Background & Aims The phenotypic and functional characteristics of natural killer (NK) cells in chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are incompletely defined and ...largely controversial. Methods We studied NK cell receptor expression, cytotoxic activity, and cytokine production in peripheral blood mononuclear cells from 35 patients with chronic hepatitis C, 22 with chronic hepatitis B, and 30 healthy controls. Results Patients with chronic HBV infection had an increased proportion of NKG2C+ NK cells with normal inhibitory receptor expression and a lower proportion of activated NK cells compared with HCV+ patients, which was associated with normal or reduced cytolytic activity and markedly dysfunctional tumor necrosis factor-α and interferon-γ production. Patients with chronic HCV infection showed a predominantly activating phenotype, featuring a decreased percentage of cells expressing the inhibitory receptor KIR3DL1 and a concomitant increase in the proportion of NKG2D+ NK cells. Expression of the CD69 early activation antigen on NK cells positively correlated with serum alanine aminotransferase and HCV RNA values, suggesting participation of virus-induced effector NK cells in liver necroinflammation. Phenotypic changes in HCV+ patients were associated with enhanced cytokine-induced cytolytic activity and increased usage of natural cytotoxicity and NKG2D receptor pathways, accompanied by defective cytokine production, although to a lesser extent than patients with chronic HBV infection. Conclusions These findings provide evidence for a functional dichotomy in patients with chronic HBV and HCV infections, featuring conserved or enhanced cytolytic activity and dysfunctional cytokine production, which may contribute to virus persistence.
Background & Aims Chronic microbial infections are frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We ...assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection. Methods We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls. B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand ± IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide ± IL-2, as innate immunity signal. Proliferation was examined by flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG. Results A significantly higher proportion of B cells from both HCV- and HBV-infected patients expressed activation markers compared with controls and a positive correlation was found between CXCR3+ B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infected patients. Moreover, patients’ activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustion marker. Conclusions B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation.
The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients ...with chronic hepatitis C by using histologic Metavir scores as reference standard.
Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis.
One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively.
Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.
Anemia is highgly prevalent among elderly and few previous studies have focused on hospitalized medical patients aged ≥ 75 years. During a four-months period of this single center prospective cohort ...study, 508 patients were admitted and studied with a standardized set of blood tests. Anemia, defined as by WHO, was present in 277 (54.5%) and in the majority of cases was mild (71.8%), normocytic (82.8%), hypoproliferative (90.5%). Most frequent diagnosis was multifactorial anemia (47.7%); anemia of chronic disease was the most frequent single cause (28.5%) and the most frequent etiologic co-factor among multifactorial anemia. Iron deficiency was found in 22.7% of cases; vitamin B12 and folate deficiency were found in 7.5% and 26.1% respectively; chronic kidney disease in 16.2%; overt bleeding anemias in 4.8% and clonal hemopathies in 3.2%. Unexplained anemia was diagnosed only in 5.1% of cases. The finding of a very high frequency of anemia of chronic disease and multifactorial anemia has implications on both the diagnostic and therapeutic grounds.
Candidemia is an emerging problem among patients hospitalized in Internal Medicine Wards (IMW). We performed a retrospective study to assess the epidemiology, species distribution, antifungal ...susceptibility and outcome of candidaemia recorded over a 3-year period (2010-2012) among IMW of community hospitals of Udine province in Italy: forty-eight patients were identified, with an overall incidence of 1.44 cases/1000 hospital admissions/year. Candida albicans was the most frequent species, followed by Candida parapsilosis that accounted for 42.9% of Tolmezzo cases. All isolates were susceptible to amphotericin and caspofungin, while 11.4% of strains were not-susceptible to voriconazole and 14.3% to fluconazole. Crude mortality was 41.7%. In conclusion, in community hospitals overall incidence of candidemia is similar to tertiary care hospitals, but 80% of cases are detected in IMW. Candida species distribution is overlapping, but differences in local epidemiology were found and should be taken into consideration. No resistance to amphotericin and caspofungin was found while resistance to azoles was observed. Knowledge of this data might be useful when planning the best therapeutic strategy.
The identification of psychoactive substances, in particular of designer drugs, on the site of their discovery is crucial to contrast the diffusion of drugs of abuse. We report here the first example ...of a nanoscale colorimetric probe, based on the nanoconfinement of a tricyclic dye and the target analytes in the cavity of cucurbit8uril. The probe selectively responds to N-(2-methoxybenzyl)phenethylamines, with a limit of detection of 3 μM. The sensing system can be deposited on paper, thus obtaining a colorimetric strip test capable of discriminating illegal drugs from other substances of common use.
The majority of acutely ill medical patients are elderly with some degree of renal impairment. In this setting, venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality ...and, to reduce this risk, a correct thromboprophylaxis is needed. The aim of this single center retrospective study was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients with renal impairment. All patients aged 60 years or over, bedridden for at least four days, with a creatinine clearance (CrCl) of 50 mL/min or under, and who had received fondaparinux during hospitalization were evaluated and followed for up to 90 days after discharge. A total of 125 patients were evaluated (34.4% males); median age was 83.0 years. Median duration of thromboprophylaxis was 9.0 days. Forty-one (32.8%) patients were treated with fondaparinux 1.5 mg daily, 84 (67.2%) with 2.5 mg daily. Inappropriately high doses of fondaparinux were used in 77 patients with CrCl 20-50 mL/min, in 12 patients with CrCl below 20 mL/min, in 14 patients with prothrombin time (PT) ratio over 1.2, in 8 patients with PT ratio over 1.5, and in 3 patients with thrombocytopenia. No episodes of VTE or of major bleeding were recorded while there were 6 episodes (2.4%) of minor bleeding. Both dosages of fondaparinux showed similar safety and efficacy. Twenty-six patients (20.8%) died; no cause of death was related to fondaparinux. In conclusion, in elderly acutely ill hospitalized medical patients with renal impairment, prophylaxis with fondaparinux 2.5 or 1.5 mg daily is safe and effective in preventing VTE without increasing bleeding risk.
BACKGROUND:Chronic hepatitis C is a global health problem. Although new, highly effective and safe direct-acting antivirals have been approved for adults, the only drugs currently registered for ...children are pegylated interferon and ribavirin. The timelines for the pediatric approval of the new treatment regimens are far off. Three phase II–III pediatric trials with direct-acting antivirals are recruiting, and the estimated dates of completion of these studies range between April 2018 and January 2023.
METHODS:The aim of this study was to evaluate the value of on-treatment virologic response (VR) as predictor of sustained virologic response (SVR) in a cohort of Italian children with chronic hepatitis C and to establish possible stopping rules.
RESULTS:Sixty-four children were enrolled (January 2012 to December 2015). SVR rate was 79.7% (51/64). VR at weeks 2 to 12 were shown to be robust predictors for the attainment of SVR. The positive predictive values of VR at weeks 8 and 12 were 98% and 92.7%, respectively. The negative predictive values at the same treatment weeks were 92.9% and 100%, indicating that no child who did not achieve VR at week 12 obtained SVR and that the likelihood of achieving SVR if still positive at week 8 was very low.
CONCLUSIONS:Our results suggest for the first time that VR at week 8 could be considered a reliable predictor of SVR. Monitoring viral kinetics is useful for predicting the success of pegylated interferon and ribavirin therapy in children.
Abstract Eradication of hepatitis C virus (HCV) by antiviral therapy is the treatment of choice for mixed cryoglobulinemia secondary to this infection, but many patients fail to achieve sustained ...viral responses and need second-line treatments. Several studies have demonstrated that the infusion of the anti-CD20 monoclonal antibody rituximab is highly effective for refractory mixed cryoglobulinemia, with a clinical response in approximately 80% of patients, although the relapse rate is high. Virtually all published studies employed a rituximab dosage of 375 mg/m2 given four times, a schedule used for treating non-Hodgkin's lymphomas. Based on a prior pilot study, we designed a phase II single-arm two-stage study (EUDRACT n. 2008-000086-38) to evaluate the efficacy of a lower dosage of rituximab, 250 mg/m2 given twice, for refractory mixed cryoglobulinemia. We present here the preliminary results in the first 27 patients enrolled. The overall response rate in 24 evaluable patients was 79%, and the mean time to relapse was 6.5 months, similar to the 6.7 months reported in studies with high-dose rituximab. Side effects were comparable to those seen in patients treated with high-dose. Increase of HCV viral load, reported in some high-dose studies, was not observed in our patients. Low-dose rituximab may provide a more cost/effective and possibly safer alternative for treating refractory HCV-associated mixed cryoglobulinemia.
Climate, environment and transmission of malaria Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina ...
Le infezioni in medicina,
2016-Jun-01, 20160601, Letnik:
24, Številka:
2
Journal Article
Recenzirano
Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, ...the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political instability and health policies that have reduced the funds for vector control, combined with the presence of migratory flows from endemic countries.
PDF
