Timely Hepatitis C RNA Testing and Treatment in the Era of Direct-Acting Antiviral Therapy among People with Hepatitis C in New South Wales,Australia

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.     

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.KEY WORDS: Immune checkpoint, Pancreatic cancer, Tumor microenvironment, Immunotherapy, Clinical development     

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.     

Novel edaravone-based azo dyes: efficient synthesis,characterization, antibacterial activity,DFT calculations and comprehensive investigation of the solvent effect on the absorption spectra

The present study deals with designing and synthesizing novel dyes using the drug combination of edaravone and azo compounds which can be used as an indicator for anions and cations. The desired product synthesis was accomplished via a two-step process involving diazotizing the aromatic amines followed by the resultant salts coupling with edaravone. The resulting dyes were obtained with high yields under mild conditions. The structures of the dyes were identified with UV-vis, FT-IR, ¹H NMR and ¹³C NMR spectra and CHN analysis. To investigate the solvatochromism effect, the interaction of different solvents with the selected dyes was evaluated using several parameters including the dielectric constant, refractive index, hydrogen bond donating ability, hydrogen bond accepting ability and dipolarity/polarizability scale. To achieve deep understanding about the stability and geometrical characteristics of the azo–hydrazo tautomers of the synthesized dyes and their UV-visible spectra prediction, some DFT calculations were also carried out on the synthesized dyes. The antibacterial activities of some synthesized compounds were also evaluated using the disk diffusion method. The results revealed different activity of the selected synthesized dyes for antibacterial tests against selected Gram positive and Gram negative bacteria.

The present study deals with designing and synthesizing novel dyes using the drug combination of edaravone and azo compounds which can be used as an indicator for anions and cations.     

Mechanism of mast cell adhesion to human tenocytes in vitro

Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cell‐fibroblast co‐culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by α5β1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte‐conditioned media; the tenocyte‐derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on α5β1 integrin and tenocyte fibronectin. Additionally, tenocyte‐derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that α5β1 integrin mediates binding of mast cells to human tenocyte and to tenocyte‐derived ECM proteins, in particular fibronectin. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:9–16, 2015.

     

Fascial Repair of Laparoscopic Ports with Allis–Hemostat Technique

Port site hernias are one of the most serious complications associated with laparoscopic surgery. In this study, we present a simple and reliable method for port site closure in laparoscopic surgery. From 2005 to 2011, 500 patients who underwent laparoscopic surgery were enrolled for the study. They were evaluated considering age, sex, indication of laparoscopic surgery, and early and late complications of port site and were followed up at least for 1 year after the surgery. In our study, 180 males and 320 females with mean age of 36 years were enrolled. The most common indication for laparoscopic surgery was cholecystectomy in 320 patients (64 %). There were no early or late complications of port site after surgery. Our method is a new modification of the procedure presented by Spalding. Using Allis forceps and putting it under the fascia seems to be a more suitable technique which facilitates the laparoscopic port repair. We found it to be extremely safe, simple, and easy to teach.