Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin’s lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy

Evolution of differences in clinical presentation across epidemic waves among patients with COVID-like-symptoms who received care at the Mexican Social Security Institute

BackgroundTimely monitoring of SARS-CoV-2 variants is crucial to effectively managing both prevention and treatment efforts. In this paper, we aim to describe demographic and clinical patterns of individuals with COVID-19-like symptoms during the first three epidemic waves in Mexico to identify changes in those patterns that may reflect differences determined by virus variants.MethodsWe conducted a descriptive analysis of a large database containing records for all individuals who sought care at the Mexican Social Security Institute (IMSS) due to COVID-19-like symptoms from March 2020 to October 2021 (4.48 million records). We described the clinical and demographic profile of individuals tested (3.38 million, 32% with PCR and 68% with rapid test) by test result (positives and negatives) and untested, and among those tested, and the changes in those profiles across the first three epidemic waves.ResultsIndividuals with COVID-19-like symptoms were older in the first wave and younger in the third one (the mean age for those positive was 46.6 in the first wave and 36.1 in the third wave; for negatives and not-tested, the mean age was 41 and 38.5 in the first wave and 34.3 and 33.5 in the third wave). As the pandemic progressed, an increasing number of individuals sought care for suspected COVID-19. The positivity rate decreased over time but remained well over the recommended 5%. The pattern of presenting symptoms changed over time, with some of those symptoms decreasing over time (dyspnea 40.6 to 14.0%, cough 80.4 to 76.2%, fever 77.5 to 65.2%, headache 80.3 to 78.5%), and some increasing (odynophagia 48.7 to 58.5%, rhinorrhea 28.6 to 47.5%, anosmia 11.8 to 23.2%, dysgeusia 11.2 to 23.2%).ConclusionDuring epidemic surges, the general consensus was that any individual presenting with respiratory symptoms was a suspected COVID-19 case. However, symptoms and signs are dynamic, with clinical patterns changing not only with the evolution of the virus but also with demographic changes in the affected population. A better understanding of these changing patterns is needed to improve preparedness for future surges and pandemics

Gobernanza y gestión del agua en el Occidente de México: la metrópoli de Guadalajara

La disponibilidad de agua como tal no es el problema más importante en la gestión del agua. La incertidumbre se sitúa en la capacidad para implementar sistemas de control, distribución y acceso al agua de una forma equitativa. Garantizar el acceso de agua potable a toda la población no es un problema financiero sino político, un asunto de prioridad .Ahora disponemos de un vasto conocimiento y herramientas aplicables en el campo de la hidrología, biotecnología e ingeniería del agua, pero nuestro entendimiento sobre procesos socioeconómicos, culturales y políticos involucrados en la gestión del agua, sigue siendo limitado. En este libro, desde diferentes ángulos, se analizan formas de gestión del agua, escenarios de gobernanza, conflictos sociales y soluciones de carácter sociopolítico y técnico encaminadas a un manejo más sustentable del agua con posibilidades de ser apropiado socialmente. La obra tiene un fuerte componente con tintes de ecología política alrededor de los conflictos por el agua en la metrópoli de Guadalajara y la cuenca Lerma–Chapala–Santiago, sobre todo en aquellos casos donde coinciden situaciones de deterioro ambiental y formas inadecuadas de desarrollo urbano. En las alternativas que se analizan y proponen, se descubre una rica diversidad que encabezan organizaciones sociales, ciudadanos, actores sociopolíticos, universidades e instituciones con diferentes niveles de impacto, vinculación y trayectorias. Se distinguen escalas y formas de gobernanza del agua a nivel de cuenca, zona metropolitana de Guadalajara, municipios y sistemas hidrográficos (microcuencas y sistemas de abastecimiento), además de revisar estilos de desarrollo urbano asociados al manejo del agua con una perspectiva de análisis y de propuesta.ITESO, A.C

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

Abstract Background In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. Methods The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. Results The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95) and women (OR 0.78; 95%CI 0.64–0.94) who reported an amount of ≥30 minutes/day of leisure-time activity, and among women who reported an amount of ≥3 hours/day of workplace activity (OR 0.75; 95%CI 0.59–0.96). Conclusion Our results indicate that both leisure-time and workplace activity at different intensity levels, including low-intensity significantly reduce the risk of MS. This finding highlights the need for more recommendations regarding the specific amount and intensity of leisure-time and workplace activity needed to prevent MS