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Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical presentation of these complications are not well understood. We used the World Health Organization's pharmacovigilance database of individual-case-safety-reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab-based therapy (monotherapy or combination with anti-programmed death-1 [PD-1]) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti-PD-1/programmed death ligand-1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms. KEY POINTS: Immune-mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs).Providers should monitor complete blood counts during treatment with ICIs.Corticosteroids are the mainstay of treatment for immune-mediated hematologic toxicities.Further research is needed to define patient-specific risk factors and optimal management strategies for hematologic toxicities.
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Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antineoplásicos Imunológicos/efeitos adversos , Doenças Hematológicas/epidemiologia , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/terapia , Humanos , Incidência , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Farmacovigilância , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Fatores de RiscoRESUMO
When recreating outdoors in remote landscapes, people are encouraged to "leave no trace". However, the mere presence of humans on a trail can elicit changes in animal behavior, potentially compromising the effectiveness of protected areas for wildlife conservation.
Assuntos
Conservação dos Recursos Naturais , Recreação , Animais , Animais Selvagens/fisiologia , Humanos , Comportamento Animal/fisiologia , SomRESUMO
Large carnivores play critical roles in terrestrial ecosystems but have suffered dramatic range contractions over the past two centuries. Developing an accurate understanding of large carnivore diets is an important first step towards an improved understanding of their ecological roles and addressing the conservation challenges faced by these species.The puma is one of seven large felid species in the world and the only one native to the non-tropical regions of the New World. We conducted a meta-analysis of puma diets across the species' range in the Americas and assessed the impact of varying environmental conditions, niche roles, and human activity on puma diets. Pumas displayed remarkable dietary flexibility, consuming at least 232 different prey species, including one Critically Endangered and five Endangered species.Our meta-analysis found clear patterns in puma diets with changing habitat and environmental conditions. Pumas consumed more larger-bodied prey species with increasing distance from the equator, but consumption of medium-sized species showed the opposite trend.Puma diets varied with their realized niche; however, contrary to our expectations, puma consumption of large species did not change with their trophic position, and pumas consumed more small prey and birds as apex predators. Consumption of domestic species was negatively correlated with consumption of medium-sized wild species, a finding which underscores the importance of maintaining intact native prey assemblages.The tremendous dietary flexibility displayed by pumas represents both an opportunity and a challenge for understanding the puma's role in ecosystems and for the species' management and conservation. Future studies should explore the linkages between availability and selection of primary and other wild prey, and consequent impacts on predation of domestic species, in order to guide conservation actions and reduce conflict between pumas and people.
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PURPOSE: COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. METHODS: Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. RESULTS: In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. CONCLUSION: During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.