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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 -
International Journal of Environmental... Jul 2022Background: This study aimed to analyze the prevalence of sarcopenia in elderly people from Northern Brazil according to muscle weakness or walking slowness. Methods:...
Background: This study aimed to analyze the prevalence of sarcopenia in elderly people from Northern Brazil according to muscle weakness or walking slowness. Methods: The sample consisted of 312 elderly people (72.6 ± 7.8 years). For walking slowness, a gait speed ≤ 0.8 m/s was used as a cut-off value, and for muscle weakness the following handgrip strength criteria were used for men and women, respectively: CI: <27.0/16.0 kg; CII: <35.5/20.0 kg; CIII: grip strength corrected for body mass index (BMI) < 1.05/0.79; CIV: grip strength corrected for total fat mass: <1.66/0.65; CV: grip strength corrected for body mass: <0.45/0.34. Results: Walking speed was reduced in 27.0% of women and 15.2% of men (p < 0.05). According to grip strength criteria, 28.5% of women and 30.4% of men (CI), 58.0% of women and 75.0% of men (CII), 66.0% of women and 39.3% of men (CIII), 28.8% of women and 19.6% of men (CIV), and 56.5% of women and 50.0% of men (CV) were identified as having sarcopenia. Conclusions: Walking slowness is more prevalent in women and muscle weakness is more prevalent in men in Northern Brazil. Walking slowness proved to be more concordant with muscle weakness in both sexes when the CI for handgrip strength was adopted.
Topics: Aged; Brazil; Cross-Sectional Studies; Female; Hand Strength; Humans; Male; Muscle Strength; Muscle Weakness; Paresis; Sarcopenia; Walking; Walking Speed
PubMed: 35954652
DOI: 10.3390/ijerph19159297 -
Journal of Cachexia, Sarcopenia and... Dec 2020
Review
Topics: Critical Illness; Female; Humans; Intensive Care Units; Male; Muscle Weakness; Muscles; Muscular Diseases; Polyneuropathies
PubMed: 32893974
DOI: 10.1002/jcsm.12620 -
Allergology International : Official... Apr 2023Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle...
BACKGROUND
Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma.
METHODS
We studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength.
RESULTS
Thirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes.
CONCLUSIONS
Cumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma.
Topics: Aged; Male; Humans; Female; Middle Aged; Frailty; Frail Elderly; Retrospective Studies; Geriatric Assessment; Muscle Weakness; Asthma; Adrenal Cortex Hormones
PubMed: 36371246
DOI: 10.1016/j.alit.2022.10.005 -
The Israel Medical Association Journal... Aug 2021Cervical spinal surgery is considered safe and effective. One of the few specific complications of this procedure is C5 nerve root palsy. Expressed primarily by deltoid...
BACKGROUND
Cervical spinal surgery is considered safe and effective. One of the few specific complications of this procedure is C5 nerve root palsy. Expressed primarily by deltoid muscle and biceps brachii weakness, it is rare and has been related to nerve root traction or to ischemic spinal cord damage.
OBJECTIVES
To determine the clinical and epidemiological traits of C5 palsy. To determine whether C5 palsy occurs predominantly in one specific surgical approach compared to others.
METHODS
A retrospective study of patients who underwent cervical spine surgery at our medical center during a consecutive 8-year period was conducted. The patient data were analyzed for demographics, diagnosis, and surgery type and approach, as well as for complications, with emphasis on the C5 nerve root palsy.
RESULTS
The study group was comprised of 124 patients. Seven (5.6%) developed a C5 palsy following surgery. Interventions were either by anterior, by posterior or by a combined approach. Seven patients developed this complication. All of whom had myelopathy and were older males. A combined anteroposterior (5 patients) and posterior access (2 patients) were the only approaches that were associated with the C5 palsy. None of the patients who were operated via an anterior approach did develop this sequel.
CONCLUSIONS
The incidence of the C5 root palsy in our cohort reached 5.6%. Interventions performed through a combined anterior-posterior access in older myelopathic males, may carry the highest risk for this complication.
Topics: Cervical Plexus; Cervical Vertebrae; Decompression, Surgical; Deltoid Muscle; Female; Humans; Intraoperative Complications; Israel; Male; Middle Aged; Muscle Weakness; Outcome and Process Assessment, Health Care; Paresis; Postoperative Complications; Retrospective Studies; Risk Assessment; Spinal Cord Ischemia
PubMed: 34392627
DOI: No ID Found -
Journal of Critical Care Dec 2021To explore the extent to which musculoskeletal (MSK) complications have been reported following critical illness, identifying evidence gaps and providing recommendations... (Review)
Review
PURPOSE
To explore the extent to which musculoskeletal (MSK) complications have been reported following critical illness, identifying evidence gaps and providing recommendations for future research.
MATERIALS AND METHODS
We searched five databases from January 1st 2000 to March 31st 2021. We included published original research reporting MSK complications in patients discharged from hospital following an admission to an intensive care unit (ICU). Two reviewers independently screened English language articles for eligibility. Data extracted included the MSK area of investigation and MSK outcome measures. The overall quality of study was evaluated against standardised reporting guidelines.
RESULTS
4512 titles were screened, and 32 met the inclusion criteria. Only one study included was interventional, with the majority being prospective cohort studies (n = 22). MSK complications identified included: muscle weakness or atrophy, chronic pain, neuromuscular dysfunction, peripheral joint impairment and fracture risk. The quality of the overall reporting in the studies was deemed adequate.
CONCLUSIONS
We identified a heterogenous body of literature reporting a high prevalence of a variety of MSK complications extending beyond muscle weakness, therefore future investigation should include evaluations of more than one MSK area. Further investigation of MSK complications could inform the development of future post critical illness rehabilitation programs.
Topics: Critical Illness; Hospitalization; Humans; Intensive Care Units; Muscle Weakness; Prospective Studies
PubMed: 34454181
DOI: 10.1016/j.jcrc.2021.08.002 -
Critical Care (London, England) Feb 2024Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute... (Review)
Review
Acute Respiratory Distress Syndrome (ARDS) is an important global health issue with high in-hospital mortality. Importantly, the impact of ARDS extends beyond the acute phase, with increased mortality and disability for months to years after hospitalization. These findings underscore the importance of extended follow-up to assess and address the Post-Intensive Care Syndrome (PICS), characterized by persistent impairments in physical, cognitive, and/or mental health status that impair quality of life over the long-term. Persistent muscle weakness is a common physical problem for ARDS survivors, affecting mobility and activities of daily living. Critical illness and related interventions, including prolonged bed rest and overuse of sedatives and neuromuscular blocking agents during mechanical ventilation, are important risk factors for ICU-acquired weakness. Deep sedation also increases the risk of delirium in the ICU, and long-term cognitive impairment. Corticosteroids also may be used during management of ARDS, particularly in the setting of COVID-19. Corticosteroids can be associated with myopathy and muscle weakness, as well as prolonged delirium that increases the risk of long-term cognitive impairment. The optimal duration and dosage of corticosteroids remain uncertain, and there's limited long-term data on their effects on muscle weakness and cognition in ARDS survivors. In addition to physical and cognitive issues, mental health challenges, such as depression, anxiety, and post-traumatic stress disorder, are common in ARDS survivors. Strategies to address these complications emphasize the need for consistent implementation of the evidence-based ABCDEF bundle, which includes daily management of analgesia in concert with early cessation of sedatives, avoidance of benzodiazepines, daily delirium monitoring and management, early mobilization, and incorporation of family at the bedside. In conclusion, ARDS is a complex global health challenge with consequences extending beyond the acute phase. Understanding the links between critical care management and long-term consequences is vital for developing effective therapeutic strategies and improving the quality of life for ARDS survivors.
Topics: Humans; Quality of Life; Activities of Daily Living; Hypnotics and Sedatives; Delirium; Muscle Weakness; Respiratory Distress Syndrome; Adrenal Cortex Hormones; Intensive Care Units
PubMed: 38395902
DOI: 10.1186/s13054-024-04810-9 -
Experimental Animals Jan 2020Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) contribute to spontaneous rhythmic activity in different tissues, including the heart and...
Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) contribute to spontaneous rhythmic activity in different tissues, including the heart and brain. Deficiency in HCN1 function is associated with sick sinus syndrome in mice and epilepsy in humans. We recently developed Hcn1-deficient rats and found that they exhibit absence epilepsy. While rearing Hcn1-deficient rats, we noticed loose muscle tension and abnormal gait. We therefore evaluated the muscle strength and motor functions of Hcn1-deficient rats. When subjected to the wire hang test, Hcn1-deficient rats fell down more easily than control F344 rats. Grip strength of Hcn1-deficient rats was significantly smaller than F344 rats. In the inclined plane test, they exhibited a smaller maximum angle. In the rotarod test, the latency to fall was shorter for Hcn1-deficient rats than F344 rats. In the footprint analysis, Hcn1-deficient rats exhibited smaller step length and wider step width than F344 rats. Instead of poor motor coordination ability and muscle weakness, Hcn1-deficient rats exhibited normal electromyograms, muscle histology, and deep tendon reflex. These findings suggest that HCN1 channels contribute to motor coordination and muscle strength, and that the muscle weakness of Hcn1-deficient rats results from the involvement not of the peripheral but of the central nervous system.
Topics: Animals; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Muscle Strength; Muscle Weakness; Potassium Channels; Psychomotor Performance; Rats
PubMed: 31292305
DOI: 10.1538/expanim.19-0067 -
International Journal of Molecular... Feb 2021Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most... (Review)
Review
Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most tissues and cells in the body, the mounting understanding of the role of vitamin D in humans indicates that it does not only play an important role in the musculoskeletal system, but has beneficial effects elsewhere as well. This review summarizes the metabolism of vitamin D, the research regarding the possible risk factors leading to vitamin D deficiency, and the relationships between vitamin D deficiency and numerous illnesses, including rickets, osteoporosis and osteomalacia, muscle weakness and falls, autoimmune disorders, infectious diseases, cardiovascular diseases (CVDs), cancers, and neurological disorders. The system-wide effects of vitamin D and the mechanisms of the diseases are also discussed. Although accumulating evidence supports associations of vitamin D deficiency with physical and mental disorders and beneficial effects of vitamin D with health maintenance and disease prevention, there continue to be controversies over the beneficial effects of vitamin D. Thus, more well-designed and statistically powered trials are required to enable the assessment of vitamin D's role in optimizing health and preventing disease.
Topics: Animals; Biological Availability; Humans; Models, Biological; Muscle Weakness; Musculoskeletal System; Vitamin D; Vitamin D Deficiency
PubMed: 33669918
DOI: 10.3390/ijms22042128 -
International Journal of Medical... 2020Burn injury induces long-term skeletal muscle pathology. We hypothesized EPO could attenuate burn-induced muscle fiber atrophy. Rats were allocated into four groups: a...
Burn injury induces long-term skeletal muscle pathology. We hypothesized EPO could attenuate burn-induced muscle fiber atrophy. Rats were allocated into four groups: a sham burn group, an untreated burn group subjected to third degree hind paw burn, and two burn groups treated with weekly or daily EPO for four weeks. Gastrocnemius muscle was analyzed at four weeks post-burn. EPO attenuated the reduction of mean myofiber cross-sectional area post-burn and the level of the protective effect was no significant difference between two EPO-treated groups (p=0.784). Furthermore, EPO decreased the expression of atrophy-related ubiquitin ligase, atrogin-1, which was up-regulated in response to burn. Compared to untreated burn rats, those receiving weekly or daily EPO groups had less cell apoptosis by TUNEL assay. EPO decreased the expression of cleaved caspase 3 (key factor in the caspase-dependent pathway) and apoptosis-inducing factor (implicated in the caspase-independent pathway) after burn. Furthermore, EPO alleviated connective tissue overproduction following burn via transforming growth factor beta 1-Smad2/3 pathway. Daily EPO group caused significant erythrocytosis compared with untreated burn group but not weekly EPO group. EPO therapy attenuated skeletal muscle apoptosis and fibrosis at four weeks post-burn. Weekly EPO may be a safe and effective option in muscle wasting post-burn.
Topics: Animals; Apoptosis; Burns; Caspase 3; Connective Tissue; Disease Models, Animal; Erythropoietin; Gene Expression Regulation; Humans; Muscle Proteins; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Rats; SKP Cullin F-Box Protein Ligases; Signal Transduction; Smad2 Protein; Transforming Growth Factor beta1
PubMed: 31929736
DOI: 10.7150/ijms.38590