Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We assessed the effect of pharmacological inhibition of DGK on pro-mitogenic signaling and proliferation in primary human ASM cells. Pretreatment with DGK inhibitor I (DGKI) significantly inhibited platelet-derived growth factor-stimulated ASM cell proliferation. Anti-mitogenic effect of DGKI was associated with decreased mTOR signaling and expression of cyclin D1. Exogenous PA promoted pro-mitogenic signaling and rescued DGKI-induced attenuation of ASM cell proliferation. Finally, house dust mite (HDM) challenge in wild type mice promoted airway remodeling features, which were attenuated in DGKζ-/- mice. We propose that DGK serves as a potential drug target for mitigating airway remodeling in asthma.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection.

Background: Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population. Methods: We retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort. Results: We diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p = 0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p = 0.25). Conclusion: No significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity.

Antecedentes: La infección por COVID-19 y el cáncer se asocian a mayor riesgo de eventos trombóticos. El objetivo de nuestro estudio es analizar la incidencia acumulada de trombosis en pacientes oncológicos con COVID-19 y detectar diferencias con la población sin cáncer y COVID-19. Métodos: Revisamos retrospectivamente 1.127 historias clínicas de los pacientes ingresados en del Hospital Infanta Leonor (Madrid, España), incluyendo 86 pacientes con cáncer activo entre el 5 de marzo y el 3 de mayo de 2020. Se analizó la incidencia acumulada de trombosis y los factores de riesgo asociados a la cohorte de pacientes con cáncer. Resultados: Diagnosticamos 10 eventos trombóticos en 8 pacientes oncológicos, con una incidencia acumulada del 9,3%. Se encontró una asociación estadísticamente significativa entre trombosis y obesidad (p = 0,009). No se detectaron diferencias relacionadas con la incidencia acumulada de trombosis entre ambos grupos (9,8%vs. 5,80%, p = 0,25). Conclusión: No se observaron diferencias significativas en la incidencia acumulada de trombosis en los 2 grupos de estudio. El efecto trombótico de la COVID-19 no es tan evidente en los pacientes con cáncer y no parece sumarse a su actividad protrombótica.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection

Background: Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population.MethodsWe retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort.ResultsWe diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p=0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p=0.25).ConclusionNo significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity. (AU)

Antecedentes: La infección por COVID-19 y el cáncer se asocian a mayor riesgo de eventos trombóticos. El objetivo de nuestro estudio es analizar la incidencia acumulada de trombosis en pacientes oncológicos con COVID-19 y detectar diferencias con la población sin cáncer y COVID-19.MétodosRevisamos retrospectivamente 1.127 historias clínicas de los pacientes ingresados en del Hospital Infanta Leonor (Madrid, España), incluyendo 86 pacientes con cáncer activo entre el 5 de marzo y el 3 de mayo de 2020. Se analizó la incidencia acumulada de trombosis y los factores de riesgo asociados a la cohorte de pacientes con cáncer.ResultadosDiagnosticamos 10 eventos trombóticos en 8 pacientes oncológicos, con una incidencia acumulada del 9,3%. Se encontró una asociación estadísticamente significativa entre trombosis y obesidad (p=0,009). No se detectaron diferencias relacionadas con la incidencia acumulada de trombosis entre ambos grupos (9,8%vs. 5,80%, p=0,25).ConclusiónNo se observaron diferencias significativas en la incidencia acumulada de trombosis en los 2 grupos de estudio. El efecto trombótico de la COVID-19 no es tan evidente en los pacientes con cáncer y no parece sumarse a su actividad protrombótica. (AU)

Manejo anestésico del paciente quemado / Anesthetic management of the burn patient

Resumen: El conocimiento de la fisiopatología de las quemaduras son base del manejo perioperatorio. Todos los órganos y sistemas resultan alterados y los cambios hemodinámicos en la fase aguda se caracterizan por una disminución del gasto cardíaco. Después de seis días de la lesión, ocurre un nuevo cambio hemodinámico, esta fase es conocida como estado hipermetabólico y su duración está en relación con la extensión y profundidad de la lesión. La lesión por inhalación es un factor importante a considerar como mal pronóstico y, de igual manera, el número de comorbilidades y/o trauma asociado. Durante este segundo período, los anestesiólogos tienen una participación continua y estrecha. Los problemas farmacológicos, manejo de vía aérea, accesos vasculares, hipotermia, monitoreo y control del dolor, entre otros, se hacen muy marcados. Por último, la fase de secuelas acompaña al paciente para toda su vida y la magnitud de los daños, costos y discapacidad serán directamente relacionados con la atención administrada durante las primeras dos fases.

Abstract: Knowledge of the pathophysiology of burns is the basis of perioperative management. All organs and systems are altered and hemodynamic changes in the acute phase are characterized by a decrease in cardiac output. After six days of injury a new hemodynamic change occurs, this phase is known as hypermetabolic state and its duration is in relation to the extent and depth of the injury. Inhalation injury is an important factor to consider as a poor prognosis and also the number of associated comorbidities and/or trauma. During this second period the Anesthesiologists have a continuous and close participation. Pharmacological problems, airway management, vascular access, hypothermia, monitoring and pain control among others become very marked. Finally, the phase of sequelae is for life and the magnitude of damages, costs and disability will be directly related to the care administered during the first two phases.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection.

BACKGROUND: Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population. METHODS: We retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort. RESULTS: We diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p=0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p=0.25). CONCLUSION: No significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity.

Covid-19 and lung cancer: A greater fatality rate?

BACKGROUND: Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes. PATIENTS AND METHODS: We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis. RESULTS: 17/1878 total diagnosis in our center had lung cancer (0.9 %) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3 %) versus 192/1878 Covid-19 patients in our center (p < 0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018). CONCLUSIONS: Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.

[Colorectal melanoma: review of two distinct forms of presentation]. / Melanoma colorrectal: revisión de dos formas diferentes de presentación.

Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45.

Melanoma colorrectal: revisión de dos formas diferentes de presentación / Colorectal melanoma: review of two distinct forms of presentation

El melanoma maligno colorrectal es una enfermedad infrecuente. El melanoma primario anorrectal se observa en el 0,1-4,6% de todos los tumores malignos anales. Por otro lado el melanoma metastásico en esta localización solo produce síntomas en el 4,4% de los pacientes con melanoma a otros niveles, siendo diagnosticado la mayoría de las veces post mórtem. Presentamos los casos de 2 pacientes con melanoma colorrectal. El primero de ellos muestra un paciente atendido por rectorragia en el que se diagnosticó una masa endoanal correspondiente a un melanoma y en el cual se practicó una resección abdominoperineal tras observar la positividad del ganglio centinela, discutiéndose su utilidad en este tipo de tumores. En el paciente del segundo caso se encontró una lesión polipoide en colon transverso correspondiente a una metástasis de un melanoma previamente diagnosticado. En ambas piezas histológicas la anatomía patológica fue característica con positividad para S-100, Melan-A y HMB-45 (AU)

Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45 (AU)

[Diet of the chub, Notropis moralesi (Pisces: Cyprinidae) in the aMacuzac River, Morelos, Mexico]. / Dieta de la carpa Notropis moralesi (Pisces: Cyprinidae) en el río Amacuzac, Morelos, México.

Notropis moralesi, locally known as "carpa tepelneme", is a small endemic fish of the Papaloapan River. We analyzed its diet and feeding habits. Specimens were captured monthly from Amacuzac, River, Morelos, Mexico. The gut content of 294 specimens was identified to the most specific taxonomic category possible. We quantified gut content by the numerical and frequency of occurrence methods and used the Levin's amplitude of trophic niche indices and MacArthur and Levin's indices for niche overlaping. The N. moralesi diet was composed by eleven prey categories, ten of which were of animal item. Chironomids and mayfly were the most consumed prey, independently of season and fish sex or size. We found ten nutritional components in the dry season, and eight in the rainy season. The estimated amplitude of trophic niche (Levin's method) revealed high values in both seasons. The diet had ten nutritional components in immatures, eight in females and five in males. A Chi-squared test showed not significant differences in the diet by development stage, sex, and season. The niche overlaping index was high (above 0.60) for all analyses. N. moralesi is a carnivorous species with entomophagus tendencies.

Dieta de la carpa Notropis moralesi (Pisces: Cyprinidae) en el río Amacuzac, Morelos, México

Diet of the chub, Notropis moralesi (Pisces: Cyprinidae) in the Amacuzac River, Morelos, Mexico. Notropis moralesi, locally known as "carpa tepelneme", is a small endemic fish of the Papaloapan River. We analyzed its diet and feeding habits. Specimens were captured monthly from Amacuzac, River, Morelos, Mexico. The gut content of 294 specimens was identified to the most specific taxonomic category possible. We quantified gut content by the numerical and frequency of occurrence methods and used the Levin’s amplitude of trophic niche indices and MacArthur and Levin`s indices for niche overlaping. The N. moralesi diet was composed by eleven prey categories, ten of which were of animal item. Chironomids and mayfly were the most consumed prey, independently of season and fish sex or size. We found ten nutritional components in the dry season, and eight in the rainy season. The estimated amplitude of trophic niche (Levin’s method) revealed high values in both seasons. The diet had ten nutritional components in immatures, eight in females and five in males. A Chi-squared test showed not significant differences in the diet by development stage, sex, and season. The niche overlaping index was high (above 0.60) for all analyses. N. moralesi is a carnivorous species with entomophagus tendencies. Rev. Biol. Trop. 57 (1-2): 195-209. Epub 2009 June 30.

Notropis moralesi, conocido comúnmente como "carpa tepelneme", es un pez endémico del río Papaloapan. Se analizó su dieta y hábitos alimentarios. Se tomaron muestras mensuales en el río Amacuzac, Morelos, México. La identificación del contenido estomacal (294 ejemplares) se llevó hasta el taxon más específico posible. Para la cuantificación se utilizaron los métodos numérico (No) y frecuencia de aparición (F.O.). Se utilizó el índice de amplitud de nicho trófico de Levin y el índice de traslape de MacArthur y Levin. N. moralesi presentó la ingestión de once componentes alimenticios, de los cuales diez son de origen animal y uno vegetal. Los quironómidos y efemerópteros fueron los más consumidos independientemente del sexo, talla y época del año. El análisis por épocas del año, reportó diez componentes en el estiaje y ocho en las lluvias. La dieta de los inmaduros estuvo constituida por diez componentes, la de las hembras por ocho y el de los machos por cinco. La prueba de Ji-cuadrada reveló que no existen diferencias significativas entre las dietas por estadio de desarrollo, sexos y épocas del año. El traslape de los nichos tróficos, reveló valores superiores a 0.60 en todas las combinaciones por sexos y épocas del año. N. moralesi es una especie carnívora con tendencias insectívoras y presenta hábitos alimentarios de tipo bentófago.