Endothelium-biomarkers for postthrombotic syndrome: a case-control study.

BACKGROUND: The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase. METHODS: A case-control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry. RESULTS: Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/µl (0.34-1.5) vs. 0.20/µl (0.11-0.77); P  = 0.04) and EPC (0.75/µl (0.38-1.52) vs. 0.09/µl (0.05-0.82); P  = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30-597.90) vs. 98.00 pg/ml (82.30-193.02); P  = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r  = 0.86, P  < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups. CONCLUSIONS: The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.

Prednisone and long-term damage in systemic lupus erythematosus: Which is the threshold dose? A pilot study.

OBJECTIVES: We aimed to study the daily dose of glucocorticoids in the first month associated with damage after 5 years of systemic lupus erythematosus (SLE) diagnosis; and to assess the daily dose of prednisone during the first year, over which damage after 5 years could be predicted. METHODOLOGY: A retrospective cohort study of SLE patients from the diagnosis and up to 5 years of follow-up was performed. Cumulative prednisone doses in the first month (T1m), at 1 year (T12m), and at 5 years (T5y) were calculated. Damage was estimated using the SLICC index and activity by the SLEDAI-2K. Damage at T5y was categorized as "present" or "absent". To determine the cutoff point of prednisone dose for the first month and for the first year of treatment, related to damage at 5 years, a ROC curve was done. A logistic regression was performed to control damage at 5 years by the activity levels, anti-DNA titers, and the corticosteroid burden between 1 and 5 years. RESULTS: Forty-eight patients were included with a mean age of 42.4 (12.6) years; 46 (95.8%) were female. The cumulative dose in T1m associated with greater sensitivity and specificity in the ROC curve (1.54; AUC 0.793; 95% CI: 0.66-0.92) to predict glucocorticoid-related damage at 5 years of follow-up was 980mg, which leads to a daily dose for the first month of 32.6 mg/day. The daily dose during the first year associated with damage at 5 years, allowed to calculate an optimal cutoff point of 7.38 mg/day, with a sensitivity of 92.9% (AUC 0.695, 95% CI: 0.52-0.86) to predict damage at 5 years. In the logistic regression, this estimate was maintained, controlling for SLEDAI-2K and for positivity or not of anti-DNA antibodies and for the cumulative dose of prednisone between T5y and T12m. CONCLUSION: This pilot study allows to estimate a threshold dose of 32.6 mg/day during the first month and 7.38 mg/day during the first year, over which the risk of permanent damage is high at 5 years, regardless of the activity levels and the glucocorticoid doses considered between the first and the fifth year of follow-up.

Mobilized and apheresis-collected endothelial progenitor cells with plerixafor.

BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

Inmunosupresores en la Esclerosis Sistémica. Uso y respuesta terapéutica

Resumen: Introducción: La esclerosis sistémica (ES) es una enfermedad compleja y heterogénea. Su abordaje terapéutico y oportunidad de inmunosupresión no está completamente sistematizada y constituye un reto. Objetivo: Describir los usos y respuesta terapéutica a los inmunosupresores (IS) en una cohorte de pacientes con ES. Metodología: Se identificaron los pacientes con Esclerosis sistémica asistidos en dos unidades de enfermedades autoinmunes sistémicas. Se incluyeron los que recibieron IS. Variables estudiadas: sexo, edad y motivo de IS. En los que presentaron compromiso respiratorio se analizaron los resultados de las pruebas de función respiratoria pre y postratamiento. Resultados: 20 pacientes, 17 de sexo femenino. Edad media 64 años. Principal indicación de IS: compromiso respiratorio seguido del cutáneo-articular. Se realizó inducción en 75% de los pacientes respiratorios vs. 12% con otro compromiso. Micofenolato mofetilo fue el inmunosupresor más utilizado. Conclusiones: El uso de IS predomina en el compromiso respiratorio de los pacientes con ES. Se observó un mayor uso de MMF respecto a otros IS así como una respuesta favorable en las pruebas de función respiratoria en los pacientes tratados con IS.

Abstract: Introduction: Systemic sclerosis (SS) is a complex and heterogeneous disease. Its therapeutic approach and immunosuppression opportunity is not completely defined, it remains a challenge. Objective: To describe the usage and therapeutic response to immunosuppressive agents (IS) in a cohort of patients with SS. Methodology: Patients with SS assisted in 2 units of systemic autoimmune diseases were selected. Those who received IS were included. Variables studied were sex, age and IS indication. Those with respiratory manifestations were assessed with functional lung tests previous and after treatment. Results: 20 patients, 17 females. The mean age was 64 years old. The main indication of IS was respiratory manifestations followed by skin and articular symptoms. Induction treatment was indicated in 75% of respiratory patients vs. 12% in those with other manifestations. Mycophenolate mofetil was the most widely immunosuppressive agent employed. Conclusions: The main prescription of IS in SS was for patients with respiratory manifestations. An increased use of MMF among other IS was observed as well as a favourable response in lung function tests in patients treated with IS.

Resumo: Introdução: A esclerose sistêmica (ES) é uma doença complexa e heterogênea. Sua abordagem terapêutica e oportunidade de imunossupressão não estão totalmente sistematizadas e constituem um desafio. Objetivo: Descreva os usos e resposta terapêutica a imunossupressores (SI) em uma coorte de pacientes com SS. Metodologia: Foram identificados pacientes com esclerose sistêmica atendidos em duas unidades de doenças autoimunes sistêmicas. Aqueles que receberam IS foram incluídos. Variáveis estudadas: sexo, idade e motivo do IS. Naqueles com comprometimento respiratório, foram analisados os resultados dos testes de função respiratória pré e pós-tratamento. Resultados: 20 pacientes, 17 mulheres. Idade média 64 anos. Principal indicação para IS: comprometimento respiratório seguido de cutâneo-articular. A indução foi realizada em 75% dos pacientes respiratórios vs. 12% com outro compromisso. O micofenolato de mofetil foi o imunossupressor mais amplamente utilizado. Conclusões: O uso de SI predomina no comprometimento respiratório de pacientes com SS. Um maior uso de MMF foi observado em comparação com outros ISs, bem como uma resposta favorável em testes de função respiratória em pacientes tratados com IS.

Nefritis lúpica: experiencia con dosis reducidas de glucocorticoides en una unidad de enfermedades autoinmunes sistémicas / Lupus nephritis: low-dose glucocorticoids in a systemic autoimmune diseases unit / Nefritis lúpica: experiência con doses reduzidas de glicocorticoides em uma unidade de doenças autoinmunes sistémicas

Resumen: Introducción: las recomendaciones actuales del tratamiento de la nefritis lúpica (NL) apuntan a dosis de glucocorticoides más bajas para lograr el control de la enfermedad y evitar el daño acumulado. Objetivo: conocer y comparar la respuesta al tratamiento de pacientes con NL proliferativa en su etapa de inducción con dos pautas de tratamiento con prednisona (PDN): dosis iniciales reducidas 30 mg/d. Método: se compararon variables clínicas, analíticas y terapéuticas de pacientes con NL proliferativa categorizados en dos grupos según la dosis inicial de prednisona (PDNi) estándar o reducida. Resultados: se estudiaron 21 pacientes con NL proliferativa (n=12 PDNi reducida vs. n=9 PDNi estándar). No hubo diferencias significativas en las variables clínicas y analíticas. Se observó una diferencia estadísticamente significativa en el número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) y en la dosis de prednisona acumulada a 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). No hubo diferencias significativas en la proporción de pacientes que alcanzaron la respuesta completa, en el tiempo hasta alcanzarla ni en los efectos adversos entre ambos grupos. Conclusiones: el esquema terapéutico del grupo PDNi <30 mg/d se asoció a una menor dosis acumulada de prednisona y una respuesta al tratamiento comparable, lo que hace presumir menor daño acumulado relacionado al uso de glucocorticoides.

Abstract: Introduction: current recommendations to treat lupus nephritis (LN) point to low-dose glucocorticoids to control the disease and avoid cumulativedamage. Objective: to learn about and compare the response of patients with proliferative LN who are treated following two prednisone therapy guidelines: reduced initial doses 30 mg/d during the induction stage. Method: clinical, analytical and therapeutic guidelines of patients with proliferative LN were compared and classified into two groups according to the standard or low-dose initial prednisone dose. Results: 21 patients with proliferative LN were studied (n=12 low-dose initial prednisonevs. n=9 standard initial prednisone). No significant differences were found between clinical and analytical variables, although a significantly different statistic difference was observed in the number of methylprednisone pulses (5 ± 2.95 initial prednisone 30 mg/d, p = 0.041) and in the prednisone dose accumulated in 6 months (12.8 mg ± 4.9 initial prednisone 30 mg/d, p =0.008). No significant differences were seen between both groups in the proportion of patients who achieved complete response, neither in terms of the time it took to achieve it or in the side effects. Conclusions: the treatment plan for the initial prednisone <30 mg/d was associated to a lower cumulative dose of response prednisone considering the comparable treatment, what suggests there being smaller cumulative harm as a consequence of the use of glucocorticoids.

Resumo: Introdução: as recomendações atuais para o tratamento da nefrite lúpica (NL) estão orientadas a doses de glicocorticoides mais baixas para controlar a enfermidade e evitar o dano acumulado. Objetivo: conhecer e comparar a resposta ao tratamento de pacientes com NL proliferativa na etapa de indução com duas pautas de tratamento com prednisona (PDN): doses iniciais reduzidas 30 mg/d. Método: foram comparadas variáveis clínicas, analíticas e terapêuticas de pacientes com NL proliferativa divididos em dois grupos segundo a dose inicial de prednisona (PDNi) padrão ou reduzida. Resultados: 21 pacientes com NL proliferativa (n=12 PDNi reduzida vs. n=9 PDNi estândar) foram estudados. Não foram observadas diferenças significativas nas variáveis clínicas e analíticas. Observou-se uma diferença estatisticamente significativa no número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) e nas doses de prednisona acumulada aos 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). Não foram observadas diferenças significativas na proporção de pacientes que alcançaram a resposta completa, no tempo até alcançá-la nem nos efeitos adversos entre ambos grupos. Conclusões: o esquema terapêutico do grupo PDNi <30 mg/d foi associado a uma menor dose acumulada de prednisona em resposta ao tratamento comparável, o que sugere menos dano cumulativo relacionado ao uso de glicocorticoides.

Lupus neuropsiquiátrico. A propósito de tres casos y revisión de la literatura / Neuropsychiatric lupus Regarding three cases and review of the literature / Lúpus neuropsiquiátrico Em relação a três casos e revisão da literatura

Resumen: Las manifestaciones neuropsiquiátricas del lupus eritematoso sistémico (LES) constituyen un amplio espectro clínico con compromiso del Sistema Nervioso Central y Periférico por parte de esta enfermedad. Afecta aproximadamente a un 56% de los pacientes con LES, frecuentemente próximo al diagnóstico. Constituye un desafío diagnóstico, especialmente en pacientes sin antecedentes de la enfermedad. El diagnóstico es de exclusión. Se encuentra en revisión el rol de algunos auto-anticuerpos y técnicas de neuroimágen en la estrategia diagnóstica de esta afección. Se presentan tres casos clínicos y realizamos una revisión de la literatura.

Abstract: The neuropsichiatric manifestations of systemic lupus erythematosus are very wide, involving central and peripheral nervous system. Affecting approximately 56% of lupus patients, with higher incidence previous or next to the diagnosis. It is a challenge for phisicians, specially for patients without previous diagnostic of the desease. Diagnostic is of exclussion, because there are not specific test. There are in disccussion the role of some autoantibodies and neuroimagenological tecniques for this purpose. We present 3 case report and review of the literature.

Resumo: As manifestações neuropsiquiátricas do lúpus constituem um amplo espectro clínico com comprometimento do Sistema Nervoso Central e Periférico por esta doença. Afeta aproximadamente 56% dos pacientes com LES, quase sempre próximos ao diagnóstico. Constitui um desafio diagnóstico, principalmente em pacientes sem histórico da doença. O diagnóstico é exclusão. O papel de alguns autoanticorpos e técnicas de neuroimagem na estratégia de diagnóstico dessa condição está sendo analisado. Três casos clínicos são apresentados e revisamos a literatura.

The Clinician Faced With Anticochlear Antibodies: What to Do With Them?

BACKGROUND: Autoimmune inner ear disease as a cause of sensorineural hearing loss is a poorly understood entity. Thus, the role of anticochlear antibodies (ACLAs) in clinical management is still not well established. OBJECTIVE: The aims of this study were to describe the use of ACLAs in our clinical setting and to understand the clinicians' therapeutic approach in these cases. We also analyzed the usefulness of these autoantibodies in clinical practice. METHODS: A retrospective study with nonprobabilistic convenience sampling of patients who were tested for ACLAs in the period from January 1, 2013, to December 31, 2015, was performed. The study was carried out in 2 stages: (1) medical records of all patients who were investigated for ACLAs were reviewed. The following variables were analyzed: age, sex, reason for requesting ACLAs, concomitant autoimmune disease, audiogram, immunosuppressive treatment, duration of treatment, and clinical response; (2) patients who received immunosuppressive therapy were contacted by telephone. A visual analog scale (VAS) (0-10) was applied to evaluate the therapeutic response. RESULTS: Thirty-nine patients who were investigated for ACLAs were identified. The mean age was 41 (SD, 16) years; there were 33 female patients. Of the 34 patients with ACLA-positive antibodies, 16 patients received immunosuppressive agents, of for management of their sensorineural hearing loss, corticosteroids was the most commonly used treatment. No clinical improvement was reported by patients after immunosuppressive treatment in this subgroup. CONCLUSIONS: The role of ACLAs in the diagnosis and management of sensorineural hearing loss remains unclear. In this small study at a single institution, ACLA testing may not have improved the outcome of sensorineural hearing loss.

Estudio de una cohorte de pacientes con enfermedad tromboembólica venosa en seguimiento ambulatorio / Cohort study of pacients with venous thromboembolic disease assisted in ambulatory care / Estudo de umacoorte de pacientes comdoença tromboembólica venosa em acompanhamentoambulatorial

Resumen: La enfermedad tromboembólica venosa (ETEV) es una patología con morbilidad y mortalidad elevadas. Su manejo diagnóstico y terapéutico está en permanente revisión. La ausencia de estudios epidemiológicos en nuestro medio implica un desconocimiento de la forma de presentación, etiología y recurrencia de la misma. Se propone un estudio descriptivo sobre la población de pacientes con ETEV en seguimiento en la policlínica de Trombosis y Hemostasis del Hospital Pasteur de Montevideo, durante el período 2015-2016. Se registraron 35 pacientes con ETEV. La ETEV provocada se asoció predominantemente a factores de riesgo mayor y en los cuales falló la adecuada prescripción de tromboprofilaxis. En los pacientes con ETEV no provocada, las trombofilias diagnosticadas fueron el síndrome de anticuerpos anti fosfolípidos, déficit de Antitrombina y mutación del gen de la protrombina heterocigoto. Los pacientes con ETEV no provocada tuvieron un elevado porcentaje de recurrencias, la mitad de ellas asociadas a trombofilia y la otra mitad sin factor de riesgo predisponente (ETEV idopática).

Abstract: Venous thromboembolic disease (VTD) is a condition with high rates of morbidity and mortality. The etiologic diagnosis and therapeutics are in a continuous review process. In our country there are still no epidemiologic studies about the clinic presentation, etiology and recurrence of VTD. This is a cohort study of patients assisted in ambulatory care at the Thrombosis and Haemostasis Clinic of the Hospital Pasteur in Montevideo, for the 2015-2016 period. 35 patients were registered with VTD. Provoked VTD was associated with major risk factors in which optimal prescription of thromboprofilaxis failed. In patients with unprovoked VTD, testing for trombophiliashowed Antitrombin deficiency, hetrocigotic mutation of the Protrombin and antiphospholipid antibodies. Patients with unprovoked VTD showed a high percentage of recurrences, half of them with associated trombophilia and the otherhalf with no risk factor (idiopatic VTD).

Resumo: O tromboembolismo venoso (VTE) é umadoençacom elevada morbilidade e mortalidade. Diagnóstico e manejo terapêutico está em constante revisão. A ausência de estudos epidemiológicos em nosso ambiente implica uma falta de apresentação, etiologia e recorrência do mesmo. Umestudodescritivonapopulação de pacientes com TEV monitorizaçãoproposto no polyclinic de Thrombosis and Haemostasis Hospital Pasteur em Montevidéu, durante o período de 2015-2016. 35 doentescom tromboembolismo venoso foramregistados. TEV causado predominantemente associada a fatores de risco aumentado e que falhou a prescriçãoadequada de tromboprofilaxia. Em pacientes com TEV não provocado os trombofilia foram diagnosticados síndrome anti fosfolipídiosdeficiência de antitrombina e mutação do heterozigoto protrombina. TEV pacientes nãocausaramuma elevada taxa de recorrência, metade delas associadacom trombofilia e meiasempredispondo factor de risco (idiopática VTD).

Evaluación de la prescripción de trombo-profilaxis farmacológica y valoración del impacto que generan distintas estrategias para mejorar su indicación / Evaluation of the prescription of pharmacological thrombo-prophylaxis and assessment of the impact generated by different strategies to improve its indication

Resumen: Introducción: La enfermedad tromboembólica venosa (ETEV) constituye la principal causa de muerte prevenible en pacientes hospitalizados. Actualmente se encuentra validado el score de Padua para detectar los pacientes con patología médica con alto riesgo de ETEV. Objetivos: analizar la prescripción de tromboprofilaxis farmacológica en pacientes internados por patología médica y analizar el impacto que genera la realización de distintas estrategias para estimular la prescripción de la misma. Material y métodos: se realizó un corte transversal de todos los pacientes internados en cuidados moderados de medicina en diciembre 2014 aplicando el score de Padua. Tras varias intervenciones de educación, se realizó un segundo corte transversal un año después aplicando la misma herramienta. Resultados: 48/67 pacientes analizados en el primer corte tenían alto riesgo de trombosis, sólo 29 tenían indicación de tromboprofilaxis farmacológica. 32/52 pacientes analizados en el segundo corte tenían indicación, estando prescripta en 26 de los mismos (p: 0,0062) Discusión: la inclusión del score de Padua en las historias clínicas, la realización de instancias de revisión de guías, promoción de tromboprofilaxis y concientización de la ETEV en el personal médico aumentaron significativamente su prescripción.

Abstract: Introduction: Venous thromboembolic disease (VTE) is the leading cause of preventable death in hospitalized patients. The Padua score is currently validated to detect patients with medical pathology with a high risk of VTE. Objectives: to analyze the prescription of pharmacological thromboprophylaxis in patients hospitalized for medical pathology and to analyze the impact of different strategies to stimulate the prescription of thromboprophylaxis. Methods: A cross-sectional study was carried out of all patients admitted to moderate medical care in December 2014 applying the Padova score. After several educational interventions, a second cross-sectional study was carried out one year later using the same tool. Results: 48/67 patients analyzed in the first cut had a high risk of thrombosis, only 29 had an indication of pharmacological thromboprophylaxis. 32/52 patients analyzed in the second section had an indication, being prescribed in 26 of them (p: 0.0062) Discussion: inclusion of the Padua score in the medical records, implementation of guidelines review, promotion of Thromboprophylaxis and ETEV awareness in the medical staff significantly increased its prescription.

Enfermedades autoinmunes sistémicas y tuberculosis: una mala asociación / Systemic autoimmune diseases and tuberculosis: a poor association

Resumen: Las enfermedades autoinmunes sistémicas son trastornos caracterizados por la alteración de los mecanismos reguladores de la identificación y tolerancia de las propias estructuras celulares con la resultante producción de autoanticuerpos e inmunocomplejos. Una de las complicaciones más frecuentes vinculadas al tratamiento de estas enfermedades es el riesgo de infecciones, entre ellas la tuberculosis, cuya prevalencia está en aumento en nuestro medio. Presentamos tres casos clínicos de patologías autoinmunes diferentes en los cuales se tuvo como complicación el desarrollo de tuberculosis en dos topografías distintas: meníngo-encefálica y pulmonar.

Abstract Autoimmune systemic diseases are characterized by the alteration of regulatory mechanisms of identification and tolerance of own cellular structures with the resulting production of autoantibodies and immune disorders. One of the most frequent complications related to the treatment of these diseases is the risk of infections, including tuberculosis, whose prevalence is increasing in our environment. We present three different clinical cases of ASD in which we observed as a complication the development of tuberculosis in two different topographies: meningoencephalic and pulmonary.