Hipofisitis e insuficiencia suprarrenal secundaria asociada a pembrolizumab

Introducción: los inhibidores de puntos de control inmunológico (IPCI) hacen parte del arsenal terapéutico contra diferentes tipos de tumores sólidos, demostrando su utilidad contra melanoma metastásico, estadio III. En Colombia, para esta indicación se cuenta con la aprobación de anticuerpos contra el antígeno 4 de los linfocitos T citotóxicos (anti-CTLA-4) y de anticuerpos contra el receptor de muerte celular programada 1 (anti-PD-1). Se han descrito eventos adversos inmunomediados, siendo las endocrinopatías uno de los más frecuentes. La hipofisitis se asocia comúnmente con terapia anti CTLA-4, siendo rara la presentación en pacientes con terapia con anti-PD-1, presentándose, en estos últimos, cuadros clínicos más larvados e inespecíficos, pero cuyas manifestaciones pueden ser graves. Objetivo: presentar un caso clínico que ilustra un efecto adverso endocrinológico, asociado a tratamiento con inmunoterapia, en paciente con melanoma metastásico, para tener en cuenta cuando se use este grupo de medicamentos. Presentación del caso: el presente artículo informa del caso de un paciente masculino de 81 años con cuadro de hipofisitis con reacción adversa grado 3, por insuficiencia suprarrenal secundaria al uso de pembrolizumab, como parte del tratamiento de un melanoma metastásico pulmonar. Debutó con síntomas generales de astenia, náuseas, hiporexia e hiponatremia hipotónica normovolémica con niveles bajos de cortisol y con ACTH (hormona adrenocorticotrópica) inapropiadamente normal. Requirió manejo intrahospitalario con glucocorticoides, con respuesta adecuada clínica y paraclínica al tratamiento. Discusión y conclusiones: los tratamientos de inmunoterapia en pacientes con enfermedad neoplásica cada vez son más utilizados y pueden llevar al desarrollo de eventos adversos. Se presenta, en el caso clínico, un evento de toxicidad por pembrolizumab que causa una insuficiencia adrenal secundaria aislada. Esta es una situación poco común y suele presentarse con una clínica inespecífica por lo que debemos tener alto nivel de sospecha para brindar un adecuado manejo; la demora para iniciar el tratamiento con corticoides tiene consecuencias en el paciente

Neuropathy induced by medical cancer therapy

  Los avances recientes en el tratamiento de las enfermedades neoplásicas han mejorado las tasas de supervivencia. Las intervenciones médicas generan diversos efectos adversos agudos que comprometen el tracto gastrointestinal y la médula ósea, mientras la neurotoxicidad tiende a ser tardía y evoluciona en el tiempo. En el sistema nervioso periférico es frecuente documentar la neuropatía inducida por el tratamiento médico del cáncer, hallazgo relacionado con la administración de agentes quimioterapéuticos utilizados para controlar los tumores hematológicos y sólidos. El tratamiento oncológico genera una gran variedad de cambios estructurales y funcionales en los nervios periféricos, incluyendo la afectación de los cuerpos neuronales del sistema de transporte axonal, del recubrimiento mielínico y de las estructuras de soporte glial. Cada agente presenta un espectro de toxicidad único que se relaciona con su mecanismo de acción, eventos que pueden mitigarse gracias a los resultados de múltiples estudios. Gracias al reconocimiento de los efectos devastadores de la neuropatía inducida por el tratamiento médico del cáncer en la calidad de vida, la investigación básica y clínica ha empezado a evaluar el papel de múltiples terapias para prevenir y tratar el daño neurológico. Esta revisión integra información seleccionada a partir de búsquedas estructuras realizadas en las bases de datos biomédicas más relevantes, haciendo énfasis en el diagnóstico y en las intervenciones farmacológicas y no farmacológicas descritas como parte del manejo de la neuropatía inducida por el tratamiento médico del cáncer, que con frecuencia es subvalorada. En conclusión, la información disponible hasta el momento permite establecer los mecanismos de la enfermedad y sugiere el desarrollo de un número mayor de estudios que permitan validar las estrategias descritas hasta el momento. (MÉD.UIS. 2010;23(2):100-19). Palabras clave: Neuropatía periférica. Neoplasia. Enfermedad de los nervios periféricos. Quimioterapia. Taxanos. Vincristina. Cisplatino. Agentes antineoplásicos. Efectos adversos.      Recent advances in the development and administration of therapy for malignant diseases have been rewarded with prolonged survival rates. Unlike more immediate toxicities that affect the gastrointestinal tract and bone marrow, chemotherapy-induced neurotoxicity is frequently delayed in onset and may progress over time. In the peripheral nervous system, the major brunt of the toxicity is directed against the peripheral nerve, resulting in cancer therapy-induced peripheral neuropathy. Chemotherapeutic agents used to treat hematologic and solid tumors target a variety of structures and functions in the peripheral nervous system, including the neuronal cell body, the axonal transport system, the myelin sheath, and glial support structures. Each agent exhibits a spectrum of effects unique to its mechanism of action, and recent studies in this field have yielded clearer ideas on how to mitigate injury. Combined with the call for a greater recognition of the devastating effects of cancer therapy-induced peripheral neuropathy on quality of life, basic and clinical researchers have begun to investigate therapy to prevent and treat neurologic damage. This review was made based on relevant information avaliable on international databases concerning cancer therapy-induced peripheral neuropathy and summarizes the evidence for diagnosis, pharmacologic and nonpharmacologic approaches to the management of this commonly unrecognized condition. In conclusion, the information avaliable in this moment establish the mechanisms of the disease and exposes the importance of the development of statistically stronger clinical trials that complement current data available in this moment. (MÉD.UIS. 2010;23(1):100-19) Key words: Peripheral neuropathy. Neoplasm. Peripheral nervous system diseases/chemicall induced. Chemotherapy. Taxane. Vincristine. Cisplatin. Antineoplastic agents. Adverse effects

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Evaluación del cumplimiento por parte del personal médico de las indicaciones de transfusión de glóbulos rojos en la población adulta en el Hospital Universitario del Caribe en el período comprendido entre septiembre de 2011 a agosto de 2012

Tesis (Especialista en Medicina interna). -- Universidad de Cartagena, Facultad de Medicina. Departamento Medico, 2013Las principales indicaciones de transfusiones de glóbulos rojos son síndrome anémico indistintamente del nivel de hemoglobina, en pacientes críticamente enfermos incluyendo shock hemorrágico, hemorragia aguda y sepsis, con niveles de hemoglobina <7g/dL, y en casos de enfermedad cardiovascular descompensada con hemoglobina <8g/dL. En Cartagena no existen estudios que hayan analizados el cumplimiento de estas indicaciones por parte del personal médico en la población adult

Health professionals’ preferences with the use of pegfilgrastim on-body injector at oncology centers in 8 cities in Colombia

Abstract Background Febrile neutropenia associated with some chemotherapy regimens can lead to potentially fatal complications and high health care costs. Administration of pegfilgrastim using an On-Body Injector (OBI) may be more convenient for cancer patients and physicians in countries with limited access to high-complexity healthcare. This study aims to describe physician and nurse preferences regarding different options for administration of pegfilgrastim at cancer centers, the chemotherapy schemes for which pegfilgrastim is most frequently prescribed and how healthcare providers prioritize certain administration schemes according to patients’ access to healthcare services. Methods Observational, descriptive, cross-sectional study and survey, conducted between 2019 and 2020, to describe physician and nurse preferences regarding options for administration of pegfilgrastim at cancer centers, the demographics of the study population and characteristics of participating cancer centers. It included 60 healthcare professionals practicing at oncology centers from 8 cities in Colombia who were contacted and surveyed via telephone. Quantitative continuous variables were summarized using central tendency and dispersion measures. Results It was found that 35% of participants are haemato-oncologists, oncologists or hematologists, 30% are general practitioners, and 35% are other healthcare professionals (i.e., nurse, oncology nurse and head nurse). Our study shows that 48% of physicians prefer the use of OBI, particularly in the scheme of 24 h after myelosuppressive chemotherapy administrations. Regardless of patient frailty and travel time to the clinic, over 90% of healthcare providers (HCPs) prefer to prioritize preventing the patient from having to return to the clinic for pegfilgrastim administration as well as to increase healthcare staff availability through the use of OBI. Conclusions The present study is the first one in Colombia that sought the reasons behind HCPs’ choice to use OBI pegfilgrastim. Our results indicate that most professionals prefer to avoid the patient having to re-enter the care center for pegfilgrastim administration to facilitate access to healthcare for patients; patient characteristics and ease of transport are determining factors for respondents when choosing an option for drug administration. We found OBI is the preferred alternative by most HCPs and a good resource optimization strategy in the context of cancer patients’ health care in Colombia

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Environments for Healthy Living (EFHL) Griffith birth cohort study: background and methods

The health of an individual is determined by the interaction of genetic and individual factors with wider social and environmental elements. Public health approaches to improving the health of disadvantaged populations will be most effective if they optimise influences at each of these levels, particularly in the early part of the life course. In order to better ascertain the relative contribution of these multi-level determinants there is a need for robust studies, longitudinal and prospective in nature, that examine individual, familial, social and environmental exposures. This paper describes the study background and methods, as it has been implemented in an Australian birth cohort study, Environments for Healthy Living (EFHL): The Griffith Study of Population Health. EFHL is a prospective, multi-level, multi-year longitudinal birth cohort study, designed to collect information from before birth through to adulthood across a spectrum of eco-epidemiological factors, including genetic material from cord-blood samples at birth, individual and familial factors, to spatial data on the living environment. EFHL commenced the pilot phase of recruitment in 2006 and open recruitment in 2007, with a target sample size of 4000 mother/infant dyads. Detailed information on each participant is obtained at birth, 12-months, 3-years, 5-years and subsequent three to five yearly intervals. The findings of this research will provide detailed evidence on the relative contribution of multi-level determinants of health, which can be used to inform social policy and intervention strategies that will facilitate healthy behaviours and choices across sub-populations

International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

<p>Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barre syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination.</p><p>Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach.</p><p>Results: We found a relative incidence of GBS of 2.42(95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09(95% CI 1.28-3.42) using the meta-analytic approach.</p><p>Conclusions: This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines. (C) 2013 Elsevier Ltd. All rights reserved.</p>