The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Safety and Efficacy of Ombitasvir, Paritaprevir With Ritonavir ± Dasabuvir With or Without Ribavirin in Patients With Human Immunodeficiency Virus-1 and Hepatitis C Virus Genotype 1 or Genotype 4 Coinfection: TURQUOISE-I Part 2.

BACKGROUND: Ombitasvir, paritaprevir with ritonavir, and dasabuvir (OBV/PTV/r ± DSV) ±ribavirin (RBV) are approved to treat hepatitis C virus (HCV) genotype 1 and 4 infection. Here, we investigate the safety and efficacy of OBV/PTV/r + DSV ±RBV for HCV genotype 1, and OBV/PTV/r + RBV for HCV genotype 4, in human immunodeficiency virus (HIV)-1 coinfected patients with or without compensated cirrhosis. METHODS: TURQUOISE-I, Part 2 is a phase 3 multicenter study. Patients with or without cirrhosis were HCV treatment-naive or -experienced, on an HIV-1 antiretroviral regimen containing atazanavir, raltegravir, dolutegravir, or darunavir (for genotype 4 only), and had plasma HIV-1 ribonucleic acid <40 copies/mL at screening. Patients received OBV/PTV/r ± DSV ±RBV for 12 or 24 weeks. RESULTS: In total, 228 patients were treated according to guidelines. Sustained virologic response at posttreatment week 12 (SVR12) was achieved by 194 of 200 (97%) and 27 of 28 (96%) patients with HCV genotype 1 and genotype 4 infection, respectively. There were 2 virologic failures: 1 breakthrough and 1 relapse in a cirrhotic and a noncirrhotic patient with genotype 1b and 1a infection, respectively. One reinfection occurred at posttreatment week 12 in a genotype 1a-infected patient. Excluding nonvirologic failures, the SVR12 rates were 98% (genotype 1) and 100% (genotype 4). Adverse events were mostly mild in severity and did not lead to discontinuation. Laboratory abnormalities were rare. CONCLUSIONS: The OBV/PTV/r ±DSV was well tolerated and yielded high SVR12 rates in patients with HCV genotype 1 or genotype 4/HIV-1 coinfection. The OBV/PTV/r ± DSV ±RBV is a potent HCV treatment option for patients with HIV-1 coinfection, regardless of treatment experience

Can the ADO Index Be Used as a Predictor of Mortality from COVID-19 in Patients with COPD?

Esra Ertan Yazar,1 Gulsah Gunluoglu,2 Burcu Arpinar Yigitbas,1 Mukadder Calikoglu,3 Gazi Gulbas,4 Nilgün Y&inodot;lmaz Demirci,5 Nurhan Sarioglu,6 Fulsen Bozkus,7 Nevin Taci Hoca,5 Nalan Ogan,8 Seda Tural Onur,2 Muzaffer Onur Turan,9 Filiz Kosar,2 Evrim Eylem Akpinar,8 Burak Mete,10 Can Ozturk5 1Department of Chest Diseases, Istanbul Medeniyet University, Medical Faculty, Istanbul, Turkey; 2Department of Chest Diseases, Yedikule Chest Disease and Chest Surgery Research and Training Hospital, Istanbul, Turkey; 3Department of Chest Diseases, Mersin University, Medical Faculty, Mersin, Turkey; 4Department of Chest Diseases, Inonu University, Medical Faculty, Malatya, Turkey; 5Department of Chest Diseases, Gazi University, Medical Faculty, Ankara, Turkey; 6Department of Chest Diseases, Balikesir University, Medical Faculty, Balikesir, Turkey; 7Department of Chest Diseases, Kahramanmaras Sutcu Imam University, Medical Faculty, Kahramanmaras, Turkey; 8Department of Chest Diseases, Ufuk University, Medical Faculty, Ankara, Turkey; 9Department of Chest Diseases, Prof Dr, Izmir Katip Celebi University, Atatürk Research and Training Hospital, Izmir, Turkey; 10Department of Public Health Çukurova University, Medical Faculty, Adana, TurkeyCorrespondence: Esra Ertan Yazar, Istanbul Medeniyet University, Medical Faculty, Department of Chest Diseases, Istanbul, Turkey, Email [email protected]: Several studies have shown that the risk of mortality due to COVID-19 is high in patients with COPD. However, evidence on factors predicting mortality is limited.Research Question: Are there any useful markers to predict mortality in COVID-19 patients with COPD?.Study Design and Methods: A total of 689 patients were included in this study from the COPET study, a national multicenter observational study investigating COPD phenotypes consisting of patients who were followed up with a spirometry-confirmed COPD diagnosis. Patients were also retrospectively examined in terms of COVID-19 and their outcomes.Results: Among the study patients, 105 were diagnosed with PCR-positive COVID-19, and 19 of them died. Body mass index (p= 0.01) and ADO (age, dyspnoea, airflow obstruction) index (p= 0.01) were higher, whereas predicted FEV1 (p< 0.001) and eosinophil count (p= 0.003) were lower in patients who died of COVID-19. Each 0.755 unit increase in the ADO index increased the risk of death by 2.12 times, and each 0.007 unit increase in the eosinophil count decreased the risk of death by 1.007 times. The optimum cut-off ADO score of 3.5 was diagnostic with 94% sensitivity and 40% specificity in predicting mortality.Interpretation: Our study suggested that the ADO index recorded in the stable period in patients with COPD makes a modest contribution to the prediction of mortality due to COVID-19. Further studies are needed to validate the use of the ADO index in estimating mortality in both COVID-19 and other viral respiratory infections in patients with COPD.Keywords: body mass index, COVID-19, eosinophils, FEV1, mortality, pneumonia, pulmonary disease, chronic obstructiv

Economic policies and methods of determining the costs of services related to national telecommunication/ICT networks: Output Report on ITU-D Question 4/1 for the study period 2018-2021

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Document de consens per a la coinfecció pel Virus de la Immunodeficiència Humana i els Virus de les Hepatitis a Catalunya

VIH; Virus de les Hepatitis; CoinfeccióVIH; Virus de las Hepatitis; CoinfecciónHIV; Hepatitis virus; CoinfectionAquest manual ha estat preparat amb la intenció d'abordar els problemes que planteja el maneig de les persones malaltes amb coinfecció pel virus de la sida i els virus de l'hepatitis. A més, facilita als metges i metgesses assistencials els recursos necessaris per al diagnòstic i la presa de decisions terapèutiques, així com els criteris per ampliar la prevenció en tots aquells grups de població exposats a contraure aquestes infeccions.Este manual ha sido preparado con la intención de abordar los problemas que plantea el manejo de las personas enfermas con coinfección por el virus del sida y los virus de la hepatitis. Además, facilita a los médicos asistenciales los recursos necesarios para el diagnóstico y la toma de decisiones terapéuticas, así como los criterios para ampliar la prevención en todos aquellos grupos de población expuestos a contraer estas infecciones

Atlas of the Global Burden of Stroke (1990-2013): The GBD 2013 Study

Background—World mapping is an important tool to visualize stroke burden and its trends in various regions and countries. Objectives—To show geographic patterns of incidence, prevalence, mortality, disability-adjusted life-years (DALYs) and years lived with disability (YLDs), and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990 to 2013. Methodology—Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated following the general approach of the Global Burden of Disease (GBD) 2010 with several important improvements in methods. Data were updated for mortality (through April 2014) and stroke incidence, prevalence, case fatality, and severity through 2013. Death was estimated using an ensemble modelling approach. A new software package, DisMod-MR 2.0 was used as part of a custom modelling process to estimate YLDS. All rates were age-standardized to new GBD estimates of global population. All estimates have been computed with 95% uncertainty intervals (UI). Results—Age-standardized incidence, mortality, prevalence and DALYs/YLDs declined over the period from 1990 to 2013. However, the absolute number of people affected by stroke has substantially increased across all countries in the world over the same time period, suggesting that the global stroke burden continues to increase. There were significant geographical (country and regional) differences in stroke burden in the world, with the majority of the burden borne by low- and middle-income countries. Conclusions—Global burden of stroke has continued to increase in spite of dramatic declines in age-standardized incidence, prevalence, mortality rates, and disability. Population growth and ageing have played an important role in the observed increase in stroke burden

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.Peer reviewe

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe