Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry.

OBJECTIVES: To evaluate the effectiveness and safety of pembrolizumab use in advanced melanoma in a real-life context; and to explore the existence of an efficacy-effectiveness gap, comparing registry data with the reference clinical trial. METHODS: This study followed the guidelines for good pharmacoepidemology practice. An ambispective cohort was constituted, initiating the observation upon drug approval (17/07/2015) and following exposed patients until death or cut-off date (15/11/2019). The primary outcome was overall survival (OS); secondary outcomes comprised progression-free survival (PFS), overall response rate (ORR) and the occurrence of adverse events (AE). For all survival analyses, the Kaplan-Meier estimator was used, considering a 95% confidence interval (CI), aside with one-year survival rates. RESULTS: A total of 125 patients constituted the cohort, originating from 16 hospitals in Portugal. Median OS was estimated to be 16.9 months (CI95% 11.3-25.5) and the probability of survival after 1 year was 57.5% (CI95% 48.4%-65.6%). Median PFS was estimated to be 4.8 months (CI95% 3.9-6.7) and the probability of remaining progression-free after 1 year was 32.8% (CI95% 24.8-41.1). ORR was 30.4% (CI95% 22.5%-39.3%). AEs were experienced by 82% of patients, and 27% experienced AE≥ grade 3. CONCLUSIONS: Our data suggest lower effectiveness in a real-life context than the efficacy reported in the clinical trial. Safety data seems, however, quite comparable to KEYNOTE-006.

Nesidioblastosis Associated with Pancreatic Heterotopia as a Differential Diagnosis of Hypoglycemia: A Literature Review and Case Report.

BACKGROUND Nesidioblastosis is a rare disease that is part of the differential diagnosis of pancreatogenic hyperinsulinemic hypoglycemia (PHH) in patients whose imaging studies do not localize insulinoma. Pancreatic heterotopia is a rare congenital abnormality characterized by pancreatic tissue anatomically separated from the main gland and found in 0.5% of abdominal surgeries. The purpose of this article is to provide a systematic review of the literature on nesidioblastosis in pancreatic ectopic tissue and to describe a case of the co-occurrence of these 2 rare conditions. CASE REPORT A 32-year-old man presented with adrenergic and neuroglycopenic symptoms, with laboratory-confirmed hyperinsulinemic hypoglycemia. There was no evidence of tumors on abdominal CT scan and MRI. Celiac trunk sampling with a calcium stimulation test was done, which showed an insulin gradient in the gastroduodenal artery. However, the intraoperative ultrasound showed a small nodule located at the pancreatic tail, leading to distal pancreatectomy. The histologic examination showed nesidioblastosis associated with pancreatic heterotopia. The patient remained asymptomatic after distal pancreatectomy. CONCLUSIONS Nesidioblastosis accounts for 0.5%-5% of all cases of PHH, with a histology showing hypertrophy and hyperplasia of pancreatic islets. Pancreatic heterotopia is a rare congenital anomaly resulting from failure of pancreatic cell migration, and is found as an incidentaloma in imaging or surgeries. Although it is a rare disease, nesidioblastosis should be considered in the investigation of hypoglycemia, even in the rare presentation of nesidioblastosis in patients with pancreatic heterotopy.

Personality and morphological traits affect pigeon survival from raptor attacks.

Personality traits have recently been shown to impact fitness in different animal species, potentially making them similarly relevant drivers as morphological and life history traits along the evolutionary pathways of organisms. Predation is a major force of natural selection through its deterministic effects on individual survival, but how predation pressure has helped to shape personality trait selection, especially in free-ranging animals, remains poorly understood. We used high-precision GPS tracking to follow whole flocks of homing pigeons (Columba livia) with known personalities and morphology during homing flights where they were severely predated by raptors. This allowed us to determine how the personality and morphology traits of pigeons may affect their risk of being predated by raptors. Our survival model showed that individual pigeons, which were more tolerant to human approach, slower to escape from a confined environment, more resistant to human handling, with larger tarsi, and with lighter plumage, were more likely to be predated by raptors. We provide rare empirical evidence that the personality of prey influences their risk of being predated under free-ranging circumstances.