and equal to 0,883. The CDS scale correlated highly with the SCL-90 and all subscales (p-value<0.0001). CONCLUSION: The psychometric strength of CDS - Greek its reliable for its future use, particularly for screening for subjects with possible diagnosis of CDS.

Aseptic abscess syndrome associated with traveler's diarrhea after a trip to Malaysia.

The first, to our knowledge, case of the aseptic abscesses syndrome as a complication of traveler's diarrhea after a trip to Malaysia is presented. The patient failed to respond to several antimicrobials. The diagnosis was histologically confirmed and the patient only responded to immunomodulatory therapy with corticosteroids and methotrexate. Travel physicians should be aware of this entity reviewed herein in the context of traveler's diarrhea.

Epstein barr virus hemophagocytic lymphohistiocytosis related to rituximab use and immunopathogenetic insights.

Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation. Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed.

'Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis).

Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear.

Impact of a hospital-wide antibiotic restriction policy program on the resistance rates of nosocomial Gram-negative bacteria.

BACKGROUND: To evaluate the impact of an antibiotic restriction policy on antibiotic consumption and Gram-negative resistance rates, in an environment of antibiotic overconsumption and increasing resistance rates for nosocomial pathogens. METHODS: The study was a 'before and after' trial of 18-month duration; the antibiotic restriction policy program was implemented in 1998-2000 and was based on a government program addressed by the Ministry of Health to public hospitals on a national basis. This included prescribing of all newer antibiotics on an order form, auditing of the order forms and consultation with infectious diseases (ID) specialists, dispensing of treatment and prophylaxis guidelines, feedback, and face-to-face education. Antibiotic consumption and Gram-negative resistance rates were recorded before and after the intervention. RESULTS: Despite the addition of a new 40-bed ID department in the hospital during the 'after' period, the consumption of restricted antibiotics was significantly reduced by 42% (and their cost by 31%). Gram-negative resistance rates for Pseudomonas, Klebsiella, and Enterobacter, serving as index microorganisms for Gram-negative nosocomial pathogens, were significantly reduced during the 'after' period, even against antibiotics for which there was an increase in consumption. CONCLUSIONS: Multidisciplinary restriction programs can reduce antibiotic consumption and Gram-negative resistance rates in the hospital setting.

Microcirculatory vascular dysfunction in HIV-1 infected patients receiving highly active antiretroviral therapy.

OBJECTIVES: We investigated whether HIV-1 infected patients receiving highly active antiretroviral therapy (HAART) and HIV-1 infected patients who had never received HAART had differences in their vascular microcirculatory function. METHODS: We assessed the forearm blood flow before and after four minutes of ischemic occlusion of the brachial artery using venous occlusion strain gauge plethysmography. The hyperaemic forearm blood flow was recorded for three minutes at 15 second intervals. We calculated the maximal percent increase of the forearm blood flow during hyperemia. Forty HIV-infected male patients receiving HAART were compared to 20 age- and BMI- matched, male HIV-infected patients who had never received HAART (control group). RESULTS: Patients on HAART had similar baseline forearm blood flow but lower maximal and percentage (%) change in forearm blood flow than control patients (4.2 +/- 1.7 vs. 4.1 +/- 1.7 l/ 100mL/min P = 0.8, 32 +/- 11.2 vs. 38.9 +/- 10.5 l/100 mL/min. P = 0.04 and 714 +/- 255 vs. 907 +/- 325%, P = 0.01, respectively). Patients receiving HAART had higher cholesterol than control patients (221 +/- 58 vs. 163 +/- 38 mg/dL, P = 0.001). HAART was associated with the percentage change in the blood flow during hyperemia (coefficient regression B = -0.32, P = 0.02) after adjustment for age, cholesterol and viral load. CONCLUSIONS: HIV-infected patients receiving HAART present abnormalities of arterial microcirculation in comparison with never-treated patients.

Association of highly active antiretroviral therapy with increased arterial stiffness in patients infected with human immunodeficiency virus.

BACKGROUND: Metabolic disorders associated with atherosclerosis and cardiovascular disease have been described in "HIV-infected" individuals. We investigated (i) whether normotensive "HIV-infected" individuals and hypertensive patients have similarities regarding their arterial elastic properties and (ii) the effect of highly active antiretroviral therapy (HAART) and metabolic factors on arterial stiffness. METHODS: In a case-control study, we compared measurements of pulse wave velocity (PWV), arterial blood pressure, and markers of metabolic profile in 56 normotensive, "HIV-infected" patients (mean age 40 +/- 13 years) to 28 age- and sex-matched newly diagnosed untreated patients with hypertension and 28 healthy individuals. RESULTS: "HIV-infected" patients had higher PWV than healthy controls but lower PWV than hypertensives (8.1 +/- 1.4 m/s vs. 6.7 +/- 1.1 m/s vs. 9.0 +/- 1.0 m/s, P = 0.003 and 0.01, respectively). However, patients on HAART had similar PWV with hypertensives (8.4 +/- 1.4 vs. 9.0 +/- 1.0 m/s P = 0.25). Patients on HAART had higher PWV than patients without (8.4 +/- 1.4 m/s vs. 7.5 +/- 1.3 m/s, P = 0.03). Patients on HAART had higher total cholesterol, triglycerides, and diastolic blood pressure than patients naive to HAART (P < 0.05). In multivariate analysis, the independent determinants of increased PWV were HAART duration (unstandardized coefficient b v = 0.007, P = 0.04), serum cholesterol (b = 0.007, P = 0.04), mean or diastolic blood pressure (b = 0.049 and b = 0.060, P < 0.01). CONCLUSIONS: "HIV-infected" individuals have increased arterial stiffness compared to healthy controls. Patients on antiretroviral therapy have similarities regarding their arterial elastic properties with patients with untreated hypertension. There is an independent association between duration of antiretroviral therapy, cholesterol levels, and blood pressure with increased arterial stiffness in "HIV-infected" patients.

HIV-positive patients treated with protease inhibitors have vascular changes resembling those observed in atherosclerotic cardiovascular disease.

A metabolic syndrome associated with atherosclerosis and cardiovascular disease has been described in HIV-positive individuals. In the present study we investigated whether HIV-positive individuals and CAD (coronary artery disease) patients have similarities in their vascular function and structure. In a case-control study, we compared measurements of carotid artery IMT (intima-media thickness) and brachial artery FMD (flow-mediated vasodilation) in HIV-positive individuals with age- and sex-matched controls with similar risk factors and patients with established CAD. Seventy-one HIV patients, age 42+/-13.9 years (91% male), were compared with 29 CAD patients and 25 controls. HIV patients had higher IMT than controls and similar IMT to CAD patients (0.64+/-0.2 compared with 0.55+/-0.05 and 0.66+/-0.08 mm respectively; F=4.2, P=0.01). Patients taking protease inhibitors had higher IMT (0.69+/-0.2 compared with 0.57+/-0.15 mm; P=0.01), blood pressure, cholesterol and triacylglycerols than those not taking protease inhibtors (P<0.05). In multiple regression analyses, increasing blood pressure (beta: 0.37, P=0.001), glucose (beta: 0.26, P=0.016), cholesterol (beta: 0.24, P=0.033), duration of HIV disease (beta: 0.33, P=0.008) and use of protease inhibitors (beta: 0.27, P=0.04) were the most important determinants of IMT respectively. FMD was associated only with triacylglycerol measurements. Patients with HIV present arterial changes resembling those found in patients with atherosclerotic cardiovascular disease. These vascular changes are closely related to protease-inhibitor-induced changes of metabolic parameters. Thus intensive treatment of these metabolic parameters might retard atherosclerosis in HIV patients.