Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection-A Systematic Review and Meta-Analysis of Their Diagnostic Accuracy According to Different Definitions.

BACKGROUND: Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions. METHODS: A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin. RESULTS: Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values. CONCLUSION: All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.

HLA class II genotyping of admixed Brazilian patients with type 1 diabetes according to self-reported color/race in a nationwide study.

The HLA region is responsible for almost 50% of the genetic risk of type 1 diabetes (T1D). However, haplotypes and their effects on risk or protection vary among different ethnic groups, mainly in an admixed population. We aimed to evaluate the HLA class II genetic profile of Brazilian individuals with T1D and its relationship with self-reported color/race. This was a nationwide multicenter study conducted in 10 Brazilian cities. We included 1,019 T1D individuals and 5,116 controls matched for the region of birth and self-reported color/race. Control participants belonged to the bone marrow transplant donor registry of Brazil (REDOME). HLA-class II alleles (DRB1, DQA1, and DQB1) were genotyped using the SSO and NGS methods. The most frequent risk and protection haplotypes were HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 (OR 5.8, p < 0.00001) and HLA~DRB1*07:01~DQA1*02:01~DQB1*02:02 (OR 0.54, p < 0.0001), respectively, regardless of self-reported color/race. Haplotypes HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 and HLA~DRB1*04:02~DQA1*03:01 g~DQB1*03:02 were more prevalent in the self-reported White group than in the Black group (p = 0.04 and p = 0.02, respectively). The frequency of haplotype HLA~DRB1*09:01~DQA1*03:01 g~DQB1*02:02 was higher in individuals self-reported as Black than White (p = <0.00001). No difference between the Brazilian geographical regions was found. Individuals with T1D presented differences in frequencies of haplotypes within self-reported color/race, but the more prevalent haplotypes, regardless of self-reported color/race, were the ones described previously in Europeans. We hypothesize that, in the T1D population of Brazil, although highly admixed, the disease risk alleles come mostly from Europeans as a result of centuries of colonization and migration.

Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case-control study in Brazil.

AIMS: The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population. METHODS: This study was a nested case-control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5 years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers. RESULTS: The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severe diabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy. CONCLUSIONS: Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy.

Self-reported color-race and genomic ancestry in an admixed population: A contribution of a nationwide survey in patients with type 1 diabetes in Brazil.

AIMS: The development of type 1 diabetes (T1D) and its chronic complications may have a genetic background. The primary objective of our study was to characterize the relationship between self-reported color-race and genomic ancestry (GA) in patients with T1D. As secondary objective, we aimed to characterize GA of patients with T1D from different urban geographical regions of Brazil, compared to healthy Brazilian controls from the same regions. METHODS: This was a cross-sectional, nationwide survey conducted in 14 public clinics from 10 Brazilian cities. Global and individual GA were inferred using a panel of 46 ancestry informative markers (AIMs) in 1698 T1D patients. Ancestry percentage was compared with published data of Brazilian healthy controls (n = 936) for the same AIMs. RESULTS: A higher median individual European ancestry was observed in T1D patients in comparison to controls 67.8 [31.2] vs. 56.3 [25.7]%, respectively (median [IQR]; p < 0.001). As for self-reported color-race in T1D group, 923 (54.3%) participants reported to be White, 610 (35.9%) Brown, 132 (7.8%) Black, 18 (1.1%) Asian and 15 (0.9%) Indigenous. European GA prevailed in those who self-reported as White (74.6%) and Brown (61.1%) and constituted 39.1% in Black self-reported patients. CONCLUSIONS: Our study showed that T1D patients presented a higher percentage of European GA than the healthy population. Additionally, European GA was found in a considerable percentage of T1D patients who self-reported as non-White. Further studies are necessary to establish the influence of GA in the development of T1D as well its related chronic complications in admixed populations.

Does ancestry influence health-related quality of life in type 1 diabetes patients? A nationwide study in Brazil.

AIMS: The aim of the present study was to evaluate the relationship between self-reported color/race and genomic ancestry with HRQoL of patients with type 1 diabetes in a highly admixed population. METHODS: This was a nationwide, cross-sectional study conducted with 1760 patients with type 1 diabetes from 2011 to 2014 at public clinics in all five Brazilian geographical regions. Information on HRQoL was obtained from two self-completed questionnaires: Short Form-6 Dimensions (SF-6D) and EuroQol-5 Dimensions (EQ-5D) with a visual analogue scale (EQ-VAS). Genomic ancestry was assessed using a Multiplex PCR methodology. Utility scores generated from the questionnaires were analyzed with multivariate logistic regression models. RESULTS: We included 1698 patients. Those patients who self-reported as black had lower EQ-VAS scores compared to the patients who self-reported as white (67.46 ± 18.45; 72.37 ± 16.44, respectively, p = 0.02). In a linear regression model, each 1% increase in African ancestry resulted in a 9.5 point decrease in EQ-VAS score (p < 0.001). In a multivariate logistic regression, after adjusting for demographic, socioeconomic status and diabetes-related variables, African ancestry remained associated with lower EQ-VAS scores. CONCLUSION: A higher level of African ancestry implicates on lower quality of life even after adjustments for sociodemographic and diabetes-related data. Gender, physical activity and diabetes-related microvascular complications were strongly associated with low HRQoL in all three questionnaires used. This fact highlights the importance of social aspects when assessing quality of life, as well as the need for regular practice of physical activity and prevention of chronic complications to improve patients' quality of life.