Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response.

Background: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.

Anti-inflammatory effect of different PRGF formulations on cutaneous surface.

Cutaneous autoimmune and inflammatory diseases are a major burden of global disease and many lack effective treatments that can derive in different dermatoses like atopic dermatitis. Despite the increase prevalence and the high health-care costs worldwide, the heterogeniety and multifactoriality of these diseases mean that effective treatment options are scarce. Plasma rich in growth factors (PRGF) technology could be an alternative approach that may help in the management of this cutaneous condition. The aim of this study was to assess the effect of two different PRGF formulations (just activated and autologous topical serum (ATS)) for the management of skin inflammation. Additionally, ATS was assessed over two patients suffering from radiotherapy induced dermatitis. Human organotypic skin explant cultures (hOSECs) were used as human skin models. To induce atopic dermatitis-like conditions, skin explants were treated with both interleukin-4 (IL-4) and interleukin-13 (IL-13). PRGF and ATS were intradermally and topically applied, respectively. Metabolic activity, reactive oxigen species (ROS), necrosis and inflammatory cytokine production were determined. Both PRGF formulations increased tissue viability and significantly reduced the excessive free radical accumulation and the cutaneous cytokine production such as TNF-α and IL-1ß. Case reports showed a positive response after ATS treatment in terms of skin quality improvement, local erythema decrease and burning and itching amelioration. The oedema, swelling and desquamation caused by radiation induced dermatitis was also reduced and the patients referred ceased pruritus and pain. This preliminary study suggests that PRGF might aid in the management of inflammatory skin conditions.

Trends in modes of death in heart failure over the last two decades: less sudden death but cancer deaths on the rise.

AIMS: Better management of heart failure (HF) over the past two decades has improved survival, mainly by reducing the incidence of death due to cardiovascular (CV) causes. Deaths due to non-CV causes, particularly cancer, may be increasing. This study explored the modes of death of consecutive patients who attended a HF clinic over 17 years. METHODS AND RESULTS: A total of 935 deaths were ascertained from 2002 to 2018 among 1876 patients (mean age 65.8 ± 12.5 years, 75% men, left ventricular ejection fraction < 50%) admitted to our HF clinic. Median follow-up was 4.2 years [1.9-7.8]. Mode of death was curated from patient health records and verified by the Catalan and Spanish health system databases. Trends for every mode of death were assessed by polynomial regression. Two trends were observed: a significant reduction in sudden death (P = 0.03) without changes in HF progression as mode of death (P = 0.26), and a significant increase in non-CV modes of death (P < 0.001). Non-CV deaths accounted for 17.4% of deaths in 2002 and 65.8% of deaths in 2018. A total 138 deaths were due to cancer (37% of non-CV deaths). A significant trend was observed towards a progressive increase in cancer deaths over time (P = 0.002). The main mode of cancer mortality was lung cancer. CONCLUSIONS: The modes of death in HF have shifted over the last two decades. Patients with HF die less due to sudden death and more due to non-CV causes, mainly cancer. Whether HF triggers cancer, or cancer develops in HF survivors, deserves further insight.

An autologous protein gel for soft tissue augmentation: in vitro characterization and clinical evaluation.

BACKGROUND: The aging process affects all organs of the body, but the skin is the most visible indicator with a great psychosocial impact. As a consequence, many skin anti-aging strategies have been developed to minimize, postpone, and even reverse the aging process. Growth factors have been widely studied in skin wound healing as these polypeptides play an essential role in the complex process of tissue regeneration. Recently, a novel 3D injectable gel based on the autologous technology platelet rich in growth factor has been described. OBJECTIVES: In this study, a comparison between hyaluronic acid (HA, the gold standard for skin rejuvenation), and this novel autologous formulation has been conducted. METHODS: Rheological and mechanical properties were determined. The in vitro biological capacity of both treatments on human dermal fibroblasts proliferation, migration, chemotaxis, and extracellular matrix synthesis was also assessed. Additionally, a clinical evaluation of the autologous platelet gel treatment was performed by macrophotographs, ultrasound analyses, and clinical and patient surveys. RESULTS: The autologous gel outperformed the general biomechanical properties of HA and kept an optimal viscoelastic gel-like behavior for soft tissue augmentation. Both formulations stimulated cell chemotaxis, migration, and type I collagen synthesis. The autologous gel induced a statistically higher cell proliferation. After the autologous formulation treatment, a soft tissue augmentation effect was also noticed along with an overall skin quality improvement in terms of hydration, elasticity, wrinkle reduction, and general satisfaction scores. CONCLUSIONS: This novel injectable formulation has desirable mechanical and bioactive properties for 3D tissue regeneration and might offer a safe and effective treatment for depressed areas of the skin.

Progress in the use of dental pulp stem cells in regenerative medicine.

The field of tissue engineering is emerging as a multidisciplinary area with promising potential for regenerating new tissues and organs. This approach requires the involvement of three essential components: stem cells, scaffolds and growth factors. To date, dental pulp stem cells have received special attention because they represent a readily accessible source of stem cells. Their high plasticity and multipotential capacity to differentiate into a large array of tissues can be explained by its neural crest origin, which supports applications beyond the scope of oral tissues. Many isolation, culture and cryopreservation protocols have been proposed that are known to affect cell phenotype, proliferation rate and differentiation capacity. The clinical applications of therapies based on dental pulp stem cells demand the development of new biomaterials suitable for regenerative purposes that can act as scaffolds to handle, carry and implant stem cells into patients. Currently, the development of xeno-free culture media is emerging as a means of standardization to improve safe and reproducibility. The present review aims to describe the current knowledge of dental pulp stem cells, considering in depth the key aspects related to the characterization, establishment, maintenance and cryopreservation of primary cultures and their involvement in the multilineage differentiation potential. The main clinical applications for these stem cells and their combination with several biomaterials is also covered.

Weight Loss in Obese Patients With Heart Failure.

BACKGROUND: In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF. METHODS AND RESULTS: Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P<0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P<0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P<0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01). CONCLUSIONS: Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF.

Progress in the Use of Autologous Regenerative Platelet-based Therapies in Implant Dentistry.

The field of medicine is rapidly moving towards the development of personalized treatments and non-invasive tools to achieve a more predictable and optimal tissue regeneration. In this sense, the goal of periodontal healing is to arrest disease progression and functionally regenerate all the tissues that comprise the periodontium. The latter implies a well-orchestrated interaction among oral cells, growth factors and extracellular matrix. Although several procedures are performed in an attempt to regenerate lost periodontal tissue, outcomes are not always predictable. Growth factors represent a class of biologically active polypeptides that have a critical role in the healing process. Their use provides a new paradigm to understand the regenerative medicine. The use of platelet- rich plasma (PRP) products as a local source and delivery system of autologous growth factors has emerged recently. Among them, PRGF stands for its remarkable stimulatory effect on oral tissue regeneration, making it a very safe and successful tool with a great value in Dentistry.

Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification. METHODS: We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis. RESULTS: We identified 55 peptides-13 in serum, 26 in plasma, and 16 in urine-that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings-ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury. CONCLUSIONS: In patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients.

An autologous platelet-rich plasma stimulates periodontal ligament regeneration.

BACKGROUND: Regeneration of periodontal tissues is one of the most important goals for the treatment of periodontal disease. The technology of plasma rich in growth factors provides a biologic approach for the stimulation and acceleration of tissue healing. The purpose of this study is to evaluate the biologic effects of this technology on primary human periodontal ligament fibroblasts. METHODS: The authors studied the response of periodontal ligament cells to this pool of growth factors on cell proliferation, cell migration, secretion of several biomolecules, cell adhesion, and expression of α2 integrin. Cell proliferation and adhesion were evaluated by means of a fluorescence-based method. Cell migration was performed on culture inserts. The release of different biomolecules by periodontal ligament fibroblasts was quantified through enzyme-linked immunosorbent assay. The α2 integrin expression was assessed through Western blot. RESULTS: This autologous technology significantly stimulated cell proliferation, migration, adhesion, and synthesis of many growth factors from cells including vascular endothelial growth factor, thrombospondin 1, connective tissue growth factor, hepatocyte growth factor, and procollagen type I. The α2 integrin expression was lower in plasma rich in growth factor-treated cells compared to non-stimulated cells, although no statistically significant differences were observed. CONCLUSION: This plasma rich in growth factors exerts positive effects on periodontal ligament fibroblasts, which could be positive for periodontal regeneration.

Plasma rich in growth factors promote gingival tissue regeneration by stimulating fibroblast proliferation and migration and by blocking transforming growth factor-ß1-induced myodifferentiation.

BACKGROUND: Periodontitis involves inflammation and infection of the ligaments and bones that support the teeth. Gingival fibroblasts are the most abundant cells in periodontal tissue, and they play a role in maintaining the structural integrity of the tissue. Plasma rich in growth factors contain a pool of proteins and growth factors that promote wound healing and tissue regeneration. In the present study, we evaluate the potential of different formulations obtained with this approach to stimulate several biologic processes involved in wound healing, including fibroblast proliferation, migration, adhesion, and the autocrine release of some angiogenic factors and extracellular matrix components. Furthermore, the ability of this technology to prevent and inhibit transforming growth factor ß1-induced myodifferentiation was also determined. METHODS: Cell proliferation was evaluated through a colorimetric assay, cell migration was performed on culture inserts, and cell adhesion was studied through a fluorescence-based method. Enzyme-linked immunosorbent assay was used to determine some of the biomolecules released by gingival fibroblasts. Smooth muscle actin expression was assessed through immunofluorescence microscopy. RESULTS: Results showed that plasma rich in growth factors significantly increased gingival fibroblast proliferation, migration, and cell adhesion on type I collagen matrix. In addition, it stimulated the autocrine expression of vascular endothelial growth factor, hepatocyte growth factor, and hyaluronic acid. The myofibroblast phenotype, which is characterized by expressing α-smooth muscle actin, was inhibited and reverted by treating with this technology. CONCLUSION: These findings suggest that plasma rich in growth factors is capable of promoting regeneration of gingival connective tissue by stimulating some of the main processes involved in wound regeneration.

Conocimiento médico sobre reanimación cardiopulmonar / Medical knowledge on resuscitation to cardiopulmonar

Presenta un estudio que es de tipo transversal de cohortes, realizado en mar. de 1995 en los hospitales estatales IESS de Quito, dirigido a 151 médicos, 14 internos rotativos, 10 estudiantes de 6to. año de medicina, con el objeto de determinar los conocimientos sobre reanimación cardiopulmonar básica avanzada (RCP). El 68.57xciento recibieron entrenamiento sobre RCP, de los cuales el 70.83xciento recibieron entrenamiento en un hospital, 20xciento en la universidad, 7.5xciento en clínicas particulares y el 1.66xciento no lo indican. Reconocen estar plenamente capacitados el 39.43xciento, y el 62.29xciento desconocen como utilizar un desfibrilador. El 2.38xciento, contestan correctamente todo el cuestionario básico, y nadie acierta en la totalidad de las 10 preguntas de reanimación cardiopulmonar avanzada. A pesar de ser un tema prioritario, no sólo para el médico sino para la población en general, los médicos no estamos teóricamente capacitados para dar una RCP adecuada a un paciente en paro cardiorespiratorio...

Abcesos intra-abdominales post-apendicectomia en el Hospital Pablo Arturo Suárez 1990-1995

Se trata de un estudio retrospectivo, en el que se analiza los pacientes que fueron diagnosticados de absceso intra-abdominal postapendicectomía (AIPA), en el Hospital Pablo Arturo Suárez, entre enero de 1990 a diciembre de 1995. El 2.25 por ciento de los pacientes apendicectomizados, tuvieron AIPA. La perforación y la gangrena apendicular fueron observadas en el 91.7 por ciento de los casos con AIPA. El promedio de horas transcurridas entre el ingreso del paciente a emergencia y la cirugía fue de 14,25 horas, rango 3-45 horas. La fosa ilíaca derecha fue la localización más frecuente de AIPA (50 por ciento). El 66.7 por ciento de los pacientes con AIPA se sometieron a drenaje quirúrgico del absceso más antibiotico-terapia. Nos se observó mortalidad en este grupo de estudio. El cirujano debe desarrollar su criterio diagnóstico, para identificar pacientes en riesgo de AIPA y dar celeridad en el tratamiento quirúrgico d este tipo de paciente...

Infección de heridas post-apendicectomia en el Hospital Pablo Arturo Suarez 1990-1995

El presente es un estudio descriptivo retrospectivo, que determina la incidencia de heridas quirurgicas infectadas post-apendicectomia, en el período comprendido entre, enero de 1990 a diciembre de 1995. Se encontró un número total de 55 pacientes diagnosticados de herida infectada post-apendicectomia y que fueron sometidos a intervención quirurgica de emergencia (apendicectomia) para la resolución satisfatoria de su patología de base (apendicectomía) para la resolución satisfactoria de su patología de base (apendicitis aguda), y en los cuales se encontraron los siguientes resultados. La incidencia de infecciones quirurgicas post-apendicectomía es del 10.35 por ciento (n=55), de acuerdo al sexo masculino es del 54.55 por ciento (n=30) y al femenino 45.45 por ciento(n=25), el promedio de edad de presentación es de 29.6 años (R= 11-62 años), el tipo de incisión que presentó mayores casos de infección fue la infraumbilical media 60 por ciento(n=33), la apendicitis aguda perforada purulenta se asocio con mayor frecuencia a infección de la herida quirurgica en 70.9 por ciento (n=39), el tiempo quirurgico en promedio fue de 1.83 hs (R=30 min - 4 hs). El promedio de días para el diagnostico fue de 4.23 días, (R= 2-7 días). El tratamiento para resolver esta complicación se basó en curación de la herida en forma exclusiva 54.5 por ciento (n=30) y en curación más antibióticoterapia 45.5 por ciento (n=25).

Conocimiento médico sobre reanimación cardiopulmonar

El estudio es de tipo transversal de cohortes, realizado en marzo de 1995 en los hospitales estatales e IESS de Quito, dirigido a 151 médicos, 14 internos rotativos, 10 estudiantes de 6to años de medicina, con el objeto de determinar los conocimientos sobre reanimación cardiopulmonar básica y avanzada (RCP). El 68.57 por ciento recibieron entrenaminto sobre RCP, de los cuales el 70.83 por ciento recibieron entrenamiento en un hospital, 20 por ciento en la universidad, 7.5 por ciento en clínicas particulares y el 1.66 por ciento no lo indican. Reconocen estar plenamente capacitados el 39.43 plor ciento y el 62.29 por ciento desconocen como utilizar un desfibrilador. Eñl 2.28 por ciento contestan correctamente todo el cuestionario básico, y nadie acierta en la totalidad de las 10 preguntas de reanimación cardiopulmonar avanzada. A pesar de ser un tema prioritario, no sólo para el médico sino para la población en general, los médicos no estamos teóricamente capacitados para dar una RCP adecuada a un paciente en para cardio-respiratorio...

Error diagnóstico de apendicitis aguda en el Hospital Pablo Arturo Suárez. Quito 1990-1994

Se trata de un estudio de tipo retrospectivo, para evaluar el error diagnóstico en apendicitis aguda. Se revisó las historias clínicas y formularios 008 del MSP de todos los pacientes que ingresaron al servicio de emergencia del HPAS con diagnóstico de apendicitis aguda o como hallazgo quirúrgico del mismo, en el período enero 1990 a diciembre 1994. El universo fue 437 pacientes, de los cuales solo 428 (97.9 por ciento) fueron intervenidos quirúrgicamente. Dentro del diagnóstico presuntivo de abdomen agudo no apendicular se encontraron 11 pacientes (2.51 por ciento), 9 de ellos tuvieron un diagnóstico inicial de abdomen agudo obstructivo. Como diagnóstico de ingreso errado de apendicitis aguda se presentaron 12 pacientes (2.44 por ciento), 8 de los cuales correspondieron a patología gineco obstétrica. Como diagnóstico asociado se determminó a 95 pacientes (21.7 por ciento). Considerando todos estos valores observamos que el 27 por ciento de todos los pacientes ingresados no tenían una orientación clínica clara en su diagnóstico inicial. La mortalidad fue del 0.22 por ciento. El médico debe considerar todas las posibilidades diagnósticas en caso de apendicitis aguda...