Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma.

BACKGROUND: Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking. OBJECTIVE: We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA). METHODS: COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed. RESULTS: Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years; total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs; there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0-156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies. CONCLUSION: These data support the long-term safety and efficacy of mepolizumab in patients with SEA.

[Pulmonary non invasive infection by Scedosporium apiospermum]. / Infección pulmonar no invasora por Scedosporium apiospermum.

We reported a case of non-invasive pulmonary infection by Scedosporium apiospermum in 67 years old female with bronchiectasis and caverns secondary to tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The patient was initially treated with itraconazole for six weeks without success and then voriconazole for 16 weeks, with good clinical response.

On the energy density of helical proteins.

We solve the problem of determining the energy actions whose moduli space of extremals contains the class of Lancret helices with a prescribed slope. We first see that the energy density should be linear both in the total bending and in the total twisting, such that the ratio between the weights of them is the prescribed slope. This will give an affirmative answer to the conjecture stated in Barros and Ferrández (J Math Phys 50:103529, 2009). Then, we normalize to get the best choice for the helical energy. It allows us to show that the energy, for instance of a protein chain, does not depend on the slope and is invariant under homotopic changes of the cross section which determines the cylinder where the helix is lying. In particular, the energy of a helix is not arbitrary, but it is given as natural multiples of some basic quantity of energy.

Occult breast cancer presenting as axillary lymphadenopathy - Case Report.

INTRODUCTION: Occult breast carcinoma (OBC) is a rare entity and therefore generates discussion regarding diagnosis, approach, and prognosis. This article aims to present a case of OBC and reviews some concepts discussed in the literature. PRESENTATION OF CASE: 43-year-old woman with right axillary adenopathies, without further complaints, whose biopsy shows a lymph node metastasis from invasive ductal carcinoma of the breast. Breast study, breast RMI and FDG-PET did not identify the primary tumour. As decided by a multidisciplinary team, the patient underwent neoadjuvant chemotherapy, axillary surgery, breast radiotherapy and hormone therapy. Four years after surgery, the patient has no evidence of the primary tumour and no axillary recurrence. DISCUSSION: OBC was described in 1907. Although the best therapeutic approach is widely discussed in the literature, it is consensual that as long as the existence of a primary tumour is excluded by breast MRI, the conservative approach (excision of axillary adenopathy and breast and axillary radiotherapy) is more advocated. CONCLUSION: Breast cancer must be considered in the differential diagnosis of a patient with axillary lymphadenopathy. The conservative approach of OBC is the preferred since breast MRI does not identify any suspicious lumps.

Challenges and Considerations on Risk-Reducing Surgery in BRCA1/2 Patients with Advanced Breast Cancer.

Cancer survivors harboring inherited pathogenic variants in the breast cancer (BC) susceptibility genes BRCA1 or BRCA2 are at increased risk of ovarian cancer (OC) and also of contralateral BC. For these women, risk-reducing surgery (RRS) may contribute to risk management. However, women with locally advanced or metastatic breast cancer (ABC) were excluded from clinical trials evaluating the benefit of these procedures in the BRCA1/2 carriers, and thus, current guidelines do not recommend RRS in this specific setting. Although ABC remains an incurable disease, recent advances in treatment have led to increased survival, which, together with improvement in RRS techniques, raise questions about the potential role of RRS in the management of BRCA1/2 ABC patients. When should RRS be discussed as an option for BRCA1/2 patients diagnosed with ABC? To address this issue, we report two clinical cases that reflect new challenges in routine oncology practice. Team experience and patient motivations may shape multidisciplinary decisions in the absence of evidence-based data. A wise rationale may be the analysis of the competing risks of death by a previous ABC against risk of death by a secondary BC or OC, tailored to patient preferences.

Incorporating New Evidence on Inhaled Medications in COPD. The Latin American Chest Association (ALAT) 2019. / Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019.

This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting ß2-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of <300 cells/µl. All this evidence, categorized according to the severity of the obstruction, symptoms, and risk of exacerbations, has been used to generate an algorithm for the use of inhaled medication in COPD.

Infección pulmonar no invasora por Scedosporium apiospermum / Pulmonary non invasive infection by Scedosporium apiospermum

We reported a case of non-invasive pulmonary infection by Scedosporium apiospermum in 67 years old female with bronchiectasis and caverns secondary to tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The patient was initially treated with itraconazole for six weeks without success and then voriconazole for 16 weeks, with good clinical response.

Reportamos el caso clínico de una infección pulmonar no invasora por Scedosporium apiospermum en una mujer de 67 años de edad, con bronquiectasias y cavernas pulmonares secundarias a una tuberculosis. El diagnóstico se realizó con la TAC pulmonar y cultivos de lavado bronquial. La paciente fue tratada inicialmente con itraconazol oral por seis semanas sin respuesta y luego voriconazol vía oral por 16 semanas, con una buena respuesta clínica.

Incorporando nuevas evidencias sobre medicamentos inhalados en la EPOC. Asociación Latinoamericana de Tórax (ALAT) 2019 / Incorporating New Evidence on Inhaled Medications in COPD. The Latin American Chest Association (ALAT) 2019

Este documento sobre EPOC de la Asociación Latinoamericana de Tórax (ALAT) 2019 analiza las nuevas evidencias de medicación inhalada utilizando la metodología de preguntas clínicas en formato PICO. Surgen de este análisis los siguientes puntos claves: 1) no hay evidencia que compare el uso de broncodilatadores de acción corta vs. larga en pacientes con EPOC leve; en aquellos con EPOC moderada-grave existe mayor beneficio de los broncodilatadores de acción larga, 2) beneficios similares de la monoterapia con antimuscarínicos de acción prolongada (LAMA) y la terapia combinada β2-agonistas de acción larga/corticosteroides inhalados (LABA/CIS), asociada esta última a mayor riesgo de neumonía, 3) mayores beneficios del LABA/LAMA en función pulmonar y riesgo de exacerbación vs. LABA/CIS (esta última con mayor riesgo de neumonía) y 4) mayores beneficios de la terapia LAMA/LABA/CIS comparada con LABA/LAMA sobre el riesgo de exacerbaciones moderadas-severas. En relación al rol de los eosinófilos para guiar el uso de los CIS: debe considerarse su retiro cuando la indicación inicial fue errada o sin respuesta, en pacientes con efectos secundarios como neumonía, y en aquellos con bajo riesgo de exacerbación con recuento de eosinófilos en sangre < 300 cél/μl. Incorporando estas evidencias según la gravedad de la obstrucción, síntomas y riesgo de exacerbaciones se genera un algoritmo para el uso de medicación inhalada en la EPOC

This document on COPD from the Latin American Chest Association (ALAT-2019) uses PICO methodology to analyze new evidence on inhaled medication and answer clinical questions. The following key points emerged from this analysis: 1) evidence is lacking on the comparison of short-acting vs. long-acting bronchodilators in patients with mild COPD; patients with moderate-to-severe COPD obtain greater benefit from long-acting bronchodilators; 2) the benefits of monotherapy with long-acting antimuscarinic agents (LAMA) and combined therapy with long-acting β2-agonists and inhaled corticosteroids (LABA/ICS) are similar, although the latter is associated with a greater risk of pneumonia; 3) LABA/LAMA offer greater benefits in terms of lung function and risk of exacerbation than LABA/ICS (the latter involve an increased risk of pneumonia), 4) LAMA/LABA/ICS have greater therapeutic benefits than LABA/LAMA on the risk of moderate-severe exacerbations. With regard to the role of eosinophils in guiding the use of ICS, ICS withdrawal must be considered when the initial indication was wrong or no response is elicited, in patients with side effects such as pneumonia, and in patients with a low risk of exacerbation and an eosinophil blood count of <300 cells/μl. All this evidence, categorized according to the severity of the obstruction, symptoms, and risk of exacerbations, has been used to generate an algorithm for the use of inhaled medication in COPD

Comparación del reflejo tusígeno desencadenado por capsaicina y ácido cítrico en sujetos normales / Comparison of cough reflex due to capsaicin and citric acid in normal subjects

El reflejo de la tos se evoca habitualmente por inhalación de aerosoles. La capsaicina (C) y el ácido cítrico (AC) han sido usados clínicamente y estimularían receptores diferentes. El objetivo del presente trabajo fue comparar la respuesta tusígena a ambas sustancias en voluntarios sanos. Estudiamos 17 sujetos (18-23 años, 11 varones) que recibieron C y AC al menos con una semana de diferencia. Las drogas se administraron con un nebulizador Hudson a 8 L/min, con una pieza bucal. La C se administró con doble ciego en dosis aleatoria (0.31-20 uM) y el AC en dosis crecientes (0.5-32 porciento) ya que este último presenta taquifilaxis. Todos los sujetos presentaron tos y no hubo efectos adversos. El número de toses fue grabado y contado en duplicado. Con ambas sustancias fue posible construir curvas dosis respuestas. La media (ñES) del total acumulativo de toses provocadas por la inhalación de C fue 15.0ñ1.8. La inhalación de AC provocó 12.9ñ1.6 toses. La concentración que produjo 2 toses (media geométrica e intervalos de confianza 95 porciento) fue 4.8 uM (3.5-6.6) para C y 5.3 porciento (3.4-8.4) para AC. El número de toses provocado por C y AC estuvo correlacionado en forma significativa (r=0.71.p=0.0012), al igual que las concentraciones que provocaron 2 toses (r=0.56,p<0.001). Concluímos que tanto el AC como la C permiten analizar el reflejo tusígeno. A pesar de su diferente farmacología existió correlación en el número de toses provocadas por ambas substancias y ello permite plantear que la respuesta tusígena está condicionada en parte por susceptibilidad individual

Síndrome de Pancoast causado por actinomicosis pulmonar / Pancoast syndrome due to pulmonary actinomycosis

Se comunica el caso clínico de un paciente no fumador de 35 años que presentó un síndrome de Pancoast causado por una actinomicosis pulmonar. La radiografía de toráx y la tomografía axial computada demostraron una masa en el vértice pulmonar izquierdo sin adenopatías ni compromiso óseo. La broncoscopía no reveló lesiones y la citilogía obtenida por este medio y por punción pulmonar no demostró células neoplásicas. La tinción de Gomori-Groccott del material obtenido por punción pulmonar mostró estructuras filamentosas típicas de la especie actinomicosis. No se efectuaron cultivos de esta muestra. El tratamiento con penicilina produjo una mejoría clínica y radiográfica sin recurrencia después de un año de seguimiento. Concluímos que en casos con síndrome de Pancoast sin factores de riesgo para cáncer bronquial debería investigarse tanto una etiología neoplásica como causas infecciosas

Resistencia a la fatiga de los músculos inspiratorios: comparación de dos métodos de medición / Inspiratory muscle endurance: comparison of 2 methods for measuring

Con el propósito de establecer si la medición de la presión inspiratoria máxima sostenible (PIMS) es un método útil para evaluar la tolerancia a la fatiga de los músculos inspiratorios, en 8 sujetos normales comparamos este método con la ventilación máxima sostenible (VMS), que es ampliamente utilizada para evaluar este aspecto de la función muscular inspiratoria. La VMS alcanzó un promedio de 88.4 ñ 28 L min -1 correspondiente a un 61 ñ 11,4% (DS) de la ventilación máxima voluntaria teórica; la PIMS fue de 94 ñ 33 cm H2O lo que correspondió a un 73 ñ 12,7% de la presión inspiratoria máxima. La carga máxima sostenible fue de 387 ñ 149 g. Se observó una correlación significativa entre PIMS y VMS (r = 0.71 p < 0.05) y entre PIMS y carga máxima sostenible (r = 0.92 p < 0.001). La relación entre esta última y la VMS no alcanzó significación estadística (r = 0.62). La duración de la medición de VMS fluctuó entre 40 y 60 minutos y la medición de la PIMS entre 15 y 20 minutos. La correlación significativa entre las dos pruebas sugiere que PIMS es un método útil para medir la resistencia a la fatiga con la ventaja de su mayor simplicidad y corta duración

Tríplice artrodese do pé na paralisia cerebral / Triple arthrodesis of the foot in cerebral plasied patients

No período entre maio de 1985 e setembro de 1995 foram submetidos a tríplice artrodese 18 pacientes (21 pTs) portadores de paralisia cerebral espástica com deformidades rígidas dos pés, dos quais 16 (18 pés) retornaram para reavaliaçäo clínica e revisäo dos prontuários. Esse grupo foi constituído de 8 pacientes do sexo feminino e 8 do masculino, com idade média na ocasiäo da cirurgia de 15 anos e 11 meses e tempo de seguimento médio de 4 anos. A indicaçäo da tríplice artrodese foi baseada na avaliaçäo clínica e radiográfica objetivando a obtençäo de pé plantígrado, estável e indolor à marcha. Procedimentos associados foram necessários no mesmo tempo operatório para correçäo de outras deformidades; o mais comum foi o alongamento do tendäo de Aquiles. A análise dos resultados baseou-se em parâmetros clínicos, radiográficos e subjetivos. Os autores obtiveram 72 por cento de resultados satisfatórios e 28 por cento de insatisfatórios.