Which factors are associated with acquired weakness in the ICU? An overview of systematic reviews and meta-analyses.

RATIONALE: Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients, characterized by muscle weakness and physical function loss. Determining risk factors for ICUAW poses challenges due to variations in assessment methods and limited generalizability of results from specific populations, the existing literature on these risk factors lacks a clear and comprehensive synthesis. OBJECTIVE: This overview aimed to synthesize risk factors for ICUAW, categorizing its modifiable and nonmodifiable factors. METHODS: An overview of systematic reviews was conducted. Six relevant databases were searched for systematic reviews. Two pairs of reviewers selected reviews following predefined criteria, where bias was evaluated. Results were qualitatively summarized and an overlap analysis was performed for meta-analyses. RESULTS: Eighteen systematic reviews were included, comprising 24 risk factors for ICUAW. Meta-analyses were performed for 15 factors, while remaining reviews provided qualitative syntheses. Twelve reviews had low risk of bias, 4 reviews were unclear, and 2 reviews exhibited high risk of bias. The extent of overlap ranged from 0 to 23% for the corrected covered area index. Nonmodifiable factors, including advanced age, female gender, and multiple organ failure, were consistently associated with ICUAW. Modifiable factors, including neuromuscular blocking agents, hyperglycemia, and corticosteroids, yielded conflicting results. Aminoglycosides, renal replacement therapy, and norepinephrine were associated with ICUAW but with high heterogeneity. CONCLUSIONS: Multiple risk factors associated with ICUAW were identified, warranting consideration in prevention and treatment strategies. Some risk factors have produced conflicting results, and several remain underexplored, emphasizing the ongoing need for personalized studies encompassing all potential contributors to ICUAW development.

Unraveling the Clinical Complexity of Thyrotoxic Periodic Paralysis: A Case Report.

Thyrotoxic periodic paralysis (TPP) is a clinical condition characterized by hypokalemia, muscle paralysis, and hyperthyroidism. TPP can be challenging to diagnose due to its low disease prevalence and the similarity of paralysis to other common conditions. Through this case report, we highlight the importance of considering hyperthyroidism as a cause of recurrent attacks of muscle paralysis, particularly in the setting of other signs of hyperthyroidism. A 32-year-old Hispanic man with a history of recurrent episodes of muscle weakness presented to the hospital with the acute onset of bilateral lower extremity weakness and an inability to ambulate. Additionally, the patient was experiencing symptoms of hyperthyroidism, including heat intolerance, weight loss, anxiety, and tremors. Lab evaluation showed hypokalemia, and the thyroid panel indicated hyperthyroidism due to Graves disease. His symptoms resolved after the replacement of potassium orally and intravenously, and he was discharged home on methimazole and propranolol. The presented case emphasizes that endocrinological and metabolic causes should be considered in the differential diagnosis of acute flaccid paralysis. The symptoms of hyperthyroidism can be subtle in many cases, which can make the diagnosis very challenging.

Atypical Presentations of Myasthenia Gravis as Acute Respiratory Failure: A Rare Case.

Myasthenia gravis (MG) is a chronic neuromuscular disease characterized by the progressive weakness of voluntary muscles, which encompass those in the face, throat, diaphragm, and those attached to bones. Patients commonly present with specific muscle weakness, such as difficulty in eye movement, facial expression, or swallowing, rather than generalized fatigue. However, as the disease advances, the majority of patients develop respiratory symptoms, which can significantly impact their quality of life. This makes the management of respiratory comorbidities essential, as respiratory tract infections can lead to exacerbations of MG and trigger a myasthenic crisis, necessitating immediate medical intervention. This report highlights a patient who initially presented with acute respiratory distress and was subsequently diagnosed with MG, underscoring the importance of recognizing respiratory symptoms in the context of this condition.

Profound cellular defects attribute to muscular pathogenesis in the rhesus monkey model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutations in the DMD gene. Muscle fibers rely on the coordination of multiple cell types for repair and regenerative capacity. To elucidate the cellular and molecular changes in these cell types under pathologic conditions, we generated a rhesus monkey model for DMD that displays progressive muscle deterioration and impaired motor function, mirroring human conditions. By leveraging these DMD monkeys, we analyzed freshly isolated muscle tissues using single-cell RNA sequencing (scRNA-seq). Our analysis revealed changes in immune cell landscape, a reversion of lineage progressing directions in fibrotic fibro-adipogenic progenitors (FAPs), and TGF-ß resistance in FAPs and muscle stem cells (MuSCs). Furthermore, MuSCs displayed cell-intrinsic defects, leading to differentiation deficiencies. Our study provides important insights into the pathogenesis of DMD, offering a valuable model and dataset for further exploration of the underlying mechanisms, and serves as a suitable platform for developing and evaluating therapeutic interventions.

Glucocorticoid treatment increases cholesterol availability during critical illness: effect on adrenal and muscle function.

BACKGROUND: Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. METHODS: In a matched set of prolonged critically ill patients (n = 324) included in the EPaNIC RCT, a secondary analysis was performed to assess the association between glucocorticoid treatment and plasma cholesterol from ICU admission to day five. Next, in a mouse model of cecal ligation and puncture-induced sepsis, septic mice were randomized to receive either hydrocortisone (1.2 mg/day) (n = 17) or placebo (n = 15) for 5 days, as compared with healthy mice (n = 18). Plasma corticosterone, cholesterol, and adrenocortical and myofiber cholesterol were quantified. Adrenal structure and steroidogenic capacity were evaluated. Muscle force and markers of atrophy, fibrosis and regeneration were quantified. In a consecutive mouse study with identical design (n = 24), whole body composition was assessed by EchoMRI to investigate impact on lean mass, fat mass, total and free water. RESULTS: In human patients, glucocorticoid treatment was associated with higher plasma HDL- and LDL-cholesterol from respectively ICU day two and day three, up to day five (P < 0.05). Plasma corticosterone was no longer elevated in hydrocortisone-treated septic mice compared to placebo, whereas the sepsis-induced reduction in plasma HDL- and LDL-cholesterol and in adrenocortical cholesterol was attenuated (P < 0.05), but without improving the adrenocortical ACTH-induced CORT response and with increased adrenocortical inflammation and apoptosis (P < 0.05). Total body mass was further decreased in hydrocortisone-treated septic mice (P < 0.01) compared to placebo, with no additional effect on muscle mass, force or myofiber size. The sepsis-induced rise in markers of muscle atrophy and fibrosis was unaffected by hydrocortisone treatment, whereas markers of muscle regeneration were suppressed compared to placebo (P < 0.05). An increased loss of lean body mass and total and free water was observed in hydrocortisone-treated septic mice compared to placebo (P < 0.05). CONCLUSIONS: Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass.

Case report: Antisynthetase syndrome with positive anti-PL7/SSA/RO52 antibodies.

Background: Antisynthetase syndrome (ASS) is a rare autoimmune disease characterized by the immune system attacking specific synthetase in the body. Due to the difficulty in clinical diagnosis, there is still a lack of effective treatment. Methods: We report a case of a 50-year-old man who presented with progressive, symmetric limb weakness, starting from the lower limbs and gradually affecting the upper limbs. He was admitted to the intensive care unit (ICU) for treatment due to recurrent fever and coma. When he was admitted to the ICU, his limbs were almost unable to move, and the levels of creatine phosphokinase and muscle glycogen were significantly elevated (2449 u/l and 1857 ng/ml). The electromyogram showed myogenic injury, and the anti-PL7 antibody, anti-SSA antibody, and anti-Ro52 antibody were positive. Pathological biopsy of the left biceps brachii showed striated muscle necrosis and macrophage infiltration. He was finally diagnosed with ASS and received treatment with methylprednisolone (subsequently changed to prednisone) and traditional Chinese medicine (Buzhongyiqi Decoction and Shenlingbaizhu powder). Results: After receiving 2 weeks of glucocorticoid and traditional Chinese medicine treatment, his muscle strength had basically recovered, reaching grade 5 in his limb muscles strength. During the 3-month follow-up period, his activity tolerance continued to improve. Conclusion: We present a case of severe anti-PL7 positive ASS with positive anti-SSA/Ro52 antibody. The disease was relieved by glucocorticoid and traditional Chinese medicine treatment. This provides an effective approach for managing ASS.

Diagnosis of "intensive care unit-acquired weakness" and "critical illness myopathy": Do the diagnostic criteria need to be revised?

Objectives: Intensive care unit acquired weakness (ICUAW) is a clinical diagnosis and an umbrella term for acquired weakness due to neuromuscular disorders such as critical illness myopathy (CIM) but also muscular inactivity/atrophy. Without a clear understanding of the distinct aetiology, it seems difficult to predict outcomes of ICUAW and to test and apply effective future treatments. The present study contrasts ICUAW with CIM and assesses the diagnostic and clinical relevance for affected patients. Methods: Data from a previous prospective cohort study investigating critically ill COVID-19 patients was analysed in a retrospective fashion. Patients were examined ten days after intubation with clinical assessment, nerve conduction studies, electromyography and muscle biopsy. Mortality was assessed during critical illness and at three months after hospital discharge. ICUAW and CIM were diagnosed according to the current diagnostic guidelines. Results: In this patient sample (n = 22), 92 % developed ICUAW, 55 % developed ICUAW and CIM, and 36 % had ICUAW but did not develop CIM. Overall, 27 % patients died during their stay in the intensive care unit. At three months after discharge, there were no further deaths, but in 14 % of patients the outcome was unknown. The diagnosis of CIM was more strongly associated with death during critical illness than ICUAW. No patient with ICUAW who did not fulfil the criteria for CIM died. Both clinical and electrophysiological criteria showed excellent sensitivity for CIM diagnosis, but only electrophysiological criteria had a high specificity. Determination of the myosin:actin ratio showed neither high sensitivity nor specificity for the diagnosis of CIM. Conclusions: The results of the present study support that ICUAW is a non-specific clinical diagnosis of low predictive power with regard to mortality. Further, diagnosing "ICUAW" seems also of little research value for both exploring the aetiology and pathophysiology of muscle weakness in critically ill patients and for evaluating potential treatment effects. Thus, more specific diagnoses such as CIM are more appropriate. Within the different diagnostic criteria for CIM, electrophysiological studies are the most sensitive and specific examinations compared to clinical and muscle tissue assessment. Significance: Avoiding an overarching diagnosis of "ICUAW" and instead focusing on specific diagnoses appears to have several relevant consequences: more precise diagnosis making, more accurate referral to aetiology and pathophysiology, improved outcome prediction, and development of more appropriate treatments.

Meta-analysis of the effects of bundle interventions on ICU-acquired weakness intervention.

BACKGROUND: Intensive care unit acquired weakness (ICU-AW) is a secondary neuromuscular complication in critically ill patients, characterized by profound weakness in all four limbs. Studies have shown that bundles of care are nursing strategies that combine a series of evidence-based interventions, which collectively optimize patients' clinical outcomes compared to individual interventions. OBJECTIVE: This study aims to conduct a meta-analysis of the effects of bundle interventions on ICU-AW deeply exploring the characteristics of bundle interventions, patient outcomes related to ICU-AW, and primarily investigating the effects of bundle interventions on ICU-AW. The main focus is to explore the clinical value of bundle interventions in treatment of ICU-acquired weakness in patients. METHODS: Computer and manual searches were conducted using keywords to retrieve relevant studies on the effects of bundle interventions on ICU-AW from databases such as PubMed, Web of Science, Cochrane Library and EMbase. The search period ranged from database inception to the present. The control group received standard ICU care, including basic nursing, while the intervention group received bundle nursing interventions. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 1545 participants (790 in the intervention group and 755 in the control group) were included. Meta-analysis results showed that the intervention group had significantly higher muscle strength (MD = 7.41, 95% CI: 6.65-8.16, P< 0.00001) and daily living ability (MD = 34.01, 95% CI: 32.54-35.48, P< 0.00001) than the control group. Additionally, the incidence of ICU-AW (OR = 0.39, 95% CI: 0.26-0.59, P< 0.00001), mechanical ventilation time (MD =-3.71, 95% CI: -3.58∼-2.76, P< 0.0001), and ICU length of stay (MD =-2.73, 95% CI: -3.14∼-2.31, P< 0.00001) were significantly lower in the intervention group than in the control group. CONCLUSION: ICU-AW has a severe negative impact on the recovery and functional restoration of ICU patients, increasing the treatment complexity for healthcare providers and the mortality and disability rates for patients. The bundled care approach may help reduce the incidence of ICU-AW, promote the restoration of daily activity function, enhance muscle strength, and reduce ICU stay and mechanical ventilation time for ICU patients. However, the long-term effects of bundle interventions still require further in-depth research.

Myositis: A Rare First Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems with a variety of clinical manifestations and serological abnormalities. Overt myositis is a rare and not well-studied manifestation of SLE, which is associated with a more severe disease course and may be overlooked by clinicians. This case report describes a rare first presentation of SLE with myositis. An 18-year-old female patient presented with a three-month history of generalized muscle weakness, polyarthralgia, and rashes. Physical examination revealed malar rash, a dry scaly pigmented rash affecting the flanks, and a non-blanching purpuric rash with mottled discoloration and a well-defined ulceration, affecting both hands, suggestive of vasculitis. A pigmented atrophic patch on the right upper chest was also suggestive of discoid lupus. Further examination findings included bilateral upper and lower limb weakness affecting proximal muscles (Medical Research Council (MRC) grade 3/5) more than the distal muscles (MRC grade 4/5). The patient's investigation panel revealed leukopenia, anemia, elevated liver enzymes, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as significant elevation in creatinine kinase. Further antibody testing revealed positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith, and anti-U1-ribonucleoprotein (U1RNP), along with electrodiagnostic study supporting the diagnosis of SLE complicated by myositis and vasculitis. Treatment was initiated with prednisolone, hydroxychloroquine, methotrexate, folic acid, and omeprazole with sunscreen. Over the next several months, the patient demonstrated significant clinical and laboratory improvement, regaining full muscle power, with her vasculitis rash also improving and steroid tapering initiated to avoid side effects. This case highlights the importance of recognizing myositis as a rare potential first presentation of SLE and the need for heightened clinical awareness as early diagnosis and treatment is vital for improving long-term outcomes. This case adds to the existing literature and provides a reference for future clinical encounters with such complex cases.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6.

Background: Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.(Arg408Cys) variant in the KBTBD13 gene, also called the Dutch founder variant. Objective: To provide a comprehensive clinical and functional characterisation of three patients to assess the pathogenicity of a newly identified variant in the KBTBD13 gene. Results: We present three cases (Patient 1: female, 76 years old; Patient 2: male, 63 years old; and his brother Patient 3: male, 61 years old) with a c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene. Patient 1 was also included previously in a histopathological study on NEM6. Symptoms of muscle weakness started in childhood and progressed to impaired functional abilities in adulthood. All three patients reported slowness of movements. On examination, they have mild axial, proximal and distal muscle weakness. None of the patients exhibited cardiac abnormalities. Spirometry in two patients showed a restrictive lung pattern. Muscle ultrasound showed symmetrically increased echogenicity indicating fatty replacement and fibrosis in a subset of muscles and histopathological analyses revealed nemaline rods and cores. Slower muscle relaxation kinetics with in vivo functional tests was observed. This was confirmed by in vitro functional tests showing impaired relaxation kinetics in isolated muscle fibres. We found a genealogic link between patient 1, and patient 2 and 3 nine generations earlier. Conclusions: The c.1222C > A p.(Arg408Ser) variant in the KBTBD13 gene is a likely pathogenic variant causing NEM6.

Utilization of condoliase therapy versus surgery for lumbar disc herniation and comparison of post-treatment motor improvement.

STUDY DESIGN: Double-center retrospective study. PURPOSE: Utilization trends in interventional treatment for lumbar disc herniation (LDH) have not yet been examined. Furthermore, limited information is currently available on motor recovery with condoliase therapy. Therefore, the present study investigated utilization trends in treatment for LDH and the effects of condoliase therapy on muscle weakness. METHODS: This retrospective, double-center study involved patients with leg pain caused by LDH who received interventional treatment between September 2017 and August 2022. LDH patients were divided into two groups: an operative treatment group and condoliase therapy group. The period between September 2017 and August 2022 was divided into 5 equal parts and changes in the percentage of intervention treatment were examined. Motor recovery was also assessed in the two groups. Patients receiving condoliase therapy were divided into two groups: an effective group and non-effective group. Sex, age, the body mass index, duration of symptoms, herniation level, neurological and radiographic findings, a visual analog scale for leg pain, and the Oswestry disability index were examined in the two groups. RESULTS: Subjects included 226 males and 115 females with a mean age of 49.2 years, mean BMI of 22.8, and mean duration of symptoms of 5.0 months. The utilization of condoliase therapy for LDH surpassed surgery in the third year after its introduction. In the fourth year, condoliase therapy became the main treatment for LDH. Lower limb muscle strength improved in 76 % of cases receiving condoliase therapy. CONCLUSIONS: Condoliase therapy has become an intermediate treatment before surgery in our institutions. Motor recovery in patients receiving condoliase therapy was not inferior to that after surgery; however, in cases with severe muscle weakness with manual muscle test ≤3, the improvement rate was approximately 60 %. These results will be useful for clinicians when providing informed consent and selecting condoliase therapy.

[Research status of lower limb exoskeleton rehabilitation robot].

Lower limb exoskeleton rehabilitation robots are used to improve or restore the walking and movement ability of people with lower limb movement disorders. However, the required functions for patients differ based on various diseases. For example, patients with weak muscle strength require power assistance, patients with spinal cord injuries require motion compensation, patients with gait abnormalities require gait correction, and patients with strokes require neural rehabilitation. To design a more targeted lower limb exoskeleton rehabilitation robot for different diseases, this article summarised and compared existing lower limb exoskeleton rehabilitation robots according to their main functions and the characteristics and rehabilitation needs of various lower limb movement disorders. The correlations between the functions of existing devices and diseases were summarised to provide certain references for the development of new lower limb exoskeleton rehabilitation robots.

What is the most appropriate handgrip strength testing protocol for sarcopenia screening in older adults with cognitive impairment?

BACKGROUND: Handgrip strength (HGS) testing is a highly recommended method for screening for sarcopenia in older adults. However, there is no consensus on the optimal protocol and number of trials for screening sarcopenia in older adults with cognitive impairment. OBJECTIVE: To investigate the use of the first trial (FT), the mean of three trials (MT), and the highest value (HT) from three trials of the HGS test to screen for sarcopenia in older adults with cognitive impairment. Additionally, to analyze the consistency, agreement, and measurement error in the diagnosis of muscle weakness. METHODS: 176 older adults with cognitive impairment were evaluated. The HGS test was repeated three times. Analyses were performed using the Friedman repeated measures test with Wilcoxon post-hoc, intraclass correlation coefficient (ICC), Standard Error of Measurement (SEM), Minimal Detectable Change (MDC95), and Kappa index tests. RESULTS: There was no significant difference between the first trial (FT) and the mean of three trials (MT) (d = 0.17 [95 % CI: -0.08, 0.42]), but both differed significantly from the highest value (HT) (p < 0.001). The ICC indicated a reliability of 0.97 (95 % CI: 0.95, 0.98) across all participants, while the kappa index demonstrated over 80 % agreement. The SEM for the first measure of HGS ranged from 0.59 to 2.12 kgf. The MDC95 ranged from 1.64 to 5.87 kgf. CONCLUSION: For HGS testing, there was excellent consistency between the FM and MT. All three testing methods demonstrated excellent agreement in diagnosing muscle weakness. The measurement errors confirm that FT can be reliably used to monitor changes during rehabilitation.

Skeletal and Non-skeletal Phenotypes in Children with Osteogenesis Imperfecta.

Although fractures are the defining characteristic of osteogenesis imperfecta (OI), the disorder affects many tissues. Here we discuss three facets of the OI phenotype, skeletal growth and development, skeletal muscle weakness and the dental and craniofacial characteristics. Short stature is almost universal in the more severe forms of OI and is probably caused by a combination of direct effects of the underlying genetic defect on growth plates and indirect effects of fractures, bone deformities and scoliosis. Recent studies have developed OI type-specific growth curves, which allow determining whether a given child with OI grows as expected for OI type. Impaired muscle function is an important OI-related phenotype in severe OI. Muscles may be directly affected in OI by collagen type I abnormalities in muscle connective tissue and in the muscle-tendon unit. Indirect effects like bone deformities and lack of physical activity may also contribute to low muscle mass and function. Dental and craniofacial abnormalities are also very common in severe OI and include abnormal tooth structure (dentinogenesis imperfecta), malocclusion, and deformities in the bones of the face and the skull. It is hoped that future treatment approaches will address these OI-related phenotypes.

Surgical Outcomes in Patients Exhibiting Muscular Weakness Postadolescence Due to Tight Filum Terminale.

INTRODUCTION: Tight filum terminale is a neurological condition marked by various symptoms, including muscle weakness. There is a notable lack of literature addressing muscle weakness, particularly in cases emerging during adolescence and beyond. The diagnosis is challenging due to a lack of radiological abnormalities, and the literature on its treatment, especially untethering, in adults is limited. This study aims to evaluate the effectiveness of untethering in improving muscle weakness and other symptoms in postadolescent patients diagnosed with tight filum terminale. METHODS: A retrospective analysis was conducted on seven postadolescent patients diagnosed with tight filum terminale and presenting muscle weakness who underwent untethering at our institution between January 2018 and August 2022. Patients were monitored for muscle strength improvement, lumbar and lower extremity pain, and bowel and bladder dysfunction (BBD) after untethering. RESULTS: Muscle weakness improved in all cases after untethering, with a mean duration of 9.1 weeks for the improvement. Patients unable to walk independently regained mobility in an average of 22.3 weeks. Lumbar and lower limb pain improved in all cases within an average of 8.1 weeks, while BBD improved in six of the seven cases within an average of 1.9 weeks. CONCLUSIONS: Our findings suggest that untethering is an effective surgical intervention for postadolescent patients diagnosed with tight filum terminale and presenting muscle weakness.

Cardiovascular disease risk factors and frailty syndrome in community-dwelling older adults: Results from the Amirkola Health and Aging Project Cohort Study.

BACKGROUND: Early diagnosis and control of risk factors affecting frailty syndrome (FS) in older adults may lead to changes in the health/disease process, prevention of disability and dependency in the older adults, and reduction of health care costs and mortality rates. The aim of this study was to determine the predictive role of CVD risk factors and FS in community-dwelling older adults of Amirkola city in Iran. METHODS: This descriptive-analytic cross-sectional study is part of the second phase of the Amirkola Health and Aging Project (AHAP) cohort study conducted since 2011 on all individuals ≥ 60 years in the city of Amirkola in northern Iran. Totally, 1000 older adults were included in the study and divided into three groups: frail (n = 299), pre-frail (n = 455), and non-frail (n = 246) older adults. In the present study, age ≥ 60 years, female sex, fasting blood sugar (FBS) ≥ 126 mg/dl, affected diabetes mellitus (DM), body mass index (BMI) ≥ 27 kg/m², waist circumference (WC) or abdominal obesity > 102 cm in men and > 88 cm in women, low-density lipoprotein (LDL) > 100 mg/dl, triglyceride > 150 mg/dl, cholesterol > 200 mg/dl, high-density lipoprotein (HDL) < 40 mg/dl and blood pressure (BP) > 90/140 mmHg, uric acid > 7 mg/dl and a positive smoking history were considered CVD risk factors. RESULTS: The results showed that with each centimeter increase in WC, the odds of frailty compared with non-frailty was 79% higher, and the odds of frailty compared with pre-frailty was 1.43 times higher in older adults. In addition, the prevalence of pre-frailty compared with non-frailty, pre-frailty, and non-frailty was 10.59 times, 6.08 times, and 73.83 times higher in older individuals > 84 years old, respectively. The results of the present study indicated that the prevalence of pre-frailty compared with non-frailty, frailty compared with pre-frailty, and frailty compared with non-frailty was 2.86 times, 3.01 times, and 14.83 times higher in older adults women, respectively. The comparison between frail and non-frail groups represented that in DM older adults, the prevalence of frailty compared with non-frailty was 1.84 times higher and that of frailty compared with pre-frailty was 98% higher. The older adults with an FBS ≥ 126 mg/dl were 53% more likely to become frail, and with each unit increase in uric acid, the odds of becoming frail increased 2.05 times compared with non-frail older adults, and pre-frail compared with non-frail increased 99%. CONCLUSION: The results demonstrated that CVD risk factors predictive of FS included central obesity, age > 84 years, female sex, DM, FBS ≥ 126, and uric acid > 7. This problem highlights the need for preventive strategies in the older adults who are simultaneously vulnerable to CVD and frailty.

Factors associated with handgrip strength across the life course: A systematic review.

BACKGROUND: Muscle strength is essential for healthy ageing. Handgrip strength (HGS) has been recommended by expert bodies as the preferred measure of muscle strength, in addition to being considered a strong predictor of overall health. Cross-sectional studies have shown several potential factors associated with HGS, but a systematic review of factors predicting HGS over time has not previously been conducted. The aim of this study is to systematically review the literature on the factors associated with adult HGS [at follow-up(s) or its rate of change] across the life course. METHODS: Searches were performed in MEDLINE via Ebsco, Embase and SPORTDiscus databases. Longitudinal studies assessing potential factors impacting adult HGS over time were included in the analyses. Based on previously established definitions of consistency of results, a semiquantitative analysis was conducted using the proportions of studies supporting correlations with HGS. RESULTS: A total of 117 articles were included in this review. Factors associated with HGS were grouped into 11 domains: demographic, socioeconomic, genetic, early life, body composition, health markers/biomarkers, health conditions, psychosocial, lifestyle, reproductive and environmental determinants. Overall, 103 factors were identified, of which 10 showed consistent associations with HGS over time (i.e., in at least four studies with ≥60% agreement in the direction of association). Factors associated with greater declines in HGS included increasing age, male sex, higher levels of inflammatory markers and the presence of cardiovascular diseases. Education level, medication use, and self-rated health were not associated with the rate of change in HGS. Increased birth weight was associated with a stronger HGS over time, whereas depressive symptoms were linked to a weaker HGS, and smoking habits showed null associations. CONCLUSIONS: Comparison between studies and estimation of effect sizes were limited due to the heterogeneity in methods. Although sex and age may be the main drivers of HGS decline, it is crucial to prioritize modifiable factors such as inflammation and cardiovascular diseases in health interventions to prevent greater losses. Interventions to improve birth weight and mental health are also likely to produce positive effects on muscle strength. Our results point to the complexity of processes involving muscle strength and suggest that the need to better understand the determinants of HGS remains.

Exploring neuronal mechanisms of osteosarcopenia in older adults.

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight-bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing-related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.

Case report: A novel mutation of the CAPN3 gene in a Chinese family with limb-girdle muscular dystrophy type 2A.

Limb-girdle muscular dystrophy type 2A (LGMD R1 Calpain 3-Related, LGMD2A/R1), an autosomal recessive disorder, is characterized by progressive muscle weakness with a prominent presentation in the proximal limb girdle muscles. LGMD2A/R1, which is caused by variants in calcium-activated neutral proteinase 3 (CAPN3), is the most common. The present study aimed at identifying the clinically significant variants in a Chinese family with LGMD2A/R1 and exploring the genotype-phenotype correlations. Clinical symptoms, laboratory findings, and physical examinations were obtained. Genomic DNA was extracted from the peripheral blood samples of this family. Whole-exome sequencing (WES) and Sanger sequencing were used to explore and validate the pathogenic genes. In this study, the proband and his sister, who had two identical mutations in the CAPN3 gene sequence, exhibited diverse clinical features, including disease onset and progression. The mutation c.2120 A>G (p. D707G) is pathogenic and has been reported in the Human Gene Mutation Database (HGMD) and the ClinVar database. c.1783-72 C>G may be a novel pathogenic mutation of LGMD2A/R1 based on the American College of Medical Genetics (ACMG) guidelines, which widens the gene variant pool in CAPN3 and improves diagnosis and genetic counseling.