Human papillomavirus viral load: a possible marker for cervical disease in HIV-infected women

n/

60PV Related Lesions in HIV Positive Subjects on HAART: Study of Viral Markers of Cervical Neoplasia Progression

Methods HIV pos women (N = 410) were followed since 1995 in a longitudinal study. Each one undergo periodic (6–12 months) colposcopy, PAP smear, biopsy if needed, and cervical sampling for HPV testing. HIV related parameters (CD4, HIV-RNA, ART) are recorded and related to cervical disease. HPV typing is performed by reverse hybridisation assays, viral load by in-house real time PCR and viral expression by E6/E7 mRNA detection. The Mann-Whitney rank sum test for non-parametric data and the association between discrete variables by Chi-square test of Fisher exact test were applied

Crossing barriers: the burden of inflammatory bowel disease across Western Europe

Disease burden; Healthcare; Inflammatory bowel diseaseCàrrega de la malaltia; Atenció sanitària; Malaltia inflamatòria de l'intestíCarga de la enfermedad; Atención sanitaria; Enfermedad inflamatoria intestinalAn estimated 2.5–3 million individuals (0.4%) in Europe are affected by inflammatory bowel disease (IBD). Whilst incidence rates for IBD are stabilising across Europe, the prevalence is rising and subsequently resulting in a significant cost to the healthcare system of an estimated 4.6–5.6 billion euros per year. Hospitalisation and surgical resection rates are generally on a downward trend, which is contrary to the rising cost of novel medication. This signifies a large part of healthcare cost and burden. Despite publicly funded healthcare systems in most European countries, there is still wide variation in how patients receive and/or pay for biologic medication. This review will provide an overview and discuss the different healthcare systems within Western Europe and the barriers that affect overall management of a changing IBD landscape, including differences to hospitalisation and surgical rates, access to medication and clinical trial participation and recruitment. This review will also discuss the importance of standardising IBD management to attain high-quality care for all patients with IBD

Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report

<p>Abstract</p> <p>Introduction</p> <p>There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.</p> <p>Conclusion</p> <p>This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.</p

Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients

BACKGROUND: Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. OBJECTIVES: To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy. PATIENTS AND METHODS: We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification. RESULTS: In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP. CONCLUSIONS: Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LF

Sustained virological response after ten days of triple anti-hepatitis C virus (HCV) therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman

The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV) genotype 1 has significantly improved the sustained virological response (SVR) rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860 C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype). Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients

Robotic rectal surgery: State of the art

Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases (PubMed and EMBASE) using the key words “rectum”, “rectal”, “cancer”, “laparoscopy”, “robot”. After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection (1450 patients, 48.1%), followed by anterior resections (997 patients, 33%), ultra-low anterior resections (393 patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultra-low anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients

Survival outcomes and effect of early vs. deferred cART among HIV-infected patients diagnosed at the time of an AIDS-defining event: a cohort analysis.

Objectives: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (< 30 days after AIDS event) or deferred (30-270 days after AIDS event) cART. Results: The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/ mL and 5.2 (4.5, 5.7) log 10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p=0.20). Conclusions: Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting

Detection of low-level HCV variants in DAA treated patients: comparison amongst three different NGS data analysis protocols

Background: Notwithstanding the efforts of direct-acting antivirals (DAAs) for the treatment of chronically infected hepatitis C virus (HCV) patients, concerns exist regarding the emergence of resistance-associated substitutions (RAS) related to therapy failure. Sanger sequencing is still the reference technique used for the detection of RAS and it detects viral variants present up to 15%, meaning that minority variants are undetectable, using this technique. To date, many studies are focused on the analysis of the impact of HCV low variants using next-generation sequencing (NGS) techniques, but the importance of these minority variants is still debated, and importantly, a common data analysis method is still not defined. Methods: Serum samples from four patients failing DAAs therapy were collected at baseline and failure, and amplification of NS3, NS5A and NS5B genes was performed on each sample. The genes amplified were sequenced using Sanger and NGS Illumina sequencing and the data generated were analyzed with different approaches. Three different NGS data analysis methods, two homemade in silico pipeline and one commercially available certified user-friendly software, were used to detect low-level variants. Results: The NGS approach allowed to infer also very-low level virus variants. Moreover, data processing allowed to generate high accuracy data which results in reduction in the error rates for each single sequence polymorphism. The results improved the detection of low-level viral variants in the HCV quasispecies of the analyzed patients, and in one patient a low-level RAS related to treatment failure was identified. Importantly, the results obtained from only two out of the three data analysis strategies were in complete agreement in terms of both detection and frequency of RAS. Conclusions: These results highlight the need to find a robust NGS data analysis method to standardize NGS results for a better comprehension of the clinical role of low-level HCV variants. Based on the extreme importance of data analysis approaches for wet-data interpretation, a detailed description of the used pipelines and further standardization of the in silico analysis could allow increasing diagnostic laboratory networking to unleash true potentials of NGS

Robotic vs laparoscopic distal gastrectomy with D2 lymphadenectomy for gastric cancer: A retrospective comparative mono-institutional study

BACKGROUND: Robotic surgery has been developed with the aim of improving surgical quality and overcoming the limitations of conventional laparoscopy in the performance of complex mini-invasive procedures. The present study was designed to compare robotic and laparoscopic distal gastrectomy in the treatment of gastric cancer. METHODS: Between June 2008 and September 2015, 41 laparoscopic and 30 robotic distal gastrectomies were performed by a single surgeon at the same institution. Clinicopathological characteristics of the patients, surgical performance, postoperative morbidity/mortality and pathologic data were prospectively collected and compared between the laparoscopic and robotic groups by the Chi-square test and the Mann-Whitney test, as indicated. RESULTS: There were no significant differences in patient characteristics between the two groups. Mean tumor size was larger in the laparoscopic than in the robotic patients (5.3 ± 0.5 cm and 3.0 ± 0.4 cm, respectively; P = 0.02). However, tumor stage distribution was similar between the two groups. The mean number of dissected lymph nodes was higher in the robotic than in the laparoscopic patients (39.1 ± 3.7 and 30.5 ± 2.0, respectively; P = 0.02). The mean operative time was 262.6 ± 8.6 min in the laparoscopic group and 312.6 ± 15.7 min in the robotic group (P < 0.001). The incidences of surgery-related and surgery-unrelated complications were similar in the laparoscopic and in the robotic patients. There were no significant differences in short-term clinical outcomes between the two groups. CONCLUSIONS: Within the limitation of a small-sized, non-randomized analysis, our study confirms that robotic distal gastrectomy is a feasible and safe surgical procedure. When compared with conventional laparoscopy, robotic surgery shows evident benefits in the performance of lymphadenectomy with a higher number of retrieved and examined lymph nodes