A tool for evaluating novel osteoarthritis therapies using multivariate analyses of human cartilage-synovium explant co-culture.

OBJECTIVE: There is a need to incorporate multiple tissues into in vitro OA models to evaluate novel therapeutics. This approach is limited by inherent donor variability. We present an optimized research tool: a human OA cartilage-synovium explant co-culture model (OA-EXM) that employs donor-matched lower and upper limit response controls combined with statistical approaches to address variability. Multiple rapid read-outs allow for evaluation of therapeutics while cataloguing cartilage-synovium interactions. DESIGN: 48-h human explant cultures were sourced from OA knee arthroplasties. An OA-like cartilage-synovium co-culture baseline was established relative to donor-matched upper limit supraphysiological pro-inflammatory cytokine and lower limit OA cartilage or synovium alone controls. 100 nM dexamethasone treatment validated possible "rescue effects" within the OA-EXM dual tissue environment. Gene expression, proteoglycan loss, MMP activity, and soluble protein concentrations were analyzed using blocking and clustering methods. RESULTS: The OA-EXM demonstrates the value of the co-culture approach as the addition of OA synovium increases OA cartilage proteoglycan loss and expression of MMP1, MMP3, MMP13, CXCL8, CCL2, IL6, and PTGS2, but not to the extent of supraphysiological stimulation. Conversely, OA cartilage does not affect gene expression or MMP activity of OA synovium. Dexamethasone shows dual treatment effects on synovium (pro-resolving macrophage upregulation, protease downregulation) and cartilage (pro-inflammatory, catabolic, and anabolic downregulation), and decreases soluble CCL2 levels in co-culture, thereby validating OA-EXM utility. CONCLUSIONS: The OA-EXM is representative of late-stage OA pathology, captures dual interactions between cartilage and synovium, and combined with statistical strategies provides a rapid, sensitive research tool for evaluating OA therapeutics.

Biomechanical comparison of conventional double-row repair versus double row repair with the parachute configuration.

INTRODUCTION: The rotator cuff tears are a very frequent condition. The rotator cuff repair is a procedure often perform by the orthopedic surgeon. There are multiple techniques and suture configurations for this type of repairs. The double row configuration is one of the most used and consider very effective for mid-size and large size rotator cuff tears. The parachute configuration for this repair is a novel technique that may be useful for mid-size and large size tears, for this repair two medial double row anchors are used and one knotless lateral anchor. Our porpoise was to compare biomechanical performance and footprint coverage of a conventional suture-bridge double-row rotator cuff repair configuration versus a double-row-parachute. METHODS: This paper shows the biomechanical behavior on a cadaver model of the parachute configuration, and also compares this conformation with a double row in a suture-bridge fashion. Our hipothesis was that the Parachute configurations biomechanical performance is equivalent to the suture-bridging double-row technique. RESULTS: The parachute configuration advantages show the advantage of using less anchors, which will decrease the surgical time and also the risks of using multiple hardware in the humeral head.

INTRODUCCIÓN: La lesión del manguito rotador es una patología común cuya reparación es un procedimiento realizado por los cirujanos ortopedistas. Existen muchas técnicas de reparación, así como múltiples configuraciones de anclas y suturas para realizar estos procedimientos. La técnica de doble fila es una de las más usadas para rupturas de tamaño mediano y grande con buenos resultados. La configuración en «paracaídas¼ para la reparación del manguito rotador puede llegar a ser útil para éstas, en este tipo de configuración se utilizan dos anclas mediales y un ancla sin nudos lateral. Nuestro objetivo fue la comparación de la eficiencia biomecánica y cobertura de la huella de una configuración convencional de doble fila «suture bridge¼ frente a una configuración en «paracaídas¼. MÉTODOS: Este trabajo revisó el comportamiento biomecánico, en piezas cadavéricas, de la configuración de paracaídas y se comparó con la configuración de doble fila tipo «suture-bridge¼. Nuestra hipótesis era que el rendimiento biomecánico de la configuración de Parachute es equivalente a la técnica de doble fila «suture bridge¼. RESULTADOS: Las posibles ventajas de la configuración de paracaídas son el uso de menos anclas, disminuyendo el tiempo quirúrgico y los riesgos de tener múltiples implantes en la cabeza humeral.

[Recommendations for in-office bio-security, operating room and hospital visit in orthopedics during the COVID-19 pandemic]. / Recomendaciones de bioseguridad en consultorio, quirófano y pase de visita en ortopedia durante la pandemia de COVID-19.

No Abstract available.

KrCl and XeCl excilamps and LP-Hg lamp for UV and UV/H2O2 decolourization of dyes in water.

In the present study, the decolourization efficiencies of LP-Hg lamp, XeCl and KrCl excilamps at the same power density were compared for the decolourization of dyes in water by UV and UV/H2O2 processes in a batch reactor. Laboratory prototypes of XeCl and KrCl excilamps and a commercial LP-Hg lamp were studied as UV sources. Methylene Blue and Eliamine Blue dyes were used as model pollutants. The effect of the initial concentrations of dye and H2O2 in the TOC removal and kinetic parameters were also studied. The ratio of dye decolourization to the electric power consumption of the KrCl excilamp and LP-Hg lamp for the decolourization of Methylene Blue and Eliamine Blue were evaluated. As a result, the KrCl excilamp showed significantly higher decolourization efficiencies than LP-Hg lamp and XeCl excilamp, but the dye removal rate was significantly slower for Methylene Blue than for Eliamine Blue with this lamp. The KrCl lamp can be an alternative to conventional LP-Hg lamp for the decolourization of dyes by photodegradation, but it depends on the type of dye treated. The addition of H2O2 in a concentration between 0.05 and 0.09%v/v increases significantly the efficiency of the decolourization of Methylene Blue, and further increase does not lead to a higher increase in conversion. The experimental data were fitted to the one phase decay kinetic model with good agreement and the kinetic parameters were reported.

Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS: We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION: Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.

Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South American Transplant Center.

BACKGROUND: Around 2.4% of the world's population is infected with hepatitis C virus (HCV), and it is the most common cause of liver transplantation (LT) in the world. Latin America (LA), with nearly 9% of the world population, has had a continuous increase in the number of LTs per year. Yet, due to the lack of mandatory data collection and a well-developed health-care system, access to transplantation is limited in most LA countries. We report the first LA experience of HCV-infected LT patients. METHODS: We performed a retrospective cohort study by reviewing the medical histories of all HCV-infected LT patients between 1996 and 2016 who acquired HCV before their LT, at the Fundación Valle del Lilí, Cali, Colombia. RESULTS: Between January 1996 and December 2015, a total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV infection. With a median follow-up time of 24.4 months (interquartile range [IQR] 4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996-2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in 30.6% of the patients, and overall postoperative complications had an incidence of 80%. CONCLUSIONS: This is the first report of LT in HCV-infected patients in Colombia and in LA. Our results are comparable to those of other transplant centers worldwide with regard to postoperative complications and patient survival. Patients with LT in the 1996-2006 time frame had higher morbidity and mortality. Studies including larger numbers of patients are needed to determine the reason for this finding.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

OBJECTIVE: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. METHOD: Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. RESULTS: Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. CONCLUSION: Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects.

Repercusión clínica de la alfa-talasemia en nuestro medio. Impacto del screeningneonatal / Clinical consequences of alpha-thalassemia in the basque country, Spain. Impact of neonatal screening

INTRODUCCIÓN: La alfa-talasemia es la hemoglobinopatía más frecuente de expresión clínica variable en función del número de alelos mutados (1-2 alelos mutados: asintomático/anemia leve, 3-4 alelos mutados: enfermedad grave). Desde mayo de 2011 se ha añadido el estudio de hemoglobinopatías al screening neonatal en la Comunidad Autónoma del País Vasco (CAPV). OBJETIVOS: Valorar el impacto de la alfa-talasemia en nuestro medio y la utilidad del screening neonatal en su detección. MÉTODO: Revisión de pacientes con estudio genético positivo para alfa-talasemia durante 2 años (2012-2013) y estudio de la edad al diagnóstico, etnia, resultados analíticos y tratamiento. RESULTADOS: Se realizó un estudio genético de alfa-talasemia a 107 pacientes, de los cuales 61 presentaron alguna mutación. El 62% tenía un alelo mutado y el 38%, 2 alelos. La edad media al diagnóstico fue de 31 años, con un 28% menores de 18 años. La mayoría eran de procedencia europea con un porcentaje no desdeñable de africanos (26%) y árabes (13%) Todos los pacientes estudiados estaban asintomáticos con anemia leve en el 28%. Dos pacientes fueron diagnosticados por screening neonatal. La mayoría de pacientes no requirió tratamiento o precisó ferroterapia. CONCLUSIONES: La presencia de una o 2 mutaciones en los genes alfa carece de repercusión clínica, y el único interés de su estudio es que permite el consejo genético. En nuestro entorno no hemos encontrado pacientes con 3-4 mutaciones ni con sintomatología grave. A diferencia de lo que ocurre con otras enfermedades, nuestros resultados no apoyan que el screening neonatal de alfa-talasemia tenga un impacto significativo en nuestro entorno

INTRODUCTION: Alpha-thalassemia is the most common hemoglobinopathy with a variable clinical manifestation depending on the number of allele mutations (asymptomatic/mild anemia if 1-2 allele mutations, severe disease if 3-4 allele mutations). A study was conducted from May 2011 on hemoglobinopathies found in the neonatal screening in the autonomous community of the Basque Country (CAPV). OBJECTIVES: To analyze the impact of alpha-thalassemia in this area and the effectiveness of its neonatal screening. METHODS: A review was made of patients with a positive gene study for alpha-thalassemia over a 2-year period (2012-2013) and an analysis was made of the age at diagnosis, ethnic group, analytical result, and treatment. RESULTS: The genetic study was performed on 107 patients, of which 61 had some mutation, with 62% having one allele mutations and 38% with two alleles. The mean age at diagnosis was 31 years, with 28% being younger than eighteen years old. Most of the patients were European with a significant number of Africans (26%) and Arabs (13%). All patients were asymptomatic, and 28% had mild anemia. Two patients were diagnosed by neonatal screening. Most of them did not need any treatment or only required iron therapy. CONCLUSIONS: The detection of one or two alpha gene mutations has no clinical impact, but allows genetic counseling. No patient was found with 3-4 mutations or severe symptoms in our region. Contrarily to the diagnosis of other diseases, our results does not support that routine neonatal screening for alpha-thalassemia has any clinical impact in our community

[Clinical consequences of alpha-thalassemia in the Basque Country, Spain. Impact of neonatal screening]. / Repercusión clínica de la alfa-talasemia en nuestro medio. Impacto del screening neonatal.

INTRODUCTION: Alpha-thalassemia is the most common hemoglobinopathy with a variable clinical manifestation depending on the number of allele mutations (asymptomatic/mild anemia if 1-2 allele mutations, severe disease if 3-4 allele mutations). A study was conducted from May 2011 on hemoglobinopathies found in the neonatal screening in the autonomous community of the Basque Country (CAPV). OBJECTIVES: To analyze the impact of alpha-thalassemia in this area and the effectiveness of its neonatal screening. METHODS: A review was made of patients with a positive gene study for alpha-thalassemia over a 2-year period (2012-2013) and an analysis was made of the age at diagnosis, ethnic group, analytical result, and treatment. RESULTS: The genetic study was performed on 107 patients, of which 61 had some mutation, with 62% having one allele mutations and 38% with two alleles. The mean age at diagnosis was 31 years, with 28% being younger than eighteen years old. Most of the patients were European with a significant number of Africans (26%) and Arabs (13%). All patients were asymptomatic, and 28% had mild anemia. Two patients were diagnosed by neonatal screening. Most of them did not need any treatment or only required iron therapy. CONCLUSIONS: The detection of one or two alpha gene mutations has no clinical impact, but allows genetic counseling. No patient was found with 3-4 mutations or severe symptoms in our region. Contrarily to the diagnosis of other diseases, our results does not support that routine neonatal screening for alpha-thalassemia has any clinical impact in our community.

Clinical description and evolution of renal transplant pediatric patients treated with alemtuzumab.

BACKGROUND: Renal transplantation is the most effective treatment for children with end-stage renal disease. Recent work suggests that induction with alemtuzumab in the pediatric population permits the use of lower doses of maintenance immunosuppressive therapy. In addition, it has a low cost compared with other induction therapies. OBJECTIVE: To conduct a clinical description of pediatric renal transplant patients comparing induction protocols to evaluate graft and patient survival, infections complications, and lymphoproliferative diseases. MATERIALS AND METHODS: This descriptive and retrospective study, of evaluated pediatric renal transplant patients between 2006 and 2010. RESULTS: The agents for induction therapy were: alemtuzumab (61.5%), daclizumab (19.25%), and thymoglobulin (19.25%). Graft survival was better among the alemtuzumab group (87.5%) compared with the other two induction therapies (80%). The frequency of acute rejection episodes during the first year posttransplantation as well as chronic rejection was lower among the alemtuzumab group. Cytomegalovirus infection was noted in 30% of patients with greater frequency among those induced with alemtuzumab. CONCLUSION: Induction therapy with alemtuzumab was safe in a pediatric population not predisposing to a greater risk of acute or chronic rejection. Except for a greater incidence of Cytomegalovirus, there was no difference in other complications.

Induction therapies in kidney transplantation: the experience of Hospital Pablo Tobon Uribe, Medellín, Colombia 2005-2010.

BACKGROUND: Induction therapies in kidney transplantation have led to prescriptions of lower doses of maintenance immunosuppression and fewer acute rejection episodes. We sought to assess the use of an affordable monoclonal antibody in terms of the incidences of rejection episodes as well as graft and patient survivals and cytomegalovirus (CMV) and opportunistic infections among our kidney transplant recipients between August 2005 and December 2010. Data were obtained for patients who had more than 20 months' follow-up. MATERIALS AND METHODS: We retrospectively analyzed data from kidney recipients between August 2005 and December 2010, using descriptive statistics and Kaplan-Meier survival analysis. We performed a multivariate analysis with logistic regression for the dependent variables of rejection episodes and death. RESULTS: Among 425 transplant patients graft survival was 89.2% and patient survival was 94.1% after 76.2% of patients received alemtuzumab, 10.7% daclizumab, 3.6% basiliximab, 2.4% thymoglobulin, and 7%, no induction therapy. Rejection incidence in general in the first year was 10.8% and CMV incidence 10%. There was an increased risk of rejection among subjects without any us with alemtuzumab induction therapy. CONCLUSION: Induction therapies show an important reduction in kidney transplant rejection incidence during the first year, allowing low doses of maintenance immunosuppressants, thereby diminishing long-term adverse effects. Alemtuzumab seemed to be a safe alternative with similar results to those obtained with standard immunosuppression.

Nuevos agentes terapéuticos en cáncer renal avanzado / New therapeutic agents in advanced renal cancer

El carcinoma de células renales es responsable del 80 al 85 por cien de todas las neoplasias renales y su diagnóstico trae consigo la necesidad de intervención oportuna por las altas tasas de morbimortalidad relacionadas con esta patología. Es conocida la posibilidad de curación con el tratamiento quirúrgico cuando la enfermedad está organoconfinada, sin embargo, en un porcentaje no despreciable de pacientes aún con este tipo de intervención pueden desarrollar metástasis o recaídas posteriores a la cirugía. El desarrollo de nuevas estrategias terapéuticas enfocadas al manejo fisiopatológico de esta enfermedad comienza a demostrar en medianos plazos respuestas que son alentadoras y que se han constituido en la herramienta terapéutica más adecuada posterior al manejo quirúrgico citorreductor. Está por definirse el papel de las terapias blanco como alternativas neoadyuvantes.

Complicaciones relacionadas con los procedimientos realizados con intención curativa en cáncer de próstata: Incontinencia urinaria y disfunción eréctil / Complications related to procedures performed with curative intent in prostate cancer: Urinary incontinence and erectile dysfunction

El manejo del Cáncer de Próstata con intención curativa ya sea mediante prostatectomía radical retropúbica, prostatectomía radical perineal, braquiterapia de baja o de alta tasa o radioterapia tiene consecuencias para el paciente en cuanto a calidad de vida se refiere. Realizamos una revisión de la literatura para evaluar los reportes de complicaciones de cada uno de estos manejos para determinar el estado actual de los efectos secundarios de estas terapias.