Differential activation of innate and adaptive lymphocytes during latent or active infection with Mycobacterium tuberculosis.

Most individuals infected with Mycobacterium tuberculosis (Mtb) have latent tuberculosis (TB), which can be diagnosed with tests (such as the QuantiFERON-TB Gold test [QFT]) that detect the production of IFN-γ by memory T cells in response to the Mtb-specific antigens 6 kDa early secretory antigenic target EsxA (Rv3875) (ESAT-6), 10 kDa culture filtrate antigen EsxB (Rv3874) (CFP-10), and Mtb antigen of 7.7 kDa (Rv2654c) (TB7.7). However, the immunological mechanisms that determine if an individual will develop latent or active TB remain incompletely understood. Here we compared the response of innate and adaptive peripheral blood lymphocytes from healthy individuals without Mtb infection (QFT negative) and from individuals with latent (QFT positive) or active TB infection, to determine the characteristics of these cells that correlate with each condition. In active TB patients, the levels of IFN-γ that were produced in response to Mtb-specific antigens had high positive correlations with IL-1ß, TNF-α, MCP-1, IL-6, IL-12p70, and IL-23, while the proinflammatory cytokines had high positive correlations between themselves and with IL-12p70 and IL-23. These correlations were not observed in QFT-negative or QFT-positive healthy volunteers. Activation with Mtb-soluble extract (a mixture of Mtb antigens and pathogen-associated molecular patterns [PAMPs]) increased the percentage of IFN-γ-/IL-17-producing NK cells and of IL-17-producing innate lymphoid cell 3 (ILC3) in the peripheral blood of active TB patients, but not of QFT-negative or QFT-positive healthy volunteers. Thus, active TB patients have both adaptive and innate lymphocyte subsets that produce characteristic cytokine profiles in response to Mtb-specific antigens or PAMPs. These profiles are not observed in uninfected individuals or in individuals with latent TB, suggesting that they are a response to active TB infection.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Pulmonary Embolism (PE) Prevalence in Mexican-Mestizo Patients With Severe SARS-COV-2 (COVID-19) Pneumonia At A Tertiary-Level Hospital: A Review.

Since the report of the first case of COVID-19 in Wuhan, China, on December 31, 2019, several associated thrombotic complications have been reported, mainly venous thromboembolic events, and myocardial infarctions, in addition to peripheral arterial thrombosis and cerebral vascular events, which have been attributed to a hypercoagulable state. We aimed to know the prevalence and prognostic biomarkers in patients with pulmonary thromboembolism (PE) and SARS Cov-2 pneumonia. Hospitalized patients with SARS Cov-2 pneumonia who have had clinical, biomarker, and imaging data (chest angiography) of pulmonary thromboembolism were included. Descriptive statistics and prevalence rates were calculated. For the analysis between the groups, the paired Student's t and the Wilcoxon test were performed. CT angiography was performed on 26 patients at our institution, with a diagnosis of severe pneumonia secondary to SARS-CoV2. 9 of the patients (34.6%) had a venous thromboembolic disease. Type 2 DM was the most frequent comorbidity up to 55.5% of the total; it was followed by obesity and overweight in 55.5%, and in third place, by systemic arterial hypertension in 33.3% of the cases, 1 (11.1%) patient had chronic kidney disease and 1 (11.1%) patient with a history of cancer, only 1 patient met criteria and was treated with thrombolysis. 6 (66.6%) of the patients had segmental PE, 3 (33.3%) patients had subsegmental PE, and 4 (44.4%) patients presented pulmonary infarction.

Changes in lactate dehydrogenase on admission throughout the COVID-19 pandemic and possible impacts on prognostic capability.

Introduction: The enzyme lactate dehydrogenase (LDH) is a good marker of general hyperinflammation correlated with mortality for COVID-19, and is therefore used in prognosis tools. In a current COVID-19 clinical randomized trial (CRT), the blood level of LDH was selected as an inclusion criterion. However, LDH decreased during the pandemic; hence, the impact of this decrease on the prognostic value of LDH for mortality was evaluated. Methods: Data on LDH levels in 843 patients were obtained and analyzed. Relative risk, standard error and receiver operating characteristic curves were calculated for two cutoff values. Results: Relative risk lost validity and the area under the curve narrowed by trimester during the pandemic. Conclusion: The progressive decrease in LDH impacted the capacity to predict mortality in COVID-19. More studies are needed to validate this finding and its implications.

Convalescent Plasma to Treat COVID-19: A Two-Center, Randomized, Double-Blind Clinical Trial.

Background: The use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of COVID-19. This study evaluated the safety and efficacy of the use of donor CP for COVID-19. Material and methods: A double-blind, randomized controlled clinical trial was conducted from May to October 2020. Thirty-nine participants with moderate (II) and severe (III) stages of COVID-19 confirmed by RT-PCR were included. The study randomization rate was set at 3:1. CPs were chosen for application with a neutralizing antibody titer of ≥1:32. Results: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 (95.0% CI [0.07−0.45, p < 0.001]) in the group receiving CP compared with the control group; protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher (512 (32−16,384) vs. 96 (32−256), p = 0.01); the PAO2/FIO2 index showed a significant improvement in the group receiving CP (251.01 (109.4) vs. 109.2 (62.4), p < 0.001, in the control group). Conclusion: CP is safe and effective, as it decreased mortality in the CP group compared with the control group.

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease.

AIM: Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. METHODS: Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n = 166) and validated (n = 170). RESULTS: Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P < 0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4 ± 341.2 vs. 41.3 ± 41.1, aspartate aminotransferase (AST) 325.3 ± 382.4 vs. 52.8 ± 47.1, lactic dehydrogenase (LDH) 764.6 ± 401.9 vs. 461.0 ± 185.6, D-dimer (DD) 7765 ± 9109 vs. 1871 ± 4146, and age 58.6 ± 12.7 vs. 49.1 ± 12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity = 0.797 and specificity = 0.391, c - statistic = 0.74; 95%IC: 0.62-0.86, P < 0.001), to predict the risk of need admission to ICU (OR = 5.8; 95% CI: 2.2-15.4, P = 0.001), was constructed. Validation cohort: in 170 different patients, the AAD model < 2.75 (c - statistic = 0.80 (95% CI: 0.70-0.91, P < 0.001) adequately predicted the risk (OR = 8.8, 95% CI: 3.4-22.6, P < 0.001) to be admitted in the ICU (27 patients, 15.95%). CONCLUSIONS: The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.

Minimización de costos de sedación usando anestesia inhalada. Análisis en la UTI durante la pandemia por COVID-19 / Minimization of sedation costs using inhaled anesthesia. Analysis in the ICU during the COVID-19 pandemic / Minimização dos custos de sedação usando anestesia inalatória. Análise na UTI durante a pandemia de COVID-19

Resumen: Introducción: los sedantes de uso no convencional y aquéllos fuera de recomendación como los anestésicos inhalados se usaron ante la escasez de medicamentos durante la pandemia por SARS-CoV-2. Objetivos: comparar el costo y resultados obtenidos con el uso de anestésicos inhalados versus sedantes intravenosos en COVID-19. Material y métodos: estudio retrospectivo en una unidad de terapia intensiva (UTI) de un hospital público de referencia. Se hizo un cálculo de costos de sedación de los dos primeros días de estancia en la UTI. Las dosis de fármacos fueron tomadas del expediente clínico y los costos de adquisición directamente de CompraNet. Se comparan medias de costos por medicamento y por grupo. Resultados: de 151 pacientes, 81 recibieron sedación intravenosa y 70 anestesia inhalada con o sin sedantes intravenosos. No hubo diferencia en mortalidad, días de ventilación mecánica, estancia en la UTI y estancia hospitalaria entre grupos. Se observó una reducción significativa de costos derivados del menor uso de midazolam, propofol y dexmedetomidina (p < 0.0001) cuando se usó anestesia inhalada y una diferencia entre medias de costos totales de sedación de $4,108.42 M.N. por día por paciente. Conclusiones: la anestesia inhalada durante la pandemia por COVID-19 permitió una reducción de costos comparada con sedación intravenosa en los primeros dos días de estancia en la UTI.

Abstract: Introduction: non-conventional sedatives and those off-label, such as inhaled anesthetics, were used due to the shortage of medicines during the SARS-CoV-2 pandemic. Objectives: to compare the cost and results obtained with the use of inhaled anesthetics versus intravenous sedatives in COVID-19. Material and methods: retrospective study in a public reference hospital ICU. A calculation of sedation costs was made of the first two days of ICU stay. Drug doses were taken from the clinical records and acquisition costs directly from CompraNet. Mean costs per medication and per group are compared. Results: of 151 patients, 81 received intravenous sedation and 70 received inhaled anesthesia with or without intravenous sedatives. There was no difference in mortality, days of mechanical ventilation, ICU stay, and hospital stay between groups. A significant reduction in costs derived from the less use of midazolam, propofol and dexmedetomidine (p < 0.0001), and a difference between means of total sedation costs of $4,108.42 Mexican pesos per patient per day was observed with inhaled anesthesia. Conclusions: inhaled anesthesia during the COVID-19 pandemic compared to intravenous sedation allowed a cost reduction in the first two days of ICU stay.

Resumo: Introdução: sedativos de uso não convencional e não recomendados, como anestésicos inalatórios, foram utilizados devido à escassez de medicamentos durante a pandemia de SARS-CoV-2. Objetivos: comparar o custo e os resultados obtidos com o uso de anestésicos inalatórios versus sedativos intravenosos na COVID-19. Material e métodos: estudo retrospectivo em uma UTI de um hospital público de referência. Foi feito um cálculo dos custos de sedação para os dois primeiros dias de internação na UTI. As doses dos medicamentos foram retiradas do prontuário clínico e os custos de aquisição diretamente do CompraNet. Os custos médios por medicamento e por grupo são comparados. Resultados: dos 151 pacientes, 81 receberam sedação intravenosa e 70 anestesia inalatória com ou sem sedativos intravenosos. Não houve diferença na mortalidade, dias em ventilação mecânica, permanência na UTI e internação entre os grupos. Uma redução significativa nos custos derivados do menor uso de midazolam, propofol e dexmedetomidina (p < 0.0001) foi observada quando a anestesia inalatória foi usada e uma diferença entre as médias dos custos totais de sedação de $4,108.42 M.N. por dia por paciente. Conclusões: a anestesia inalatória durante a pandemia de COVID-19 permitiu redução de custos em comparação com a sedação endovenosa nos primeiros dois dias de internação na UTI.