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Journal of Cachexia, Sarcopenia and... Feb 2022Muscle weakness is a frequently occurring complication of sepsis, associated with increased morbidity and mortality. Interestingly, obesity attenuates sepsis-induced...
BACKGROUND
Muscle weakness is a frequently occurring complication of sepsis, associated with increased morbidity and mortality. Interestingly, obesity attenuates sepsis-induced muscle wasting and weakness. As the adipokine leptin is strongly elevated in obesity and has been shown to affect muscle homeostasis in non-septic conditions, we aimed to investigate whether leptin mediates the protective effect of obesity on sepsis-induced muscle weakness.
METHODS
In a mouse model of sepsis, we investigated the effects of genetic leptin inactivation in obese mice (leptin-deficient obese mice vs. diet-induced obese mice) and of leptin supplementation in lean mice (n = 110). We assessed impact on survival, body weight and composition, markers of muscle wasting and weakness, inflammation, and lipid metabolism. In human lean and overweight/obese intensive care unit (ICU) patients, we assessed markers of protein catabolism (n = 1388) and serum leptin (n = 150).
RESULTS
Sepsis mortality was highest in leptin-deficient obese mice (53% vs. 23% in diet-induced obese mice and 37% in lean mice, P = 0.03). Irrespective of leptin, after 5 days of sepsis, lean mice lost double the amount of lean body mass than obese mice (P < 0.0005). Also, irrespective of leptin, obese mice maintained specific muscle force up to healthy levels (P = 0.3) whereas lean mice suffered from reduced specific muscle force (72% of healthy controls, P < 0.0002). As compared with lean septic mice, both obese septic groups had less muscle atrophy, liver amino acid catabolism, and inflammation with a 50% lower plasma TNFα increase (P < 0.005). Conversely, again mainly irrespective of leptin, obese mice lost double amount of fat mass than lean mice after 5 days of sepsis (P < 0.0001), showed signs of increased lipolysis and ketogenesis, and had higher plasma HDL and LDL lipoprotein concentrations (P ≤ 0.01 for all). Muscle fibre type composition was not altered during sepsis, but a higher atrophy sensitivity of type IIb fibres compared with IIa and IIx fibres was observed, independent of obesity or leptin. After 5 days of critical illness, serum leptin was higher (P < 0.0001) and the net waste of nitrogen (P = 0.006) and plasma urea-to-creatinine ratio (P < 0.0001) was lower in overweight/obese compared with lean ICU human patients.
CONCLUSIONS
Leptin did not mediate the protective effect of obesity against sepsis-induced muscle wasting and weakness in mice. Instead, obesity-independent of leptin-attenuated inflammation, protein catabolism, and dyslipidaemia, pathways that may play a role in the observed muscle protection.
Topics: Animals; Dyslipidemias; Humans; Leptin; Mice; Muscle Weakness; Obesity; Sepsis
PubMed: 34994068
DOI: 10.1002/jcsm.12904 -
Cancer May 2015Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with... (Review)
Review
Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with new-onset chronic health conditions and mortality among both older adults and childhood cancer survivors. Mounting evidence suggests that poor fitness, muscular weakness, and cognitive decline are common among adults treated for childhood malignancies, and that risk factors for these outcomes are not limited to those treated with cranial radiation. Although the pathobiology of this phenotype is not known, early cellular senescence, sterile inflammation, and mitochondrial dysfunction in response to initial cancer or treatment-related insults are hypothesized to play a role. To the authors' knowledge, interventions to prevent or remediate frailty among childhood cancer survivors have not been tested to date. Pharmaceutical, nutraceutical, and lifestyle interventions have demonstrated some promise.
Topics: Adult; Cellular Senescence; Child; Chronic Disease; Cognitive Dysfunction; Cranial Irradiation; Dietary Supplements; Exercise Tolerance; Hand Strength; Humans; Incidence; Inflammation; Mitochondria; Muscle Weakness; Neoplasms; Risk Factors; Risk Reduction Behavior; Survivors
PubMed: 25529481
DOI: 10.1002/cncr.29211 -
International Journal of Molecular... Oct 2020Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and... (Review)
Review
Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -β/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARβ/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut-muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting.
Topics: Animals; Energy Metabolism; Humans; Microbiota; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Peroxisome Proliferator-Activated Receptors; Signal Transduction
PubMed: 33137899
DOI: 10.3390/ijms21218056 -
Progress in Cardiovascular Diseases 2022Exercise limitation is a cardinal manifestation of many cardiovascular diseases (CVD) and is associated with poor prognosis. It is increasingly well understood that... (Review)
Review
Exercise limitation is a cardinal manifestation of many cardiovascular diseases (CVD) and is associated with poor prognosis. It is increasingly well understood that exercise-based cardiac rehabilitation (CR) is an intervention that portends favorable clinical outcomes, including improvements in exercise capacity. The etiology of exercise limitation in CVD is multifactorial but is typically governed by terminal sensations of pain, fatigue, and/or breathlessness. A known but perhaps underestimated complication of CVD that contributes to breathlessness and exercise intolerance in such patients is inspiratory muscle dysfunction. For example, inspiratory muscle dysfunction, which encompasses a loss in muscle mass and/or pressure generating capacity, occurs in up to ~40% of patients with chronic heart failure and is associated with breathlessness, exertional intolerance, and worse survival in this patient population. In this review, we define inspiratory muscle weakness, detail its prevalence in a range of CVDs, and discuss how inspiratory weakness impacts physiological function and clinical outcomes in patients with CVD often referred to CR. We also evaluate the available evidence addressing the effects of exercise-based CR with and without concurrent specific inspiratory muscle training (IMT) on inspiratory muscle function, general physiological function, and clinical outcomes in patients with CVD. Finally, we consider whether the assessment of global respiratory muscle function should become standard as part of the patient intake assessment for phase II CR programs, giving practical guidance on the implementation of such measures as well as IMT as part of phase II CR.
Topics: Cardiac Rehabilitation; Cardiovascular Diseases; Dyspnea; Exercise Tolerance; Humans; Muscle Strength; Muscle Weakness; Respiratory Muscles
PubMed: 34688670
DOI: 10.1016/j.pcad.2021.10.002 -
BMC Medicine May 2013Neuromuscular electrical stimulation (NMES) therapy may be useful in early musculoskeletal rehabilitation during acute critical illness. The objective of this systematic... (Review)
Review
BACKGROUND
Neuromuscular electrical stimulation (NMES) therapy may be useful in early musculoskeletal rehabilitation during acute critical illness. The objective of this systematic review was to evaluate the effectiveness of NMES for preventing skeletal-muscle weakness and wasting in critically ill patients, in comparison with usual care.
METHODS
We searched PubMed, CENTRAL, CINAHL, Web of Science, and PEDro to identify randomized controlled trials exploring the effect of NMES in critically ill patients, which had a well-defined NMES protocol, provided outcomes related to skeletal-muscle strength and/or mass, and for which full text was available. Two independent reviewers extracted data on muscle-related outcomes (strength and mass), and participant and intervention characteristics, and assessed the methodological quality of the studies. Owing to the lack of means and standard deviations (SDs) in some studies, as well as the lack of baseline measurements in two studies, it was impossible to conduct a full meta-analysis. When means and SDs were provided, the effect sizes of individual outcomes were calculated, and otherwise, a qualitative analysis was performed.
RESULTS
The search yielded 8 eligible studies involving 172 patients. The methodological quality of the studies was moderate to high. Five studies reported an increase in strength or better preservation of strength with NMES, with one study having a large effect size. Two studies found better preservation of muscle mass with NMES, with small to moderate effect sizes, while no significant benefits were found in two other studies.
CONCLUSIONS
NMES added to usual care proved to be more effective than usual care alone for preventing skeletal-muscle weakness in critically ill patients. However, there is inconclusive evidence for its benefit in prevention of muscle wasting.
Topics: Critical Illness; Electric Stimulation Therapy; Humans; Muscle Strength; Muscle Weakness; Neuromuscular Junction; Randomized Controlled Trials as Topic
PubMed: 23701811
DOI: 10.1186/1741-7015-11-137 -
Nutricion Hospitalaria Jul 2019Polyneuropathy in the critically ill patient was defined as a generalized weakness, acquired during Intensive Care Unit (ICU) admittance and attributed to lesion of the... (Review)
Review
Polyneuropathy in the critically ill patient was defined as a generalized weakness, acquired during Intensive Care Unit (ICU) admittance and attributed to lesion of the peripheral nerve. Research in this field progressed over time, revealing the crucial role of muscle injury in this disease, to the point of re-naming the disorder as ICU adquired weakness (ICUAW). Muscle damage is common in severe illness, and may be classified in qualitative (weakness) or quantitative (decrease in mass) muscle loss. The most frequent scenario in these patients, is simultaneous change in quality and quantity of muscle; resulting in a challenging and delayed recovery during hospital admittance and after discharge. Multiple causes have been identified in the pathogenesis of this disorder, such as: prolonged bed rest, inadequate intake of nutrients and exposure to drugs that affect muscle structure and contraction. The assessment of muscle mass using images provided by ultrasound or computerized tomography may guide follow up. The prevention and treatment of ICUAW requires a multimodal approach: early mobilization and exercise, appropriate nutritional prescription and, occasionally, muscle protein synthesis stimulants. Further studies will clarify more aspects regarding critically ill patients suffering from muscle injury, in order to better address prevention and treatment of ICUAW.
Topics: Critical Care; Critical Illness; Muscle Strength; Muscle Weakness; Muscle, Skeletal; Polyneuropathies
PubMed: 31189318
DOI: 10.20960/nh.02676 -
Clinical Medicine (London, England) Jul 2022
Topics: Autoantibodies; Humans; Muscle Weakness
PubMed: 36220211
DOI: 10.7861/clinmed.22-4-s35 -
Iranian Journal of Kidney Diseases May 2015Chronic hypernatremia due to adipsia is very rare and occasionally presents with muscle weakness and rhabdomyolysis. We report a patient with chronic hypernatremia...
Chronic hypernatremia due to adipsia is very rare and occasionally presents with muscle weakness and rhabdomyolysis. We report a patient with chronic hypernatremia without thirst sensation who presented with muscle weakness and was treated successfully with prescribed water intake.
Topics: Aged; Diagnosis, Differential; Drinking; Fluid Therapy; Humans; Hypernatremia; Male; Muscle Weakness; Rhabdomyolysis; Thirst; Treatment Outcome
PubMed: 25957431
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Apr 2023Intensive care unit-acquired weakness (ICUAW) is one of the most common causes of muscle atrophy and functional disability in critically ill intensive care patients.... (Review)
Review
Intensive care unit-acquired weakness (ICUAW) is one of the most common causes of muscle atrophy and functional disability in critically ill intensive care patients. Clinical examination, manual muscle strength testing and monitoring are frequently hampered by sedation, delirium and cognitive impairment. Many different attempts have been made to evaluate alternative compliance-independent methods, such as muscle biopsies, nerve conduction studies, electromyography and serum biomarkers. However, they are invasive, time-consuming and often require special expertise to perform, making them vastly impractical for daily intensive care medicine. Ultrasound is a broadly accepted, non-invasive, bedside-accessible diagnostic tool and well established in various clinical applications. Hereby, neuromuscular ultrasound (NMUS), in particular, has been proven to be of significant diagnostic value in many different neuromuscular diseases. In ICUAW, NMUS has been shown to detect and monitor alterations of muscles and nerves, and might help to predict patient outcome. This narrative review is focused on the recent scientific literature investigating NMUS in ICUAW and highlights the current state and future opportunities of this promising diagnostic tool.
Topics: Humans; Muscle Weakness; Intensive Care Units; Critical Care; Neuromuscular Diseases; Electromyography; Frailty
PubMed: 37241077
DOI: 10.3390/medicina59050844 -
Pain Physician May 2021Herpes zoster is an acute infectious skin disease that is induced by the re-activation of the virus incubated in nerve ganglions following initial infection with... (Review)
Review
BACKGROUND
Herpes zoster is an acute infectious skin disease that is induced by the re-activation of the virus incubated in nerve ganglions following initial infection with varicella-zoster virus in childhood. Herpes zoster mainly affects sensory nerves, resulting in severe acute pain, which is also the most common reason for medical intervention in this patient group. The concurrent involvement of motor nerves could induce the symptoms of segmental zoster paresis, which is manifested by localized asymmetric myasthenia, whose range generally follows the distribution of myomere with skin rashes. Due to the low incidence and unspecific clinical manifestations, segmental zoster paresis has not been sufficiently recognized by clinicians, and can easily be misdiagnosed.
OBJECTIVE
To summarize the previous studies on segmental zoster paresis and analyze the pathogeneses, diagnosis, and treatment of this disease, as well as stress the challenges in current treatment, which could provide useful evidence for the clinical diagnosis and better the treatment of patients with segmental zoster paresis in the future.
STUDY DESIGN
We conducted a narrative review.
SETTING
Hospitals, neurology departments, pain departments, and private practices.
METHODS
We searched PubMed and Chinese CNKI libraries using the terms "herpes zoster," "muscle paresis," "segmental zoster paresis," and "motor nerve." Clinical trials, reviews, and case reports were collected and reviewed.
RESULTS
As a rare complication following varicella-zoster virus infection, segmental zoster paresis has not been sufficiently recognized by clinicians, and there are still no guidelines available to guide the clinical treatments. The exact mechanism of segmental zoster paresis is still unclear. Electromyographic and magnetic resonance imaging examinations could be used as auxiliary diagnostic methods for segmental zoster paresis. Early regular anti-viral therapy could substantially decrease the risk of herpes zoster related complications. Combined application of glucocorticoids and some other physical therapy may also be useful in certain patients. The general prognosis of segmental zoster paresis is relatively good, with 67% patients achieving complete or almost complete recovery of the muscle function.
LIMITATIONS
More clinical trials are needed to clarify the exact mechanisms and best treating methods.
CONCLUSION
As the symptom in most segmental zoster paresis patients is self-limited, and the patients' prognosis is generally good, early diagnosis of the disease is especially important, due to the avoidance of unnecessary diagnostic procedures and incorrect treatments. Standard treatment guidelines regarding the functional rehabilitation are still needed for patients with refractory segmental zoster paresis.
Topics: Herpes Zoster; Humans; Magnetic Resonance Imaging; Muscle Weakness; Paresis; Skin
PubMed: 33988945
DOI: No ID Found