scholarly journals Plasma C-Terminal Agrin Fragment as an Early Biomarker for Sarcopenia: Results from the Genofit Study

Author(s):  
Jedd Pratt ◽  
Giuseppe De Vito ◽  
Marco Narici ◽  
Ricardo Segurado ◽  
Ludmilla Pessanha ◽  
...  

Abstract Barriers associated with direct muscle quantification have prevented a consistent implementation of therapeutic measures for sarcopenia. Recently, the relevance of circulating C-terminal agrin fragment (CAF) as an accessible screening method alternative for sarcopenia has gained credence. Accordingly, this study aimed to verify the pertinence of plasma CAF as a biomarker for sarcopenia. Three-hundred healthy adults aged between 50-83 years took part in this study. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People criteria. Body composition was assessed using dual-energy x-ray absorptiometry, while muscle strength was examined using hand dynamometry. Plasma CAF concentrations were determined using a commercially available ELISA kit. CAF concentrations were significantly associated with appendicular lean mass (ALM), but not grip strength (p=0.028, p=0.575, respectively). Plasma CAF concentrations were significantly elevated in sarcopenic individuals compared to non-sarcopenic (p<0.001). Overall, individuals with low grip strength or low ALM displayed significantly higher CAF levels compared to healthy controls, after adjusting for age and body mass index (p=0.027, p=0.003, respectively). In males, those with low grip strength or low ALM had significantly elevated CAF levels (p=0.039, p=0.027, respectively), while in females, only those with low ALM had significantly raised CAF concentrations, compared to healthy controls (p=0.035). Our findings illuminate the potential relevance of CAF as an accessible biomarker for skeletal muscle health. CAF determination may enhance clinical practise by facilitating more widespread treatment strategies for sarcopenia. Nevertheless, future research is needed to confirm the diagnostic pertinence of CAF concentrations in screening for sarcopenia.

2021 ◽  
pp. 088307382199988
Author(s):  
Giuseppina Pilloni ◽  
Martin Malik ◽  
Raghav Malik ◽  
Lauren Krupp ◽  
Leigh Charvet

Aim: To adopt a computer-based protocol to assess grip fatigability in patients with pediatric-onset multiple sclerosis to provide detection of subtle motor involvement identifying those patients most at risk for future decline. Method: Pediatric-onset multiple sclerosis patients were recruited during routine outpatient visits to complete a grip assessment and compared to a group of healthy age- and sex-matched controls. All participants completed a computer-based measurement of standard maximal grip strength and repetitive and sustained grip performance measured by dynamic and static fatigue indices. Results: A total of 38 patients with pediatric-onset multiple sclerosis and 24 healthy controls completed the grip protocol (right-hand dominant). There were no significant group differences in maximal grip strength bilaterally (right: 21.8 vs 19.9 kg, P = .25; left: 20.4 vs 18.7 kg, P = .33), although males with pediatric-onset multiple sclerosis were significantly less strong than healthy controls (right: 26.53 vs 21.23 kg, P = .009; left; 25.13 vs 19.63 kg, P = .003). Both dynamic and static fatigue indices were significantly higher bilaterally in pediatric-onset multiple sclerosis compared with healthy control participants (left-hand dynamic fatigue index: 18.6% vs 26.7%, P = .003; right-hand static fatigue index: 28.3% vs 41.3%, P < .001; left-hand static fatigue index: 31.9% vs 42.6%, P < .001). Conclusion: Brief repeatable grip assessment including measures of dynamic and sustained static output can be a sensitive indicator of upper extremity motor involvement in pediatric-onset multiple sclerosis, potentially identifying those in need of intervention to prevent future disability.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rizwan Qaisar ◽  
Asima Karim ◽  
Tahir Muhammad ◽  
Islam Shah ◽  
Javaidullah Khan

AbstractLoss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81–87/group), aged 55–74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738–0.845, p < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.


2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
K Ibrahim ◽  
M A Mullee ◽  
G Lily Yao ◽  
S Zhu ◽  
M Baxter ◽  
...  

Abstract Introduction Osteoporosis and sarcopenia often co-exist (osteo-sarcopenia) and both are associated with increased risk of falls and fractures. Early identification and treatment of sarcopenia among older people with fragility arm fractures could prevent further fractures. This study evaluated the feasibility of assessing sarcopenia in a fracture clinic. Methods People aged 65+ years with arm fracture attending fracture clinics in one acute trust were recruited. Sarcopenia was assessed using gait speed, grip strength with unfractured arm (hand dynamometer using appropriate cut off adjusted for age and gender), skeletal muscle mass index SMI (Bioimpedance BIA), SARC-F questionnaire, the European Working Group on Sarcopenia in Older People (EWGSOP) I and II criteria. The sensitivity and specificity of each measure was calculated against the EWGSOP II criteria as the standard reference. Results 100 patients (Mean age 75 years±7.2; 80 female) were recruited. Sarcopenia was identified among 4% (EWGSOP I), 5% (SMI), 13% (EWGSOP II), 16% (gait speed test), 18% (SARC-F) and 39% (grip strength) and was more prevalent among men. SARC-F had the best sensitivity and specificity (100% and 96% respectively) when compared to the EWGSOP II criteria. Sensitivity and specificity for the remaining measures were respectively (100%, 71%) for grip strength, (75%, 94%) for gait speed, (25%, 97%) with SMI and (25%, 99%) for EWGSOP I. Time needed to complete the assessments was 1–2 minutes for gait speed, grip strength and SARC-F; five minutes for BIA test, and nine minutes when EWGSOP I and II criteria were applied. Data were complete for grip strength and SARC-F. Missing data was reported among 2% for gait speed, 8% for BIA test, 8% for EWGSOP II and 10% for EWGSOP I. Conclusion It was feasible to assess sarcopenia in fracture clinics and SARC-F was a quick, simple and sensitive tool suitable for routine use.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mullavelil ◽  
V George ◽  
A Thannikkal ◽  
R Aravindakshan ◽  
D John ◽  
...  

Abstract Background Only little attention has been paid to treatment strategies of chronic disease conditions that require long term treatment and repeated hospitalizations Purpose Our aim was to review cost-effectiveness of guideline directed medical therapy of heart failure in India and identify drugs that can be made available free of cost or at subsidized rates to the patient population. Methods Data extracted from ten landmark trials in heart failure was used to compute Number Needed to Treat (NNT) and Cost Needed to Treat (CNT) of drugs used in heart failure, to prevent cardiovascular mortality and heart failure re-hospitalization using HDS Plotter- Incremental Cost Effectiveness Calculator. Since various brands (i.e. trade names) with wide cost range are available in Indian market, the average retail price in Indian Rupees for year 2019 was considered and converted to US dollars and used for the analysis.NNT and CNT of each drug was computed and the cost-effectiveness was analyzed. WHO recommendation of three times per capita GDP was used as the cost effectiveness threshold. Results Medications that were labeled as class I for the treatment of heart failure, were included in our analysis. Ivabradine, Valsartan and Angiotensin Receptor Neprilysin inhibitor (ARNi) did not meet the cost effectiveness criteria for preventing cardio-vascular mortality. For prevention of heart failure re-hospitalization, all drugs except ARNi, met the cost effectiveness threshold. Conclusion Any future research would need to consider compliance factor along with Willingness to Pay (WTP) to understand the real acceptance of these drugs on the ground in India. Log prices (in US$) of various HF drugs Funding Acknowledgement Type of funding source: None


Author(s):  
Rashid Iqbal ◽  
Muhammad Javaid Asad ◽  
Saima Siddiqi ◽  
Raja Tahir Mahmood ◽  
Muhamamd Baseer Shah ◽  
...  

Objective: To examine clinical features, biochemical markers, demographic features, antecedent infections, frequency and treatment strategies. Methods: This case-control study was conducted at Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan and District Headquarters Hospital (DHQ), Rawalpindi, Pakistan from 2018 to 2020. Ninety consecutive patients of Guillain-Barré syndrome (GBS) and 77 healthy controls were enrolled. Patients were diagnosed by clinical presentation, Nerve conduction study (NCS), Electromyography (EMG), Cerebrospinal fluid analysis (CSF) and biochemical profile. Data was analyzed on IBM SPSS version 23. Results: Symmetrical ascending weakness was the striking clinical feature. Mean age was 40.20±14.90 years and male to female ratio was 2.1:1. Acute inflammatory demyelinating polyneuropathy (AIDP) was found to be the most common electrophysiological variant of GBS (46%). There was considerable difference in Interleukin-17(IL-17) levels between GBS patients 23.12 ± 3.41 pg/ml and healthy controls 8.82 ± 2.49. Mean IL-17 level was markedly increased in GBS patients, P=0.006, P<0.05. Gastrointestinal infection was the most common preceding infection (56.66%). Mean CSF protein was 100.83 g/dl with ± 51.32 standard deviation and albumio cytologic dissociation (ACD) was different in all four variants of GBS, P= 0.005. Conclusion: GBS was presented by all ages. Males were more affected than females. About two third of GBS patients showed an antecedent infection before GBS onset. Increased levels of cytokine (IL-17) showed involvement of autoimmunity. ACD differentiated it from poliomyelitis. Plasmapheresis and intravenous immunoglobulin (IVIG) therapy were used to treat patients. Key words: Guillain-Barré Syndrome; cerebrospinal fluid; albuminocytologic dissociation; nerve conduction studies; variants; electromyography Continuous....


2020 ◽  
Vol 49 ◽  
Author(s):  
D. P. Kurmayev ◽  
S. V. Bulgakova ◽  
N. O. Zakharova

Rationale: The progressive decline in skeletal muscle strength and function during aging can lead to disability and premature death. It is of interest to evaluate the potential of bioimpedance phase angle (PhA) as an instrumental marker of sarcopenia in clinical practice.Aim: To identify an association between the phase angles determined by the bioimpedance analysis of body composition, with functional activity parameters in elderly women with multiple comorbidities.Materials and methods: The study included 146  elderly women (aged 75 to 84  years, mean age 79.44±2.56  years). Assessments consisted of the Charlson comorbidity index, “Vozrast ne pomekha” (Age is not a hindrance) questionnaire, the Barthel index, the sit-to-stand five-repeat test, the standardized 4-meter walking speed test, and bioimpedance analysis of body composition (ABC02, Medass, Russia). Muscle strength parameters were assessed by wrist dynamometry with a mechanical wrist dynamometer. The hand dynamometry index was calculated by dividing the hand grip strength by the patient's squared height. According to the EWGSOP2 guidelines for the critical cur-off for hand dynamometry, the patients were divided into two groups: those with the hand grip strength>16 kg (n=41) and those with<16 kg (n=105).Results: There were significant correlations of PhA with age (r=-0.369; p=0.017), the results of the screening questionnaire “Vozrast ne pomekha” (Age is not a hindrance) (r=-0.359; p=0.023), Barthel index (r=0.375; p=0.018), hand dynamometry (r=0.395; p=0.014), hand dynamometry index (r=0.340; p=0.021), lean body mass (r=0.414; p=0.009), musculoskeletal mass (r=0.819; p<0.001), proportion of musculoskeletal mass (r=0.796; p<0.001), walking speed (r=0.670; p<0.001), and the results of the sit-to-stand test (r=-0.541; p<0.001). Sarcopenia was diagnosed in 61 women (41.8%). There were also significant differences in age, hand dynamometry results, hand dynamometry index, walking speed and results of the sit-to-stand test between the two groups depending on their hand grip strength.Conclusion: The use of hand dynamometry, physical activity tests, and bioimpedance phase angle can be used in clinical practice to diagnose sarcopenia.


2018 ◽  
Vol 314 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Noriaki Manabe ◽  
Ken Haruma ◽  
Rui Nakato ◽  
Hiroaki Kusunoki ◽  
Tomoari Kamada ◽  
...  

Ultrasound tissue Doppler imaging (US-TDI) has been used to diagnose regional wall motion (WM) abnormalities in coronary artery disease but has not been applied to oropharyngeal diseases. This study aimed first to validate an US-TDI method to assess cervical esophageal (CE) WM and secondly to use the method to evaluate CE WM in patients with oropharyngeal dysphagia (OD). First, we enrolled 22 healthy men (mean age: 59.7 yr) who all underwent both US-TDI and videofluoroscopy (VF) and then esophageal high-resolution manometry (HRM) in the same week. We evaluated the reproducibility of the US-TDI and the relationship between US-TDI and other modalities (VF and HRM). Second, we enrolled 56 mild OD patients (mean age: 58.0 yr) and age- and sex-matched healthy controls. Difference in CE WM between these groups was evaluated by US-TDI. All healthy subjects underwent US-TDI, VF, and HRM successfully, with a sufficiently high reproducibility coefficient for this method, and significant correlation between US-TDI and VF/HRM parameters. US-TDI showed mean time to open CE wall and mean velocity of CE wall opening significantly differed between patients and healthy controls ( P < 0.01). In conclusion, we have developed a US-TDI method for easily assessing CE WM in daily practice and also found significant differences in CE WM between mild OD patients and healthy controls. NEW & NOTEWORTHY A new ultrasonographic screening method using tissue Doppler imaging for oropharyngeal dysphagia was found to be a reliable, reproducible, and well-tolerated method. There is a significant correlation between this new method and conventional methods. This method revealed that patients having mild symptoms of oropharyngeal dysphagia had already significantly delayed cervical esophageal wall opening.


2015 ◽  
Vol 89 (1) ◽  
pp. 122-127 ◽  
Author(s):  
Cristina Mariana Nastasă ◽  
Mihaela Duma ◽  
Adrian Pîrnău ◽  
Laurian Vlase ◽  
Brîndușa Tiperciuc ◽  
...  

Background and aims. In the context of the increasing phenomenon of microbial resistance to usual drugs, the development of new treatment strategies and new therapeutic protocols is a constant need. Thiazolidinedione and chromone represent two important scaffolds in medicinal chemistry due to their large pharmacological applicability.Methods. We synthesized a new 5-(chromene-3-yl)methylene-2,4-thiazolidinedione starting from 6,8-dichloro-4-oxo-4H-chromene-3-carbaldehyde. Then, by treating with different α-bromoalkylarylketones, we obtained N-substituted derivatives. All new compounds were investigated for their antimicrobial potential, using the diffusion method, against Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 49444, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028 and Candida albicans ATCC 10231. Three concentrations, 10 mg/ml, 5 mg/ml and 1 mg/ml of compounds were used. The results were evaluated by the measurement of the inhibition zone diameters and compared to those of gentamicin and fluconazole respectively, as reference drugs.Results. All new synthesized compounds were characterized using physico-chemical and spectrometric methods. They displayed modest to good antimicrobial activity. New molecules 8, 9 and 10 may represent promising candidates, showing zone inhibition diameters superior to those of reference drugs.Conclusions. This work presents chemical synthesis, characterization and investigation of the antibacterial and antifungal potential of 5-(chromene-3-yl)methylene-2,4-thiazolidinedione derivatives, which may be worthy of future research for designing new chemical entities.


Retos ◽  
2015 ◽  
pp. 197-202
Author(s):  
Jennifer L. Etnier ◽  
Chia-Hao Shih ◽  
Aaron Piepmeier

With the growing population of older adults, the identification of treatment strategies to prevent or ameliorate age-related cognitive decline has been an important topic in recent years. After reviewing cross-sectional, longitudinal, and experimentally designed studies, as well as evidence from narrative and meta-analytic reviews, the authors concluded that behavioral approaches such as physical activity, cognitive training, and dietary interventions show promising results. In addition, given the likelihood that multiple underlying mechanisms support cognitive function, research is currently focusing on how to combine lifestyle factors into multi-component interventions to generate greater and more meaningful effects. Though evidence for these enhanced benefits exists from animal studies, few multi-component studies have been performed with humans. However, the findings from these studies are promising and a continued pursuit of multi-component behavioral interventions to benefit cognitive performance is warranted. Given the world’s aging population and accompanying age-related health issues such as cognitive decline and dementia, future research should focus on understanding the biological mechanisms responsible for these effects in order to allow for the development of behavioral lifestyle prescriptions to benefit cognitive performance.Keywords. aging, cognitive function, exercise intervention, oxidative stress, cognitive engagement.Resumen. Con la creciente población de adultos mayores, la identificación de las estrategias de tratamiento para prevenir o mejorar el deterioro cognitivo relacionado con la edad ha sido un tema importante en los últimos años. Después de revisar estudios con diseños transversales, longitudinales y experimentales, así como la evidencia de revisiones de literatura narrativa y meta-analítica, los autores concluyen que los enfoques conductuales como la actividad física, el entrenamiento cognitivo y las intervenciones dietéticas muestran resultados prometedores. Además, dada la probabilidad de que múltiples mecanismos subyacentes apoyan la función cognitiva, las investigaciones se enfocan actualmente en la manera de cómo combinar factores del estilo de vida en las intervenciones con múltiples componentes para generar efectos mayores y más significativos. Aunque existe evidencia de estos beneficios a partir de estudios en animales, se han realizado pocos estudios de componentes múltiples en humanos. Sin embargo, los resultados de estos estudios son prometedores y se garantiza un seguimiento continuo de las intervenciones conductuales de componentes múltiples para beneficiar el rendimiento cognitivo. Teniendo en cuenta el envejecimiento de la población mundial y los problemas de salud relacionados con la edad que la acompañan, tales como el deterioro cognitivo y la demencia, la investigación futura debería centrarse en la comprensión de los mecanismos biológicos responsables de estos efectos con el fin de permitir el desarrollo de las prescripciones de comportamiento de estilo de vida para beneficiar el rendimiento cognitivo.Palabras claves. envejecimiento, funcionamiento cognitivo, intervención con ejercicio, estrés oxidativo, participación cognitiva.


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