Lipid Metabolism and Cardiovascular Risk in HIV-1 Infection and HAART: Present and Future Problems

Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN

A multi-centre study in Northern Italy to evaluate the impact of a Sepsis bundle in Obstetric Settings: the SOS study

Background In 2018, Lombardy's “Fight against Sepsis in Obstetrics” group developed a regional sepsis management bundle for obstetric patients. This study aimed to evaluate the impact of this bundle on maternal and neonatal clinical outcomes and on process measures. Methods Multicentre, observational, retrospective study including data from pregnant and puerperal adult patients diagnosed with sepsis according to the Surviving Sepsis Campaign guidelines in two periods: May 2015-May 2018 (pre-bundle) and July 2018-January 2023 (post-bundle). Results Eighty women were included, 24 (30.0%) in the pre-bundle and 56 (70.0%) in the post-bundle period. The primary source of infection was urinary (40.0%), with Escherichia coli being the most common pathogen isolated from blood cultures. Regarding clinical outcomes, no deaths occurred in both pre- and post-bundle periods. For mothers there was no significant difference in median length of stay (LOS) between the two groups, while neonatal intensive care unit (NICU) admissions of neonates significantly decreased from 85.7% to 31.3% (p=0.013). Regarding process measures there was only a significant increase in ID specialist consultations in the post-bundle period (75.0%) compared to the pre-bundle period (50.0%) (p=0.029). Conclusion The implementation of a regional maternal sepsis management bundle did not significantly alter maternal outcomes, but was associated with a reduction in NICU admissions, although uncertainty remains as to what role the bundle implementation had in this change. More ID consultations post-bundle highlight the potential role of the bundle increasing sepsis awareness of physicians dealing with these patients

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC. © 2013 Worm et al.; licensee BioMed Central Ltd

Cost of human immunodeficiency virus infection in Italy, 2007-2009: effective and expensive are the new drugs worthwhile?

Background: In recent years, the increased efficacy and effectiveness of antiretroviral treatment has led to longer survival of patients infected with human immunodeficiency virus (HIV), but has also raised the question of what happens to consumption of resources. Early highly active antiretroviral treatment (HAART), management of hepatitis C virus (HCV) coinfection, and expensive newly marketed drugs may affect the economic sustainability of treatment from the point of view of the National Healthcare Services. The present study aimed to provide information on the economic burden of HIV-positive patients resident in the Lombardy region using a three-year time horizon. Methods: This was a retrospective, observational, budget impact study, based on information collected for the period 2007–2009, including hospitalizations, outpatient services, and HAART and non-HAART drug utilization. Patients with confirmed HIV infection, aged >=18 years, resident in the Lombardy region, and followed at the "L Sacco" Hospital in Milan from 2007 to 2009 were eligible. Results: A total of 483 patients (mean age 44.1 years) were included in the study. The mean CD4+ cell count increased over the study period from 462 ± 242 cells/mm3 in 2007, to 513 ± 267 cells/mm3 in 2008, to 547 ± 262 cells/mm3 in 2009. In total, 162 subjects (33.5%) were coinfected with HCV. Hospitalizations and HAART costs increased from 2007 to 2009, whereas outpatient visits and non-HAART drug costs decreased slightly over time. The total cost increase was also significant when limiting the analysis to experienced patients, HCV-negative patients, and experienced HCV-negative patients. Conclusion: CD4+ cell count, a major predictor of costs, increased over the study period. However, immunological improvement was achieved by greater expense in the short term. Whether this may be compensated by a long-term decrease in opportunistic infections and in the costs of management of HIV-related events is an area still to be investigated

Applicazione dell'approccio patient based per la determinazione dei costi sanitari diretti pubblici della cura e assistenza per l'infezione da HIV

La possibilità di stimare in modo accurato l'assorbimento di risorse economiche del Servizio Sanitario Regionale (SSR) in base alle caratteristiche della popolazione residente, risulta essere di centrale rilevanza per poter programmare accuratamente la spesa legata ai servizi erogati all'utenza. Attraverso l’esempio di una ricerca condotta su una coorte di pazienti HIV positivi afferenti all’Azienda Ospedaliera "Ospedale Luigi Sacco" di Milano, viene mostrato come l’utilizzo di un approccio patient based nella determinazione dei costi sanitari diretti pubblici, attraverso l'integrazione di database di tipo clinico e amministrativo (spese per terapia antiretrovirale, altri farmaci, specialistica ambulatoriale e ospedalizzazioni negli anni 2004-2007) dà la possibilità di individuare quali caratteristiche cliniche possono portare ad un aumento dei costi per il SSR e poter stimare costi standard per patologia, offrendo uno strumento per il monitoraggio dell'andamento della spesa e per il controllo dell'appropriatezza delle cure.The forecasting of economic resources utilisation of the resident population for a Regional Healthcare Service, based on its clinical characteristics, it is of high relevance in order to plan the regional healthcare budget. The usefulness of a patient based approach to determine public direct healthcare costs is presented through research conducted within Regione Lombardia on a cohort of HIV positive patients referring to Hospital Authority “Ospedale Luigi Sacco”, Milan. All the costs related to HAART , other drugs, outpatient and inpatient activity between 2004 and 2007 were assessed, integrating information within clinical and administrative databases. This allowed the possibility to identify the clinical characteristics which lead to an increase of costs for a Regional Healthcare System, and to assess standard costs per pathology, providing a tool to monitor the costs trends and to control the appropriateness of healthcare services

Raltegravir central nervous system tolerability in clinical practice

Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug-related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors that can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms, and therefore their monitoring in clinical practice

Raltegravir central nervous system tolerability in clinical practice: results from a multicenter observational study

Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug-related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors that can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms, and therefore their monitoring in clinical practice