Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope.

INTRODUCTION: Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. MATERIAL AND METHODS: We conducted an observational study that included patients with syncope and who underwent TTE between 1990 and 2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). RESULTS: The study included 3302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. CONCLUSIONS: The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope.

Efecto de la edad y el sexo en el rendimiento diagnóstico del ecocardiograma en pacientes con síncope / The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope

Introducción El síncope es motivo de numerosas pruebas diagnósticas, entre las que está el ecocardiograma transtorácico (ETT). Existe evidencia previa que sugiere escasa utilidad de esta prueba. Nuestro objetivo fue evaluar su rendimiento diagnóstico en el síncope, analizando el efecto de la edad y el sexo. Materiales y métodos Estudio observacional en el que se incluyeron pacientes con síncope y ETT entre 1990 y 2015. Se definieron hallazgos diagnósticos relacionados con el síncope. Realizamos un análisis descriptivo evaluando el rendimiento diagnóstico en global, y en función de edad y sexo. Resultados Se incluyeron 3.302 pacientes, siendo el rendimiento diagnóstico del 8,8%; el hallazgo más frecuente fue disfunción ventricular (4,5%). La probabilidad de ETT diagnóstico aumentó significativamente con la edad (p<0,001), siendo baja en menores de 50 años (2,3%). El sexo masculino se relacionó significativamente con ETT diagnóstico (p<0,001), a expensas de mayor frecuencia de disfunción ventricular. Conclusiones El rendimiento diagnóstico del ETT en pacientes con síncope es moderado, siendo bajo en edades inferiores a 50 años, y menor en mujeres que en hombres. Estos factores deben ser tenidos en cuenta a la hora del estudio diagnóstico de los pacientes con síncope (AU)

Introduction Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. Material and methods We conducted an observational study that included patients with syncope and who underwent TTE between 1990-2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). Results The study included 3,302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. Conclusions The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope (AU)

Resultados de la reparación de Bankart/plicatura y remplissage en el tratamiento de la luxación anteroinferior recurrente del hombro. Correlación con la escala de ISIS / Bankart repair and remplissage in recurrent anteroinferior shoulder dislocation, Correlation with ISIS scale

Introducción: La luxación recurrente anteroinferior del hombro es consecuencia de una luxación aguda traumática que, en pacientes jóvenes, menores de veinte años, se ha estimado puede llegar al 97% de recurrencia, pero que disminuye a medida que aumenta la edad, excepto en pacientes mayores con rupturas asociadas del manguito rotador. Al ser una patología incapacitante que afecta la calidad de vida de las personas, hay una mayor tendencia a tratarla por métodos quirúrgicos que con rehabilitación. La lesión fundamental es el desprendimiento del labrum anterior de la glenoides conocida como la lesión de Bankart-Perthes, estructura que tiene limitaciones para cicatrizar de manera anatómica con tratamientos incruentos, perpetuando la inestabilidad. A medida que recurre la luxación se presentan lesiones óseas asociadas tanto en la glenoides denominada Bankart ósea, así como en la cabeza humeral en su región posterosuperior o lesión de Hill-Sachs, que aumentan la posibilidad de recurrencia. Se han descripto diferentes técnicas abiertas y artroscópicas para corregir la luxación, pero por la heterogeneidad de la lesión no hay un tratamiento para corregirla que sea patrón de oro. Nuestro objetivo es describir los resultados clínicos en pacientes con luxación recurrente anteroinferior de hombro que fueron sometidos a cirugía artroscópica de reparación de Bankart/plicatura y remplissage y correlacionar los resultados con la escala preoperatoria de ISIS. Materiales y métodos: se revisaron las historias clínicas de pacientes con diagnóstico de luxación de la articulación del hombro (S430) (M253), que fueron llevados a cirugía entre junio de 2015 y enero de 2019, analizando características de la(s) lesión(es), clasificación preoperatoria de acuerdo con la escala de ISIS, tipo de procedimiento(s) quirúrgico realizado y número de implantes. Resultados: de veinticinco pacientes operados por el autor senior (MMA) de luxación recurrente de hombro, veintitrés completaron el seguimiento con los procedimientos de reparación de Bankart/plicatura y la adición de un remplissage en casos de lesiones Hill-Sachs enganchantes. Todos tenían una escala de ISIS preoperatoria igual o inferior a 6. Al final del seguimiento ningún paciente reportó recurrencia de su luxación. Conclusión: en nuestra casuística, la reparación de Bankart/plicatura en pacientes con lesiones Hill-Sachs no enganchantes en asocio del remplissage produce excelentes resultados a corto y mediano plazo cuando la escala de ISIS es igual o inferior a 6. Nivel de evidencia: IV

Introduction: Recurrent anteroinferior shoulder dislocation is the consequence of an acute traumatic dislocation which, in young patients, under twenty years old, has been estimated to reach 97% of recurrence, but which decreases with increasing age, except in older patients with associated rotator cuff tears. Being a disabling pathology that affects people's quality of life, there is a greater tendency to treat it by surgical methods than with rehabilitation. The fundamental lesion is the detachment of the anterior labrum of the glenoid known as the Bankart-Perthes lesion, a structure that has limitations to heal anatomically with bloodless treatments, perpetuating instability. As the dislocation recurs, there are associated bone lesions both in the glenoid called Bony Bankart, as well as in the humeral head in its posterior superior region or Hill-Sachs lesion, which increase the possibility of recurrence. Different open and arthroscopic techniques have been described to correct dislocation, but due to the heterogeneity of the lesion, there is no gold standard treatment to correct it. Our objective is to describe the clinical results in patients with recurrent anteroinferior shoulder dislocation who underwent arthroscopic Bankart/plication repair and fill surgery and correlate the results with the preoperative ISIS scale. Materials and methods: the medical records of patients with a diagnosis of shoulder joint dislocation (S430) (M253), who were taken to surgery between June 2015 and January 2019, were reviewed, analyzing characteristics of the injury(s), classification preoperative according to the ISIS scale, type of surgical procedure(s) performed and number of implants. Results: of twenty-five patients operated by the senior author (MMA) for recurrent shoulder dislocation, twenty-three completed follow-up with Bankart/plication repair procedures and the addition of a fill in Hill-Sachs engaging lesions. All had a preoperative ISIS scale equal to or less than 6. At the end of follow-up, no patient reported recurrence of their dislocation.Conclusion: in our casuistry, Bankart/plication repair in patients with non-engaging Hill-Sachs lesions in association with filling produces excellent results in the short and medium term when the ISIS scale is equal to or less than 6. Level of Evidence: IV

Un incremento exagerado de la presión arterial con el ejercicio no predice mortalidad ni eventos cardiovasculares graves en mujeres referidas a ecocardiografía de ejercicio por razones clínicas / An exaggerated increase in blood pressure with exercise does not predict mortality or severe cardiovascular events in women referred for exercise echocardiography for clinical reasons

FUNDAMENTO Y OBJETIVOS: La asociación entre un incremento exagerado de la presión arterial sistólica con el ejercicio (IEPASE) y la probabilidad de eventos cardiovasculares es controvertida y poco estudiada en población femenina. Nuestro propósito fue determinar la posible asociación de un IEPASE con mortalidad y eventos cardiovasculares en mujeres referidas a ecocardiografía de ejercicio por enfermedad coronaria conocida o sospechada. PACIENTES Y MÉTODOS: Se realizó ecocardiografía de ejercicio a 3.942 mujeres con enfermedad coronaria conocida o sospechada. El IEPASE se definió como un incremento de la presión arterial sistólica con el ejercicio ≥70mmHg. Los objetivos fueron mortalidad global y cardíaca, infarto agudo de miocardio (IM), accidente cerebrovascular (ACV) e intervenciones de revascularización coronaria. RESULTADOS: Trescientas treinta y dos mujeres desarrollaron IEPASE durante los test. En el seguimiento se registraron un total de 458 muertes (162 de origen cardíaco), 212 IM, 89 ACV y 345 intervenciones de revascularización coronaria. La tasa anual de mortalidad global y cardiaca fue inferior en el subgrupo de pacientes con IEPASE (0,15% vs. 2,3%, p = 0,02 y 0,01% vs. 0,2%, p = 0,015, respectivamente). No observamos diferencias significativas en las tasas de IM, ACV y de intervenciones de revascularización coronaria, que fueron, respectivamente, del 1,1%, 0,43% y 2,24% en pacientes con IEPASE y del 0,09%, 0,05% y 0,13% en aquellas mujeres sin IEPASE (p = 0,66; p = 0,57; p = 0,19, respectivamente), Tras un ajuste multivariante el IEPASE no resultó predictor de mortalidad ni de eventos cardiovasculares. CONCLUSIONES: El IEPASE no se asoció con mortalidad ni eventos cardiovasculares graves en mujeres con enfermedad coronaria conocida o sospechada

BACKGROUND AND OBJECTIVES: The association between an exaggerated systolic blood pressure increase with exercise (EBPIE) and the probability of cardiovascular events is controversial and poorly studied in the female population. Our aim was to determine the possible association between EBPIE on one hand and mortality and cardiovascular events on the other in women referred for exercise echocardiography due to known or suspected coronary artery disease. PATIENTS AND METHODS: A total of 3942 women with known or suspected coronary artery disease underwent exercise echocardiography. We defined EBPIE as a ≥70mm Hg increase in systolic blood pressure with exercise. The study endpoints were overall and cardiac mortality, acute myocardial infarction (MI), stroke and coronary revascularisation procedures. RESULTS: A total of 332 women developed EBPIE during the test. During the follow-up, 458 deaths (162 of cardiac origin), 212 MIs, 89 strokes and 345 coronary revascularisation procedures were recorded. The annual rates of overall and cardiac mortality were lower in the patient subgroup with EBPIE (0.15% vs. 2.3%, P=.02 and 0.01% vs. 0.2%, P=.015, respectively). There were no significant differences in the rates of MI, stroke and the need for coronary revascularisation procedures, which occurred in 1.1%, 0.43% and 2.24% of the patients with EBPIE, respectively, and occurred in 0.09%, 0.05% and 0.13% of the women without EBPIE (P=.66; P=.57; P=.19, respectively). After a multivariate adjustment, EBPIE was not a predictor of mortality or cardiovascular events. CONCLUSIONS: EBPIE is not associated with mortality or severe cardiovascular events in women with known or suspected coronary artery disease

Dermatosis Terra Firma-Forme / Terra Firma-Forme Dermatosis

RESUMEN Presentamos un caso típico de Dermatosis Terra Firma-Forme en un adolescente sano de 13 años de edad, visto recientemente en el Servicio de Dermatología de nuestro hospital. Con este caso queremos mostrar las características clínicas de esta dermatosis que con frecuencia no es correctamente diagnosticada o bien pasa desapercibida durante años lo que origina preocupación y ansiedad en el paciente además de pruebas diagnósticas innecesarias. Su diagnóstico es clínico apoyado en la dermatoscopía y el tratamiento sencillo, presentando escasas recidivas.

SUMMARY We report a typical case of a Terra Firma-Forme Dermatosis in a 13-year-old healthy male recently seen in the Dermatology Department of our hospital. The aim of the authors is to show clinical features of this frequently misdiagnosed and underreported dermatosis causing concern and anxiety in the patient as well as unnecessary diagnostic tests. Its diagnosis is clinical supported by dermoscopy and its simple treatment presents few recurrences.

An exaggerated increase in blood pressure with exercise does not predict mortality or severe cardiovascular events in women referred for exercise echocardiography for clinical reasons. / Un incremento exagerado de la presión arterial con el ejercicio no predice mortalidad ni eventos cardiovasculares graves en mujeres referidas a ecocardiografía de ejercicio por razones clínicas.

BACKGROUND AND OBJECTIVES: The association between an exaggerated systolic blood pressure increase with exercise (EBPIE) and the probability of cardiovascular events is controversial and poorly studied in the female population. Our aim was to determine the possible association between EBPIE on one hand and mortality and cardiovascular events on the other in women referred for exercise echocardiography due to known or suspected coronary artery disease. PATIENTS AND METHODS: A total of 3942 women with known or suspected coronary artery disease underwent exercise echocardiography. We defined EBPIE as a ≥70mm Hg increase in systolic blood pressure with exercise. The study endpoints were overall and cardiac mortality, acute myocardial infarction (MI), stroke and coronary revascularisation procedures. RESULTS: A total of 332 women developed EBPIE during the test. During the follow-up, 458 deaths (162 of cardiac origin), 212 MIs, 89 strokes and 345 coronary revascularisation procedures were recorded. The annual rates of overall and cardiac mortality were lower in the patient subgroup with EBPIE (0.15% vs. 2.3%, P=.02 and 0.01% vs. 0.2%, P=.015, respectively). There were no significant differences in the rates of MI, stroke and the need for coronary revascularisation procedures, which occurred in 1.1%, 0.43% and 2.24% of the patients with EBPIE, respectively, and occurred in 0.09%, 0.05% and 0.13% of the women without EBPIE (P=.66; P=.57; P=.19, respectively). After a multivariate adjustment, EBPIE was not a predictor of mortality or cardiovascular events. CONCLUSIONS: EBPIE is not associated with mortality or severe cardiovascular events in women with known or suspected coronary artery disease.

The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope. / Efecto de la edad y el sexo en el rendimiento diagnóstico del ecocardiograma en pacientes con síncope.

INTRODUCTION: Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. MATERIAL AND METHODS: We conducted an observational study that included patients with syncope and who underwent TTE between 1990-2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). RESULTS: The study included 3,302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. CONCLUSIONS: The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope.

Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.