Differences In Adipose Tissue And Lean Mass Distribution In Patients With Collagen Vi Related Myopathies Are Associated With Disease Severity And Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients

Differences in Adipose Tissue and Lean Mass Distribution in Patients with Collagen VI Related Myopathies Are Associated with Disease Severity and Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Valoración urológica del lesionado medular traumático tras más de diez años de evolución

Descripció del recurs: 29 gener 2010OBJETIVOS Objetivo principal Describir el estado urológico de los pacientes con lesión medular traumática tras más de diez años de evolución de la lesión. Objetivos específicos -Describir las características demográficas de los pacientes con lesión medular que siguen control periódico en un servicio especializado en vejiga neurógena en un hospital de tercer nivel de Barcelona. - Valorar las condiciones urológicas en las que estos pacientes fueron dados de alta hospitalaria y ver la evolución, complicaciones, tratamientos y diferencias en cuanto al control urológico que han tenido lugar tras más de diez años de evolución. -Comprobar si existen diferencias entre los pacientes intervenidos de cirugía endoscópica desobstructiva y los que no han sido operados. -Describir las condiciones sociales de los pacientes tras más de diez años de lesión medular y ver si existen diferencias según el nivel de lesión o el sexo del paciente. -Valorar las relaciones sexuales existentes en estos pacientes y comprobar si existen diferencias según el nivel de lesión o el sexo del paciente. PACIENTES Y MÉTODOS Criterios de inclusión: -lesionados medulares de origen traumático. -atendidos en el Hospital Vall d'Hebrón de Barcelona en la fase aguda de la lesión medular. -con más de diez años de evolución de la lesión medular. -que acuden, con una asiduidad no menor de tres años, a visita de control en el servicio de NeuroUrología del Hospital. Cuestionario con 86 variables (datos previos a la lesión, complicaciones durante el seguimiento y estado urológico, sexual, reproductivo y social del paciente tras más de 10 años de la lesión). Método estadístico SPSS. Test T-Student y Variación del Test-Chicuadrado. Valores significativos p <0,05. RESULTADOS 126 pacientes. En su mayoría varones (4 /1), con lesión medular completa ASIA A y afectación cervical o dorsal, secundaria a accidente de tráfico. De los datos obtenidos de su seguimiento, de más de 10 años de evolución, llegamos a las siguientes conclusiones: Condiciones urológicas 1-. La mujer utiliza con mayor frecuencia la sonda vesical permanente, mientras que el colector es el sistema de vaciado vesical más utilizado por los hombres en todos los niveles lesionales. Con el transcurso de los años aumenta el uso del colector y el del sondaje vesical permanente, mientras que disminuye el uso del cateterismo intermitente. 2-. Una alta proporción de nuestros pacientes utilizan maniobras facilitadoras de la micción: estimulación suprapúbica (28%), maniobra de Credé (28%) y prensa abdominal (14%). 3.- La media de infecciones urinarias, sin indicación de ingreso hospitalario, es de 1,4 infecciones/paciente/año. 4-. Las complicaciones urológicas constituyen el 20% de los motivos de reingreso. Las que se presentan con mayor frecuencia durante el seguimiento son: litiasis renovesical (18%), reflujo vesicoureteral (13%), hidronefrosis (11%), orquitis (12%), divertículos vesicouretrales (10%), pielonefritis (9%) e ITU de repetición con necesidad de antibiótico profiláctico (6%). La presencia de litiasis vesical es más frecuente en la mujer, con independencia del sistema de vaciado vesical empleado. 5-. Durante el ingreso hospitalario, una cuarta parte de los pacientes son sometidos a cirugía endoscópica desobstructiva (CED), cifra que asciende al 43% durante todo el período de seguimiento. El 16% de los pacientes sometidos a CED son reesfinteromizados; de éstos la mitad han precisado una segunda reesfinterotomía. 6-. El 28% de los pacientes han precisado de otras intervenciones quirúrgica urológicas diferentes a la CED (circuncisión, litotricia, cirugía prostática, resolución de fístula uretroescrotal, cirugía uretral, nefrectomía y orquiectomía). Condición social 7-. La mitad de los pacientes vive en pareja y una cuarta parte vive solo. Sólo una pequeña proporción precisará una residencia con el transcurso de los años de evolución. Vida sexual 8-. El 41% de los pacientes no tiene pareja estable tras los años de evolución, sin diferencias entre sexos. 9-. La mitad de nuestros pacientes no mantiene relaciones sexuales, sin diferencias en cuanto a sexos. Los que mantienen relaciones sexuales regulares en mayor proporción son los menores de 35 años y los lesionados a nivel lumbar. 10-. De los pacientes que mantienen relaciones sexuales, un 66% presenta erección (la mitad de ellos no completa). La mitad de los hombres que mantienen relaciones sexuales no sigue tratamiento para la disfunción eréctil y son los menores de 35 años los que lo siguen con más frecuencia. Los pacientes intervenidos de CED presentan en menor proporción erección. 11-. Una cuarta parte de los pacientes con relaciones sexuales consiguen eyaculación y tres cuartas partes coito. Los pacientes sometidos a CED presentan proporción menor de eyaculación y coito. 12-. Un 42% de los pacientes que mantienen relaciones sexuales no presentan orgasmo. La presencia de orgasmo es manifestada en mayor proporción en mujeres, en menores de 35 años y en pacientes no intervenidos de CED. 13-. Una baja proporción de los pacientes tienen hijos tras la lesión medular, sin diferencias en cuanto a sexo o nivel de lesión medular.OBJECTIVES Main objective Describe the state of urological patients with traumatic spinal cord injury after more than ten years of evolution of the lesion. Specific objectives -To describe the demographic characteristics of patients with spinal cord injury who are visited in a neurogenic bladder department in a tertiary hospital in Barcelona. - Rate urological conditions in which these patients were discharged from hospital and see the progress, complications, treatments, and differences in the urological monitoring that took place after more than ten years of evolution. -Check whether there are differences between patients undergoing sphincterotomy and those who have not been operated on. -Describe the social conditions of the patients after more than ten years of spinal cord injury and see if there are differences depending on the level of injury or the sex of the patient. -Rate sexual function in these patients and see whether there are differences depending on the level of injury or the sex of the patient. PATIENTS AND METHODS Inclusion criteria: -Spinal cord injuries with traumatic origin. -treated at the Hospital Vall d'Hebron in Barcelona in the acute phase of spinal cord injury. -with over ten years of development of spinal cord injury. -that come, with an attendance of not less than three years, to the control visit in the Neurogenic Bladder Department in the Hospital. Questionnaire with 86 variables (data prior to the injury, complications during follow-up, and urological status, sexual, reproductive and social life of the patient more than 10 years after the injury). SPSS statistical method. Student T-Test and Chisquare-Test. Significant values p <0.05. RESULTS 126 patients. In most men (4 / 1), with complete ASIA A spinal cord injury and dorsal or cervical level, secondary to traffic accident. Of data obtained from follow-up of more than 10 years of evolution, we reached the following conclusions: Urological Conditions 1 -. Women use most often permanent indwelling catheter, while the collector is the more frequent emptying bladder system used by men at all levels of injuries. Over the years the use of the collector and the urinary catheter permanently increases, while the use of intermittent catheterization decreases. 2 -. A high proportion of our patients use maneuvers enabling urination: suprapubic stimulation (28%), Crede maneuver (28%) and abdominal press (14%). 3 .- The mean urinary infections, with no indication of hospitalization was 1.4 infections / patient / year. 4 -. Urological complications account for 20% of the reasons for readmission in hospital. Which occur more frequently during follow-up are: bladder or urethra stones (18%), bladder-urethra reflux (13%), hydronephrosis (11%), orchitis (12%), bladder-urethra diverticuli (10%), pyelonephritis (9%), repetitive urinary infections with need of antibiotic prophylaxis (6%). The presence of bladder stones are more common in women, regardless of the bladder emptying employed. 5 -. During hospitalization, one quarter of patients undergo sphincterotomy, a figure which amounts to 43% throughout the monitoring period. 16% of patients need a second sphincterotomy; half of them have a third sphincterotomy. 6 -. 28% of patients are needed in other urologic surgical interventions other than sphincterotomy (circumcision, lithotripsy, prostate surgery, resolution urethra-scrotum fistula, urethral surgery, nephrectomy and orchiectomy). Social Conditions 7 -. Half of the patients live in couple and one quarter live alone. Only a small proportion will require a residence with the years of evolution. Sexual life 8 -. 41% of patients do not have stable couple after years of evolution, with no differences between sexes. 9 -. Half of our patients did not have sex, without regard to gender differences. Those who regularly have sex in a greater proportion are under 35 years and those injured at the lumbar spine. 10-. Of the patients who have sex, 66% had an erection (half of them not complete). Half of men who have sex do not follow a treatment for erectile dysfunction. Patients underwent sphincterotomy presents erection in lesser proportion. 11-. One quarter of patients with sexual ejaculation achieve ejaculation and three quarters coitus. Sphincterotomed patients have smaller proportion of sexual intercourse and ejaculation. 12-. 42% of patients who have sex, not have orgasm. The presence of orgasm is expressed in higher proportion in women, patients under 35 years and in sphincterotomed patients. 13-. A low proportion of the patients had children after spinal cord injury without regard to sex differences or level of spinal cord injury

Evaluation of an exercise-enabling control interface for powered wheelchair users: a feasibility study with Duchenne muscular dystrophy

Background Powered wheelchairs are an essential technology to support mobility, yet their use is associated with a high level of sedentarism that can have negative health effects for their users. People with Duchenne muscular dystrophy (DMD) start using a powered wheelchair in their early teens due to the loss of strength in their legs and arms. There is evidence that low-intensity exercise can help preserve the functional abilities of people with DMD, but options for exercise when sitting in a powered wheelchair are limited. Methods In this paper, we present the design and the feasibility study of a new version of the MOVit device that allows powered-wheelchair users to exercise while driving the chair. Instead of using a joystick to drive the wheelchair, users move their arms through a cyclical motion using two powered, mobile arm supports that provide controller inputs to the chair. The feasibility study was carried out with a group of five individuals with DMD and five unimpaired individuals. Participants performed a series of driving tasks in a wheelchair simulator and on a real driving course with a standard joystick and with the MOVit 2.0 device. Results We found that driving speed and accuracy were significantly lowered for both groups when driving with MOVit compared to the joystick, but the decreases were small (speed was 0.26 m/s less and maximum path error was 0.1 m greater). Driving with MOVit produced a significant increase in heart rate (7.5 bpm) compared to the joystick condition. Individuals with DMD reported a high level of satisfaction with their performance and comfort in using MOVit. Conclusions These results show for the first time that individuals with DMD can easily transition to driving a powered wheelchair using cyclical arm motions, achieving a reasonable driving performance with a short period of training. Driving in this way elicits cardiopulmonary exercise at an intensity found previously to produce health-related benefits in DMD.Peer ReviewedPostprint (published version

Evaluation of an exercise-enabling control interface for powered wheelchair users: a feasibility study with Duchenne muscular dystrophy

Background: Powered wheelchairs are an essential technology to support mobility, yet their use is associated with a high level of sedentarism that can have negative health effects for their users. People with Duchenne muscular dystrophy (DMD) start using a powered wheelchair in their early teens due to the loss of strength in their legs and arms. There is evidence that low-intensity exercise can help preserve the functional abilities of people with DMD, but options for exercise when sitting in a powered wheelchair are limited. Methods: In this paper, we present the design and the feasibility study of a new version of the MOVit device that allows powered-wheelchair users to exercise while driving the chair. Instead of using a joystick to drive the wheelchair, users move their arms through a cyclical motion using two powered, mobile arm supports that provide controller inputs to the chair. The feasibility study was carried out with a group of five individuals with DMD and five unimpaired individuals. Participants performed a series of driving tasks in a wheelchair simulator and on a real driving course with a standard joystick and with the MOVit 2.0 device. Results: We found that driving speed and accuracy were significantly lowered for both groups when driving with MOVit compared to the joystick, but the decreases were small (speed was 0.26 m/s less and maximum path error was 0.1 m greater). Driving with MOVit produced a significant increase in heart rate (7.5 bpm) compared to the joystick condition. Individuals with DMD reported a high level of satisfaction with their performance and comfort in using MOVit. Conclusions: These results show for the first time that individuals with DMD can easily transition to driving a powered wheelchair using cyclical arm motions, achieving a reasonable driving performance with a short period of training. Driving in this way elicits cardiopulmonary exercise at an intensity found previously to produce health-related benefits in DMD.This research has been partially supported by Grant 17.008 funded by Duchenne Parent Project Netherlands, and by the Juan de la Cierva Formación postdoctoral fellowship FJCI-2017-31754, which is funded by the Spanish Ministry of Science and Innovation (MCI)-Agencia Estatal de Investigación (AEI) along with the European Regional Development Fund (ERDF)

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy

[EN] Background and purpose Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients. Methods Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included. Bedside functional scales (Egen Klassification [EK2], Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) were also collected when available. Spearman's rho correlations (rs) and Bangdiwala's concordance test (B) were used to evaluate the scales' construct validity. Monthly slopes of change were used to calculate their responsiveness of the scales. Results The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong correlations with each other (rs > 0.70). A floor effect in motor function scales was found in the weakest patients (HFMSE 60 and RULM > 35). The ALSFRS-R (B = 0.72) showed a strong ability to discriminate between walkers, sitters and non-sitters, and the HFMSE (B = 0.86) between walkers and sitters. The responsiveness was low overall, although in treated patients a moderate responsiveness was found for the ALSFRS-R and HFMSE in walkers (0.69 and 0.61, respectively) and for EK2 in sitters (0.65) and non-sitters (0.60). Conclusions This study shows the validity and limitations of the scales most frequently used to assess adult SMA patients. Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness.CUIDAME, Grant/Award Number: PIC188-18; FUNDAME, Grant/Award Number: FUN-000-2017-01; Generalitat Valenciana, Grant/Award Number: EMERGENTES/2021/055PIJFVC; Instituto de Salud Carlos III, Grant/Award Number: JR19/00030 PI JFVC, 21/00737 PI JFVC and 19/01178 PI TSVázquez-Costa, JF.; Povedano, M.; Nascimiento-Osorio, AE.; Moreno Escribano, A.; Kapetanovic Garcia, S.; Dominguez, R.; Exposito, JM.... (2022). Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy. European Journal of Neurology. 29(12):3666-3675. https://doi.org/10.1111/ene.1554236663675291

Multidimensional Biomechanics-Based Score to Assess Disease Progression in Duchenne Muscular Dystrophy

(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease’s evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases

Differences In Adipose Tissue And Lean Mass Distribution In Patients With Collagen Vi Related Myopathies Are Associated With Disease Severity And Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients