Different patterns of HIV-1 DNA after therapy discontinuation

BACKGROUND: By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 - 24 weeks to study the possible relationship between DNA and RNA viral load. METHODS: The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load). RESULTS: Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. CONCLUSION: Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects. Key words: HIV-1DNA viral load, therapy interruption

Mutational analysis of EGFR, c-KIT, PDGFRs, BRAF and KRAS, and expression of ALK and PD-L1 in a series of 103 thymic epithelial tumors with different histology

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Durability of different initial regimens in HIV-infected patients starting antiretroviral therapy with CD4+ counts <200 cells/mm³ and HIV-RNA >5 log₁₀ copies/mL

OBJECTIVES: Our aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts 5 log10 copies/mL. METHODS: This was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ 5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone. RESULTS: A total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29-2.03) versus starting with NNRTIs; P 5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03–2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94–1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

Ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP): outcomes on a large cohort

Purpose: To assess the effects of a new ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) technique on sexual functions and micturition, in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to evaluate how the surgical technique of ES-ThuLEP can lead to ejaculation preservation. Methods: A prospective study was carried out between January 2015 and January 2018 on patients with surgical indication for BPH, who wished to preserve ejaculation. The patients were treated with ES-ThuLEP and were evaluated before and 3 and 6&nbsp;months after surgery. Three validated questionnaires (ICIQ-MLUTSsex, IIEF-5 and IPSS) were used to assess changes in ejaculation, erectile function and urinary symptoms. Uroflowmetry (Qmax and Qavg), post-void residual volume and voided volume were also evaluated, to assess micturition improvement. Patients with moderate to severe erectile dysfunction were excluded. Statistical analysis was performed with the Student\u2019s t test, Chi-square test and logistic regression analysis. Results: Two hundred and eighty three patients were enrolled. Ejaculation was spared in 203 and 219 patients at 3 and 6&nbsp;months after surgery. No significant differences were observed between erectile function before and after surgery: baseline IIEF-5 = 16.2 \ub1 4.47 vs 16.7 \ub1 2.9 (p = 0.419) and 17.7 \ub1 3.2 (p = 0.410) at 3 and 6&nbsp;months. Significant improvement in urinary symptoms was achieved: baseline IPSS = 19.4 \ub1 7.24 vs 5.8 \ub1 4.3 (p = 0.032) and 3.9 \ub1 4.1 (p = 0.029) at 3 and 6&nbsp;months. Conclusion: ES-ThuLEP effectively preserved ejaculation in over two thirds of the patients without compromising micturition improvement or erectile function. ES-ThuLEP could be a valid treatment option for BPH in young and sexually active men

Triglyceride/HDL ratio and its impact on the risk of diabetes mellitus development during ART

OBJECTIVES: Our primary aim was to study diabetes mellitus (DM) arising during combination ART (cART) and to attempt to identify associations between these cases and triglycerides (TRG) and the TRG to HDL-cholesterol (TRG/HDL) ratio. Our secondary aim was to analyse the association between DM development and hepatic fibrosis.METHODS: This was a retrospective cohort study. Patients from the Icona Foundation study initiating first-line cART between 1997 and 2013 were selected and observed until new-onset DM or most recent clinical follow-up. The predictive value of TRG and TRG/HDL ratio levels on DM was evaluated using multivariable Poisson regression models.RESULTS: Three-thousand, five-hundred and forty-six patients (males, 73.7%; median age, 38 years; median BMI, 23.1 kg/m(2); and hepatitis C virus antibody positive, 22.1%) were included. Of these, 80 developed DM over 13 911 person-years of follow-up (PYFU), corresponding to 5.7 cases per 1000 PYFU (95% CI = 4.6-7.1). At multivariable analysis, latest TRG/HDL ratio, when high, was associated with significant increases in DM risk [relative risk (RR) = 1.63; 95% CI = 1.32-2.01 per 10 points higher], while current TRG, in contrast, was associated with new-onset DM only at crude analysis. Advanced liver fibrosis (defined as fibrosis-4 index &gt;3.25) was also shown to be an independent risk factor for DM (RR = 2.91; 95% CI = 1.10-7.72).CONCLUSIONS: High TRG/HDL ratio predicted risk of new-onset DM, independently of other traditional risk factors. Furthermore, our findings suggest that advanced hepatic fibrosis, estimated using the fibrosis-4 score, could provide an additional predictor for DM

A prospective multicenter randomized comparison between Holmium Laser Enucleation of the Prostate (HoLEP) and Thulium Laser Enucleation of the Prostate (ThuLEP)

Purpose: To compare intra and perioperative parameters between HoLEP and ThuLEP in the treatment of benign prostatic hyperplasia and to evaluate clinical and functional outcomes of the two procedures with a 12-month follow-up. Methods: A prospective randomized study was performed on 236 consecutive patients who underwent ThuLEP (n = 115), or HoLEP (n = 121) in three different centers. Intra and perioperative parameters were analyzed: operative time, enucleated tissue weight, irrigation volume, blood loss, catheterization time, hospital stay and complications. Patients were evaluated preoperatively and 3 and 12&nbsp;months postoperatively with the international prostate symptom score (IPSS), the quality of life (QoL) score, post-void residual volume (PVR), PSA and maximum flow rate (Qmax). Results: Preoperative variables in each study arm did not show any significant difference. Compared to HoLEP, ThuLEP showed similar operative time (63.69 vs 71.66&nbsp;min, p = 0.245), enucleated tissue weight (48.84 vs 51.13&nbsp;g, p = 0.321), catheterization time (1.9 vs 2.0&nbsp;days, p = 0.450) and hospital stay (2.2 vs 2.8&nbsp;days, p = 0.216), but resulted in less haemoglobin decrease (0.45 vs 2.77&nbsp;g/dL, p = 0.005). HoLEP presented a significantly higher number of patients with postoperative acute urinary retention and stress incontinence. No significant differences were found in PSA, Qmax, PVR, IPSS and QoL score during follow-up. Conclusion: ThuLEP and HoLEP both relieved lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP detemined reduced blood loss and early postoperative complications. Catheterization time, enucleated tissue, hospital stay, operative time and follow-up parameters did not show any significant difference

Ex vivo fluorescence confocal microscopy: prostatic and periprostatic tissues atlas and evaluation of the learning curve

Ex vivo fluorescence confocal microscopy (FCM) is an optical technology that provides fast H&amp;E-like images of freshly excised tissues, and it has been mainly used for “real-time” pathological examination of dermatological malignancies. It has also shown to be a promising tool for fast pathological examination of prostatic tissues. We aim to create an atlas for FCM images of prostatic and periprostatic tissues to facilitate the interpretation of these images. Furthermore, we aimed to evaluate the learning curve of images interpretation of this new technology. Eighty fresh and unprepared biopsies obtained from radical prostatectomy specimens were evaluated using the FCM VivaScope® 2500&nbsp;M-G4 (Mavig GmbH, Munich, Germany; Caliber I.D.; Rochester NY, USA) by two pathologists. Images of FCM with the corresponding H&amp;E are illustrated to create the atlas. Furthermore, the two pathologists were asked to re-evaluate the 80 specimens after 90&nbsp;days interval in order to assess the learning curve of images’ interpretation of FCM. FCM was able to differentiate between different types of prostatic and periprostatic tissues including benign prostatic glands, benign prostatic hyperplasia, high-grade intraepithelial neoplasm, and prostatic adenocarcinoma. As regards the learning curve, FCM demonstrated a short learning curve. We created an atlas that can serve as the base for urologists and pathologists for learning and interpreting FCM images of prostatic and periprostatic tissues. Furthermore, FCM images is easily interpretable; however, further studies are required to explore the potential applications of this new technology in prostate cancer diagnosis and management

The use of Versius CMR for pelvic surgery: a multicentric analysis of surgical setup and early outcomes

IntroductionVersius CMR is a novel robotic system characterized by an open surgical console and independent bedside units. The system has potentials of flexibility and versatility, and has been used in urological, gynecological, and general surgical procedure. The aim is to depict a comprehensive analysis of the Versius system for pelvic surgery.MethodsThis is a study involving two Institutions, ASST Santi Paolo and Carlo, Milan, and Apuane Hospital, Massa, Italy. All interventions performed in the pelvic area with the Versius were included. Data about indications, intra-, and post-operative course were prospectively collected and analyzed.ResultsA total of 171 interventions were performed with the Versius. Forty-two of them involved pelvic procedures. Twenty-two had an oncological indication (localized prostate cancer), the remaining had a non-oncological or functional purpose. The mostly performed pelvic procedure was radical prostatectomy (22) followed by annexectomy (9). No intra-operative complication nor conversion to other approaches occurred. A Clavien II complication and one Clavien IIIb were reported. Malfunctioning/alarms requiring a power cycle of the system occurred in 2 different cases. An adjustment in trocar placement according to patients' height was required in 2 patients undergoing prostatectomy, in which the trocar was moved caudally. In two cases, a pelvic prolapse was repaired concomitant with other gynecological procedures.ConclusionsPelvic surgery with the Versius is feasible without major complications; either dissection and reconstructive steps could be accomplished, provided a proper OR setup and trocar placement are pursued. Versius can be easily adopted by surgeons of different disciplines and backgrounds; a further multi-specialty implementation is presumed and long-term oncological and functional outcomes are awaited

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count &gt;500/ mm3 plus HIV-RNA &lt;500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA &lt;500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p &lt;0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p &lt;0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p &lt;0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p &lt;0.0001) or at year 3 (17.1% vs. 13.8%, p &lt;0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved