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Journal of Cachexia, Sarcopenia and... Feb 2024Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed... (Meta-Analysis)
Meta-Analysis Review
Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed sarcopenia. The extent of skeletal muscle wasting in clinical and preclinical CKD populations is unclear. We evaluated skeletal muscle atrophy in preclinical and clinical models of CKD, with multiple sub-analyses for muscle mass assessment methods, CKD severity, sex and across the different preclinical models of CKD. We performed a systematic literature review of clinical and preclinical studies that measured muscle mass/size using the following databases: Ovid Medline, Embase and Scopus. A random effects meta-analysis was utilized to determine standard mean difference (SMD; Hedges' g) between healthy and CKD. Heterogeneity was evaluated using the I statistic. Preclinical study quality was assessed via the Systematic Review Centre for Laboratory Animal Experimentation and clinical studies quality was assessed via the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42020180737) prior to initiation of the search. A total of 111 studies were included in this analysis using the following subgroups: 106 studies in the primary CKD analysis, 18 studies that accounted for diabetes and 7 kidney transplant studies. Significant atrophy was demonstrated in 78% of the preclinical studies and 49% of the clinical studies. The random effects model demonstrated a medium overall SMD (SMD = 0.58, 95% CI = 0.52-0.64) when combining clinical and preclinical studies, a medium SMD for the clinical population (SMD = 0.48, 95% CI = 0.42-0.55; all stages) and a large SMD for preclinical CKD (SMD = 0.95, 95% CI = 0.76-1.14). Further sub-analyses were performed based upon assessment methods, disease status and animal model. Muscle atrophy was reported in 49% of the clinical studies, paired with small mean differences. Preclinical studies reported significant atrophy in 78% of studies, with large mean differences. Across multiple clinical sub-analyses such as severity of CKD, dialysis modality and diabetes, a medium mean difference was found. Sub-analyses in both clinical and preclinical studies found a large mean difference for males and medium for females suggesting sex-specific implications. Muscle atrophy differences varied based upon assessment method for clinical and preclinical studies. Limitations in study design prevented conclusions to be made about the extent of muscle loss with disease progression, or the impact of dialysis. Future work would benefit from the use of standardized measurement methods and consistent clinical staging to improve our understanding of atrophy changes in CKD progression, and analysis of biological sex differences.
Topics: Humans; Female; Male; Renal Insufficiency, Chronic; Muscular Atrophy; Renal Dialysis; Muscle, Skeletal; Diabetes Mellitus
PubMed: 38062879
DOI: 10.1002/jcsm.13400 -
Journal of Neuroimaging : Official... Nov 2018Spinal cord atrophy (SCA) is an important emerging outcome measure in multiple sclerosis (MS); however, there is limited consensus on the magnitude and rate of atrophy.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Spinal cord atrophy (SCA) is an important emerging outcome measure in multiple sclerosis (MS); however, there is limited consensus on the magnitude and rate of atrophy. The objective of this study was to synthesize the available data on measures of SCA in MS.
METHODS
Using published guidelines, relevant literature databases were searched between 1977 and 2017 for case-control or cohort studies reporting a quantitative measure of SCA in MS patients. Random-effects models pooled cross-sectional measures and longitudinal rates of SCA in MS and healthy controls (HCs). Student's t-test assessed differences between pooled measures in patient subgroups. Heterogeneity was assessed using DerSimonian and Laird's Q-test and the I -index.
RESULTS
A total of 1,465 studies were retrieved including 94 that met inclusion and exclusion criteria. Pooled estimates of mean cervical spinal cord (SC) cross-sectional area (CSA) in all MS patients, relapsing-remitting MS (RRMS), all progressive MS, secondary progressive MS (SPMS), primary-progressive MS (PPMS), and HC were: 73.07 mm (95% CI [71.52-74.62]), 78.88 mm (95% CI [76.92-80.85]), 69.72 mm (95% CI [67.96-71.48]), 68.55 mm (95% CI [65.43-71.66]), 70.98 mm (95% CI [68.78-73.19]), and 80.87 mm (95% C I [78.70-83.04]), respectively. Pooled SC-CSA was greater in HC versus MS (P < .001) and RRMS versus progressive MS (P < .001). SCA showed moderate correlations with global disability in cross-sectional studies (r-value with disability score range [-.75 to -.22]). In longitudinal studies, the pooled annual rate of SCA was 1.78%/year (95%CI [1.28-2.27]).
CONCLUSIONS
The SC is atrophied in MS. The magnitude of SCA is greater in progressive versus relapsing forms and correlates with clinical disability. The pooled estimate of annual rate of SCA is greater than reported rates of brain atrophy in MS. These results demonstrate that SCA is highly relevant as an imaging outcome in MS clinical trials.
Topics: Atrophy; Case-Control Studies; Disability Evaluation; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Spinal Cord
PubMed: 30102003
DOI: 10.1111/jon.12553 -
International Journal of Cardiology Nov 2016The widespread use of brain imaging has led to increased recognition of subclinical brain abnormalities, including white matter hyperintensities (WMH) and silent brain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The widespread use of brain imaging has led to increased recognition of subclinical brain abnormalities, including white matter hyperintensities (WMH) and silent brain infarctions (SBI), which have a vascular origin, and have been associated to a high risk of stroke, disability and dementia. Carotid atherosclerosis (CA) may be causative in the development of WMH, SBI and eventually brain atrophy. Aim of the present systematic review and meta-analysis was to assess the existing evidence linking CA to WMH, SBI and brain atrophy.
METHODS
The relation between CA and WMH, SBI and brain atrophy was investigated through the systematic search of online databases up to September 2015 and manual searching of references and related citations. Pooled estimates were calculated by random-effects model, using restricted maximum likelihood method with inverse variance weighting method.
RESULTS
Of the 3536 records identified, fifteen were included in the systematic review and 9 were found to be eligible for the meta-analysis. CA was significantly associated with the presence of WMH (Odds Ratio, OR 1.42, confidence interval, CI 1.22-1.66, p<0.0001) and of SBI (OR 1.89, CI 1.46-2.45, p<0.0001). No meta-analysis could be performed for the relation between CA and brain atrophy due to the lack of suitable studies.
CONCLUSIONS
CA was found to be associated to WMH and SBI. While no causative association can be inferred from the available data, the presence of carotid plaque may be considered a significant risk factor for subclinical cerebral damage.
Topics: Atrophy; Brain; Brain Infarction; Carotid Artery Diseases; Humans; Magnetic Resonance Imaging; Risk Factors
PubMed: 27568989
DOI: 10.1016/j.ijcard.2016.08.234 -
Ageing Research Reviews Nov 2023Living alone can cause social isolation and is correlated with multiple adverse health outcomes. Evidence about the association of living alone and social isolation with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Living alone can cause social isolation and is correlated with multiple adverse health outcomes. Evidence about the association of living alone and social isolation with sarcopenia is limited. This meta-analysis aims to investigate the correlation between living alone, social isolation, and sarcopenia.
METHODS
According to the PRISMA guidelines, we systematically searched Medline, Embase, Web of Science, and Scopus for literature published up to June 30, 2023. We conducted reference checking to supplement the references. Two investigators independently screened the references for eligibility and assessed the quality of the references. We included references involving data on living alone, social isolation, and sarcopenia. Two investigators recorded study data for meta-analysis and study characteristics.
RESULTS
Data regarding living alone and sarcopenia were available from 13 studies. Meta-analysis demonstrated that living alone is correlated with sarcopenia (odds ratio, 1.51; 95 % CI, 1.31-1.75; p < 0.001). The gender-stratified analysis demonstrated that women living alone are more likely to have sarcopenia (odds ratio, 1.81; 95 % CI, 1.32-2.48; p < 0.001) but not men (odds ratio, 1.24; 95 % CI, 0.56-2.74; p = 0.60). Data regarding social isolation and sarcopenia were available from five studies. Social isolation is also associated with sarcopenia (odds ratio, 1.70; 95 % CI, 1.51-1.92; p < 0.001). And subgroup analysis demonstrated that social isolation is a risk factor for sarcopenia (odds ratio, 1.79; 95 % CI, 1.55-2.06; p < 0.001).
CONCLUSIONS
This meta-analysis revealed the association of living alone and social isolation with sarcopenia. Gender differences can help to screen high-risk groups of sarcopenia and reduce healthcare expenditures. As a further development of living alone, social isolation may play a more important role in sarcopenia than living alone.
Topics: Humans; Female; Sarcopenia; Home Environment; Social Isolation; Risk Factors
PubMed: 37647996
DOI: 10.1016/j.arr.2023.102043 -
Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211 -
Journal of Cachexia, Sarcopenia and... Apr 2023Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions.... (Meta-Analysis)
Meta-Analysis Review
Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions. The aim of this systematic review and meta-analysis was to investigate the association of sarcopenia with polypharmacy and higher number of medications. A systematic literature search of observational studies using PubMed, Web of Science, Scopus and Cochrane Library databases was conducted from inception until June 2022. To determine if sarcopenia is associated with a higher risk of polypharmacy and increased number of medications, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42022337539). Twenty-nine studies were included in the systematic review and meta-analysis. Sarcopenia was associated with a higher prevalence of polypharmacy (odds ratio [OR]: 1.65, 95% confidence interval [CI] [1.23, 2.20], I = 84%, P < 0.01) and higher number of medications (mean difference: 1.39, 95% CI [0.59, 2.19], I = 95%, P < 0.01) compared with individuals without sarcopenia. Using meta-regression, a high variance was observed due to different populations (i.e., community-dwelling, nursing home residents, inpatients, outpatients) for both outcomes of polypharmacy (r = -0.338, SE = 0.1669, 95% CI [-0.67, -0.01], z = -2.03, P = 0.04) and number of medications (r = 0.589, SE = 0.2615, 95% CI [0.08, 1.10], z = 2.25, P = 0.02). This systematic review and meta-analysis reported a significantly increased risk of polypharmacy and higher number of medications in people with sarcopenia compared with individuals without this condition. Future research should clarify whether the specificity and number of medications is a direct contributor in accelerating the progression of muscle wasting and dysfunction contributing to sarcopenia in older adults.
Topics: Humans; Aged; Sarcopenia; Polypharmacy; Independent Living
PubMed: 36781175
DOI: 10.1002/jcsm.13190 -
Journal of Clinical Hypertension... Sep 2023This meta-analysis aimed to explore the potential relationship between senile sarcopenia and hypertension in older people. A comprehensive search was conducted in... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to explore the potential relationship between senile sarcopenia and hypertension in older people. A comprehensive search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library, up to November 2022. Ten studies comprising 14 804 participants were enrolled. The odds ratio (OR) and 95% confidence interval (CI) was pooled to evaluate the correlation between sarcopenia and hypertension in older people utilizing a random-effects model. Subgroup and sensitivity analyses were then carried out to explore the potential sources of heterogeneity. The results revealed a substantial correlation between sarcopenia and hypertension among older people (OR = 1.39, 95% CI: 1.15-1.67, p < .01). Further subgroup analysis revealed an association between sarcopenic obesity and hypertension (OR = 1.49, 95% CI: 1.37-1.62, p < .01). In conclusions, our findings highlighted a significant relationship between sarcopenia and hypertension among older people, with sarcopenic obesity amplifying this risk.
Topics: Humans; Aged; Sarcopenia; Hypertension; Obesity; Odds Ratio
PubMed: 37594142
DOI: 10.1111/jch.14714 -
Clinical Nutrition (Edinburgh, Scotland) May 2021Bioelectrical impedance analysis-derived phase angle (PhA) has been gaining attention in the clinical evaluation of nutritional status because it is thought to be a...
BACKGROUND & AIMS
Bioelectrical impedance analysis-derived phase angle (PhA) has been gaining attention in the clinical evaluation of nutritional status because it is thought to be a proxy of water distribution and body cell mass; it is also associated to muscle strength and is an effective predictor of different clinical outcomes. Since an association may be expected between PhA and sarcopenia (defined by low skeletal muscle mass and impaired muscle function), the aim of this systematic review was to evaluate: a) changes in PhA due to sarcopenia; b) prevalence of sarcopenia according to PhA values; c) derivation of phase angle cut-offs for detecting sarcopenia; d) sarcopenia and PhA as predictors of clinical outcomes.
METHODS
A systematic research on electronic databases (PubMed, Embase, Scopus and Web of Science) from inception to January 31st, 2020 was performed according to PRISMA checklist. Using PICOS strategy, "P" corresponded to participants of any age, gender or ethnicity, "I" designated diagnosis of sarcopenia, "C" indicated subjects without sarcopenia, "O" corresponded to PhA, and "S" selected all study types. Methodological quality was assessed using the National Institute of Health (NIH) quality assessment tool.
RESULTS
Through the initial literature search and after removing duplicates and excluding papers by screening titles and abstracts, 79 potentially relevant studies were examined. Thirteen studies (7668 subjects) met the inclusion criteria. The overall risk of bias was low. Sarcopenia was associated with a significant lower PhA in seven studies out of eight, while five studies out of six reported a high prevalence of sarcopenia was in patients with low PhA. Different cut-off point values from 4.05 to 5.05° have been derived for the identification of sarcopenia. PhA and sarcopenia were independent predictors of survival in cancer patients and geriatric hospitalized patients.
CONCLUSIONS
Data from the selected papers demonstrate that PhA is decreased in sarcopenic subjects and the prevalence of sarcopenia is higher in subjects with low PhA. Further studies are needed to determine to what extent PhA may be valuable in detecting low muscle quality and/or identifying sarcopenia.
Topics: Electric Impedance; Humans; Sarcopenia
PubMed: 33183880
DOI: 10.1016/j.clnu.2020.10.048 -
Clinical Breast Cancer Dec 2023Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing... (Meta-Analysis)
Meta-Analysis Review
Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Topics: Female; Humans; Breast Neoplasms; Cancer Survivors; Neoplasm Recurrence, Local; Vaginal Diseases; Vagina; Estradiol; Survivors; Testosterone; Estrogens; Atrophy; Estriol
PubMed: 37806915
DOI: 10.1016/j.clbc.2023.08.003 -
Nutrients Jan 2024Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several... (Review)
Review
Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several studies present contradictory results of treatment protocols and therapeutic effects. Therefore, the objective of this systematic review was to investigate the current literature showing the molecular mechanism and clinical protocol of epicatechin in muscle atrophy in humans, animals, and myoblast cell-line. The search was conducted in Embase, PubMed/MEDLINE, Cochrane Library, and Web of Science. The qualitative analysis demonstrated that there is a commonness of epicatechin inhibitory action in myostatin expression and atrogenes MAFbx, FOXO, and MuRF1. Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin). Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise. Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.
Topics: Animals; Humans; Catechin; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; MyoD Protein; TOR Serine-Threonine Kinases
PubMed: 38276564
DOI: 10.3390/nu16020326