Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Allografts Use in Nasal Reconstruction

The outcomes of destructive processes of the nasal structure such as infection, chronic inflammation, or resective procedures can lead to the need of complex reconstruction of the nasal framework [1]. Various types of grafts and implants have been employed [2]. When dealing with a nasal reconstruction of whatever kind, the surgeon is faced by a clinical dilemma: which is the best material for reconstructive purposes in that patient? The materials used for augmentation are therefore an important issue among reconstructive rhinoplasty surgeons [3, 4]. A basic differentiation must be outlined between the terms of grafts and implants: a graft is made of tissue either from the same patient (autograft) or from a member of the same species (homograft). Implants are synthetic and if implantable are called alloplasts [5]. Alloplastic material is deemed desirable if noncarcinogenic, nonallergenic, readily available, resistant to mechanical strain, and entirely reabsorbable and still reliable. It is commonly perceived that autologous grafts are the first choice for augmenting the nose; unfortunately, this material is not always available or sufficient in cases of atrophic changes of the nose of whatever cause to fulfill the needs. However, limited availability, unpredictable resorption rates, difficulty of handling, and donor-site morbidity are possible drawbacks. In such instances, other choices must be considered, and alloplastic materials can represent an attractive alternative tool to take into account [6]. On the other hand, their efficacy complications and limited usage are 192 debated, such not uniform feelings and disputed possibilities have given rise to the development of different technologies to possibly reach ideal grafting substance (Fig. 16.1). In Western countries, surgeons prefer costal or auricular cartilage when septal cartilage is not available or insufficient, whereas alloplastic materials are more widely used in Asia [7]. Since the very beginning of the rhinoplasty history, many efforts have been made over time to use implants such as gold, iron, ivory, paraffin, celluloid, glass, and cork, eventually discorded due to unsurpassable troubles [8] (Figs. 16.2 and 16.3). Today, commonly used alloplastic materials are silicon, Gore-Tex® (Surgiform Technology, SC, USA), Medpor® (Stryker Corporate, a b c d Fig. 16.1 (a) CT scan and pathology specimen showing foreign body cystic reaction. Fibrous capsule with implant inside. (b) Latex implant of the dorsum (implanted 10 years previously), at moment inflamed, cistic and mobile, removed. (c) The removing of latex implant. (d) A fibrous capsule with implant inside P. G. Giacomini et al. 193 a b Fig. 16.2 (a) Kirschner steel wire and preserved costal cartilage implant of dorsum (10 years previously), for cocaine abuse outcomes. (b) Picture 6 months after removal a b Fig. 16.3 (a) CT scan, showing implant and the infected. (b) Mobile dorsal implant 16 Allografts Use in Nasal Reconstruction 194 MI, USA), and polydioxanone plate (PDS Flexible Plate, Johnson & Johnson Company, Langhorne, Pennsylvania, USA) [9]. An overview of their pros and cons will be conducted on the basis of the literature data and personal experience to highlight their possible use in case of atrophic nose outcomes that require surgical correction. Some exemplificative clinical cases of patients treated at the ENT Dept., School of Medicine, University of Rome Tor Vergata, at Nose Plastic Surgery Clinic in the past 10 years for complications associated with alloplastic materials used in atrophic rhinitis of various etiologies are reported. Clinical profiles: eight cocaine abuse, one purulent chronic infection, two outcomes of facial trauma, and one previous nasal surgery. M/F ratio: 1:4. The patients’ age ranged from 42 to 81 years (mean: 49 years). The follow-up period was 3–15 years (mean: 4.2 years). All had been treated elsewhere for augmentation rhinoplasty with alloplastic materials end eventually revised for complications occurred. Type of alloplastic materials used, complications developed, and results obtained were revised by medical charts, photo documentation, and histopathologic data examined. Literature data were considered in order to define alloplastic materials possibilities in this kind of nasal reconstruction