[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? / Inmunoterapia vs. terapia diana en el paciente con melanoma avanzado y mutación BRAF V600, ¿por cuál comenzar?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

Breast cancer in the 21st century: from early detection to new therapies. / El cáncer de mama en el siglo XXI: de la detección precoz a los nuevos tratamientos.

The analysis of the causes that have given rise to a change in tendency in the incidence and mortality rates of breast cancer in the last few decades generates important revelations regarding the role of breast screening, the regular application of adjuvant therapies and the change of risk factors. The benefits of early detection have been accompanied by certain adverse effects, even in terms of an excessive number of prophylactic mastectomies. Recently, several updates have been published on the recommendations in breast cancer screening at an international level. On the other hand, the advances in genomics have made it possible to establish a new molecular classification of breast cancer. Our aim is to present an updated overview of the epidemiological situation of breast cancer, as well as some relevant issues from the point of view of diagnosis, such as molecular classification and different strategies for both population-based and opportunistic screening.

Moderate-intensity aerobic exercise training as an adjunct to trauma-focused psychotherapy in traumatized refugees and asylum seekers: study protocol of a randomized controlled trial.

Background: Refugees with exposure to multiple traumatic events are at high risk for developing posttraumatic stress disorder (PTSD) and depression. Narrative exposure therapy (NET) is an effective treatment for the core symptoms of PTSD, but it does not reliably reduce depressive symptoms. Endurance exercise on the other hand was consistently found to be effective in treating depression making it a promising adjunct to NET. Up to date, no studies exist investigating the combination of NET and endurance exercise in a sample of refugees with PTSD and comorbid depression.Objectives: In the proposed randomized controlled trial, we aim to investigate whether a combination of NET and moderate-intensity aerobic exercise training (MAET) enhances treatment outcome for refugees with PTSD and comorbid depressive symptoms. We expect a greater improvement in psychopathology in participants who receive the combined treatment.Methods and analysis: 68 refugees and asylum seekers with PTSD and clinically relevant depressive symptoms will be recruited in the proposed study. Participants will be randomly assigned to receive either NET only (NET-group) or NET plus MAET (NET+-group). All participants will receive 10 NET sessions. Participants in the NET+-group will additionally take part in MAET. Primary (PTSD, depression) and secondary (general mental distress, agoraphobia and somatoform complaints, sleep quality) outcome measures will be assessed before treatment, after treatment, and at six-month follow-up. The hypotheses will be tested with multiple 2 × 3 mixed ANOVA's.Trial registration: German Clinical Trials Register identifier: DRKS00022145.

Refugees are at particularly high risk of developing posttraumatic stress disorder and comorbid depressive symptoms due to exposure to multiple man-made traumatic events.Narrative exposure therapy reliably reduces symptoms of posttraumatic stress disorder, but many patients retain their clinical diagnosis, untreated comorbid depressive symptoms may interfere with treatment response.The randomized controlled trial aims to investigate whether combining narrative exposure therapy with moderate-intensity aerobic exercise training enhances treatment outcomes for refugees with posttraumatic stress disorder and comorbid depressive symptoms, compared to narrative exposure therapy as a stand-alone treatment.

Treatment in esophagogastric junction cancer: Past, present and future. / Tratamientos oncológicos en el cáncer de unión esofagogástrica: pasado, presente y futuro.

Adenocarcinomas of the gastroesophageal junction represent 27% of all gastric tumors. n recent years, it has been classified as an entity of its own, with specific treatments that are sometimes differentiated from gastric treatments. Treatment can be based on chemotherapy (CTx) or chemoradiotherapy (CRTx) that is administered preoperatively (neoadjuvant), postoperatively (adjuvant) or perioperatively. There are studies that have tested several treatment modalities, but there is currently no single protocolized sequence. The results point to an improvement in survival when we administer preoperative treatment, with evidence in favor of CRTx and CTx. Studies are already underway with targeted treatment that aim to increase the activity of traditional chemotherapy. In the next few years, we should know the role of immunotherapy in this group of patients.

Intranasal self-administration of local anesthetic (ropivacaine) for sphenopalatine ganglion block, for treatment of second trigeminal branch neuralgia secondary to maxillary sinus curettage: A case report. / Autoadministración intranasal de anestésico local (ropivacaína) para bloqueo del ganglio esfenopalatino, para tratamiento de neuralgia de la segunda rama del trigémino secundaria a curetaje del seno maxilar: informe de un caso.

Trigeminal neuralgia (TN) is a severe and often underestimated facial pain that affects quality of life. Pharmacological treatment is insufficient for pain control in 30% of cases and, although intervention techniques may be effective, there is a possibility of relapse and associated complications. The second division of the trigeminal nerve (V2) runs through the sphenopalatine ganglion (SPG), which is anatomically accessible to blocking due to its superficial location in the nasal cavity. We report a clinical case of a patient with uncontrolled V2 TN that was put on ambulatory self-administered SPG block with nasal swabs soaked in 0.75% ropivacaine. In the follow-up visits, we confirmed that this adjuvant treatment provided a significant pain relief over 24hours with a decrease in the number of exacerbations.

Lymph Node Dissection in Patients With Melanoma and Sentinel Lymph Node Metastasis: An Updated, Evidence-Based Decision Algorithm. / Disección ganglionar en el paciente con melanoma y metástasis en el ganglio centinela: propuesta de decisión basada en la evidencia actual.

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with low-risk sentinel node metastasis (sentinel node tumor load ≤1mm).

Role of voltage-gated sodium channel blockers in the treatment of chronic pain: Potential uses in clinical practice based on available evidence. / Papel de los bloqueadores de los canales de sodio dependientes de voltaje en el tratamiento del dolor crónico: usos potenciales en la práctica clínica según la evidencia disponible.

Once patients have failed first line therapy, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose amongst alternative agents, an understanding of pharmacology, pharmacokinetics, and available evidence in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of voltage-gated sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine acetate) for adjunct pain medication management; including research updates in pharmacology, pharmacokinetics, and evidence for pain along on this therapeutic group with promising future areas of research. Although evidence for voltage-gated sodium channel blockers in chronic pain management is limited, emerging research has identified this area as promising for additional clinical trials to better guide clinical practice.

Rol del tratamiento sistémico en el cáncer gástrico

El cáncer gástrico en estadios tempranos es curable con cirugía, pero en muchos otros casos es mortal. La adición de quimioterapia y radioterapia a la cirugía ha mejorado la supervivencia general en estadios localizados. Los tratamientos sistémicos, que incluyen quimioterapia, inmunoterapia, anticuerpos monoclonales, otras terapias dirigidas, o combinaciones de éstas se están usando en estadios avanzados para mejorar la supervivencia y paliar síntomas.

Pterigión recidivante y sus alternativas terapéuticas / Recurrent pterygium and its therapeutic alternatives

RESUMEN El pterigión se trata de un crecimiento fibrovascular de morfología triangular que se extiende desde la conjuntiva hacia la córnea. Está clasificado dentro de las degeneraciones no involutivas o tumoraciones epiteliales benignas corneales y se presenta en el 10,2 por ciento de la población. El tratamiento quirúrgico es el más indicado, y tiene una tasa de recidiva independientemente de la técnica quirúrgica utilizada del 10,7 por ciento; esta tasa de recidiva se evidencia por la neovascularización y el tejido cicatrizal antes de los dos meses después de la cirugía. Lo anterior ha incentivado la investigación de nuevos tratamientos que disminuyan esta complicación, por lo que el objetivo de esta revisión bibliográfica fue la búsqueda de alternativas terapéuticas para el pterigión recidivante. Se realizó una búsqueda automatizada sobre el tema, utilizando la plataforma Infomed, cuya información fue resumida para la elaboración del informe final. Concluimos que existen diferentes tratamientos adyuvantes para disminuir la tasa de recurrencia, y es necesario realizar estudios donde se determine el tiempo y la frecuencia en la aplicación de estos para obtener resultados más efectivos en su uso(AU)

ABSTRACT Pterygium is a fibrovascular growth of triangular shape that extends from the conjunctiva to the cornea. It has been classified as a noninvolutionary degeneration or benign corneal epithelial tumor which affects 10.2 percent of the population. The treatment most commonly indicated is surgery, which has a recurrence rate of 10.7 percent, irrespective of the surgical technique used. Recurrence takes the form of neovascularization and scar tissue within two months after surgery. This has fostered research into new treatments to reduce this complication. The objective of the present bibliographic review was precisely to search for therapeutic alternatives for recurrent pterygium. An automated search was conducted about the topic on the platform Infomed. Data were summarized to write the final report. We concluded that there are several adjuvant treatments to reduce recurrence, and it is necessary to carry out studies determining the time and frequency of their application to obtain more effective results(AU)

Terapia complementaria a la insulina en el tratamiento de niños y adolescentes con diabetes mellitus tipo 1- (DM1) / Therapies complementaries to insulin in the treatment of children and adolescents with type 1 diabetes mellitus (T1DM)

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.

Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.

Ejercicio físico como tratamiento adyuvante de los trastornos mentales. Una revisión narrativa / Physical exercise as an adjuvant treatment of mental disorders. A narrative review

El ejercicio físico puede ser una herramienta importante para el manejo de personas con enfermedades psiquiátricas, puesto que un notable número de estudios longitudinales y transversales ha demostrado que el mismo se constituye en una estrategia preventiva y en un enfoque adyuvante del tratamiento de los trastornos mentales. En ese sentido, se ha evidenciado que las formas más efectivas de ejercicio físico son los ejercicios aeróbicos (tales como caminar, trotar, andar en bicicleta, nadar, entre otros) y los de fortalecimiento. El objetivo de este artículo es presentar una actualización general acerca del ejercicio físico como tratamiento adyuvante de los trastornos mentales. Esta es una revisión narrativa, no sistemática, centrada en literatura primaria seleccionada de una búsqueda en PubMed, SciELO y LILACS. Los términos clave que se utilizaron fueron los siguientes: "ejercicio físico y salud mental", "fisioterapia y salud mental", "ejercicio físico y trastornos mentales" y "ejercicio físico y psiquiatría". Se complementaron estos artículos con libros y capítulos de libros, resaltando hallazgos duplicados. Todos los miembros del equipo de investigación participaron en la revisión de la literatura. Aunque existen excelentes estudios y revisiones que analizan detalladamente el papel del ejercicio físico en el tratamiento específico de algunos trastornos mentales, se consideró que se necesitaba una revisión más general para brindar orientación a médicos psiquiatras y a fisioterapeutas en este campo de integración de la salud física y mental.

Physical exercise can be an important part of the management of people with psychiatric illnesses, since a considerable number of longitudinal and cross-sectional studies has shown that it constitutes a preventive strategy and an adjuvant approach to the treatment of mental disorders. In that sense, it has been demonstrated that the most effective forms of physical exercise are aerobic exercises (such as walking, jogging, cycling, swimming, among others) and strengthening. The aim of this article is to present a general update about physical exercise as an adjuvant treatment of mental disorders. This is a narrative review, not systematic, focused on primary literature selected from a search in PubMed, SciELO and LILACS. The key terms used were: "physical exercise and mental health", "physiotherapy and mental health", "physical exercise and mental disorders" and "physical exercise and psychiatry." These articles were supplemented with books and book chapters, highlighting duplicate findings. All members of the research team participated in the review of the literature. Although there are excellent studies and reviews that analyze in detail the role of physical exercise in the specific treatment of some mental disorders, it was considered that a more general revision was needed to provide guidance to psychiatrists and physiotherapists in this field of integration of physical and mental health.

Observaciones críticas en torno al ganglio centinela en el cáncer colorrectal / Critical observations about the sentinel lymph node in colorectal cancer

Introducción: La identificación del ganglio centinela durante el tratamiento quirúrgico del cáncer colorrectal puede ayudar a la correcta estadificación posoperatoria y trascender a la quimioterapia adyuvante en el seguimiento a fin de mejorar la supervivencia de estos enfermos. Objetivo: Identificar las técnicas utilizadas para detectar el ganglio centinela mediante acceso convencional o laparoscópico: tinción o radiotrazador, ex vivo o in vivo así como su influencia en la estadificación posoperatoria y en el tratamiento adyuvante correlacionado con la evolución del cáncer de colon. Material y Métodos: Revisión documental en formato electrónico e impreso de publicaciones actualizadas sobre el tema. Desarrollo: El estudio de los linfáticos supone el factor pronóstico más importante en el cáncer colorrectal sin metástasis. La detección del ganglio centinela es la técnica que mejor predice el estado ganglionar de un paciente y permite realizar estudios intensivos que mejoran la estadificación. Conclusiones: El estudio del ganglio centinela es una práctica reproducible sin aumento significativo del tiempo y costos. En el seguimiento de los enfermos clasificados N0 con ganglio centinela positivo parece haber tendencia a un porcentaje mayor de recidivas, lo que podría trascender a cambios en las pautas de tratamiento adyuvante en aras de mejorar la supervivencia(AU)

Introduction: The identification of the sentinel lymph node during surgical treatment of colorectal cancer can help the correct postoperative staging and go beyond adjuvant chemotherapy in the follow-up of patients with the aim to improve survival of these sick people. Objective: To identify the techniques used to detect the sentinel lymph node through either conventional or laparoscopic approach: staining or radiotracer ex vivo or in vivo, as well as its influence in postoperative staging and the adjuvant treatment correlated with the evolution of colon cancer. Material and Methods: Document review of up-to-date publications about the topic in both electronic and printed formats. Development:The study of lymphatics is considered the most important prognostic factor in the colorectal cancer without metastases. The detection of the sentinel node is the technique that best predicts the lymph node status in a patient, and allows to conduct intensive studies to improve staging. Conclusions:The study of the sentinel lymph node is a reproducible practice without a significant increase in time and costs. The follow-up of patients classified as NO with a positive sentinel lymph node seems to have a tendency to a higher percentage of relapses, which could go beyond changes in the adjuvant treatment guidelines aimed at improving survival(AU)

Experiencia clínica en el tratamiento adyuvante de los pacientes con melanoma de tronco y extremidades estado III en un hospital del Tercer Mundo / Clinical experience with adjuvant treatment of patients with Stage III melanoma of the trunk and extremities in a developing country

Objetivos: describir la experiencia del uso de interferón adyuvante en altas dosis en pacientes con melanoma de tronco y extremidades estadio III y establecer las causas por las que los pacientes con indicación del tratamiento adyuvante no lo recibieron, así como la toxicidad y los principales desenlaces. Materiales y métodos: se trata de una cohorte retrospectiva de pacientes con diagnóstico de melanoma de tronco y extremidades, que fueron llevados a tratamiento quirúrgico de la lesión primaria y vaciamiento ganglionar durante 10 años en el INC (1999-2009) y que tenían indicación de tratamiento adyuvante con interferon. Resultados: se identificaron 88 pacientes con melanoma de tronco y extremidades estado clínico ni, de los cuales 50 (56,8%) recibieron tratamiento adyuvante con Interferón. Entre las principales razones por las cuales los 38 pacientes restantes no lo recibieron se encontraban la edad y comorbilidades asociadas (21), consulta diferida a oncología (5), decisión del oncólogo clínico (5). Solo el 36% (18) pacientes recibió el interferón por más de 10 meses y el 62% (N = 31) de los pacientes suspendió el tratamiento por progresión de la enfermedad (N = 16, 51,6%) y 25 pacientes (28,4%) presentaron toxicidad grado III. Se encontró una menor tasa de incidencia de recaídas en el grupo que recibió el medicamento. Conclusión: en esta cohorte se encontró que los pacientes con melanoma estado III que recibieron tratamiento adyuvante con interferón tenían una menor tasa de recaída y una mejor supervivencia libre de enfermedad, lo cual se relaciona con lo reportado en la literatura.

Objectives: To describe the experience with the use of adjuvant high-dose interferon in patients with stage III melanoma of the trunk and extremities, establishing the causes why patients with an indication of adjuvant treatment did not receive it, as well as major toxicity and outcomes. Materials and Methods: This is a retrospective study of a cohort of patients diagnosed with melanoma of the trunk and extremities, who were subjected to surgical treatment of the primary lesion and lymph node dissection in the INC over a ten-year period (1999-2009), and who had an indication for Interferon adjuvant treatment. Results: A total 88 patients were diagnosed with Stage III melanoma of the trunk and extremities, of whom 50 (56.8%) were identified to have received adjuvant treatment with interferon. Among the main reasons why the remaining 38 patients did not receive it were, age and associated comorbidities (21), delayed oncology consultation (5), and decision of medical oncologist (5). Only 36% (18) patients received interferon for more than 10 months, and 62% of patients (N = 31) discontinued treatment. The main reason for suspending treatment was disease progression (N = 16, 51.6%), and 25 patients had grade III toxicity. A lower incidence of relapse was found in the group receiving the drug. Conclusion: In this cohort it was found that patients with stage III melanoma receiving adjuvant interferon therapy had a lower relapse rate and better disease-free survival, which is in agreement with that reported in the literature.

Pentoxifylline as Adjunctive Therapy in Children with Acute Bacterial Meningitis

Introduction. Pentoxifylline, an inhibitor of tumor necrosis factor, has been shown in animal models of acute bacterial meningitis that reduce the host inflammatory response. Objective. To evaluate the effect of pentoxifylline administrated as adjunctive therapy in the treatment of acute bacterial meningitis in children. Material and methods. Prospective and open study that included children, between 3 months to 15 years old hospitalized in the Institute of Tropical Medicine, of Asunción, Paraguay, with the diagnosis of acute bacterial meningitis. Patients were randomly assigned, to receive in addition to antibiotic therapy (cefotaxime or ceftriaxone) pentoxifylline, dexamethasone, or neither. The presenting status was recorded and the course of disease monitored with preset criteria. The primary endpoints comprised death and severe neurological sequelae. Results. Eighty seven children received as adjunctive drug pentoxifylline (n=35), dexamethasone (n=30) and neither (n=22). At admission, the demographic, clinical and laboratory characteristics of the patients were comparable. There were no significant differences among the three groups regarding to the duration of fever and meningeal symptoms after admission. The mortality were comparable (11% in pentoxifylline, 13% in dexamethasone and 9% in control group) (p>0.6). Among the survivor patients, unfavorable outcome (severe sequelae) was observed in 13%, 20% and 15% for pentoxifylline-, dexamethasone- and control-group, respectively (p>0.5). Conclution. The data of the present study do not support the routine use of pentoxifylline as adjunctive therapy for bacterial meningitis in children.

Resumen Introducción. La pentoxifilina, un inhibidor del factor de necrosis tumoral, se ha demostrado en modelos animales de la meningitis bacteriana aguda que reducen la respuesta inflamatoria del huésped. Objetivo. Para evaluar el efecto de la pentoxifilina se administra como terapia auxiliar en el tratamiento de la meningitis bacteriana aguda en niños. Material y métodos. Estudio prospectivo y abierto que incluyó a los niños, entre 3 meses a 15 años de edad hospitalizado en el Instituto de Medicina Tropical, de Asunción, Paraguay, con el diagnóstico de la meningitis bacteriana aguda. Los pacientes fueron asignados al azar para recibir, además de la terapia con antibióticos (cefotaxima o ceftriaxona) pentoxifilina, dexametasona, o ninguno. El estado de presentación se registró y el curso de la enfermedad monitorizó con criterios preestablecidos. Los criterios de valoración primarios comprenden la muerte y secuelas neurológicas graves. Resultados: Ochenta y siete niños recibieron pentoxifilina drogas como adyuvante (n = 35), dexametasona (n = 30) y no (n = 22). Al ingreso, las características demográficas, clínicas y analíticas de los pacientes eran comparables. No hubo diferencias significativas entre los tres grupos en cuanto a la duración de la fiebre y los síntomas meníngeos después de la admisión. La mortalidad fue comparable (11% en pentoxifilina, 13% en dexametasona y 9% en el grupo control) (p > 0,6). Entre los pacientes sobrevivientes, se observó un resultado desfavorable (secuelas graves) en el 13%, 20% y 15% para pentoxifylline-, dexamethasone- y el control de grupos, respectivamente (p> 0,5). Conclución. Los datos del presente estudio no apoyan el uso rutinario de la pentoxifilina como tratamiento adyuvante para la meningitis bacteriana en niños.