Cost-utility analysis of a palliative care program in Colombia.

BACKGROUND: The economic assessment of health care models in palliative care promotes their global development. The purpose of the study is to assess the cost-effectiveness of a palliative care program (named Contigo) with that of conventional care from the perspective of a health benefit plan administrator company, Sanitas, in Colombia. METHODS: The incremental cost-utility ratio (ICUR) and the incremental net monetary benefit (INMB) were estimated using micro-costing in a retrospective, analytical cross-sectional study on the care of terminally ill patients enrolled in a palliative care program. A 6-month time horizon prior to death was used. The EQ-5D-3 L questionnaire (EQ-5D-3 L) and the McGill Quality of Life Questionnaire (MQOL) were used to measure the quality of life. RESULTS: The study included 43 patients managed within the program and 16 patients who received conventional medical management. The program was less expensive than the conventional practice (difference of 1,924.35 US dollars (USD), P = 0.18). When compared to the last 15 days, there is a higher perception of quality of life, which yielded 0.25 in the EQ-5D-3 L (p < 0.01) and 1.55 in the MQOL (P < 0.01). The ICUR was negative and the INMB was positive. CONCLUSION: Because the Contigo program reduces costs while improving quality of life, it is considered to be net cost-saving and a model with value in health care. Greater availability of palliative care programs, such as Contigo, in Colombia can help reduce existing gaps in access to universal palliative care health coverage, resulting in more cost-effective care.

In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.

Diferencias en el funcionamiento ejecutivo en boxeadores universitarios amateurs con distintos niveles de experiencia y categoría de peso / Diferenças no funcionamento executivo em boxeadores universitários amadores com diferentes níveis de experiência e classes de peso / Differences in executive functioning in amateur college boxers with different levels of experience and weight category

El boxeo es un deporte popular que implica golpes repetitivos a la cabeza, los cuales podrían producir alteraciones en el funcionamiento cerebral. Aunque existe evidencia del daño cerebral causado por la práctica del boxeo a nivel profesional, permanece la controversia sobre los posibles riesgos en el boxeo aficionado. El objetivo del presente estudio fue analizar si existen diferencias en el funcionamiento ejecutivo en boxeadores amateur universitarios en función de su nivel de experiencia en la práctica deportiva y su interacción con la categoría/peso. Método: Participaron mexicanos amateurs agrupados en novatos y experimentados y por su categoría de peso en ligero y medio. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas y Lóbulos Frontales BANFE-2 (Flores-Lázaro et al., 2014). Resultados: se realizó un MANOVA, los contrastes multivariados indican que hay diferencias en la interacción de las variables dependientes, de acuerdo con el nivel de experiencia F (4,17) = 3.75, p = .023, ηp2 = .469, 1-β=.56. En particular, las tareas en que se observan diferencias significativas son aquellas que evalúan el control inhibitorio (stroop) y la toma de decisiones de riesgo beneficio (juego de cartas), procesos que se encuentran asociados al funcionamiento de la corteza prefrontal orbito medial. Los hallazgos sugieren que la evaluación del funcionamiento ejecutivo puede ser una herramienta útil para evidenciar cambios funcionales en boxeadores amateur. (AU)

Boxing is a popular sport that involves repetitive blows to the head, which may cause disturbances in brain function. Although there is evidence of brain damage caused byprofessional boxing, controversy remains about the possible risks in amateur boxing. The aim of this study was to analyze whether there are differences in executive functioning in amateur college boxers based on their level of experience in sports practice and their interaction with category/ weight. Method: 24 mexican amateur boxers participated, grouped into novice and experienced and by their weight category (light and médium). The neuropsychological battery of executive functions and frontal lobes BANFE-2 (Flores-Lázaro et al., 2014) was used. Results: a MANOVA was performed, the multivariate contrasts indicate that there are differences in the interaction of the dependent variables, according to the level of experience F(4,17)= 3.75, p= .023, ηp2= .469, 1-β= .56. In particular, the tasks in which significative differences are observed are those that assess inhibitory control (stroop) and risk-benefit decision-making (card game), processes that areassociated with the functioning of the orbito-medial prefrontal cortex. The findings suggest that the evaluation of executive functioning can be a useful tool to demonstrate functional changes in amateur boxers. (AU)

O boxe é um esporte comum que envolve golpes repetitivos na cabeça dos atletas, o que pode causar distúrbios nas funções cerebrais. Embora hajam evidências de danos cerebrais causados pelo boxe profissional, a controvérsia permanece sobre os possíveis riscos no boxe amador. O objetivo do presente estudo foi analisar se existiam diferenças no funcionamento executivo de atletas de boxe amador universitários com base no nível de experiência, na prática esportiva e na interação com a categoria / peso. Método: participaram 24 boxeadores amadores, agrupados em novatos e experientes e por categoria de peso leve e médio. Foi utilizada a Bateria Neuropsicológica de Funções Executivas e Lobos Frontais BANFE-2 (Flores-Lázaro et al., 2014). Resultados: foi feito uma MANOVA, os contrastes multivariados indicaram que existiram diferenças na interação das variáveis dependentes, de acordo com o nível de experiência F(4,17) = 3.75, p= .023, ηp2= .469, 1-β= .56. Em particular, as tarefas em que se observaram diferenças são aquelas que avaliam o controlo inibitório (stroop) e a tomada de decisão risco-benefício (jogo de cartas), processos que estão associados ao funcionamento do córtex pré-frontal órbito-medial. Os resultados sugerem que a avaliação do funcionamento executivo pode ser uma ferramenta útil para demonstrar mudanças funcionais em pessoas que praticam o boxe amador. (AU)

Diagnóstico y tratamiento de los tumores de la unión esofagogástrica. Experiencia en el Instituto Nacional de Cancerología / Diagnosis and treatment of esophagogastric junction tumors. Experience at the National Cancer Institute

Introducción. El diagnóstico adecuado de los tumores de la unión esofagogástrica es esencial para el tratamiento de estos pacientes. La clasificación propuesta por Siewert-Stein define las características propias, factores de riesgo y estrategias quirúrgicas según la localización. El objetivo de este estudio fue describir las características de los pacientes con adenocarcinoma de la unión esofagogástrica tratados en nuestra institución. Métodos. Estudio retrospectivo, descriptivo, de corte longitudinal, que incluyó los pacientes con diagnóstico de adenocarcinoma de la unión esofagogástrica intervenidos quirúrgicamente en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre enero de 2012 y mayo de 2017. Resultados. Se operaron 59 pacientes (84,7 % hombres), con una edad media de 62,5 años. En su orden de frecuencia los tumores fueron tipo II (57,6 %), tipo III (30,7 %) y tipo I (11,9 %). El 74,6 % recibieron neoadyuvancia y se realizó gastrectomía total en el 73 % de los pacientes. La concordancia diagnóstica moderada con índice Kappa fue de 0,56, difiriendo con la endoscópica en 33,9 %. El 10,2 % de los pacientes presentó algún tipo de complicación intraoperatoria. La supervivencia a tres años en los tumores tipo II fue del 89,6 % y del 100 % en aquellos con respuesta patológica completa. Conclusión. Es necesario el uso de diferentes estrategias para un proceso diagnóstico adecuado en los tumores de la unión esofagogástrica. En esta serie, los pacientes Siewert II, aquellos que recibieron neoadyuvancia y los que obtuvieron una respuesta patológica completa, tuvieron una mejor supervivencia a tres años

Introduction: Proper diagnosis of gastroesophageal junction tumors is essential for the treatment of these patients. The classification proposed by Siewert-Stein defines its own characteristics, risk factors and surgical strategies according to the location. This study describes the characteristics of patients with adenocarcinoma of the esophagogastric junction treated at our institution. Methods. Retrospective, descriptive, longitudinal study, which includes patients diagnosed with adenocarcinoma of the esophagogastric junction who underwent surgery at the National Cancer Institute in Bogotá, Colombia, between January 2012 and May 2017. Results. Fifty-nine patients (84.7% men) were operated on, with a mean age of 62.5 years. In their order of frequency, the tumors were type II (57.6%), type III (30.7%) and type I (11.9%). 74.6% received neoadjuvant therapy and total gastrectomy was performed in 73% of the cases. The moderate diagnostic concordance with the Kappa index was 0.56, differing from the endoscopic one in 33.9%. 10.2% of the patients presented some type of intraoperative complication. Three-year survival in type II tumors was 89.6% and 100% in those with complete pathologic response. Conclusion. The use of different strategies is necessary for an adequate diagnostic process in tumors of the esophagogastric junction. In this series, Siewert II patients, those who received neoadjuvant therapy, and those who obtained a complete pathological response had a better three-year survival

Manejo de perforaciones, fugas y fístulas del tracto gastrointestinal con clip sobre el endoscopio. Experiencia de un centro oncológico Latinoamericano / Management of perforations, leaks and fistulas of the gastrointestinal tract with over the scope clip. Experience at a Latin American cancer center

Introducción. Las fístulas derivadas de enfermedades neoplásicas del tracto digestivo, así como las fugas posteriores a procedimientos quirúrgicos, no son infrecuentes y ocasionan una morbilidad importante cuando se manejan de forma quirúrgica. También durante los procedimientos endoscópicos se pueden presentar perforaciones y, si se logra un manejo no operatorio, se alcanza una adecuada recuperación. El objetivo de este estudio fue describir las características clínicas y los resultados de los pacientes con perforaciones, fístulas y fugas del tracto gastrointestinal, manejadas endoscópicamente con clip sobre el endoscopio. Métodos. Estudio descriptivo, retrospectivo, de pacientes con perforación, fuga o fístula postoperatoria, llevados a endoscopía digestiva con colocación de clip sobre el endoscopio, en el Instituto Nacional de Cancerología en Bogotá, D.C., Colombia, entre enero de 2016 y abril de 2020. Resultados. Se incluyeron 21 pacientes, 52,4 % de ellos mujeres. La mediana de edad fue de 66 años y del diámetro del defecto fue de 9 mm. En el 95 % se logró éxito técnico. Hubo éxito clínico temprano en el 85,7 % de los casos. El 76,1 % de los pacientes permanecieron sin síntomas a los 3 meses de seguimiento. Conclusiones. El manejo de perforaciones, fugas y fístulas con clip sobre el endoscopio parece ser factible y seguro. En la mayoría de estos pacientes se logró la liberación del clip y la identificación endoscópica del cierre inmediatamente después del procedimiento; sin embargo, en el caso de las fístulas, no se alcanzó el éxito clínico tardío en todos los casos

Introduction. Fistula of the digestive tract derived from neoplastic diseases as well as leaks following surgical procedures are not uncommon and usually cause significant morbidity when are managed surgically. Diagnostic and therapeutic endoscopic procedures may present perforations during their performance; if they are managed non-operatively, an adequate recovery is obtained. The purpose of this study was to describe the clinical characteristics and the short- and long-term outcomes of patients with perforations, fistulas and leaks of the gastrointestinal tract managed endoscopically with over the scope clip (OTSC). Methods. Descriptive, retrospective study of patients brought to digestive endoscopy with OTSC placement with diagnosis of postoperative perforation, leak or fistula at the National Cancer Institute in Bogota, Colombia, between January 2016 and April 2020. Results. Twenty-one patients were taken for OTSC application for the management of perforations, leaks and fistulas of the gastrointestinal tract, 52.4% of them were women. The median age was 66 years. The median diameter of the defect was 9 mm. Technical success was achieved in 95%. Early clinical success was described in 85.7% of the cases; 76.1% of patients remained symptom-free at 3-month follow-up. Conclusions. Management of perforations, leaks and fistulas with OTSC appears to be feasible and safe. In most of these patients, clip release and endoscopic identification of closure was achieved immediately after management; however, in the case of fistulas, late clinical success was not achieved in all cases

Enfermedad pulmonar intersticial difusa secundaria a neumonitis por hipersensibilidad de patrón mixto: reporte de caso y revisión de literatura / Diffuse interstitial lung disease secondary to mixed pattern hypersensitivity pneumonitis: Case report and literature review

La enfermedad pulmonar intersticial difusa (EPID) supone un amplio grupo heterogéneo de enfermedades caracterizadas por hallazgos en su intersticio pulmonar, específicamente relacionados con su engrosamiento, lo cual impacta significativamente en el intercambio gaseoso y la mecánica ventilatoria del paciente. El diagnóstico se genera acorde a la clínica del paciente, el uso de imágenes y la histopatología. El tratamiento guarda relación directa con el patrón pulmonar estructural que presente la EPID. Se presenta el caso clínico de una paciente femenina de 32 años, indígena, quien ingresa por exacerbación de disnea, con antecedente de neumonitis por hipersensibilidad, adicional a otros antecedentes clínicos que guardan relación estrecha con la EPID.

Diffuse interstitial lung disease (ILD) is a large heterogeneous group of diseases characterized by findings in the pulmonary interstitium, specifically changes related to thickening of the interstitium, which significantly impacts the patient's gas exchange and ventilatory mechanics. The diagnosis is generated according to the patient's clinical presentation, imaging and histopathology. The treatment is directly related to the structural pulmonary pattern of ILD. We present the clinical case of a 33-year-old female patient of indigenous ethnicity who is admitted for exacerbation of dyspnea, with a history of hypersensitivity pneumonitis in addition to other clinical antecedents that are closely related to ILD.

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: ¿Cómo lo estamos haciendo?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento.

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary.

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: Cómo lo estamos haciendo? / Current situation of staging laparoscopy in patients with gastric cancer in Colombia: How are we doing it?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary

Cuerpo extraño como causa de apendicitis aguda complicada / Foreign body as a cause of complicated acute appendicitis

La apendicitis aguda es una de las patologías más comunes en el ámbito hospitalario. Las formas complicadas pueden ser causadas por objetos puntigudos, afilados, delgados o alargados, ingeridos de forma accidental, y representan una causa inusual con una prevalencia del 0,0005 %

Acute appendicitis is one of the most common pathologies in the hospital setting. The complicated forms can be caused by pointed, sharp, thin or elongated objects, accidentally ingested, and represent an unusual cause with a prevalence of 0.0005%.

Hernia de Amyand tipo 2: apendicectomía y hernioplastia con malla de baja densidad / Amyand's hernia type 2: appendectomy and hernioplasty withlow density mesh

La incidencia de las hernias inguinales en Colombia es de aproximadamente 15 por cada 1000 habitantes, y el riesgo de presentar una hernia inguinal durante la vida es del 27 % en hombres y del 3 % en mujeres. Existen presentaciones poco frecuentes como la hernia de Amyand que consiste en la protrusión del apéndice cecal, inflamada o no, dentro del contenido del saco herniario. A nivel global, tiene una incidencia del 0,13 % al 1 % y su tratamiento se realiza basándose en la clasificación de Losanoff y Basson. Sin embargo, una de las controversias aún existentes respecto al manejo quirúrgico, es la indicación del uso o no de mallas al momento de realizar la hernioplastia y el resultado final del mismo, así que este es el punto donde se centra la revisión de nuestro artículo. Se presenta el caso de un paciente de 79 años con una hernia de Amyand tipo 2, a quien se le practicó hernioplastia con malla de baja densidad absorbible, con adecuada evolución posquirúrgica

The incidence of inguinal hernias in Colombia is approximately 15 per 1000 inhabitants, and the risk of presenting an inguinal hernia during life is 27% in men and 3% in women. There are rare presentations such as Amyand's hernia, which consists of the protrusion of the cecal appendix, inflamed or not, within the content of the hernial sac. At a global level, it has an incidence of 0.13% to 1% and its treatment is based on the Losanoff and Basson classification. However, one of the still existing controversies regarding surgical management is the indication of the use or not of meshes at the time of performing the hernioplasty, and the final result of it, this is the point where the review of our article focuses. We present the case of a 79-year-old patient with a type 2 Amyand hernia who underwent hernioplasty with a low-density absorbable mesh, with adequate postoperative evolution

"Bad things come in small packages": predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters

Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables. Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites.Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR=2.70 (95%CI 1.15-6.37); p=.021] and by snakes with white tail tip [OR=1.98 (95%CI 1.15–3.41); p=.013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p=.214) or age (p=.254). Patients bitten by neonate (p=.024) or juvenile snakes (p<.0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema. Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Introduction: Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy. Methods: This is a prospective study of Bothrops snakebite patients (n=100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up. Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12h after the antivenom therapy. Three patients developed systemic bleeding 48h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths. Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Bothrops atrox, the most important snake involved in human envenomings in the amazon: how venomics contributes to the knowledge of snake biology and clinical toxinology

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke

Bad things come in small packages: predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters

Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables. Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites.Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR=2.70 (95%CI 1.15-6.37); p=.021] and by snakes with white tail tip [OR=1.98 (95%CI 1.15–3.41); p=.013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p=.214) or age (p=.254). Patients bitten by neonate (p=.024) or juvenile snakes (p<.0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema. Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Introduction: Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy. Methods: This is a prospective study of Bothrops snakebite patients (n=100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up. Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12h after the antivenom therapy. Three patients developed systemic bleeding 48h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths. Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Bothrops atrox, the most important snake involved in human envenomings in the amazon: how venomics contributes to the knowledge of snake biology and clinical toxinology

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke

Schwannoma pélvico retroperitoneal que simula un leiomioma: reporte de un caso y revisión bibliográfica / Pelvic retroperitoneal schwannoma presenting as a leiomyoma: Case report and review of literature

Resumen OBJETIVO Exponer el caso de una paciente con una masa pélvica que se reportó como mioma y resultó ser un schwannoma. CASO CLÍNICO Paciente de 53 años que consultó por dolor abdominal, lumbalgia, distensión, estreñimiento y dispareunia durante tres meses. La ecografía transvaginal sugirió un leiomioma. En la histerectomía laparoscópica se observó una masa retroperitoneal de 9 cm sobre el sacro. La resonancia magnética reportó un tumor sólido, presacro, de 8 cm. El diagnóstico histológico final fue: schwannoma celular S-100 positivo y actina de la musculatura lisa negativa. El seguimiento a los seis meses posteriores demostró disminución significativa del dolor abdominal inferior. CONCLUSIONES Los schwannomas se manifiestan, excepcionalmente, como masas pélvicas, como fue el caso aquí comunicado que se diagnosticó como fibroma uterino, pero que posteriormente se demostró era un schwannoma retroperitoneal. Este tumor pocas veces genera síntomas y cuando los hay suelen ser inespecíficos, por eso frecuentemente el diagnóstico es erróneo. Por la falta de características distintivas en los estudios de imagen el diagnóstico preoperatorio de un schwannoma no es fácil; su pronóstico es excelente y la escisión suele ser curativa.

Abstract OBJECTIVE Present the case of a patient with a pelvic mass which was reported as myoma and turned out to be a schwannoma. CLINICAL CASE We report a case of a 53 year old female that presented with abdominal and low back pain, also distention, constipation and dyspareunia for 3 months. Transvaginal ultrasound suggested leiomyoma. Laparoscopic hysterectomy was planned. On laparoscopy, a retroperitoneal 9 cm mass was seen over de sacrum. The procedure was stopped for further studies. Magnetic resonance images detected a large presacral solid, tumor of 8 cm. The patient was scheduled for laparoscopy with oncology group and the mass was resected. No complications were experienced intra or postoperatively. The final histological diagnosis was a cellular schwannoma, that was S-100- positive, and smooth muscle actin-negative. A follow up consultation 6 months later showed a significant improvement of the lower abdominal pain. CONCLUSIONS Schwannomas rarely present as pelvic masses. We report a woman with a pelvic mass initially diagnosed as a uterine fibroid but subsequently proven to be a retroperitoneal schwannoma. This rare entity is usually asymptomatic or has nonspecific symptoms leading to misdiagnosis. Preoperative diagnosis of a schwannoma is not easy for a lack of distinguishing features on imaging studies. The prognosis of schwannoma is excellent, and the excision is usually curative.