Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Epirubicin, cisplatin plus ifosfamide versus standard chemotherapeutic regimens for advanced/unresectable primary thoracic sarcomas.

PURPOSE: Thoracic sarcomas are rare malignancies, with limited data for unresectable/advanced scenarios. Our goal is to provide insights of a three-drug chemotherapy regimen improving patient survival compared to standard regimens. METHODS: Retrospective cohort analysis of patients diagnosed with unresectable/advanced primary thoracic sarcoma divided between primary pulmonary sarcomas (PPS) and chest wall sarcomas (CWS) comparing chemotherapeutical regimens efficacy. Not true soft tissue sarcomas (STS) for PPS were excluded from the analysis. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier with hazard ratio (HR) obtained via Mantel-Haenszel or log rank. RESULTS: 157 total cases were included, from which 50 cases were PPS and 107 cases CWS. For PPS, 4 cases were excluded from the analysis as they were not true STS. The most common histology was undifferentiated sarcomas, 63% of cases were treated with E/C/I and 37% with another regimen. The E/C/I regimen demonstrated a benefit for both OS (p = 0.020) and PFS (p = 0.010) when compared to any other regimen as well as when compared to non-platinum regimens (p = 0.016 and p = 0.001). Regarding CWS, the most common histology was synovial and undifferentiated sarcomas, 55.1% were treated with E/C/I and 44.9% treated with another regimen. The E/C/I regimen did not demonstrate a benefit for OS or PFS compared to any other regimen, neither when compared to other non-platinum regimens. However, a benefit was observed in favor of E/C/I when compared to other platinum regimens in both OS (p = 0.049) and PFS (0.015). Both analyses for PPS and CWS demonstrated a benefit in favor of cisplatin therapies compared to carboplatin in both OS and PFS. CONCLUSION: This study demonstrates that platinum therapy alone does not work, and that cisplatin must be the agent of choice and it's used in combination could increase treatment response. The E/C/I regimen demonstrated a in PPS but not for CWS, this is due do their rarity of PPS and that no standard treatment is established yet. The regimen proposed here could represent a possible new standard of treatment for PPS as long as it is validated in a prospective study.

Knowledge and attitudes towards organ donation in a sample of physicians from two hospitals in Mexico.

INTRODUCTION: For many patients, organ transplantation is the only life-saving treatment. There is a severe shortage of organs for transplantation, and Mexico has one of the lowest organ donation rates. Health professionals are the link between society and the health system, and can promote and increase organ donation. OBJECTIVE: To explore general knowledge and attitudes of Mexican physicians with regard to cadaveric organ donation. METHODS: Cross-sectional, observational study. Two questionnaires were applied to 219 physicians either from an institution where transplants are carried out or from a hospital where the procedure is not performed. RESULTS: Most participants had not received any training on organ donation. The main deficits in their knowledge were related to the criteria for being a donor and to the position of the Church on organ donation. Knowledge predicted attitudes towards organ donation: it was negatively associated with unfavorable and mistrust attitudes, whereas it was positively associated with favorable attitudes and willingness to be a donor. CONCLUSION: It is necessary to implement programs aimed at physicians in order to provide them with tools that help promote organ donation culture.

INTRODUCCIÓN: Para numerosos pacientes, el trasplante de órganos es el único tratamiento para sobrevivir. Hay una grave escasez de órganos para trasplantes y México tiene una de las tasas más bajas de donación de órganos. Los profesionales de la salud son el vínculo entre la sociedad y el sistema de salud, y pueden promover e incrementar la donación de órganos. OBJETIVO: Explorar los conocimientos generales y las actitudes de médicos mexicanos respecto a la donación de órganos provenientes de cadáveres. MÉTODOS: Estudio observacional transversal. Se aplicaron dos cuestionarios a 219 médicos de una institución donde se realizan trasplantes y de un hospital en donde no se llevan a cabo. RESULTADOS: La mayoría de los participantes no había recibido entrenamiento sobre donación de órganos. Las principales deficiencias en sus conocimientos estuvieron relacionadas con los criterios para ser donador y la postura de la iglesia sobre la donación de órganos. El conocimiento predijo las actitudes hacia la donación de órganos; este se asoció negativamente a actitudes desfavorables y de desconfianza, mientras que se asoció positivamente a actitudes favorables y la disposición a ser donador. CONCLUSIÓN: Es necesario implementar programas dirigidos a los médicos para dotarlos de herramientas que ayuden a fomentar la cultura de donación de órganos.

Survival prognostic factors in unresectable/advanced primary thoracic sarcomas.

Background: Primary thoracic sarcomas (PTS) including primary pulmonary and chest wall sarcomas (CWS), are aggressive lung malignancies with limited information specially in an advanced/unresectable setting. Unfortunately, prognostic factors for these malignancies are not well identified. Methods: Retrospective cohort analysis of patients diagnosed with unresectable/advanced soft tissue PTS from a third level reference institute. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier method. Results: A total of 157 patients were identified, 55.4% female, mean age 51.8 years (range, 18-90 years), 19.1% tobacco exposure and 10.8% asbestos exposure. The most common performance status was Eastern Cooperative Oncology Group (ECOG) 1 (38.9%), most common clinical presentation cough (58.4%) and thoracic pain (55.4%). Undifferentiated sarcoma (37.6%) followed by synovial sarcoma (34.4%) were the most common histologies. Most patients received five chemotherapeutic cycles (37.6%), 57.3% of patients obtained a partial response and 61.1% an overall response rate (ORR). Median PFS was 9 months [95% confidence interval (CI): 8.717-9.283 months]. The multivariable analysis identified ECOG ≥2, a poorer response to chemotherapy (less number of chemotherapy cycles) and an increase Response Evaluation Criteria in Solid Tumors (RECIST) to be associated with a shorter progression-free period. Median OS was 11 months (95% CI: 10.402-11.958 months) with an ECOG ≥2 and a poorer response to chemotherapy (less number of chemotherapy cycles) associated with a shorter survival. Conclusions: Age, gender, comorbidities, tobacco and asbestos exposure, clinical presentation and histopathological diagnosis are not useful prognostic factors in unresectable/advanced PTS, however, an adequate initial ECOG, RECIST and a better response to chemotherapy should be used as prognostic factors in the management of these tumors.

Conocimientos y actitudes hacia la donación de órganos en una muestra de médicos de dos hospitales en México / Knowledge and attitudes towards organ donation in a sample of physicians from two hospitals in Mexico

Resumen Introducción: Para numerosos pacientes, el trasplante de órganos es el único tratamiento para sobrevivir. Hay una grave escasez de órganos para trasplantes y México tiene una de las tasas más bajas de donación de órganos. Los profesionales de la salud son el vínculo entre la sociedad y el sistema de salud, y pueden promover e incrementar la donación de órganos. Objetivo: Explorar los conocimientos generales y las actitudes de médicos mexicanos respecto a la donación de órganos provenientes de cadáveres. Métodos: Estudio observacional transversal. Se aplicaron dos cuestionarios a 219 médicos de una institución donde se realizan trasplantes y de un hospital en donde no se llevan a cabo. Resultados: La mayoría de los participantes no había recibido entrenamiento sobre donación de órganos. Las principales deficiencias en sus conocimientos estuvieron relacionadas con los criterios para ser donador y la postura de la iglesia sobre la donación de órganos. El conocimiento predijo las actitudes hacia la donación de órganos; este se asoció negativamente a actitudes desfavorables y de desconfianza, mientras que se asoció positivamente a actitudes favorables y la disposición a ser donador. Conclusión: Es necesario implementar programas dirigidos a los médicos para dotarlos de herramientas que ayuden a fomentar la cultura de donación de órganos.

Abstract Introduction: For many patients, organ transplantation is the only life-saving treatment. There is a severe shortage of organs for transplantation, and Mexico has one of the lowest organ donation rates. Health professionals are the link between society and the health system, and can promote and increase organ donation. Objective: To explore general knowledge and attitudes of Mexican physicians with regard to cadaveric organ donation. Methods: Cross-sectional, observational study. Two questionnaires were applied to 219 physicians either from an institution where transplants are carried out or from a hospital where the procedure is not performed. Results: Most participants had not received any training on organ donation. The main deficits in their knowledge were related to the criteria for being a donor and to the position of the Church on organ donation. Knowledge predicted attitudes towards organ donation: it was negatively associated with unfavorable and mistrust attitudes, whereas it was positively associated with favorable attitudes and willingness to be a donor. Conclusion: It is necessary to implement programs aimed at physicians in order to provide them with tools that help promote organ donation culture.

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico.

There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

Expression of Claudin-4 in Lung Ischemia-Reperfusion Injury in Experimental Lung Transplantation.

OBJECTIVE: To assess the presence of CLDN4 in bronchoalveolar lavage fluid (BALF) and pulmonary tissue as an early indicator of LIRI and its relationship with changes in pulmonary physiology, edema formation and histology in an experimental porcine model of LTx with CIT of 50 min or 6 h. METHODS: In 12 pigs, LIRI was produced by: group I (n = 6) LTx with 50 min of CIT (LTx-50 min-CIT); and group II (n = 6) LTx with 6 h of CIT (LTx-6h-CIT). The lung function, edema formation, macroscopic and microscopic changes were assessed. CLDN4 expression in BALF and pulmonary tissue were determined. RESULTS: Both groups presented similar clinical, edema, and histological damage, as well as similar expression of CLDN4 in BALF and tissue (p > 0.05, RM-ANOVA). CONCLUSION: CLDN4 expressed in BALF and the pulmonary tissue during the first 5 h within 72 h of the PGD window are not associated by the deterioration of lung function, edema and lung histological injury, in LTx with CIT 50 min or 6 h, CLDN4 does not seem to be a valuable indicator of LIRI.

A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma.

BACKGROUND: Immunotherapy has demonstrated an improved overall survival (OS) and progression-free survival (PFS) as second-line treatment and subsequent lines compared with chemotherapy. MATERIALS & METHODS: This was a retrospective review among eight medical centers comprising 100 patients with a confirmed diagnosis of non-small-cell lung carcinoma, in their second-line treatment or beyond with immune checkpoints inhibitors treatment. The current study aimed to analyze effectiveness of immunotherapy in second-line treatment or further in the Mexican population, using PFS rate, OS rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. RESULTS: In total, 100 patients met the criteria for enrollment in the current study. From the total study population, 49 patients (49.0%) were male and 51 (51.0%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the study. A total of 61 patients (61.0%) had partial response; 11 (11.0%) stable disease; 2 (2.0%), complete response, 4 (4.0%), progression; and 22 (22.0%) were nonevaluable. We found a median PFS of 4 months (95% CI: 3.2-4.7 months) and an OS of 9 months (95% CI: 7.2-10.7 months). CONCLUSION: The response to immunotherapy is similar, with an improvement in OS and PFS, independent of which drug is used. Patients using nivolumab had a better survival, although that was not statistically significant.

Spontaneous pneumomediastinum in COVID-19 patients. Case series.

Spontaneous pneumomediastinum is defined as the presence of free air within the mediastinum without an apparent cause such as chest trauma. It is a benign, self-limiting condition that is conservatively treated. Clinical diagnosis is based on two symptoms: chest pain and dyspnea; and on a particular sign: subcutaneous emphysema. It has been reported in patients with influenza A (H1N1) and severe acute respiratory syndrome; however, it has been rarely observed in COVID-19 patients. In this work, we describe six male patients with COVID-19, aged between 27 and 82 years, who presented with spontaneous pneumomediastinum and subcutaneous emphysema; both conditions were completely resorbed with conservative management.

El neumomediastino espontáneo es la presencia de aire libre en el mediastino sin el antecedente de alguna causa como trauma de tórax. Es una condición benigna autolimitada que se trata en forma conservadora. El diagnóstico clínico se basa en dos síntomas: dolor torácico y disnea; y en un signo en particular: enfisema subcutáneo. Ha sido reportado en pacientes con influenza A (H1N1) y síndrome respiratorio agudo grave; sin embargo, ha sido raramente observado en pacientes con COVID-19. En este trabajo describimos seis pacientes del sexo masculino con COVID-19, con edades entre 27 y 82 años, que presentaron neumomediastino espontáneo y enfisema subcutáneo; ambos se reabsorbieron totalmente con manejo conservador.

Clinical and Immunological Factors That Distinguish COVID-19 From Pandemic Influenza A(H1N1).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.

Low Incidence and Mortality by SARS-CoV-2 Infection Among Healthcare Workers in a Health National Center in Mexico: Successful Establishment of an Occupational Medicine Program.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthcare workers (HCWs) constitute a population which is significantly affected by SARS-CoV-2 infection worldwide. In Mexico, the Instituto Nacional de Enfermedades Respiratorias (INER) is the principal national reference of respiratory diseases. Aim: To evaluate the efficiency of the INER-POL-TRAB-COVID19 program to mitigate the SARS-CoV-2 infection risk among the INER-healthcare workers (INER-HCW). Methods: Currently, the INER has 250 beds and 200 respiratory ventilators to support COVID-19 patients in critical condition. On March 1st, 2020, the INER-POL-TRAB-COVID19 program was launched to mitigate the SARS-CoV-2 infection risk among the INER-HCW. Findings: From March 1st to October 1st, 2020, 71.5% of INER-HCWs were tested for SARS-CoV-2 infection, and 77% of them were frontline workers. Among the tested INER-HCWs, 10.4% were positive for SARS-CoV-2 infection. Nonetheless, nosocomial infection represented only 3.8% of the cases and the mortality was null. Fifty-three of INER-HCWs positive to SARS-CoV-2 had a negative test 42-56 days post-diagnosis and were returned to service. Finally, although a change in the PPE implemented on May 11th, 2020, the incidence of SARS-CoV-2 infection was not affected. Conclusion: INER has a lower incidence of HCWs infected with SARS-CoV-2 as compared to the mean of the national report. The implementation of the INER-POL-TRAB-COVID19 program is efficient to decrease the risk of infection among the HCWs. Our findings suggest that the implementation of a similar program at a national level can be helpful to provide a safe environment to HCWs and to prevent the collapse of health institutions.

Neumomediastino espontáneo en pacientes COVID-19. Serie de casos / Spontaneous pneumomediastinum in COVID-19 patients. Case series

Resumen El neumomediastino espontáneo es la presencia de aire libre en el mediastino sin el antecedente de alguna causa como trauma de tórax. Es una condición benigna autolimitada que se trata en forma conservadora. El diagnóstico clínico se basa en dos síntomas: dolor torácico y disnea; y en un signo en particular: enfisema subcutáneo. Ha sido reportado en pacientes con influenza A (H1N1) y síndrome respiratorio agudo grave; sin embargo, ha sido raramente observado en pacientes con COVID-19. En este trabajo describimos seis pacientes del sexo masculino con COVID-19, con edades entre 27 y 82 años, que presentaron neumomediastino espontáneo y enfisema subcutáneo; ambos se reabsorbieron totalmente con manejo conservador.

Abstract Spontaneous pneumomediastinum is defined as the presence of free air within the mediastinum without an apparent cause such as chest trauma. It is a benign, self-limiting condition that is conservatively treated. Clinical diagnosis is based on two symptoms: chest pain and dyspnea; and on a particular sign: subcutaneous emphysema. It has been reported in patients with influenza A (H1N1) and severe acute respiratory syndrome; however, it has been rarely observed in COVID-19 patients. In this work, we describe six male patients with COVID-19, aged between 27 and 82 years, who presented with spontaneous pneumomediastinum and subcutaneous emphysema; both conditions were completely resorbed with conservative management.

Retos de los Comités de Ética en Investigación en Animales. Experiencia de México / Challenges for Ethic Committees in Animal Research. Mexican experience

La aprobación de proyectos de investigación biomédica y prácticas en animales depende de los comités de ética para el cuidado y uso de animales, quienes deben evaluar los aspectos éticos y metodológicos de los proyectos que se realizan, y así garantizar el buen manejo y uso de los animales, desde su obtención hasta su muerte, con base en los conocimientos científicos actuales, el análisis riesgo-beneficio, la implementación de las Tres Erress que se refieren al reemplazo, reducción y refinamiento y en los criterios de la ciencia del bienestar animal. La atención a cada una de las etapas del diseño y evaluación de proyectos es a menudo subestimada tanto por los científicos como por los integrantes de comités, quienes deben asumir la responsabilidad de disminuir el dolor y el malestar de los animales a lo largo de la investigación. Por otro lado, se exponen algunas de las limitaciones que enfrentan dichos comités para realizar su trabajo y asegurar que los animales sean utilizados siempre y cuando se justifique (AU)

The approval of the use of animals in biomedical research projects depends on the ethics committees for the care and use of laboratory animals, who must evaluate ethical and methodological aspects of the projects that are carried out and are intended to ensure the proper management and use of animals, from obtaining to death based on current scientific knowledge, risk-benefit analysis, the implementation of the three R's (3R's) applied to replacement, reduction and refinement, and the criteria of animal welfare science. Attention to each stage of project design and evaluation is often underestimated by both scientists and committee members, who must take responsibility for reducing pain and discomfort to animals throughout the investigation. On the other hand, some of the limitations that these committees face in carrying out their work and ensuring that animals are used are exposed as long as it is justified (AU)

L'aprovació de projectes de recerca biomèdica i pràctiques en animals depèn dels comitès d'ètica per a la cura i ús d'animals, els qui han d'avaluar els aspectes ètics i metodològics dels projectes que es realitzen, i així garantir el bon maneig i ús dels animals, des de la seva obtenció fins a la seva mort, amb base en els coneixements científics actuals, l'anàlisi risc-beneficio, la implementació de les Tres Erress que es refereixen al reemplaçament, reducció i refinament i en els criteris de la ciència del benestar animal. L'atenció a cadascuna de les etapes del disseny i avaluació de projectes és sovint subestimada tant pels científics com pels integrants de comitès, els qui han d'assumir la responsabilitat de disminuir el dolor i el malestar dels animals al llarg de la recerca. D'altra banda, s'exposen algunes de les limitacions que enfronten aquests comitès per a fer el seu treball i assegurar que els animals siguin utilitzats sempre que es justifiqui (AU)

The low-harm score for predicting mortality in patients diagnosed with COVID-19: A multicentric validation study.

Objective: We sought to determine the accuracy of the LOW-HARM score (Lymphopenia, Oxygen saturation, White blood cells, Hypertension, Age, Renal injury, and Myocardial injury) for predicting death from coronavirus disease 2019) COVID-19. Methods: We derived the score as a concatenated Fagan's nomogram for Bayes theorem using data from published cohorts of patients with COVID-19. We validated the score on 400 consecutive COVID-19 hospital admissions (200 deaths and 200 survivors) from 12 hospitals in Mexico. We determined the sensitivity, specificity, and predictive values of LOW-HARM for predicting hospital death. Results: LOW-HARM scores and their distributions were significantly lower in patients who were discharged compared to those who died during their hospitalization 5 (SD: 14) versus 70 (SD: 28). The overall area under the curve for the LOW-HARM score was 0.96, (95% confidence interval: 0.94-0.98). A cutoff > 65 points had a specificity of 97.5% and a positive predictive value of 96%. Conclusions: The LOW-HARM score measured at hospital admission is highly specific and clinically useful for predicting mortality in patients with COVID-19.

Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR-mutated lung adenocarcinoma.

BACKGROUND: A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR-mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. METHODS: This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR-mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. RESULTS: EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response (P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression-free survival (P = 0.025 and P = 0.030). CONCLUSIONS: The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.