HIV/HCV Co-infection: Pathogenesis, Clinical Complications, Treatment, and New Therapeutic Technologies

World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies

Prognostic Impact of Blood Transfusion in Patients Undergoing Primary Surgery and Free-flap Reconstruction for Oral Squamous Cell Carcinoma

BACKGROUND: The objective of this study was to assess the impact of perioperative transfusion on the prognosis of patients who underwent complete (RO) resection of oral squamous cell carcinoma and reconstruction by microvascular flaps. METHODS: By following an inclusion and exclusion protocol, 223 patients were included in the study who underwent RO resection of oral squamous cell carcinoma and reconstruction by rnicrovascular flaps at a single center. Clinical and pathologic factors as well as transfusion data were retrieved from a prospective database and analyzed retrospectively. Survival data were assessed using the method of Kaplan and Meier. For multivariate analysis the accelerated failure time model (Weibull distribution) was chosen. RESULTS: The overall survival rate was 71% at 1 year, 67% at 3 years, and 55% at 5 years. In univariate analysis, age (P = .003), tumor size (P = .005), lymph node status (P = .008), tumor differentiation (P = .008), transfusion (P = .006), American Society of Anesthesiologists (ASA) class (P = .001), and mandibular reconstruction (P = .045) were associated significantly with overall survival. Multivariate analysis identified only age, histopathologic differentiation, and ASA class as independent risk factors (P < .001, P = .04, and P = .049, respectively). Age was identified as the strongest independent predictor for overall survival (hazards ratio for each 13-year increase in age, 1,97; 95% confidence interval, 1.36-2.85). CONCLUSIONS: Transfusion of >4 U of blood did not appear to influence overall survival in patients who underwent primary surgery for oral squamous cell carcinoma. Because age and ASA class evolved as the strongest predictors of shortened overall survival, associated comorbidities may require more attention, particularly in elderly or socially deprived patients. Cancer 2009;115:1481-8. (C) 2009 American Cancer Society

Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months follow-up

This is a prospective clinical study aimed at assessing the success rate of osteotomy and primary wound closure in patients with bisphosphonate-associated osteonecrosis of the jaw (BONJ). Fifty patients who had received bisphosphonates intravenously and subsequently suffered from BONJ were included in the study. All patients underwent osteotomy of the affected jaw bone region and primary wound closure under general anaesthesia. They were followed up bimonthly for a period of 12 months. Macroscopically altered bone could be completely removed in all cases. In two patients with plasmocytoma, major bleeding occurred postoperatively that required monitoring in an intensive care unit. In two cases, recurrence of BONJ was diagnosed during the first 2 months. In three patients, recurrence appeared between the fourth and the sixth month. In these cases, an additional osteotomy had to be performed. Six patients died during the follow-up period. In the remaining 39 patients, no signs of recurrence could be detected during the follow-up of 12 months. The success rate of the surviving patients was 89% after 1 year. Due to the high success rate of osteotomy and primary wound closure, it should be checked for every patient suffering from BONJ if osteotomy is a viable treatment option

Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs

The failure of β cells to secrete sufficient amounts of insulin is a key feature of diabetes mellitus. Each β cell secretes only a small amount of insulin upon stimulation in a highly regulated fashion: young insulin is preferentially released, whereas old insulin is mainly degraded within the β cell. How this process is regulated in vivo and likely altered in diabetes is currently unknown. We present here a transgenic pig model that allows the in vivo fluorescent labeling of age-distinct insulin secretory granule pools, hence providing a close-to-life readout of insulin turnover. This will enable the study of alterations in β cell function in an animal model close to humans

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance-associated substitutions in naïve patients from Argentina

Abstract: Direct acting antiviral (DAA) therapy against hepatitis C virus (HCV) increases sustained virologic response rates. Nevertheless, drug resistance has occasionally been associated with failure to DAA. However, the information about the prevalence of NS5A and NS5B resistance-associated substitutions (RASs) in Argentina is very scarce. In this study, we determine the prevalence of NS5A and NS5B resistances to treatment in Argentinean DAA treatment-naïve patients chronically infected with genotype 1 (HCV-1). In this retrospective cross-sectional study, 108 HCV-1-infected patients were studied. RASs in NS5A and NS5B were analyzed by Sanger at baseline and phylogenetic analysis was performed. NS5A and NS5B RASs were detected in 25.8% and 6.3% of the analyzed sequences, respectively. The most frequent primary RASs for NS5A were L31M (7.5%) and Y93H (3.2%) and for NS5B was L159F (3.8%). No association between the presence of RASs and the outcome of DAA treatment was found in this study. Additionally, most of the Argentinean samples were randomly distributed among sequences around the world in the phylogenetic analysis. Only one significant Argentinean cluster was observed in both regions but without any particular RASs pattern. Baseline RASs in NS5A and NS5B were frequently observed in HCV-1-infected patients from Buenos Aires, Argentina but not related to treatment outcome. No clusters related to RASs transmission were observed in the phylogenetic analysis. The frequency of RASs detected in this study supports the need for more molecular epidemiology studies on RASs to adjust local treatment guidelines with the incorporation of autochthonous data.Fil: Martínez, Alfredo P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: García, Gabriel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Culasso, Andrés Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Pereson, Matías J.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Neukam, Karin. Universidad de Sevilla; EspañaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin