Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients.

Currently, tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb) that primarily affects the lungs. The severity of active pulmonary TB (APTB) is an important determinant of transmission, morbidity, mortality, disease experience, and treatment outcomes. Several publications have shown a high prevalence of disabling complications in individuals who have had severe APTB. Furthermore, certain strains of Mtb were associated with more severe disease outcomes. The use of biomarkers to predict severe APTB patients who are candidates for host-directed therapies, due to the high risk of developing post-tuberculous lung disease (PTLD), has not yet been implemented in the management of TB patients. We followed 108 individuals with APTB for 6 months using clinical tools, flow cytometry, and whole-genome sequencing (WGS). The median age of the study population was 26.5 years, and the frequency of women was 53.7%. In this study, we aimed to identify biomarkers that could help us to recognize individuals with APTB and improve our understanding of the immunopathology in these individuals. In this study, we conducted a follow-up on the treatment progress of 121 cases of APTB. The follow-up process commenced at the time of diagnosis (T0), continued with a control visit at 2 months (T2), and culminated in an exit appointment at 6 months following the completion of medical treatment (T6). People classified with severe APTB showed significantly higher levels of IL-6 (14.7 pg/mL; p < 0.05) compared to those with mild APTB (7.7 pg/mL) at T0. The AUCs for the ROC curves and the Matthews correlation coefficient values (MCC) demonstrate correlations ranging from moderate to very strong. We conducted WGS on 88 clinical isolates of Mtb, and our analysis revealed a total of 325 genes with insertions and deletions (Indels) within their coding regions when compared to the Mtb H37Rv reference genome. The pattern of association was found between serum levels of CHIT1 and the presence of Indels in Mtb isolates from patients with severe APTB. A key finding in our study was the high levels of CHIT1 in severe APTB patients. We identified a biomarker profile (IL-6, IFN-γ, IL-33, and CHIT1) that allows us to identify individuals with severe APTB, as well as the identification of a panel of polymorphisms (125) in clinical isolates of Mtb from individuals with severe APTB. Integrating these findings into a predictive model of severity would show promise for the management of APTB patients in the future, to guide host-directed therapy and reduce the prevalence of PTLD.

Large genomic deletions delineate Mycobacterium tuberculosis L4 sublineages in South American countries.

Mycobacterium tuberculosis (Mtb) is still one of the primary pathogens of humans causing tuberculosis (TB) disease. Mtb embraces nine well-defined phylogenetic lineages with biological and geographical disparities. The lineage L4 is the most globally widespread of all lineages and was introduced to America with European colonization. Taking advantage of many genome projects available in public repositories, we undertake an evolutionary and comparative genomic analysis of 522 L4 Latin American Mtb genomes. Initially, we performed careful quality control of public read datasets and applied several thresholds to filter out low-quality data. Using a genome de novo assembly strategy and phylogenomic methods, we spotted novel south American clades that have not been revealed yet. Additionally, we describe genomic deletion profiles of these strains from an evolutionary perspective and report Mycobacterium tuberculosis L4 sublineages signature-like gene deletions, some of the novel. One is a specific deletion of 6.5 kbp that is only present in sublineage 4.1.2.1. This deletion affects a complex group of 10 genes with putative products annotated, among others, as a lipoprotein, transmembrane protein, and toxin/antitoxin system proteins. The second novel deletion spans for 4.9 kbp and specific of a particular clade of the 4.8 sublineage and affects 7 genes. The last novel deletion affects 4 genes, extends for 4.8 kbp., and is specific to some strains within the 4.1.2.1 sublineage that are present in Colombia, Peru and Brasil.

¿Cómo ha afectado el COVID-19 a traumatólogos y residentes de traumatología en Chile? / How has covid-19 affected orthopedic surgeons and residents in chile?

INTRODUCCIÓN Desde marzo del 2020, Chile se ha visto afectado por la pandemia por coronavirus 2019 (coronavirus disease 2019, COVID-19, en inglés), que ha provocado alteraciones en todo el mundo, causando un gran impacto en los servicios de salud y el personal sanitario. OBJETIVO Describir características demográficas y laborales relacionadas al contagio de COVID-19 en traumatólogos y residentes de traumatología en Chile. MÉTODOS Realizamos una encuesta on-line, solicitando información demográfica, datos laborales, exposición y contagio de COVID-19, sintomatología y medidas de protección. RESULTADOS En total, 567 médicos contestaron. De ellos, 37 (6,4%) tuvieron COVID-19, sin diferencia significativa respecto a género. Se observó mayor contagio entre residentes, 9 de 73 (12,3%), que entre traumatólogos, 28 de 494 (5,7%), así como mayor contagio entre quienes trabajaron más de 60 horas (p <0,05). De los contagiados, 31 (83,8%) eran de la Región Metropolitana (RM), cuyo contagio es significativamente mayor que en el resto de las regiones (p < 0,05). Sólo 8 (21,6%) de los contagiados presentaban antecedentes médicos. Requirieron hospitalización 3 (5,4%), 1 de los cuales en Unidad de Cuidados Intensivos (UCI), y el resto fue manejado en forma domiciliaria. El sitio de contagio más frecuente fue el trabajo, siendo las áreas comunes las más sospechadas, seguidas de la atención ambulatoria y las áreas de hospitalización traumatológica. Un 40.5% (15) reportó haber contagiado a alguien más. Hubo además un impacto en los ingresos de los traumatólogos: un 14,8% (84) refirió una disminución menor al 20%, y un 45%, disminución mayor al 50%. Esta fue mayor en los traumatólogos que en los residentes, y en aquellos de la RM que en otras regiones (p < 0,05). CONCLUSIÓN Aunque la actividad traumatológica se ha visto disminuida por la pandemia, los traumatólogos se han visto expuestos al riesgo de contagio por COVID-19. El trabajo parece ser el lugar de mayor riesgo, sobre todo las áreas comunes.

BACKGROUND Since March 2020, Chile has been affected by the coronavirus disease 2019 (COVID-19) pandemic, which has caused disruptions throughout the world, greatly impacting health services and healthcare workers. OBJETIVE To describe the demographic characteristics related to the COVID-19 pandemic in orthopedic surgeons and orthopedic surgery residents in Chile. METHODS We conducted an on-line survey requesting data on demographics, work, exposure to and infection by COVID-19, symptoms, and protection practices. RESULTS A total of 567 surgeons answered the survey; 37 (6.4%) had had COVID-19, without gender differences. There was a higher rate of infection among residents, 9 from 73 (12.3%), than among surgeons, 28 from 494 (5.7%), as well as higher rates of infection among those working more than 60 hours (p < 0.05). Among those infected, 31 (83.8%) were from the Metropolitan Region (MR), where the rate of infection was significantly higher compared with other regions (p < 0.05). Only 8 (21.6%) of those infected had medical history. Hospitalization was required by 3 (5.4%), 1 of them in the Intensive care Unit (ICU), and the remaining were handled at home. The most frequent location of infection was the workplace, with the common areas being the main suspected sites, followed by outpatient clinics and orthopedic surgery wards. In total, 40.5% (15) of the sample reported having infected other individuals. There was also an impact in the surgeon's income: 14.8% (84) reported a decrease lower than 20%, and 45% (256), a decrease higher than 50%. This decrease was higher among surgeons than among residents, and higher among those from the MR compared to other regions (p < 0.05). CONCLUSION Even though orthopedic surgery practice has been reduced by the pandemic, orthopedic surgeons have been exposed to the risk of infection by COVID-19. The workplace seems to be the site that poses the greatest risk, especially the common areas.