Patrón inflamatorio de las vías aéreas en pacientes fumadores con enfermedad pulmonar obstructiva crónica / Inflammatory pattern of the airways in COPD smokers

Introducción: La enfermedad pulmonar obstructiva crónica cursa con un patrón inflamatorio en la vía aérea que incluye neutrófilos, macrófagos, linfocitos, los cuales se pueden obtener mediante un cepillado bronquial citológico. Objetivos: Identificar patrón inflamatorio según células inflamatorias presentes en la vía aérea, mediante el cepillado bronquial citológico e índice tabáquico de paquetes/año en pacientes con enfermedad pulmonar obstructiva crónica. Métodos: Se realizó un estudio descriptivo transversal en pacientes con enfermedad pulmonar obstructiva crónica, que concurrieron al Hospital Neumológico Benéfico-Jurídico, en el período comprendido de junio de 2018 a junio de 2019, con indicación para la realización de fibrobroncoscopía con cepillado bronquial. Resultados: El 53,1 por ciento de los pacientes corresponden al sexo masculino. Un 46,1 por ciento presentó un índice tabáquico de paquetes/año entre 21-40. Predominaron las criptas y estrías como hallazgos broncoscópicos con un 51 por ciento y 40,8 por ciento respectivamente en pacientes con índice paquetes/año mayor que 40. De los pacientes con índice paquetes/año mayor de 40 (13 para un 26,5 por ciento) presentaron hiperplasia de células basales. El 46,9 por ciento de los pacientes presentaron un patrón inflamatorio neutrofílica. Conclusiones: Se identificaron a los pacientes con EPOC que presentaron patrón inflamatorio neutrofílica en la vía aérea y elevado índice tabáquico y desde el punto de vista broncoscópico tienen varios hallazgos que sugieren cronicidad(AU)

Introduction: Chronic obstructive pulmonary disease presents with an inflammatory pattern in the airway that includes neutrophils, macrophages, and lymphocytes, which can be obtained by cytological bronchial brushing. Objectives: To identify inflammatory pattern according to inflammatory cells present in the airway, through cytological bronchial brushing and smoking rate of packs/year in patients with chronic obstructive pulmonary disease. Methods: A cross-sectional descriptive study was carried out in patients with chronic obstructive pulmonary disease, who attended Benefico-Jurídico Pneumological Hospital, from June 2018 to June 2019, with an indication for fiberoptic bronchoscopy with bronchial brushing. Results: 53.1percent of the patients correspond to the male sex. 46.1percent ad a smoking rate of packs/year between 21-40. Crypts and striae predominated as bronchoscopic findings with 51percent and 40.8percent respectively in patients with a pack/year index greater than 40. Patients with a pack/year index greater than 40 (13 for 26.5percent) showed basal cell hyperplasia. 46.9percent of the patients had a neutrophilic inflammatory pattern. Conclusions: Patients with COPD who had a neutrophilic inflammatory pattern in the airway and high smoking index were identified, and from the bronchoscopic point of view they have several findings that suggest chronicity(AU)

Avaliação de seguimento do Estudo Fibra: caracterização sociodemográfica, cognitiva e de fragilidade dos idosos em Campinas e Ermelino Matarazzo, SP / Follow-up evaluation of the Fibra Study: sociodemographic, cognitive, and frailty characterization of older adults in Campinas and Ermelino Matarazzo, SP

Resumo Objetivo Investigar e comparar o perfil sociodemográfico, cognitivo e de fragilidade dos participantes do Estudo Fragilidade em Idosos Brasileiros em medidas de seguimento (SG) e linha de base (LB) realizadas em 2016-2017 e 2008-2009, respectivamente. Métodos Participaram da LB 1.284 idosos residentes em Campinas e Ermelino Matarazzo (SP), Brasil, que compuseram amostra única. No SG foram novamente entrevistados 549 participantes (42,5%); 192 tinham falecido (14,9%) e 543 foram perdidos (42,4%). Em ambos os momentos, foram avaliadas as variáveis sexo, idade, escolaridade, estado conjugal, renda familiar, arranjo de moradia, status cognitivo (Mini-Exame do Estado Mental) e fenótipo de fragilidade (três ou mais de cinco critérios). As diferenças intergrupos e intragrupos foram verificadas pelos testes qui-quadrado de Pearson e de McNemar, respectivamente. O nível de significância foi estabelecido em p<0,05. Resultados Entre os sobreviventes, os participantes eram mais jovens (72,2±5,3 anos) do que entre os falecidos (75,5±6,8 anos) e havia mais idosos casados, com nível educacional mais elevado, sem deficit cognitivo e pré-frágeis. Da LB para o SG, houve aumento estatisticamente significativo do número de idosos que moravam sozinhos (17,1% vs. 22,0%), não tinham companheiro(a) (46,4% vs. 55,4%), tinham renda familiar menor que três salários-mínimos (52,2% vs. 62,2%), apresentavam deficit cognitivo (17,7% vs. 23,5%) e eram frágeis (9,8% vs. 24,5%) Conclusão Da LB para o SG, ocorreu aumento da vulnerabilidade física, cognitiva e social dos idosos. Estes resultados reforçam a importância de políticas públicas que favoreçam a qualidade de vida dos idosos e a redução das iniquidades de saúde ao longo da vida.

Abstract Objective To investigate and compare the sociodemographic, cognitive and frailty profile of participants from the Frailty in Brazilian Older Adults (Fibra) study regarding follow-up (FW) and baseline (BL) measurements carried out in 2016-2017 and 2008-2009, respectively. Methods A total of 1,284 older adults living in Campinas and Ermelino Matarazzo (SP), Brazil, participated in the BL, comprising a pooled sample. At FW, 549 older adults (42.7%) were interviewed again; 192 had died (14.9%) and 543 were lost to follow-up (42.4%). Sex, age, education, marital status, family income, housing arrangement, cognitive status (Mini-Mental State Examination) and frailty phenotype (score ≥3 out of 5) were evaluated at both timepoints. Intergroup and intragroup differences were verified by Pearson's chi-square and McNemar's tests. Statistical significant level was set at p<0.05 Results The survivors were younger (72.2±5.3 years) than the deceased (75.5±6.8 years) and individuals included in the FW were mostly married, higher educated, cognitively unimpaired and pre-frail. Between BL and FW there was an increase in the number of participants who lived alone (17.1% vs. 22.0%), had no partner (46.4% vs. 55.4%), a family income <3 minimum wages (52.2% vs. 62.2%), cognitive impairment (17.7% vs. 23.5%) and frailty (9.8% vs. 24.5%). Conclusion Between BL and FW there was an increase in the physical, cognitive and social vulnerability of the older adults. These results reinforce the importance of public policies that favor the quality of life of older people and a reduction in health inequities throughout life.

Hábito de fumar y comorbilidad en pacientes con enfermedad pulmonar obstructiva crónica / Smoking habit and comorbidity in patients with chronic obstructive pulmonary disease

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica constituye un problema de salud en Cuba y el mundo; su pronóstico está en relación con varios factores. Objetivo: Caracterizar a una serie de pacientes hospitalizados con enfermedad pulmonar obstructiva crónica, según edad, sexo, fenotipo, hábito de fumar y enfermedades comórbidas. Métodos: Se realizó un estudio descriptivo transversal que incluyó a los 296 pacientes que ingresaron en el Servicio de Medicina Interna del Hospital Militar Central "Dr. Carlos J. Finlay" con el diagnóstico de enfermedad pulmonar obstructiva crónica, en el período de dos años. Se determinaron las enfermedades comórbidas, el fenotipo dado por la forma clínica de presentación de los pacientes (A, B, C y D); la edad, sexo, hábito de fumar, tiempo y cantidad que fuma. Se utilizó el índice de comorbilidad de Charlson, para valorar la comorbilidad asociada en la enfermedad. Resultados: El 54 % de los pacientes fueron masculinos, el 96,9 % mayor de 50 años, el 36,1 % del fenotipo C y el 76,6 % fumadores. La hipertensión arterial fue más frecuente en los fenotipos B, C y D, en más del 70 %, la diabetes mellitus en el 73,7 % del fenotipo B y la cardiopatía isquémica en el 61,7 % del fenotipo D. Conclusiones: La mayoría de los pacientes estudiados fueron masculinos, mayores de 50 años, fumadores por más de 10 años y del fenotipo C. Las enfermedades comórbidas más frecuentes fueron la hipertensión arterial, la diabetes mellitus y la cardiopatía isquémica.

ABSTRACT Introduction: Chronic obstructive pulmonary disease constitutes a health problem in Cuba and the world, its prognosis is related to several factors. Objective: To characterize a series of hospitalized patients with chronic obstructive pulmonary disease, according to age, sex, phenotype, smoking habit and comorbid diseases. Method: A descriptive cross-sectional study was carried out that included the 296 patients who were admitted to the Internal Medicine Service of the Central Military Hospital Dr. Carlos J. Finlay with the diagnosis of chronic obstructive pulmonary disease in the period of two years. Comorbid diseases were determined, the phenotype given by the clinical presentation of the patients (A, B, C and D); age, sex, smoking habit, time and amount of smoking. The Charlson comorbidity index was used to assess the associated comorbidity in COPD. Results: 54% of the patients were male, 96,9% older than 50 years, 36,1% phenotype C, and 76,6% smokers. Hypertension was more frequent in phenotypes B, C and D, in more than 70%, diabetes mellitus in 73,7% of phenotype B, and ischemic heart disease in 61,7% of phenotype D. Conclusions: Most of the patients studied were male, older than 50 years, smokers for more than 10 years and phenotype C. The most frequent comorbid diseases were arterial hypertension, diabetes mellitus and ischemic heart disease.

Epidemiología y fenotipo de la enfermedad de Crohn en un hospital de referencia en Lima Perú / Epidemiology and phenotype of Crohn's disease in a reference hospital in Lima Peru

RESUMEN La enfermedad de Crohn (EC) es una patología inflamatoria crónica del tracto digestivo con gran impacto en la calidad de vida de los pacientes. La epidemiología mundial está cambiando en los últimos años y su prevalencia está aumentando en Latinoamérica. Objetivo: Evaluar las características epidemiológicas, fenotipo, curso clínico, diagnóstico y tratamiento de la EC. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo de pacientes con diagnóstico de EC desde enero 2004 a diciembre 2019 en el servicio de gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen, LimaPerú. Resultados: Se incluyó 55 pacientes, con edad promedio de 56 ± 8,2 años. Predominio masculino (62%). El tiempo promedio de diagnóstico fue de 18 ± 6,1 meses. Los síntomas más frecuentes fueron: dolor abdominal 72,7% y baja de peso 60%. Las manifestaciones extraintestinales se presentaron en 20%. La localización ileal (36,4%) fue la más frecuente, seguida de la colónica (32,7%). Predominó el fenotipo inflamatorio en la mitad de los pacientes, seguido de estenosante en 25,5%. La actividad clínica y endoscópica más frecuente fue moderada. Para el tratamiento de inducción y mantenimiento, los corticoides sistémicos y la terapia biológica con anti-TNF fueron los más utilizados respectivamente. Aproximadamente un tercio de pacientes requirieron cirugía durante la evolución de la enfermedad. La mortalidad fue del 5,4%. Conclusiones: La EC es una enfermedad cada vez más frecuente en nuestro país, con características epidemiológicas y fenotípicas que difieren de otros continentes.

ABSTRACT Crohn's disease (CD) is a chronic inflammatory pathology of the digestive tract with great impact on the quality of life of patients. Global epidemiology is changing in recent years and its prevalence is increasing in Latin America. Objective: To evaluate the epidemiological characteristics, phenotype, clinical course, diagnosis and treatment of CD. Materials and methods: Retrospective, descriptive, observational study of patients diagnosed with CD from January 2004 to December 2019 in the gastroenterology service of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. Results: 55 patients with an average age of 56 ± 8.2 years were included. Male predominance (62%). The average diagnosis time was 18 ± 6.1 months. The most frequent symptoms were: abdominal pain 72.7% and weight loss 60%. Extraintestinal manifestations occurred in 20%. The ileal location (36.4%) was the most frequent, followed by colonic (32.7%). The inflammatory phenotype predominated in half of the patients, followed by stenosing in 25.5%. The most frequent activity clinical and endoscopic was moderate. For induction and maintenance treatment, systemic corticosteroids and biological therapy with anti-TNF were the most widely used, respectively. Approximately a third of patients required surgery during the evolution of the disease. Mortality was 5.4%. Conclusions: CD is an increasingly frequent disease in our country, with epidemiological and phenotypic characteristics that differ from other continents.

Influência da reabilitação pulmonar no paciente com Doença Pulmonar Obstrutiva Crônica fenótipo exacerbador / Influence of pulmonary rehabilitation in patients with Chronic Obstructive Pulmonary Disease exacerbator phenotype

RESUMO Objetivo Verificar se existem diferenças em pacientes com doença pulmonar obstrutiva crônica (DPOC) fenótipos exacerbador e não exacerbador submetidos a um programa de reabilitação pulmonar (PRP). Métodos Estudo retrospectivo de vida real que incluiu pacientes com DPOC da rede pública de atendimento ambulatorial em nível de atenção primária, que completaram o PRP, com duração de 12 semanas, três vezes por semana. Todos foram avaliados antes e depois do PRP, por meio do teste de caminhada dos seis minutos (TC6min), índice de dispneia (mMRC), qualidade de vida e índice BODE. Resultados Dos 151 pacientes analisados, a média de idade foi 65,0 ± 8,1 anos e a média VEF1% do predito foi de 39,8 ± 15,9. O gênero predominante foi o masculino (66,9%). Desses pacientes, 31 (20,5%) eram fenótipo exacerbador. Houve melhora significativa na média da distância percorrida no TC6min em ambos os grupos, sendo a maior mudança observada no grupo exacerbador [mΔ(IC95%): 84,9 (57,1-112,6) vs. 48,6 (37-60,2); p = 0,018]. Redução significativa da dispneia pela escala mMRC ocorreu em ambos os grupos, sendo de maior intensidade no grupo exacerbador [mΔ(IC95%): -0,8 (-1,11 a 0,51) vs. -1,6 (-2,20 a -1,13); p = 0,006]. Melhora no índice BODE ocorreu em ambos os grupos, mas a variação média também foi significativamente maior no grupo exacerbador [mΔ(IC95%): -1,44 (-2,17 a -0,70); p = 0,045]. Conclusão Os pacientes com DPOC fenótipo exacerbador apresentaram maior magnitude de resposta ao PRP (36 metros) quando comparados ao não exacerbador, independentemente da gravidade da obstrução do fluxo aéreo, impactando a melhora no prognóstico medido pelo índice BODE.

ABSTRACT Objective To verify if there are differences in Chronic Obstructive Pulmonary Disease (COPD) patient exacerbator and non-exacerbator phenotypes undergoing a Pulmonary Rehabilitation Program (PRP). Methods A real life retrospective study included outpatients with COPD from public primary care who completed a 12-weeks PRP, three times a week. All were assessed before and after PRP using the six-minute walk test (6MWT), the modified Medical Research Council (mMRC) dyspnea index, quality of life and Body-mass Index, airflow Obstruction, Dyspnea and Exercise (BODE index). Results A total of 151 patients were analyzed and mean age was 65.0 ± 8.1 years and mean Forced Expiratory Volume (FEV) 1% of predicted was 39.8 ± 15.9. The predominant gender was male (66.9%). Of these patients 31 (20.5%) were exacerbator phenotype There was a significant improvement in the mean distance in the 6MWT in both groups, with the largest change observed in the exacerbator group [mΔ (95% CI): 84.9 (57.1-112.6) vs. 48.6 (37-60.2) p= 0.018]. Significant reduction in dyspnea on the mMRC scale occurred in both groups, with the highest intensity in the exacerbator group [mΔ (95% CI): - 0.8 (-1.11 to 0.51) vs. -1.6 (-2.20 to -1.13) p = 0.006]. Improvement in the BODE index occurred in both groups, but the mean variation was also significantly greater in the exacerbator group [mΔ (95% CI): -1.44 (-2.17 to -0.70) p= 0.045]. Conclusion Patients with COPD exacerbator phenotype had a greater magnitude of response to PRP (36 meters) when compared to non-exacerbator phenotype regardless the severity of airflow obstruction, also showing improvement in prognosis measured by the BODE index.

Frailty-associated factors among Brazilian community-dwelling elderly people: longitudinal study

ABSTRACT BACKGROUND: Frailty among elderly people is associated with negative health outcomes. Through gaining better understanding of this syndrome over different time periods, healthcare actions that take predictive factors into consideration may be facilitated. OBJECTIVE: To identify factors associated with frailty syndrome among community-dwelling elderly people over a two-year follow-up. DESIGN AND SETTING: Longitudinal study on elderly people living in Uberaba (MG), Brazil. Methods: Elderly individuals were selected through multiple-stage conglomerate sampling from a national database. Participants were interviewed and evaluated in 2014 and again in 2016. Predictors were considered at the baseline, and frailty categories (frail, pre-frail or non-frail) at the follow-up. Frailty was identified based on the Fried criteria. Associations with socioeconomic factors, health status and physical performance were investigated using multinomial logistic regression. RESULTS: 353 individuals participated in both assessments. The final model showed that age over 80 years was predictive of both pre-frailty and frailty (odds ratio, OR 4.92; 95% confidence interval, CI: 1.57-15.38; OR 8.64; 95% CI: 2.05-36.35, respectively), while dependency regarding basic activities of daily living (OR 3.66; 95% CI: 1.22-11.02) and poor lower-limb physical performance (OR 7.87; 95% CI: 1.97-31.39) predicted frailty. A one-unit increased score for advanced activities of daily living decreased the frailty rate by 15% (OR 0.85; 95% CI: 0.74-0.99). CONCLUSION: Age over 80 years was predictive of pre-frailty and frailty, while dependency in basic activities of daily living and poor physical performance predicted frailty. A one-unit increased score for advanced activities of daily living decreased the frailty rate by 15%.

Small airway disease in COPD associated to biomass exposure

Abstract Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world's population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors

Abstract: BACKGROUND: Approximately five to 10% of all melanomas occur in families with hereditary predisposition and the main high-risk melanoma susceptibility gene is the CDKN2A. OBJECTIVES: To describe, after a five-years study, the clinical data of patients (probands) from familial melanoma kindreds, and the pathological characteristics of their melanoma. METHODS: The inclusion criteria were melanoma patients with a family history of melanoma or pancreatic cancer (first- or second-degree relatives) or patients with multiple primary melanomas (MPM). RESULTS: A total of 124 probands were studied, where 64 were considered familial cases and 60 MPM. Mean age at diagnosis was 50 years. Our results show that the following characteristics were prevalent: skin phototype I/II (89.5%), sunburn during childhood (85.5%), total number of nevi ≥50 (56.5%), Breslow thickness ≤1.0mm (70.2%), tumors located on the trunk (53.2%) and superficial spreading melanomas (70.2%). STUDY LIMITATIONS: Analyses of probands' relatives will be demonstrated in future publication. CONCLUSIONS: Our findings are in agreement with previous familial melanomas reports. Fifteen new melanomas in 11 patients were diagnosed during follow up, all of which were ≤1.0 mm. This is the largest dataset of Brazilian melanoma prone kindreds to date, thus providing a complete database for future genetic studies.

Hypertriglyceridemic Waist Phenotype and Changes in the Fasting Glycemia and Blood Pressure in Children and Adolescents Over One-Year Follow-Up Period / Fenótipo Cintura Hipertrigliceridêmica e mudanças na glicemia de jejum e pressão arterial de crianças e adolescentes após um ano de seguimento

Abstract Background: The hypertriglyceridemic waist (HTW) phenotype is defined as the simultaneous presence of increased waist circumference (WC) and serum triglycerides (TG) levels and it has been associated with cardiometabolic risk in children and adolescents. Objective: The objective was to evaluate the influence of HTW phenotype in the fasting glycemia and blood pressure in children and adolescents over one-year follow-up period. Methods: It is a cohort study involving 492 children and adolescents from 7 to 15 years old, both genders, who were submitted to anthropometric, biochemical and clinical evaluation at the baseline, and also after 6 and 12 months of follow-up. Generalized Estimating Equation (GEE) models were calculated to evaluate the longitudinal influence of the HTW phenotype in the glycemia and blood pressure over one-year. Results: It was observed a prevalence of 10.6% (n = 52) of HTW phenotype in the students. The GEE models identified that students with HTW phenotype had an increase of 3.87 mg/dl in the fasting glycemia mean (CI: 1.68-6.05) and of 3.67mmHg in the systolic blood pressure (SBP) mean (CI: 1.55-6.08) over one-year follow-up, after adjusting for confounding variables. Conclusions: The results of this study suggest that HTW phenotype is a risk factor for longitudinal changes in glycemia and SBP in children and adolescents over one-year follow-up period.

Resumo Fundamento: O fenótipo de cintura hipertrigliceridêmica (CHT) é definido como a presença simultânea de circunferência de cintura (CC) e níveis séricos de triglicérides (TG) aumentados e tem sido associado com risco cardiometabólico em crianças e adolescentes. Objetivo: Avaliar a influência do fenótipo CHT na glicemia de jejum e na pressão arterial em crianças e adolescentes em um período de acompanhamento de um ano. Métodos: Trata-se de um estudo de coorte envolvendo 492 crianças e adolescentes de 7 a 15 anos de ambos os sexos, que foram submetidos à avaliação antropométrica, bioquímica e clínica no início e também após 6 e 12 meses de seguimento. Os modelos de Equação de Estimulação Generalizada (GEE) foram calculados para avaliar a influência longitudinal do fenótipo CHT na glicemia e na pressão arterial ao longo de um ano. Resultados: Foi observada uma prevalência de 10,6% (n = 52) do fenótipo CHT nos estudantes. Os modelos GEE identificaram que os estudantes com fenótipo CHT apresentaram aumento de 3,87 mg/dl na média de glicemia em jejum (IC: 1,68-6,05) e de 3,67 mmHg na pressão arterial sistólica media (PAS) (IC: 1,55-6,08) depois de um ano de acompanhamento, após ajuste para variáveis de confusão. Conclusões: Os resultados deste estudo sugerem que o fenótipo CHT é um fator de risco para alterações longitudinais da glicemia e da PAS em crianças e adolescentes em um período de um ano de seguimento.

Kraepelin's description of chronic mania: a clinical picture that meets the behavioral variant frontotemporal dementia phenotype / A descrição de Kraepelin de mania crônica: um quadro clínico que corresponde ao fenótipo da variante comportamental da demência fronto-temporal

ABSTRACT Chronic mania is an under-investigated condition and few reports have associated this disorder with an organic background. The present work examines Kraepelin’s reliable description of chronic mania from a current behavioral neurology viewpoint. Kraepelin had described a cluster of symptoms that are now recognized as core manifestations of the behavioral variant frontotemporal dementia (bvFTD) clinical phenotype. We also carried out additional reviews of original manuscripts from Kraepelin’s peers, in order to find any case reports that might fulfill the current diagnostic proposal for bvFTD. Even though we failed to find an ideal case, we found some scholars who seemed to agree that chronic mania should be considered a special form of dementia. The present work highlights, through historical data, the possible overlapping features between primary psychiatric disorders and neuropsychiatric symptoms secondary to neurodegenerative conditions.

RESUMO A mania crônica constitui uma condição subinvestigada e alguns trabalhos têm associado esta desordem a um substrato orgânico. O presente manuscrito analisa a descrição fidedigna de Kraepelin de mania crônica a partir de um ponto de vista atual da neurologia comportamental. Concebemos que ele havia descrito um conjunto de sintomas que atualmente é reconhecido como manifestações centrais do fenótipo clínico da variante comportamental da demência frontotemporal (bvFTD). Também realizamos uma revisão adicional de manuscritos originais de pares contemporâneos de Kraepelin, a fim de procurar por um único relato de caso que poderia preencher critério diagnóstico atual de bvFTD. Mesmo que não tenhamos conseguido encontrar um caso perfeitamente exemplar, identificamos que alguns estudiosos da época pareciam concordar que a mania crônica devesse ser considerada uma forma especial de demência. O presente trabalho destaca por meio de dados históricos a sobreposição entre transtornos psiquiátricos primários e sintomas neuropsiquiátricos secundários a doenças neurodegenerativas.

Perspectiva sobre el perfil microbiológico de las neumonías asociadas a ventilación mecánica en hospitales de alta complejidad en Latinoamérica / Perspective on the microbiological profile of pneumonia associated with mechanical ventilation in high complexity hospitals in Latin America

La prevalencia de infección es elevada en hospitales de alta complejidad y es una de las causas más importantes de mortalidad a nivel mundial. Dentro de las infecciones intrahospitalarias más comunes y con una de las tasas de mortalidad más elevadas se encuentra la neumonía asociada a ventilación mecánica (NAVM), infección pulmonar que se desarrolla 48 horas o más después de un proceso de intubación traqueal sin evidencia previa de incubación microbiana del tracto respiratorio. La evidencia actual sugiere que la NAVM se relaciona con un incremento de la mortalidad, una prolongación de la estancia en unidades de cuidados intensivos y mayores costos de hospitalización. El objetivo de este artículo es describir las características patogénicas y los factores de riesgo que impactan en la mortalidad y supervivencia de los pacientes que desarrollan NAVM en hospitales de alta complejidad en Latinoamérica con el fin de facilitar la toma de decisiones por parte del médico tratante al momento de enfrentar esta patología.

The prevalence of infection is higher in hospitals of high complexity and is one of the most important causes of mortality worldwide. Ventilator associated pneumonia (VAP) is one of the most common infection and have one of the highest mortality rates of nosocomial infections. VAP is defined like a lung infection that develops 48 hours or more after tracheal intubation process without prior evidence of microbial incubation in the respiratory tract. Current evidence suggests that VAP is associated with increased mortality, prolonged Intensive Care Unit stay and higher hospitalization costs. The aim of this article is to describe the pathogenic characteristics and risk factors that impact on mortality and survival of patients who develop VAP in major hospitals in Latin America in order to facilitate decision-making by the treating physician in this disease.

Frecuencia de genes HLA en pacientes con insuficiencia renal crónica procedentes del occidente y centro de Cuba / Frequency of HLA genes in patients with chronic kidney insufficiency, from western and central Cuba

Introducción: el trasplante es la terapia que permite la mayor sobrevida a los pacientes con insuficiencia renal crónica. Para prevenir el rechazo del órgano, en primer lugar es necesario un estudio de la compatibilidad de los antígenos leucocitarios humanos (HLA) del paciente y de los posibles donantes. En Cuba solo se había realizado la tipificación HLA por métodos serológicos, pero en la actualidad se emplean técnicas moleculares. Objetivo: caracterizar el polimorfismo de los alelos HLA A, B, DR y DQ por métodos moleculares en pacientes cubanos en espera de trasplante renal. Métodos: se estudiaron 410 pacientes con insuficiencia renal crónica de las regiones occidental y central del país a los que se les realizó tipificación molecular de los loci mencionados. Los resultados se expresaron según la nueva nomenclatura y fueron registrados en una base de datos confeccionada al efecto. Se compararon las frecuencias alélicas de la población blanca y no blanca y se determinó el porcentaje de frecuencia de los haplotipos para los alelos clase I y II. Resultados: los alelos A*11, A*30, A*74, B*42, B*51 y B*53 fueron más frecuentes en la población blanca mientras que los alelos B*58 y DRB1* 15 predominaron en los no blancos. Las frecuencias haplotípicas más encontradas en la clase I en la población blanca fueron A*02 B*51, A*02 B*44, A*02 B*35; y en la no blanca, A*01B*08, A*02B*51, A*02B*44. Para los alelos de la clase II, en la población blanca fueron DQB1*03, DRB1*04, DQB1*06, DRB1*13, DRB1*05, DRB1*01; y en los no blancos, DQB1*03, DRB1*04, DQB1*06, DRB1*13, DQB1*05, DRB1*01. Conclusiones: la caracterización de los pacientes con insuficiencia renal crónica con respecto a su tipificación HLA permitirá trazar estrategias futuras relacionadas con la donación y el trasplante en todo el país(AU)

Introduction: transplantation is the therapy allowing the highest possible survival in patients with chronic kidney insufficiency. To prevent rejection of the organ, first of all it is necessary to make a compatibility test of human leukocyte antigens (HLA) from the patient and the possible donors. In Cuba, only serological HLA typing had been made but at present, molecular techniques are being applied. Aim: characterization of polimorfirsm of alleles HLA A, B, DR y DQ by molecular techniques in Cuban patients awaiting renal transplantation. Methods: four hundred and ten patients with chronic kidney insufficiency from Western and Central Cuba were studied by molecular typing of the above mentioned loci. Results were expressed by the new nomenclature and were registered In a data base prepared for that purpose. Allele frequencies of white and no white population were compared and percentage of haplotype frequencies for alleles class I and II were determined. Results: alleles A*11, A*30, A*74, B*42, B*51and B*53 were more frequent in white population while B*58 y DRB1*, 15 were mostly found in no whites. Haplotypic frequencies most found in class I in white population were A*02 B*51, A*02 B*44, A*02 B*35; and in no whites, A*01B*08, A*02B*51, A*02B*44. For class II alleles, DQB1*03, DRB1*04, DQB1*06, DRB1*13, DRB1*05, DRB1*01 were the most found in white population; and in no whites, DQB1*03, DRB1*04, DQB1*06, DRB1*13, DQB1*05, DRB1*01. Conclusions: characterization of patients with chronic kidney insufficiency in respect to HLA typing will allow future strategies related to kidney donation and transplantation in the whole country(AU)

Fenotipos clínicos en enfermedad pulmonar obstructiva crónica: ¿volver al futuro? / Clinical phenotypes in chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, that is defined by the degree of obstruction rendered by the forced expiratory volume in the first second (FEVj). This is a good parameter to define the severity of the disease but does not account for its heterogeneity and does not provide a good comprehension of its different clinical behaviors and responses to treatment. Therefore, the classification of these patients in different clinical phenotypes has been attempted, trying to search for common clinical behaviors and responses to treatment. These phenoptypes must be validated in longitudinal studies. Some of the phenotypes detected are COPD with chronic respiratory failure and responsive to home oxygen therapy, COPD with upper lobe emphysema and responsive to volume reduction surgery, COPD with frequent exacerbation behavior, COPD resembling bronchitis and responsive to Roflumilast and possibly, COPD with systemic involvement. Historically, the phenotypes pink puffer, blue bloater, chronic bronchitis were defined. In the next years, we will know if the definitions of these phenotypes will aid in the management of patients with COPD.

A Imunologia da infecção pelo HIV em pacientes com idade avançada: caracterização fenotípica e funcional da resposta imune mediada pela célula T CD4+ / Immunology of HIV infection in patients with advanced age: phenotypic and functional immune response mediated by CD4+ cell

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-y. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN-y e hiperprodução de IL-10, como na resposta ao TT...

The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-y. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN-y and hyperproduction of IL-10, like in response to TT...

Gender differences in obsessive-compulsive disorder: a literature review / Diferenças de gênero no transtorno obsessivo-compulsivo: uma revisão da literatura

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a heterogeneous condition, in which subtypes have been proposed. Previous studies suggested that gender plays a relevant role in OCD phenotypic expression. This study aimed to review the literature on gender differences in clinical, genetic or familial aspects of OCD. METHOD: A conventional review was conducted, including all papers that investigated demographic, clinical, and genetic aspects of OCD according to gender. The search was based on data available in Medline and PsycINFO databases in the last 20 years, using as keywords: obsessive-compulsive disorder; and: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTS: Sixty three of 487 phenotypical and genetics studies were selected. Most studies indicate that male patients are more likely than females to be single, present early onset of symptoms and chronic course of the disorder, greater social impairment, more sexual-religious and aggressive symptoms, and greater comorbidity with tic and substance use disorders. Female patients present more contamination/cleaning symptoms and greater comorbidity with eating and impulse-control disorders. Genetic and family studies are inconclusive, but suggest that gender may play a role in the disease expression. CONCLUSIONS: Gender is a relevant factor that should be taken into account when evaluating OCD patients. More studies are necessary to determine whether in fact it defines a homogeneous and particular group in OCD.

INTRODUÇÃO: O transtorno obsessivo-compulsivo (TOC) é um quadro heterogêneo, no qual subtipos têm sido propostos. Estudos anteriores sugerem que gênero desempenha papel relevante na expressão fenotípica. O objetivo foi realizar uma revisão convencional da literatura sobre diferenças de gênero em relação a aspectos clínicos e genéticos ou familiares do TOC. MÉTODO: Realizou-se uma revisão convencional da literatura incluindo todos os artigos que investigaram aspectos sociodemográficos, clínicos e genéticos do TOC, de acordo com o gênero. A pesquisa foi baseada em publicações disponíveis nas bases de dados Medline e PsycInfo nos últimos 20 anos, usando como palavras-chave: obsessive-compulsive disorder (OCD), e: gender, sex, male, female, demographic characteristics, clinical features, clinical characteristics, genetic, genes, genetics gender OCD, genes OCD, genes OCD males, genes OCD females. RESULTADO: Sessenta e três artigos de fenótipo e genética foram selecionados. Na maioria dos estudos, o sexo masculino associou-se mais que o feminino com: ser solteiro, apresentar início mais precoce dos sintomas, maior prejuízo social, mais sintomas sexuais, religiosos e de agressão, e mais comorbidade com transtorno de tiques e abuso de substâncias. Pacientes do sexo feminino apresentam mais sintomas de contaminação/limpeza e mais comorbidade com transtornos alimentares e do controle de impulsos. Estudos genéticos e familiares são controversos, mas indicam que o gênero pode desempenhar um papel na expressão da doença. CONCLUSÃO: Gênero é um fator relevante a ser considerado na avaliação de pacientes com TOC. São necessários mais estudos para determinar se este fator define de fato um grupo homogêneo e particular de TOC.

Hemoglobin S/hemoglobin city of hope compound heterozygote with a subsaharan genetic background and severe bone marrow hypoplasia

Hemoglobin City of Hope (HbCH) (HBB: c.208G>A, beta 69 (E13)Gly>Ser) is a rare, anomalous change. Seven independent carriers reported so far, had not displayed any hematological manifestations. The ethnic origin of the known instances is presumably heterogeneous, although they are mainly Mediterraneans or equatorial West Africans. We describe the case of a compound heterozygote in trans for Hb S (Glu6Val) and Hb City of Hope (Gly69Ser) in an anemic two year-old boy with a severe immune-deficient phenotype and fatal chronic parvovirus B19 infection. Haplotype with the Hb S was Bantu; while it was a mixed atypical Benin/Cameroon for Hb CH. Remote ancestral origin of the City of Hope mutation in this family seems to be SubSaharan African. The compound heterozygosis in trans for hemoglobins S and City of Hope, jointly with an unfavorable HBB control region background and a viral chronic infection, seemed the cause of the fatal outcome in the patient. When accompanied by other Hb deleterious mutations in trans, Hb CH should not be considered any longer as an innocuous or functionally silent variant.

La hemoglobina City of Hope (HbCH) (HBB: c.208G>A, beta 69 (E13)Gly>Ser) es una variante infrecuente, considerada como anómala. Ninguno de los siete heterocigotos simples, genéticamente no relacionados, reportados hasta ahora, ha mostrado hemopatología. El origen étnico de esos casos es presuntamente heterogéneo, pero la mayoría parece mediterráneo o africano-ecuatorial occidental. Se describe el caso de un niño de dos años de edad con fenotipo hipoplásico mieloeritroideo severo e infección crónica por parvovirus B19, heterocigoto compuesto en trans para las hemoglobinas S (Glu6Val) y City of Hope (Gly69Ser ). El haplotipo en fase con la Hb S fue Bantú, mientras que el de la Hb CH fue un combinado atípico Benin/Camerún. El origen ancestral remoto de la mutación City of Hope (y de la Hb S) en esta familia es africano subsahariano. La heterocigosis compuesta en trans para las hemoglobinas S y City of Hope y una secuencia génica predisponente en la región de control de HBB, conjuntamente con la infección por parvovirus B19 pueden ser la causa del curso fatal del paciente. En presencia de otras mutaciones de hemoglobina deletéreas, la Hb City of Hope no debiera ser considerada una variante inocua o funcionalmente silenciosa.

Fibrosis quística: la frontera del conocimiento molecular y sus aplicaciones clínicas / Cystic fibrosis: molecular update and clinical implications

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic pneumopathy, pancreatic insufficiency, elevated sweat chloride levels and male infertility. It is caused by defects in the CF trans membrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel. The identification of the CF-causing gene was a landmark in molecular medicine. Currently, over 1,300 disease-causing mutations have been reported to the Cystic fibrosis genetic analysis consortium. ÁF508 mutation is the most common CF alíele, however a high heterogeneity of the CFTR mutations spectrum has been observed in populations, particularly in southern Europe and Latin America. Depending on the effect at the protein level, CFTR mutations can be divided in at least 5 classes. These mutations could cause totally (classes I-III) or partially (classes IV and V) loss of the protein function. The molecular defects resulting from different mutations in CFTR partially explain the clinical heterogeneity of the disease, suggesting the existence of modifier genes that are involved in modulating the phenotype and severity of the CF. In this review, we discuss the fundamental aspects and the recent progress that could give to the lector, the knowledge to understand the CFTR gene structure, the function of the CFTR protein, how CF mutations disrupt it, its phenotype consequences and finally, the strategies to design new therapies for the disease.

La fibrosis quística (FQ) es un padecimiento autosómico recesivo que se caracteriza por neumopatía crónica, insuficiencia pancreática, elevación de cloruros en sudor e infertilidad masculina. Esta patología es causada por la presencia de mutaciones en el gen CFTR que codifica para un canal de cloro denominado proteína reguladora de la conductancia transmembranal (CFTR). Hasta la fecha se han reportado alrededor de 1,300 mutaciones diferentes, cuya frecuencia varía entre los diversos grupos étnicos. Estas mutaciones condicionan la pérdida total (clases I, II y III) o parcial (clases IV y V) de la función de la proteína y causan un defecto en el transporte de electrólitos en la membrana apical de las células epiteliales. Con excepción de la función pancreática, las manifestaciones clínicas de la FQ son variables aun en pacientes con el mismo genotipo, por lo que la presencia de las diferentes mutaciones en el CFTR explica sólo parcialmente la heterogeneidad clínica de la FQ. Recientemente se ha propuesto que otros genes denominados genes modificadores participan en la gravedad del cuadro clínico. Así, la FQ es una enfermedad genética que resulta en un amplio espectro de manifestaciones clínicas que pueden ir desde muy leves hasta conducir a la muerte durante los primeros meses de vida, por lo que en algunos casos el diagnóstico es sumamente complejo. En los últimos años, el gran alud de conocimientos ha permitido entender el defecto básico de la enfermedad y los mecanismos que la condicionan, por lo que en esta revisión se discuten los fundamentos para el entendimiento de la fisiopatología de la FQ, desde los aspectos clínicos hasta los avances moleculares más recientes.

Estimation of malaria transmission in high-risk provinces of Morocco

The malaria transmission level of Plasmodium vivax was monitored in four high-risk provinces in Morocco. Intensive mosquito collection by light traps and manual catches resulted in the capture of four species: Anopheles labranchiae, An. sergenti, An. cinereus, and An. claviger. All An. sergenti and An. labranchiae females collected were tested for the presence of two phenotypes of P. vivax [PVK210 and PVK247] antigen by enzyme-linked immunosorbent assay [ELISA]. No P. vivax antigen was detected in 1347 mosquitoes analysed. A parallel parasitological investigation was conducted. Of 2665 slides examined from a population of 4343 people for detection of P. vivax, no slide was positive. The results confirm the break in malaria transmission in residual foci. The use of ELISA is recommended in future epidemiological studies of human malaria