Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic lowgrade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Fat Distribution and Differential Effects on Metabolic Liver Fat Infiltration in Young Mexicans in Reynosa, Mexico: A Collaborative Study across the U.S.-Mexico Border

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a descriptive term for NAFLD (Non-alcoholic) physiopathology associated with obesity. The age of onset linked to body fat distribution is poorly studied. Therefore, we aimed to assess the body fat effect on liver fat infiltration and stiffness (LSt) mediated by insulin resistance (IR). Methods: After obtaining informed consent, five hundred freshmen from two universities in Reynosa, Mexico (UMAN & UAT) were enrolled in the study. They completed a questionnaire focused on familial cardiometabolic risk and provided anthropometric measurements. In a subset of N=200, we obtained blood samples for biochemical measurements, body fat percentage (BF%) by bioimpedance, LSt (kPa), and fat infiltration (Continued Attenuation Parameter, CAP) by elastography. We used mediation analysis with structural equation models (Stata v16.1) to determine the relationship between BMI, BF%, and abdominal obesity with IR and liver stiffness and fat infiltration. The term “-\u3e” means ‘explain’ or ‘cause’. Results: We found that AO-\u3eIR (standardized values b=0.53, p=0.005), AO-\u3eCAP (b=0.69, pIR (b=0.23, p=0.007). BMI did not have an effect on CAP or IR. Also, BMI-\u3eLS (b=0.47, p=0.05) but AO-\u3eLS was absent. Finally, there was a bidirectional relationship between LS and IR [LS-\u3eIR (b=0.18, p=0.001), and IR-\u3eLS (b=0.27, p=0.001)]. Conclusion: Our findings suggest the adipose tissue measured as AO or BMI showed different phenotypic effects on liver fat infiltration or stiffness. Visceral fat had a direct effect on IR, meanwhile, subcutaneous adipose tissue was associated with liver stiffness. Our findings suggest that early age interventions should be focused on reducing visceral fat deposition

High prevalence of autoantibodies to RNA helicase A in Mexican patients with systemic lupus erythematosus

Introduction: Autoantibodies to RNA helicase A (RHA) were reported as a new serological marker of systemic lupus erythematosus (SLE) associated with early stage of the disease. Anti-RHA and other autoantibodies in Mexican SLE patients and their correlation with clinical and immunological features were examined.Methods: Autoantibodies in sera from 62 Mexican SLE patients were tested by immunoprecipitation of 35S-labeled K562 cell extract and enzyme-linked immunosorbent assay (anti-U1RNP/Sm, ribosomal P, ?2GPI, and dsDNA). Anti-RHA was screened based on the immunoprecipitation of the 140-kDa protein, the identity of which was verified by Western blot using rabbit anti-RHA serum. Clinical and immunological characteristics of anti-RHA-positive patients were analyzed.Results: Anti-RHA was detected in 23% (14/62) of patients, a prevalence higher than that of anti-Sm (13%, 8/62). Prevalence and levels of various autoantibodies were not clearly different between anti-RHA (+) vs. (-) cases, although there was a trend of higher levels of anti-RHA antibodies in patients without anti-U1RNP/Sm (P = 0.07). Both anti-RHA and -Sm were common in cases within one year of diagnosis; however, the prevalence and levels of anti-RHA in patients years after diagnosis did not reduce dramatically, unlike a previous report in American patients. This suggests that the high prevalence of anti-RHA in Mexican patients may be due to relatively stable production of anti-RHA.Conclusions: Anti-RHA was detected at high prevalence in Mexican SLE patients. Detection of anti-RHA in races in which anti-Sm is not common should be clinically useful. Racial difference in the clinical significance of anti-RHA should be clarified in future studies. � 2010 V�zques-Del Mercado et al; licensee BioMed Central Ltd

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

The Hypertriglyceridemic Waist Phenotype Is Associated with Several Cardiovascular Risk Factors in Women with Rheumatoid Arthritis

Rheumatoid arthritis (RA) associates with cardiovascular risk factors (CVRF) such as dyslipidemias and systemic inflammation. Cardiovascular Disease (CVD) is the leading cause of mortality. The hypertriglyceridemic waist phenotype (HTWP) identifies increased CVRF; however, information about HTWP on RA is scarce. Objective: To evaluate the association of HTWP with CVRF in RA. Material and methods: Cross-sectional study. Women (125) with RA were included (ACR, 1987). Anthropometry, bioimpedance, body mass index (BMI), disease activity score 28 (DAS28), and health assessment questionnaire disability index (HAQ-Di) were determined. The lipid profile determination includes the atherogenic index (AI) (TC/HDL) and Framingham Risk Score. HTWP is defined as a waist circumference ≥88 cm and triglycerides ≥ 150 mg/dL. Chi-squared and Student’s t-tests were applied for comparisons. Results: HTWP was found in 38 (30.4%) patients. The subgroup with HTWP had a greater frequency of arterial hypertension (AHT) (57.9 vs. 37.9, p = 0.04), Type 2 DM (23.7 vs. 8.0, p= 0.02), BMI (29.7 ± 3.2, vs. 26.8 ± 4.3, p < 0.001), fat mass (39.3 ± 4.8 vs. 34.7 ± 6.8, p < 0.001), and AI (4.7 ± 1.2 vs. 3.7 ± 1.0, p < 0.001). No differences between DAS28 and HAQ-Di were found. HTWP was associated with the presence of MetS and CVR (p < 0.001 and p = 0.012, respectively). Conclusion: The HTWP in RA is associated with CVRF, and its potential predictive role should be evaluated in longitudinal studies

The Hypertriglyceridemic Waist Phenotype Is Associated with Several Cardiovascular Risk Factors in Women with Rheumatoid Arthritis

Rheumatoid arthritis (RA) associates with cardiovascular risk factors (CVRF) such as dyslipidemias and systemic inflammation. Cardiovascular Disease (CVD) is the leading cause of mortality. The hypertriglyceridemic waist phenotype (HTWP) identifies increased CVRF; however, information about HTWP on RA is scarce. Objective: To evaluate the association of HTWP with CVRF in RA. Material and methods: Cross-sectional study. Women (125) with RA were included (ACR, 1987). Anthropometry, bioimpedance, body mass index (BMI), disease activity score 28 (DAS28), and health assessment questionnaire disability index (HAQ-Di) were determined. The lipid profile determination includes the atherogenic index (AI) (TC/HDL) and Framingham Risk Score. HTWP is defined as a waist circumference ≥88 cm and triglycerides ≥ 150 mg/dL. Chi-squared and Student’s t-tests were applied for comparisons. Results: HTWP was found in 38 (30.4%) patients. The subgroup with HTWP had a greater frequency of arterial hypertension (AHT) (57.9 vs. 37.9, p = 0.04), Type 2 DM (23.7 vs. 8.0, p= 0.02), BMI (29.7 ± 3.2, vs. 26.8 ± 4.3, p p p p p = 0.012, respectively). Conclusion: The HTWP in RA is associated with CVRF, and its potential predictive role should be evaluated in longitudinal studies