RESUMEN

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

Asunto(s)

Factor 15 de Diferenciación de Crecimiento , Hiperemesis Gravídica , Náusea , Vómitos , Animales , Femenino , Humanos , Ratones , Embarazo , Talasemia beta/sangre , Talasemia beta/metabolismo , Feto/metabolismo , Factor 15 de Diferenciación de Crecimiento/sangre , Factor 15 de Diferenciación de Crecimiento/metabolismo , Hormonas/sangre , Hormonas/metabolismo , Hiperemesis Gravídica/complicaciones , Hiperemesis Gravídica/metabolismo , Hiperemesis Gravídica/prevención & control , Hiperemesis Gravídica/terapia , Náusea/sangre , Náusea/complicaciones , Náusea/metabolismo , Placenta/metabolismo , Vómitos/sangre , Vómitos/complicaciones , Vómitos/metabolismo

RESUMEN

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

RESUMEN

Anti-Ro/SSA-antibody-mediated endocardial fibroelastosis (EFE) without atrioventricular (AV) block at presentation is a rare cardiac phenotype. We report on 11 fetuses with this rare type of anti-Ro/SSA-antibody-mediated cardiac involvement, presenting with a distinctive echocardiographic pattern of EFE. Eleven fetuses with isolated EFE at presentation were included from four cardiac centers, and experienced fetal cardiologists reached a consensus regarding EFE location on echocardiography at presentation. Interval changes to subsequent fetal and postnatal echocardiograms were assessed to evaluate response to therapy. Echocardiographic markers of cardiac performance, including diastolic function and AV conduction, were reviewed. Ten fetuses were found to have EFE of the aortic root, proximal aorta and/or left ventricular outflow tract. In the same 10 cases, EFE of the pulmonary root, pulmonary artery and/or right ventricular outflow tract was identified. Six cases had atrial EFE and six had EFE of the crux. Four cases were known to be positive for anti-Ro/SSA antibodies prior to diagnosis, whereas, in the remaining seven, echocardiographic findings prompted testing, which was positive in all cases. The AV interval at presentation was normal in all cases, but one fetus subsequently developed AV block. Nine patients were treated with transplacental dexamethasone, five of which also received intravenous immunoglobulin (IVIG), and one received IVIG only. Of the 10 treated cases, six had improvement in EFE as shown by serial imaging and, in four cases, the severity was unchanged. All patients were liveborn. In our cohort, EFE of the aortic and pulmonary arteries and outflow tracts was nearly universal, and involvement of the atria and the crux of the heart was also common. The high survival rate and low burden of AV block are also suggestive of a distinct phenotype of anti-Ro/SSA-antibody-mediated cardiac disease with a favorable prognosis. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Asunto(s)

Bloqueo Atrioventricular , Fibroelastosis Endocárdica , Embarazo , Femenino , Humanos , Inmunoglobulinas Intravenosas , Feto , Fibroelastosis Endocárdica/diagnóstico por imagen , Ecocardiografía/métodos

RESUMEN

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Asunto(s)

Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Piridazinas , Antineoplásicos/efectos adversos , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/genética , Humanos , Imidazoles , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Niacinamida/análogos & derivados , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles , Piridazinas/efectos adversos , Estudios Retrospectivos

RESUMEN

Introducción: El aumento de la prevalencia de osteoporosis asociado al envejecimiento y a los accidentes deportivos y de tráfico, son los responsables del incremento de las fracturas de tobillo. Este hecho pone de manifiesto la necesidad de protocolizar su asistencia para proporcionar un mayor beneficio clínico al paciente y una disminución de costes al sistema. Objetivo y métodos: En la actualidad, no existe un marco común para la implantación de protocolos y circuitos internos en los centros españoles para la realización de fracturas de tobillo por la vía de la cirugía mayor ambulatoria (CMA), objetivo que persigue el presente documento de posicionamiento. Para ello se revisa la evidencia clínica y económica de la CMA, el entorno local y las estrategias para su implementación, haciendo referencia a las fracturas de tobillo. Evidencia clínica y económica: Los resultados mostraron una mejor relación coste-beneficio en pacientes ambulatorios respecto a la tradicional hospitalización, con complicaciones y tasas de reingreso menores y, por tanto, ahorro de costes significativos. Barreras y estrategias: Se revisan las barreras generales y específicas, así como las estrategias y los circuitos para la correcta implementación. Resultados: Los resultados muestran una reducción de las tasas de complicaciones y reingresos, así como un ahorro de costes. Supone una mejor relación coste-beneficio en la atención ambulatoria en comparación con la hospitalización tradicional. Posicionamiento: La implantación de la CMA contribuye a mejorar la calidad asistencial, la satisfacción del paciente y del equipo asistencial, así como la optimización de recursos. Las fracturas de tobillo en pacientes seleccionados tanto por la patología de base, riesgo anestésico y tipo de fractura pueden intervenirse de manera satisfactoria en régimen de CMA.(AU)

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Introduction: The increase in the prevalence of osteoporosis associated with ageing, and sports and traffic accidents, are responsible for the increase in ankle fractures. This fact emphasises the need to protocolise their care in order to provide greater clinical benefit to patients, and better cost–benefit ratios to the health system. Aim and method: At present, there is no common framework for implementation of protocols and internal circuits of the Spanish centres for ankle fractures by means of major outpatient surgery (MOS), which is the final objective of this position paper. For this, the clinical and economic evidence of MOS, the local environment and the strategies for its implementation are reviewed, related to ankle fractures. Clinical and economic vidence: The results showed a better cost–benefit ratio in outpatients compared to traditional hospitalisation, with lower complications and readmission rates and therefore significant cost savings. Barriers and strategies: General and specific barriers are reviewed, as well as strategies and circuits for proper implementation. Results: The results show lower complication and readmission rates together with significant cost savings. It entails a better cost–benefit ratio in outpatient care compared to traditional hospitalisation. Position statement:The implementation of MOS contributes to improve the quality of care, and the satisfaction of both, patient and health care team, while optimising the utilisation of resources. Ankle fractures in patients selected for both the underlying pathology, anaesthetic risk, and the type of fracture can be operated satisfactorily under the MOS.(AU)

Asunto(s)

Fracturas de Tobillo/cirugía , Fracturas de Tobillo/terapia , Osteoporosis/diagnóstico , Envejecimiento , Protocolos Clínicos , Accidentes de Tránsito , Traumatismos en Atletas , Ortopedia , Traumatología

RESUMEN

Introduction: The increase in the prevalence of osteoporosis associated with ageing, and sports and traffic accidents, are responsible for the increase in ankle fractures. This fact emphasises the need to protocolise their care in order to provide greater clinical benefit to patients, and better cost–benefit ratios to the health system. Aim and method: At present, there is no common framework for implementation of protocols and internal circuits of the Spanish centres for ankle fractures by means of major outpatient surgery (MOS), which is the final objective of this position paper. For this, the clinical and economic evidence of MOS, the local environment and the strategies for its implementation are reviewed, related to ankle fractures. Clinical and economic vidence: The results showed a better cost–benefit ratio in outpatients compared to traditional hospitalisation, with lower complications and readmission rates and therefore significant cost savings. Barriers and strategies: General and specific barriers are reviewed, as well as strategies and circuits for proper implementation. Results: The results show lower complication and readmission rates together with significant cost savings. It entails a better cost–benefit ratio in outpatient care compared to traditional hospitalisation. Position statement:The implementation of MOS contributes to improve the quality of care, and the satisfaction of both, patient and health care team, while optimising the utilisation of resources. Ankle fractures in patients selected for both the underlying pathology, anaesthetic risk, and the type of fracture can be operated satisfactorily under the MOS.(AU)

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Introducción: El aumento de la prevalencia de osteoporosis asociado al envejecimiento y a los accidentes deportivos y de tráfico, son los responsables del incremento de las fracturas de tobillo. Este hecho pone de manifiesto la necesidad de protocolizar su asistencia para proporcionar un mayor beneficio clínico al paciente y una disminución de costes al sistema. Objetivo y métodos: En la actualidad, no existe un marco común para la implantación de protocolos y circuitos internos en los centros españoles para la realización de fracturas de tobillo por la vía de la cirugía mayor ambulatoria (CMA), objetivo que persigue el presente documento de posicionamiento. Para ello se revisa la evidencia clínica y económica de la CMA, el entorno local y las estrategias para su implementación, haciendo referencia a las fracturas de tobillo. Evidencia clínica y económica: Los resultados mostraron una mejor relación coste-beneficio en pacientes ambulatorios respecto a la tradicional hospitalización, con complicaciones y tasas de reingreso menores y, por tanto, ahorro de costes significativos. Barreras y estrategias: Se revisan las barreras generales y específicas, así como las estrategias y los circuitos para la correcta implementación. Resultados: Los resultados muestran una reducción de las tasas de complicaciones y reingresos, así como un ahorro de costes. Supone una mejor relación coste-beneficio en la atención ambulatoria en comparación con la hospitalización tradicional. Posicionamiento: La implantación de la CMA contribuye a mejorar la calidad asistencial, la satisfacción del paciente y del equipo asistencial, así como la optimización de recursos. Las fracturas de tobillo en pacientes seleccionados tanto por la patología de base, riesgo anestésico y tipo de fractura pueden intervenirse de manera satisfactoria en régimen de CMA.(AU)

Asunto(s)

Fracturas de Tobillo/cirugía , Fracturas de Tobillo/terapia , Osteoporosis/diagnóstico , Envejecimiento , Protocolos Clínicos , Accidentes de Tránsito , Traumatismos en Atletas , Ortopedia , Traumatología

RESUMEN

INTRODUCTION: The increase in the prevalence of osteoporosis associated with ageing, and sports and traffic accidents, are responsible for the increase in ankle fractures. This fact emphasises the need to protocolise their care in order to provide greater clinical benefit to patients, and better cost-benefit ratios to the health system. AIM AND METHOD: At present, there is no common framework for implementation of protocols and internal circuits of the Spanish centres for ankle fractures by means of major outpatient surgery (MOS), which is the final objective of this position paper. For this, the clinical and economic evidence of MOS, the local environment and the strategies for its implementation are reviewed, related to ankle fractures. CLINICAL AND ECONOMIC EVIDENCE: The results showed a better cost-benefit ratio in outpatients compared to traditional hospitalisation, with lower complications and readmission rates and therefore significant cost savings. BARRIERS AND STRATEGIES: General and specific barriers are reviewed, as well as strategies and circuits for proper implementation. RESULTS: The results show lower complication and readmission rates together with significant cost savings. It entails a better cost-benefit ratio in outpatient care compared to traditional hospitalisation. POSITION STATEMENT: The implementation of MOS contributes to improve the quality of care, and the satisfaction of both, patient and health care team, while optimising the utilisation of resources. Ankle fractures in patients selected for both the underlying pathology, anaesthetic risk, and the type of fracture can be operated satisfactorily under the MOS.

RESUMEN

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Asunto(s)

Desarrollo Infantil/fisiología , Estado Nutricional/fisiología , Pubertad/fisiología , Receptor de Melanocortina Tipo 3/metabolismo , Maduración Sexual/fisiología , Adolescente , Anciano de 80 o más Años , Animales , Niño , Ciclo Estral/genética , Ciclo Estral/fisiología , Femenino , Homocigoto , Humanos , Hipotálamo/citología , Hipotálamo/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Melanocortinas/metabolismo , Menarquia/genética , Menarquia/fisiología , Ratones , Fenotipo , Pubertad/genética , Receptor de Melanocortina Tipo 3/deficiencia , Receptor de Melanocortina Tipo 3/genética , Maduración Sexual/genética , Factores de Tiempo , Aumento de Peso

RESUMEN

OBJECTIVE: To quantify the proportion of postpartum venous thromboembolism (VTE) readmissions, including those that occur at different hospitals from index admission, and describe risk factors for this outcome. DESIGN: Retrospective observational study. SETTING: US hospitals included in the Nationwide Readmissions Database. SAMPLE: A total of 3 719 238 patients >14 years of age with a delivery-associated hospitalisation in 2014. METHODS: Univariate analysis was performed to identify patient and hospital factors associated with readmissions. Significant factors were included in multivariate logistic regression to identify independent risk factors. Results were weighted for national estimates. MAIN OUTCOME MEASURES: Readmission with VTE to both index and different hospitals at 30, 60 and 90 days. RESULTS: The VTE cumulative readmission rate was 0.053% (n = 1477), 0.063% (n = 1765) and 0.069% (n = 1938) at 30, 60 and 90 days, respectively. Patients were readmitted to different hospitals 31% of the time within 90 days. Risk factors for different hospital VTE readmission were unique and included younger age and initial admission to a small/medium-sized hospital. Initial admission to a for-profit hospital increased the likelihood of readmission to a different hospital. CONCLUSIONS: Nearly one in three postpartum VTEs are missed by the current quality metrics, with significant implications for outcomes and quality. For-profit hospitals have a significant portion of their VTE readmissions hidden, falsely lowering their readmission rates relative to public hospitals. TWEETABLE ABSTRACT: US analysis shows 1 in 3 readmissions for postpartum venous thromboembolism currently missed.

Asunto(s)

Atención Prenatal , Trastornos Puerperales/epidemiología , Tromboembolia Venosa/epidemiología , Adolescente , Adulto , Bases de Datos Factuales , Femenino , Humanos , Persona de Mediana Edad , Readmisión del Paciente , Embarazo , Trastornos Puerperales/etiología , Factores de Riesgo , Estados Unidos/epidemiología , Tromboembolia Venosa/etiología , Adulto Joven

RESUMEN

BACKGROUND: Glucose management for people with diabetes approaching the end of life can be very challenging. The aim is to balance a minimally invasive approach with avoidance of symptomatic hypo- and hyperglycaemia. CASE REPORT: We present a case of a hospitalized individual whose glucose was managed with closed-loop insulin delivery within a randomized controlled trial setting during a period of terminal illness. During the time in which closed-loop insulin delivery was used, glucose control was safe, with no glucose-related harm. The mean ± sd sensor glucose for this individual was 11.3 ± 4.3 mmol/l, percentage of time spent in target glucose range between 6 and 15 mmol/l was 70.5%, time spent in hypoglycaemia was 2.0% and time spent in significant hyperglycaemia >20 mmol/l was 2.6%. CONCLUSION: Closed-loop systems can accommodate personalized glucose targets and highly variable insulin requirements. Factory-calibrated continuous glucose sensors and insulin pump therapy are less intrusive than finger-stick glucose measurements and insulin injections, respectively. Closed-loop systems may provide a safer and less burdensome approach to glucose management towards the end of life.

Asunto(s)

Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Cuidado Terminal/métodos , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resultado Fatal , Femenino , Humanos

RESUMEN

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1ß, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373-378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1.

Asunto(s)

Cuidadores/psicología , Conocimientos, Actitudes y Práctica en Salud , Salud Bucal , Padres/psicología , Maestros/psicología , Niño , Preescolar , Atención a la Salud , Caries Dental/epidemiología , Caries Dental/prevención & control , Inglaterra/epidemiología , Grupos Focales , Promoción de la Salud , Accesibilidad a los Servicios de Salud , Humanos , Renta , Percepción , Pobreza , Investigación Cualitativa , Gales/epidemiología

RESUMEN

La enfermedad tromboembólica venosa es un proceso patológico que abarca tanto la trombosis venosa profunda como el tromboembolismo pulmonar. Son muchos los estudios que recogen la alta incidencia de esta enfermedad en pacientes afectos de lesiones neurológicas como la lesión medular, el traumatismo craneoencefálico o el ictus, todos ellos pacientes susceptibles de ingreso en centros de rehabilitación. En la literatura publicada existe controversia acerca de la necesidad de screening de enfermedad tromboembólica venosa en estos pacientes, el tiempo de mantenimiento de la profilaxis o los fármacos a utilizar tanto en la profilaxis como una vez se establece la sospecha o el diagnóstico definitivo de dicha enfermedad. Con esta revisión de la literatura pretendemos hacer un consenso para intentar aclarar dudas y establecer unas directrices de sospecha, diagnóstico y tratamiento que nos ayuden en la práctica clínica diaria

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Venous thromboembolism is a disease that includes both deep vein thrombosis and pulmonary embolism. Many studies reflect the high incidence of this disease in patients with neurological injuries such as, spinal cord injury, traumatic brain injury, or stroke, and all these patients are candidates for admission to rehabilitation centres. There is controversy in the published literature on the need for screening of deep vein thrombosis in these patients, time on prophylaxis drug maintenance or the drugs to use for prophylaxis once suspected or when the definite diagnosis of this disease is established. A review of the literature is presented in order to attempt to clarify these doubts and establish guidelines for suspicion, diagnosis and treatment to help us in daily clinical practice

Asunto(s)

Humanos , Masculino , Femenino , Tromboembolia/patología , Tromboembolia/prevención & control , Tromboembolia , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal , Ultrasonografía Doppler/instrumentación , Ultrasonografía Doppler/métodos , Ultrasonografía Doppler , Factores de Riesgo , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/prevención & control , Trombosis de la Vena/terapia , Flebografía/instrumentación , Flebografía/métodos , Flebografía , Trombosis/complicaciones , Trombosis/prevención & control , Trombosis

RESUMEN

BACKGROUND: Expanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. METHODS: After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up). RESULTS: In 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P<0.0001), seminal vesicle invasion (SVI, P=0.02), extracapsular extension (ECE, P<0.0001) and Gleason score (GS, P<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence-free, overall and disease-specific survival by multivariable Cox proportional hazard model (hazards ratio (HR)=1.04-1.1, P=0.02-0.0008). High Ki67 score (defined as ⩾5%) was significantly associated with worse RFS (HR=1.47, P=0.0007) and worse overall survival (HR=2.03, P=0.03). CONCLUSIONS: In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE and greater probability of recurrence.

Asunto(s)

Antígeno Ki-67/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/mortalidad , Proliferación Celular , Humanos , Estimación de Kaplan-Meier , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Recurrencia , Análisis de Matrices Tisulares

RESUMEN

Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2(tm1a/tm1a)) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2(tm1a/tm1a) mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2(tm1a/tm1a) mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling.

Asunto(s)

Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Colesterol/sangre , Metabolismo Energético/genética , Proteínas Modificadoras de la Actividad de Receptores/metabolismo , Proteínas Represoras/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Ansiedad/genética , Ansiedad/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Conducta Animal/fisiología , Peso Corporal/genética , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Ingestión de Alimentos/genética , Metabolismo de los Lípidos/genética , Ratones , Ratones Noqueados , Actividad Motora/genética , Neuronas/metabolismo , Oxitocina/genética , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Proteínas Modificadoras de la Actividad de Receptores/genética , Proteínas Represoras/genética , Hormona Liberadora de Tirotropina/genética , Hormona Liberadora de Tirotropina/metabolismo

RESUMEN

BACKGROUND: Osteochondroma is the most common non-malignant tumour of bone, accounting for approximately one third of benign lesions in the skeleton. They often develop around the knee in the distal femur and in the proximal tibia and fibula. They present as a painless slow growing mass during adolescence and have been reported to cause damage to adjacent structures such as blood vessels; arterial damage is more common than venous injury and is usually a result of compression, stretching, and rubbing of the arterial wall. Such lesions include stenosis, thrombosis, and pseudoaneurysm formation possibly causing lower limb claudication or acute limb ischemia. METHODS: An 18 year old male patient with a 4 week history of pain, hematoma, and oedema of the left calf without previous trauma is reported. A computed tomography scan (CT) revealed a large popliteal artery pseudoaneurysm and its close relationship to a protrusion of the proximal tibia. RESULTS: The popliteal artery was repaired by an external saphenous patch and the exostosis was removed. The patient had palpable popliteal and distal pulses after surgery and during the first year follow-up. CONCLUSIONS: Tibial osteochondroma should be considered in the differential diagnosis in young patients, among the potential causes of pseudoaneurysm of the femoral or popliteal artery. Surgical repair should be performed to restore normal blood flow with resection of the exostosis to prevent recurrence.

RESUMEN

BACKGROUND AND AIMS: Prescribing errors cause significant patient morbidity and mortality. Current legislation allows prescribing by different health professions. Inter-professional collaboration and learning may result in safer prescribing practice. This study aimed to develop, pilot and test the feasibility of a simulated inter-professional prescribing masterclass for non-medical prescribing students, medical students and pharmacists. METHODS AND RESULTS: A three-scenario, simulated patient session was designed and implemented by an expert panel. Medical students, non-medical prescribing students and pharmacists worked together to formulate and implement evidence-based prescriptions. The Readiness for Inter-professional Learning Score (RIPLS) and a self-efficacy score were administered to the students and the Trust in Physician Score to the simulated patients. Overall, the RIPLS and self-efficacy scores increased. Pharmacists showed the highest rating in the Trust in Physician score. Post masterclass group discussions suggested that the intervention was viewed as a positive educational experience. CONCLUSION: An inter-professional prescribing masterclass is feasible and acceptable to students. It increases self-efficacy, readiness for inter-professional learning and allows students to learn from, about and with each other. A larger study is warranted and the use of feedback from simulated patients explored further.

Asunto(s)

Prescripciones de Medicamentos/normas , Educación Médica Continua/métodos , Educación en Farmacia/métodos , Farmacéuticos , Pautas de la Práctica en Medicina/normas , Competencia Profesional/normas , Estudiantes de Enfermería , Actitud del Personal de Salud , Humanos , Relaciones Interprofesionales , Proyectos Piloto , Autonomía Profesional , Evaluación de Programas y Proyectos de Salud , Escocia , Estudiantes de Medicina

RESUMEN

OBJECTIVE: The aim of this work was to review the incidence of monoclonal gammopathy of undetermined significance (MGUS) and complications in kidney transplant (KT) patients at the Puerta del Mar Hospital in Cádiz, Spain. This diagnosis was not considered to be a contraindication for transplantation. METHODS: To estimate the incidence of MGUS in KT patients we used the database of our hospital, which included 1,016 patients who received a KT from 1992 to 2012 with a median follow-up of 30 months. The incidence of MGUS in non-transplant patients was estimated from the literature. RESULTS: Out of 1,016 KT patients, 16 developed MGUS; 10 (72.5%) were >50 years old. Two patients developed post-transplantation lymphoproliferative disorders. No cases of progression to multiple myeloma or amyloidosis were seen during immune suppression therapy or after. CONCLUSIONS: MGUS was >100 times more frequent in KT recipients than in the general population (P < .05). But in contrast to MGUS in general population, progression to plasma cell dyscrasia in these patients was absent and its incidence is unknown in KT patients.

Asunto(s)

Trasplante de Riñón , Gammopatía Monoclonal de Relevancia Indeterminada/etiología , Complicaciones Posoperatorias , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , España

RESUMEN

OBJETIVO: Valorar la mortalidad y complicaciones postoperatorias durante el primer mes de los aneurismas de aorta abdominal rotos (AAAr), en función de la técnica quirúrgica empleada, reparación endovascular de aneurisma (EVAR). Analizar los factores pronósticos que influyen en la mortalidad. MATERIAL Y MÉTODOS: Estudio de cohortes históricas de los pacientes con AAAr infrarrenales y yuxtarrenales sometidos a tratamiento quirúrgico (EVAR o cirugía abierta) en nuestro centro. Los criterios de elección para EVAR son anatomía favorable y estabilidad hemodinámica. Las variables recogidas fueron características demográficas, factores de riesgo cardiovascular y patología asociada, técnica quirúrgica, lugar de procedencia, demora en la intervención, situación preoperatoria, complicaciones médico-quirúrgicas postoperatorias, estancia en unidad de reanimación posquirúrgica (URP) y en planta de hospitalización y mortalidad. RESULTADOS: Entre enero de 2011 y agosto del 2013 se intervinieron 31 varones con edad media de 71 años. La mortalidad global fue del 45% (mortalidad del 61% en cirugía abierta frente al 23% con EVAR, p 0,06). Hipotensión preoperatoria < 80 mmHg (p < 0,004), creatinina > 2,1 mg/dl (p 0,018) e inestabilidad hemodinámica en quirófano (p < 0,05) se asocian con la mortalidad de forma significativa, independientemente de la técnica quirúrgica empleada. La estancia media en URP fue de 10 días en cirugía abierta frente a 2 días en EVAR (p 0,04). La estancia media hospitalaria fue de 19 días en cirugía abierta frente a 6,5 días en EVAR. CONCLUSIONES: La introducción del EVAR para el tratamiento de los AAAr en nuestro centro ha disminuido la morbimortalidad, la estancia media en URP y en planta de hospitalización

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OBJECTIVE: A study was conducted on the 30-day mortality and postoperative complications after endovascular repair (EVAR) and open surgery in patients with ruptured abdominal aortic aneurysms (rAAA). An analysis was made of the prognostic factors influencing the mortality. MATERIAL AND METHODS: A review was conducted on a cohort of patients with infrarenal and juxtarenal rAAA undergoing surgical treatment (EVAR and open surgery). The selection criteria used for EVAR were favourable anatomy and hemodynamic stability. The variables collected were demographic characteristics, cardiovascular risk factors and associated diseases, surgical technique, place of origin, delayed intervention, preoperative status, postoperative medical and surgical complications, postoperative stay in intensive care unit (ICU) and days of hospital stay, and mortality. RESULTS: A total of 31 males with a mean age of 71 years were operated on between January 2011 and August 2013. Mortality was 45% (a mortality of 61% in open surgery compared to 23% with EVAR, p = .06). Variables significantly associated with 30-day mortality were preoperative hypotension < 80 mmHg (p = 0.004), creatinine > 2.1 mg / dl (p = 0.018), and hemodynamic instability during surgery (p < 0.05), regardless of the surgical technique used. The average stay in the ICU was 10 days in open surgery versus 2 days for EVAR (p = 0.04). The average hospital stay was 19 days in open surgery versus 6.5 days for EVAR. CONCLUSIONS: EVAR for treatment of rAAA in this hospital has decreased morbidity and mortality rates, the average stay in ICU, and hospitalization stay

Asunto(s)

Humanos , Masculino , Adulto , Indicadores de Morbimortalidad , Procedimientos Endovasculares , Procedimientos Endovasculares/mortalidad , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/metabolismo , Cirugía Torácica/ética , Procedimientos Endovasculares , Aneurisma de la Aorta Abdominal/clasificación , Aneurisma de la Aorta Abdominal/mortalidad , Cirugía Torácica/instrumentación , Cirugía Torácica/normas