Handgrip Strength to Predict the Risk of All-Cause and Premature Mortality in Korean Adults: A 10-Year Cohort Study

The prospective association of muscular weakness with the risk of all-cause and premature mortality in a general population remains unknown. The aim of this study was to investigate the prospective effects of handgrip strength and muscular weakness on risk for all-cause and premature mortality over 10 years using a large nationwide sample of Korean adults. The study participants included 9229 middle and older adults (4131 males and 5098 females), using data from the Korean Longitudinal Study of Ageing 2006–2016. Muscular strength was measured using handgrip strength. Muscle weakness was defined using the sex-specific handgrip strength index based on the Asian Working Group on Sarcopenia in Older People (AWGSOP). The primary outcome was all-cause and premature mortality assessed based on the death certificate. The hazard ratio (HR) for all-cause mortality was negatively associated with level of handgrip strength independent of potential confounding factors (HR: 2.06, 95% confidence interval [CI]: 1.62–2.63 for lowest quartile vs. highest quartile). When examined using muscle weakness defined using the AWGSOP diagnosis, the mortality was 1.56 times higher in the weak group (HR: 1.56, 95% CI: 1.36–1.78). We also found that risk of premature mortality was observed in the lowest quartile (HR: 2.34, 95% CI: 1.80–3.05) and the muscle weakness group (HR: 1.80, 95% CI: 1.52–2.13) in the fully adjusted model. Our 10-year prospective cohort study showed that handgrip strength and muscle weakness are strongly associated with an increased risk of all-cause and premature mortality in healthy middle-aged and older adults.

Non-compaction cardiomyopathy, Becker muscular dystrophy, neuropathy and recurrent syncope

We present the case of a 50-year-old man presenting with new heart failure symptoms. He had no evidence of any ischaemic cardiomyopathy, however, further cardiac imaging showed a left ventricular non-compaction cardiomyopathy. He was noted to have muscular weakness and an exhaustive search for associated comorbidities yielded a diagnosis of Becker muscular dystrophy. In this report, we review the pathophysiology, comorbidities and diagnostic workup in patients presenting with left ventricular non-compaction in the context of dystrophinopathy. Ultimately, we suggest the consideration of rare cardiomyopathies in all patients presenting with neuromuscular syndromes and vice versa.

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.

Handgrip strength to predict extubation outcome: a prospective multicenter trial

Background ICU-acquired weakness (ICUAW) has been shown to be associated with prolonged duration of mechanical ventilation and extubation failure. It is usually assessed through Medical Research Council (MRC) score, a time-consuming score performed by physiotherapists. Handgrip strength (HG) can be monitored very easily at the bedside. It has been shown to be a reproducible and reliable marker of global muscular strength in critical care patients. We sought to test if muscular weakness, as assessed by handgrip strength, was associated with extubation outcome. Methods Prospective multicenter trial over an 18 months period in six mixed ICUs. Adults receiving mechanical ventilation for at least 48 h were eligible. Just before weaning trial, HG, Maximal Inspiratory Pressure (MIP), Peak Cough Expiratory Flow (PCEF) and Medical Research Council (MRC) score were registered. The attending physicians were unaware of the tests results and weaning procedures were conducted according to guidelines. Occurrence of unscheduled reintubation, non-invasive ventilation (NIV) or high-flow nasal continuous oxygen (HFNC) because of respiratory failure within 7 days after extubation defined extubation failure. The main outcome was the link between HG and extubation outcome. Results 233 patients were included. Extubation failure occurred in 51 (22.5%) patients, 39 (17.2%) required reintubation. Handgrip strength was 12 [6–20] kg and 12 [8–20] kg, respectively, in extubation success and failure (p = 0.85). There was no association between extubation outcome and MRC score, MIP or PCEF. Handgrip strength was well correlated with MRC score (r = 0.718, p < 0.0001). ICU and hospital length of stay were significantly higher in the subset of patients harboring muscular weakness as defined by handgrip performed at the first weaning trial (respectively, 15 [10–25] days vs. 11 [7–17] days, p = 0.001 and 34 [19–66] days vs. 22 [15–43] days, p = 0.002). Conclusion No association was found between handgrip strength and extubation outcome. Whether this was explained by the appropriateness of the tool in this specific setting, or by the precise impact of ICUAW on extubation outcome deserves to be further evaluated. Trial registration Clinical Trials; NCT02946502, 10/27/2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=gripwean&cntry=&state=&city=&dist=

miRNome profiling in Duchenne Muscular Dystrophy; Identification of Asymptomatic and Manifesting Female Carriers

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder that occurs due to inactivating mutations in DMD gene, leading to muscular dystrophy. Prediction of pathological complications of DMD and the identification of female carriers are important research points that aim to reduce disease burden. Herein, we describe a case of a late DMD patient and his immediate female family members, who all carry same DMD mutation and exhibited varied degrees of symptoms. In our study, we sequenced the whole miRNome in leukocytes and plasma of the family members and results were validated using Real-Time PCR. Our results highlighted the role of miR-409-3p, miR-424-5p, miR-144-3p as microRNAs that show correlation with the extent of severity of muscular weakness and can be used for detection of asymptomatic carriers. Cellular and circulating levels of miR-494-3p had showed significant increase in symptomatic carriers, which may indicate significant roles played by this miRNA in the onset of muscular weakness. Interestingly, circulating levels of miR-206 and miR-410-3p were significantly increased only in the severely symptomatic carrier. In conclusion, our study highlighted several miRNA species, which could be used in predicting the onset of muscle and/or neurological complications in DMD carriers.

Updates in Diagnosis and Managements of Polymyositis: Simple Review

Idiopathic inflammatory myopathies (IIMs) includes an unusual group of acute, chronic, and subacute developed diseases of skeletal muscle characterized by moderate to severe muscle weakness and inflammation.Polymyositis is generally considered to be a prototypic T cell-mediated autoimmune myopathy, while DM was traditionally associated with a humoral-driven microangiopathy, though the putative autoantibodies and their targets have yet to be identified, and there is increasing evidence implicating the type I interferon pathway in the pathogenesis of the disease. Women between the ages of 50 and 70 are the most typically affected. Proximal muscular weakness is the most common clinical symptom. Inflammatory arthritis, Raynaud's phenomenon, myocarditis, and interstitial lung disease are all examples of extramuscular involvement. In this review, we overview updates in diagnosis and managements of polymyositis.

Myositis and myasteniform syndrome related to pembrolizumab

This case report concerns a 63-year-old man affected by metastatic undifferentiated liposarcoma. After receiving pembrolizumab as a second-line treatment in a clinical trial, the patient experienced an immune-mediated myocarditis, myositis and myasteniform syndrome. The last two adverse events showed significant clinical relevance in terms of severity, duration and the required specific treatment.Initial treatment approach consisted in pulses of 1 g of methylprednisolone, followed by 2 mg/kg/day, with clinical improvement. After 12 days, the immune-mediated myasteniform syndrome worsened, with dysphagia, dysphonia, bilateral palpebral ptosis and respiratory difficulty. Due to the refractoriness to glucocorticoid treatment, it was decided to initiate intravenous immunoglobulin at 2 g/kg, followed by 2 mg/kg every 4 weeks once discharged and mycophenolate 500 mg/12 hours, in order to reduce the dose of glucocorticoids.After 2 months, the patient presented an optimal clinical evolution, without muscular weakness and referred to an improvement in dysphagia and speech.

Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases

Background. This study deals with a rare (orphan) monogenic connective tissue disorder - Ehlers-Danlos syndrome kyphoscoliotic type 2 (EDSKS2). Kyphoscoliotic type 2 Ehlers-Danlos syndrome is an autosomal recessive disorder caused by mutations in the FKBP14 gene (7p14.3), which encodes the FKBP22 protein. According to the 2017 classification, this type is in group seven - collagen spatial structure and cross-linking defects. We present results of clinical examination and molecular genetic analysis for five patients with age varying from two to fifteen years. Methods. Five patients were examined using clinical and laboratory methods. DNA samples used for the analysis were extracted from whole blood samples using a Wizard® Genomic DNA Purification Kit (Promega, USA) according to the manufacturer's protocol. Results. The major clinical findings were kyphoscoliosis, early motor development delay, muscular weakness, hypotonia and hearing loss. Molecular genetic analysis detected a homozygous c.362dupC duplication in exon 3 of the FKBP14 gene in all five patients. This mutation is common in various countries. Differential diagnostics were carried out to exclude other Ehlers-Danlos syndrome types and myopathies. Conclusions. Literature analysis and examination of five EDSKS2 patients demonstrated the involvement of major organs and systems, such as joints, spine, muscles, cardiovascular system, respiratory system, hearing, and vision, into the pathological process. Kidney mobility increases and nephroptosis seems to be secondary caused by muscular weakness. During molecular genetic analysis, to verify EDSKS2 it is recommended to initially search for the c.362dupC duplication, which appears to be common in European countries, including Russia.