An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

ABSTRACT: BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within [PLUS-MINUS SIGN]1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa--to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was [LESS-THAN OR EQUAL TO]29 weeks. Overall, the proportion of patients with hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2--13) to 54% (Weeks 18--25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449.     

Intraocular endoscopy: A review

Optimal visualization is one of the most challenging aspects of performing vitreoretinal surgery. In situations where conventional microscopic techniques provide poor posterior visualization, the adjunctive skill set of endoscopic visualization may be needed. This allows for by-passing the opaque anterior segment media and getting access to the posterior segment pathology. Endoscopic vitrectomy is a useful and unique adjunct to microincision vitreoretinal surgery. The optical set-up of endoscopy allows for clinical approaches that are impossible with regular microscope viewing systems. These include the ability to observe across optically significant anterior segment opacities and directly visualize the posterior segment of the eye. It also allows for visualizing the difficult-to-access retroirideal, retrolental, and anterior retinal structures. Surgical access to anatomic spaces like the pars plana, pars plicata, ciliary sulcus, ciliary body, and peripheral lens is tedious. This is made simpler by endoscopy. In this review, we summarize and review the usage of the intraocular endoscope as a diagnostic and therapeutic armamentarium across a wide spectrum of ocular pathologies.     

Simple organocatalyst component system for asymmetric hetero Diels–Alder reaction of isatins with enones

A simple two catalyst component system consisting of primary β-amino alcohols as a catalyst and amino acids as a co-catalyst put together works as an efficient organocatalyst system in the hetero Diels–Alder reaction of isatins with enones to afford the chiral spirooxindole–tetrahydropyranones in good chemical yields and stereoselectivities (up to 86%, up to 85 : 15 dr., up to 95% ee).

A simple two catalysts component system of β-amino alcohols (catalyst) and amino acids (co-catalyst) works as an efficient organocatalysts in hetero Diels–Alder reaction of isatins with enones to afford chiral spirooxindole-tetrahydropyranones.     

Prostate cancer may trigger paraneoplastic limbic encephalitis: A case report and a review of the literature

We present a case of a previously healthy and active 64‐year‐old man who experienced a rapid neuropsychiatric decline. All tests for metabolic causes, neuroinfection, intracranial infarction or tumor were negative. By the means of magnetic resonance imaging, electroencephalography and the anti‐Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer‐related paraneoplastic limbic encephalitis. High‐risk prostate cancer can trigger paraneoplastic limbic encephalitis, a rapidly progressive neurological syndrome with a bad prognosis.