Mutational status of PIK3ca oncogene in oral cancer-In the new age of PI3K inhibitors.

In the new age of PI3K inhibitors, the mutational status of PI3Kca oncogene in the Cavity Squamous Cell Carcinoma (OC-SCC) needs further analysis. It is the sixth most common cancer in the world. The aim of this study was to evaluate PI3Kca oncogene mutations and to correlate them with the clinical-histological characteristics of individuals presenting these tumors. We recruited 74 individuals with OC-SCC diagnosis (period 2000-2014). Histological sections were used. DNA was purified; PIK3ca gene exons 9 and 20 were amplified and sequenced. In 49/74 cases (66 %), the complete sequence of both codons was analyzed by Sanger method. We found that 7/49 (14 %) individuals mutated. In exon 9 we found 1/49 (2 %), and in exon 20 M1043I 8/49 (16 %). We have found the coexistence of more than one mutation in a same individual (E542 K and M1043I). A positive association was observed between the mutational status of the codon 9 (E542 K) and the tongue location. In conclusion, the frequency of PI3Kca gene mutation in OC-SCC was 16 %, which is similar to that reported for other populations. We found a mutation not previously described (M1043I) in this pathology. Should its biological effect be confirmed, it must be added to the list of PIK3ca mutations. Total mutations in the PIK3ca were 32 %, with tongue being the site at the greatest risk (E542K-E545K-M1043I). These findings would facilitate the identification of patients with therapeutic targets in the near future.

Expresión inmunohistoquímica de p53 en individuos con liquen / Immunohistochemical expression of p53 in individuals with lichen planus

Objetivo: Estimar el riesgo del potencial de malignización del liquen plano bucal analizando la expresión de la proteína p53. Materiales y metodos: Se realizó un diseño de cohorte de sujetos con diagnostico histopatológico de liquen. El desenlace fue el desarrollo de cáncer si/no. El total de individuos que cumplió con los criterios de inclusión/exclusión fue de 58. A los 58 sujetos se les realizó la determinación de p53. Resultados: Cuarenta y nueve individuos mostraron una expresión de p53 menor al 5% con una P>0,05% intrasujeto no transformado. En los 9 individuos transformados se observaron diferencias significativas entre la determinación pre y post de la proteína p53. El Riesgo Relativo fue de 188 con una significación estadística de P< 0,01. Conclusion: La expresión de la proteína p53 en los individuos con liquen apoya la hipótesis que niveles superiores al 5%constituye un factor de incremento del riesgo en la transformación maligna de esta patología. Nuestros hallazgos deberían ser corroborados en el futuro con mayor número de individuos. La determinación de la p53 mediante IHQ en individuos con liquen plano bucal podría modificar el seguimiento clínico de estos individuos. Esto permitiría un diagnóstico precoz de cualquier alteración que pueda indicar un posible cambio hacia la malignización.

Objective: To determine the risk for potential malignant transformation of oral lichen planus by analyzing protein p53 expression. Materials and methods: Cohort study of subjects with a histopathologic diagnosis of lichen. The study analyzed whether or not subjects developed cancer. A total of 58 subjects fulfilled the inclusion/exclusion criteria, and were analyzed for p53. Results: Fortynine(49) subjects showed a p53 expression <5%, with a p>0.05 among subjects undergoing no transformation. In the 9 subjects undergoing malignant transformation, significant differences were observed between pre and post p53 expression. The relative risk was 188, with a statistical significance of p< 0.01. Conclusions: Protein p53 expression in subjects with lichen supports the hypothesis that levels >5% are associated with an increased risk of malignant transformation of this condition. Should our findings be proved in a larger series in the future, the clinical follow-up of these subjects could be modified. This would allow an early diagnosis of any disorder indicative of a potential malignant transformation.

Paid employment in subjects with and without chronic obstructive pulmonary disease in five Latin American cities: the PLATINO study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a costly condition that frequently causes permanent work disabilities. Little information exists regarding the impact of COPD on work force participation and the indirect costs of the disease in developing countries. OBJECTIVE: To examine the frequency of paid employment and factors influencing it in a Latin-American population-based study. METHODS: Post-bronchodilator FEV(1)/FVC < 0.70 (forced expiratory volume in 1 s/forced vital capacity) was used to define COPD. Information regarding paid work was assessed by the question 'At any time in the past year, have you worked for payment?' RESULTS: Interviews were conducted with 5571 subjects; 5314 (759 COPD and 4554 non-COPD) subjects underwent spirometry. Among the COPD subjects, 41.8% reported having paid work vs. 57.1% of non-COPD (P < 0.0001). The number of months with paid work was reduced in COPD patients (10.5 ± 0.17 vs. 10.9 ± 0.06, P < 0.05). The main factors associated with having paid work in COPD patients were male sex (OR 0.33, 95%CI 0.23-0.47), higher education level (OR 1.05, 95%CI 1.01-1.09) and younger age (OR 0.90, 95%CI 0.88-0.92). COPD was not a significant contributor to employment (OR 0.83, 95%CI 0.69-1.00, P = 0.054) in the entire population. CONCLUSIONS: Although the proportion of persons with paid work is lower in COPD, having COPD appears not to have a significant impact on obtaining paid employment in the overall population of developing countries.

Sex-related differences in COPD in five Latin American cities: the PLATINO study.

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥ 2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40-1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56- -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.

Pericardial tamponade in a patient with polymyalgia rheumatica.

We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory-immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment.

Worldwide burden of COPD in high- and low-income countries. Part II. Burden of chronic obstructive lung disease in Latin America: the PLATINO study.

SETTING: Five Latin American cities: São Paulo, Brazil; Mexico City, Mexico; Montevideo, Uruguay; Santiago, Chile; Caracas, Venezuela. OBJECTIVE: To describe the burden of chronic obstructive pulmonary disease (COPD) in Latin America. DESIGN: This is a multicentre study. Post-bronchodilator spirometry was used and the main outcome measure was FEV(1)/FVC < 0.7 (fixed ratio criterion). Global Obstructive Lung Disease (GOLD) stages were also analysed. RESULTS: The combined population aged > or =40 years in the five countries included in the study was approximately 85.3 million. Of these, it was estimated that 12.2 million have airflow obstruction, which corresponds to our prevalence estimate of 14.3%. The proportion of subjects in Stages II-IV of the GOLD classification was 5.6%. Risk factors presenting the highest aetiological fractions for COPD were age, current smoking, indoor exposure to coal and exposure to dust in the workplace. Smoking, the modifiable factor with the strongest aetiological fraction for COPD, affects 29.2% of adults aged > or =40 years in these cities, corresponding to approximately 25 million smokers in this age group. CONCLUSION: Prevention of smoking and exposure to pollutants, such as coal and dust, are the interventions most likely to succeed against COPD in Latin America. The information obtained by a collaborative study has been vast and encouraging for other similar studies.

Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America.

The aim of the present study was to evaluate the association between history of tuberculosis and airflow obstruction. A population-based, multicentre study was carried out and included 5,571 subjects aged > or =40 yrs living in one of five Latin American metropolitan areas: Sao Paulo (Brazil); Montevideo (Uruguay); Mexico City (Mexico); Santiago (Chile); and Caracas (Venezuela). Subjects performed pre- and post-bronchodilator spirometry and were asked whether they had ever been diagnosed with tuberculosis by a physician. The overall prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity post-bronchodilator <0.7) was 30.7% among those with a history of tuberculosis, compared with 13.9% among those without a history. Males with a medical history of tuberculosis were 4.1 times more likely to present airflow obstruction than those without such a diagnosis. This remained unchanged after adjustment for confounding by age, sex, schooling, ethnicity, smoking, exposure to dust and smoke, respiratory morbidity in childhood and current morbidity. Among females, the unadjusted and adjusted odds ratios were 2.3 and 1.7, respectively. In conclusion, history of tuberculosis is associated with airflow obstruction in Latin American middle-aged and older adults.

Prevalence of oxygen desaturation and use of oxygen at home in adults at sea level and at moderate altitude.

The aim of this study was to determine the prevalence of oxygen desaturation in adults aged>or=40 yrs as altitude above sea level increases. A population-based, cross-sectional study with a multistage cluster sampling of 1,063 subjects from metropolitan Mexico City (Mexico; 2,240 m above sea level), 1,357 from Caracas (Venezuela; 950 m) and 943 from Montevideo (Uruguay; 35 m). The mean of six measurements of arterial oxygen saturation (SP,O2) was estimated using a pulse oximeter. Mean SP,O2 decreased with altitude. No subject from Montevideo had a mean SP,O288%. In conclusion, the prevalence of hypoxaemia was closely related to altitude. Priorities for oxygen prescription must be defined in moderate altitudes because it is unfeasible to provide it to all subjects fulfilling the criteria commonly used.

Prevalencia de la enfermedad pulmonar obstructiva crónica y sus principales factores de riesgo: proyecto PLATINO en Montevideo / Prevalence and risk factors of chronic obstructive pulmonary disease: the PLATINO project in Montevideo

La enfermedad pulmonar obstructiva crónica (EPOC), caracterizada por limitación al flujo aéreo, se ha convertido en una causa mayor de morbimortalidad en los países desarrollados. En américa LAtina los datos epidemiológicos son escasos. PLATINO (Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar) es un estudio multicéntrico dirigido a medir la prevalencia de esta enfermedad en 5 ciudades latinoamericanas, sus principales factores de riesgo, describir los síntomas respiratorios, evaluar la sensibilidad y especificidad de los mismos así como correlacionar el diagnóstico médico previo con el diagnóstico funcional de EPOC. La selección de la muestra fue realizada en varias etapas, agrupada por conglomerads, de manera de analizar una población representativa de la ciudad de Montevideo y el aréa metropolitana con edad mayor o igual a 40 años. De 1.140 sujetos elegibles contestaron un cuestionario estandarizado 943 personas y se completaron 885 espirometrías posbroncodilatador. La prevalencia de EPOC considerando los principales criterios funcionales diagnósticos fue: para la relación volumen respiratorio forzado en el primer seguno/capacidad vital forzada (VEF1/CVF) <70: 19,7 por ciento. Según la definición del Global Initiative for Chronic Obstructive Lung Disease (GOLD) (VEF1/CVF <70 por ciento y VEF1 <80 por ciento predicto) fue 7,8 por ciento ya que cuantifica además el grado de severidad de la enfermedad (estadio II). El tabaquismo actual se presentó en 28 por ciento de los sujetos encestados. Estos presentaron 47 por ciento más EPOC que los no fumadores; esta probabilidad fue 78 por ciento mayor para aquellos fumadores con un índice de paquetes/año mayor a 10. La baja sensibilidad y especificidad de los síntomas respiratorios y el subdiagnóstico de esta enfermedad deben promover la detección temprana de limitación de flujo aéreo por espirometría, para instrumentar medidas terapéuticas adecuadas.