The influence of hiv coinfection on the natural history of hcv infection

In the United States, it is estimated that more than 4 million people are infected with the hepatitis C virus (HCV) and over 1.25 million are infected with HIV. With common routes of transmission, approximately 30% of HIV-infected individuals are coinfected with HCV. Deaths due to opportunistic infections from HIV declined with the advent of highly active antiretroviral therapy, whereas manifestations of end-stage liver disease have become more apparent with the increased longevity. Current efforts are directed toward understanding whether HIV/HCV coinfection affects the natural history of each virus. Early outcomes in treating coinfected patients for their HCV were below expectations, whereas recent treatment trials with highly selected patients and newer therapeutic agents have shown greater success. The aim of this paper is to review the epidemiology, natural history, and treatment outcomes, as well as unique challenges in the management of HIV/HCVcoinfected patients.     

Combined viscocanalostomy-trabeculectomy for management of far-advanced glaucoma: evaluation of the early postoperative course

BACKGROUND AND OBJECTIVE: To study the early postoperative efficacy and safety of combined viscocanalostomy with trabeculectomy (VISCO-TRAB) for treating far-advanced glaucoma. PATIENTS AND METHODS: Patients with far-advanced glaucoma scheduled for glaucoma surgery were enrolled in the study. Surgery included viscocanalostomy until Schlemm's canal was deroofed and dilated with viscoelastic, followed by penetrating corneotrabeculectomy, peripheral iridectomy, and tight closure of lamellar flap. Patients with severe glaucoma who were treated with trabeculectomy only (TRAB) in the preceding year were used for comparison. RESULTS: The study included 39 eyes in the VISCO-TRAB group and 40 eyes in the TRAB group. Mean intraocular pressure was significantly lower in the VISCO-TRAB group during the early postoperative period (P < .05). The postoperative course was less eventful in the VISCO-TRAB group with minimal hypotony or suture lysis-related complications. CONCLUSION: During the early postoperative period, VISCO-TRAB proved efficacious and safe in reducing intraocular pressure to target levels in patients with far-advanced glaucoma.     

An overview of targeted treatments in cancer

BACKGROUND: The concept behind cancer treatment has evolved over the past decade from systemic, nonspecific, high-dose chemotherapy to targeted therapy and the introduction of cancer vaccines. Advanced technology and a better understanding of the cellular mechanisms that control cancer biology have helped in the development of such targeted treatment. OBJECTIVE: The aim of this article was to review some of the new and commonly used targeted treatments in cancer, emphasizing their mechanisms of action, safety profiles, and clinical applications. METHODS: The terms cancer, chemotherapy, monoclonal antibodies, targeted treatment, tyrosine kinase, epidermal growth factors, epidermal growth factor receptor, and cancer vaccines were used to search MEDLINE for English-language studies in humans, published between 1966 and March 2003. Identified publications addressing the objectives of this article were selected for review. RESULTS: All-trans-retinoic acid, imatinib, gemtuzumab ozogamicin, rituximab, alemtuzumab, trastuzumab, cetuximab, and gefitinib are recently developed cancer therapies that target specific types of cells and receptors. They have been used in a variety of hematologic and solid tumors, and their tolerability makes them attractive for use even in elderly and extensively pretreated patients. Vaccines using dendritic cells, tumor cells, and fusions of tumor cells and antigen-presenting cells have also shown some promise in research, but further study is needed to obtain better, sustained results. CONCLUSIONS: Targeted treatment and cancer vaccines are novel approaches in the treatment of cancer. Both fields are expanding rapidly, with new technology and ongoing medical research. The clinical implications of such agents, administered either solely or in combination with established chemotherapeutic agents, may ultimately lead to better regimens and improved clinical responses.     

Novel nonnucleoside inhibitor of hepatitis C virus RNA-dependent RNA polymerase

A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 microM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log10 reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log10 reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays.     

Outcomes of Living Donor Liver Transplantation for Patients with Preoperative Portal Vein Problems

Background

Portal vein thrombosis (PVT) is a common complication for patients with end-stage liver disease. The presence of PVT used to be a contraindication to living donor liver transplantation (LDLT). The aim of this study is to evaluate the influence of preoperative PVT on perioperative and long-term outcomes of the recipients after LDLT.

Methods

We reviewed the data of patients who underwent LDLT during the period between 2004 till 2017.

Results

During the study period, 500 cases underwent LDLT. Patients were divided into three groups. Group I included non-PVT, 446 patients (89.2%); group II included attenuated PV, 26 patients (5.2%); and group III included PVT, 28 patients (5.6%). Higher incidence of hematemesis and encephalopathy was detected in PVT (p?=?0.001). Longer anhepatic phase was found in PVT (p?=?0.013). There were no significant differences between regarding operation time, blood loss, transfusion requirements, ICU, and hospital stay. The 1-, 3-, and 5-year overall survival (OS) rates of non-PVT were 80.5%, 77.7%, and 75%, and for attenuated PV were 84.6%, 79.6%, and 73.5%, and for PVT were 88.3%, 64.4%, and 64.4%, respectively. There was no significant difference between the groups regarding OS rates (logrank 0.793).

Conclusion

Preoperative PVT increases the complexity of LDLT operation, but it does not reduce the OS rates of such patients.

     

Intra-articular versus intravenous administration of dexmedetomidine in arthroscopic knee surgeries under local anesthesia: A prospective randomized study

Background

An intra-articular injection is considered the leading method for postoperative analgesia after knee surgery. Dexmedetomidine has peripheral and central analgesic effect. The study was conducted to compare between the analgesic effect of intra-articular and intravenous dexmedetomidine in arthroscopic knee surgery.