ABSTRACT
BACKGROUND: TB in low-incidence countries is characterised by changes in age distribution towards larger numbers of cases among the elderly.OBJECTIVES: To investigate clinical features and outcomes of TB treatment in older patients and identify predictors of poor outcome.METHODS: Multicentre retrospective study of new TB cases from 53 hospitals included in the registry of the Integrated Tuberculosis Research Programme of the Spanish Society of Pulmonology and Thoracic Surgery (Sociedad Española de Neumología y Cirugía Torácica) between 2006 and 2020.RESULTS: We identified 731 patients aged ≥75 years from a cohort of 7,505 patients with TB. In the elderly, weight loss, disseminated disease and normal X-rays or infiltrates without cavitation were more common. All-cause mortality was 16% (5% of deaths due to TB). The elderly had higher rates of toxicity (6.7%) and hospital admissions (36%). In the multivariate analysis of predictors of TB mortality in ≥75-year-olds, only weight, age and treatment with non-standard regimens remained significant.CONCLUSIONS: TB in older patients needs more attention and remains a challenge because of a lack of specific clinical and radiological features. Standard treatment is effective, although mortality is higher than in young patients. Low weight, non-standard regimens and age are significant predictors of TB mortality.
Subject(s)
Pulmonary Medicine , Thoracic Surgery , Tuberculosis , Age Distribution , Aged , Humans , Retrospective Studies , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiologyABSTRACT
Hip fracture registries have helped improve quality of care and reduce variability, and several audits exist worldwide. The results of the Spanish National Hip Fracture Registry are presented and compared with 13 other national registries, highlighting similarities and differences to define areas of improvement, particularly surgical delay and early mobilization. INTRODUCTION: Hip fracture audits have been useful for monitoring current practice and defining areas in need of improvement. Most established registries are from Northern Europe. We present the results from the first annual report of the Spanish Hip Fracture Registry (RNFC) and compare them with other publically available audit reports. METHOD: Comparison of the results from Spain with the most recent reports from another ten established hip fracture registries highlights the differences in audit characteristics, casemix, management, and outcomes. RESULTS: Of the patients treated in 54 hospitals, 7.208 were included in the registry between January and October 2017. Compared with other registries, the RNFC included patients ≥ 75 years old; in general, they were older, more likely to be female, had a worse prefracture ambulation status, and were more likely to have extracapsular fractures. A larger proportion was treated with intramedullary nails than in other countries, and spinal anesthesia was most commonly used. With a mean of 75.7 h, Spain had by far the longest surgical delay, and the lowest proportion of patients mobilized on the first postoperative day (58.5%). Consequently, development of pressure ulcers was high, but length of stay, mortality, and discharge to home remained in the range of other audits. CONCLUSIONS: National hip fracture registries have proved effective in changing clinical practice and our understanding of patients with this condition. Such registries tend to be based on an internationally recognized common dataset which would make comparisons between national registries possible, but variations such as age inclusion criteria and follow-up are becoming evident across the world. This variation should be avoided if we are to maximize the comparability of registry results and help different countries learn from each other's practice. The results reported in the Spanish RNFC, compared with those of other countries, highlight the differences between countries and detect areas of improvement, particularly surgical delay and early mobilization.
Subject(s)
Hip Fractures/therapy , Osteoporotic Fractures/therapy , Age Factors , Aged , Aged, 80 and over , Anesthesia/methods , Databases, Factual , Early Ambulation/statistics & numerical data , Europe , Female , Fracture Fixation/methods , Fracture Fixation/standards , Hip Fractures/epidemiology , Humans , Internationality , Length of Stay/statistics & numerical data , Male , Medical Audit/methods , Middle Aged , Osteoporotic Fractures/epidemiology , Quality of Health Care , Registries , Spain/epidemiology , Time-to-TreatmentABSTRACT
Resumen: Introducción: La fractura de cadera (FC) se considera la consecuencia más grave de las caídas y la osteoporosis. Dieciocho por ciento de las mujeres sufrirán una FC y 25% muere en el primer año. Sólo 73% de los supervivientes caminará como lo hacía previamente. Conocemos poco de la asistencia y evolución de la FC en México. Objetivo: Revisar el estado actual de la literatura mexicana sobre FC, comparar estudios mexicanos entre sí y con los indicadores de calidad. Metodología: Se realizó una búsqueda de artículos mexicanos publicados entre 2000 y 2017 con las palabras clave: fractura de cadera, ancianos, México y hip fracture en las bases de datos PubMed, EBSCO y Bibliomed. Resultados: Se incluyeron 22 artículos. No se encontraron ensayos clínicos, informes de unidades multidisciplinarias, registros, ni metaanálisis. La media de edad fue de 76.9 años y 67.2% fueron mujeres. No se encontraron trabajos que reportaran indicadores de calidad. La comorbilidad se describe poco. Las complicaciones más frecuentes de la FC fueron delirium, neumonía y úlceras por presión. La mortalidad en la fase aguda fue de 0.97 a 12.5%. No se reportaron unidades ortogeriátricas. El costo de atención osciló entre 1,261 y 13,641 dólares estadounidenses (USD). Conclusiones: La información científica sobre FC en México es escasa, heterogénea y no permite obtener resultados concluyentes. Se requiere aumentar la cantidad y la calidad de la investigación en FC en México. Sería también conveniente difundir la utilidad de los equipos multidisciplinarios y registros de FC, lo que contribuiría a mejorar la atención.
Abstract: Introduction: Hip fracture is considered the most serious consequence of falls and osteoporosis. 18% of women will suffer one and 25% die in the first year. Only 73% of survivors will walk as they did previously. We know little about the assistance and evolution of it in Mexico. Our goal was to review the current state of Mexican literature on hip fracture, compare Mexican studies with each other and with quality indicators. Methods: We conducted a search of Mexican articles published between 2000-2017 with the key words: hip fracture, elderly, Mexico and hip fracture (in English) in the databases PubMed, EBSCO and Bibliomed. Results: Twenty-one articles were included. No clinical trials, multidisciplinary unit reports, records, or meta-analyses were found. The average age was 76.9 years and 67.2% were women. No papers were found to report quality indicators. Comorbidity is reported little. The most common complications of hip fractures were delirium, pneumonia and pressure ulcers. Mortality in the acute phase was 0.97 to 12.5%. Special units were not reported. The cost of care oscillated between 1,261 and 13,641 USD. Conclusions: The scientific information on hip fractures in Mexico is sparse, heterogeneous and does not allow for conclusive results. Increasing the amount and quality of research in hip fractures in Mexico is required. It would also be advisable to disseminate the usefulness of multidisciplinary teams and registry of hip fractures, which would help to improve attention.
Subject(s)
Humans , Female , Aged , Hip Fractures/therapy , Quality Indicators, Health Care , MexicoABSTRACT
Objective: To ascertain the current situation and clinical variability of the provision of care for Hip Fracture (HF) in Spain and the factors related to it by using a National Registry (NHFR) with high patient numbers and territorial representation NHFR, and to compare results on a national and international level and propose standards and criteria to improve healthcare quality. Design: Continuous registry for at least three years of a representative sample of patients admitted to Spanish hospitals due to HF using the Minimum Common Dataset - international Fragility Fracture Network (FFN) MCD, adapted for Spanish. Study scope and subjects: all patients over the age of 74 years who are hospitalized with a diagnosis of a fragility HF at the participating hospitals distributed throughout the Spanish territory. Initially 48 hospitals are included, and we expect to incorporate the highest number of sites possible. Results: It is expected to ascertain the current situation of provision of care for HF in Spain. Each hospital will be offered information regarding their results and their situation compared to the rest. The results from national hospitals will be compared to others included in the registry and to hospitals abroad, which use the same database. Variability will be studied, care standards will be established, and objectives will be proposed for the continuous improvement of the care process of this condition
Objetivo: Conocer la situación actual y la variabilidad clínica del proceso asistencial a la Fractura de Cadera (FC) en España y los factores relacionados con la misma mediante la utilización de un Registro Nacional (RNFC) con elevada casuística y representación territorial RNFC, así como comparar resultados en el ámbito nacional e internacional y proponer estándares y criterios para mejorar la calidad asistencial. Diseño: Registro continuo durante al menos tres años de una muestra representativa de los pacientes ingresados por FC en los hospitales españoles mediante el Minimum Common Dataset - MCD internacional de la Fragility Fracture Network (FFN) adaptado al castellano. Ámbito y sujetos del estudio: se incluirán todos los pacientes mayores de 74 años hospitalizados con el diagnóstico de FC por fragilidad en los hospitales participantes repartidos por el territorio español. Inicialmente están incluidos 48 hospitales, a los que se espera que se vayan incorporando el mayor número posible de centros. Resultados: Se pretende conocer la situación actual de la atención a este proceso en España Se ofrecerá a cada hospital la información de sus resultados y su situación en relación al resto, se compararán los resultados de los hospitales nacionales entre sí y con los hospitales extranjeros incluidos en registros que usan la misma base de datos. Se estudiará la variabilidad, se establecerán estándares asistenciales y se plantearán objetivos para la mejora continua del proceso en la atención a esta patología
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Hip Fractures/epidemiology , Osteoporotic Fractures/epidemiology , Diseases Registries/statistics & numerical data , Risk Factors , Frail Elderly/statistics & numerical data , Hospitalization/statistics & numerical data , Spain/epidemiologyABSTRACT
Introducción: Hay una proporción de pacientes con fractura de cadera que tienen una fractura de miembro superior concomitante. Queremos conocer si estos pacientes muestran un peor nivel funcional y si presentan diferencias en distintos parámetros clínicos con respecto a los que tienen una fractura aislada de cadera. Material y métodos: Se han revisado retrospectivamente 1.061 informes de alta de la Unidad de Ortogeriatría del H. U. La Paz de Madrid. Se recopiló información sobre distintos parámetros clínicos de las fracturas presentadas. Posteriormente se comparó el grupo de fractura asociada con el de fractura aislada mediante un análisis estadístico. Resultados: Se detectaron 44 pacientes con una fractura de miembro superior asociada, el 90,9% fueron mujeres (40) y la media de edad fue de 84,45años. El 81,8% de las fracturas de miembro superior fueron de radio distal o de húmero proximal. La demora quirúrgica fue de 2,60días y la estancia media hospitalaria, de 12,30días. El 64,3% fueron intervenciones con clavo-tornillo y el 31%, artroplastias. La media del índice de Barthel fue de 84,88 (p=0,021). El 52,5% de los pacientes del grupo a estudio fueron derivados a un centro de apoyo funcional (p=0,03). La mortalidad global intrahospitalaria fue del 4,2%, sin diferencias entre los grupos. Conclusiones: Los pacientes que presentan una fractura asociada tienen mayor capacidad funcional previa y son más independientes. Tras la fractura necesitan una mayor ayuda por parte del sistema sanitario para su óptima recuperación funcional
Introduction: Some patients with a hip fracture also present a concomitant upper limb fracture. We want to know whether these patients have a worse functional level and whether they have any differences in various clinical parameters compared with patients with an isolated hip fracture. Material and methods: We retrospectively reviewed 1061 discharge reports from the Orthogeriatrics Unit. We collected information on several clinical parameters of the fractures. Subsequently, we performed a statistical analysis of the data by comparing the associated fracture group with the isolated fracture group. Results: We detected 44 patients with associated upper limb fracture, 90.9% were women (40) and the average age was 84.45years. Eighty-one point eight percent of the upper limb fractures were distal radius or proximal humerus. Pertrochanteric fractures were the most common (none of them were subtrochanteric fractures). Surgical delay was 2.60days and the average hospital stay was 12.30days. Sixty-four point three percent were nail surgery and 31% arthroplasty. The mean Barthel index score was 84.88 (P=.021). Fifty-two point 5 percent of the patients in the study group were referred to a functional support unit (P=.03). The in-hospital mortality rate was 4.2%, with no differences between groups. Conclusions: Patients with an associated fracture have a higher previous functional capacity and they are more independent. Nevertheless, after the fracture they need more help from the healthcare system for optimal functional recovery
Subject(s)
Humans , Male , Female , Aged, 80 and over , Hip Fractures/rehabilitation , Upper Extremity/injuries , Trauma Severity Indices , Comorbidity , Fractures, Multiple/complications , Treatment Outcome , Recovery of Function , Retrospective StudiesABSTRACT
BK virus (BKV) infection occurs during childhood and remains latent in the urinary tract. The virus is reactivated in immunosuppressed patients, particularly in those with cellular immunity deficiency, allowing its detection in urine and blood. Nephropathy caused by the virus in renal transplantation recipients may lead to graft failure. The purpose of this study is to know the prevalence of BKV variables in renal transplantation recipients and to evaluate their clinical evolution through molecular methods of "in house" development. Urine and peripheral blood samples from 66 renal transplantation recipients from the province of Buenos Aires, Argentina, were systematically analyzed every 3 months as well as when there was graft dysfunction. Renal biopsies, which were included in the BKV detection study, were performed on those patients with graft dysfunction. Genotyping of 24 BKVs was performed, and the following distribution was found: 21 (87.5%) belonged to subtype I, 3 (12.5%) to subtype II. BKV belonging to subtypes III or IV were not found. As regards subtype I subgroups, the following were identified: 1 (4.76%) from Ia, 10 (47.61%) from Ib1 and 10 (47.61%) from Ib2. Presence of subgroup Ic was not shown. Viremia presented in 33.33% of cases, whereas 75% corresponded to subgroup Ib 1. Genotype Ib1 is prevailing in Southeast Asia, while Ib2 is prominent in Europe. Although an important proportion of the inhabitants of the province of Buenos Aires are European descendants, the prevailing genotype is Ib1, the Asian type. Genotyping might be related to the evolution of the disease in the recipient.
Subject(s)
Kidney Transplantation/adverse effects , Polyomavirus Infections/epidemiology , Polyomavirus Infections/virology , Tumor Virus Infections/epidemiology , Tumor Virus Infections/virology , Adult , Argentina , BK Virus/physiology , Europe , Female , Genotype , Humans , Immunocompromised Host/immunology , Male , Polyomavirus Infections/immunology , Prevalence , Transplant Recipients , Tumor Virus Infections/immunology , Virus Activation/immunologyABSTRACT
OBJECTIVE: To ascertain the current situation and clinical variability of the provision of care for Hip Fracture (HF) in Spain and the factors related to it by using a National Registry (NHFR) with high patient numbers and territorial representation NHFR, and to compare results on a national and international level and propose standards and criteria to improve healthcare quality. DESIGN: Continuous registry for at least three years of a representative sample of patients admitted to Spanish hospitals due to HF using the Minimum Common Dataset - international Fragility Fracture Network (FFN) MCD, adapted for Spanish. STUDY SCOPE AND SUBJECTS: all patients over the age of 74 years who are hospitalized with a diagnosis of a fragility HF at the participating hospitals distributed throughout the Spanish territory. Initially 48 hospitals are included, and we expect to incorporate the highest number of sites possible. RESULTS: It is expected to ascertain the current situation of provision of care for HF in Spain. Each hospital will be offered information regarding their results and their situation compared to the rest. The results from national hospitals will be compared to others included in the registry and to hospitals abroad, which use the same database. Variability will be studied, care standards will be established, and objectives will be proposed for the continuous improvement of the care process of this condition.
Subject(s)
Hip Fractures/therapy , Registries , Aged , Hip Fractures/epidemiology , Humans , Spain/epidemiologyABSTRACT
INTRODUCTION: Hip fracture is considered the most serious consequence of falls and osteoporosis. 18% of women will suffer one and 25% die in the first year. Only 73% of survivors will walk as they did previously. We know little about the assistance and evolution of it in Mexico. Our goal was to review the current state of Mexican literature on hip fracture, compare Mexican studies with each other and with quality indicators. METHODS: We conducted a search of Mexican articles published between 2000-2017 with the key words: hip fracture, elderly, Mexico and hip fracture (in English) in the databases PubMed, EBSCO and Bibliomed. RESULTS: Twenty-one articles were included. No clinical trials, multidisciplinary unit reports, records, or meta-analyses were found. The average age was 76.9 years and 67.2% were women. No papers were found to report quality indicators. Comorbidity is reported little. The most common complications of hip fractures were delirium, pneumonia and pressure ulcers. Mortality in the acute phase was 0.97 to 12.5%. Special units were not reported. The cost of care oscillated between 1,261 and 13,641 USD. CONCLUSIONS: The scientific information on hip fractures in Mexico is sparse, heterogeneous and does not allow for conclusive results. Increasing the amount and quality of research in hip fractures in Mexico is required. It would also be advisable to disseminate the usefulness of multidisciplinary teams and registry of hip fractures, which would help to improve attention.
INTRODUCCIÓN: La fractura de cadera (FC) se considera la consecuencia más grave de las caídas y la osteoporosis. Dieciocho por ciento de las mujeres sufrirán una FC y 25% muere en el primer año. Sólo 73% de los supervivientes caminará como lo hacía previamente. Conocemos poco de la asistencia y evolución de la FC en México. OBJETIVO: Revisar el estado actual de la literatura mexicana sobre FC, comparar estudios mexicanos entre sí y con los indicadores de calidad. METODOLOGÍA: Se realizó una búsqueda de artículos mexicanos publicados entre 2000 y 2017 con las palabras clave: fractura de cadera, ancianos, México y hip fracture en las bases de datos PubMed, EBSCO y Bibliomed. RESULTADOS: Se incluyeron 22 artículos. No se encontraron ensayos clínicos, informes de unidades multidisciplinarias, registros, ni metaanálisis. La media de edad fue de 76.9 años y 67.2% fueron mujeres. No se encontraron trabajos que reportaran indicadores de calidad. La comorbilidad se describe poco. Las complicaciones más frecuentes de la FC fueron delirium, neumonía y úlceras por presión. La mortalidad en la fase aguda fue de 0.97 a 12.5%. No se reportaron unidades ortogeriátricas. El costo de atención osciló entre 1,261 y 13,641 dólares estadounidenses (USD). CONCLUSIONES: La información científica sobre FC en México es escasa, heterogénea y no permite obtener resultados concluyentes. Se requiere aumentar la cantidad y la calidad de la investigación en FC en México. Sería también conveniente difundir la utilidad de los equipos multidisciplinarios y registros de FC, lo que contribuiría a mejorar la atención.
Subject(s)
Hip Fractures , Aged , Female , Hip Fractures/therapy , Humans , Mexico , Quality Indicators, Health CareABSTRACT
INTRODUCTION: Some patients with a hip fracture also present a concomitant upper limb fracture. We want to know whether these patients have a worse functional level and whether they have any differences in various clinical parameters compared with patients with an isolated hip fracture. MATERIAL AND METHODS: We retrospectively reviewed 1061 discharge reports from the Orthogeriatrics Unit. We collected information on several clinical parameters of the fractures. Subsequently, we performed a statistical analysis of the data by comparing the associated fracture group with the isolated fracture group. RESULTS: We detected 44 patients with associated upper limb fracture, 90.9% were women (40) and the average age was 84.45years. Eighty-one point eight percent of the upper limb fractures were distal radius or proximal humerus. Pertrochanteric fractures were the most common (none of them were subtrochanteric fractures). Surgical delay was 2.60days and the average hospital stay was 12.30days. Sixty-four point three percent were nail surgery and 31% arthroplasty. The mean Barthel index score was 84.88 (P=.021). Fifty-two point 5 percent of the patients in the study group were referred to a functional support unit (P=.03). The in-hospital mortality rate was 4.2%, with no differences between groups. CONCLUSIONS: Patients with an associated fracture have a higher previous functional capacity and they are more independent. Nevertheless, after the fracture they need more help from the healthcare system for optimal functional recovery.
Subject(s)
Hip Fractures/diagnosis , Humerus/injuries , Radius Fractures/diagnosis , Aged , Aged, 80 and over , Female , Fracture Fixation , Frail Elderly , Frailty/complications , Frailty/diagnosis , Health Status , Hip Fractures/complications , Hip Fractures/mortality , Hip Fractures/surgery , Humans , Humerus/surgery , Male , Prognosis , Radius Fractures/complications , Radius Fractures/mortality , Radius Fractures/surgery , Recovery of Function , Retrospective StudiesABSTRACT
Objetivo. Desarrollar recomendaciones sobre el proceso de evaluación y manejo del paciente con artrosis de rodilla e indicación de artroplastia basadas en la mejor evidencia científica disponible y la experiencia de un panel de expertos. Métodos. Se seleccionó un grupo multidisciplinar de 12 expertos que definieron: alcance, usuarios, apartados del documento, revisiones sistemáticas a realizar y a quienes se asignaron tareas. Se realizaron 3 revisiones sistemáticas en pacientes con indicación de artroplastia de rodilla sobre: 1) eficacia y seguridad de los protocolos de fast-track; 2) papel de las intervenciones cognitivo-conductuales en sujetos con catastrofismo, y 3) efecto del control del dolor agudo posquirúrgico en los resultados. Se realizaron 2 revisiones narrativas sobre la sensibilización central en este grupo y sobre la eficacia de la rehabilitación preoperatoria. Los expertos redactaron los apartados y generaron las recomendaciones. Estas recomendaciones se consensuaron mediante la metodología Delphi en un grupo multidisciplinar de 85 expertos. Se estableció también el nivel de evidencia de cada recomendación. Resultados. Se generaron 20 recomendaciones. Todas alcanzaron un nivel de acuerdo mayor del 80%. El mayor acuerdo se alcanzó en la necesidad de realizar informe de alta completo, en informar adecuadamente al paciente sobre el proceso y en seguir las recomendaciones de las guías clínicas disponibles. Conclusiones. Existe consenso entre los responsables del manejo de los pacientes con artrosis de rodilla e indicación de artroplastia en que es necesario protocolizar el proceso de sustitución articular, realizando una correcta evaluación y seguimiento del paciente, de forma integral y coordinada y con especial atención al procedimiento quirúrgico y al postoperatorio (AU)
Objective. To develop recommendations on the evaluation and management procedure in patients undergoing total knee replacement based on best evidence and the experience of a panel of experts. Methods. A multidisciplinary group of 12 experts was selected that defined the scope, users and the document parts. Three systematic reviews were performed in patients undergoing knee replacement: (I) efficacy and safety of fast-tracks; (II) efficacy and safety of cognitive interventions in patients with catastrophic pain, and (III) efficacy and safety of acute post-surgical pain management on post-surgical outcomes. A narrative review was conducted on the evaluation and management of pain sensitization, and about the efficacy and safety of pre-surgical physiotherapy. The experts generated the recommendations and explicative text. The level of agreement was evaluated in a multidisciplinary group of 85 experts with the Delphi technique. The level of evidence was established as well for each recommendation. Results. A total of 20 recommendations were produced. An agreement higher than 80% was reached in all of them. We found the highest agreement on the need for a full discharge report, on providing proper information about the process and on following available guidelines. Conclusions. There is consensus among professionals involved in the management of patients undergoing total knee replacement, in that it is important to protocolize the replacement process, performing a proper, integrated and coordinated patient evaluation and follow-up, paying special attention to the surgical procedure and postoperative period (AU)
Subject(s)
Humans , Consensus Development Conferences as Topic , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/surgery , Arthroplasty/methods , Pain Management/methods , Evidence-Based Medicine/methods , Delphi Technique , Surveys and Questionnaires , Psychopathology/methodsABSTRACT
OBJECTIVE: To develop recommendations on the evaluation and management procedure in patients undergoing total knee replacement based on best evidence and the experience of a panel of experts. METHODS: A multidisciplinary group of 12 experts was selected that defined the scope, users and the document parts. Three systematic reviews were performed in patients undergoing knee replacement: (i)efficacy and safety of fast-tracks; (ii)efficacy and safety of cognitive interventions in patients with catastrophic pain, and (iii) efficacy and safety of acute post-surgical pain management on post-surgical outcomes. A narrative review was conducted on the evaluation and management of pain sensitization, and about the efficacy and safety of pre-surgical physiotherapy. The experts generated the recommendations and explicative text. The level of agreement was evaluated in a multidisciplinary group of 85 experts with the Delphi technique. The level of evidence was established as well for each recommendation. RESULTS: A total of 20 recommendations were produced. An agreement higher than 80% was reached in all of them. We found the highest agreement on the need for a full discharge report, on providing proper information about the process and on following available guidelines. CONCLUSIONS: There is consensus among professionals involved in the management of patients undergoing total knee replacement, in that it is important to protocolize the replacement process, performing a proper, integrated and coordinated patient evaluation and follow-up, paying special attention to the surgical procedure and postoperative period.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee/surgery , Perioperative Care/methods , Delphi Technique , Humans , Osteoarthritis, Knee/rehabilitation , Physical Therapy Modalities , Postoperative Complications/therapyABSTRACT
Disorders in cell signaling mediated by ATP or histamine, activating specific membrane receptors, have been frequently associated with tumorigenesis. Among the elements of response to purinergic (and histaminergic) signaling, ion channel activation controls essential cellular processes in cancer, such as cell proliferation, motility, and death. Here, we studied the effects that ATP had on electrical properties of human ovarian adenocarcinoma cells named SKOV-3. ATP caused increase in intracellular Ca2+ concentration ([Ca2+]i) and, concurrently, it evoked a complex electrical response with a conspicuous outward component. This current was generated through P2Y2 receptor activation and opening of K+ channels, KCa3.1, as indicated by electrophysiological and pharmacological analysis, as well as by immunodetection and specific silencing of P2Y2 or KCa3.1 gene by esiRNA transfection. Low µM ATP concentration increased SKOV-3 cell migration, which was strongly inhibited by KCa3.1 channel blockers and by esiRNA-generated P2Y2 or KCa3.1 downregulation. Finally, in human ovarian tumors, the P2Y2 and KCa3.1 proteins are expressed and co-localized in neoplastic cells. Thus, stimulation of P2Y2 receptors expressed in SKOV-3 cells promotes motility through KCa3.1 activation. Since P2Y2 and KCa3.1 are co-expressed in primary tumors, our findings suggest that they may play a role in cancer progression.
Subject(s)
Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism , Ion Channel Gating , Receptors, Purinergic P2Y2/metabolism , Adenosine Triphosphate/metabolism , Calcium/metabolism , Calcium Signaling/drug effects , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Dose-Response Relationship, Drug , Female , Gene Expression , Gene Silencing , Humans , Intermediate-Conductance Calcium-Activated Potassium Channels/agonists , Intermediate-Conductance Calcium-Activated Potassium Channels/genetics , Ions/metabolism , Membrane Potentials , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Potassium Channel Blockers/pharmacology , RNA, Small Interfering/geneticsABSTRACT
OBJECTIVES: The aim of the study was to study the factors associated with immunological recovery in HIV-infected patients with suppressed viral load. METHODS: Nadir and current CD4 cell counts were recorded in 821 patients, as well as many demographic, epidemiological, lifestyle, clinical, therapeutic, genetic, laboratory, liver fibrosis and viral hepatitis parameters. RESULTS: The median age of the patients was 44.4 years [interquartile range (IQR) 40.3-48.0 years], the median time since HIV diagnosis was 15.3 years (IQR 10.5-18.9 years), the median time of suppressed viral load was 7.0 years (IQR 4.0-10.0 years) and the median time on the current antiretroviral regimen was 2.8 years (IQR 1.4-4.7 years). The median nadir and current CD4 counts were 193.0 (IQR 84.0-301.0) and 522.0 (IQR 361.0-760) cells/µL, respectively, separated by a median period of 10.2 years (IQR 5.9-12.9 years). The median CD4 count gain during follow-up was 317.0 (IQR 173.0-508.0) cells/µL. Many variables were associated with CD4 cell gains in univariate analyses, including age, gender, epidemiology, prior clinical conditions, fibrosis stage, transient elastometry, aspartate aminotransferase (AST), nadir CD4 count and hepatitis B and C virus infections and genotypes, as well as the durations of follow-up since nadir CD4 count, overall antiretroviral treatment, current antiretroviral regimen, protease inhibitor therapy and suppression of viral load. Multivariate analysis revealed that longer duration of HIV suppression (P < 0.0001), more advanced clinical Centers for Disease Control and Prevention (CDC) stages (P < 0.0001), younger age (P = 0.0003), hepatitis C virus genotypes 1 and 4 (P = 0.003), sexual acquisition of HIV (P = 0.004), and lower transient elastometry values (P = 0.03) were independent predictors of CD4 cell gains. Overall, the model accounted for 14.2% of the variability in CD4 count. CONCLUSIONS: In addition to the duration of HIV suppression, HIV-related diseases, HIV epidemiology, age, hepatitis C virus genotypes, and liver fibrosis were independently associated with long-term immunological recovery.
Subject(s)
Anti-Retroviral Agents/therapeutic use , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , Adult , CD4 Lymphocyte Count , Cohort Studies , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Extracellular nucleotides are signaling elements present in the tumor microenvironment; however, their role in tumor growth is not completely understood. In the present study, we asked whether nucleotides regulate cell migration in ovarian carcinoma-derived cells. We observed that 100 µM UTP induced migration in SKOV-3 cells (1.57 ± 0.08 fold over basal), and RT-PCR showed expression of transcripts for the P2RY2 and P2RY4 receptors. Knockdown of P2RY2 expression in SKOV-3 cells (P2RY2-KD) abolished the UTP-induced migration. The mechanism activated by UTP to induce migration involves transactivation of the epidermal growth factor receptor (EGFR) since we observed that the EGFR kinase inhibitor AG1478 and the PI3K inhibitor Wortmannin inhibit this response (to 0.76 ± 0.23 and 0.46 ± 0.14 relative to the control, respectively). In agreement with these observations, UTP was able to modify the phosphorylation state of the EGFR; likewise, the induction of ERK1/2 phosphorylation promoted by UTP was abolished by a 30-60 min treatment with AG1478. Our data also suggested that the enhanced cell migration involves the epithelium to mesenchymal transition (EMT) process, since a 12 h stimulation of SKOV-3 cells with 100 µM UTP showed an increase in vimentin and SNAIL protein levels (459.8 ± 132.4% over basal for SNAIL). Interestingly, treatment with apyrase (10 U/mL) reduces the migration of control cells and induces a considerable enrichment of E-cadherin in the cell-cell contacts, favoring an epithelial phenotype and strongly suggesting that the nucleotides released by tumor cells and acting through the P2RY2 receptor are potential regulators of invasiveness.
Subject(s)
Epithelial Cells/drug effects , Epithelial-Mesenchymal Transition/drug effects , ErbB Receptors/genetics , Gene Expression Regulation, Neoplastic , Receptor Cross-Talk/drug effects , Receptors, Purinergic P2Y2/genetics , Uridine Triphosphate/pharmacology , Androstadienes/pharmacology , Cadherins/genetics , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , ErbB Receptors/metabolism , Female , Humans , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Ovary/drug effects , Ovary/metabolism , Ovary/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Quinazolines/pharmacology , Receptors, Purinergic P2Y2/metabolism , Signal Transduction , Snail Family Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Tyrphostins/pharmacology , Uridine Triphosphate/metabolism , Vimentin/genetics , Vimentin/metabolism , WortmanninABSTRACT
No disponible
Subject(s)
Female , Humans , Male , Osteoporosis/epidemiology , Osteoporosis/prevention & control , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Risk Factors , Densitometry/instrumentation , Densitometry/methods , Vitamin D/therapeutic use , Osteoporosis/diagnosis , Osteoporosis/therapy , Diagnosis, Differential , Osteoporotic Fractures , Orthopedics/methods , Glucocorticoids/therapeutic use , AlgorithmsSubject(s)
Osteoporosis , Osteoporotic Fractures , Absorptiometry, Photon , Algorithms , Bone Density Conservation Agents/therapeutic use , Clinical Decision-Making , Combined Modality Therapy , Decision Support Techniques , Female , Fracture Fixation/methods , Health Status Indicators , Hip Fractures/diagnosis , Hip Fractures/etiology , Hip Fractures/therapy , Humans , Male , Osteoporosis/complications , Osteoporosis/diagnosis , Osteoporosis/therapy , Osteoporotic Fractures/diagnosis , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Osteoporotic Fractures/therapy , Risk Assessment , Risk Factors , Spain/epidemiology , Spinal Fractures/diagnosis , Spinal Fractures/etiology , Spinal Fractures/therapy , Tomography, X-Ray Computed , Vitamin D/therapeutic use , Vitamins/therapeutic useABSTRACT
Matrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P = 0.0001), MMP-3(-1612 5A/6A) SNP (P = 0.001), higher levels of TIMP-4 (P = 0.004) and MMP-8 (P = 0.006) and lower levels of MMP-1 (P = 0.03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.
Subject(s)
Matrix Metalloproteinases/blood , Matrix Metalloproteinases/genetics , Polymorphism, Single Nucleotide , Tissue Inhibitor of Metalloproteinases/blood , Adult , Aged , Alleles , Anti-Retroviral Agents/therapeutic use , Coinfection/blood , Coinfection/drug therapy , Coinfection/genetics , Female , Gene Frequency , Genotype , HIV Infections/blood , HIV Infections/genetics , HIV Infections/virology , HIV-1/drug effects , HIV-1/physiology , Hepacivirus/drug effects , Hepacivirus/physiology , Hepatitis C/blood , Hepatitis C/genetics , Hepatitis C/virology , Humans , Male , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/genetics , Middle Aged , Multivariate Analysis , Sepsis/blood , Sepsis/genetics , Sex FactorsABSTRACT
Objetivo: Desarrollar recomendaciones basadas en la mejor evidencia y experiencia sobre el manejo del dolor en pacientes con artrosis de rodilla o cadera e indicación de artroplastia. Métodos: Las recomendaciones se emitieron siguiendo la metodología de grupos nominales. Se seleccionó un grupo director de expertos (5 traumatólogos y un anestesiólogo) que definieron el alcance, usuarios, apartados del documento, posibles recomendaciones, revisiones sistemáticas y se asignaron tareas. Se realizaron 3 revisiones sistemáticas sobre: la eficacia y seguridad de la analgesia prequirúrgica en relación al dolor posquirúrgico; la eficacia y seguridad de la analgesia preventiva, y sobre los factores prequirúrgicos que influyen en el dolor posquirúrgico. Los expertos redactaron los apartados y generaron las recomendaciones correspondientes. El nivel de evidencia y grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo por técnica Delphi (2 rondas). El Delphi se amplió a 39 traumatólogos y anestesiólogos. El documento completo circuló entre el grupo director para su última revisión. Resultados: Se generaron 21 recomendaciones. Incluye el manejo farmacológico específico, la evaluación y monitorización de estos pacientes que están en tratamiento, y el tratamiento preventivo del dolor posquirúrgico. Existió consenso mayor del 70% en 19 de ellas. Conclusiones: En el paciente pendiente de artroplastia de cadera o rodilla se debe hacer una correcta evaluación, seguimiento y manejo farmacológico y no farmacológico de los factores que predicen un mal resultado de la intervención, en particular del dolor prequirúrgico. Estas actuaciones pueden mejorar el dolor posquirúrgico y el resultado de la artroplastia (AU)
Objective: To develop recommendations, based on best evidence and experience, on pain management in patients undertaking total knee or hip replacement. Methods: Nominal group methodology was followed. A group of experts was selected (5 orthopedics, 1 anesthesiologist), who defined the scope, users, topics, preliminary recommendations, and 3 systematic reviews: efficacy and safety of pre-surgical analgesia regarding to post-surgical pain, efficacy and safety of pre-emptive analgesia and pre-operative factors of post-operative pain. The level of evidence and grade of recommendation was established using the Oxford Centre for Evidence Based Medicine, and the level of agreement with the Delphi technique (2 rounds). The Delphi was extended to 39 orthopedics and anesthesiologists. The whole document was reviewed by all the experts. Results: A total of 21 recommendations were produced. They include specific pharmacological treatment, as well as the evaluation and monitoring of patients on this treatment, and post-operative pre-emptive treatment. Agreement above 70% was reached in 19 recommendations. Conclusions: In patients undergoing total knee or hip replacement, a proper evaluation, follow-up, pharmacological and non-pharmacological treatment of predictors of poor surgical outcomes should be performed, especially those related to pre-operative pain. This can improve post-operative pain and surgery outcomes (AU)
Subject(s)
Humans , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/surgery , Pain Management/methods , Analgesics/administration & dosage , Preoperative Period , Arthroplasty , Practice Patterns, Physicians' , Analgesia/methodsABSTRACT
Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.
Subject(s)
Anti-Retroviral Agents/administration & dosage , Anti-Retroviral Agents/adverse effects , Cytokines/blood , HIV Infections/complications , HIV Infections/drug therapy , HIV-Associated Lipodystrophy Syndrome/pathology , Lectins/blood , Retinol-Binding Proteins, Plasma/analysis , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Cytokines/genetics , Enzyme-Linked Immunosorbent Assay , Female , GPI-Linked Proteins/blood , GPI-Linked Proteins/genetics , Genotype , Humans , Lectins/genetics , Male , Middle Aged , Plasma/chemistry , Polymorphism, Genetic , Retinol-Binding Proteins, Plasma/genetics , Young AdultABSTRACT
OBJECTIVE: To develop recommendations, based on best evidence and experience, on pain management in patients undertaking total knee or hip replacement. METHODS: Nominal group methodology was followed. A group of experts was selected (5 orthopedics, 1 anesthesiologist), who defined the scope, users, topics, preliminary recommendations, and 3 systematic reviews: efficacy and safety of pre-surgical analgesia regarding to post-surgical pain, efficacy and safety of pre-emptive analgesia and pre-operative factors of post-operative pain. The level of evidence and grade of recommendation was established using the Oxford Centre for Evidence Based Medicine, and the level of agreement with the Delphi technique (2 rounds). The Delphi was extended to 39 orthopedics and anesthesiologists. The whole document was reviewed by all the experts. RESULTS: A total of 21 recommendations were produced. They include specific pharmacological treatment, as well as the evaluation and monitoring of patients on this treatment, and post-operative pre-emptive treatment. Agreement above 70% was reached in 19 recommendations. CONCLUSIONS: In patients undergoing total knee or hip replacement, a proper evaluation, follow-up, pharmacological and non-pharmacological treatment of predictors of poor surgical outcomes should be performed, especially those related to pre-operative pain. This can improve post-operative pain and surgery outcomes.