Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial.

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration.Registration: ClinicalTrials.gov NCT04443673, 23/06/2020.

Molecular transition of SARS-CoV-2 from critical patients during the first year of the COVID-19 pandemic in Mexico City.

Background: The SARS-CoV-2 virus has caused unprecedented mortality since its emergence in late 2019. The continuous evolution of the viral genome through the concerted action of mutational forces has produced distinct variants that became dominant, challenging human immunity and vaccine development. Aim and methods: In this work, through an integrative genomic approach, we describe the molecular transition of SARS-CoV-2 by analyzing the viral whole genome sequences from 50 critical COVID-19 patients recruited during the first year of the pandemic in Mexico City. Results: Our results revealed differential levels of the evolutionary forces across the genome and specific mutational processes that have shaped the first two epidemiological waves of the pandemic in Mexico. Through phylogenetic analyses, we observed a genomic transition in the circulating SARS-CoV-2 genomes from several lineages prevalent in the first wave to a dominance of the B.1.1.519 variant (defined by T478K, P681H, and T732A mutations in the spike protein) in the second wave. Conclusion: This work contributes to a better understanding of the evolutionary dynamics and selective pressures that act at the genomic level, the prediction of more accurate variants of clinical significance, and a better comprehension of the molecular mechanisms driving the evolution of SARS-CoV-2 to improve vaccine and drug development.

Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: A cohort study.

INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Major Depressive Disorder and Pulmonary Tuberculosis Comorbidity Exacerbates Proinflammatory Immune Response-A Preliminary Study.

BACKGROUND: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. METHODS: Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. RESULTS: We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-12-producing cells was similar between MDD-TB and TB patients. Likewise, MDD-TB and TB patients showed similar serum pro-inflammatory cytokine and chemokine levels, which were significantly lower than those in MDD patients. By multiple correspondence analyses, we observed that low levels of serum IL-4, IL-10, and IL-13 were powerfully associated with TB comorbidities with MDD. CONCLUSIONS: A high frequency of IFN-γ-producing cells is associated with low levels of serum anti-inflammatory cytokines in MDD-TB patients.

Guía de Práctica Clínica para el diagnóstico temprano y la referencia oportuna del cáncer de pulmón.

OBJETIVO: Proporcionar recomendaciones para la detección temprana de pacientes con alto riesgo de desarrollar cáncer de pulmón (CP) en el primer nivel de atención y su referencia oportuna. Material y métodos. Se realizó una búsqueda detallada de la evidencia científica disponible para responder las preguntas de investigación clínica y se utilizó el Panel Delphi modificado para lograr un consenso entre expertos. RESULTADOS: Se generaron 14 recomendaciones siguiendo los estándares de una GPC. Conclusión. El CP representa un problema de salud pública en México; por ello, esta guía establece recomendaciones que apoyan la toma de decisiones sobre la detección precoz y la referencia de pacientes con sospecha de CP en el primer nivel de atención.

Clinical Impact of the COVID-19 Pandemic in Mexican Patients with Thoracic Malignancies.

BACKGROUND: Accumulated evidence indicates that patients with lung cancer are a vulnerable population throughout the pandemic. Limited information is available in Latin America regarding the impact of the pandemic on medical care. The goal of this study was to describe the clinical and social effect of COVID-19 on patients with thoracic cancer and to ascertain outcomes in those with a confirmed diagnosis. MATERIALS AND METHODS: This cohort study included patients with thoracic neoplasms within a single institution between March 1, 2020, and February 28, 2021. All variables of interest were extracted from electronic medical records. During this period, the Depression Anxiety and Stress Scale 21 (DASS-2) was applied to evaluate and identify more common psychological disorders. RESULTS: The mean age for the total cohort (n = 548) was 61.5 ± 12.9 years; non-small cell lung cancer was the most frequent neoplasm (86.9%), advanced stages predominated (80%), and most patients were under active therapy (82.8%). Any change in treatment was reported in 23.9% of patients, of which 78.6% were due to the COVID-19 pandemic. Treatment delays (≥7 days) were the most frequent modifications in 41.9% of cases, followed by treatment suspension at 37.4%. Patients without treatment changes had a more prolonged progression-free survival and overall survival (hazard ratio [HR] 0.21, p < .001 and HR 0.28, p < .001, respectively). The mean DASS-21 score was 10.45 in 144 evaluated patients, with women being more affected than men (11.41 vs. 9.08, p < .001). Anxiety was reported in 30.5% of cases, followed by depression and distress in equal proportions (18%). Depressed and stressed patients had higher odds of experiencing delays in treatment than patients without depression (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.53-13.23, p = .006 and OR 3.18, 95% CI 1.2-10.06, p = .006, respectively). CONCLUSION: Treatment adjustments in patients with thoracic malignancies often occurred to avoid COVID-19 contagion with detrimental effects on survival. Psychological disorders could have a role in adherence to the original treatment regimen. IMPLICATIONS FOR PRACTICE: The pandemic has placed an enormous strain on health care systems globally. Patients with thoracic cancers represent a vulnerable population, with increased morbidity and mortality rates. In Mexico, treatment modifications were common during the pandemic, and those who experienced delays had worse survival outcomes. Most treatment modifications were related to a patient decision rather than a lockdown of health care facilities in which mental health impairment plays an essential role. Moreover, the high case fatality rate highlights the importance of improving medical care access. Likewise, to develop strategies facing future threats that may compromise health care systems in non-developed countries.

Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients.

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS-), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS-), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS- patients from H/CS- controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.

Case-control study about magnitude of exposure to wood smoke and risk of developing lung cancer.

INTRODUCTION: Exposure to biomass combustion products, particularly firewood, has been considered as a potential carcinogen for developing lung cancer. In this regard, current evidence is widely heterogeneous; besides, in most studies, wood smoke exposure is not appropriately quantified, which further complicates the analysis of wood smoke as a potential carcinogen. The aim of the present study was to estimate the risk of developing lung cancer according to the degree of exposure to wood smoke in patients who use firewood for cooking. MATERIAL AND METHODS: We performed a case-control study that included 482 patients with lung cancer (cases) and 592 hospital controls. Exposure to wood smoke was evaluated as a dichotomous variable (i.e. yes or no); in patients with prior wood smoke exposure, an index of exposure in hours per year was calculated (WSEI). Using bivariate and multivariate logistic regression analyses, the odds ratio (OR) between wood smoke exposure and lung cancer were calculated. RESULTS: The ORs for developing lung cancer (raw and adjusted) for a WSEI > 100 h/year were OR 1.55 [95% confidence interval (CI), 1.06-2.26) and OR 2.26 (95% CI, 1.50-3.40), respectively; the ORs (raw and adjusted) for WSEI >300 h/year were OR 1.76 (95% CI, 1.06-2.91) and OR 3.19 (95% CI, 1.83-5.55), respectively. CONCLUSIONS: Exposure to wood smoke is a risk factor for lung cancer; furthermore, this effect maintains a dose-response relationship which has a multiplicative effect with smoking.

Parapneumonic effusion and thoracic empyema in adults. Clinical aspects, microbiology and frequency of surgical outcome.

BACKGROUND: To date, information about the outcome of patients with parapneumonic effusion and empyema is limited. OBJECTIVE: To describe the clinical characteristics, the microbiological study and the frequency and type of surgical treatment in adult patients with parapneumonic effusion or empyema. METHOD: A prospective cross-sectional study of patients admitted with parapneumonic effusion or empyema, from August 2011 to July 2014, in a reference hospital for respiratory diseases in Mexico City, was conducted. Clinical characteristics, microbiology, risk categories for poor prognosis in empyema and frequency and type of surgical treatment were studied. RESULTS: We studied 284 patients whose median age was 47 years, 75% were men, and 57.7% were transferred from other hospitals. In 38.5% of the cases a microorganism was identified and there was a predominance of Gram negative. 153 (53.9%) required surgical treatment, of which 90% were thoracotomy with decortication. Hospital mortality was 5.63%. CONCLUSIONS: Most of the patients arrived in advanced stages of the disease, so more than half required surgery, of which 90% was decortication. It is desirable to favor mechanisms for early diagnosis and treatment to reduce the need for surgical treatment.

ANTECEDENTES: La información sobre el tipo y la frecuencia del tratamiento quirúrgico en los casos de empiema torácico es escasa. OBJETIVO: Describir las características clínicas, el estudio microbiológico y la frecuencia y el tipo de tratamiento quirúrgico en pacientes adultos con derrame pleural paraneumónico o empiema. MÉTODO: Estudio transversal prospectivo de pacientes con diagnóstico de derrame pleural paraneumónico o empiema, de agosto de 2011 a julio de 2014, en un hospital de referencia para enfermedades respiratorias en la Ciudad de México. Se estudiaron las características clínicas, las categorías de riesgo para mal pronóstico en empiema y la frecuencia y el tipo de tratamiento quirúrgico. RESULTADOS: Se estudiaron 284 pacientes cuya mediana de edad fue de 47 años y el 75% eran hombres. El 57.7% fueron traslados de otros hospitales. En el 38.8% de los casos se identificó un microorganismo, con predominio de gramnegativos. Requirieron tratamiento quirúrgico 153 pacientes (53.9%), de los cuales en el 90% fue toracotomía con lavado y decorticación. La mortalidad hospitalaria fue del 5.63%. CONCLUSIONES: La mayor parte de los pacientes llegaron en etapas avanzadas de la enfermedad, y por ello más de la mitad requirieron cirugía, de los cuales en el 90% fue lavado y decorticación. Es deseable favorecer mecanismos para realizar un diagnóstico y un tratamiento tempranos con el fin de disminuir la necesidad de tratamiento quirúrgico.

Predictive model for mortality in adults hospitalized for community-acquired pneumonia.

INTRODUCTION: There is lack of information about predictive variables for pneumonia mortality in the Mexican population. OBJECTIVE: To identify a model for predictive variables for mortality in adults hospitalized with community acquired pneumonia (CAP). MATERIAL AND METHODS: Case-control study of patients hospitalized with CAP. The cases were incident cases with CAP that died during hospitalization and controls were those that did not die. The patients were followed during the study time until the discharge or outcome of each patient. The association between the independent variables (clinical, severity indices for pneumonia) with the outcome variable (in-hospital mortality) was evaluated by logistic regression. RESULTS: The model of associated variables with mortality were stratified age from 50-70 years (odds ratio [OR] 2.35; 95% confidence interval [95% CI: 1.06-5.17) and age >70 years (OR: 2.75; 95% CI: 1.18-6.37), woman (OR: 2.05; 95% CI: 1.11-3.8), antecedent of arterial hypertension (OR: 0.40; 95% CI: 0.20-0.80), tachycardia (OR: 2.68; 95% CI: 1.16-6.17), tachypnea (OR: 2.85; 95% CI: 1.54-5.29), leukocytes ≥ 12,000 (OR: 2.17; 95% CI: 1.21-3.87) and urea nitrogen > 30 mg/dL (OR: 4.85; 95% CI: 2.55-9.24). CONCLUSIONS: The proposed risk model is easy to document with clinical history and routine clinical laboratory variables.

ANTECEDENTES: Existe escasa información sobre variables predictoras para mortalidad por neumonía en población mexicana. OBJETIVO: Identificar un modelo de variables predictoras para mortalidad en adultos hospitalizados por neumonía adquirida en la comunidad (NAC). MÉTODO: Estudio de casos y controles de pacientes hospitalizados por NAC. Los casos fueron pacientes con NAC que fallecieron durante la hospitalización y los controles fueron pacientes que no fallecieron. Los pacientes se siguieron durante el tiempo de estudio hasta el egreso o el desenlace de cada uno. La asociación entre las variables independientes (clínicas, índices de gravedad para neumonía) con la variable desenlace (muerte hospitalaria) se evaluó mediante regresión logística. RESULTADOS: Las variables asociadas a mortalidad fueron la edad estratificada de 50-70 años (odds ratio [OR] 2.35; intervalo de confianza del 95% [IC 95%]: 1.06-5.17) y > 70 años (OR 2.75; IC 95%: 1.18-6.37), ser mujer (OR 2.05; IC 95%: 1.11-3.8), antecedente de hipertensión arterial (OR 0.40; IC 95%: 0.20-0.80), taquicardia (OR 2.68; IC 95%: 1.16-6.17), taquipnea (OR 2.85; IC 95%: 1.54-5.29), leucocitos ≥ 12,000 (OR 2.17; IC 95%: 1.21-3.87) y nitrógeno de la urea >30 mg/dl (OR 4.85; IC 95%: 2.55-9.24). CONCLUSIONES: El modelo de riesgo que se propone es fácil de documentar con la historia clínica y las pruebas de laboratorio habituales.

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major cause of morbidity and mortality worldwide. In the host's immune response system, T cells play a critical role in mediating protection against Mtb infection, but the role of CD8+ T cells is still controversial. We evaluated the phenotypical characterization and cytotoxic ability of CD8+ T cells by flow cytometry-based assay. Cytokine levels in serum were measured by multiplex cytokine assay. Our data show that cells from TB patients have an increased percentage of peripheral blood CD8+ αß+ T (p = 0.02) and CD56+ CD8+ T (p = 0.02) and a decreased frequency of NKG2D+ CD8+ T (p = 0.02) compared with healthy donors. Unlike CD8+ T cells from healthy donors, CD8+ T cells from TB patients exhibit greater cytotoxicity, mediated by HLA class I molecules, on autologous monocytes in the presence of mycobacterial antigens (p = 0.005). Finally, TB patients have a proinflammatory profile characterized by serum high level of TNF-α (p = 0.02) and IL-8 (p = 0.0001), but, interestingly, IL-4 (p = 0.002) was also increased compared with healthy donors. Our data show evidence regarding the highly cytotoxic status of CD8+ T cells in Mtb infection. These cytotoxic cells restricted to HLA-A, B, and C could be used to optimize strategies for designing new TB vaccines or for identifying markers of disease progression.

Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion / Exactitud de la biopsia pleural cerrada para el diagnóstico de derrame pleural maligno

ABSTRACT Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

RESUMEN Objetivo: Estudios previos demuestran que la biopsia pleural cerrada (BPC) para diagnóstico de malignidad tiene una sensibilidad menor al 60%, por lo que recientemente ha despertado controversia su valor como prueba diagnóstica. Nuestro objetivo fue evaluar la exactitud de la BPC para diagnóstico de malignidad en pacientes con derrame pleural. Métodos: Estudio prospectivo de 8 años en individuos que se sometieron a la realización de BPC para establecer la etiología del derrame. La información de cada paciente se tomó de los registros de anatomopatología y del expediente clínico. Cuando el resultado de la BPC demostró malignidad o tuberculosis, esto se tomó como biopsia diagnóstica y quedó éste como diagnóstico definitivo. En los casos en que el resultado del estudio histopatológico de la biopsia resultó inespecífico, el diagnóstico definitivo se estableció en base a otros procedimientos diagnósticos, como toracoscopia, toracotomía, fibrobroncoscopia, estudio bioquímico y celular del líquido pleural y/o pruebas microbiológicas. Mediante una tabla de contingencia de 2 × 2 se midieron los indicadores para una prueba diagnóstica. Resultados: Se estudiaron 1034 biopsias de pacientes con derrame pleural, de las cuales se excluyeron 171 (16.54%) por muestra inadecuada o información insuficiente. El desempeño para malignidad fue: sensibilidad, 77%; especificidad, 98%; valores predictivos positivo y negativo, 99% y 66%, respectivamente; índices de probabilidad positivo y negativo, 38.5 y 0.23, respectivamente; probabilidad antes y después de la prueba, 2.13 y 82, respectivamente. Conclusión: La BPC es útil como prueba diagnóstica en la práctica clínica, debido a que produce un cambio importante de la probabilidad antes de la prueba a la probabilidad después de la prueba.

An international epidemiological analysis of young patients with non-small cell lung cancer (AduJov-CLICaP).

BACKGROUND: A proportion of patients with NSCLC is diagnosed at 40 years or younger. These patients tend to be never-smokers, usually present with stage IV adenocarcinoma, and have somatic genomic alterations. Few studies have documented and analyzed epidemiological characteristics of this population. MATERIALS AND METHODS: We performed an international epidemiological analysis of 389 young patients with NSCLC. Data was collected from centers participating in the Latin American Consortium for Lung Cancer Research (AduJov-CLICaP). Patients were identified and data was retrospectively collected from different Latin American countries and Canada (Argentina=6, Canada=19, Colombia=29, Costa Rica=9, Mexico=219, Nicaragua=2, Panama=19, Perú=76 and Venezuela=10). The period of study was from 2012 to 2017. Inclusion criteria were: age 40 years or less and a histologically confirmed NSCLC. Clinical data was obtained, and EGFR mutation status and EML4-ALK translocation were collected. RESULTS: NSCLC patients aged 40 years or less accounted for approximately 4% of the total NSCLC population. Female patients accounted for 54.5%, while median age was of 37 years. Adenocarcinoma accounted for 86.1% (n=335/389), 72.5% (n=282/389; unknown=5) of patients were non-smokers, and 90.3% (n=351/389) had stage IV disease. Site of metastasis was obtained from 260/351 (unknown=91) stage IV patients (lung metastasis=40.0%, CNS metastasis=35.7%, and bone metastasis=31.5%). OS for the total population was 17.3 months (95%CI=13.9-20.7). OS for EGFRm(+)=31.4months (95%CI=11.6-51.3), EGFRm(-)=14.5months (95%CI=11.0-17.9) (p=0.005). OS for alk(+)=9.8months (95%CI=3.1-16.5) and alk(-)=5.6months (95%CI=3.9-7.3) (p=0.315). CONCLUSIONS: Patients aged 40 years or less account for a small but important proportion of NSCLC cases. Younger patients may have different characteristics compared to the older population. EGFRm and EML4-alk translocation frequency is higher than that of the general population.

[Results of the First Mexican Consensus of Vaccination in the Adult]. / Resultados del Primer Consenso Mexicano de Vacunación en el Adulto.

For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.

[First Mexican Consensus of Vaccination in Adults]. / 1º Consenso Mexicano de Vacunación en el Adulto.

For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.

Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion.

OBJECTIVE: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. METHODS: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. RESULTS: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. CONCLUSIONS: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

BACKGROUND: Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. OBJECTIVE: To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. MATERIALS AND METHODS: We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. RESULTS: Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. CONCLUSIONS: The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.

La exploración del tórax: una guía para descifrar sus mensajes / Thoracic exploration: a guide to decipher their messages

Resumen La exploración adecuada del tórax tiene una secuencia que ayuda al clínico a seguir varios pasos e integrar sus hallazgos en síndromes, mismos que lo llevarán con más seguridad hacia el diagnóstico más adecuado. Al cumplirse los 200 años de la invención del estetoscopio por René Laënec, tomamos esta oportunidad para recordarlo y detallar los pasos de la exploración del tórax. El hecho de contar con más herramientas tecnológicas para el diagnóstico, no le resta importancia a esta etapa tan importante de la relación entre el médico y su paciente, que es la exploración.

Abstract Thoracic exploration has a sequence of steps that help the clinician to integrate its findings in syndromes, which will lead the physician to better diagnosis. This year the stethoscope, invented by René Laënec, turns 200 years old and we use this opportunity to remember him and provide a detailed description of the thoracic exploration. To have access to more sophisticated diagnostic tools should not diminish the relevance of a direct exploration of the patient, which is a very important step in the patient-physician relationship.

Estrógenos y su influencia en el cáncer pulmonar / The influence of estrogens in lung cancer

Resumen Actualmente, el cáncer pulmonar es un problema de salud importante a nivel mundial porque presenta una alta incidencia y mortalidad tanto en hombres como en mujeres. Su forma más común es el adenocarcinoma (ADC), que es una entidad patológica interesante ya que de todas las formas de cáncer pulmonar, es la que se asocia menos con el tabaquismo y un porcentaje importante de pacientes con adenocarcinoma son no fumadores. De modo que otros factores como la exposición al humo de leña, a los contaminantes del aire, la historia familiar de cáncer, entre otros, son importantes para el desarrollo del ADC pulmonar. Actualmente el ADC pulmonar es la principal forma de cáncer pulmonar en las mujeres y se ha reportado que las mujeres premenopáusicas presentan peor pronóstico y los tumores son más agresivos cuando se comparan con los hombres y las mujeres posmenopáusicas. Estos datos han sugerido el papel de los estrógenos en el cáncer pulmonar, principalmente en el ADC. Aunque existe vasta evidencia epidemiológica que demuestra esta relación, hay controversia en cuanto al papel de los estrógenos en esta patología. De igual manera no hay una opinión generalizada sobre los mecanismos por los cuales los estrógenos podrían favorecer la carcinogénesis. Sin embargo, cada vez es más clara la importancia de éstas hormonas en la carcinogénesis pulmonar. En esta revisión se muestran estos datos y se discute la relevancia de los estrógenos en el cáncer pulmonar, una patología cuya dependencia hormonal es cada vez más clara.

Abstract Lung cancer is currently a worldwide health issue because of the mortality and high incidence of this pathology in both men and women. The most common form of lung cancer is adenocarcinoma (ADC); It is an interesting disease entity because among every type of lung cancer it has the lower association with smoking and a significant percentage of patients with adenocarcinoma are not smokers. Hence other factors such as exposure to wood-smoke, air pollutants, family history of cancer, among others, are important in the development of lung ADC. Nowadays, lung ADC is the main form of lung cancer in women and reports show that premenopausal women have the worse prognosis and have more aggressive tumors compared to men and postmenopausal women. These data suggests that estrogens have a particular role in lung cancer physiopathology mainly in ADC. Although there is sufficient epidemiological evidence that indicates a relationship between sexual hormones and lung cancer, the role of estrogens in this pathology is still controversial. Furthermore there is no general consent regarding the known mechanisms by which these hormones could promote carcinogenesis and because the scarce information about the implication of these hormones in lung carcinogenesis more studies are needed. In this review we discuss the role and relevance of estrogens in lung cancer, a pathology whose hormonal dependency is becoming clearer.