Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors.

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.

Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.

From cardiac tissue engineering to heart-on-a-chip: beating challenges.

The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in engineering functional cardiac tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from cardiac tissue engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in engineering cardiac tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the cardiac models.

Atención de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico / Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center

La incidencia global de las emergencias y urgencias médicoquirúrgicas en pacientes con cáncer ha sido descrita esporádicamente. El objetivo del estudio fue identificar los principales síntomas y diagnósticos de los pacientes que acudieron al Servicio de Urgencias del Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social. El diseño fue observacional y retrospectivo. La información fue obtenida del registro de la consulta diaria del Servicio de Admisión Continua. En un periodo de seis meses fueron atendidos 4,937 pacientes. Los cuadros clínicos evaluados como emergencias correspondieron a 3.7 %, como condiciones médicas urgentes 52.5 % y como condiciones no urgentes, 43.7 %. Los síntomas más frecuentes motivo de las consultas de emergencia o urgencias en los pacientes con cáncer fueron dolor grave en 69.5 % y deshidratación con desequilibrio hidroelectrolítico en 11.4 %. Los principales síntomas fueron provocados por el tumor primario o su diseminación metastásica, en 89 %. Los tumores malignos sólidos más frecuentes fueron los carcinomas mamario, de colon/recto, cervicouterino, broncogénico y gástrico. Las principales emergencias registradas en los pacientes con cáncer en este estudio fueron choque séptico y neutropenia severa (20 %), choque hipovolémico por sangrado en diversos sitios (16.5 %) y disnea agudizada por neumonía o derrame pleural (12 %). En aproximadamente 80 % de quienes son tratados paso a paso de manera racional, el dolor por cáncer pudo ser controlado sólo con analgésicos. La analgesia no efectiva se asoció frecuentemente con prescripción inadecuada o ingesta insuficiente de analgésicos opioides. Los servicios de urgencias establecidos funcionalmente en los hospitales monográficos de cáncer ofrecen la mejor oportunidad de tratamiento a los pacientes con cáncer con condiciones emergentes o urgentes.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center 21st Century, Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.

[Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center]. / Atencián de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center "21st Century," Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.