Efficacy of IFN-γ, sCD40L, and Poly(I:C) Treated Bone Marrow-Derived Macrophages in Murine Mammary Carcinoma.

INTRODUCTION: Here, we explored methods to generate anti-tumor bone marrow-derived macrophages (BMDM) and how delivery of the BMDM at early tumor sites could impact disease progression. METHODS: BMDM treated with IFN-γ, sCD40L, poly(I:C), and a combination of the three were assessed. RESULTS: Treatment with sCD40L had no significant impact on the BMDM. Treating BMDM with IFN-γ impacted IL-1ß, MHC Class II, and CD80 expression. While poly(I:C) treatment had a greater impact on the BMDM than IFN-γ when assessed by the in vitro assays, the BMDM treated with poly (I:C) had mixed results in vivo where they decreased growth of the EMT6 tumor, did not impact growth of the 168 tumor, and enhanced growth of the 4T1 tumor. The combination of poly(I:C), IFN-γ, and sCD40L had the greatest impact on the BMDM in vitro and in vivo. Treatment with all three agonists resulted in increased IL-1ß, TNF-α, and IL-12 expression, decreased expression of arginase and mrc, increased phagocytic activity, nitrite production, and MHC Class II and CD80 expression, and significantly impacted growth of the EMT6 and 168 murine mammary carcinoma models. DISCUSSION: Collectively, these data show that treating BMDM with poly(I:C), IFN-γ, and sCD40L generates BMDM with more consistent anti-tumor activity than BMDM generated with the individual agonists.

A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and Neisseria meningitidis outer membrane vesicles.

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

A cell-based ELISA as surrogate of virus neutralization assay for RBD SARS-CoV-2 specific antibodies.

SARS-CoV-2, the cause of the COVID-19 pandemic, has provoked a global crisis and death of millions of people. Several serological assays to determine the quality of the immune response against SARS-CoV-2 and the efficacy of vaccines have been developed, among them the gold standard conventional virus neutralization assays. However, these tests are time consuming, require biosafety level 3 (BSL3), and are low throughput and expensive. This has motivated the development of alternative methods, including molecular inhibition assays. Herein, we present a safe cell-based ELISA-virus neutralization test (cbE-VNT) as a surrogate for the conventional viral neutralization assays that detects the inhibition of SARS-CoV-2 RBD binding to ACE2-bearing cells independently of species. Our test shows a very good correlation with the conventional and molecular neutralization assays and achieves 100% specificity and 95% sensitivity. cbE-VNT is cost-effective, fast and enables a large-scale serological evaluation that can be performed in a BSL2 laboratory, allowing its use in pre-clinical and clinical investigations.

Remodelado estructural y riesgo de recurrencia en la fibrilación auricular / Structural remodeling and risk of recurrence in atrial fibrillation / Remodelação estrutural e risco de recidiva na fibrilação atrial

RESUMEN La fibrilación auricular es la disrritmia sostenida más frecuente del pasado siglo; con el fin de caracterizar el riesgo de recurrencia de la fibrilación auricular y su relación con el remodelado estructural cardiaco, se realizó un estudio descriptivo de serie de casos, en el Hospital Vladimir Ilich Lenin, en el año 2017. El análisis de la información referida a 100 pacientes con diagnóstico de fibrilación auricular identificó los resultados siguientes: de los pacientes estudiados 41 (54.7%) fueron del sexo femenino y mayor de 55 años; los indicadores del índice pronóstico prevalecieron en el riesgo elevado de recurrencia; el riesgo de recurrencia elevado en válvulopatas mitrales con predominio de la estenosis mitral alcanzo el 40.7% de los pacientes, así como la dilatación de la aurícula izquierda en este mismo grupo, con un total de 22 pacientes (81.4%). Un total de 15 pacientes, que representó el 55.6 %, tuvieron una fracción de eyección del ventrículo izquierdo disminuida con un riesgo de recurrencia elevado. El mayor por ciento de los pacientes presentaron un valor de p significativo y muy significativo; y por último el 22 % de los pacientes con riesgo elevado de recurrencia presentaron remodelado estructural cardiaco. Se concluyó que la afección estudiada predominó en pacientes mayores de 55 años, del sexo femenino, con riesgo elevado de recurrencia en relación con los indicadores del índice pronostico y predictores del remodelado estructural, lo que justifica la hipótesis alternativa, con un elevado valor clínico y estadístico.

ABSTRACT Atrial fibrillation is the most frequent sustained dysrhythmia of the past century; In order to characterize the risk of recurrence of atrial fibrillation and its relationship with cardiac structural remodeling, a descriptive study of a series of cases was conducted at the Vladimir Ilich Lenin Hospital in 2017. The analysis of the referred information 100 patients diagnosed with atrial fibrillation identified the following results: of the patients studied, 41 (54.7%) were female and over 55 years old; the indicators of the prognostic index prevailed in the high risk of recurrence; the risk of high recurrence in mitral valvelets with predominance of mitral stenosis reached 40.7% of patients, as well as dilation of the left atrium in this same group, with a total of 22 patients (81.4%). A total of 15 patients, who represented 55.6%, had a decreased left ventricular ejection fraction with a high risk of recurrence. The highest percent of patients presented a significant and very significant p value; and finally, 22% of the patients with high risk of recurrence presented structural cardiac remodeling. It was concluded that the studied condition predominated in patients over 55 years old, female, with a high risk of recurrence in relation to the indicators of the prognostic index and predictors of structural remodeling, which justifies the alternative hypothesis, with a high clinical value and statistical.

RESUMO A fibrilação atrial é a arritmia sustentada mais comum século passado; a fim de caracterizar o risco de recorrência de fibrilação atrial e a sua relação com a remodelação cardíaca estrutural, uma série de casos descritiva foi realizado no Hospital Lênin Vladimir Ilich em 2017. A análise das informações referidas 100 pacientes diagnosticados com fibrilação atrial identificados os seguintes resultados: 41 dos pacientes (54,7%) eram do sexo feminino e 55 do sexo mais; os indicadores do índice prognóstico prevaleceram no alto risco de recidiva; o alto risco de recorrência em válvulopatas mitral lojas atingiu estenose mitral com 40,7% dos pacientes e dilatação do átrio esquerdo do mesmo grupo, com um total de 22 pacientes (81,4%). Um total de 15 doentes, correspondendo a 55,6%, tinha uma fracção de ejecção do ventrículo esquerdo diminuída com um risco elevado de recidiva. O maior percentual de pacientes apresentou valor p significativo e muito significativo; e, finalmente, 22% dos pacientes com alto risco de recorrência mostrou remodelação cardíaca estrutural. Concluiu-se que a condição estudada predominaram em pacientes com mais de 55 anos de idade, do sexo feminino, com alto risco de recorrência em relação ao índice de indicadores de prognóstico e preditores de remodelação estrutural, o que justifica a hipótese alternativa, com um valor clínico de alta e estatística.

Spectral-domain optical coherence tomography evaluation of choroidal melanoma and nevus fine-needle aspiration biopsy incision sites.

The authors present three cases in which spectral-domain optical coherence tomography was used to identify fine-needle aspiration biopsy incision sites. These biopsies were performed to obtain tissue for gene expression profiling of choroidal tumors. A transvitreal route into the apex of the tumors was utilized for the biopsies while the patients underwent pars plana vitrectomy, membrane peel, laser ablation, phacoemulsification with posterior chamber intraocular lens implantation, and intravitreal triamcinolone acetonide. To the best of the authors' knowledge, this is the first report documenting fine-needle aspiration biopsy incision wound architecture of the posterior segment with optical coherence tomography.

Uveal melanoma gene expression status post radiotherapy.

PURPOSE: Gene expression profiling has been shown to yield two distinct molecular genetic signatures for uveal melanoma. These class designations tend to predict tumor aggressiveness and the likelihood of metastasis. Tumors with a class 1 genetic signature are generally much less aggressive than tumors with a class 2 genetic signature. Gene expression analysis for previously treated uveal melanoma has not yet been reported. The authors report three cases where genetic analysis was successfully obtained from uveal melanoma that was previously treated years earlier with radiotherapy. CASE REPORT: The patients in all three cases received globe-conserving radiotherapy for treatment of choroidal melanoma before gene expression profiling was readily available. The patients in cases 1 and 2 received 125I plaque brachytherapy while the patient in case 3 received proton irradiation therapy. When secondary surgery was necessary to stabilize these eyes from the effects of radiation retinopathy, fine-needle aspiration biopsy was also performed for gene expression profiling. Genomic analysis revealed a class 1 molecular signature for the patient in case 1 and a class 2 molecular signature for the patients in cases 2 and 3. CONCLUSIONS: Gene expression profiling for uveal melanoma may be obtained from patients who were previously treated with radiotherapy; however, the implication of these results will benefit from ongoing clinical evaluation.

Posterior uveal melanoma coexistent with macular hole.

PURPOSE: Three rare cases of macular holes coexistent with posterior uveal melanoma are presented. The possible pathogenesis of a macular hole secondary to uveal melanoma growth is discussed, as well as strategies to treat uveal melanoma before attempting macular hole repair. CASE REPORT: Each patient from all three cases had a macular hole and uveal melanoma at the initial presentation. The macular holes were present before uveal melanoma treatment in cases 1 and 2. The patient in case 3 had already been treated elsewhere with iodine-125 plaque brachytherapy for her melanoma. It was not known if macular hole formation occurred before or after that treatment. Macular hole repair was performed in case 1, and the hole was successfully closed. CONCLUSIONS: To the best of the authors' knowledge, there are now only nine documented cases of macular holes accompanying posterior uveal melanoma. Successful macular hole repair may prove difficult because the melanoma must first be properly treated and then monitored carefully to establish tumor inactivity.

Long-term followup comparing two treatment dosing strategies of (125) I plaque radiotherapy in the management of small/medium posterior uveal melanoma.

Objective. To investigate the efficacy of two different dosing strategies of radioactive iodine-125 ((125)I) in the management of small- and medium-sized posterior uveal melanoma. Patients and Methods. The medical records of consecutive patients with choroidal melanomas between 1.5 and 5.0 mm in apical height treated initially with (125)I plaque radiotherapy were reviewed. Patients were treated with one of the following two treatment dosing strategies: (1) 85 Gy to the apical height of the tumor (group 1) or (2) 85 Gy to a prescription point of 5.0 mm (group 2). Results. Of 95 patients, 55 patients were treated to the apical height of the tumor, and 40 were treated to a prescription point of 5.0 mm. Comparative analysis of the incidence rates of specific complications between the two groups demonstrates that group 2 had a significantly higher incidence of radiation retinopathy, radiation optic neuropathy, and/or visually significant cataract formation than group 1 (P = 0.028). Conclusion. Treatment of choroidal melanomas less than 5 mm in apical height with (125)I brachytherapy to the true apical height is equally effective when compared to treatment with 85 Gy to 5.0 mm. Treatment to the apical height of the tumor may result in lower incidence of radiation-related complications.

Ecocardiografía transesofágica intraoperatoria: utilidad en la monitorización cardiovascular durante la cirugía abdominal / Intraoperative transesophageal echocardiography: usefulness for cardiovascular monitoring during abdominal surgery

Antecedentes: la ecocardiografía transesofágica (ETE) puede ser un sistema útil de monitorización cardiovascular intraoperatoria durante una cirugía no cardíaca, con la ventaja de ser una técnica mínimamente invasiva que brinda información anatómica y funcional sobre el corazón y sus grandes vasos en tiempo real. Objetivo: Evaluar la utilidad de ETE intraoperatoria en el manejo hemodinámico de pacientes con alto riesgo cardiovascular sometidos a cirugía abdominal. Lugar: Servicio de Anestesiología de Hospital Clínico Universitario. Diseño: Estudio prospectivo de casos clínicos. Población: Adultos portadores de patología cardiovascular sometidos a cirugía abdominal. Método: Se monitorizaron pacientes con ETE utilizando transductor multiplanar, describiéndose características y tipos de cirugías. Para objetivar la utilidad clínica, al finalizar la monitorización se clasificó a cada paciente en uno de los siguientes grupos: 1= ETE sin utilidad, 2 = la ETE cambió el manejo de volúmenes y fármacos, 3 = nuevo diagnóstico y 4 = la ETE fue sustituta del catéter de arteria pulmonar. Resultados: De un total de 98 pacientes estudiados, solo 2 (2 por ciento) fueron clasificados en el grupo 1; 45 pacientes (51 por ciento), en el grupo 2; 21 (24 por ciento) en el grupo 3 y 30 (34 por ciento) en el grupo 4. No hubo complicaciones con la técnica. Conclusiones: La ETE durante el intraoperatorio de cirugía abdominal permitió al anestesiólogo manejar mejor, en forma adecuada y segura el estado hemodinámico de pacientes con riesgo cardiovascular, ya que las imágenes y mediciones obtenidas fueron de alta calidad y sencillas de obtener en tiempo real.

Backgroung: Intraoperative transesophageal echocardiography (TEE) is a minimally invasive technique that can be helpful for cardiovascular monitoring during non-cardiac surgery, because it provides real time anatomical and functional information of the heart and great vessels. Objective: Evaluation of the utility of TEE during abdominal surgery in high-risk cardiovascular patients. Site of application: Anesthesiology Department of University Hospital. Design: Prospective Study of patients. Population: Adults with cardiovascular pathology subjected to abdominal surgery. Method: Patients were monitored with TEE. At the end of surgery each patient was classified in one of the following groups: group: 1 = TEE no utility, 2 = TEE useful for volume and drug guidance; 3 = new diagnosis and 4 = TEE was a substitute for the pulmonary artery catheter. Results: 98 patients were studied. Only two cases were classified in group 1, 45 patients (51 per cent) in group 2, 21 patients (21,5 per cent) in group 3 and 30 patients (30,5 per cent) in group 4. There were no complications following the use of TEE. Conclusions: Intraoperative TEE during abdominal surgery allowed the anesthesiologist a safe and adequate hemodynamic management of high-risk cardiovascular patients. TEE provided high quality and easy to obtain images and measurements in real time.

Antecedentes: A ecocardiografia transesofágica (ETE) pode ser um sistema útil de monitoramento cardiovascular intraoperatório durante uma cirurgia nao cardiaca, com a vantagem de ser uma técnica minimamente invasiva que proporciona informação anatómica e funcional em tempo real sobre o coração e seus grandes vasos. Objetivo: Avaliar a utilidade da ETE intraoperatória no manejo hemodinamico de pacientes com alto risco cardiovascular submetidos à cirurgia abdominal. Lugar: Serviço de Anestesiologia do Hospital Clínico Universitário. Desenho: Estudo prospectivo de casos clínicos. População: Adultos portadores de patología cardiovascular submetidos à círurgia abdominal. Método: Foram monitorizados pacientes com ETE utilizando transductor multiplanar, sendo descritas características e tipos de cirurgias. Finalizado o monitoramento, e a fim de ponderar a utilidade clínica, cada paciente foi classificado em um dos seguintes grupos: 1 = ETE sem utilidade, 2 = a ETE mudou o manejo de volumes e fármacos, 3 = novo diagnóstico e 4 = a ETE substituiu o cateter da artéria pulmonar. Resultados: De 98 pacientes estudados, somente 2 (2 por cento) foram classificados no grupo 1; 45 pacientes (51 por cento), no grupo 2; 21 (24 por cento) no grupo 3 e 30 (34 por cento) no grupo 4. Não houve complicações com a técnica. Conclusoes: Com a ETE, o anestesiologista conseguiu manejar melhor, de forma adequada e segura o estado hemodinamico de pacientes com risco cardiovascular durante o intraoperatório de cirurgia abdominal, pois as imagens e medições foram de alta qualidade e simples de se obter em tempo real.

La verdad de la dosis renal de dopamina / The truth about the renal dose of dopamine

La dopamina se ha utilizado para prevenir y tratar la falla renal aguda. Ejerce su efecto dependiendo de la dosis que se administre por vía endovenosa, siendo la dosis renal de 3 µg / kg / min. Sus efectos sobre el riñón son mediados por la estimulación de los receptores dopaminérgicos, donde el más importante es la vasodilatación de la arteriola aferente. Se postula, además, que actuaría como una hormona natriurética intrarrenal debido a cambios en el túbulo distal.Existen estudios a favor del uso de la dosis renal de dopamina que han demostrado un aumento de la diuresis o el inicio de ésta en pacientes con falla renal aguda. Sin embargo, estos estudios son no controlados, con un número pequeño de pacientes y en los cuales no se han considerado los efectos adversos de esta droga, por lo tanto, sin significancia estadística. Nuevos estudios controlados, randomizados, doble ciego y estadísticamente significativos, han demostrado que los beneficios de la dopamina son escasos o nulos comparados con un placebo, incluso su uso perjudicaría aún más la función renal y la sobrevida de los pacientes. El por qué se sigue utilizando en la práctica clínica y qué otras alternativasexisten para prevenir y tratar la falla renal aguda, formarán parte de la discusión de este trabajo.

Punción venosa central: incidencia de complicaciones locales en pacientes con y sin efecto heparínico / Central venous punction: incidence of local complications in patients with and without heparinic effects

Por tratarse de un procedimiento invasivo la punción venosa central no está exenta de complicaciones tanto locales como generales. Existe una población de pacientes portadores de patología coronaria, que tienen indicación absoluta de infusión de heparina para lograr anticoagulación total y que debe ser mantenida incluso hasta la llegada del paciente a pabellón. Se estudió una muestra de pacientes (n=72) sometidos a cirugía cardiovascular con circulación extracorpórea (CEC) y con indicación de Swan Ganz en un período de 15 meses en forma prospectiva. Se evaluó entonces la incidencia de complicaciones locales, esto es presencia de hematomaas y hemorragias, al realizar la punción central, postcec y 24 horas postoperatorio en un gupo de pacientes (n=42) sometidos a infusión de heparina hasta su llegada a pabellón comparándola con la incidencia de complicaciones de un grupo de pacientes que no recibió heparina ev (n=32) en ningún momento del preoperatorio. No se encontró diferencias estadísticas en las complicaciones entre ambos grupos