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Aims: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI). Methods: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD). Results: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted. Conclusions: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI.

Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Vaginal microbes and their metabolic products have crucial functions, affecting local immunity development and maternal-fetal health. The composition of the vaginal microbiome can vary in response to various factors, including body mass index (BMI), and diet. In this study we get new insights into the vaginal ecosystem of Caucasian women (n = 24) at the first trimester of pregnancy, assessing whether pre-pregnancy diet can affect the structure of the vaginal environment in terms of bacterial composition and vaginal metabolite concentration. We characterized 1) the vaginal bacterial composition (Nugent score), 2) the vaginal metabolic profiles (1H-NMR spectroscopy), and 3) the dietary nutrient intake by means of a validated food frequency questionnaire. Pre-pregnancy BMI was negatively related to vaginal health status, indicating that women who begin pregnancy overweight/obese have a greater occurrence of vaginal dysbiosis during pregnancy. A lactobacilli-dominated vaginal microbiota was negatively associated with higher pre-pregnancy intake of animal-sourced protein. Conversely, a higher pre-pregnancy consumption of total carbohydrates and sugars seemed to be a protective factor for vaginal health. The vaginal environment of BV-women was characterized by higher levels of biogenic amines and organic acids, whereas higher levels of phenylpropionate and diverse amino acids were fingerprints of a healthy vaginal status. A significant association between a higher pre-pregnancy BMI and several dysbiosis-related vaginal metabolites was also found. Our study shed light on the role of pre-pregnancy BMI and diet on the vaginal environment during pregnancy, underlining the importance of limiting protein intake from animal foods to maintain a healthy lactobacilli-dominated microbiota.

Despite being considered a tropical disease, visceral leishmaniasis (VL) caused by L. infantum is also endemic in the Mediterranean Europe and represents an increasing cause of morbidity and mortality in solid organ transplant (SOT) recipients. VL occurring in kidney transplant recipients is a severe event, often worsening the renal damage and leading to poor outcome. It is believed that most of VL cases in transplant recipients are caused by reactivation of a pre-existent, dormant leishmanial infection induced by the immunosuppressive drugs. Nevertheless, the prevalence of asymptomatic Leishmania infection in candidates to kidney transplant residing in or visiting endemic areas is unknown. As L. infantum is highly circulating in northeastern Italy, we aimed to examine the occurrence of this parasitic infection in 119 dialysis patients living in the mentioned area, 71 of whom were potential candidates to kidney transplant. By employing a combination of sensitive serological and molecular methods, we observed a prevalence of 15.9% asymptomatic Leishmania infection in the study cohort. This finding emphasizes the need of further evaluating potential screening strategies for Leishmania infection in solid organ transplant candidates residing in or visiting endemic areas.

Funder: Alma Mater Studiorum - Università di Bologna, STUDY DESIGN: To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET). METHODS: We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD). RESULTS: Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001). CONCLUSIONS: In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.

Objectives Human leishmaniasis can be severe and fatal, yet in the Mediterranean region only a small percentage of infections progress to clinical disease. We evaluated the percentage of asymptomatic Leishmania infection in the Bologna province, northeastern Italy. Methods We examined the presence of specific antibodies by Western Blot (WB) and parasitic DNA by real time PCR in peripheral blood of 240 blood donors residing in the Bologna province. Results Anti-Leishmania IgG were detected by WB in 27 subjects (11.2%, 95% CI 7%-15%), while Leishmania kinetoplast DNA was detected in peripheral blood specimens of 4 out of 240 donors (1.7%, 95% CI 0.2%-3.2%). Overall, the prevalence of Leishmania infection in the blood donor cohort was 12.5%, thus indicating an elevated cumulative exposure to the Leishmania parasite in the examined municipality. Conclusions Our results suggest that a surveillance system for monitoring Leishmania infection in blood donors and/or strategies of protozoan inactivation in whole blood should be taken into consideration in areas with circulation of the Leishmania parasite.

Toscana virus (TOSV) is a Phlebovirus transmitted by phlebotomine sand flies and is an important etiological agent of summer meningitis in the Mediterranean basin. Since TOSV infection is often asymptomatic, we evaluated the seroprevalence in blood donors (BDs) in the Bologna and Ferrara provinces (Northeastern Italy)&mdash, the areas with the highest and lowest numbers of TOSV neuroinvasive cases in the region, respectively. A total of 1208 serum samples from BDs were collected in April&ndash, June 2014 and evaluated for the presence of specific TOSV-IgG by ELISA. The IgG-reactive samples were confirmed by indirect immunofluorescence assay (IIF) and by microneutralization test (MN). Serum samples were defined as positive for anti-TOSV IgG when reactive by ELISA and by at least one second-level test, TOSV seroprevalence was 6.8% in the Bologna province, while no circulation of TOSV was detected in the Ferrara province. Sand fly abundance in 2014 was also estimated by a geographic information system using a generalized linear model applied to a series of explanatory variables. TOSV seroprevalence rate was strongly associated with the sand fly abundance index in each municipality, pointing out the strong association between sand fly abundance and human exposure to TOSV.

Objectives Active screening is a crucial element for the prevention of carbapenemase-producing Enterobacteriaceae (CPE) transmission in healthcare settings. Here we propose a culture-based protocol for rectal swab CPE screening that combines CPE detection with identification of the carbapenemase type. Methods The workflow integrates an automatic digital analysis of selective chromogenic media (WASPLab®; Copan), with subsequent rapid tests for the confirmation of carbapenemase production [i.e. detection of Klebsiella pneumoniae carbapenemase (KPC)-specific peak by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) or a multiplex immunochromatographic assay identifying the five commonest carbapenemase types]. To evaluate the performance of this protocol in depth, data for 21 162 rectal swabs submitted for CPE screening to the Microbiology Unit of S. Orsola-Malpighi Hospital (Bologna, Italy) were analysed. Results Considering its ability to correctly segregate plates with/without Enterobacteriaceae, WASPLab Image Analysis Software showed globally a sensitivity and specificity of 100% and 79.4%, respectively. Of the plates with bacterial growth (n = 901), 693 (76.9%) were found to be positive for CPE by MALDI-TOF/MS (KPC-specific peak for K. pneumoniae) or by immunochromatographic assay. Only 2.8% (16/570) of KPC-positive K. pneumoniae strains were missed by the specific MALDI-TOF/MS algorithm, being detected by the immunochromatographic assay. The mean turnaround time needed from sample arrival to the final report ranged between 18 and 24 h, representing a significant time saving compared with manual reading. Conclusion This workflow proved to be fast and reliable, being particularly suitable for areas endemic for KPC-producing K. pneumoniae and for high-throughput laboratories.

Immunological tests, including the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, represent an important aid for diagnosing active tuberculosis (TB) and latent TB infections in children, but concerns about their use in children

OBJECTIVES An observational, prospective, cohort study was performed to assess changes in insulin sensitivity and serum leptin level after a switch from a ritonavir-boosted PI (PI/r) to raltegravir or dolutegravir in HIV-infected adults on stable combination ART (cART). METHODS Non-diabetic HIV-infected patients receiving suppressive cART including tenofovir disoproxil fumarate/emtricitabine plus one PI/r, who underwent a switch from the PI/r to raltegravir (group A) or dolutegravir (group B), were enrolled in the study. Serum levels of insulin, leptin and the homeostasis model assessment of insulin resistance (HOMA) index were evaluated during a 12 month follow-up. RESULTS Overall, 86 patients were enrolled: 45 patients were included in group A and 41 were included in group B. The mean age was 45.7 years and 74 (86%) patients were male. After 12 months of follow-up, a significant reduction in the mean concentration of leptin and insulin was reported both in group A [-0.61 ng/mL (P

In 2017, a chikungunya outbreak in central Italy later evolved into a secondary cluster in southern Italy, providing evidence of disease emergence in new areas. Officials have taken action to raise awareness among clinicians and the general population, increase timely case detection, reduce mosquito breeding sites, and promote mosquito bite prevention.

Objectives: Combination therapy has been recommended when using ceftazidimeâavibactam (CAZâAVI) for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal combination is unknown. Six common antimicrobial agents (ertapenem, imipenem, meropenem, gentamicin, tigecycline, and ciprofloxacin) were evaluated for synergy with the recently approved cephalosporinâβ-lactamase inhibitor combination CAZâAVI in this study. Methods: Different antimicrobial combinations were tested against 13 KPC-Kp, including CAZâAVI-susceptible (n = 11) and resistant (n = 2) clinical isolates. In vitro interactions of CAZâAVI with different antimicrobials were tested using the gradient synergy test. Changes in the minimum inhibitory concentration (MIC) value were interpreted using the fractional inhibitory concentration (FIC) index and susceptible breakpoint index (SBPI). Results: The combination of CAZâAVI with gentamicin or ciprofloxacin displayed no synergism against any of the KPC-Kp isolates, whereas synergistic activity was observed with imipenem and meropenem against all KPC-Kp isolates. Notably, CAZâAVI reduced MICs for meropenem and imipenem below the resistance breakpoints against all strains. The SBPI analysis showed that CAZâAVI in combination with imipenem achieved higher SBPI values than other CAZâAVI-based combinations. Conclusions: These data suggest that combinations of CAZâAVI with imipenem may be considered a useful therapeutic option for the treatment of KPC-Kp infections. Keywords: KPC-producing Klebsiella pneumoniae, Ceftazidimeâavibactam, Synergy, Carbapenem, Imipenem

Background: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class. Methods: We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks. Results: As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (-85.2 mg/dL), in the prevalence of tubular proteinuria (-56%) and in the mean level of interleukin-6 (-0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events. Conclusion: In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism.

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.

Background The new Xpert MTB/RIF Ultra assay (Ultra, Cepheid, Sunnyvale, USA) is a cartridge-based automated diagnostic test that can simultaneously identify Mycobacterium tuberculosis complex (MTB) and resistance to Rifampicin (RIF). With respect to the previous version Xpert MTB/RIF assay (Xpert), IS6110/IS1081 repetitive elements probes have been added allowing the detection of lower MTB load, defined by the new semi-quantitative category “trace” with indeterminate RIF resistance. The aim of this study was to evaluate performance of the new version Ultra on Xpert-negative, but TB culture-positive clinical samples. Methods The de-identified frozen samples (-20 °C) collected over a 4-year period (February 2014-October 2017), which had previously resulted smear-negative, Xpert-negative but MTB culture-positive, were analyzed with Ultra. The de-frosted samples were loaded into the cartridge using the same process as the previous version, according to manufacturer’s instruction. Results During the study period 382 MTB culture-positive samples were archived: 314 resulted Xpert-positive and 68 Xpert-negative. Thirty-one of the 68 Xpert-negative samples resulted positive with Ultra, with an overall improvement in MTB detection of 45.6%. Out of 36 Xpert-negative respiratory samples, 18 resulted Ultra-positive with the following semi-quantitative loads: “low”(n = 1), “very low”(n = 11), “trace”(n = 6), with an improvement in MTB detection of 50%. The best performance was achieved on bronchoalveolar lavage specimens (53.8%). Out of 32 Xpert-negative non-respiratory samples, 13 resulted Ultra-positive with the following semi-quantitative loads: “very low”(n = 7), “trace”(n = 6), with an improvement in MTB detection of 40.6%. The best performance was achieved on biopsies (55.6%) and lymph nodes (50%). The new category “trace” detected 12 out of the 31 Ultra-positive MTB samples; in the remaining 19 samples RIF susceptibility was determined with 100% concordance with the phenotypic susceptibility test. The mean time to positivity of samples found negative by Ultra was significantly longer in comparison to positive samples in liquid culture. Conclusions Our results are consistent with the few studies published so far and confirm the better performance of Ultra compared to the previous version in both respiratory and non-respiratory smear-negative samples, with an overall improvement of 45.6%.

Kluyvera is considered a benign saprophyte commonly present in the environment and also in the human gastrointestinal tract. Kluyvera infections in humans are rare and the pathogenic role of Kluyvera remains uncertain.1 In recent years, sporadic cases of Kluyvera species carrying class A carbapenemase genes (blaGES-5 and blaKPC-2) have been reported.2,3 Herein we describe the complete nucleotide sequence of an IncA plasmid carrying blaVIM-1 recovered from a Kluyvera cryocrescens strain isolated in Italy. This is, to our knowledge, the first report about a Kluyvera strain with an acquired class B carbapenemase.

Background The management of visceral leishmaniasis (VL) in HIV-infected patients is often complex with patients experiencing higher mortality rates, more toxic side effects and a higher possibility of treatment failure and relapse than HIV-negative individuals with VL. Case presentation We report on successful salvage therapy in two HIV-infected patients suffering with disseminated cutaneous and visceral leishmaniasis, recalcitrant to therapy with liposomal amphotericin B. After the employment of combination anti-leishmanial treatment, parasite genomes were not detectable up to the last follow up visit, 57 and 78 weeks after treatment onset, respectively. CD4+ lymphocyte counts fluctuated over time, but were generally higher than counts detected at treatment onset, which likely contributed to protection against VL relapse. Conclusions Results achieved with the anti-leishmanial combination treatment were promising, but are based on only two patients. Future investigation is necessary to confirm the efficacy of this salvage therapy in sustaining the immunological response and control of VL.

The increasing spread of carbapenem-resistant Klebsiella pneumoniae represents a serious threat to public health and a major concern for clinicians. In K. pneumoniae, KPC is the most important determinant of carbapenem resistance owing to its distribution worldwide and to the high mortality rates associated with infections due to KPC-producing K. pneumoniae (KPC-Kp) strains

Background: Hyperlipidaemia is a risk factor for the progression of chronic kidney disease (CKD), which is a frequent comorbidity in patients with HIV-1 infection, but the renal effects of statins remain unclear. Methods: We performed an observational, prospective study of HIV-infected patients on suppressive antiretroviral therapy, with CKD and hyperlipidaemia, and starting a lipid-lowering treatment with rosuvastatin, atorvastatin or omega-3 fatty acids. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2for >3 months. Results: As a whole, 69 patients (53 men, 58 Caucasian, median age 56.2 years) were enrolled. Overall, 25 patients started rosuvastatin (10 mg daily, group A), 23 patients atorvastatin (20 mg daily, group B), and 21 started omega-3 fatty acids (3 g daily, group C). At baseline, median eGFR was 54.4 mL/min/1.73 m2, and the eGFR ranged between 50 and 60 mL/min/1.73 m2in 87% of patients. After 12 months, the median eGFR decline was significantly lower in group A (−0.84 mL/min/1.73 m2) and in group B (−0.91 mL/min/1.73 m2) in comparison with the group C (−1.53 mL/min/1.73 m2; p

Background: The ritonavir-boosted protease inhibitor (PI/r)-based dual regimens are warranted in order to optimize the combination antiretroviral therapy (cART), prevent the long-term toxicity and reduce the cost of treatments. Methods: We performed an observational, retrospective study of HIV-infected patients on suppressive antiretroviral therapy who switched to a dual regimen containing lamivudine (3TC) plus darunavir/ritonavir (DRV/r) 800/100 mg qd or atazanavir/ritonavir (ATV/r) 300/100 mg qd. Results: As a whole, 122 well-treated patients (mean age, 45.2 years; mean CD4 T + lymphocyte count, 589 cells/mm3; mean duration of current cART, 3.1 years) were enrolled. Current antiretroviral regimen included tenofovir/emtricitabine in 91 subjects, abacavir/lamivudine in 25, lopinavir/r in 41, DRV/r in 38 and ATV/r in 33. Baseline mean estimated glomerular filtration rate (eGFR) was 94.2 mL/min/1.73 m2, and proteinuria was detected in 46 subjects (38%). Overall 70 subjects switched to 3TC + DRV/r (group A) and 52 to 3TC + ATV/r (group B). After 12 months, 65 patients (92.8%) in group A and 46 (88.4%) in group B showed HIV RNA 

Objectives Recent clinical studies and one meta-analysis have shown a modest but significant increase in the incidence of diabetes mellitus associated with statin exposure, so this correlation was investigated in a cohort of HIV-positive subjects. Methods A retrospective cohort study including adult HIV-1-infected patients followed at our Clinic of Infectious Diseases between 2007 and 2014 was performed. Results We assessed 3170 HIV-positive patients with a median follow-up of 5.2 years. The incidence of diabetes mellitus was 1.2 per 100 person-years and it was not significantly associated with the prescription of statins [hazard ratio (HR) 1.09 per year of statin exposure; 95% confidence interval (CI) 0.7–1.49; P = 0.067], while it was associated with older age, chronic hepatitis C, antiretroviral-naive vs. antiretroviral experienced condition, high body mass index, and high serum concentration of triglycerides. Conclusions In our study, a higher risk of diabetes mellitus was not associated with statin treatment, but with some traditional risk factors.

Background Several studies have shown a significant association between vitamin D deficiency and an increased risk of statin-related symptomatic myalgia in the general population, but there are no data among HIV-infected persons. Methods A retrospective, cohort study was conducted to assess the incidence of symptomatic myalgia and elevation in serum creatine kinase level among HIV-positive adults on combination antiretroviral therapy and treated with atorvastatin or rosuvastatin for at least 12 months between 2011 and 2015 in our outpatient unit. Results A total of 545 patients (mean age 53.4 years) were enrolled into the study. Atorvastatin was prescribed in 55.8% of patients and rosuvastatin in 44.2%. After a mean duration of statin therapy of 29 months, an isolated symptomatic myalgia was diagnosed in 42 patients (7.7%) and a myalgia associated with elevated creatine kinase level in 25 (4.6%). The mean concentration of 25-hydroxyvitamin D was significantly lower in patients with myalgia (19.4 ng/ml) and with creatine kinase elevation and myalgia (22.8 ng/ml) than in those without muscle toxicity (32.1 ng/ml; P = 0.017 and 0.024, respectively). In stratified multivariable-adjusted logistic regression models, there was a statistically significant association between vitamin D deficiency and occurrence of symptomatic myalgia (P = 0.009) or creatine kinase elevation and myalgia (P = 0.046). Other factors significantly associated with development of myalgia were duration of statin therapy more than 24 months, history of myalgia, and age older than 60 years. Discussion In our observational study, vitamin D deficiency was significantly associated with a statin-induced myalgia among HIV-infected patients on combination antiretroviral therapy, in conformity with data of the general population.

Background: Persistent residual viremia (RV) and low grade inflammation and immune activation have been associated with non-AIDS defining events. The impact of persistent RV and HIV-DNA load on immune activation/inflammation remains unclear. The purpose of this study was to gain new insights into the relation between viremia, markers of inflammation and HIV-DNA levels. Methods: Three hundred and twenty-one HIV-infected patients were studied. A retrospective analysis of viremia values, prospectively collected for 48 months, was performed. Patients were separated into three groups: 113 TND (Target Not Detected, patients with sustained undetectable viremia); 113 RV (Residual Viremia, patients who had at least three detectable viral load (VL) values 37 but

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods: Patients on 3-drug ART with stable HIV-1 RNA

Statins have shown anti-inflammatory and immune-modulatory properties in both general and HIV-infected population, but their effect on plasma D-dimer levels is controversial and it has not been investigated to date in HIV-positive patients. The aim of our study was to assess the effect of rosuvastatin on D-dimer and other serum inflammation markers among these subjects.Prospective, cohort study of HIV-1-infected adult patients receiving a stable combination antiretroviral therapy (cART), who started a lipid-lowering therapy with rosuvastatin (10 mg daily) and were followed up for at least 12 months. The primary endpoint was the change at month 12 in the median plasma concentration of D-dimer. The secondary endpoints included the variation in median plasma levels of these inflammatory biomarkers: interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12).Sixty-two patients were enrolled in the study, and the endpoints were available for 54 subjects. After 12 months, a significant decrease in median plasma concentration of D-dimer was observed (-21.4%; interquartile range [IQR], -35.5; -4.2; p = .029). With regard to the inflammatory biomarkers, a significant decrease in median levels of IL-8 (-24.6%; IQR, -30.8; -1.8; p = .012) and IL-12 (-18.7%; IQR, -25.8; +2.5; p = .033) was also observed. Rosuvastatin led to a significant reduction in serum lipid values and showed a good tolerability profile.Our findings show that a 12-month treatment with rosuvastatin associated with an effective cART can significantly decrease the plasma levels of D-dimer, IL-8, and IL-12, and suggest a potential role for this statin to reduce activated coagulation and systemic inflammation among HIV-infected persons.

Objectives: An observational, prospective, cohort study was performed to compare efficacy and safety of a switch from ritonavir-boosted protease inhibitor (PI/r) to nevirapine or raltegravir with that of rosuvastatin addition to current antiretroviral therapy in HIV-infected patients with hyperlipidaemia. Methods: All HIV-infected patients receiving a stable PI/r-based antiretroviral regimen, with persistently suppressed viremia, naïve to non-nucleoside analogues and to integrase strand transfer inhibitors, with mixed hyperlipidaemia, and who underwent a switch from PI/r to nevirapine (Group A) or raltegravir (Group B) or who started rosuvastatin at 10 mg daily (group C) with unchanged antiretroviral regimen were enrolled into the study. Results: Overall, 136 patients were enrolled: 43 patients were included in the group A, 46 in the group B, and 47 in the group C. The mean age was 46.6 years, and 108 (79.4%) were males. After 48 weeks of follow-up, a significantly greater reduction in the mean low-density lipoprotein (LDL) cholesterol level was reported in group C (-28.2%) than in group A (−10.2%; p

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Its clinical course is typically indolent; however, based on a series of pathobiological, clinical, genetic, and phenotypic parameters, patient survival varies from less than 5 to more than 20 years. In this paper, we show for the first time that the expression of the interferon-inducible DNA sensor IFI16, a member of the PYHIN protein family involved in proliferation inhibition and apoptosis regulation, is associated with the clinical outcome in CLL. We studied 99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression profiling. We found quite variable degrees of IFI16 expression among CLLs cases. Noteworthy, we observed that a reduced IFI16 expression was associated with a very poor survival, but only in cases with ZAP70/CD38 expression. Furthermore, we found that IFI16 expression was associated with a specific gene expression signature. As IFI16 can be easily detected by immunohistochemistry or flow cytometry, it may become a part of phenotypic screening in CLL patients if its prognostic role is confirmed in independent series.

A 30-year-old man was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography examination showed a ST segment elevation involving the lower-lateral leads. A trans-thoracic ultrasonography showed findings compatible with an acute myopericarditis. All performed serological testings excluded other recent infections with cardiac tropism. Among screening tests, a peripheral lymphocyte subset analysis was performed and an inversion of the CD4/CD8 ratio was found. Therefore, HIV testing was performed and proved positive for HIV-1 antibodies. The discovery of a primary HIV infection with involvement of a vital organ led us to start HAART. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy. During the following days, the clinical conditions of our patient improved, and a further heart ultrasonography documented a mild pericardial thickening as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis. The histopathologic studies revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with a recent myocarditis. At the real-time PCR analysis on bioptic sample, only HHV6 DNA and HIV-DNA were reactive. An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented can be referred to the recent primary HIV-infection.

none 6 no The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. mixed Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi

The research reported in this article underlines the need to adopt a reflective attitude to the use of digital resources in teaching and learning. This relates to a growing body of research by different scholars in many countries. the present study underlines the need to adopt a reflective attitude to the use of digital resources in teaching and learning. The research starts from the assumption that students can develop their writing and critical thinking skills thatnks to specific writing activities. Such activities regard th eelaboration of short essays, both by hand and on computer keyboards, with the aim to highlight the difference in results. Within the paper a specific assessment grid was outlined to evaluate students' essays. Short essays written by students were produced in two different ways: by hand or keyboard. All data have been colelcted and analysed to highlight the different results in skylls development, according to the writing tool employed. From the analyses carried out and the results collected, handwritten short essays got higher scores than computer written texts: computer use in writing activities apparently reduces performances level in the majority of stduents taken into consideration.

Background: The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density. Objective: We selected some antiretroviral compounds used in clinical practice, to study their impact on bone health and their possible implication in the onset of bone disease. Method: Scalar concentrations of several antiretroviral drugs (used in single and in combination) were tested on an osteoblast-like cell line, HOBIT cells, to analyse cell survival and gene expression of selected bone markers. Results: None of the tested concentrations of Tenofovir, Emtricitabine, Nevirapine, Maraviroc or Raltegravir induced any significant apoptosis activation at our experimental conditions. Only some protease inhibitors and Efavirenz, at high concentration, determined a significant activation of programmed cell death. In parallel experiments, protease inhibitors used in combination with Tenofovir and Emtricitabine, increased apoptosis. Furthermore, we performed a study of mRNA expression of specific genes involved in osteoblast biology and in bone synthesis and observed that some protease inhibitors induced a selective decrease of some osteogenic markers. Conclusion: All the protease inhibitors included in this study trigger apoptosis at the highest concentration analysed, suggesting great caution in HIV-patients co-infected with HBV or HCV, where elevated plasma concentrations of drugs could be reached as a consequence of liver failure. Lastly, an increased apoptosis rate and an impairment of osteogenic markers were recorded only in the presence of Nelfinavir, suggesting a role of protease inhibitors in the alteration of osteoblast biology.

Background and aims HIV‐1 RNA viral load (VL) in plasma samples of HIV‐1–positive patients is used to assess the level of viral replication, the risk of disease progression, and the response and efficacy to antiretroviral treatment. Knowing the performance of different tests for HIV‐1 RNA detection is, therefore, important for clinical care. This study compared the performance of the recently introduced Aptima HIV‐1 Quant Dx assay (Hologic, Inc) and the standard COBAS AmpliPrep/COBAS TaqMan HIV‐1 v2.0 Test (CAP/CTM2) (Roche Molecular System, Inc) for HIV‐1 RNA quantitation. Methods Assay performance was assessed using 335 clinical samples, a standard HIV‐1 low VL panel, and 2 diluted samples from well‐characterized patients infected with different HIV‐1 subtypes tested in 5 replicates over 3 days. All samples were tested on both assays to evaluate inter‐assay agreement, both qualitatively and quantitively. Altogether, we evaluated assay sensitivity, linearity, accuracy, precision, repeatability, and reproducibility. Results Assay agreement for qualitative results in 335 clinical samples was fair (80.6%). Correlation of quantitative assay results (n = 164) was excellent (R 2 = 0.97), with 96.3% of the results within the 95% limit of assay agreement (−0.42 to +0.86 log), and 98.8% within 1 log of each other. Aptima‐HIV‐1 yielded results, on average, 0.22 log higher than CAP/CTM2. Both assays accurately quantitated the HIV‐1 standard at low VL (R 2 ≥ 0.94), with all samples within 0.5 log of the target. Conclusion Aptima‐HIV‐1 assay demonstrated sensitivity, accuracy, reproducibility, and precision for the detection and quantitation of HIV‐1 RNA across a wide dynamic range of VLs. Its performance, together with full automation and high throughput, suggests that Aptima‐HIV‐1 could be a suitable assay for reliable monitoring of HIV‐1 VL in patients undergoing treatment.