Efectos adversos inmunomediados gastrointestinales y hepáticos inducidos por los inhibidores del punto de control inmunitario: estudio descriptivo observacional

Introducción Los inhibidores del punto de control inmunitario (immune checkpoint inhibitors [ICI]) son fármacos eficaces en el tratamiento de diversas neoplasias. Sin embargo, se han relacionado con eventos adversos inmunomediados (EAI) gastrointestinales y hepáticos que pueden desencadenar su interrupción temporal o definitiva. Objetivo Evaluar, en condiciones de práctica real, la eficacia y la toxicidad gastrointestinal y hepática de los ICI en tratamientos oncológicos. Material y métodos Estudio retrospectivo con inclusión de pacientes con diagnóstico de neoplasia avanzada que habían recibido al menos una dosis de ICI entre mayo de 2015 y septiembre de 2018. Resultados Se incluyeron 132 pacientes con neoplasia de pulmón no microcítico (65, 15%, n = 86), melanoma (22, 7%, n = 30), carcinoma renal (9, 09%, n = 12) y otros tumores (3%, n = 4). Los fármacos empleados fueron nivolumab (n = 82), pembrolizumab (n = 28), atezolizumab (n = 13), durvalumab (n = 2), ipilimumab (n = 1) y la combinación anti-CTLA-4/PD-1 (n = 6). El 38, 6% (n = 51) desarrollaron EAI, de tipo gastrointestinal en el 12, 9% (n = 17). De ellos, el 47% (n = 8) requirieron esteroides, y un paciente precisó cirugía por perforación intestinal. En el 3, 03% (n = 4) se objetivaron EAI hepáticos grado I: el 50% (n = 2) requirieron corticoterapia y en un paciente fue preciso interrumpir el tratamiento. Entre los pacientes con tratamiento combinado, el 66, 6% (n = 4) presentaron EAI gastrointestinales. La incidencia de EAI no se relacionó con la edad, ni con el sexo, ni con la respuesta al fármaco empleado. Conclusiones Los EAI gastrointestinales figuran entre los más frecuentemente observados en pacientes en tratamiento con ICI. El manejo multidisciplinar y un mayor conocimiento de dichos eventos podrían ayudarnos a reducir su morbilidad, así como las interrupciones del tratamiento. Introduction Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. Aim The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. Material and methods Patients with advanced cancer who received at least 1 ICI dose between May 2015 and September 2018 were retrospectively assessed. Results 132 patients with non-small cell lung cancer (65.15%, n = 86); melanoma (22.7%, n = 30); renal carcinoma (9.09%, n = 12); and other tumours (3%, n = 4) were included. The treatments administered were nivolumab (n = 82), pembrolizumab (n = 28), atezolizumab (n = 13), durvalumab (n = 2), ipilimumab (n = 1) and the antiCTLA-4/PD-1 combination (n = 6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1 patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. Conclusions GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation

Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges

Epilepsy is the second most prevalent neurological disease worldwide. It is mainly characterized by an electrical abnormal activity in different brain regions. The massive entrance of Ca2+ into neurons is the main neurotoxic process that lead to cell death and finally to neurodegeneration. Although there are a huge number of antiseizure medications, there are many patients who do not respond to the treatments and present refractory epilepsy. In this context, nanomedicine constitutes a promising alternative to enhance the central nervous system bioavailability of antiseizure medications. The encapsulation of different chemical compounds at once in a variety of controlled drug delivery systems gives rise to an enhanced drug effectiveness mainly due to their targeting and penetration into the deepest brain region and the protection of the drug chemical structure. Thus, in this review we will explore the recent advances in the development of drugs associated with polymeric and lipid-based nanocarriers as novel tools for the management of epilepsy disorders. Keywords: epilepsy; lipid nanoparticles; nanomedicine; nanotechnology; neurodegenerative diseases; polymeric nanoparticles

Procesos educativos sobre enfermedad de Chagas con escolares de nivel básico de escuelas públicas de México

Se presentan los cambios en conocimientos y prácticas sobre el vector y la enfermedad de Chagas con escolares de México posterior a una intervención educativa. La identificación del vector aumentó posterior a las sesiones educativas (pre=36,15% vs post=79,30%). Aumentaron los conocimientos acerca de la enfermedad de Chagas (30,90% vs 64,72%, valor de p< 0,0001) y de las acciones preventivas para evitar que el vector habite dentro de sus entornos (14,29% vs 61,81%, valor de p< 0,0001). Los escolares pueden jugar un papel fundamental en la prevención de esta problemática

At the beginnings of the funerary Megalithism in Iberia at Campo de Hockey necropolis

The excavations undertaken at the Campo de Hockey site in 2008 led to the identification of a major Neolithic necropolis in the former Island of San Fernando (Bay of Cádiz). This work presents the results of the latest studies, which indicate that the site stands as one of the oldest megalithic necropolises in the Iberian Peninsula. The main aim of this work is to present with precision the chronology of this necropolis through a Bayesian statistical model that confirms that the necropolis was in use from c. 4300 to 3800 cal BC. The presence of prestige grave goods in the earliest and most monumental graves suggest that the Megalithism phenomenon emerged in relation to maritime routes linked to the distribution of exotic products. We also aim to examine funerary practices in these early megalithic communities, and especially their way of life and the social reproduction system. As such, in addition to the chronological information and the Bayesian statistics, we provide the results of a comprehensive interdisciplinary study, including anthropological, archaeometric and genetic data.Archaeological background: the Campo de Hockey settlement Methods - Tomb typology - Radiocarbon dates and Bayesian analysis. - Bioarchaeology. - DNA - Grave goods Results - Tomb typology - Radiocarbon dating: Bayesian analysis - Bioarchaeology. - DNA - Grave goods. Discussion and conclusions

Changes in the socio-ecological system of a protected area in the yucatan peninsula: A case study on land-use, vegetation cover, and household management strategies

Protected areas (PA) are effective means for protecting biodiversity, but less is known about their effect on the social-ecological system (SES). Using a semi-experimental approach and a descriptive case study based evaluation, we analyzed the effect of a PA in the Yucatan Peninsula on land-cover and household resource management strategies in time and space (before and after the PA establishment; inside and outside its limits). To assess the changes of land-use practices in the areas surrounding the communities inside and outside the PA, and their change over time (from 2003 to 2015), we used remote sensing analysis and semi-structured interviews. Our results show that after the PA was established, the forest increased and agricultural plots decreased inside and to a lesser extent outside the PA. However, fires reduced the area of old-growth forest and increased young secondary forest, highlighting the system’s vulnerability to uncommon events. Resource management strategies were also affected: while inside the PA households tended toward specializing on tourism, outside the PA household strategies implied a diversification of productive activities. Overall, the establishment of the PA proved to be an effective tool to promote forest recovery and prevent deforestation in the regions surrounding the communities both inside and outside the PA

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet =4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. Results: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and =6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

Objectives: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. Methods: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. Results: Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). Conclusions: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement

Interventions in health organisations to reduce the impact of adverse events in second and third victims

Background Adverse events (AE) are also the cause of suffering in health professionals involved. This study was designed to identify and analyse organization-level strategies adopted in both primary care and hospitals in Spain to address the impact of serious AE on second and third victims. Methods A cross-sectional study was conducted in healthcare organizations assessing: safety culture; health organization crisis management plans for serious AE; actions planned to ensure transparency in communication with patients (and relatives) who experience an AE; support for second victims; and protective measures to safeguard the institution’s reputation (the third victim). Results A total of 406 managers and patient safety coordinators replied to the survey. Deficient provision of support for second victims was acknowledged by 71 and 61 % of the participants from hospitals and primary care respectively; these respondents reported there was no support protocol for second victims in place in their organizations. Regarding third victim initiatives, 35 % of hospital and 43 % of primary care professionals indicated no crisis management plan for serious AE existed in their organization, and in the case of primary care, there was no crisis committee in 34 % of cases. The degree of implementation of second and third victim support interventions was perceived to be greater in hospitals (mean 14.1, SD 3.5) than in primary care (mean 11.8, SD 3.1) (p?<?0.001). Conclusions Many Spanish health organizations do not have a second and third victim support or a crisis management plan in place to respond to serious AEs

The aftermath of adverse events in spanish primary care and hospital health professionals

Background Adverse events (AEs) cause harm in patients and disturbance for the professionals involved in the event (second victims). This study assessed the impact of AEs in primary care (PC) and hospitals in Spain on second victims. Methods A cross-sectional study was conducted. We carried out a survey based on a random sample of doctors and nurses from PC and hospital settings in Spain. A total of 1087 health professionals responded, 610 from PC and 477 from hospitals. Results A total of 430 health professionals (39.6%) had informed a patient of an error. Reporting to patients was carried out by those with the strongest safety culture (Odds Ratio –OR- 1.1, 95% Confidence Interval –CI- 1.0-1.2), nurses (OR 1.9, 95% CI 1.5-2.3), those under 50 years of age (OR 0.7, 95% CI 0.6-0.9) and primary care staff (OR 0.6, 95% CI 0.5-0.9). A total of 381 (62.5%, 95% CI 59-66%) and 346 (72.5%, IC95% 69-77%) primary care and hospital health professionals, respectively, reported having gone through the second-victim experience, either directly or through a colleague, in the previous 5 years. The emotional responses were: feelings of guilt (521, 58.8%), anxiety (426, 49.6%), re-living the event (360, 42.2%), tiredness (341, 39.4%), insomnia (317, 38.0%) and persistent feelings of insecurity (284, 32.8%). In doctors, the most common responses were: feelings of guilt (OR 0.7 IC95% 0.6-0.8), re-living the event (OR 0.7, IC95% o.6-0.8), and anxiety (OR 0.8, IC95% 0.6-0.9), while nurses showed greater solidarity in terms of supporting the second victim, in both PC (p?=?0.019) and hospital (p?=?0.019) settings. Conclusions Adverse events cause guilt, anxiety, and loss of confidence in health professionals. Most are involved in such events as second victims at least once in their careers. They rarely receive any training or education on coping strategies for this phenomenon

Relación entre la grasa corporal y la expresión de ira en personas que realizan ejercicio regularmente

La actividad física proporciona benecios, tanto a la población sana como enferma, pero también puede derivar en problemas psicológicos y emocionales como respuesta al estrés. Además, aquellos atletas con menor peso corporal presentan indicadores más elevados de depresión e ira. Se plantea determinar la relación de la grasa corporal sobre la expresión de ira y entender la relación entre distintos comportamientos psicológicos, en personas físicamente activas. 264 sujetos cumplimentaron el Inventario de Expresión de Ira Estado-Rasgo, versión 2, para el estudio sobre las características de la ira y sus efectos en la salud mental y física. Se tomaron medidas antropométricas (peso, talla, IMC, porcentaje de grasa corporal, masa libre de grasa). Se calcularon distintos percentiles en función del género y edad, clasicando a los participantes en tres grupos: percentil &lt;45, entre 45 y 55 y &gt;55 de grasa corporal. Se analizaron distintos comportamientos en relación al STAXI-2 y a los distintos percentiles, pero sin encontrar diferencias significativas entre la ira y los tres grupos.