Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Background and aims Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). Methods sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. Results At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with highsCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. Conclusions These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection

VI Seminario di studio. Salute globale e scenari attuali. Nuovi contributi di ricerca. Istituto Superiore di Sanità. Roma, 16 aprile 2015. Riassunti

Esiste un bisogno crescente di chiare evidenze scientifiche che possano supportare le politiche per la salute. Questo vale per una serie di aspetti che vanno dai protocolli diagnostici applicati alle malattie trasmissibili, agli approcci terapeutici, agli studi epidemiologici, alla definizione e identificazione dei determinanti della salute con partico lare riguardo alle situazioni di grave diseguaglianza, alle contaminazioni ambientali, alla relazione tra malattia e diritti così come alla relazione tra malattia e diritto. L’obiettivo del Dottorato di Ricerca in Malattie Infettive, Microbiologia e Scienze della Salute è proprio quello di fornire momenti di crescita, finalizzati alla formazione di nuovi ricercatori, nel campo delle malattie infettive, della microbiologia, della parassitologia, della sanità pubblica e medicina sociale, nella medicina legale e nelle scienze forensi. L’obiettivo di questo sesto appuntamento, nell’ambito della collaborazione tra Istituto Superiore di Sanità e l’Università̀ Sapienza di Roma, con i dottorandi è proprio quello di fornire una cornice il più possibile unitaria a un quadro complesso di ricerche di base e applicate nell’ambito degli obiettivi del dottorato.There is a growing need for clear scientific evidence that can support health policies. This applies to a number of issues including diagnostic protocols applied to communicable diseases, therapeutic approaches, epidemiological studies, the definition and identification of the health determinants (with particular reference to situations of severe inequality), environmental contamination, the relationship between disease and rights as well as the relationship between disease and law. The objective of the PhD Program in Infectious Diseases, Microbiology and Health Sciences is precisely to provide moments of intellectual growth, aimed at the trai ning of new researchers in the field of infectious diseases, microbiology, parasitology, public health and social medicine, in forensic medicine and forensic sciences. The objective of the sixth meeting with graduate students, part of the collaboration between the Italian National Institute of Health, and the Sapienza University of Rome, is precisely to provide a frame as unitary as possible to a complex picture of basic and applied research within the objectives of the doctorat

Physical performance and clinical outcomes in dialysis patients: a secondary analysis of the EXCITE trial.

Background/Aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was observed for cardiovascular events but this relationship did not reach statistical significance (P=0.09). Conclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk populatio

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Successful Vaginal Delivery after Induction of Labour in a Patient Treated for Non-Hodgkin’s Lymphoma of the Cervix: A Case Report and Literature Review

OBJECTIVE: Primary non-Hodgkin's lymphomas of the cervix are rare; they represent about 1% of all cases. There are no available guidelines regarding the safest mode of delivery after treatment and resolution of a cervical lymphoma. Case Report. We report the first case of a successful vaginal delivery after induction of labour in a woman recovered from a primary large B-cell lymphoma of the cervix and a literature review. CONCLUSION: In carefully selected patients with fully treated non-Hodgkin's lymphoma of the cervix with no residual disease, induction of labour via prostaglandins pessary may be a safe option if indicated

Myeloid and lymphoid activation markers in AIDS and non-AIDS presenters

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Myeloid dendritic cell (mDC), plasmacytoid dendritic cell (pDC), slanDC, monocyte and T-lymphocyte cell counts and activation status, were assessed by flow cytometry in peripheral blood samples. Soluble (s)CD14 and sCD163 were assessed in plasma samples using ELISA assays. Statistical analyses were performed using GraphPad Prism and Minitab Express. Thirty-four ART naïve HIV-1 infected subjects were enrolled in this study (22 non-AIDS and 12 AIDS presenters). Seventeen healthy donors (HD) were included as control group. Although circulating mDC levels resulted unchanged, HLA-DR expression was decreased on mDCs of HIV positive subjects compared to HD (p < 0,0001). AIDS presenters showed the lowest level of expression of HLA-DR on mDCs. Circulating levels of pDCs were decreased in HIV patients compared to HD (p < 0,001), without any changes in HLA-DR expression. SlanDC cell counts were extremely reduced in AIDS presenters, compared to non-AIDS presenters and HD (p < 0,01 and p < 0,0001, respectively) and showed higher HLA-DR expression in HIV patients compared to HD (p < 0,01). Intermediate monocyte (IM) cell counts were increased in AIDS and non-AIDS presenters compared to HD (p < 0,001 and p < 0,001 respectively). Furthermore, IM expansion was directly correlated to HIV viral load (p = 0,036) and independent from CD4 cell counts and activation levels. Plasma concentrations of sCD14 and sCD163 resulted increased in HIV infected subjects compared to HD (p < 0,0001 and p < 0,001), with the highest levels observed in AIDS presenters. After 1 year, ART was able to increase pDC and decrease IM absolute cell counts and modify HLA-DR expression on mDCs and slanDCs, approaching the levels observed in HD. ART reduced also CD4 and CD8 activation levels. In conclusion, in untreated HIV infected subjects circulating dendritic cells resulted altered either in numbers or in HLA-DR expression, especially in AIDS presenters. IM absolute counts were equally increased in AIDS and non-AIDS presenters. ART was able to reduce myeloid and lymphoid inflammation in both advanced and non-advanced HIV patients, confirming the role of ART in hampering disease progression and immune activation associated non-AIDS events

Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection

Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunological modifications following HCV eradication. We studied the dynamics of blood myeloid dendritic cells, monocytes, slan-DCs, and T lymphocytes during IFN-free and IFN-based regimens in hepatitis C virus infection