HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents

Hepatitis C virus (HCV) infection is a systemic disorder that frequently associates with extrahepatic manifestations, including nephropathies. Cryoglobulinemia is a typical extrahepatic manifestation of HCV infection that often involves kidneys with a histological pattern of membranoproliferative glomerulonephritis. Other, less common renal diseases related to HCV infection include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. Over the last decades, the advent of direct-acting antiviral therapies has revolutionized treatment of HCV infection, dramatically increasing the rates of viral clearance. In patients where antiviral therapy alone fails to induce renal disease remission add-on B-cell depleting agents represent an alternative to counteract the synthesis of pathogenic antibodies. Immunosuppressive therapies, such as steroids, alkylating agents, and plasma exchanges, may still represent an effective option to inhibit immune-complex driven inflammatory response, but the potentially associated increase of HCV replication and worsening of liver disease represent a serious limitation to their use

A Comprehensive Phenotypic and Functional Immune Analysis Unravels Circulating Anti-Phospholipase A2 Receptor Antibody Secreting Cells in Membranous Nephropathy Patients

Introduction: Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited. Methods: We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq). Results: After adjusting for multiple testing, plasma cells and regulatory B cells (BREG) were significantly higher (P < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels (P = 0.042) and were associated with disease activity. Ex vivo-expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies (P < 0.001) in MN patients. Tumor necrosis factor-alpha (TNF-alpha) was the only significantly increased cytokine in MN patients (P < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire. Conclusion: This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity

The management of healthcare employees’ job satisfaction: optimization analyses from a series of large-scale surveys

Abstract Background Measuring employees’ satisfaction with their jobs and working environment have become increasingly common worldwide. Healthcare organizations are not extraneous to the irreversible trend of measuring employee perceptions to boost performance and improve service provision. Considering the multiplicity of aspects associated with job satisfaction, it is important to provide managers with a method for assessing which elements may carry key relevance. Our study identifies the mix of factors that are associated with an improvement of public healthcare professionals’ job satisfaction related to unit, organization, and regional government. Investigating employees’ satisfaction and perception about organizational climate with different governance level seems essential in light of extant evidence showing the interconnection as well as the uniqueness of each governance layer in enhancing or threatening motivation and satisfaction. Methods This study investigates the correlates of job satisfaction among 73,441 employees in healthcare regional governments in Italy. Across four cross sectional surveys in different healthcare systems, we use an optimization model to identify the most efficient combination of factors that is associated with an increase in employees’ satisfaction at three levels, namely one’s unit, organization, and regional healthcare system. Results Findings show that environmental characteristics, organizational management practices, and team coordination mechanisms correlates with professionals’ satisfaction. Optimization analyses reveal that improving the planning of activities and tasks in the unit, a sense of being part of a team, and supervisor’s managerial competences correlate with a higher satisfaction to work for one’s unit. Improving how managers do their job tend to be associated with more satisfaction to work for the organization. Conclusions The study unveils commonalities and differences of personnel administration and management across public healthcare systems and provides insights on the role that several layers of governance have in depicting human resource management strategies

ERitropoietina, ormone tuttofare

Over the past two decades it has been shown that, in addition to erythropoietic activity, erythropoietin (EPO) has numerous other functions, including neuro-protective, anti-apoptotic, antioxidant, angiogenic and immunomodulatory functions. EPO action is expressed through the interaction with two different forms of its receptor (EPOR): a homodimeric, responsible for the erythropoietic effects, and a heterodimeric one, responsible for the non-erythropoietic effects. Stimulation of this latter receptor has also been shown to be effective in prolonging organ transplant survival, both in murine models and in humans. The development of new molecules that act selectively on heterodimeric EPOR, devoid of erythropoietic activity, has allowed to begin to evaluate the effect of long-term treatments, avoiding the possible complications, mainly of a cardiovascular nature, linked to the increase in the hematocrit

Acute Kidney Injury (AKI) before and after Kidney Transplantation: Causes, Medical Approach, and Implications for the Long-Term Outcomes

Acute kidney injury (AKI) is a common finding in kidney donors and recipients. AKI in kidney donor, which increases the risk of delayed graft function (DGF), may not by itself jeopardize the short- and long-term outcome of transplantation. However, some forms of AKI may induce graft rejection, fibrosis, and eventually graft dysfunction. Therefore, various strategies have been proposed to identify conditions at highest risk of AKI-induced DGF, that can be treated by targeting the donor, the recipient, or even the graft itself with the use of perfusion machines. AKI that occurs early post-transplant after a period of initial recovery of graft function may reflect serious and often occult systemic complications that may require prompt intervention to prevent graft loss. AKI that develops long after transplantation is often related to nephrotoxic drug reactions. In symptomatic patients, AKI is usually associated with various systemic medical complications and could represent a risk of mortality. Electronic systems have been developed to alert transplant physicians that AKI has occurred in a transplant recipient during long-term outpatient follow-up. Herein, we will review most recent understandings of pathophysiology, diagnosis, therapeutic approach, and short- and long-term consequences of AKI occurring in both the donor and in the kidney transplant recipient

The representativeness of a European multi-center network for influenza-like-illness participatory surveillance.

BACKGROUND: The Internet is becoming more commonly used as a tool for disease surveillance. Similarly to other surveillance systems and to studies using online data collection, Internet-based surveillance will have biases in participation, affecting the generalizability of the results. Here we quantify the participation biases of Influenzanet, an ongoing European-wide network of Internet-based participatory surveillance systems for influenza-like-illness. METHODS: In 2011/2012 Influenzanet launched a standardized common framework for data collection applied to seven European countries. Influenzanet participants were compared to the general population of the participating countries to assess the representativeness of the sample in terms of a set of demographic, geographic, socio-economic and health indicators. RESULTS: More than 30,000 European residents registered to the system in the 2011/2012 season, and a subset of 25,481 participants were selected for this study. All age classes (10 years brackets) were represented in the cohort, including under 10 and over 70 years old. The Influenzanet population was not representative of the general population in terms of age distribution, underrepresenting the youngest and oldest age classes. The gender imbalance differed between countries. A counterbalance between gender-specific information-seeking behavior (more prominent in women) and Internet usage (with higher rates in male populations) may be at the origin of this difference. Once adjusted by demographic indicators, a similar propensity to commute was observed for each country, and the same top three transportation modes were used for six countries out of seven. Smokers were underrepresented in the majority of countries, as were individuals with diabetes; the representativeness of asthma prevalence and vaccination coverage for 65+ individuals in two successive seasons (2010/2011 and 2011/2012) varied between countries. CONCLUSIONS: Existing demographic and national datasets allowed the quantification of the participation biases of a large cohort for influenza-like-illness surveillance in the general population. Significant differences were found between Influenzanet participants and the general population. The quantified biases need to be taken into account in the analysis of Influenzanet epidemiological studies and provide indications on populations groups that should be targeted in recruitment efforts