Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.

[Delphi Consensus of Argentine Pulmonologists on the Management of Patients with COPD in Real Life]. / Consenso Delphi de neumólogos argentinos sobre el manejo de los pacientes con EPOC en la vida real.

Introduction: COPD is the third cause of death globally and in Argentina COPD has a prevalence of 14.5%, but the management of patients in real life is unknown. The objectives of this work were: a) To know the opinions of pulmonologists in Argentina who manage patients with COPD in different aspects of daily practice. b) Compare our findings with specialists from Spain and c) Consider our results to plan future directives in the management of COPD in our country. Material and methods: 89 pulmonologists from Argentina, experts in COPD, participated in a Delphi consensus, who responded to a survey with five domains. a) Adherence to treatment, b) Control of COPD, c) Treatable features, d) Inhalation devices and e) Accessibility to therapeutic resources. Results: After two rounds of questions, total consensus was achieved in 77.6% of the statements and discriminating by domain: Treatment adherence: 5/9 (55.5%). COPD control: 10/14 (71.4%). Treatable traits: 6/6 (100%). Inhalation devices: 10/14 (71.4%) and Accessibility to treatment: 6/6 (100%). In most of the affirmations, the results were similar to those obtained by Spanish pulmonologists. Conclusions: Pulmonologists from Argentina manage COPD patients in a similar way and with minimal differences with our Spanish colleagues. It became evident that, in daily practice, there are factors that negatively impact access to the indicated treatments. Our work could serve as a starting point to improve this situation.

Real-life experience with a generic formulation of lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation.

INTRODUCTION: Cystic fibrosis (CF) is the most frequent recessive autosomal disorder in the Caucasian population. It is caused by mutations that result in a deficient or dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Among CFTR modulators, potentiator compounds increase channel opening, whereas corrector compounds increase CFTR quantity in the cell surface. OBJECTIVE: To report real-life effects of a generic formulation of lumacaftor-ivacaftor use in patients with CF homozygous for the Phe508del CFTR mutation. PATIENTS AND METHODS: Clinical variables (body mass index [BMI], pulmonary exacerbations, sweat test, and pulmonary function) were analyzed in 30 CF patients homozygous for the Phe508del CFTR mutation, treated with lumacaftor-ivacaftor for 12 months, at the Respiratory Center of Hospital de Niños Ricardo Gutiérrez. These clinical variables were compared with those before the use of modulators. RESULTS: A total of 30 patients with CF homozygous for the Phe508del CFTR mutation receiving lumacaftor-ivacaftor therapy were included in this study. The median (interquartile range [IQR]) age at the start of treatment was 10.79 (7.08-14.05) years. Nineteen patients were male. Before treatment, median (IQR) sweat chloride concentration was 80 (72-92) mEq/L, and it had decreased to 74 (68-78) mEq/L (p = .05) 12 months after treatment. Median (IQR) BMI z-score improved from -0.33 (-0.86 to 0.21) to -0.13 (-0.66 to 0.54) (p = .003). A spirometry was performed in 28 of 30 patients. Median (IQR) ppFEV1 was 83.5 (71-91) before treatment and 86.5 (67-103) after treatment (p = .38), 73.3% of patients referred decreased sputum production and 40% reported improvement in their dyspnea at 12 months. Severe pulmonary exacerbations significantly decreased from 60% in the year before treatment, to 30% at 12 months after treatment (p = .037); 13 patients showed an improvement in their exacerbation rates, 2 showed an increased rate, and 15 showed no change. CONCLUSIONS: The use of a generic formulation of lumacaftor-ivacaftor in patients homozygous for the Phe508del CFTR mutation was associated with improvement in nutritional status and respiratory symptoms, and a significant reduction in severe pulmonary exacerbations.

Real-world study: drug reduction in children with allergic rhinitis and asthma receiving immunotherapy.

Background: The reduction of pharmacological treatment after allergen immunotherapy (AIT) for house dust mites (HDMs) has been little studied in children. Objective: To evaluate the reduction of pharmacological treatment comparing children that receive HDM immunotherapy (AIT group) versus only pharmacotherapy. Methods: A historic cohort of children with rhinitis or asthma was assessed. The main outcome was the frequency of complete drug discontinuation. Results: 100% drug reduction was higher for rhinitis (4-year cumulative incidence: 30 vs 10.7%) and asthma (24.1 vs 10.5%) in the AIT group (n = 987) than in the pharmacotherapy group (n = 2012). Conclusion: Immunotherapy is associated with a significant reduction of pharmacotherapy in children. This is a marker of clinical control and could be associated with positive economic impact.

The benefits of allergen immunotherapy for house dust mites has been little studied in children. The usefulness of this treatment in asthma over the use of pharmacotherapy has also not been clearly evaluated. The use of immunotherapy allowed greater reductions in pharmacological treatment in children with rhinitis and asthma. Immunotherapy is a useful treatment for childhood rhinitis and asthma and reduces the risk of adverse effects from pharmacological treatments.

Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience.

PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

Economic burden of severe asthma treatment: A real-life study.

Background: Individuals with severe asthma represent 5%-10% of the general asthmatic population. Despite the use of biologic drugs during clinical management, inadequate control of the disease has translated into high economic impact. In Mexico, however, these costs have not yet been assessed. Methods: A retrospective cohort study was carried out in 2018 and 2019 at Regional Hospital Lic. Adolfo López Mateos, ISSSTE. The assessment of direct costs included pharmacological treatment, clinical tests, days of hospitalization, admissions to the emergency room, and scheduled consultations. The evaluation involved 2 groups of patients-with controlled severe asthma (CSA) and uncontrolled severe asthma (UCSA)-according to presence of exacerbations. Results: 60 patients (18-75 years old, 51 women) were included in the study. In 2018, 23 of them (38.3%) were categorized as belonging to the UCSA group; in 2019, 22 patients (36.7%) were in this condition (exacerbations: median = 1.5, maximum = 6). Of the 60 patients, 12 (20%) presented between 2 and 9 exacerbations in the study's two-year period (median = 3) after between 4 and 10 years (median = 7.8) of complementary anti-immunoglobulin E (IgE) therapy with omalizumab. The cost for all patients in the 2018-2019 period was 993,289.60 USD. The mean cost per patient was higher for those with UCSA (16,392 USD) than for those with CSA (16,246 USD, p = 0.02). We found a positive association between cost and exacerbations, with an increase of 350 USD per exacerbation (p˂0.0001). Our results indicate that 62% of patients respond to complementary anti-IgE treatment, while 38%-and especially 20%-do not respond optimally to this treatment. Conclusions: Poor asthma control in this latter group of 38% of patients leads to lower quality of life and higher costs associated with pharmacological treatment.

Hepatocellular carcinoma: A real-life experience in a specialized center in Bogotá, Colombia / Hepatocarcinoma: experiencia de la vida real en un centro especializado de Bogotá, Colombia

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.

Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.

Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population.

INTRODUCTION AND OBJECTIVES: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. MATERIAL AND METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. RESULTS: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. CONCLUSIONS: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Rendimiento del ASAS Health Index en pacientes con Espondiloartritis de la vida real / Performance of ASAS Health Index in real life spondyloarthritis patients

Introducción: El cuestionario "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) fue desarrollado para medir de manera global la funcionalidad y el estado de salud en pacientes con espondiloartritis (EspA). Se han propuesto puntos de corte para determinar diferentes estados de salud que fueron poco evaluados en pacientes de la vida real. Objetivos: Describir el estado de salud medido por ASAS-HI en pacientes argentinos con EspA axial (EspAax) y periférica (EspAp) en la práctica diaria y evaluar los factores asociados al pobre estado de salud. Materiales y métodos: Estudio de corte transversal, analítico y multicéntrico. Se incluyeron consecutivamente pacientes con EspAax y EspAp según criterios ASAS, de 15 centros argentinos. Análisis estadístico: Se realizó estadística descriptiva, análisis bivariado y multivariado (regresión logística múltiple) para evaluar los factores asociados al pobre estado de salud (ASAS-HI ≥12). Para analizar la validez de constructo de la herramienta se realizó correlación de Spearman entre el ASAS-HI y otros parámetros de evaluación de la enfermedad. Resultados: Se incluyeron 274 pacientes con EspA, con una edad media de 49 (±14) años y una duración mediana de la enfermedad de 62 meses (p25-75: 24-135), 155 (56,6%) de los pacientes eran de sexo masculino, 129 pacientes (47%) con EspAax y 145 (52,9%) EspAp. Según el ASAS-HI 119 pacientes (43,4%) presentaban buen estado de salud, 117 (42,7%) tenían estado de salud moderado y 38 (13.9%) pobre estado de salud. En los pacientes con EspAp el valor de ASAS-HI mediano fue de 7 (p25-75: 3-10). El ASAS-HI correlacionó positivamente con: DAS28: rho: 0.5 (p<0.001) y HAQ: rho: 0.54 (p<0.001). La variable asociada de manera independiente con pobre estado de salud fue el DAS28 (OR: 1.9, IC95% 1.1-3.4, p: 0.029). En los pacientes con EspAax el valor de ASAS-HI mediano fue de 6 (p25-75: 2.75-10). El ASAS-HI mostró correlación con: BASDAI: rho: 0.7 (p<0.001), ASDAS-ERS: rho: 0.7 (p<0,001), ASQoL: rho: 0.8 (p<0.001), BASFI rho: 0.75 (p<0.001). La variable que se asoció de manera independiente a pobre estado de salud fue el ASDAS-ERS (OR 6.6, IC95% 2-22, p 0.002). Conclusión: Un pobre estado de salud se asoció independientemente a mayor actividad de la enfermedad en pacientes con EspAax y EspAp. El ASAS-HI correlacionó con otros parámetros de la enfermedad, lo que refuerza la validez de constructo de esta nueva herramienta.

Introduction: The "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) questionnaire was developed to globally measure function and health status in patients with spondyloarthritis (SpA). Cut-off points have been proposed to determine different health states that were poorly evaluated in real-life patients. Objectives: To describe the health status measured by ASAS-HI in Argentine patients with axial SpA (AxSpA) and peripheral SpA (SpAp) in daily practice and to evaluate the factors associated with poor health. Materials and methods: Cross-sectional, analytical and multicenter study. Patients with SpAax and SpAp were consecutively included according to ASAS criteria, from 15 Argentine centers. Statistical analysis: Descriptive statistics, bivariate and multivariate analysis (multiple logistic regression) were performed to evaluate the factors associated with poor health status (ASAS-HI ≥12). To analyze the construct validity of the tool, Spearman correlation was performed between the ASAS-HI and other disease evaluation parameters. Results: 274 patients with SpA were included, with a mean age of 49 (± 14) years and a median duration of the disease of 62 months (p25-75: 24-135), 155 (56.6%) were male, 129 patients (47%) with AxSpA and 145 (52.9%) SpAp. According to the ASAS-HI, 119 patients (43.4%) had good health, 117 (42.7%) had moderate health and 38 (13.9%) had poor health. In patients with SpAp, the mean ASAS-HI value was 7 (p25-75: 3-10). The ASAS-HI positively correlated with: DAS28: rho: 0.5 (p <0.001) and HAQ: rho: 0.54 (p <0.001). The variable independently associated with poor health status was DAS28 (OR: 1.9, 95% CI 1.1-3.4, p: 0.029). In patients with AxSpA, the mean ASAS-HI value was 6 (p25-75: 2.75-10). The ASAS-HI showed correlation with: BASDAI: rho: 0.7 (p <0.001), ASDAS-ERS: rho: 0.7 (p <0.001), ASQoL: rho: 0.8 (p <0.001), BASFI rho: 0.75 (p <0.001). The variable that was independently associated with poor health was the ASDAS-ERS (OR 6.6, 95% CI 2-22, p 0.002). Conclusion: Poor health status was independently associated with higher disease activity in patients with AxSpA and SpAp. The ASAS-HI correlated with other parameters of the disease, which reinforces the construct validity of this new tool.

High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Management Recommendations: Data From a Large Real-Life Study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. OBJECTIVE: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. METHODS: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. RESULTS: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). CONCLUSION: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.

Real-life data of survival and reasons for discontinuation of biological disease-modifying drugs 'in' rheumatoid arthritis.

Background Rheumatoid arthritis is a chronic, autoimmune disease in which treatment has evolved with a variety of therapeutic classes. Biological disease-modifying antirheumatic drugs have improved therapy; however, the continued long-term use of these drugs with sustained safety and efficacy remains a challenge. ObjectiveThe objective of this study was to analyze time of use and reasons for discontinuation of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.SettingIt is as part of REAL (Rheumatoid Arthritis in Real Life), a multicenter project that evaluated Brazilian patients with rheumatoid arthritis in a real-life setting. Eleven referral centers for the treatment in the public network participated in the study.MethodsWe conducted a cross-sectional analysis of data collected in the REAL study from August to October 2015 study. The patients were submitted to clinical evaluation and analysis of medical records.Results1125 patients were included (89.5% women; median age: 56.6 years; and disease time: 12.8 years). A total of 406 (36.09%) participants were on a biological disease-modifying antirheumatic drugs. Infliximab was the drug with the longest time of use (12 years). Most (64.4%) drug suspension episodes were due to inefficacy. Adalimumab and certolizumab had a greater number of suspensions due to primary inefficacy, while discontinuations for abatacept were due more to secondary inefficacy. Infliximab had fewer suspensions due to primary inefficacy and golimumab had fewer episodes of secondary inefficacy. Regarding side effects, infliximab was suspended a greater number of times because of clinical and laboratory side effects. Abatacept and adalimumab had fewer suspensions due to clinical side effects, and certolizumab, rituximab and tocilizumab had fewer laboratory adverse effects. Conclusion Among the biological disease-modifying antirheumatic drugs being used for long periods, infliximab had greater time of use. Most drug suspensions (64%) were due to primary or secondary inefficacy. Number of discontinuations due to clinical and laboratory adverse effects for each drug was analyzed, and these data should be confirmed by other real-life studies. Knowledge of what is happening in real life is essential to health professionals, who need to be aware of the most common adverse effects and to health managers, who aim for greater cost-effectiveness in the choice of medications.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real-life study in Brazil.

INTRODUCTION: The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre-specified timepoints after ART onset. However, data from real-life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil. METHODS: Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir-boosted atazanavir (regimen 3)). RESULTS AND DISCUSSION: We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12-month cumulative viraemia. The model predicted a 45-unit increase in log10 copy-days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70-unit increase in log10 copy-days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir-lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders. CONCLUSIONS: Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

Intermediate-advanced hepatocellular carcinoma in Argentina: Treatment and survival analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC. AIM: To describe real-life treatments performed in patients with intermediate-advanced HCC before the approval of new systemic options. METHODS: This longitudinal observational cohort study was conducted between 2009 and 2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer (BCLC) HCC stages (BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios (HR) calculations and 95% confidence intervals (95%CI). RESULTS: From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D. Corresponding median survival were 15 mo (IQR 5-26 mo), 5 mo (IQR 2-13 mo) and 3 mo (IQR 1-13 mo) (P < 0.0001), respectively. Among BCLC-B patients (n = 135), 57% received TACE with a median number of 2 sessions (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR = 0.29 (CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15 (CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C (87.8%). However, 12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo (IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients, treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013]. CONCLUSION: In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.

Multicenter prospective observational long-term follow-up study of endocardial cardiac resynchronization therapy using the Jurdham procedure.

BACKGROUND: Endocardial cardiac resynchronization therapy (eCRT) avoids the limitations and failures of coronary sinus (CS) resynchronization. However, data regarding long-term outcomes are lacking. OBJECTIVE: The purpose of this study was to report the long-term outcome of eCRT performed using the Jurdham procedure in a real-world setting. METHODS: eCRT was performed in patients who failed a CS implant or failed to respond to cardiac resynchronization therapy (CRT), or in selected patients requiring lifelong oral anticoagulation (OAC). Left ventricular ejection fraction (LVEF), New York Heart Association functional class (NYHA FC), and left ventricular stimulation parameters were assessed during long-term follow-up (FU). RESULTS: From August 2009 to March 2018, the Jurdham procedure was performed in 88 patients at 15 centers in 8 countries, with FU of 32.88 ± 61.52 months (range 0-88 months; 196 patient-years). NYHA FC improved from 2.9 preimplant to 1.3 during FU. LVEF increased <10 percentage points from baseline in 7% of patients, between 10 and 20 percentage points in 11% of patients, and >20 percentage points in 82% of patients. All-cause mortality at 60 months was 30.5%. Three transient ischemic attacks (1.53 per 100 patient-years) and 6 strokes (3.06 per 100 patient-years) occurred. Of the 6 patients with stroke, 4 (66%) had almost complete recovery. CONCLUSION: eCRT using the Jurdham procedure is an effective and safe technique in anticoagulated patients. This approach may be an attractive option for patients with failed CS implants or nonresponders to CS CRT. In addition, it might be a reasonable approach as a first option for treatment of patients requiring lifelong OAC.

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.

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico]. / Resumen ejecutivo de ARIA 2019: Vías integradas de atención para la rinitis alérgica en Argentina, España y México.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

Sorafenib for Advanced Hepatocellular Carcinoma: A Real-Life Experience.

INTRODUCTION: Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur. OBJECTIVES: The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy. METHODS: This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected. RESULTS: From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0-34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, p < 0.001). There was no difference in survival between BCLC-B and C (p = 0.405), as well as CP-A and B (p = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated. CONCLUSION: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases.