Observaciones a partir del registro de evaluación cardiológica pos-COVID-19

Objetivo: Evaluar la prevalencia y características de los hallazgos cardiológicos "de Novo" (HCDN) en pacientes pos-COVID a partir de una secuencia diagnóstica cardiológica básica; asimismo, describir los resultados obtenidos en estos pacientes con los distintos métodos diagnósticos, detectar variables clínicas asociadas a la aparición de HCDN durante la evaluación y, por último, detectar el valor diagnóstico de distintos datos de la historia clínica (HC). Materiales y métodos: Se evaluó a pacientes >18 años que padecieron la COVID-19, internados o en su domicilio, mediante interrogatorio, examen físico, electrocardiograma (ECG), ecocardiograma (ECO), rutina de laboratorio y biomarcadores cardíacos entre los 30 y 120 días después del alta. Se incluyeron 246 pacientes (edad: 52 ± 13 años; mujeres: 48 %; COVID-19 leve [37 %], moderado [39 %], grave [24 %]). El 24 % de la población no presentaba síntomas en el momento de la evaluación; en los sintomáticos, la disnea fue lo más frecuente (28 %). El interrogatorio fue el método que reveló mayor porcentaje de sospecha (45 %). El examen físico, el ECG, el ECO y los biomarcadores fueron normales en el 60 %, 55 %, 75 % y 96 % de los pacientes, respectivamente. Resultados: Se detectaron HCDN en 62 pacientes (25,2 %): trastornos del ritmo en 42 (17 %) y disfunción ventricular en 20 (8 %). Cinco presentaron enfermedad coronaria; 6, miocarditis, y 2, valvulopatías. Además, se detectó tromboembolismo pulmonar (TEP) pos-COVID en 10 pacientes, de los cuales seis (2,4 %) debieron internarse nuevamente. Asimismo, en un análisis multivariado, las variables predictoras independientes de los HCDN fueron antecedentes de enfermedad pulmonar obstructiva crónica (EPOC), intervalo QTc > 440 ms, leucocitosis y complicación cardiológica intra-COVID (CCIC). La HC mostró baja sensibilidad y valor predictivo positivo para los HCDN. Conclusiones: Aunque los HCDN se observaron en un cuarto de la población, solo fueron relevantes en el 2 %. De acuerdo con estos datos, mediante esta secuencia diagnóstica y en este lapso, el énfasis debería estar puesto en los pacientes con antecedentes de EPOC y/o complicaciones cardiológicas durante la etapa aguda y/o intervalo QTc prolongado. Los síntomas pos-COVID tuvieron un valor limitado para el diagnóstico de arritmias o disfunción ventricular.

Objective: To evaluate the prevalence and characteristics of "de novo" cardiovascular findings (DNCFs) among post-COVID-19 patients based on a basic cardiovascular diagnostic procedure. Moreover, to describe the patients' results obtained by means of different diagnostic methods, to determine the clinical variables associated with DNCFs during the examination and, finally, to find out the diagnostic value of different data from medical records (MRs). Materials and methods: Patients aged > 18 years who had COVID-19 either at the hospital or at home were evaluated by clinical interviews, physical examination, electrocardiogram (EKG), echocardiogram, routine lab tests and cardiac biomarkers between 30 and 120 days after discharge. A total of 246 patients (age: 52 ± 13 years; women: 48 %; mild, moderate and severe COVID-19: 37 %, 39 % and 24 %, respectively) were included in the study. Twenty-four percent of the population were asymptomatic at the time of the evaluation. In those patients who developed symptoms, dyspnea was the most frequent one (28 %). Interviews were the method with the highest index of suspicion (45 %). Physical examination, EKG, echocardiogram and biomarkers showed normal values among 61 %, 60 %, 75 % and 96 % of the patients, respectively. Results: DNCFs were found in 62 patients (25.2 %): heart rhythm disorders in 42 (17 %) and ventricular dysfunction in 20 (8 %). Five patients had coronary artery disease, six had myocarditis and two had valvular heart disease. In addition, post-COVID-19 pulmonary embolism (PE) was detected in 10 patients, six of whom (2.4 %) had to be rehospitalized. Furthermore, in a multivariate analysis, the independent predictive variables of DNCFs were prior history of chronic obstructive pulmonary disease (COPD), QTc > 440 msec, leukocytosis and intra-COVID-19 cardiovascular complication. MRs showed both low sensitivity and positive predictive value for DNCFs. Conclusions: Although DNCFs were observed in 25 % of the population, only 2 % were significant. According to the data collected from this diagnostic procedure and in this time frame, special attention should be paid to patients with prior history of COPD and/or cardiovascular complications during the acute stage and/or prolonged QTc interval. Post-COVID-19 symptoms were of limited value for the diagnosis of arrhythmias or ventricular dysfunction.

Valor pronóstico de los niveles plasmáticos de IL13 en pacientes con artritis reumatoidea y enfermedad pulmonar intersticial: estudio de cohorte prospectiva / Prognostic value of IL13 plasmatic levels in patients with rheumatoid arthritis and interstitial lung disease: a prospective cohort study

Introducción: el objetivo de este estudio fue analizar la relación entre los valores de IL13 y su pronóstico en pacientes con artritis reumatoidea (AR) y enfermedad pulmonar intersticial (EPI). Materiales y métodos: estudio de cohorte prospectiva. Se midió IL13 en suero y se dividió la cohorte en dos grupos con la mediana de IL13 como punto de corte. Se estudió el tiempo hasta una caída de la capacidad vital forzada (CVF) mayor o igual al 5% con el método de Kaplan Meier (KM) y regresión de Cox. Resultados: se incluyeron 47 pacientes. La media (DE) de tiempo de seguimiento fue de 12,7 (12,5) meses. El estimador de KM a 15 meses fue de 0,48 (IC 95% 0,13-0,76) en el grupo con valores elevados de IL13 y de 0,86 (IC 95% 0,54-0,93) en el otro grupo (p=0,037). En el análisis de Cox multivariado los valores elevados de IL13 se asociaron con una caída de la CVF mayor o igual al 5% en el seguimiento (HR 17.64 (IC 95% 1,89-164,1) p=0,012). Conclusiones: los valores elevados de IL13 se asociaron con peor evolución funcional en esta cohorte prospectiva de pacientes con AR y EPI.

Introduction: the aim of our study was to analyze the relationship between the concentrations of IL13 in serum and the prognosis of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Materials and methods: we conducted a prospective cohort study. We measured IL13 levels in serum. Patients were divided in two groups using the median of IL13 value as cut off point. Time to a decline of 5% or more in FVC% from basal measurement was estimated using Kaplan Meier method. Univariate and multivariate Cox models were applied. Results: we included 47 patients. The mean (SD) time of follow-up was 12.7 (12.5) months. The Kaplan Meier estimator at 15 months was 0.48 (CI 95% 0.13-0.76) in the group with higher values of IL13, and 0.86 (CI95% 0.54-0.93) in the other group (p=0.037). In the Cox multivariate analysis, the values of IL13 were significantly associated with a decline of 5% or more in FVC% in the follow-up (HR 17.64 (CI 95% 1.89-164.1) p=0.012). Conclusions: our results indicate that patients with higher values of IL13 in serum presented higher decline in FVC% during their follow-up.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.

Lung involvement prevalence in patients with early rheumatoid arthritis without known pulmonary disease: a multicentric cross sectional study.

BACKGROUND: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. METHODS: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. RESULTS: We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1-6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. CONCLUSION: Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.

Analysis of Oxygen Blood Saturation/Respiratory Rate Index, NEWS2, CURB65, and quick Sequential Organ Failure Assessment Scores to Assess Prognosis in Patients with Mild Coronavirus Disease 2019.

BACKGROUND: Hospital bed saturation has been one of the problems to solve during the SARS-CoV-2 pandemic. However, not every patient who is admitted requires close monitoring or specific therapeutics. Mild cases could be managed in the outpatient setting. OBJECTIVE: Our study aimed to analyze the accuracy of the oxygen saturation/respiratory rate (sat/RR) index, NEWS2, CURB65, and quick Sequential Organ Failure Assessment (qSOFA) scores to predict supplemental oxygen requirement and prolonged hospital stay in patients with mild coronavirus disease 2019 (COVID-19). METHODS: A prospective cohort study in an academic medical center. We compared the values of these scores according to the occurrence or not of each outcome. When differences between groups were statistically significant, the discriminatory capacity of the score for that outcome was analyzed. RESULTS: We included 271 patients. Of them, 11.07% required supplemental oxygen, showing significantly higher values of NEWS2 score and qSOFA score, and lower values of Sat/RR index. About 38% presented prolonged hospital stay, with significantly higher values of NEWS2 score and lower values of sat/RR index. The ROC curve area under the curve (AUC) of sat/RR index to discriminate the requirement of supplemental oxygen was 0.72 (CI 95% 0.61-0.84). The ROC curve of NEWS2 and qSOFA for the same outcome was 0.75 (95% [95% CI 0.65-0.85]) and 0.66 (95% CI 0.57-0.76), respectively. The ability of the Sat/RR index to discriminate the requirement of prolonged hospitalization showed an AUC of 0.67 (95% [95% CI 0.60- 0.73]). The NEWS2 score showed an AUC of 0.63 (CI 95% 0.56-0.70) for the same outcome. CONCLUSIONS: sat/RR index and NEWS2 score have a good capacity to discriminate patients at risk of clinical worsening, being the Sat/RR index simpler and easier to calculate.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Development of simple and sensitive score to assess the risk of pneumonia in Covid-19 patients

ABSTRACT Background: Severe pneumonia is the most common cause of intensive care unit (ICU) admission and death due to novel coronavirus (SARS-CoV-2) respiratory disease (COVID-19). Due to its rapid outbreak, units for the evaluation of febrile patients in the pre-hospital setting were created. Objective: The objective of the study was to develop a sensitive and simple tool to assess the risk of pneumonia in COVID-19 patients and thus select which patients would require a chest imaging study. Materials and Methods: We conducted a cross-sectional study in a cohort of individuals with suspected COVID-19 evaluated in a public academic healthcare center in Buenos Aires city. All adult patients with positive RT-PCR assay for SARS-COV2 between April 24 and May 19 of 2020 were included in the study. Pneumonia was defined as the presence of compatible signs and symptoms with imaging confirmation. Univariate and multivariate logistic regression was performed. A risk indicator score was developed. Results: One hundred and forty-eight patients were included, 71 (48%) received the diagnosis of pneumonia. The final clinical model included four variables: age ≥ 40 years, cough, absence of sore throat, and respiratory rate ≥ 22. To create the score, we assigned values to the variables according to their ORs: 2 points for respiratory rate ≥ 22 and 1 point to the other variables. The AUC of the ROC curve was 0.80 (CI 95% 0.73-0.86). A cutoff value of 2 showed a sensitivity of 95.7% and a specificity of 43.24%. Conclusion: This sensible score may improve the risk stratification of COVID-19 patients in the pre-hospital setting. (REV INVEST CLIN. 2021;73(1):52-8)

Lung involvement prevalence in patients with early rheumatoid arthritis without known pulmonary disease: a multicentric cross sectional study

Abstract Background: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. Methods: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. Results: We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1-6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. Conclusion: Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.

Development of Simple and Sensitive Score to Assess the Risk of Pneumonia in COVID-19 Patients.

BACKGROUND: Severe pneumonia is the most common cause of intensive care unit (ICU) admission and death due to novel coronavirus (SARS-CoV-2) respiratory disease (COVID-19). Due to its rapid outbreak, units for the evaluation of febrile patients in the pre-hospital setting were created. OBJECTIVE: The objective of the study was to develop a sensitive and simple tool to assess the risk of pneumonia in COVID-19 patients and thus select which patients would require a chest imaging study. MATERIALS AND METHODS: We conducted a cross-sectional study in a cohort of individuals with suspected COVID-19 evaluated in a public academic healthcare center in Buenos Aires city. All adult patients with positive RT-PCR assay for SARS-COV2 between April 24 and May 19 of 2020 were included in the study. Pneumonia was defined as the presence of compatible signs and symptoms with imaging confirmation. Univariate and multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: One hundred and forty-eight patients were included, 71 (48%) received the diagnosis of pneumonia. The final clinical model included four variables: age >- 40 years, cough, absence of sore throat, and respiratory rate >- 22. To create the score, we assigned values to the variables according to their ORs: 2 points for respiratory rate >- 22 and 1 point to the other variables. The AUC of the ROC curve was 0.80 (CI 95% 0.73-0.86). A cutoff value of 2 showed a sensitivity of 95.7% and a specificity of 43.24%. CONCLUSION: This sensible score may improve the risk stratification of COVID-19 patients in the pre-hospital setting.

Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

INTRODUCTION: Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease with limited treatment response and bad prognosis. Sometimes it is indistinguishable from idiopathic pulmonary fibrosis (IPF) becoming one of the main differential diagnosis. The aim of our study is to compare survival and functional decline between these two entities. METHODS: Survival and functional decline more than 10% in FVC were compared using Kaplan Meier (KM) method between patients with CHP and IPF. Cox proportional hazard analysis was used to identify independent predictors of survival and functional decline. RESULTS: 146 patients were included, 54 with CHP and 92 with IPF. KM rate for 2 years survival was 0.71 (CI 95% 0,6-0,8) for CHP group and 0,83 (CI 95% 0,66 - 0,92) for IPF (p=0,027). Nevertheless this difference disappeared using Cox proportional hazard analysis, the adjusted HR for survival among CHP patients was 0,53 (CI 95% 0,25-1,15) (p=0,11). There was no difference in functional evolution between the two groups. KM rate for a decline more than or equal to 10% was 0,64 for CHP (CI 95% 0,43-0,79) and 0,78 for IPF (IC 95% 0,6-0,88) (p=0,22). This observation did not change after using Cox proportional hazard analysis. CONCLUSIONS: Our study shows that both IPF and CHP are fibrosing interstitial diseases with a similar evolution and survival. It might be possible that therapeutic approach in patients with CHP should change in the light of these observations.

Rehabilitación respiratoria en pacientes con enfermedad pulmonar intersticial difusa. Experiencia de un hospital especializado de Argentina / Pulmonary Rehabilitation in Patients with Interstitial Lung Disease. Experience in a Specialized Hospital in Argentina

Introducción: Las enfermedades pulmonares intersticiales difusas generan en los pacientes intolerancia al ejercicio, disnea, y una disminución de la calidad de vida relacionada con la salud. La rehabilitación respiratoria tiene un rol importante en el cuidado estos pacientes. Materiales y Métodos: Se realizó un estudio retrospectivo en una cohorte de pacientes con enfermedad pulmonar intersticial difusa (EPID) sometida a rehabilitación respiratoria (RR) durante los años 2012 a 2015. Los pacientes realizaron 4 meses de RR, basado en entrenamiento aeróbico y fortalecimiento muscular de extremidades y tronco y educación en salud. Se estudió la calidad de vida con el cuestionario Saint George´s (SGRQ) y tolerancia al ejercicio (TE) con test de marcha de 6 minutos (TM6M) previo y posterior a RR. Se compararon los resultados entre pacientes con fibrosis pulmonar idiopática (FPI) y otras EPID. Resultados: Se incluyeron 93 pacientes (46 hombres), de los cuales 42 (44.09%) completaron el programa. Luego de la RR la media de puntaje del SGRQ disminuyo 8.7 puntos (IC 95%: 2.85-14.42), sin diferencia entre FPI y otros diagnósticos. La media de metros caminados en el TM6M mejoró 14.07 m sin alcanzar la significancia estadísticamente (p = 0.132). En el subgrupo de pacientes que caminó inicialmente menos de 400 m (n = 18), la mejoría fue clínica y estadísticamente significativa (40.8 m; p = 0.025). No encontramos diferencias en esta prueba en función del diagnóstico. Conclusiones: La RR en esta cohorte de pacientes con EPID demostró mejorar la calidad de vida y la tolerancia al ejercicio, sin diferencias en cuanto al diagnóstico específico.

Pulmonary Rehabilitation in Patients with Interstitial Lung Disease. Experience in a Specialized Hospital in Argentina / Rehabilitación respiratoria en pacientes con enfermedad pulmonar intersticial difusa. Experiencia de un hospital especializado de Argentina

Introduction: Interstitial lung diseases generate in patients exercise intolerance, dyspnea, and a decrease in health-related quality of life. Pulmonary Rehabilitation plays an important role in the treatment of these patients. Materials and Methods: We conducted a retrospective study in a cohort of patients with interstitial lung disease (DILD) who underwent Pulmonary Rehabilitation (PR) between 2012 and 2015. Patients completed a 4-month treatment program including aerobic, core, and upper and lower limbs strength training and health education. Quality of life was measured with the St. George´s Respiratory Questionnaire (SGRQ), and exercise tolerance with the 6-minute walk test (6MWT) pre- and post-PR. Results were compared among patients with idiopathic pulmonary fibrosis (IPF) and other ILDs. Results: 93 patients were included (46 male); 42 (44.09%) completed the program. After the PR, the SGRQ mean score decreased by 8.7 (95% CI [confidence interval]: 2.85-14.42), with no differences between the IPF and other diagnoses. The results of the 6MWT showed mean improvement of 14.07 m, not reaching statistical significance (p = 0.132). The subgroup of patients who walked less than 400 m (n = 18) showed clinical and statistically significant improvement (40.8 m; p = 0.025). We didn't find differences in this test in terms of diagnosis. Conclusions: PR in this cohort of patients with ILD showed improvement in quality of life and exercise tolerance, with no differences regarding the specific diagnosis.

Real-Life Experience with Pirfenidone in Idiopathic Pulmonary Fibrosis in Argentina. A Retrospective Multicenter Study. / Experiencia de la vida real con pirfenidona en la fibrosis pulmonar idiopática en Argentina. Estudio retrospectivo multicéntrico.

INTRODUCTION: Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation. MATERIALS AND METHODS: Retrospective observational study conducted in 4 specialized centers in Argentina. We analyzed the medical records of patients with IPF who received pirfenidone between June 2013 and September 2016. Adverse events (AE) and the variables that could influence these results were analyzed. Forced vital capacity (FVC%) parameters were also compared between the pre-pirfenidone and post-pirfenidone periods. RESULTS: Fifty patients were included, 38 (76%) men, with mean age (SD) 67.8 (8.36) years. Mean (SD) exposure to pirfenidone was 645.68 (428.19) days, with a mean daily dose (SD) of 2,064.56mg (301.49). Nineteen AEs in 15 patients (30%) were reported: nausea (14%), asthenia (10%) and skin rash (8%). A total of 18 patients (36%) interrupted treatment, only 1 definitively. The most frequent reason for discontinuation was failure of suppliers to provide the drug (9 subjects; 18%). We compared the evolution of FVC% between the pre-pirfenidone and post-pirfenidone periods, and found a mean (SD) FVC% decline of 4.03% (7.63) pre-pirfenidone and 2.64% (7.1) post-pirfenidone (P=.534). CONCLUSIONS: In our study, pirfenidone was well tolerated and associated with a reduction in FVC decline, although without reaching statistical significance.

Evaluación infectológica inicial y seguimiento prospectivo de una cohorte de pacientes sometidos a inmunosupresión inducida / Initial assessment and prospective follow-up of a cohort of patients with immunosuppressive therapy by an infectious diseases physician

El uso de inmunosupresores generó una población creciente de pacientes con defectos en el sistema inmune. Creamos un consultorio especializado en la atención infectológica de dichos pacientes. Objetivos: Describir los antecedentes clínicos y la prevalencia de infecciones latentes, evaluar el estado de vacunación, determinar la necesidad de profilaxis antimicrobiana. Describir la frecuencia de aparición infecciones oportunistas (IO). Materiales y métodos: estudio descriptivo, prospectivo de pacientes atendidos en un consultorio que estuvieran bajo tratamiento inmunosupresor (noviembre 2015-enero 2017). Se recolectaron datos demográficos, clínicos y factores de riesgo para IO. Se realizó pesquisa de tuberculosis (TB), serologías para HIV, hepatitis A, B y C, sífilis, toxoplasmosis, Chagas, búsqueda de Strongyloides spp. Se indicaron vacunas de acuerdo con las recomendaciones actuales. Se realizó seguimiento para detección de IO. Resultados: n=197, media de edad 50,7 años (DE 14), mujeres 79,7%. Enfermedades de base: artritis reumatoidea 52%, lupus 12%. Drogas inmunosupresoras: metotrexato 45%, corticoides 16%, biológicos anti-TNF 15%, micofenolato 10%, ciclofosfamida 4%. Se diagnosticaron 49 (25%) infecciones: 15 Chagas, 15 anti-HBc positivo aislado, 7 sífilis, 4 HIV, 4 TB latentes, 2 HBV, 1 HCV, 1 estrongiloidiosis. Se indicó profilaxis antimicrobiana en 27 (14%) pacientes. En todos se intervino indicando o completando los esquemas de vacunación. Se detectaron 7 IO. Conclusiones: En el 39% de los pacientes, la evaluación sistematizada arrojó hallazgos que motivaron intervenciones, ya sea terapéuticas o de monitoreo. En el 100% fue necesaria la prescripción de vacunas. Esto pone en evidencia la importancia de evaluar sistemáticamente en consultorios especializados a estos pacientes

Introduction: The extensive use of immunosuppressive drugs resulted in a growing population of patients with defects in the immune system. We opened an infectious diseases practice focused on the attention of these patients. Our objectives were to describe the clinical history and prevalence of latent infections, evaluate the vaccination status, determine the need for antimicrobial prophylaxis and describe the frequency of opportunistic infections (OI). Methods: We performed a descriptive and prospective study of patients seen at a medical practice who were under immunosuppressive therapy (November 2015-January 2017). Demographic and clinical history, as well as risk factors for OI were collected. Tuberculosis (TB) screening, serologies for HIV, hepatitis A, B and C, syphilis, toxoplasmosis, Chagas and Strongyloides spp. screening were performed. Vaccines were indicated according to current recommendations. Follow-up was performed for IO detection. Results: n=197. Mean age: 50.7 years (SD 14). Female 79.7%. Underlying diseases: rheumatoid arthritis 52%, 12% lupus. Immunosuppressive drugs: methotrexate 45%, corticoids 16%, biological anti-TNF agents 15%, mycophenolate 10%, cyclophosphamide 4%. Forty-nine (25%) infections were diagnosed: 15 Chagas, 15 anti-HBc positive isolated, 7 syphilis, 4 HIV, 4 latent TB, 2 HBV, 1 HCV, 1 strongyloidiosis. Antimicrobial prophylaxis was indicated in 27 (14%) patients. In all cases, vaccination schemes were indicated or completed. Seven IO were detected. Conclusions: In 39% of the patients, the systematized evaluation revealed findings that motivated interventions, either therapeutic or monitoring. In 100% the prescription of vaccines was necessary. These findings highlight the importance of a systematically evaluation of these patients in specialized care centers.

Correlation between Lung and Joint Involvement in Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Cross-Sectional Study.

BACKGROUND: Rheumatoid arthritis (RA) can affect the lungs in different manners, with interstitial lung disease (ILD) as the most serious manifestation. Although lung and joint compromise could be thought to evolve in parallel, there are data suggesting the opposite. In this study, we evaluated the relationship between lung and joint involvement in RA ILD. METHODS: An observational cross-sectional study of RA ILD patients evaluated from January 2015 to February 2017. Joint disease assessment included number of tender and swollen joints, patient's global assessment of disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein, and disease activity score (DAS28). Lung disease assessment included forced vital capacity, diffusion capacity (DLCO), and Goh high-resolution computed tomography (HRCT) score for total extent, ground glass, and reticular pattern. We studied the correlation between both components of the disease. RESULTS: We included 46 patients, 14 (30.4%) men, with a mean (SD) of the age of 59.9 years (11.89). 12 (26.09) patients were in remission or had low disease activity measured with DAS28. The HRCT showed usual interstitial pneumonia (UIP) pattern in 10 (21.7%), possible UIP in 18 (39.1%), and inconsistent with UIP in 18 (39.1%). We found a good correlation between the ESR and the ground glass score in the HRCT (r = 0.39; p = 0.03). However, we found no correlation between lung function tests or HRCT scores and the other components of the DAS28. CONCLUSIONS: We only found a good correlation between ESR and ground glass score. It is possible that different pathways of the immune response mediate damage in lungs and joints.

Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease Based on its Proven and Hypothetical Mechanisms.

The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

[Hyperammonemic encephalopathy and fibrolamellar hepatocellular carcinoma]. / Encefalopatía hiperamoniémica y hepatocarcinoma fibrolamelar.

We present the case of a young woman, 22 years old, with an aggressive form of fibrolamellar hepatocellular carcinoma. She began with the signs and symptoms of a hyperammonemic encephalopathy, an uncommon form of presentation. Fibrolamellar carcinoma is a rare liver tumor, which affects young patients without previous liver disease. Its etiology is unknown, and it has been considered as a tumor with a better prognosis than the classic hepatocellular carcinoma.