Adverse effects of cell-free and concentrated ascites reinfusion therapy for malignant ascites: a single-institute experience.

BACKGROUND: Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute. METHODS: We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute. RESULTS: The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids. CONCLUSIONS: The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.

Current Preventions and Treatments of aGVHD: From Pharmacological Prophylaxis to Innovative Therapies.

Graft versus host disease (GVHD) is one of the main causes of mortality and the reason for up to 50% of morbidity after hematopoietic stem cell transplantations (HSCT) which is the treatment of choice for many blood malignancies. Thanks to years of research and exploration, we have acquired a profound understanding of the pathophysiology and immunopathology of these disorders. This led to the proposition and development of many therapeutic approaches during the last decades, some of them with very promising results. In this review, we have focused on the recent GVHD treatments from classical chemical and pharmacological prophylaxis to more innovative treatments including gene therapy and cell therapy, most commonly based on the application of a variety of immunomodulatory cells. Furthermore, we have discussed the advantages and potentials of cell-free therapy as a newly emerging approach to treat GVHD. Among them, we have particularly focused on the implication of the TNFα-TNFR2 axis as a new immune checkpoint signaling pathway controlling different aspects of many immunoregulatory cells.

Pre-culture in endothelial growth medium enhances the angiogenic properties of adipose-derived stem/stromal cells.

Considerable progress has been made on the development of adipose-derived stem/stromal cells (ASCs) as pro-angiogenic therapeutic tools. However, variable clinical results highlight the need for devising strategies to enhance their therapeutic efficacy. Since ASCs proliferate and stabilize newly formed vessels during the angiogenic phase of adipose tissue formation, we hypothesized that mimicking an angiogenic milieu during culture of ASCs would enhance their capacity to support endothelial cell survival and angiogenesis. To test this, we compared the effect of an endothelial growth medium (EGM-2) and conventional media (αMEM) on the progenitor and angiogenic properties of ASCs. ASCs cultured in EGM-2 (ASC-EGM) displayed the highest clonogenic efficiency, proliferative potential and multilineage potential. After co-culture under growth factor starvation, only ASC-EGM attenuated luciferase-expressing human umbilical vein endothelial cells (HUVECluc) apoptosis and supported the formation of endothelial cords in a dose-dependent manner. These effects were recapitulated by the conditioned medium of ASC-EGM, which displayed a 100-fold higher expression of hepatocyte growth factor in comparison with ASC-αMEM. Next, HUVECluc and ASCs were co-transplanted subcutaneously into immunodeficient mice, and the survival of HUVECluc was monitored by bioluminescent imaging. After 60 days, the survival of HUVECluc transplanted alone was equivalent to that of HUVECluc co-transplanted with ASC-αMEM (15.0 ± 0.7 vs. 13.0 ± 0.5%). Strikingly, co-transplantation with ASC-EGM increased HUVECluc survival to 105.0 ± 3.5%, and the resulting organoids displayed functional vasculature with the highest human-derived vascular area. These findings demonstrate that pre-conditioning of ASCs in endothelial growth medium augment their pro-angiogenic properties and could enhance their therapeutic efficacy against ischemic diseases.

El CIREN y la nueva neurología / CIREN and new neurology

Introducción: Con la creación en 1989 del CIREN, Cuba entró en la nueva era de la neurología. Durante la segunda mitad del siglo XX los conceptos de la neurociencia evolucionaron del estatismo a un sistema adaptable y cambiante, moldeado por la experiencia, a través de la propiedad de plasticidad neuronal. El objetivo del trabajo es presentar los logros más relevantes de este esfuerzo de investigación enesta institución.Desarrollo: Además de la atención de pacientes cubanos y extranjeros, se ha desarrollado una intensa investigación sobre todas las herramientas potenciales que podrían servir para recuperar o restaurar la función nerviosa afectada por traumatismos o enfermedad. El paso inicial fue el trasplante neural de células dopaminérgicas a pacientes parkinsonianos. Otras intervenciones de la neurocirugía funcional o resectiva también se intentaron para trastornos del movimiento o epilepsia. La investigación básica ha contribuido a confirmar los beneficios esperados para tratar con éxito los trastornos degenerativos, y los programas de neurorrehabilitación diseñados tratan deinducir un entorno promotor de la plasticidad para maximizar la recuperación.Conclusiones: La investigación en el CIREN ocupa un lugar privilegiado. Algunos resultados han traído nuevos tratamientos clínicos y quirúrgicos. Otros, principalmente los de investigación básica, aún no han encontrado una traducción terapéutica. Pero todos han contribuido en gran medida a dar forma al perfil único de esta institución cubana. La manera de avanzar en los pasos firmes hacia eseobjetivo, es el camino de una ciencia sólida y de alto nivel(AU)

Introduction: With the creation in 1989 of CIREN, Cuba entered the new era of neurology. During the second half of the twentieth century the concepts of neuroscience evolved from statist to an adaptable and changing system, shaped by experience, through the property ofneuronal plasticity. The objective of the work is to present the most relevant achievements of this research effort in this institution.Development: In addition to the care of Cuban and foreign patients, an intense research has been developed on all the potential tools that could be used to recover or restore nerve function affected by trauma or disease. The initial step was the neural transplantation of dopaminergic cells to parkinsonian patients. Other interventions of functional or resective neurosurgery were also tried for movement disorders or epilepsy. Basic research has helped to confirm benefits expected to successfully treat degenerative disorders, andneurorehabilitation programs designed to induce a plasticity promoting environment to maximize recovery.Conclusions: Research at CIREN occupies a privileged place in the interests of the institution. Some results have brought new clinical andsurgical treatments. Others, mainly those of basic research, have not yet found a therapeutic translation. But all have contributed greatly to shaping the unique profile of this Cuban institution. The way to advance in the firm steps towards that goal is the trend of a solid and high level science(AU)

Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies: Controversies in Meta-Analyses Results on Cardiac Cell-Based Regenerative Studies.

In contrast to multiple publication-based meta-analyses involving clinical cardiac regeneration therapy in patients with recent myocardial infarction, a recently published meta-analysis based on individual patient data reported no effect of cell therapy on left ventricular function or clinical outcome. A comprehensive review of the data collection, statistics, and the overall principles of meta-analyses provides further clarification and explanation for this controversy. The advantages and pitfalls of different types of meta-analyses are reviewed here. Each meta-analysis approach has a place when pivotal clinical trials are lacking and sheds light on the magnitude of the treatment in a complex healthcare field.

Terapia com células da medula óssea em modelo experimental de insuficiência hepática aguda induzida por acetominofen / Therapy with bone marrow cells in an experimental model of heart failure liver induced by acute acetaminophen

Introdução e objetivos: a insuficiência hepática aguda (IHA), apesar de rara, permanece como uma condição rapidamente progressiva e frequentemente fatal. A intoxicação por acetaminofen (APAP) induz necrose hepática maciça e frequentemente leva à morte por edema cerebral. Terapias celulares são de grande interesse como potenciais tratamentos para IHA. Neste projeto foi avaliado o potencial terapêutico das células mononucleares da medula óssea (CMMO) em um modelo experimental de IHA induzida por APAP em camundongos. Métodos: A IHA foi induzida em camundongos C57Bl/6, previamente submetidos à dieta alcoólica por três semanas, através da administração de APAP na dose de 300 mg/kg por via intraperitoneal. Após a indução da IHA, os camundongos foram transplantados, por via endovenosa, com 107 CMMO...

Introduction and objectives: a cute liver failure (IHA), although rare, remains a rapidly progressive and often fatal condition. Poisoning by acetaminophen (APAP) induces a massive hepatic necrosis and often leads to death by cerebral edema. Cell therapies are of great interest as potential treatments for IHA. In this project we evaluated the therapeutic potential of bone marrow mononuclear cells (BMC) in an experimental model of IHA induced by APAP in mice. Methods: The IHA was induced in C57BL/6 mice previously submitted to the alcohol diet for three weeks by the administration of APAP at a dose of 300 mg / kg, intraperitoneally. After induction of IHA, the mice were transplanted intravenously with 107 BMC...