Analysis of Patients' Characteristics and Treatment Profile of People Who Use Drugs (PWUDs) with and without a Co-Diagnosis of Viral Hepatitis C: A Real-World Retrospective Italian Analysis.

Purpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS). Patients and Methods: During 01/2011-06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated. Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases. Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.

Ultrasound imaging of the axilla.

Axilla is a pyramidal-in-shape "virtual cavity" housing multiple anatomical structures and connecting the upper limb with the trunk. To the best of our knowledge, in the pertinent literature, a detailed sonographic protocol to comprehensively assess the axillary region in daily practice is lacking. In this sense, the authors have briefly described the anatomical architecture of the axilla-also using cadaveric specimens-to propose a layer-by-layer sonographic approach to this challenging district. The most common sonographic pathological findings-for each and every anatomical compartment of the axilla-have been accurately reported and compared with the corresponding histopathological features. This ultrasound approach could be considered a ready-to-use educational guidance for the assessment of the axillary region. CRITICAL RELEVANCE STATEMENT: Axilla is a pyramidal-in-shape "virtual cavity" housing multiple anatomical structures and connecting the upper limb with the trunk. The aim of this review article was to describe the anatomical architecture of the axilla, also using cadaveric specimens, in order to propose a layer-by-layer sonographic approach to this challenging district.

Are monoclonal antibodies effective in patients with severe obesity in SARS-CoV-2 infected?

It is important to block SARS-CoV-2 infection immediately with early therapies, such as monoclonal antibodies (MonoAbs). Also, several studies show that obesity is associated with a high risk of severe COVID-19 disease. We enrolled 32 SARS-CoV-2 infected patients who received MonoAbs, all patients were not vaccinated for SARS-CoV-2, and they received therapy after 7 ± 2 days from the onset of COVID-19 symptoms. In the days following administration, patients followed home therapy with Pidotimod 800 mg bid for 10 days and cholecalciferol 2000 UI for 20 days, prescribed the same day they received MonoAbs therapy. Our study found that there are no differences in the therapeutic response between obese and nonobese patients with SARS-CoV-2 infection undergoing MonoAbs therapy, in fact, none of them underwent hospitalization. Furthermore, the effect of the immunostimulant Pidotimod and cholecalciferol may have contributed to the resolution of COVID-19 symptoms in these patients.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

New Therapeutic Options in Mild Moderate COVID-19 Outpatients.

Background: In recent years, the therapeutic options for COVID have significantly improved; however, the therapies are expensive with restricted access to drugs, and expeditious and difficult to manage at home. We investigated the effect of pidotimod in preventing hospitalization in patients with mild-moderate COVID-19. Methods: A total of 1231 patients between January and June 2021 were screened. A total of 184 patients with mild-moderate COVID-19 were enrolled and divided into two groups: group-A (97) had undergone therapy with pidotimod 800 mg bid for 7−10 days and group-B (87) had other therapies. We excluded those who had undergone complete vaccination course, monoclonal anti-spike/antivirals or the co-administration of pidotimod-steroid. The primary outcome chosen was the emergency room, hospitalization, and deaths for COVID-related causes; the secondary outcome chosen was the duration of COVID-19 illness. Results: A total of 34 patients (18.5%) required hospital treatment, 11 in group-A and 23 in group-B (11.3% vs. 26.4%, p = 0.008). The median disease duration in group-A was 21 days (IQR 17−27) vs. 23 (IQR 20−31) in group-B (p = 0.005). Patients in the pidotimod group had higher SpO2 in the walking test (IQR 96−99% vs. IQR 93−98%, p = 0.01) and a lower need for steroid rescue therapy (11.5% vs. 60.9%, p < 0.001). Conclusions: In the first phase of disease, pidotimod can represent an effective, low-cost, weapon, without restrictions of use, that is able to prevent a second aggressive phase and promote faster virological recovery.

Molnupiravir as an Early Treatment for COVID-19: A Real Life Study.

OBJECTIVES: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. MATERIALS AND METHODS: We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). RESULTS: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0-13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. CONCLUSION: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events.

Early detection of pleuro-pulmonary tuberculosis by bedside lung ultrasound: A case report and review of literature.

We present a case in which lung ultrasound (LUS) was relevant to reach an early diagnosis of lung tuberculosis and to manage the patient in the right setting. Moreover, ultrasound allowed to detect and treat massive pleural effusion through an ultrasound-guided thoracentesis.

Anaerobic bloodstream infections in Italy (ITANAEROBY): A 5-year retrospective nationwide survey.

INTRODUCTION: A lack of updated data on the burden and profile of anaerobic bloodstream infections (ABIs) exists. We assessed the incidence of ABIs and trends in antimicrobial resistance in anaerobes isolated from blood in Italy. MATERIAL AND METHODS: We conducted a retrospective study on 17 Italian hospitals (2016-2020). Anaerobes isolated from blood culture and their in vitro susceptibility profiles (EUCAST-interpreted) were registered and analyzed. RESULTS: A total of 1960 ABIs were identified. The mean age of ABIs patients was 68.6 ± 18.5 years, 57.6% were males. The overall incidence rate of ABIs was 1.01 per 10.000 patient-days. Forty-seven% of ABIs occurred in medical wards, 17% in ICUs, 14% in surgical wards, 7% in hemato-oncology, 14% in outpatients. The three most common anti-anaerobic tested drugs were metronidazole (92%), clindamycin (89%) and amoxicillin/clavulanate (83%). The three most common isolated anaerobes were Bacteroides fragilis (n = 529), Cutibacterium acnes (n = 262) and Clostridium perfringens (n = 134). The lowest resistance rate (1.5%) was to carbapenems, whereas the highest rate (51%) was to penicillin. Clindamycin resistance was >20% for Bacteroides spp., Prevotella spp. and Clostridium spp. Metronidazole resistance was 9.2% after excluding C. acnes and Actinomyces spp. Bacteroides spp. showed an increased prevalence of clindamycin resistance through the study period: 19% in 2016, 33% in 2020 (p ≤ 0.001). CONCLUSIONS: Our data provide a comprehensive overview of the epidemiology of ABIs in Italy, filling a gap that has existed since 1995. Caution is needed when clindamycin is used as empirical anti-anaerobic drug.

Risk Factors Associated with Poor Outcome in Patients with Infective Endocarditis: An Italian Single-Center Experience.

Background: Nowadays, infective endocarditis (IE) is still burdened by a high mortality. In the absence of an adequate prognostic stratification system, it is important to assess new predictors of poor outcomes. The aim of our study is to evaluate which factors were associated with higher mortality in IE patients. Methods: A retrospective cohort study enrolled patients with an IE diagnosis at the Infectious Diseases Clinic of the University 'G. D'Annunzio', Chieti, Italy from January 2013 to December 2019. For each patient, demographic, anamnestic and clinical information, embolic phenomena, laboratory and microbiologic data, treatment, and outcomes were collected and analyzed. A correlation analysis was performed. Results: Sixty-eight patients with EI were studied; among them, the mortality was 17.6%, 20.6%, and 23.5%, intra-hospital, at 1 month from discharge and at 6 months from discharge, respectively. Mortality was significantly correlated with age, estimated glomerular filtration rate, and procalcitonin values when considering either basal values (r = 0.266, p = 0.029), or values at 48−72 h from the start of an antibiotic therapy (r = 0.222; p < 0.05), cerebral embolization for 6-month mortality (r = 0.284; p = 0.019), and inadequate antibiotic therapy (r = 0.232, p < 0.05). Conclusions: Procalcitonin values, at EI diagnosis and at 48−72 h after starting antibiotics, are prognostic factors useful for stratifying patient risk, and for setting up a personalized treatment. Of note, cerebral embolization and an inappropriate empirical treatment were associated with a higher mortality in the short- and long-term.

Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features.

Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 ± 0.2 cm. US features included a symmetric cortex with hilum evidence (4/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna's mRNA-1273 (60% of patients, 4/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient's clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients' clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Effects of Probiotic Mixture Supplementation on the Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine in People Living with HIV.

BACKGROUND: In people living with HIV, combination antiretroviral therapy (cART) reduces the risk of death, but the persistent immune-deficient state predisposes them to pneumococcal infections. Current guidelines encourage administering pneumococcal vaccine Prevenar 13 to patients living with HIV. Since probiotic supplementation could act as adjuvants and improve vaccine immunogenicity by modulating gut microbiota, the present study aimed to assess whether the effect of a formulation containing a combination of specific probiotics (Vivomixx®) could improve the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) in adult people living with HIV. METHODS: Thirty patients who were clinically stable and virologically suppressed, without opportunistic infections during this time and no ART changes in the 12 months before the study started were enrolled. Patients were divided into two groups: (1) received a placebo dose and (2) received Vivomixx® (1800 billion CFU) for four weeks before and after the vaccination with a single dose of PCV13. RESULTS: Vivomixx® supplementation induced a better response to PCV13 immunization, as shown by greater change in anti-Pn CPS13 IgG and increase in salivary IgA, IL-10 and IL-8. CONCLUSIONS: Additional investigations will help to clearly and fully elucidate the optimal strains, doses, and timing of administration of probiotics to improve protection upon vaccination in immunocompromised individuals and the elderly.

It is Not Always COVID-19: Case Report about an Undiagnosed HIV Man with Dyspnea.

BACKGROUND: The current COVID-19 pandemic has attracted great attention from the medical world. In the past year, there have been reports of missed or delayed treatments for conditions that mimic COVID-19. The main symptoms caused by SARS-CoV-2, such as fever and cough, belong to different clinical conditions. It is of the utmost importance that the diagnostic thinking used to analyze data and information to reach a COVID-19 diagnosis does not overlook the plethora of different diagnoses related to these symptoms. CASE REPORT: The aim of this work is to present the clinical case of a patient having unrecognized HIV infection with a 4-week history of fever, cough, and hypoxia. When tests were allowed to highlight HIV-related immunodeficiency status, a CMV assay was performed in order to evaluate opportunistic pneumonia. Through this, diagnosis of HIV combined with CMV pneumonia was made, thus excluding COVID-19 respiratory insufficiency. CONCLUSION: The diagnosis of the two conditions in the COVID-19 era is challenging due to overlapping clinical and radiological features and limitations of current diagnostic assays. This causes clinical implications due to diagnostic delays.

Parameters associated with diagnosis of COVID-19 in emergency department.

OBJECTIVES: We designed this study to identify laboratory and radiological parameters, which could be useful to guide the clinician, in the evaluation of a suspected case of coronavirus disease 19 (COVID-19). METHODS: This retrospective, observational, single-center-study recruited patients with a suspect of COVID-19 data were extracted from electronic medical records using a standardized data collection form. RESULTS: A total of 566 patients with suspect COVID-19 infection were enrolled (280 were COVID-19+). The COVID-19 population was characterized with bilateral-pneumonia, a lower count of neutrophil, lymphocyte and monocyte, a lower neutrophil to lymphocyte-ratio (NLR). Lower of platelet count, d-dimer, troponin I, and serum calcium were in COVID-19 patients. The occurrence of COVID-19 diagnosis increased, independently of other variables, with pneumonia (odds ratio [OR]: 3.60; p < .001), neutrophil below normal range (OR: 4.15; p < .05), lactate dehydrogenase (OR: 2.09; p < .01) and sodium above normal range (OR: 2.34; p < .01). In patients with possible respiratory acute affections we found a higher neutrophil, higher monocyte, a higher NLR and a more elevation in d-dimer. In the Sepsis group showed higher level of white blood cell, C-reactive protein, d-dimer, and procalcitonin. CONCLUSIONS: Our study confirms that patients with COVID-19 have typical radiological and laboratory characteristics. The parameters highlighted in the study can help identify COVID-19 patients, also highlighting which are the main differential diagnoses to be made and the parameters that facilitate the differential diagnosis.

Normal breathing releases SARS-CoV-2 into the air.

This study tests the release of SARS-CoV-2 RNA into the air during normal breathing, without any sign of possible risk of contagion such as coughing, sneezing or talking. Five patients underwent oropharyngeal, nasopharyngeal and salivary swabs for real-time reverse transcriptase PCR (RT-PCR) detection of SARS-CoV-2 RNA. Direct SARS-CoV-2 release during normal breathing was also investigated by RT-PCR in air samples collected using a microbiological sampler. Viral RNA was detected in air at 1 cm from the mouth of patients whose oropharyngeal, nasopharyngeal and salivary swabs tested positive for SARS-CoV-2 RNA. In contrast, the viral RNA was not identified in the exhaled air from patients with oropharyngeal, nasopharyngeal and salivary swabs that tested negative. Contagion of SARS-CoV-2 is possible by being very close to the mouth of someone who is infected, asymptomatic and simply breathing.

Efficacy of canakinumab in mild or severe COVID-19 pneumonia.

BACKGROUND: Clinicians all around the world are currently experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several therapeutic strategies have been used until now but, to date, there is no specific therapy to treat SARS-CoV-2 infection. In this study, we used canakinumab, a human monoclonal antibody targeting interleukin-1 beta to improve respiratory function and laboratory parameters compared with standard therapy (hydroxycloroquine plus lopinavir/ritonavir). METHODS: We enrolled 34 patients with mild or severe non intensive care unit (ICU) coronavirus disease 2019 (COVID-19): 17 patients treated with standard therapy and 17 patients treated with a subcutaneous single dose of canakinumab 300 mg. We collected data about oxygen supports and laboratory parameters such as inflammation indices and hemogasanalysis. We compared the data collected before the administration of canakinumab (T0), 3 days after T0 (T1) and 7 days after T0 (T2) with the same data from patients taking the standard therapy. RESULTS: We observed a reduction in inflammation indices and a significant and rapid increase in P/F ratio in canakinumab group, with improvement of 60.3% after the administration. We reported a significant reduction in oxygen flow in patients treated with canakinumab (-28.6% at T1 vs. T0 and -40.0% at T2 vs. T1). Conversely, the standard group increased the supply of high oxygen at T1 versus T0 (+66.7%), but reduced oxygen flows at T2 versus T1 (-40.0%). CONCLUSION: In hospitalized adult patients with mild or severe non ICU COVID-19, canakinumab could be a valid therapeutic option. Canakinumab therapy causes rapid and long-lasting improvement in oxygenation levels in the absence of any severe adverse events.

Pidotimod and Immunological Activation in Individuals Infected with HIV.

BACKGROUND: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. METHODS: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1ß, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2). RESULTS: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels. CONCLUSION: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.

Circulating extracellular vesicles as new inflammation marker in HIV infection.

BACKGROUND: Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. METHODS: We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a-/CD45-, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. RESULTS: Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. CONCLUSION: These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.