Occurrence of Blastocystis-subtypes in patients from Italy revealed association of ST3 with a healthy gut microbiota

An epidemiological survey on Blastocystis was carried out enrolling a total of 2524 subjects referred to the Umberto I Academic Hospital in Rome, for the routine parasitological exams, during 2017–2018. The studied population included a sample of immunocompromised individuals (N = 130) followed at the same hospital. DNA sequencing of the small subunit rRNA gene (SSU rDNA) locus was performed on samples positive to the coproparasitological analysis to molecular characterize the Blastocystis-subtypes. Microscopical analysis detected Blastocystis in 192/2524 (7.6%) of the enrolled subjects. It was the organism most frequently identified in the analysed faecal samples diagnosed in single infection (5.6%) or in co-infection with other enteric protozoa (2%). Furthermore, it was found mainly in immunocompromised patients (22.3%) compared to immunocompetent ones (6.8%). As expected, ST3 was the most occurring subtype identified in 40% of the subjects, followed by ST1 (29%), ST2 (16%), ST4 (12%), and ST7 (3%). Next-generation sequencing (NGS) of the 16S rDNA was performed on a sub-sample of Blastocystis-ST3-carriers, homogenous by age and gender, as well as on Blastocystis-free subjects, to profile and compare their gut bacterial composition. A higher bacterial diversity was found in ST3-Blastocystis-carriers, which exhibited a high abundance of Prevotella, Methanobrevibacter and Ruminococcus while, a high percentage of Bacteroides was found in Blastocystis-free subjects. This study evidenced the presence of Blastocystis in 7.6% of faecal samples in Italy and a high circulation of the protist among immunocompromised patients (22.3%). Molecular characterization of positive samples evidenced the occurrence of five different subtypes, including zoonotic ST such as the ST7, highlighting the risk of transmission from animals. Study of the gut microbiota composition confirms previous evidences according to which, the colonisation by Blastocystis would be linked with an eubiotic gut characterized by potentially beneficial species such as Prevotella and Ruminococcus, rather than with a dysbiotic state, with a high abundance of Enterobacteriaceae, and corroborated the role of the protist as “an old friend” of the human gut

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Short-and long-term immunological responses in chronic HCV/HIV co-infected compared to HCV mono-infected patients after DAA therapy

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients

Corticosteroid use, myocardial injury and in-hospital cardiovascular events in patients with community-acquired pneumonia

Background and Purpose: Corticosteroids are often prescribed to community-acquired pneumonia (CAP) patients, but the relationship with major cardiovascular events (MACEs) is unclear. Experimental Approach: 541 CAP patients were recruited (334 males, mean age 71.9 ± 16.2 years). High-sensitivity troponin T (hs-cTnT) was measured at admission, during the hospital stay and at discharge. MACE occurrence was registered during a long-term follow-up. Key Results: Overall, 318 patients (59%) showed hs-cTnT elevation >99th percentile (>0.014 μg/L). Age, heart failure and the increasing quintiles of hs-cTnT (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.82-2.58, P <.001) predicted MACEs. Among patients with hs-cTnT >0.014 μg/L at admission, 102 patients (31%) were on corticosteroids and showed lower hs-cTnT increase (P =.021), (NADPH) oxidase-2 (Nox2) activation (P =.005) and incidence of MACEs than untreated ones (HR 0.64, 95% CI 0.41-0.97, P =.038); no effect of corticosteroids on MACEs was observed in CAP patients with normal troponin. In vitro study showed that glucocorticoids have an antioxidant effect via downregulation of Nox2 activity. Conclusion and Implications: The study provides evidence that corticosteroid use is associated with lower increase of hs-cTnT and incidence of MACEs in CAP patients

Relation of cardiac complications in the early phase of community -acquired pneumonia to long-term mortality and cardiovascular events

Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p <0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p <0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up

Corticosteroid use and incident myocardial infarction in adults hospitalized for community-acquired pneumonia

Rationale: Adults hospitalized for community-acquired pneumonia (CAP) have an increased risk of myocardial infarction. Corticosteroid treatment lowers CAP morbidity and mortality, but it is not known whether it influences in-hospital myocardial infarction. Objectives: The aim of the present study was to investigate the potential interplay between corticosteroid treatment and in-hospital myocardial infarction in adults with CAP. Methods: We retrospectively analyzed adults with CAP referred to the University Hospital Policlinico Umberto I (Rome, Italy), consecutively recruited, and prospectively followed until discharge. The primary outcome was the occurrence of myocardial infarction during hospitalization. We used propensity score–adjusted Cox models to examine the association between corticosteroid use and myocardial infarction. Results: Seven hundred fifty-eight patients (493 males, 265 females; mean 6 standard deviation age, 71.7 6 14.4 yr) were included in the study. Of these, 241 (32%) were treated with systemic corticosteroids (methylprednisolone, betamethasone, or prednisone). During followup, 62 (8.2%) had a myocardial infarction during their hospitalization (incidence, 0.72 per 100 person-days; 95% confidence interval [CI], 0.55 to 0.92). Those treated with corticosteroids had a lower incidence of myocardial infarction (0.42 per 100 person-days) than those not treated with corticosteroids (0.89 per 100 person-days; absolute rate difference, 20.48 per 100 person-days; 95% CI, 20.85 to 20.10). In a propensity score–adjusted Cox model, corticosteroid use was associated with a lower incidence of myocardial infarction (hazard ratio, 0.46; 95% CI, 0.24 to 0.88; P = 0.02). Conclusions: We found that in-hospital corticosteroid treatment was associated with a lower incidence of myocardial infarction in adults hospitalized with CAP