Patient-specific organotypic blood vessels as an in vitro model for anti-angiogenic drug response testing in renal cell carcinomaResearch in context

Background: Anti-angiogenic treatment failure is often attributed to drug resistance, unsuccessful drug delivery, and tumor heterogeneity. Recent studies have speculated that anti-angiogenic treatments may fail due to characteristics inherent to tumor-associated blood vessels. Tumor-associated blood vessels are phenotypically different from their normal counterparts, having defective or permeable endothelial monolayers, abnormal sprouts, and abnormal vessel hierarchy. Therefore, to predict the efficacy of anti-angiogenic therapies in an individual patient, in vitro models that mirror individual patient's tumor vascular biology and response to anti-angiogenic treatment are needed. Methods: We used a microfluidic in vitro organotypic model to create patient-specific biomimetic blood vessels from primary patient-specific tumor endothelial cells (TEnCs) and normal endothelial cells (NEnC). We assessed number of sprouts and vessel organization via microscopy imaging and image analysis. We characterized NEnC and TEnC vessel secretions via multiplex bead-based ELISA. Findings: Using this model, we found that TEnC vessels exhibited more angiogenic sprouts than NEnC vessels. We also found a more disorganized and gap-filled endothelial monolayer. NEnCs and TEnC vessels exhibited heterogeneous functional drug responses across the five patients screened, as described in the clinic. Interpretation: Our model recapitulated hallmarks of TEnCs and NEnCs found in vivo and captured the functional and structural differences between TEnC and NEnC vessels. This model enables a platform for therapeutic drug screening and assessing patient-specific responses with great potential to inform personalized medicine approaches. Funding: NIH grants R01 EB010039, R33 CA225281, R01CA186134 University of Wisconsin Carbone Cancer Center (CA014520), and University of Wisconsin Hematology training grant T32 HL07899. Keywords: Organotypic, Lumen, Model, Anti-angiogenic, Renal, Carcinom

Ecografía Multiórgano en infección por SARS-COV2

Objetivo: Existe una creciente evidencia con respecto a los hallazgos ecográficos y la COVID-19, destacando la ecografía multiórgano para el diagnóstico y el seguimiento de estos pacientes. El objetivó fue describir los hallazgos ecográficos a nivel pulmonar, cardiaco y del sistema venoso profundo de extremidades inferiores en pacientes con infección por SARS-COV-2. Material y Métodos: Estudio prospectivo, transversal y observacional realizado en pacientes con COVID-19 confirmado a los que se les realizó una ecografía multiórgano en el punto de atención durante la hospitalización. Resultados: Un total de 107 pacientes se inscribieron. El 100% de los pacientes tenían afectación pulmonar (93,4% bilateral). Las zonas pulmonares más afectadas fueron la posteroinferior (94,39%) y la lateral (89,72%). Se observó consolidaciones subpleurales en el 71% de los pacientes y consolidaciones mayores de 1 cm en el 25%. A mayor afectación pulmonar ecográfica, mayor grado de insuficiencia respiratoria. 2 pacientes presentaron TVP proximal en extremidades inferiores. Se realizaron 27 Angiotomografía computarizada confirmándose tromboembolismo pulmonar en 14 pacientes. Los hallazgos ecocardiográficos más frecuentes fueron: alteración de la relajación del ventrículo izquierdo e hipertrofia ventricular izquierda. Todos los pacientes con enfermedad tromboembólica tenían una afectación pulmonar ecográfica grave o crítica. Conclusión: la ecografia multiórgano puede ser útil para las manifestaciones de la COVID-19. El grado de afectación ecográfica pulmonar se relacionó con el grado de insuficiencia respiratoria y con la presencia de ETEV. La relación entre TVP y TEP fue más baja de lo esperado. La afectación cardiaca fue poco relevante en nuestra serie

Importance of Lung Ultrasound Follow-Up in Patients Who Had Recovered from Coronavirus Disease 2019: Results from a Prospective Study

There is growing evidence regarding the imaging findings of coronavirus disease 2019 (COVID-19) in lung ultrasounds, however, their role in predicting the prognosis has yet to be explored. Our objective was to assess the usefulness of lung ultrasound in the short-term follow-up (1 and 3 months) of patients with SARS-CoV-2 pneumonia, and to describe the progression of the most relevant lung ultrasound findings. We conducted a prospective, longitudinal and observational study performed in patients with confirmed COVID-19 who underwent a lung ultrasound examination during hospitalization and repeated it 1 and 3 months after hospital discharge. A total of 96 patients were enrolled. In the initial ultrasound, bilateral involvement was present in 100% of the patients with mild, moderate or severe ARDS. The most affected lung area was the posteroinferior (93.8%) followed by the lateral (88.7%). Subpleural consolidations were present in 68% of the patients and consolidations larger than 1 cm in 24%. One month after the initial study, only 20.8% had complete resolution on lung ultrasound. This percentage rose to 68.7% at 3 months. Residual lesions were observed in a significant percentage of patients who recovered from moderate or severe ARDS (32.4% and 61.5%, respectively). In conclusion, lung injury associated with COVID-19 might take time to resolve. The findings in this report support the use of lung ultrasound in the short-term follow-up of patients recovered from COVID-19, as a radiation-sparing, easy to use, novel care path worth exploring