Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology.

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN's multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

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.

Phase Angle and Nutritional Status: The Impact on Survival and Health-Related Quality of Life in Locally Advanced Uterine Cervical Cancer.

The phase angle, an indicator of muscle mass status and membrane cell integrity, has been associated with low survival, poorer clinical outcomes, and worse quality of life among cancer patients, but information on women with uterine cervical cancer (UCCa) is scarce. In this prospective study, we used a bioelectrical impedance analyzer to obtain the PA of 65 women with UCCa. We compared the health-related quality of life and inflammatory and nutritional indicators between low PA and normal PA. The mean age was 52 ± 13. The low PA and normal PA groups differed in terms of the C-reactive protein (15.8 ± 19.6 versus 6.82 ± 5.02, p = 0.022), glucose (125.39 ± 88.19 versus 88.78 ± 23.08, p = 0.021), albumin (3.9 ± 0.39 versus 4.37 ± 0.30, p = 0.000), EORTC QLQ-C30 loss of appetite symptom scale score (33.33 (0.0-100.00) versus 0.0 (0.0-0.0), p = 0.005), and EORTC QLQ-CX24 menopausal symptoms scale score (0.0 (0.0-33.33) versus 0.0 (0.0-100.0), p = 0.03). The main finding of the present study is the interaction between PA and obesity as critical cofactors in the UCCa adeno and adenosquamous histologic variants, to a greater extent than cervical squamous cell carcinoma.

Prevalence of Sexual Dysfunction in Mexican Women with Rheumatoid Arthritis.

We estimate the prevalence and identified the associated factors of sexual dysfunction in Mexican women with rheumatoid arthritis (RA). A cross-sectional survey was applied to 100 women with RA and compared with 100 healthy, sexually active, adult women. Assessments included an interview using the Female Sexual Function Index (FSFI). Assessment of factors related to sexual dysfunction included gynecologic characteristics, disease activity (DAS-28), and functioning questionnaire (HAQ-DI). Mann-Whitney U test and the Chi-square test were used to compare medians and proportions between the groups. A multivariate logistic regression was performed using sexual dysfunction according to impairments shown by the FSFI. A higher proportion of RA patients had sexual dysfunction compared with controls. Domains with higher impairment in RA patients were desire, arousal, lubrication, and orgasm. A decrease in sexual function correlated with age (r = −0.365 p < 0.001) and higher scores in HAQ-DI (r = −0.261 p = 0.009). Those patients with a higher disability had higher impairments in desire, arousal, lubrication, and satisfaction. In the multivariate analysis, menopause was associated with sexual dysfunction (OR: 10.02; 95% CI: 1.05−95.40, p = 0.04), whereas use of methotrexate was a protective factor (OR: 0.32; 95% CI: 0.11−0.92, p = 0.03). Sexual dysfunction is highly prevalent in Mexican women with RA. Clinicians should systematically evaluate the impairment in sexual function in women with RA.

Impaired muscle strength is associated with ultrastructure damage in myositis.

The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2ß) and quantified cytokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM.

Phase Angle, a Cornerstone of Outcome in Head and Neck Cancer.

In patients with head and neck cancer, malnutrition is common. Most cases are treated by chemo-radiotherapy and surgery, with adverse effects on the aerodigestive area. Clinical and biochemical characteristics, health-related quality of life, survival, and risk of death were studied. The selected subjects were divided into normal- and low-phase-angle (PA) groups and followed up for at least two years. Mean ages were 67.2 and 59.3 years for low and normal PA, respectively. Patients with PA < 4.42° had significant differences in age, anthropometric and biochemical indicators of malnutrition, and inflammatory status compared to patients with PA > 4.42°. Statistical differences were found in the functional and symptom scales, with lower functional scores and higher symptom scores in patients with low PA. Median survival was 19.8 months for those with PA < 4.42° versus 34.4 months for those with PA > 4.42° (p < 0.001).The relative risk of death was related to low PA (2.6; p < 0.001). The percentage of living patients (41.7%) is almost the same as the percentage of deceased subjects (43.1%; p = 0.002), with high death rates in patients with PA < 4.42°. Phase angle was the most crucial predictor of survival and a risk factor for death in the studied cases.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old.

Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.

Correlation between percentage of fat mass and level of disease activity in rheumatoid arthritis.

Introduction: Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation. Objective: To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis. Materials and methods: This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28). Results: The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson's correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76). Conclusion: The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.

Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity.

BACKGROUND: Health-related quality of life (QoL) is a measure that allows us to know the patient's perception of well-being and how it is affected by their disease and treatments. In cancer patients, sarcopenia has been associated with low scores on various instruments used to assess the QoL; however, little information is available on the effects of sarcopenia and sarcopenic obesity on the QoL of patients with head and neck cancer (H&NC). METHODS: In this cross-sectional study with 71 H&NC patients aged between 40 and 80 years, we describe the scores on the instruments EORTC QLQ C-30 and EORTC QLQ-H&N35 according to the sarcopenia phenotype (NSG, nonsarcopenic group; SG, sarcopenic group; and SOG, sarcopenic obesity group), hand-grip strength, gait speed, total lymphocyte count, albumin, cholesterol and C-reactive protein, and the relationships between these variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 48% and 28%, respectively. The QoL analysis showed that NSG had higher scores on the physical functioning scale [NSG 93 (83-100); SG 73 (52-88); SOG 83 (53-93), P = .009] and lower scores on the fatigue scale [NSG 11 (0-22); S 39 (30-67); SOG 44 (14-56); P = .004]. The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001), and a lower C-reactive protein. The SG and SOG showed no differences between them. CONCLUSIONS: Patients with sarcopenia or sarcopenic obesity have lower physical performance and a higher level of fatigue than nonsarcopenic patients. This loss of function can maintain or worsen sarcopenia due to the patient's self-restraint in physical exertion that encourages an increase in muscle tissue.

Body Composition and Biochemical Parameters of Nutritional Status: Correlation with Health-Related Quality of Life in Patients with Colorectal Cancer.

Up to 60% of colorectal cancer (CRC) patients develop malnutrition, affecting treatment effectiveness, increasing toxicity, postoperative complications, hospital stay, and worsening health-related quality of life (HRQOL). This cross-sectional study analyzed data from 48 women and 65 men with CRC. We correlated scores of the scales from the questionnaires EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ)-C30 and Colorectal Cancer module Colorectal 29 (QLQ-CR29) with patients' body composition and clinical and biochemical indicators of nutritional status. Results: Scores on quality of life were negatively associated with the lymphocyte count (rP = -0.386) and the fat trunk percentage (rP = -0.349) in the women's group. Scores on the physical and role functioning were inversely associated with the adiposity percentage (rP = -0.486 and rP = -0.411, respectively). In men, total skeletal muscle mass (SMM) was positively associated with emotional functioning (rP = 0.450); the trunk SMM was negatively related to fatigue (rP = -0.586), nausea and vomiting (rP = -0.469), pain (rP = -0.506), and financial difficulties (rP = -0.475); additionally, serum albumin was positively related to physical, emotional, and social functioning scales (rPs = 0.395, 0.453, and 0.363, respectively) and negatively to fatigue (rP = -0.362), nausea and vomiting (rP = -0.387), and appetite loss (rP = -0.347). Among the men, the reduced SMM and biochemical, nutritional parameters were related to low scores on the EORTC QLQ-C30 and QLQ-CR29 functioning scales. In conclusion, in patients with CRC, malnourishment could have a profound effect on the patients' functionality and QoL (quality of life).

Serum Neuropeptide Y Levels Are Associated with TNF-α Levels and Disease Activity in Rheumatoid Arthritis.

BACKGROUND: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with effects on the regulation of inflammatory cells. The role of NPY on autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is not completely understood. Therefore, we evaluate if NPY levels are markers of disease activity in RA and if there is a correlation between NPY levels and tumor necrosis factor-alpha (TNF-α), leptin, and interleukin 6 (IL-6) levels. METHODS: Cross-sectional design, including 108 women with RA. We assessed disease activity by DAS28-ESR (considering active disease a score of ≥2.6). Serum NPY levels and anti-CCP2 antibody, TNF-α, IL-6, and leptin levels were quantified (ELISA). RESULTS: Sixty-eight RA had an active disease (RA-active), and 40 were in remission (RA-remission). RA-active patients had higher NPY levels vs. RA-remission (22.8 ± 13.6 vs. 17.8 ± 10.3; p = 0.04). NPY levels correlated with increased TNF-α levels (r = 0.32, p = 0.001). Leptin or IL-6 did not correlate with NPY levels. In the logistic regression analysis, NPY increased the risk of disease activity (OR: 1.04, 95% CI 1.006-1.09, and p = 0.03). CONCLUSION: Higher NPY levels are an independent marker of disease activity in RA. This study encourages the quantification of NPY levels as a surrogate marker for RA-active. Future studies evaluating the role of NPY levels interacting with other proinflammatory cytokines are required.

Breast benign disease and breast cancer risk. Overweight-obesity, biochemical, anthropometry. / Enfermedad mamaria benigna y riesgo de cáncer de mama: sobrepeso-obesidad, bioquímica, antropometría.

BACKGROUND: The immunologic, metabolic and anthropometric disturbances of overweight-obesity phenomena are risk factors to breast cancer (BC), particularly in proliferative benign breast disease women (PBBD). OBJECTIVE: To describe the adipocytokine levels, metabolic alteration and anthropometric characteristics in PBBD and its role as risk estimator to BC in a population with high overweight-obesity prevalence. MATERIAL AND METHODS: A cross-sectional study. We realized nutritional diagnosis, anthropometry, and we calculated the waist-height rate (WHR); serum measurement of adipocytokines, insulin and glucose and, HOMA IR determination in 27 PBBD and 27 BC women. We calculated mean, standard deviation, Pearson and Spearman correlation coefficients, Odds Ratio (OR) and confidence intervals through logistic regression as risk estimators of BC; p < 0.05 values were considered significant. RESULTS: Mean age in the PBBD group was minor than BC group, the humeral diameter was greater in BC group women. We did not find differences in anthropometry or adipocytokine levels; in both groups, the predominant somatotype was the endo-mesomorphic. We found higher insulin levels in BC group and a higher percentage of women with WHR > 0.5 too. The WHR > 0.5 + age over 50 were considered risk estimators to develop breast cancer in PBBD women group. CONCLUSION: The WHR >0.5 in women with PBBD over 50 years old could be considered an anthropometric risk estimator to develop BC.

INTRODUCCIÓN: La inflamación, las alteraciones metabólicas y antropométricas del fenómeno sobrepeso-obesidad son factores de riesgo para cáncer de mama (CaM) particularmente en mujeres con enfermedad mamaria benigna proliferativa (EMBP). OBJETIVO: Describir los niveles de adipocitocinas, alteraciones metabólicas y antropométricas en la EMBP y su papel como estimadores de riesgo para CaM en una población con prevalencia de sobrepeso-obesidad de más del 70%. MATERIAL Y MÉTODOS: Estudio transversal analítico en 27 mujeres con CaM y 27 con EMBP. Se realizó diagnóstico nutricional, antropometría y cálculo del índice cintura-talla (ICT); determinación sérica de adipocitocinas, insulina, glucosa y estimación de HOMA IR. Se calcularon promedio y desviaciones estándar, correlaciones de Pearson y Spearman; Odds Ratio (OR) e intervalos de confianza mediante regresión logística como estimadores de riesgo de CaM. Se consideró significativo un valor de p < 0.05. RESULTADOS: La edad del grupo EMBP fue menor. No se observaron diferencias en adipocitocinas ni antropometría (excepto el diámetro humeral fue mayor en CaM). Se observaron mayores niveles de insulina en CaM, y mayor porcentaje de mujeres con ICT > 0.5. El ICT > 0.5 + edad > 50 fueron estimadores de riesgo para CaM. CONCLUSIÓN: Un ICT > 0.5 en mujeres mayores de 50 años podría ser un estimador antropométrico de riesgo de CaM en mujeres con EMBP.

Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: Insulin resistance (IR) is frequently observed in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In clinical practice, IR assessment is limited to a low proportion of patients due to cost and equipment and technical expertise requirements. The surrogate index of triglycerides and glucose (TyG index) has been validated in non-rheumatic populations, showing adequate sensitivity and specificity for IR, although this index has not yet been used in connective tissue disorders. The aim of this study was to evaluate the frequency of insulin resistance (IR) using the validated surrogate index of triglycerides and glucose (TyG index) and to explore factors associated with IR in Mexican women with RA or SLE. METHODS: Ninety-five female RA and 57 SLE patients were included in a cross-sectional study. Clinical and epidemiological variables were evaluated. IR was assessed using the TyG index with a cutoff value of > 4.68. Logistic regression analysis was performed to identify factors associated with IR excluding confounders. RESULTS: IR frequency in the entire sample was 50%, higher than the 10% observed in non-rheumatic controls (p < 0.001). The frequency of IR was similar in SLE (49.1%) and RA (50.5%, p = 0.8) patients. IR was associated with a longer duration of hypertension and higher total cholesterol and low density lipoprotein cholesterol levels. Based on multivariate analysis, the duration of hypertension (OR: 1.06; 95% CI 1.002-1.12, p = 0.04), waist circumference (OR: 1.04; 95% CI 1.01-1.08, p = 0.007), uric acid levels (OR: 1.46; 95% CI 1.08-1.97, p = 0.01), RA (OR: 4.87; 95% CI 1.31-18.78, p = 0.01) and SLE (OR: 4.22; 95% CI 1.06-16.74, p = 0.04) were the main risk factors for IR. CONCLUSIONS: This study shows that the TyG index is a useful screening test for IR in RA and SLE patients. Future longitudinal studies should be performed with the aim of identifying the predictive value of TyG index results for identifying complications linked to IR.

miRNA-24 Gene Sequence, DHFR -829C-T Genotypes, and Methotrexate Response in Mexican Patients with Rheumatoid Arthritis.

AIM: The present study looked for variation in the miRNA-24 sequence, and evaluated the associations between the dihydrofolate reductase (DHFR) gene-829 C-T polymorphism and plasma DHFR concentrations with response to methotrexate (MTX) treatment in Mexican patients with rheumatoid arthritis (RA). METHODS: A total of 135 women with RA were classified as responders (disease activity score [DAS28] <3.2) or nonresponders to MTX (DAS28 > 3.2). We determined the genotype of the patients using the polymerase chain reaction-restriction fragment length polymorphism method. Plasma DHFR enzyme levels and mi-RNA24 sequences were assessed by enzyme-linked immunosorbent assay (ELISA) and Sanger sequencing, respectively. Allelic frequencies and the genotypic distribution of the polymorphism were analyzed by the chi-square test. RESULTS: The genotype frequencies of the DHFR -829C-T polymorphism among responders were 37.0% CC, 52.1% CT, and 10.9% TT and for nonresponders were 33.9% CC, 56.4% CT, and 9.7% TT. No significant differences in genotype frequencies were found between the groups (p = 0.88). The DHFR levels relative to genotype for responders were 6.8 ± 2.7, 6.1 ± 2.7, and 6.5 ± 1.5 ng/mL for CC, CT, and TT, respectively, and for nonresponders were 6.5 ± 2.0, 6.1 ± 3.1, and 7.4 ± 1.8 ng/mL for CC, CT, and TT, respectively. No significant differences were found between the two groups. Similarly, both groups showed no sequence variations in miRNA-24 gene. CONCLUSION: The -829C-T polymorphism of DHFR gene was not associated with response to MTX by RA patients, and no variations were found in the miRNA-24 sequence that might modify the response to treatment or DHFR enzyme levels in a Mexican population with RA.

Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clinical Trial.

Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.