Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains

Occipital tip injury with homonymous central scotoma: OCT-NFL and RGC correlation

Purpose: To report one case of homonymous paracentral scotoma with corresponding optical coherence tomography (OCT) findings in a young woman after injury to the left occipital lobe tip. Observations: A young woman with past medical history of Hodgkin's lymphoma and large B-cell lymphoma metastatic to the left occipital lobe status post resection presented to the eye clinic with a chief complaint of a “blind spot” in the right eye since her surgery. Humphrey visual field (HVF) showed a right homonymous paracentral scotoma corresponding to the non-decussating and decussating optic radiation for central vision originating from the left lateral geniculate nucleus (LGN). OCT confirmed atrophy of the right nasal hemifovea with fibers originating from the papillomacular bundle and the left temporal hemifovea with fibers originating from the superior temporal segment of the optic nerve. These fibers correspond to the central vision involved with the left posterior occipital lobe tip. Conclusions and Importance: We report a case of right homonymous central vision loss as a result of injury to the left posterior occipital lobe tip with certain unique features. Here, a small lesion in the posterior visual pathway led to a relatively large loss of ganglion cell layer. Keywords: Ganglion cell layer, Nerve fiber layer, Homonymous hemianopia, Thinnin

Rate of bleeding-related episodes in elderly patients with primary immune thrombocytopenia: a retrospective cohort study

<p><b>Objective:</b> Immune thrombocytopenia (ITP) is characterized by low platelet counts and a tendency toward increased bleeding and bruising. We aimed to describe bleeding frequency and use of rescue ITP therapy to treat or prevent bleeding in elderly ITP patients in a real-world setting.</p> <p><b>Methods:</b> Using Medicare 20% sample data, 2007–2012, we identified elderly (ages ≥67 years) Medicare fee-for-service enrollees diagnosed with primary ITP between 1 January 2009 and 30 September 2012. Bleeding-related episodes (BREs) were defined as ≥1 bleeding event or use of ITP therapies commonly considered for rescue or emergency therapy. BRE rates were examined for the cohort overall, by time since ITP onset, and by splenectomy status. Patients were followed from ITP onset until the earliest of death, disenrollment from fee-for-service coverage, or 31 December 2012.</p> <p><b>Results:</b> We identified 3007 elderly patients diagnosed with primary ITP (mean [SD] age: 79.6 [7.5] years; 55% female); 2178 (72%) experienced at least one BRE (8867 BREs); 92 (3%) underwent splenectomy. Nearly half of BREs were defined by rescue therapy use alone. The overall rate was 1.72 BREs per patient-year (95% CI; 1.68–1.75); rates were higher during the first 3 months after ITP onset and after splenectomy.</p> <p><b>Conclusion:</b> Elderly ITP patients experienced about two BREs per patient-year after ITP onset. Most patients experienced at least one BRE. These real-world results demonstrate the importance of examining both bleeding and use of rescue or emergency ITP therapy in the assessment of disease burden in elderly patients with ITP.</p

Quantifying the reduction in immunoglobulin use over time in patients with chronic immune thrombocytopenic purpura receiving romiplostim (AMG 531)

Patients with Immune thrombocytopenic purpura (ITP) often require immunoglobulin (Ig) therapy with intravenous 19 (IVIG) or anti-D to prevent or treat the serious bleeding events. Because the thrombopoietin (TPO) mimetic romiplostim (AMG 531; Nplate) elevates platelet counts in patients with chronic ITP, we quantified to what extent it reduced the incidence of Ig rescue therapy in two randomized (vs. placebo) trials of romiplostim for chronic ITP. Our analysis shows that significantly fewer romiplostim patients than placebo patients required Ig therapy over the course of 24 weeks (1-6% vs. 19-37%, respectively; P <0.05 for each 4-week interval), and romiplostim-treated patients were 5.31-fold less likely to receive Ig therapy (P <0.001)

First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors

BACKGROUND: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors. METHODS: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every 4 weeks (Q4W)) intravenously. Dose-expansion: patients with melanoma (n=10) and NSCLC (n=20) who progressed on prior anti-programmed death receptor 1/programmed death ligand-1 and/or anti-cytotoxic T-lymphocyte-associated antigen 4 (melanoma) received ivuxolimab 30 mg Q2W intravenously plus utomilumab 20 mg Q4W intravenously. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events V.4.03 and efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and immune-related RECIST (irRECIST). Paired tumor biopsies and whole blood were collected to assess pharmacodynamic effects and immunophenotyping. Whole blood samples were collected longitudinally for immunophenotyping. RESULTS: Dose-escalation: 57 patients were enrolled; 2 (3.5%) patients with melanoma (0.3 mg/kg+20 mg and 0.3 mg/kg+100 mg) achieved partial response (PR), 18 (31.6%) patients achieved stable disease (SD); the disease control rate (DCR) was 35.1% across all dose levels. Dose-expansion: 30 patients were enrolled; 1 patient with NSCLC achieved PR lasting >77 weeks. Seven of 10 patients with melanoma (70%) and 7 of 20 patients with NSCLC (35%) achieved SD: median (range) duration of SD was 18.9 (13.9-49.0) weeks for the melanoma cohort versus 24.1 (14.3-77.9+) weeks for the NSCLC cohort; DCR (NSCLC) was 40%. Grade 3-4 treatment-emergent AEs were reported in 28 (49.1%) patients versus 11 (36.7%) patients in dose-escalation and dose-expansion, respectively. There were no grade 5 AEs deemed attributable to treatment. Ivuxolimab area under the concentration-time curve increased in a dose-dependent manner at 0.3-3 mg/kg doses. CONCLUSIONS: Ivuxolimab+utomilumab was found to be well tolerated and demonstrated preliminary antitumor activity in selected groups of patients. TRIAL REGISTRATION NUMBER: NCT02315066