A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Deconstructing Phenotypes in COPD: an Analysis of the TRACE Cohort. / Deconstruyendo los fenotipos en la EPOC: un análisis de la cohorte TRACE.

OBJECTIVES: In a clinical phenotype-based management strategy for COPD, it would be preferable to at least assign all patients to a phenotype, but to a single phenotype only. The aim of this study was to evaluate whether all patients are assigned to one and only one phenotype using the Spanish COPD guidelines (GesEPOC) and to evaluate the criteria that define these categories. METHOD: The Time-based Register and Analysis of COPD Endpoints study (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients attending annual visits since 2012, which collects GesEPOC phenotypes. Although the GesEPOC recommends that patients considered to be at low risk are not phenotyped, an analysis of the criteria for identifying high- and low-risk phenotypes was performed, comparing the distribution of phenotypes and the criteria applied between these 2 groups. RESULTS: The cohort included 970 patients with a confirmed diagnosis of COPD, divided into 427 (44.02%) low-risk and 543 (55.9%) high-risk patients. The most frequent phenotype was the non-exacerbator (44.9% of high-risk patients). Overall, 20.6% of low-risk patients met criteria for asthma-COPD overlap syndrome, while 9.2% of the cohort did not meet the diagnostic criteria for any phenotype, and 19.1% met the criteria for 2 phenotypes, with no differences between risk groups. CONCLUSIONS: Our data highlight some of the weaknesses of the current clinical phenotype strategy, revealing overlapping categories in some cases, and patients to whom no phenotype was assigned.

Bronchiectasis: A Complex, Heterogeneous Disease. / Las bronquiectasias: una enfermedad compleja y heterogénea.

Most areas of respiratory medicine continue to use an Oslerian approach, based on signs and symptoms, in which the disease is the center of all activity. However, this paradigm is changing. Now that lung diseases have been recognized as heterogeneous and complex, we are moving towards more personalized, precise, patient-oriented medicine. The aim of this review was to define the current state of the knowledge on bronchiectasis, or, more accurately, the bronchiectasis syndrome, as a multidimensional, systemic, heterogeneous, complex disease. We explore the advances that have already been made, and above all the many steps that are still to be taken. We also propose some tools which might facilitate the application of these concepts in clinical practice, and help us continue our journey towards a more holistic view of this disease.

Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. METHODS: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n=91) and controls (n=97). RESULTS AND CONCLUSIONS: The 857GA genotype was more prevalent among nonwhite SLE patients (OR=4.01, 95% CI=1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR=1.97; 95% CI=1.01-3.81).

Fenotipos clínicos en el síndrome de apnea obstructiva del sueño / Clinical phenotypes in obstructive sleep apnea

El síndrome de apnea e hipopnea obstructiva del sueño se caracteriza por episodios repetitivos de obstrucción de vía aérea superior y es reconocida cada vez más, como un trastorno heterogéneo y complejo, proponiéndose múltiples fenotipos en base a su mecanismo patogénico, alteraciones polisomnográficas y la presentación clínica. El fenotipo clínico se enfoca en identificar características de un paciente basándose en signos, síntomas, antropometría, comorbilidades, medidas fisiológicas, anatómicas o respuesta al tratamiento. Al ser una enfermedad sub diagnosticada, de alta prevalencia y que produce elevada morbi-mortalidad, se debe estar atento a la pesquisa precoz y en las poblaciones de riesgo. Su diagnóstico se basa en el índice de apnea-hipopnea (IAH) y se requiere un IAH •5 eventos/hora para confirmar el diagnóstico. Sin embargo, cada vez hay más evidencia que el IAH por sí solo es insuficiente para comprender la presentación clínica, respuesta al tratamiento, calidad de vida y mortalidad de los pacientes con apnea del sueño. El fenotipo clínico puede servir de este modo, para entender mejor las diferentes formas de presentación teniendo como finalidad la medicina personalizada con el objetivo de favorecer la conducta terapéutica individualizada. El objetivo de esta revisión es abordar los fenotipos clínicos y proponer una huella digital en los pacientes con apnea del sueño

Obstructive sleep apnea and hypopnea syndrome is characterized by repetitive episodes of upper airway obstruction and is increasingly recognized as a heterogeneous and complex disorder, proposing multiple phenotypes based on its pathogenic mechanism, polysomnographic alterations, and clinical presentation. The clinical phenotype focuses on identifying a patient's characteristics based on signs, symptoms, anthropometry, comorbidities, physiological, anatomical measures or response to treatment. As it is an underdiagnosed disease of high prevalence associated to high morbidity and mortality, we must be alert to early screening and risk populations. Diagnosis is based on the apnea-hypopnea index (AHI) AHI •5 events/hour is required to confirm it, however, there is increasing evidence that AHI alone is insufficient to understand the clinical presentation, the response to treatment, the quality of life and the mortality of patients with sleep apnea. In this way, the clinical phenotype can serve to better understand the different forms of presentation and looks for a personalized medicine that favors an individualized therapeutic behavior. The aim of this review is to address clinical phenotypes and propose a fingerprint in patients with sleep apnea

Fenotipos clínicos de la enfermedad pulmonar obstructiva crónica en los pacientes atendidos en el Hospital neumológico de La Habana / Clinical phenotypes of chronic obstructive pulmonary disease in patients treated at the Hospital Neumológico de La Habana

Introducción: La identificación de los fenotipos clínicos son claves en la modulación de la expresión clínica, para un tratamiento integrado de la EPOC. Objetivos: Caracterizar los fenotipos clínicos de la EPOC en los pacientes atendidos en el Hospital Neumológico Benéfico Jurídico. Métodos:Se realizó un estudio observacional descriptivo retrospectivo, en 172 pacientes con diagnóstico de EPOC, en el Hospital Neumológico Benéfico Jurídico durante el año 2017.Resultados: El 38,4 % de los pacientes tenían edad entre 70-79 años. Del total de pacientes, el 54,6 % eran del sexo masculino. El 52,9 % eran fumadores activos y el 41,3 % exfumadores. Aunque las diferencias no fueron significativas, la edad avanzada y el sexo masculino fueron más frecuentes en el fenotipo enfisematoso agudizador y agudizador bronquítico crónico. El tabaquismo activo fue más frecuente en el fenotipo enfisematoso agudizador. Todos los pacientes con el fenotipo agudizador bronquítico crónico tuvieron dos o más exacerbaciones, mientras que el enfisematoso agudizador se relacionó con una severidad grave de la EPOC (46,7 %). Conclusiones: El sexo masculino y la edad avanzada muestran una tendencia a relacionarse con el fenotipo enfisematoso agudizador y agudizador bronquítico crónico, mientras que el tabaquismo activo es más frecuente en el fenotipo enfisematoso agudizador. El fenotipo agudizador bronquítico crónico se relaciona con mayores exacerbaciones y el enfisematoso agudizador con una mayor severidad de la EPOC.

Introduction: The identification of clinical phenotypes are key in the modulation of clinical expression, for an integrated treatment of COPD. Objectives: To characterize the clinical phenotypes of COPD in patients treated at the Hospital Neumológico Benéfico Jurídico. Methods: A retrospective descriptive observational study was carried out in 172 patients with a diagnosis of COPD at the Hospital Neumológico Benéfico Jurídico in 2017. Results: 38.4 % of the patients were between 70-79 years of age. Of the total number of patients, 54.6 % were male. 52.9 % were active smokers and 41.3 % ex-smokers. Although the differences were not significant, advanced age and male sex were more frequent in the exacerbator emphysematous and chronic bronchial exacerbator phenotype. Active smoking was more frequent in the exacerbating emphysematous phenotype. All patients with the chronic bronchial exacerbator phenotype had two or more exacerbations, while exacerbation emphysematous was associated with severe severity of COPD (46.7 %). Conclusions: Male sex and advanced age show a tendency to be related to the exacerbating emphysematous phenotype and chronic bronchitis exacerbator, while active smoking is more frequent in the exacerbating emphysematous phenotype. The chronic bronchitis exacerbator phenotype is related to greater exacerbations and exacerbation emphysematous with a greater severity of COPD

Prognostic value of capillaroscopy in organ involvement and identification of subtypes in systemic sclerosis (SS): A systematic literature review / Valor pronóstico de la capilaroscopia en el compromiso de órganos e identificación de subtipos en la esclerosis sistémica (ES): una revisión sistemática de la literatura

ABSTRACT Background: Capillaroscopy is an essential tool for the diagnosis of systemic sclerosis. Using this exam as a prognostic factor will allow earlier intervention and probably, delay on disease progression. We aimed to evaluate the prognostic value of capillaroscopy for the prediction of systemic compromise and subtype differentiation in systemic sclerosis. Methods: A systematic literature search was applied in the following electronic databases: Medline, PubMed, Embase, Cochrane, and Lilacs. The research question was designed based on the PICOT model, and the search strategy was built using the MeSH terms "Microscopic Angioscopy," "Scleroderma systemic," "Scleroderma diffuse," Scleroderma Limited," "Early Diagnosis" and Boolean operators. The language was restricted to papers published in Spanish or English, from 1990 to 2019. The search terms were explored for each database, and new terms were added, as appropriate. The searches were made again before the final analyses and further studies were retrieved for inclusion at that time. Reference lists of included studies and recent aligned systematic reviews were also screened. Gray literature was not considered in this review. Results: A total of 183 articles were found in the selected databases: Medline (n: 115), Embase (n: 66), Cochrane (n: 2), Lilacs (n: 0). After excluding articles due to duplication, a total of 66 studies were selected. Within these articles, a screening process was applied based on the title and abstract, taking into account the eligibility criteria, finally obtaining 21 references. Two researchers assessed the selected articles, and all disagreements were solved by consensus. Finally, a total of 14 articles were included. Conclusions: The different abnormalities found in capillaroscopy, especially loss of capillaries, have been consistently associated not only with organ involvement but also with severity of the disease, especially with vascular manifestations (digital ulcers and pulmonary hypertension). The importance of capillaroscopy is not only its diagnostic value but also its predictive value with its consequent implications in the follow-up and management of systemic sclerosis.

RESUMEN Introducción: La capilaroscopia es una herramienta esencial para el diagnóstico de la esclerosis sistémica. Usar este examen como factor pronóstico permitirá realizar una intervención temprana y probablemente retardará la progresión de la enfermedad. Se realizó una revisión de la literatura evaluando el valor pronóstico de la capilaroscopia para predecir el compromiso sistémico de la esclerosis sistémica y su diferenciación por subtipos. Métodos: Se realizó una revisión sistemática de la literatura en las siguientes bases de datos: Medline, PubMed, Embase, Cochrane y Lilacs. La búsqueda se hizo basada en el modelo PICOT y la estrategia de búsqueda fue construida mediante los términos MeSH «Microscopic angioscopy¼, «Scleroderma systemic¼, «Scleroderma diffuse¼, «Scleroderma limited¼, «Early diagnosis¼ y operadores booleanos. El lenguaje fue restringido a artículos publicados en español e inglés desde 1990 hasta 2019. Se realizó la búsqueda en cada base de datos y se adicionaron nuevos términos según fuera apropiado. La búsqueda se realizó de nuevo al final del análisis y se incluyeron los estudios más recientes. La lista de referencias de los estudios incluidos y las revisiones sistemáticas recientemente adicionadas también fueron registradas. No se consideró literatura gris en esta revisión. Resultados: Un total de 183 artículos fueron encontrados en las siguientes bases de datos: Medline (n = 115), Embase (n = 66), Cochrane (n = 2), Lilacs (n = 0). Después de excluir los que estaban duplicados, un total de 66 estudios fueron seleccionados. Dentro de estos artículos, se realizó un proceso de selección basado en título y resumen tomando en cuenta los criterios de elegibilidad, obteniendo finalmente 21 referencias. Dos investigadores revisaron los artículos seleccionados y todas las discrepancias fueron resueltas en consenso. Finalmente, un total de 14 artículos fueron incluidos. Conclusiones: Las diferentes anormalidades encontradas en la capilaroscopia, especialmente la pérdida de capilares, han sido constantemente asociadas no solo con compromiso de órganos sino también a la severidad de la enfermedad, especialmente con manifestaciones vasculares (úlceras digitales e hipertensión pulmonar). La importancia de la capilaroscopia no solo es por su valor diagnóstico sino también por su valor predictivo en relación al seguimiento y manejo de la esclerosis sistémica.

Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus / Polimorfismos no gene NAT2 (N-acetiltransferase 2) em pacientes com lúpus eritematoso sistêmico

ABSTRACT Objective: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. Methods: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n = 91) and controls (n = 97). Results and conclusions: The 857GA genotype was more prevalent among nonwhite SLE patients (OR = 4.01, 95% CI = 1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR = 1.97; 95% CI = 1.01-3.81).

RESUMO Objetivo: Investigar potenciais associações de quatro substituições do gene NAT2 (N-acetiltransferase 2) e do fenótipo acetilador de NAT2 com o lúpus eritematoso sistêmico (LES) e os fenótipos clínicos. Métodos: A análise molecular das substituições 481C > T, 590G > A, 857G > A e 191G > A do gene NAT2 foi feita com a técnica de PCR-RFLP, usando DNA extraído de amostras de sangue periférico obtidas de pacientes com LES (n = 91) e controles (n = 97). Resultados e conclusões: O genótipo 857GA foi mais prevalente entre pacientes com LES não brancas (OR = 4,01, IC 95% = 1,18-13,59). O alelo 481 T apresentou associação positiva com as alterações hematológicas que envolvem mecanismos autoimunes, especificamente anemia hemolítica autoimune ou trombocitopenia autoimune (OR = 1,97; IC 95% = 1,01-3,81).