Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis

Instituto Mexicano del Seguro Social, Fondo de Investigacion en Salud, FIS/IMSS/PROT/MD16/1565Supplemental Digital Content is available in the text Myostatin is a cytokine produced and released by myocytes that might have an outstanding role not only in muscle wasting during cachexia but also in inflammation. Herein we explore the association between myostatin levels and inflammatory parameters in rheumatoid arthritis (RA). One hundred twenty-seven women without rheumatic diseases and 84 women with a diagnosis of RA were assessed in a cross-sectional study. Outcomes reflecting the activity of the arthritis including Disease Activity Score (DAS28-ESR) and impairment in functioning by the Health Assessment Questionnaire-Disability Index were assessed in RA. We obtained Skeletal muscle mass index (SMI), fat-free mass index (FFMI), and fat mass index using dual-energy x-ray absorptiometry. Serum myostatin was determined by enzyme-linked immunosorbent assay. Myostatin levels were correlated with disease activity and parameters of muscle mass. The SMI was lower and concentration of myostatin was higher in RA patients than in controls (P = .008 and P < .001, respectively). Myostatin significantly positively correlated with C-reactive protein (rho = 0.48, P < .001), erythrocyte sedimentation rate (rho = 0.28, P = .009), and DAS28-ESR (rho = 0.22, P = .04), and negatively correlated with SMI (rho = −0.29, P = .008), (FFMI) (rho = −0.24, P = .027). In the multivariate logistic regression analysis, levels of myostatin remained associated with disease activity in RA (P = .027). In our study, myostatin was associated with disease activity in RA patients, suggesting a mechanistic link between myostatin, muscle wasting and inflammation in RA

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients

Association Analysis Between -308G/A and -238G/A TNF-Alpha Gene Promoter Polymorphisms and Insulin Resistance in Mexican Women With Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM

Association of Depression, Anxiety, Stress and Stress-Coping Strategies with Somatization and Number of Diseases According to Sex in the Mexican General Population

Somatization and number of diseases are interrelated variables, whose association with stress-coping strategies, according to sex, has not been investigated. Therefore, the aim of this study was to investigate such association in a sample of the Mexican general population. The general population was invited to answer an electronic questionnaire via the social networks&mdash;e-mail, WhatsApp and Facebook&mdash;by the research team. A sample of 1008 adults was obtained, of which 62.2% were women, in whom we detected higher levels of negative psychological variables, somatization and number of diseases and lower levels of sleep quality. Positive moderate correlations were found between depresion, anxiety and stress with somatization, on one hand, and with the number of diseases, on the other, and negative moderate correlations were found between sleep quality and the two dependent variables. As for the coping strategies, self-blame, behavioral disengagement, denial, self-distraction and substance use were positively correlated with somatization. Of these, self-blame, substance use, and self-distraction also showed a positive correlation with number of diseases in both sexes. Negative correlations were detected for active coping and the two dependent variables in men and for religion and planning with somatization in women. In conclusion, the coping strategies showed significant correlations with somatization and number of diseases in both sexes

Steroid Resistance Associated with High MIF and P-gp Serum Levels in SLE Patients

Approximately 30% of patients with systemic lupus erythematosus (SLE) present steroid resistance (SR). Macrophage migration inhibition factor (MIF) and P-glycoprotein (P-gp) could be related to SR. This work aims to evaluate the relationship between MIF and P-pg serum levels in SR in SLE. Methods: Case&ndash;control study including 188 SLE patients who were divided into two groups (90 in the steroid-resistant group and 98 in the steroid-sensitive (SS) group) and 35 healthy controls. MIF and P-gp serum levels were determined by ELISA. Multivariable logistic regression and chi-squared automatic interaction detection (CHAID) were used to explore risk factors for SR. Results: The steroid-resistant group presented higher MIF and P-gp serum levels in comparison with the SS (p &lt; 0.001) and reference (p &lt; 0.001) groups. MIF correlated positively with P-gp (rho = 0.41, p &lt; 0.001). MIF (&ge;15.75 ng/mL) and P-gp (&ge;15.22 ng/mL) were a risk factor for SR (OR = 2.29, OR = 5.27). CHAID identified high P-gp as the main risk factor for SR and high MIF as the second risk factor in those patients with low P-gp. Conclusions: An association between MIF and P-gp serum levels was observed in SR. CHAID identified P-gp &ge; 15.22 ng/mL as the main risk factor for SR. More studies are needed to validate these results