Beneficios del plasma rico en plaquetas en el tratamiento de las úlceras crónicas por pie diabético / Benefits of Platelet-Rich Plasma in the Treatment of Chronic Diabetic Foot Ulcers

La Diabetes Mellitus es una enfermedad crónica que afecta a millones de personas en todo el mundo causando problemas socioeconómicos y emocionales; una de las complicaciones más temidas de la enfermedad son las úlceras crónicas por pie diabético (UCPD), ya que constituyen una de las principales causas de amputación de miembros inferiores, la prevalencia más alta se halló en Norteamérica (13%), en Bolivia la diabetes tipo 2 tuvo una prevalencia nacional para adultos de 6,5% y de ellos aproximadamente el 20% desarrollaron las UCPD. Por ello, fue indispensable contar con un tratamiento efectivo que evite la cronicidad, infección y amputación del miembro afectado por las úlceras. El Plasma rico en plaquetas es un producto derivado de la sangre con varios elementos que intervienen en la regeneración de tejidos y con efectos antiinflamatorios en varias lesiones; por tal motivo, surge como una opción promisoria para el tratamiento de las UCPD sin importar el grado de lesión (grados de Wagner).Para exponer sus beneficios y considerarlo como tratamiento de primera línea, se efectuó una revisión sistemática, con objetivos de carácter descriptivo-exploratorio; la recolección de la literatura se realizó de fuentes primarias (últimos 5 años), secundarias y terciarias. Finalmente, tras el análisis de los resultados se concluye indicando que el PRP como tratamiento disminuye el tiempo de curación de las úlceras del pie diabético, riesgo de infección, etc.

Diabetes Mellitus is a chronic disease that affects millions of people around the world, causing socioeconomic and emotional problems; one of the most feared complications of the disease are chronic diabetic foot ulcers (UCPD), since they constitute one of the main causes of lower limb amputation, the highest prevalence was found in North America (13%), in Bolivia the Type 2 diabetes had a national adult prevalence of 6.5%, and approximately 20% of them developed UCPD. Therefore, it was essential to have an effective treatment that prevents chronicity, infection and amputation of the limb affected by ulcers. Platelet-rich plasma (PRP) is a blood-derived product with several elements involved in tissue regeneration and with anti-inflammatory effects on various lesions; For this reason, it emerges as a promising option for the treatment of UCPD regardless of the degree of injury (Wagner grades). To expose its benefits and consider it as first-line treatment, a systematic review was carried out, with descriptive-exploratory objectives; the literature was collected from primary (last 5 years), secondary and tertiary sources. Finally, after analyzing the results, it is concluded that PRP as a treatment decreases the healing time of diabetic foot ulcers, the risk of infection, etc.

Catalytic Nanomedicine - A new Approach and Solution for Chronic Ulcers: Case Series.

Chronic ulcers are a major public health problem, due to their chronic nature, their poor response to treatment, the high frequency of recurrences, and their affection to the patient's quality of life. Even with the development of new therapies in the field of chronic wound care, chronic ulcers remain a clinical problem. As a novel branch of research, Catalytic Nanomedicine has offered promising results in disinfection and treatment of chronic wounds through the use of bionanocatalysts, organically functionalized mesoporous nanostructured materials with catalytic properties. Particularly, Cu/TiO2-SiO2 mixed oxide bionanocatalysts have shown favorable results for chronic ulcer healing. In this work, we present the treatment of 15 patients (8 females and 7 males, mean age of 69.59 ± 12.07 years old) affected with chronic ulcers (wound age ranging from 4 months to 10 years old, mean size of 12.94 ± 18.20 cm2) by the administration of Cu/TiO2-SiO2 bionanocatalysts embedded in a nanoemulsion matrix. In all cases, complete epithelialization and healing of the lesions was achieved (healing time from 3 to 35 weeks), without the appearance of side effects. Wound healing time was analyzed in the context of initial wound size, wound's age, patient's age, and concomitant conditions, being wound size and patient's age the main factor affecting the duration of the treatment with the bionanocatalysts.

Epstein-Barr virus-positive ulcer in the oral cavity.

Epstein-Barr virus-positive ulcer (EBV + U) is a recently reported B cell lymphoproliferative disorder in the oral cavity, oropharynx, gastrointestinal tract and skin, principally in immunosuppressed patients. A 53-year-old female patient with rheumatoid arthritis treated with methotrexate, presenting ulcers of unknown duration on the dorsum and the lateral left border of the tongue. Excisional biopsy, histopathological analysis and histochemical stains for syphilis (Warthin-Starry), mycotic diseases (Grocott silver methenamine), tuberculosis (Ziehl-Neelsen), immunohistochemistry tests for herpesvirus type 8 (CMV), EBV (LMP-1) and DNA extraction for polymerase chain reaction (PCR) assay to CMV, EBV and herpes simplex virus-1 were performed. Posterior to PCR assay, the final diagnosis was EBV + U in the oral cavity. Acyclovir® was prescribed, showing clinical improvement. A case of EBV + U with clinical characteristics similar to other lesions or conditions has been reported. Special assays are necessary for an accurate diagnosis and treatment.

The great imitator with no diagnostic test: pyoderma gangrenosum.

Pyoderma gangrenosum is a rare, neutrophil-mediated, auto-inflammatory dermatosis that wound care specialists must be prepared to recognise. This condition has clinical features analogous to infectious processes. There is no specific diagnostic test and the diagnosis is usually obtained from exclusion. Its early recognition and proper management with prompt initiation of immunosuppressive therapy are essential to improve the quality of life and the prognosis of patients.

Medicina Regenerativa para Úlceras Crónicas: Aplicación Cutánea de Células Troncales Mesenquimales de Gelatina de Wharton / Regenerative Medicine for Chronic Ulcers: Cutaneous Application of Mesenchymal Stem Cells of Wharton's Jelly

Resumen El empleo de células mesenquimales ha emergido como una parte importante en la medicina regenerativa con efectos positivos en la recuperación de tejidos dañados o perdidos. Las úlceras crónicas incluyen lesiones cutáneas que afectan a una gran parte de la población con diabetes mellitus, (por ejemplo 9.14% desarrollan lesiones por pie diabético según ENSANUT 2016) y representan gastos económicos considerables, debido a la pobre calidad de vida que llevan los pacientes. El tratamiento convencional que se lleva a cabo en estos casos es a largo plazo, y los efectos benéficos generados que se presentan son limitados, ya que las lesiones reinciden por no contar con un tratamiento específico y regenerativo, solo paliativo. Es por ello que en este trabajo se obtuvieron y emplearon células troncales mesenquimales derivadas de gelatina de Wharton (CTM-GW) bajo los criterios propuestos por la Sociedad Internacional de la Terapia Celular. El tratamiento fue aplicado en dos pacientes con úlceras crónicas flebostáticas de diferentes condiciones médicas y se monitoreo a corto plazo, por lo que fue un estudio limitado. Los resultados mostraron que las CTM-GW indujeron la reconstrucción cutánea mediante formación de tejido de granulación, además de disminuir el proceso inflamatorio crónico en la zona de daño, lo que favoreció el índice de cierre de la herida. Por lo anterior, se propone la utilización de CTM-GW en úlceras flebostáticas crónicas como tratamiento en la regeneración de la estructura tisular con resultados a corto plazo.

Abstract Use of mesenchymal cells has emerged as an important part in regenerative medicine with positive effects in the recovery of damaged or lost tissues. Chronic ulcers include skin lesions that affect a large part of the population with diabetes mellitus, (for example, 9.14 develop diabetic foot according to ENSANUT 2016) and represent considerable economic expenses, due to poor quality of life in patients. The conventional treatment that is carried out in these cases is long term, and the generated beneficial effects that are presented are limited, since the injuries recur due to not having a specific and regenerative treatment, only palliative. That is why in this work they were obtained and used mesenchymal stem cells derived from Wharton's jelly (MSC-WJ) under the criteria proposed by the International Society for Cell Therapy. The treatment was applied in two patients with chronic ulcers phlebostatic of different medical conditions and short-term monitoring, so it was a limited study. The results showed that MSC-WJ induced skin reconstruction by tissue formation granulation, in addition to decreasing the chronic inflammatory process in the area of damage, which favored the index of wound healing. Therefore, the use of MSC-WJ in chronic phlebostatic ulcers is proposed as a treatment in the regeneration of the tissue structure with short-term results.

Regeneration of Diabetic Foot Ulcers Based on Therapy with Red LED Light and a Natural Latex Biomembrane.

This study analyzes the effects of the Rapha® system, which employs red light therapy (RLT) and a natural latex biomembrane in the healing of neuropathic ulcers associated with the diabetic foot. We conducted a randomized, controlled, blinded clinical trial with 15 participants that were divided into three groups (GI, GII and GIII): (i) Rapha® system application by the participant and a health professional at home, with clinical status evaluation every 2 weeks at the hospital (GI); (ii) standard protocol used in Brazil, performed by a health professional at the hospital (GII; control); and (iii) the Rapha® system applied by the participant at home and clinical status evaluation every 2 weeks at the hospital (GIII). We used image processing techniques on photographic recordings of the lesions, and several statistical tests were used to analyze the data, allowing for the comparison of the average results for all groups. The average healing rates of GI, GII, and GIII were 77.0, 51.4, and 80%, respectively. The granulation tissue evaluation indicated a higher efficacy in the tissue repair of lesions treated with the Rapha® system. In conclusion, the Rapha® system proved to be an effective healing system, even when self-applied at the patient's home.

¿Qué hay de nuevo en calcifilaxia? / ¿What is new in calciphylaxis? / ¿O que há de novo na calcifilaxia?

Objetivo: Revisar la literatura científica publicada en las principales bases de datos, entre los años 1962 y 2016, cuyo objetivo fue abordar el tema de la calcifilaxia y sus principales características. Metodología: Se llevó a cabo una revisión de la literatura en las principales bases de datos de las Ciencias de la Salud y las Ciencias Sociales (medline-pubmed, cinhal, web of science, lilacs, sociological abstracts, cuiden, embase, psycoinfo e isi web of knowledge). Se emplearon descriptores en español, inglés y portugués: Calcifilaxis, diálisis, hiperparatiroidismo, necrosis, gangrena, calcificación vascular, cuidados de enfermería y diagnósticos de enfermería. Se hizo una revisión sistemática de los artículos seleccionados utilizando un protocolo para extraer los datos. Resultado: Se encontraron 45 artículos que cumplían con los criterios de búsqueda establecidos, 35 reportaron los resultados de ensayos clínicos o estudios cualitativos, 4 correspondían a revisiones sistemáticas y 6 se catalogaron como estudios retrospectivos. Los autores señalaron las principales características de la enfermedad, de los pacientes y los tratamientos más usados, pero poco del cuidado que debe brindar el profesional enfermero. Conclusión: En los estudios analizados se identificaron principalmente aspectos sobre el curso de la enfermedad y el tratamiento; se reportó la efectividad de algunos tratamientos utilizadas en la atención de dichos pacientes, pero ninguna de ellas definitiva, lo que permite proponer algunas acciones desde la disciplina enfermera.

Objective: To analyze the scientifi c literature published in the main databases between 1962 and 2016, whose objective was to address the issue of calciphylaxis and its main characteristics? Methodology: A literature review was carried out in the main databases of the Health Sciences and Social Sciences (medline-pubmed, cinhal, web of science, lilacs, sociological abstracts, cuiden, embase, psycoinfo and isi web of knowledge). An analytical review of the selected articles was made using a protocol to extract the data. Results: 45 articles were found that fulfi lled the established search criteria, 35 reported the results of clinical trials or qualitative studies, 4 corresponded to systematic reviews and 6 were classifi ed as retrospective studies. The authors pointed out the main characteristics of the disease, the patients and the most used treatments, but little of the care that should be provided by the nurse practitioner. Conclusion: In the analyzed studies, aspects regarding the course of the disease and treatment were identifi ed; it was reported the effectiveness of some treatments used in the care of these patients, but none of them defi nitive, which allows to propose some actions from the nurse discipline.

Objetivo: Revisar a literatura científica publicada nas principais bases de dados, entre os anos 1962 e 2016, cujo objetivo era abordar o tema da calcifilaxia e suas principais características. Metodologia: Uma revisão da literatura foi realizada nas principais bases de dados das Ciências da Saúde e das Ciências Sociais (Medline-Pubmed, Cinhal, Web of Science, Lilacs, Sociological abstracts, Cuiden, Embase, Psycoinfo e Isi Web of Knowledge). Foram usados descritores em espanhol, inglês e português: calcifilaxia, diálise, hiperparatiroidismo, necrose, gangrena, calcificação vascular, cuidados de enfermagem e diagnósticos de enfermagem. Foi feita uma revisão sistemática dos artigos selecionados utilizando um protocolo para extrair os dados. Resultados: Encontraram-se 45 artigos que cumpriam com os critérios de busca estabelecidos, 35 reportaram os resultados de ensaios clínicos ou estudos qualitativos, quatro (4) correspondiam a revisões sistemáticas e seis (6) se catalogaram como estudos retrospectivos. Os autores apontaram as principais características da doença, dos pacientes e os tratamentos mais usados, mas pouco do cuidado que debe oferecer o professional da enfermagem. Conclusão: Nos estudos analisados se identificaram principalmente aspectos sobre o curso da doença e o tratamento; se reportou a efetividade de alguns tratamentos utilizados no atendimento desses pacientes, mas nenhum deles definitivo, o que permite propor algumas ações desde a profissão da enfermagem.

Therapeutic effectiveness of a Calendula officinalis extract in venous leg ulcer healing.

OBJECTIVE: Non-healing venous leg ulcers (VLUs) have a significant effect on patients' quality of life and substantially increase expenditures in health-care systems. The aim of this study was to evaluate the clinical efficacy of the Calendula officinalis extract, Plenusdermax, in the treatment of VLUs. METHOD: Patients treated with Calendula officinalis extract (n=38) and control patients (n=19) were evaluated every two weeks for 30 weeks or until their ulcers healed. Assessments included determination of the wound area by planimetry, infection control, and evaluation of the clinical aspects of the wounds. The percentage of healing velocity per week (%HVw), taking the initial area at baseline into account, was also determined. RESULTS: The proportion of the treatment patients achieving complete epithelialisation was 72 % and 32 % in the treatment and control groups, respectively. The average healing time was approximately 12 weeks in the treatment group and 25 % in control patients. Patients with ulcers treated with Calendula officinalis extract had a significant 4-fold increase in percentage healing velocity per week, 7.4 %, compared with 1.7 % in the control group. No adverse events were observed during the Calendula officinalis extract treatment. CONCLUSION: Our findings indicate that Calendula officinalis extract is an effective treatment for VLUs. DECLARATION OF INTEREST: The authors have no conflict of interest.

Células tronco mesenquimales: definiciones, cultivo y aplicaciones potenciales / Mesenchymal stem cells: definitions, culture and potential applications

RESUMEN En los últimos años, las células troncales mesenquimales (Mesenchymal Stem Cells, MSC) han adquirido mucha importancia debido a su gran plasticidad y su capacidad de liberar factores paracrinos con capacidad de interactuar con diversos tipos celulares, tejidos y órganos. El uso de MSC en medicina regenerativa es importante debido a que, al no expresar las moléculas del complejo mayor de histocompatibilidad (MHC) clase II ni moléculas co-estimuladoras y tener baja expresión del MHC clase I, haría que no sean rechazadas por individuos de la misma especie, es posible utilizarlas no sólo de manera autóloga, sino también, eventualmente, alogénica. Sin embargo, es importante demostrar científicamente muchas de sus propiedades, entre ellas las inmunomoduladoras. Al tener varias fuentes de obtención, se debe estandarizar la que sea la mejor para garantizar la pureza y calidad de las MSC. Finalmente, es importante que cuando se trabaje con estas células se demuestre completamente las características del cultivo celular, la inmunotipificación y su capacidad de diferenciación. Se están ensayando muchas aplicaciones clínicas de las MSC. Dentro de ellas, su capacidad para mejorar la recuperación y potencial curación de úlceras crónicas como las diabéticas, ha atraído la atención por su potencial impacto terapéutico.

ABSTRACT In recent years, mesenchymal stem cells (MSC) have become very important due to their high plasticity and their ability to release paracrine factors able to interact with various cell types, tissues and organs. The use of MSC in regenerative medicine became of vital importance, since they do not express histocompatibility MHC molecules class II nor costimulant molecules, and low expression of MHC class I, will not be rejected by individuals of same species, they could be used in an autologous, and eventually, allogeneic manner. However, it is important to scientifically demonstrate many properties, including immunomodulatory ones. Having several sources of obtaining, it should be standardized the best one to ensure the purity and quality of these cells. Finally, it is important when working with these cells, that characteristics of cell culture, immunophenotyping and differentiation capacity are fully demonstrated. MSC have been applied in several clinical uses. Among them, their ability to improve, and even heal chronic ulcers, as diabetic, has attracted attention for its potential therapeutic impact.

Suscetibilidade antimicrobiana de bactérias ocorrentes em úlceras crônicas aos extratos brutos de Prosopis juliflora / Antimicrobial susceptibilit y of bacteria in chronic ulcers to crude extracts of Prosopis juliflora

Úlceras crônicas são suscetíveis à infecção devido à perda estéril da função de barreira inata da pele e dos anexos cutâneos, facilitando o desenvolvimento de comunidades microbianas. O objetivo do estudo foi investigar a suscetibilidade de bactérias associadas a úlceras crônicas aos extratos brutos de Prosopis juliflora. Os testes in vitro foram realizados com extratos brutos das folhas e casca do caule contra as estirpes de Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) e Proteus mirabilis (ATCC 7002), por meio de ensaio de difusão em agar com poço e determinação da Concentrações Inibitórias Mínimas (MIC). Os resultados mostraram que as estirpes de E. coli, P. aeruginosa, S. aureus e P. mirabilis foram mais susceptíveis aos extratos brutos da folha, com diâmetro de zona de inibição de 21,0; 33,0; 20,0; 21,0 mm, respectivamente, enquanto, E. coli e S. aureus foram mais susceptíveis aos extratos brutos da casca do caule, com diâmetro da zona de inibição de 21,5 e 20,0 mm, respectivamente. Os melhores valores de CIM foram registrados para EBF de P. juliflora. Estudo químico para a extração e o isolamento de compostos ativos é recomendado para realização de ensaios in vitro para investigar a atividade antimicrobiana destes compostos.

Chronic ulcers are prone to infection due to the sterile lossof the innate barrier of the skin and cutaneous annexes, coupled to the development of microbial communities. Current study investigates the susceptibility of bacteria associated with chronic ulcers to crude extracts of Prosopis juliflora. In vitro tests with the crude extracts of leaves and stem bark were performed against strains of Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) and Proteus mirabilis (ATCC 7002), by a diffusion assay in agar and determination of Minimum Inhibiory Concentration (MIC). Results showed that E. coli, P. aeruginosa, S. aureus and P.mirabilis strains were affected by the crude extracts of the leaves, with a diameter of the inhibition zone measuring respectively 21.0; 33.0; 20.0; 21.0 mm, whereas E. coli and S. aureus were more affected to the crude extracts of the stem bark, with an inhibition zone diameter of 21.5 and 20.0 mm, respectively. Best MIC rates were reported for the crude extracts of P. juliflora leaves. Chemical studies for the extraction and isolation of compounds are recommended for the execution of in vitro assays to investigate the compounds´ antimicrobial activity.

Tratamiento de las úlceras crónicas en los miembros inferiores con un equivalente cutáneo autólogo y desbridación con larvas de Lucilia sp. (Diptera: Calliphoridae). Reporte de un caso / Chronic lower limb ulcers treatment with autologous skin equivalent and larvae debriding (Diptera Calliphoridae)

Introducción: las úlceras en los miembros inferiores constituyen una causa importante de hospitalización y deterioro en la calidad de vida de los pacientes, al interferir con sus actividades laborales y sociales. Estas lesiones obedecen a diferentes enfermedades, la más frecuente de las cuales en Medellín es la insuficiencia venosa; una vez diagnosticadas, existen muchas alternativas de tratamiento, que buscan crear un lecho apropiado para el cierre de la herida. El uso de larvas para el desbridamiento es una alternativa rápida y de bajo costo, con la cual se logra un tejido de granulación adecuado para la aplicación de equivalentes cutáneos autólogos, que constituyen una opción para pacientes refractarios a otros tratamientos. Materiales y métodos: se seleccionó y evaluó a una paciente de acuerdo con los criterios de inclusión establecidos para el estudio. Para desbridar la úlcera se recurrió a la aplicación de larvas de Lucilia sp. (Diptera: Calliphoridae), btenidas a partir de huevos previamente desinfectados con hipoclorito de sodio y sembrados en un medio de cultivo con antibióticos. Se aplicaron las larvas directamente en la lesión y posteriormente se procedió a tapar esta con muselina, permitiendo la obtención de oxígeno y facilitando el drenaje del tejido necrótico. Las larvas se dejaron por 48 horas, al cabo de las cuales se retiraron con una pinza estéril y se descartaron en alcohol al 70%; luego se procedió a evaluar la limpieza de la lesión. Este procedimiento se llevó a cabo en el Laboratorio de Entomología (GIEM) de la Universidad Antioquia. Se procesó una biopsia de piel de la paciente, obtenida siguiendo un protocolo previamente establecido, para obtener queratinocitos y fibroblastos. Para el cultivo primario de queratinocitos el 90% de las células obtenidas de la biopsia se sembró en cajas de cultivo de 75 cm2, en presencia de 7 x 106 células de la línea 3T3-Swiss tratadas con mitomicina C (10 μg/mL) como capa alimentadora; para el cultivo primario de fibroblastos, se sembró el 10% de las células en cajas de cultivo de 75 cm2 con el medio DMEM suplementado. En la producción del equivalente cutáneo se utilizó un gel obtenido con una mezcla de plasma humano de sangre AB de banco de sangre, 6-7,5 x 104 fibroblastos, CaCl2 y ácido tranexámico. Sobre dicho gel se sembraron luego los queratinocitos provenientes del cultivo primario y se hizo seguimiento del cultivo en microscopio invertido. Cuando se obtuvo una confluencia celular cercana al 100%, se desprendió el equivalente cutáneo con pinzas estériles para aplicarlo inmediatamente sobre la úlcera. Se reportan los resultados del tratamiento de una úlcera en el miembro inferior izquierdo de una paciente de 66 años con la terapia combinada de desbridamiento con larvas y cultivo de equivalentes cutáneos autólogos. Después de 15 meses de iniciado el tratamiento, la úlcera continúa cerrada y la paciente no tiene dolor ni impedimentos funcionales en la extremidad.