scholarly journals Comprehensive Multi-cohort Transcriptional Meta-analysis of Muscle Diseases Identifies a Signature of Disease Severity

2022 ◽  
Author(s):  
Christopher James Walsh ◽  
Jane Batt ◽  
Margaret Herridge ◽  
Sunita Mathur ◽  
Gary D Bader ◽  
...  
Keyword(s):  
Disease Severity ◽  
Meta Analysis ◽  
Disease Patient ◽  
Gene Signature ◽  
Muscle Disease ◽  
Additional Patient ◽  
Shoulder Abduction ◽  
P Value ◽  
Muscle Diseases ◽  
Muscle Biopsies

Abstract Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: i) Immobility, ii) inflammatory myopathies, iii) ICU acquired weakness (ICUAW), iv) congenital muscle diseases, v) chronic systemic diseases, vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a “leave-one-disease-out” analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r =-0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r=-0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r=0.88, p-value=1.62x10−3) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 x 10−9). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.

scholarly journals N-CAM expression: The study of muscle disease in a tertiary center of Thailand

2020 ◽  
Author(s):  
Kanyarat Laoyoung ◽  
Phu Waisayarat ◽  
Charungthai Dejthevaporn ◽  
Chaiyos Khongkhatithum ◽  
Jariya Waisayarat
Keyword(s):  
Muscular Dystrophy ◽  
Mitochondrial Myopathy ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
P Value ◽  
Thai Population ◽  
Muscle Diseases ◽  
Tertiary Center ◽  
Chi Squared ◽  
The Mean

Abstract Objectives To evaluate the correlation between N-CAM expression and diagnosis of common muscle diseases in the Thai population.Methods The expression of N-CAM was interpreted in 75 muscle biopsy specimens diagnosed with myopathies in a 3-year retrospective study. We used anti-CD56 (MRQ-42) rabbit monoclonal primary antibody (1:200, Cell Marque, MilliporeSigma, Rocklin, CA, USA) in our immunohistochemical study.Results Of our 75 patients, 41 cases were female and 34 were male. The mean age of the patients was 35-year-old, with the range from 3 months to 83 years. 35 (46.67%) of the specimens were N-CAM-positive, and 40 (53.33%) were N-CAM-negative. There were 35 (46.67%) cases diagnosed with nonspecific myopathy, 17 (22.67%) with inflammatory myopathy, 9 (12.00%) with neurogenic dystrophy, 7 (9.33%) with muscular dystrophy, 5 (6.67%) with non-diagnostic myopathy, and 2 (2.67%) with mitochondrial myopathy. Chi-squared testing was used to analyze the N-CAM expression data and the diagnosis. There is a statistically significant correlation between inflammatory myopathy and N-CAM positivity (p-value <0.001, OR 14.250, 95% CI 2.960-68.606), with 15 out of 17 cases being N-CAM-positive. N-CAM was also positive in muscular dystrophy, neurogenic myopathy, and nonspecific myopathy but they were not statistically significant. We did not find N-CAM expression in our 2 mitochondrial myopathy cases, nor in the 5 non-diagnostic myopathy cases.Conclusion N-CAM expression can be a complementary tool for diagnostic evaluation in muscle diseases with regeneration or denervation of muscle fibers. We recommend further study in a larger group.

Z-line degradation and phagocytosis of sarcomeric fragments in myonecrosis

1983 ◽  
Vol 41 ◽  
pp. 790-791
Author(s):  
Melinda L. Estes ◽  
Samuel M. Chou
Keyword(s):  
Vastus Lateralis ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
White Female ◽  
Inflammatory Cell Infiltrate ◽  
Limb Weakness ◽  
Muscle Diseases ◽  
History Of ◽  
The Right ◽  
Mononuclear Inflammatory Cell

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.

SERUM PROLACTINE LEVEL IN PATIENTS OF PSORIASIS VULGARIS AND ITS CORRELATION WITH DISEASE SEVERITY: A CASE-CONTROL STUDY

2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Pawan Kumar Saini ◽  
Devendra Yadav ◽  
Rozy Badyal ◽  
Suresh Jain ◽  
Arti Singh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Prolactin Level ◽  
Case Control Study ◽  
Statistical Significance ◽  
Case Control ◽  
Serum Prolactin ◽  
P Value ◽  
Serum Prolactin Level ◽  
R Value ◽  
Control Study

Background: Psoriasis is an autoimmune chronic inflammatory disorder affecting the skin mediated by T-lymphocytes resulting in production of cytokines which cause hyperproliferation of keratinocytes.  Several factors and hormones like Prolactin have an action similar to these cytokines in promoting the multiplication of keratinocytes and other cells like lymphocytes and epithelial cells may have a role on the etiopathogenesis of psoriasis. Aim:-The aim of study is to compare the serum Prolactin levels in patients of psoriasis with a control group. Setting and study design: This is a case-control study conducted in the department of Dermatology, Venereology and Leprosy GMC, Kota over a period of 1year from July 2017 to June 2018 Material and method: The study included 100 cases of psoriasis (60 males and 40 females) and 100 controls similar for age and sex. Serum Prolactin levels were measured by ECLIA and results were obtained. Statistical analysis: Mean and standard deviation were calculated for each variable. Statistical significance of the results was analyzed using correlation analysis (Pearson correlation coefficient) and independent samples t-test. Statistical significance was assumed at p value<0.05. Result: Serum Prolactin level was significantly higher in cases of psoriasis compared to controls (p-value <0.001). PASI score and serum Prolactin levels were found to have a positive correlation (r value = 0.337; p-value: 0.001). No significant  correlation was found between serum levels of Prolactin and duration of disease r value= -0.034, P value =0.733). Serum Prolactin level was higher in male patients compared to females patients. Conclusion:- High serum Prolactin may be a biological marker of disease severity in psoriasis and may have a role in the pathogenesis of psoriasis. Further studies with large sample size are required to confirm this hypothesis.

D-Dimer, Disease Severity, and Deaths (3D-Study) in Patients with COVID-19: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Seshadri Reddy Varikasuvu ◽  
Naveen Dutt ◽  
Saurabh Varshney ◽  
Shahir Asfahan ◽  
Paresh P. Kulkarni ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Meta Analysis ◽  
D Dimer

scholarly journals Zumba®, Fat Mass and Maximum Oxygen Consumption: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 18 (1) ◽  
pp. 105
Author(s):  
Manuel Chavarrias ◽  
Santos Villafaina ◽  
Ana Myriam Lavín-Pérez ◽  
Jorge Carlos-Vivas ◽  
Eugenio Merellano-Navarro ◽  
...  
Keyword(s):  
Systematic Review ◽  
Oxygen Consumption ◽  
Body Mass ◽  
Fat Mass ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
P Value ◽  
Maximum Oxygen Consumption ◽  
Mass Percentage ◽  
Large Heterogeneity

Background and objectives: Obesity or overweight is associated with many health risk factors and preventable mortality. Even people with normal weight and without history of obesity or overweight should avoid weight gain to reduce health risks factors. In this regard Latin aerobic dances involved in Zumba® practice make this modality motivating for people. Apart from weight loss and VO2peak benefits, Zumba practice is also interesting by the increase in adherence which can also avoid weight regain. The aim was to systematically review the scientific literature about the effects of any randomized intervention of Zumba® practice on total fat mass (%) and maximum oxygen consumption (VO2peak), besides establishing directions for the clinical practice. Evidence acquisition: Two systematic searches were conducted in two electronic databases following the PRISMA guidelines. The eligibility criteria were (a) outcomes: body mass or VO2peak data including mean and standard deviation (SD) before and after Zumba® intervention, (b) study design: randomized controlled trial (RCT) and (c) language: English. GRADE guidelines were used to assess the quality of evidence. A meta-analysis was performed to determine mean differences. Nine and four studies were selected for fat mass percentage and VO2peak in the systematic review, respectively. However, only eight studies for fat mass percentage and three for VO2peak could be included in the meta-analysis. Evidence synthesis: The overall standardized mean difference for fat mass was −0.25 with a 95% CI from −0.67 to 0.16 with a p-value of 0.69, with large heterogeneity. On the other hand, the overall effect size for VO2peak was 0.53 (95% CI from 0.04 to 1.02 with a p-value of 0.03) with large heterogeneity. Conclusions: Based on the evidence, we cannot conclude that Zumba® is effective at reducing body mass but it may improve VO2peak. However, the limited number of studies that met the inclusion criteria makes it too early to reach a definite conclusion, so more research is needed.

scholarly journals The Effects of Sterilization Procedures on the Cutting Efficiency of Endodontic Instruments: A Systematic Review and Network Meta-Analysis

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1559
Author(s):  
Mario Dioguardi ◽  
Enrica Laneve ◽  
Michele Di Cosola ◽  
Angela Pia Cazzolla ◽  
Diego Sovereto ◽  
...  
Keyword(s):  
Systematic Review ◽  
Selection Process ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Physical And Mechanical Properties ◽  
Surface Characteristics ◽  
Cyclic Fatigue ◽  
P Value ◽  
Cutting Efficiency ◽  
Dental Instruments

Sterilization processes guarantee the sterility of dental instruments but can negatively affect instrument features by altering their physical and mechanical properties. The endodontic instrumentation can undergo a series of alterations, ranging from corrosion to variation in the cutting angle and then changes in the torsional properties and torsional fatigue resistance. This systematic literature review and meta-analysis aims to investigate alterations to the cutting efficiency of endodontic instruments that are induced by procedures for their disinfection and sterilization. Methodologies adopted for this investigation follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The following were used as search terms on PubMed and Scopus: “endodontic sterilization”, “endodontic autoclave”, “cyclic fatigue”, “torsional”, “cutting efficiency”, “sterilization”, “surface characteristics”, and “corrosion”. At the end of the selection process, 36 articles were identified, and seven of them are included in this systematic review. The results of a meta-analysis conducted for the use of 10 autoclaving cycles shows a standardized mean difference (SMD) of 0.80 with a p-value equal to 0.04 with respect to effect on cutting efficiency. The network meta-analysis, through direct and indirect comparison between the different autoclave cycles (0, 1, 5, 10, and 15 cycles), revealed that treatment involving 15 autoclave cycles produced the most robust results in terms of having the greatest effects in terms of altered cutting efficiency with a probability of 57.7% and a SUCRA (surface under the cumulative ranking) of 80%. The alterations in the effects on cutting efficiency appear to be triggered after five cycles of sterilization by heat (autoclave). In conclusion, the meta-analysis of the data indicates that the autoclave sterilization protocol must not be repeated more than five times to preserve cutting efficiency. Within the limitations of this review, we can therefore establish that sterilization by autoclaving alone results in steel and NiTi instruments becoming less efficient in cutting after five cycles, as measured by a reduction in cutting efficiency.

scholarly journals Clinical Stratification of Pregnant COVID-19 Patients based on Severity: A Single Academic Center Experience

2021 ◽  
Vol 38 (05) ◽  
pp. 515-522
Author(s):  
Marissa Berry ◽  
Amanda Wang ◽  
Shannon M. Clark ◽  
Hassan M. Harirah ◽  
Sangeeta Jain ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Disease Severity ◽  
Gestational Age ◽  
Laboratory Data ◽  
Population Characteristics ◽  
Neonatal Outcomes ◽  
P Value ◽  
Asymptomatic Patients ◽  
Increased Risk ◽  
Maternal And Neonatal Outcomes

Objective This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes. Study Design This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p-value <0.05 was considered statistically significant. Results Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19. Conclusion Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy. Key Points

scholarly journals Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis

2021 ◽  
Author(s):  
Panagiotis Paliogiannis ◽  
Arduino Aleksander Mangoni ◽  
Michela Cangemi ◽  
Alessandro Giuseppe Fois ◽  
Ciriaco Carru ◽  
...  
Keyword(s):  
Systematic Review ◽  
Serum Albumin ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Geographic Area ◽  
Adverse Outcomes ◽  
Poor Outcome ◽  
Standard Mean Difference ◽  
Meta Regression Analysis

AbstractCoronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t =  − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t =  − 2.77, p = 0.008) and C-reactive protein (t =  − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

scholarly journals AB0156 NMR-BASED MUSCLE METABOLOMICS IN INFLAMMATORY MYOSITIS- UNDERSTANDING CHANGES IN SERUM AS A REFLECTION OF THE MUSCLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1378.2-1379
Author(s):  
L. Gupta ◽  
U. Kumar ◽  
A. Anuja ◽  
P. Sharma ◽  
A. Guleria ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Muscle Disease ◽  
P Value ◽  
Healthy Controls ◽  
Inflammatory Myositis ◽  
Activity Assessment ◽  
Muscle Tissues ◽  
Low Levels ◽  
Serum Metabolomics ◽  
Research Grant

Background:We have previously found promise in NMR as a tool to distinguish sera of active from inactive inflammatory myositis (IIM)1. To understand the changes previously found in sera and urine we studied muscle tissue of patients with myositis.Objectives:To identify differences in metabolome on inflamed muscle tissues of patients with active myositis from that of healthy controls and infectious polymyositis.Methods:Muscle (n=17) from patients classifiable as myositis by the ACR-EULAR criteria [34 years (23.5 - 50.5 IQR), M/F 1:3] were compared with healthy controls [n=11, age= 44 (35-50) years, M/F-1:1]. Two disease controls with infectious polymyositis were also compared. Findings were applied to muscle biopsy tissues of two patients with established myositis and superadded infections (HBV, Histoplasmosis) to assess discriminatory potential.Metabolic profiles were obtained at 800 MHZ NMR spectrometer and compared using multivariate partial least-squares discriminant analysis (PLS-DA). The discriminatory metabolites were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p-value <0.05). Paired T tests, ANNOVA and correlation of individual metabolites were done after normalizing for formate.Results:Metabolomics profiles in IIM were distinct from healthy controls (Fig. 1A).Of the various discriminatory metabolites (Fig. 1B), Succinate had the highest discriminatory potential (AUC 0.8, P=0.01) followed by citrate, glycine, glycerol, glucose, creatine and lactate. (Fig. 1C) Both glucose and creatine were decreased in IIM (Fig. 1D,E) and this was uniform across all types of IIM. However, glycine levels differed across different myositis subsets supporting the fact that they might differ in pathogenesis. (Fig. 1E) Amongst various serum biomarkers of muscle disease and damage, serum Aspartate Transaminase correlated with glutamate (r=0.6, p=0.01), and serum creatinine correlated negatively with glycerol (r-0.8, p=0.04),Biopsies of infectious polymyositis suggested difference in spectra from IIM (Fig. 2A). Trends were observed towards lower succinate and higher citrate levels suggesting metabolomics could possibly be useful to differentiate the two. Muscle of both patients with IIM with superadded infectious polymyositis also exhibited low succinate and elevated citrate.Conclusion:Muscle metabolomics of active myositis is distinctive. Amino acids and creatine are lower in diseases muscle suggesting active breakdown and loss, in turn explaining previous findings of low levels in serum in active disease. Certain metabolite composition differ in different types of myositis supporting different pathogenesis.Infectious polymyositis might exhibit different metabolome from IIM with potential as a biomarker though this needs to be confirmed in larger numbers.Disclosures:Funded by APLAR research grant 2017 awarded to Dr Latika Gupta.References:[1]Gupta L, Kumar D, Gulerai A, Kumar U, Misra R. “NMR-Based Serum, Urine and Muscle Metabolomics in Inflammatory Myositis for Diagnosis and Activity Assessment: Serum Metabolomics Can Differentiate Active from Inactive Myositis” Oral presentation at the ACR, Atlanta 2019.Acknowledgments:MSA and metabolomics supported by APLAR research grant.Disclosure of Interests:None declared

Sign in / Sign up

Export Citation Format

Share Document