Inflammasome genes polymorphisms and susceptibility to gout. Is there a link?

Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1ß release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1ß rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Association of TLR4 gene polymorphisms with sepsis after a burn injury: findings of the functional role of rs2737190 SNP.

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is associated with sepsis after burn trauma. Interestingly, the G allele and GG genotype were associated with a lower risk of developing sepsis. Since the rs2737190 SNP is in the promoter region of the TLR4 gene, we analyzed the possibility that this polymorphism regulates the TLR4 pathway. We cultured peripheral blood mononuclear cells from different genotype carriers and found, after stimulation with LPS, that carriers of the GG genotype showed a higher expression of TLR4, IL6, and TNFα than AA genotype carriers. The results suggest that the GG genotype produces an increase in the TLR4 expression, and therefore an improvement in the immune response. We conclude that the rs2737190 polymorphism may become a useful marker for genetic studies of sepsis in patients after a burn injury.

High risk of lumbar spine osteoporosis with the RANK rs3018362 polymorphism.

Osteoporosis is characterized by reduced bone mineral density (BMD) and quality, increasing the risk of fractures. A large number of genes involved in bone metabolism have been implicated in the genesis of osteoporosis; these include RANK and RANKL. Polymorphisms of these genes have been implicated in osteoporosis. The aim of this study was to determine the association of the RANK rs3018362 and RANKL rs12585014 polymorphisms with risk of osteoporosis. Four hundred Mexican women aged 40 years old or above were genotyped by real-time PCR and several demographic and risk factors were explored. The GA and AA genotypes of the rs3018362 polymorphism were associated with a high risk of osteoporosis in the dominant model (p=.0062; OR = 2.16, 95% CI: 1.24-3.78). In summary, the rs3018362 polymorphism in the RANK gene seems to be associated with osteoporosis of the lumbar spine while the RANKL rs12585014 is not, although more studies are needed to confirm these results.

Low prevalence of subclinical synovitis in patients with juvenile idiopathic arthritis (JIA) in long-term clinical remission on medication.

Subclinical synovitis is highly prevalent in patients with JIA in clinical remission (CR) with a short duration. The objective was to evaluate its prevalence by ultrasound (US) in patients with JIA in long CR during a one-year follow-up. In this prospective and longitudinal study, we included 76 patients with JIA according to ILAR with CR by the Wallace modified criteria and JADAS27 and compared them with 22 patients with active disease. Clinical and demographic characteristics were recorded. US evaluation was by 10-joint count. Differences in US evaluations were analyzed by the Mann-Whitney U test. There were no differences among the two group with regard to disease duration at enrollment, and age (p = 0.540 and p = 0.080, respectively), but JADAS 27, CHAQ, and acute phase reactants were significantly higher (p < 0.001) in the clinically active group. The prevalence of subclinical synovitis at baseline and the end of the study in the CR group was 18.4% and 11.8%, respectively, while it was 100% and 40.9% in the active disease group. Subclinical synovitis at baseline was significantly more prevalent in the clinically active group (elbow, p = 0.01; wrist, p = 0.001; MCP 2, p = 0.001; knee, p = 0.001 and ankle p = 0.001; and PD only in the ankle, p = 0.002). The concordance of inter-reader reliability in all evaluated joints was excellent (p = 0.001). Although the prevalence of subclinical synovitis is low in patients with JIA with long-term clinical remission on medication, a percentage of patients continue to have subclinical involvement that could predict the risk of relapse and structural damage. Key Points • Subclinical synovitis is less prevalent in JIA in long-term clinical remission compared to patients in short-term remission. • The persistence of imaging signs of inflammation in a significant percentage of patients may indicate the need for ongoing medication.

Entheseal Involvement in Spondyloarthritis (SpA) and Gout: An Ultrasound Comparative Study.

Objective: To compare the assessment of entheses in subjects with spondyloarthritis (SpA) with patients with gout by the Madrid Sonographic Enthesis Index (MASEI). Method: This cross-sectional study includes videos of entheses evaluated by ultrasound (US) of 30 patients with SpA diagnosed according to the ASAS criteria and 30 patients with gout established by the presence of monosodium urate crystals. Entheses were evaluated for MASEI in 2 Institutes located in two different countries. Demographic and clinical data were registered. Total MASEI score, MASEI-inflammatory, and MASEI-chronic damage were analyzed. Comparisons between groups were obtained by chi-square test and Student's t-test. An inter-reading US reliability was realized. Results: Patients with gout were older and had significantly more comorbidities than those with SpA. The total MASEI score was not significantly different among diseases (p = 0.07). MASEI-inflammatory was significantly more prevalent at the Achilles tendon in SpA, while the proximal patellar tendon was in gout. Power Doppler was higher in SpA compared to gout (p = 0.005). MASEI-chronic damage related to calcification/enthesophytes predominated in gout (p = 0.043), while calcaneal erosions did in SpA (p = 0.008). The inter-reader concordance was excellent (0.93, CI 95% 0.87-0.96, p = 0.001). Conclusions: SpA and gout similarly involve entheses according to MASE, however, some inflammatory and chronic lesions differ significantly depending on the underlying disease and tendon scanned.

Serological prevalence of SARS-CoV-2 infection and associated factors in healthcare workers in a "non-COVID" hospital in Mexico City.

BACKGROUND: Mexico is one of the countries with the highest number of deaths from the COVID-19 pandemic. In spite of this high mortality, in Mexico the number of confirmed cases and diagnostic tests per million population are lower than for other comparable countries, which leads to uncertainty about the actual extent of the pandemic. In Mexico City, healthcare workers represent an important fraction of individuals with SARS-CoV-2 infection. We performed a cross-sectional study whose objective was to estimate the frequency of antibodies to SARS-CoV-2 and identify associated factors in healthcare workers at a large hospital in Mexico City. METHODS: We conducted a serological survey in a non-COVID national referral teaching hospital. The study population included all the personnel that works, in any capacity, in the hospital. From this population we selected a representative sample of 300 individuals. Blood samples were collected and questionnaires were applied between August 10th and September 9th, 2020. RESULTS: ELISA results indicate a serological prevalence of SARS-CoV-2 infection of 13.0%. Working in the janitorial and security groups, having an educational level below a university degree, and living with a larger number of people, were all identified as sociodemographic factors that increase the probability of having SARS-CoV-2 infection. CONCLUSIONS: Less favored socioeconomic groups face significantly higher prospects of experiencing SARS-CoV-2 infection and in institutions such as ours, providing janitorial and security workgroups with additional testing and counseling could help to limit the spread of contagion. The rate from the official number of confirmed cases in Mexico City is substantially smaller than the seropositive rate identified in this work.

Subclinical Interstitial Lung Disease in Patients with Systemic Sclerosis. A Pilot Study on the Role of Ultrasound. / Intersticiopatía pulmonar subclínica en pacientes con esclerosis sistémica. Estudio piloto sobre el papel del ultrasonido.

INTRODUCTION: Interstitial lung disease (ILD) is a common comorbidity present in patients with systemic sclerosis (SSc). Employment of high-resolution computed tomography (HRCT) is very limited and lung ultrasound (LUS) can be an alternative tool for the early evaluation of ILD. OBJECTIVE: To determine the validity of LUS in the early detection of ILD in patients with SSc. METHODS: Sixty-eight patients with SSc ≥18 years without respiratory symptoms were included. A rheumatologist rated the subclinical respiratory condition, another rheumatologist blinded to the clinical assessment performed the LUS. To determine validity HRCT was performed as well. RESULTS: Prevalence of ILD in SSc patients was 41.2% in contrast to the 4.8% healthy controls (P=.0001). Variables associated with LUS and HRCT findings were anti-centromere antibodies (P=.005) and the Rodnan skin score (P=.004). A positive correlation was present between the findings of HRCT and LUS (P=.001). Sensitivity and specificity were 91.2% and 88.6% respectively. Good reliability in the LUS findings was found between observers (k=.72). CONCLUSIONS: By proving to be a valid, trustworthy and feasible alternative tool, we consider that LUS can be implemented for the early detection of ILD in SSc.

Microbiology and Infection Profile of Electric Burned Patients in a Referral Burn Hospital in Mexico City.

Electrical burn injuries are one of the most severe forms of trauma. This study aims to investigate the infection complications in electrical burn patients in a referral hospital in Mexico City. A longitudinal retrospective study was conducted, involving electrical burn patients admitted from April 2011 to December 2016. Demographic and clinical data including type of electric burns, infection complications, and mortality was sought. Data were collected at admission and daily until discharge. Number and type of infections and microorganism isolations were sought. Risk factors for death were analyzed. A total of 111 patients were included, of which 96.4% were males, mean age of 31.6±16.22, most injuries were high voltage associated. The total body surface area average was 27.8% ± 19.63. The overall infection rate was 72.9 cases per 100 patients. Mortality was observed in 4 (3.6%) patients. About 59.1% (443/749) had growth for Gram-negative bacteria. Multidrug-resistant Pseudomonas aeruginosa was the most frequent microorganism isolated. Fungi were present in 4.9% of cases. Electrical burn injuries occurred in young males in our study. Infection was frequent, most of them caused by Gram-negative rods with an important rate of antimicrobial resistance; however, an important microbial diversity was present.

Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in patients with rheumatoid arthritis treated with synthetic drugs, in clinical remission by DAS28.

OBJECTIVE: To identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). METHODS: This is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. RESULTS: Patients' mean age was 49.1±13.7 years; 83% were women. The mean disease duration was 8±7 years and remission lasted for 27.5±31.8 months. The mean DAS28 score was 1.9±0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI 95%, 0.34-0.81) and 0.81, p<0.0001 (CI 95%, 0.27-0.83) respectively. CONCLUSIONS: Low percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity.

Factors associated with occasional and recurrent falls in Mexican community-dwelling older people.

Falls are a frequent event among older adults that can cause wounds, disability, psychological disorders, and premature death. Although the large number of existing studies on the issue, few have been conducted in middle- and low-income countries. The objective of the present study is to identify the sociodemographic, medical, and functional performance factors associated with occasional and recurrent falls in Mexican older adults dwelling in community. Cross-sectional analysis of 9 598 adults ≥60 years old who participated in the fourth round (2015) of the Mexican Health and Aging Study. Bivariate tests were performed to evaluate the differences between covariates by distinct fall groups (no falls, occasional falls, and recurrent falls). Multiple logistic regressions with unadjusted and adjusted models were estimated. Approximately 46% of older adults had had at least one fall during the previous two years (one fall 16% and recurrent falls 30%). Occasional falls were only associated with being a woman; in addition to the sex, recurrent falls were strongly associated with advanced age, rural residence, bad and very bad self-perception of health status, activity-limiting pain, urinary incontinence, depression, arthritis, limitations in basic activities of daily living, and limitations in advanced activities of daily living. Falls, primarily recurrent falls, deserve to be addressed through multifactorial strategies that include different areas of intervention.

Inflammasome Genes Polymorphisms and Susceptibility to Gout. Is There a Link?

ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Reliability of ultrasound grading traditional score and new global OMERACT-EULAR score system (GLOESS): results from an inter- and intra-reading exercise by rheumatologists.

This study aims to test the reliability of ultrasound to graduate synovitis in static and video images, evaluating separately grayscale and power Doppler (PD), and combined. Thirteen trained rheumatologist ultrasonographers participated in two separate rounds reading 42 images, 15 static and 27 videos, of the 7-joint count [wrist, 2nd and 3rd metacarpophalangeal (MCP), 2nd and 3rd interphalangeal (IPP), 2nd and 5th metatarsophalangeal (MTP) joints]. The images were from six patients with rheumatoid arthritis, performed by one ultrasonographer. Synovitis definition was according to OMERACT. Scoring system in grayscale, PD separately, and combined (GLOESS-Global OMERACT-EULAR Score System) were reviewed before exercise. Reliability intra- and inter-reading was calculated with Cohen's kappa weighted, according to Landis and Koch. Kappa values for inter-reading were good to excellent. The minor kappa was for GLOESS in static images, and the highest was for the same scoring in videos (k 0.59 and 0.85, respectively). Excellent values were obtained for static PD in 5th MTP joint and for PD video in 2nd MTP joint. Results for GLOESS in general were good to moderate. Poor agreement was observed in 3rd MCP and 3rd IPP in all kinds of images. Intra-reading agreement were greater in grayscale and GLOESS in static images than in videos (k 0.86 vs. 0.77 and k 0.86 vs. 0.71, respectively), but PD was greater in videos than in static images (k 1.0 vs. 0.79). The reliability of the synovitis scoring through static images and videos is in general good to moderate when using grayscale and PD separately or combined.

Cross-Cultural Adaptation and Validation of the Spanish-Language Version of the SARC-F to Assess Sarcopenia in Mexican Community-Dwelling Older Adults.

OBJECTIVES: To cross-culturally adapt and validate the Spanish-language version of the SARC-F in Mexican community-dwelling older adults. DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: The FraDySMex study, a 2-round evaluation of community-dwelling adults from 2 municipalities in Mexico City. PARTICIPANTS: Participants were 487 men and women older than 60 years, living in the designated area in Mexico City. MEASUREMENTS: Information from questionnaires regarding demographic characteristics, comorbidities, mental status, nutritional status, dependence in activities of daily living, frailty, and quality of life. Objective measurements of muscle mass, strength and function were as follows: skeletal muscle mass index (SMI) was taken using dual-energy x-ray, grip strength using a hand dynamometer, 6-meter gait speed using a GAIT Rite instrumented walkway, peak torque and power for knee extension using a isokinetic dynamometer, lower extremity functioning measured by the Short Physical Performance Battery (SPPB), and balance using evaluation on a foam surface, with closed eyes, in the Modified Clinical Test of Sensory Integration. The SARC-F scale translated to Spanish and the consensus panels' criteria from European, international, and Asian sarcopenia working groups were applied to evaluate sarcopenia. RESULTS: The Spanish language version of the SARC-F scale showed reliability (Cronbach alfa = 0.641. All items in the scale correlated to the scale's total score, rho = 0.43 to 0.76), temporal consistency evaluated by test-retest (CCI = 0.80), criterion validity when compared to the consensus panels' criteria (high specificity and negative predictive values). The scale was also correlated to other measures related to sarcopenia (such as age, quality of life, self-rated health status, cognition, dependence in activities of daily living, nutritional status, depression, gait speed, grip strength, peak torque and power for knee extension, SPPB, balance, SMI, and frailty). CONCLUSION: The SARC-F scale was successfully adapted to Spanish language and validated in community-dwelling Mexican older adults.

Cross-Cultural Adaptation and Validation of the FRAIL Scale to Assess Frailty in Mexican Adults.

OBJECTIVES: The objectives of this study were to cross-culturally adapt and validate the FRAIL scale in Mexican community-dwelling adults. DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: The FraDysMex study, a 2-round evaluation of community-dwelling adults from 2 municipalities in Mexico City. PARTICIPANTS: Participants were 606 men and women living in the designated area in Mexico City. MEASUREMENTS: Interviewers obtained data regarding demographics, comorbidities, mental status, nutritional status, dependency in activities of daily living, quality of life, mobility, balance, and strength. The FRAIL scale translated to Spanish and the Fried criteria were applied to screen frailty. RESULTS: The Mexican Spanish version of the FRAIL scale showed internal consistency (4 of 5 items in the scale correlated to the scale's total score, rho = 0.41-0.74), external consistency (interrater correlation CCI = 0.82), known-group validity based on age (9.6% of frailty in persons ≥50 years × 3.2% in persons <50 years, P = .001), convergent validity with the Fried criteria (CCI = 0.63), and the scale was also correlated with other measures related to frailty (such as age, quality of life, self-rated health status, cognition, dependency, nutritional status, depression, and physical performance). CONCLUSION: The FRAIL scale was successfully adapted to Mexican Spanish and validated in community-dwelling Mexican adults.