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INTRODUCTION Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis. MATERIAL AND METHODS This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects. RESULTS A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically. CONCLUSION Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.

Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [18F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, 19FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC50], 26-32 nM). The radiotracer, [18F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[18F]fluoronicotinate ([18F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [18F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [18F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [18F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.

Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis.This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects.A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically.Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.

Anhydrous indium trichloride (InCl3) is found to catalyze the electrophilic substitution reaction of indole with aromatic aldehydes and Schiff's bases which resulted in an efficient synthesis of bis-indolylmethanes in good to excellent yield.

Anhydrous indium trichloride (InCl3) is found to catalyze the electrophilic substitution reaction of indole with aromatic aldehydes and Schiff's bases which resulted in an efficient synthesis of bis-indolylmethanes in good to excellent yield.