Evaluación in vivo e in vitro del tratamiento con plasma rico en plaquetas en osteoartrosis de rodilla.

Mario Alberto Simental Mendía Fecha de Graduación: Agosto, 2016 Universidad Autónoma de Nuevo León Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina Título de la Tesis: Evaluación in vivo e in vitro del tratamiento con plasma rico en plaquetas en osteoartrosis de rodilla. Número de páginas: Área de Estudio: Terapia Celular. Introducción. La osteoartrosis (OA) de rodilla es una enfermedad degenerativa y progresiva del cartílago articular y se caracteriza por presentar un estado catabólico en el cartílago inducido por citocinas pro-inflamatorias. La infiltración de plasma rico en plaquetas (PRP) autólogo se ha propuesto como una alternativa terapéutica, debido a su contenido de citocinas biológicamente activas. Además, el PRP ha mostrado tener propiedades anti-inflamatorias y regenerativas en cartílago articular dañado. Los mejores resultados del uso de esta terapia se han obtenido en cartílago con un menor grado de lesión y de OA. Objetivos. 1) Comparar la respuesta clínica a la infiltración con PRP y al tratamiento convencional en pacientes con OA leve, y 2) determinar el efecto in vitro del PRP sobre la expresión de marcadores genéticos específicos y sobre la matriz extracelular del cartílago. Materiales y Métodos. Se analizó un total de 65 pacientes con diagnóstico clínico y radiográfico de OA grado I y II. Los pacientes se aleatorizaron en dos grupos: a 32 se les trató con paracetamol (500 mg/8 h) por 6 semanas, y 33 recibieron 3 infiltraciones intra-articulares de PRP (una cada dos semanas). Todos los pacientes fueron evaluados con la Escala Visual Análoga (EVA), el índice de OA de Western Ontario and McMaster Universities (WOMAC) y la encuesta de salud SF-12 al inicio del tratamiento y 6, 12 y 24 semanas después. Se obtuvieron explantes de cartílago y PRP de 10 donadores que fueron sometidos a cirugía de reemplazo articular de rodilla. Los explantes se cultivaron en frascos spinner por hasta 28 días, en agitación constante y en presencia de interleucina-1β (IL-1β), PRP o PRP/IL-1β. Se cuantificó la expresión de genes asociados a inflamación y degradación de la matriz del cartílago (MMP-13, ADAMTS5, IL-1β) y de aquellos involucrados en la restauración de la matriz extracelular (colágeno tipo II, agrecano y SOX9). Se realizó un análisis histológico de acuerdo a la escala de Mankin modificada y a la cuantificación del marcaje por inmunohistoquímica de colágeno tipo II y tipo I. Resultados. Comparación de la respuesta clínica a la infiltración con PRP y del tratamiento convencional. Ambos tratamientos mostraron una disminución significativa en la EVA desde la semana 6. La disminución en el nivel de dolor de EVA fue mayor en el grupo tratado con PRP. Los pacientes tratados con PRP tuvieron una mejoría sostenida en la funcionalidad de la rodilla, al menos hasta las 24 semanas. Los resultados de SF-12 indican una mejoría en la calidad de vida sólo en el grupo tratado con PRP a las 6, 12 y 24 semanas. Evaluación del efecto in vitro del PRP sobre la expresión de marcadores genéticos específicos y sobre la matriz extracelular del cartílago. La expresión de los genes catabólicos y el valor de la escala de Mankin xiii fueron menores en los explantes tratados con PRP y PRP/IL-1β que en los tratados con IL-1β. Se observó una mayor expresión de los genes involucrados en la síntesis de matriz extracelular en los explantes tratados con PRP y PRP/IL-1β en comparación con el explantes tratados con IL-1β. Los explantes tratados con PRP y PRP/IL-1β mostraron una mayor presencia de proteoglicanos y colágeno tipo II, así como una menor presencia de colágeno tipo I; estos explantes también tuvieron una mejor integridad de la superficie y un incremento significativo en el número de condrocitos al compararlos con los explantes tratados con IL-1β. Conclusiones. El tratamiento con PRP presentó un mejor resultado clínico que el tratamiento convencional con paracetamol, con una disminución sostenida en los puntajes de las escalas EVA y WOMAC y una mejor calidad de vida de los pacientes. Además, el PRP favoreció la restauración de la matriz extracelular en explantes de cartílago con OA leve y disminuyó el efecto pro-inflamatorio de la IL-1β. El uso del PRP es una terapia prometedora para el cartílago dañado en OA temprana, ya que promueve la reparación de la matriz extracelular, disminuye la inflamación y retrasa la degeneración del cartílago. ____________________________________ Dra. C. Herminia Guadalupe Martínez Rodríguez Directora de Tesi

Plantar Fasciitis—A Comparison of Treatment with Intralesional Steroids versus Platelet-Rich Plasma

Background: Many treatment options for plantar fasciitis currently exist, some with great success in pain relief. The objective of our study was to compare the use of intralesional steroids with platelet-rich plasma (PRP), using pain scales and functional evaluation, in patients with plantar fasciitis who did not respond to conservative treatment. Methods: A controlled, randomized, blinded clinical assay was performed. Patients were assigned to one of the two groups by selecting a sealed envelope. The steroid treatment group received 8 mg of dexamethasone plus 2 mL of lidocaine as a local anesthetic. The PRP treatment group received 3 mL of PRP activated with 0.45 mL of 10% calcium gluconate. All of the patients were evaluated at the beginning of the study, and at 2, 4, 8, 12, and 16 weeks post-treatment with the Visual Analog Scale (VAS), Foot and Ankle Disability Index (FADI), and American Orthopedic Foot and Ankle Society (AOFAS) scale. Results: The right foot was the most frequently affected foot (63%). The average age of the patients was 44.8 years (range, 24–61 years). All scales used (VAS, FADI and AOFAS) showed that the difference was not statistically significant between the two groups. Conclusions: We can conclude that the use of PRP is an effective treatment method for patients with plantar fasciitis who do not respond to conservative treatment because PRP demonstrates an efficacy equal to that of steroids. However, the cost and the time for preparation the PRP are two of the disadvantages of this treatment. (J Am Podiatr Med Assoc 107(6): 490-496, 2017

Repair of ovine peripheral nerve injuries with xenogeneic human acellular sciatic nerves prerecellularized with allogeneic Schwann-like cells—an innovative and promising approach

Introduction: The iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs. Methods: We compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT). Results: All sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted. Conclusions: Xenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair

Magnesium and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational and intervention studies

Purpose: To map and grade all health outcomes associated with Magnesium (Mg) intake using an umbrella review. Methods: Umbrella review of systematic reviews with meta-analyses of observational studies and randomised controlled trials (RCTs) using placebo/no intervention as control group. We assessed meta-analyses of observational studies based on random-effects summary effect sizes and their P-values, 95% prediction intervals, heterogeneity, small-study effects and excess significance. For meta-analyses of RCTs, outcomes with a random effects P-value <0.005 and a high GRADE assessment, were classified as strong evidence. Results: From 2,048 abstracts, 16 meta-analyses and 55 independent outcomes were included (36 in RCTs and 19 in observational studies). In RCTs of Mg versus placebo/no active treatment, 12 over 36 outcomes reported significant results (p<0.05). A strong evidence for decreased need for hospitalization in pregnancy and for decreased risk of frequency and intensity of migraine relapses in people with migraine was observed using the GRADE assessment. In observational studies, 9/19 outcomes were significant (p<0.05). However, only one outcome presented highly suggestive evidence (lower incidence of type 2 diabetes in people with higher Mg intake at baseline) and one suggestive (lower incidence of stroke associated with higher Mg intake at baseline). Conclusion: Strong evidence according to the GRADE suggests that Mg supplementation can decrease the risk of hospitalization in pregnant women and reduce the intensity/frequency of migraine. Higher Mg intake is associated with a decreased risk of type 2 diabetes and stroke with highly suggestive and suggestive evidence, respectively, in observational studies