Increased serum carboxylesterase-1 levels are associated with metabolic dysfunction associated steatotic liver disease and metabolic syndrome in children with obesity.

BACKGROUND: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. METHODS: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. RESULTS: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. CONCLUSIONS: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity.

PON1 enzyme activity assays for serum and heparinized plasma in horses and stability evaluation of the enzyme activity over different freeze-thaw cycles and mimic transportation.

Consistent information and standardization procedures regarding the time of storage for frozen samples and the effects of storage time on enzyme activity are still missing in the literature. Thus, we evaluated the effects of different storage temperatures (-20 °C and - 80 °C), three repetitive freeze/thaw cycles, and 24-h mimic transportation on the activities of PON1 (paraoxonase and arylesterase), enzymes involved in the protection and detoxification processes of reactive molecules. PON1 enzymes' activity was validated on serum and heparinized plasma in horses. The results revealed that conditions and time of storage of blood samples for PON1 analyses altered the activities of both enzymes in both sample types, evidencing that these conditions can lead to protein degradation or general alteration. Specifically, paraoxonase and arylesterase activities significantly decreased among storage temperatures, with major effects detected at -20 °C. The repeated freeze/thaw cycles at -20 °C and 24-h mimic transport conditions also generated an expected degradation of the arylesterase in both serum and heparinized plasma while freeze/thaw cycles at -80 °C caused an increase of both arylesterase and paraoxonase activities on both sample types. In general, similar enzyme responses were detected between serum and heparinized plasma.

Paraoxonase 1 Activity and Phenotype Distribution in Lumbar Disc Herniation Patients.

AIM: To compare the Paraoxonase 1 (PON1) activity and phenotype distribution between lumbar disc herniation (LDH) patients and healthy individuals. MATERIAL AND METHODS: This research included 40 LDH patients and 42 healthy individuals. Spectrophotometric assays were performed to determine the serum PON1 and arylesterase activities. The PON1 ratio, which represents the salt-stimulated PON/ arylesterase level, demonstrated a trimodal distribution. This ratio was applied to identify the different phenotypes; QQ, QR, and RR of each subject. RESULTS: The LDH patients had lower PON1 activity than the healthy individuals (p < 0.05). LDH patients had a statistically significant QQ phenotype compared to the healthy subjects (p < 0.05). CONCLUSION: LDH patients had statistically lower PON1 activity, suggesting that the low PON1 activity and PON1 QQ phenotype may be a risk factor for LDH occurrence.

Investigation of oxidant-antioxidant status in patients treated with hirudotherapy: an experimental study.

Objectives: To examine the influence of hirudotherapy on parameters of oxidative stress. METHODS: The cross-sectional study was conducted from March 29 to September 29, 2021, at the Alanya Research and Training Hospital's Traditional and Complementary Medicine Application Centre, Turkey, and comprised adult volunteers of either gender. The participants were subjected to two sessions of hirudotherapy 4 weeks apart. Total antioxidant status, total oxidant status, oxidative stress index values, ischaemia-modified albumin level, paraoxonase 1, disulfide, native thiol, total thiol, and arylesterase levels were assessed at baseline and after the second hirudotherapy session. Data was analysed using SPSS 15. RESULTS: Of the 50 subjects, 30(60%) were females and 20(40%) were males. The overall mean age was 47.10±15.16 years. Oxidative stress, ischaemia-modified albumin and disulfide levels decreased, but not significantly (p>0.05). The reduction in disulfide levels was significant (p=0.021). CONCLUSIONS: Hirudotherapy, within its limitations, could reduce oxidative stress.

The Effect of ABCB1 and CES1 Polymorphisms on Plasma Levels of Dabigatran and Risk of Hemorrhagic Complications in Ischemic Stroke Patients.

BACKGROUND: Dabigatran directly inhibits thrombin and is used in primary and secondary stroke prevention in individuals with nonvalvular atrial fibrillation. The prodrug dabigatran etexilate is absorbed by enteral P-glycoprotein (ABCB1) and then activated by hepatic and intestinal carboxylesterases (CES1) to produce active metabolites. Variations in dabigatran metabolism because of genetics may affect concentration levels and clinical outcomes. STUDY QUESTION: We conducted a study to assess how polymorphisms in the CES1 (rs2244613) and ABCB1 (rs4148738) genes affect the through plasma level (c min ) of dabigatran and its correlation to clinical outcomes. STUDY DESIGN: Retrospective multicentric study of consecutive patients on dabigatran therapy. Examination of CES1 rs2244613 and ABCB1 rs4148738 polymorphisms, c min 12 hours after administration, clinical follow-up (ischemic stroke, major or clinically relevant hemorrhage, myocardial infarction, other thromboembolism, and death). MEASURES AND OUTCOMES: A total of 432 patients received treatment for an average of 19.78 months (SD of 20.165). The sex distribution of the patients was 56.5% male, and the average age was 67.56 years (SD of 14.7). The ABCB1 variant genotype was present in 67.8% of patients, whereas 37.5% carried the CES1 polymorphism. RESULTS: Compared with wild-type patients, patients with the CES1 variant had significantly lower dabigatran plasma levels (with a mean difference of 16.986; 95% confidence interval, 5.794-28.178 ng/mL, P = 0.003). We also found a significant risk of major bleeding in patients carrying the ABCB1 rs4148738 allele (hazard ratio = 1.99, confidence interval 95% 1.10 to 3.59, P = 0.024). CONCLUSIONS: The CES1 variant genotype rs2244613 is closely linked with reduced c min of dabigatran. Carriers of the ABCB1 rs4148738 polymorphism exhibit a tendency toward higher plasma levels of dabigatran, which leads to a significantly increased risk of bleeding.

Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology.

BACKGROUND: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. PATIENTS AND METHODS: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. RESULTS: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). CONCLUSIONS: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

Investigation of oxidative stress status in cumulus cells in patients with in vitro fertilization

Background/aim: The negative impact of oxidative stress on oocytes obtained from in vitro fertilization (IVF) patients is a challenge for the optimization of live birth rates. In this study, it is aimed to investigate whether oxidant/antioxidant parameters have a predictive value in terms of determining the count and quality of oocytes. Materials and methods: Catalase (CAT), glutathione-S-transferase (GST), arylesterase (ARE) enzyme activities, and malondialdehyde (MDA) levels were analysed in cumulus cells of poor responder (n = 28, oocyte count ≤ 4), normo responder (n = 48, 5 ≤ oocyte count ≤ 14), and high responder (n = 26, oocyte count ≥ 15) patient groups continuing IVF treatment. Results: The cumulus cell GST enzyme activity were statistically significantly increased in the high responders group compared to the poor responder and the normo responder's groups (p < 0.001 and p = 0.002, respectively). The cumulus cell MDA levels were significantly decreased in the high responder group compared to the poor responder group (p = 0.008). The cumulus cell CAT (p = 0.175) and ARE (p = 0.124) enzyme activities were examined but no statistically significant difference found between the groups. Conclusion: The significant increase in GST enzyme activity and significant decrease in MDA levels in the high responder group indicate that oxidative stress has an effect oocyte status and quality.

Association between inflammatory markers and serum paraoxonase and arylesterase activities in the general population: a cross-sectional study.

BACKGROUND: Recent studies focused on modulating factors of paraoxonase-1 (PON1) activity. In some studies the association between pro-inflammatory markers and PON1 activity was examined, but so far no population-based investigations on this issue have been conducted. The present study investigated the relationships between the pro-inflammatory markers tumor necrosis factor (TNF)-α, leptin, interleukin (IL)-6, and high-sensitive C-reactive protein (hs-CRP) and paraoxonase and arylesterase, two hydrolytic activities of PON1, in the population-based Bavarian Food Consumption Survey II. METHODS: Based on 504 participants (217 men, 287 women), the relationship between the pro-inflammatory markers and the outcomes paraoxonase and arylesterase activities were investigated using multivariable linear models. RESULTS: Circulating plasma levels of leptin (P-value < 0.0001), hs-CRP (P-value = 0.031) and IL-6 (P-value = 0.045) were significantly non-linearly associated with arylesterase activity. Leptin levels were also significantly associated with paraoxonase activity (P-value = 0.024) independently from confounding factors, including high-density lipoprotein (HDL) cholesterol. With increasing levels of these inflammatory parameters, arylesterase and paraoxonase activities increased; however, at higher levels (> 75th percentile) the activities reached a plateau or even decreased somewhat. After Bonferroni-Holm correction, only leptin remained non-linearly but significantly associated with arylesterase activity (adjusted overall P-value < 0.0001). Neither age nor sex nor obesity modified the associations. No association was found between TNF-α and paraoxonase or arylesterase activity. CONCLUSIONS: The present findings suggest that in persons with very high levels of inflammation, PON1 activity may be impaired, a fact that might subsequently be accompanied by a higher risk for cardiometabolic diseases. Whether or not the measurement of PON1 activity in combination with a lipid profile and certain inflammatory markers could improve the prediction of cardiometabolic diseases in middle-aged individuals from the general population should be evaluated in clinical studies.

Copy number variation in the CES1 gene and the risk of non-alcoholic fatty liver in a Chinese Han population.

A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. A case-control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. The distribution of CES1 CNVs showed a higher frequency of CNVs loss (< 2) among patients; however, the difference was not significant (P = 0.05). After controlling for other known or suspected risk factors for NAFLD, CES1 CNVs loss was significantly associated with greater risk of NAFLD (adjusted OR = 2.75, 95% CI 1.30-5.85, P = 0.01); while CES1 CNVs gain (> 2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P = 0.07). Copy number losses (< 2) of CES1 contribute to susceptibility to NAFLD in the Chinese Han population.

SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate.

By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 × 10-13 mol·L-1, and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng·mL-1, the SERS signal intensity of benzidine at 1609 cm-1 gradually decreases with the increase of hCE 1 concentration (R2 = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.

Paraoxonase (PON)-1 activity in septic neonates: One more arrow in the quiver of biomarkers of neonatal sepsis?

Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls. PON-1 activity was decreased at the acute phase of sepsis in comparison with values at recovery and values in controls. Paraoxonase or arylesterase at enrollment correlated significantly with serum Amyloid-A, CRP and IL-6 and could also discriminate septic than non-septic neonates. In conclusion, our results are promising regarding the role of PON-1 as a biomarker of neonatal sepsis. Larger studies are needed to validate the clinical utility of PON-1 in neonatal medicine.

Effect of CES1 and ABCB1 genotypes on the pharmacokinetics and clinical outcomes of dabigatran etexilate in patients with atrial fibrillation and chronic kidney disease.

Background Despite the well-studied safety profile of dabigatran, its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). The study assessed whether genetic factors can contribute to CKD and alter dabigatran concentration. Methods Patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110 or 150 mg have been included in the study. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Results A total of 96 patients aged 51-89 years (median age: 75 years) were evaluated. Patients on a reduced regimen of 110 mg twice a day were older (79.8 vs. 67.9, p < 0.0001) and had lower creatinine clearance (49.7 vs. 62.3 mL/min/1.73 m2, p = 0.015). Patients with the rs2244613 CC genotype had lower C/D values (70% reduction in the mean C/D vs. AA genotype, p = 0.001). Linear stepwise regression has shown the CKD epidemiology collaboration to be the only significant predictor of C/D among genetic factors and kidney function characteristics. During the median follow-up of 15 months, there were 15 bleedings in 13 patients. Conclusions Polymorphism of CES1 rs2244613 can contribute to the safety of dabigatran in patients with AF and CKD. There was no influence of the aforementioned polymorphisms of ABCB1 on dabigatran trough plasma concentrations and C/D. Kidney function is a mainstay of clinical decision-making on direct oral anticoagulant (DOAC) dose, and further knowledge should be accumulated on the role of genetic factors.

A magnetic SERS immunosensor for highly sensitive and selective detection of human carboxylesterase 1 in human serum samples.

Hepatocellular carcinoma (HCC) is a common and lethal cancer. New serum markers for detecting HCC are urgently needed. Human carboxylesterase 1 (hCE1) is an important member of the serine hydrolase superfamily and is closely related to the occurrence of HCC. It can be used as a good serum marker for early diagnosis of HCC. Here, we developed a surface enhanced Raman scattering (SERS)- based magnetic immunosensor that specifically recognizes and detects trace amounts of hCE1 in human serum via a sandwich structure consisting of a SERS tags, magnetic supporting substrates, and target antigen (hCE1). The SERS tags are 4-mercaptobenzoic acid (4-MBA)-labeled AgNPs, and the SERS supporting substrates are composed of a raspberry-like morphology of Fe3O4@SiO2@AgNPs magnetic nanocomposites surface-functionalized with a hCE1 antibody. The prepared SERS magnetic immunosensor exhibits excellent selectivity and extremely high sensitivity for hCE1 detection. The SERS signal and logarithm of hCE1 concentration presented a wide linear response range of 0.1 ng mL-1 to 1.0 mg mL-1, and the detection limit of hCE1 was 0.1 ng mL-1. The results indicate that the immunosensor can be used for the rapid determination of hCE1 in human serum without a complicated sample pre-treatment. Furthermore, the immunosensor has good reproducibility and stability, and has a promising prospect for the quantitative detection of other tumor markers in early clinical diagnosis.

Rhodesian Ridgebacks have an increased risk to develop benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an age-dependent primarily non-inflammatory enlargement of the accessory gland in the intact dog. The aim of the present study was to control a previously raised suspicion of a breed-related higher incidence of BPH in dogs of the Rhodesian Ridgeback breed. For this, 18 Labrador Retrievers/LR and 20 Rhodesian Ridgebacks/RR were assigned to the age groups 18-24 months (n = 12), 25-48 months (n = 13) and 49-72 months (n = 13). Prostate gland status was determined by rectal palpation, B-mode ultrasound, calculation of the prostate gland volume and semen analysis regarding haemospermia and was classified according to blood plasma concentrations of canine prostate-specific arginine esterase (CPSE) (normal ≤ 60 ng/ml, increased ≥ 61 ng/ml; Pinheiro et al., 2017). Concentrations of testosterone, 5α-dihydrotestosterone and estradiol were analysed in peripheral blood serum or plasma for detecting breed-specific conditions regarding the endocrine metabolism. Prostatic volume was significantly larger in RR irrespective of the CPSE status. In RR, BPH occurred more frequently and started at an earlier age compared with the LR. Breed-related specificities in steroid metabolism in the RR were indicated by correlations of 5α-dihydrotestosterone and estradiol with age and of testosterone with prostate gland volume. Although the incidence of sonographic signs of BPH and haemospermia did not fit with normal and increased CPSE concentrations, a breed-specific higher incidence of BPH in the RR breed could be clearly verified.

Effects of the rs2244613 polymorphism of the CES1 gene on the antiplatelet effect of the receptor P2Y12 blocker clopidogrel.

Background The aim of this study was to evaluate the association of the carriage of the rs2244613 polymorphism of the CES1 gene with clopidogrel resistance as well as to evaluate the effectiveness of antiplatelet therapy in the carriers of this marker who have had acute coronary syndrome (ACS). This study also analyzes the procedure of percutaneous coronary intervention and compares the rs2244613 carrier rate between patients with ACS and healthy participants. Methods The study involved 81 patients diagnosed with ACS and 136 conditionally healthy participants. The optical detection of platelet agglutination by VerifyNow was employed to measure residual platelet reactivity in patients with ACS. The rs2244613 polymorphism was determined using real-time polymerase chain reaction. Results According to the results, the AA genotype of the rs2244613 polymorphism of the CES1 gene was detected in 37 patients (45.6%), the CA genotype in 42 patients (51.8%) and the CC genotype in 2 patients (2.6%). The level of residual platelet reactivity in rs2244613 carriers was higher compared with patients who did not have this allelic variant: 183.23 PRU ± 37.24 vs. 154.3 PRU ± 60.36 (p = 0.01). The frequencies of the minor allele C were 28.4% and 28.3% in patients with ACS and healthy participants, respectively. The results of the linear statistical model PRU due to CES1 genotype were as follows: df = 1, F = 6.96, p = 0.01). The standardized beta was 0.285 (p = 0.01) and R2 was 0.081. However, we also added CYP2C19*2 and *17 into the linear regression model. The results of the model were as follows: df = 3, F = 5.1, p = 0.003) and R2 was 0.166. Conclusions We identified a statistically significant correlation between the carriage of the rs2244613 polymorphism of the CES1 gene and the level of residual platelet aggregation among patients with ACS and the procedure of percutaneous coronary intervention.

Paraoxonase-1 Polymorphisms (L55M/Q192R) and Activities (PONase/AREase) in Patients with Idiopathic Recurrent Early Pregnancy Loss: A Preliminary Study.

Aim: To evaluate the associations between idiopathic recurrent early pregnancy loss (REPL) and paraoxonase-1 (PON1) polymorphisms and the activities of its encoded enzymes. Materials and Methods: Ninety-eight women were enrolled in this study, including 21 currently pregnant multiparous women without a history of miscarriage; 18 multiparous women who were not pregnant during the study; 30 women with a history of idiopathic REPL who were pregnant; and 29 who were not. Paraoxonase (PONase) and arylesterase (AREase) activities, two activities of the PON1 enzyme, were measured through commercially available kits (Relassay, Gaziantep, Turkey). PON1 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Data were analyzed using SPSS for Windows version 19.0 (SPSS). Results: There was no association between idiopathic REPL and PON1 polymorphisms or PONase activity. The AREase activity of the PON1 enzyme trended higher in the healthy pregnant group than in the healthy nonpregnant group (p = 0.067), and was higher in the pregnant group with a history of idiopathic REPL than in the nonpregnant group with a history of idiopathic REPL (p = 0.041). Conclusions: Despite there being no detected association between PON1 activities or genotype and idiopathic REPL, we showed that AREase activity increased during early gestation. New studies, including longitudinal changes in serum AREase activity throughout normal pregnancy, should be carried out to further evaluate the association between PON encoded enzymatic activities and early gestational pathophysiology.

Development and Validation of an Evidence-Based Algorithm for Diagnosing Periprosthetic Joint Infection.

BACKGROUND: The guidelines for diagnosis of periprosthetic joint infection (PJI) introduced by the American Academy of Orthopaedic Surgeons served the orthopedic community well. However, they have never been validated and do not account for newer diagnostic modalities. Our aim was to update current guidelines and develop an evidence-based and validated diagnostic algorithm. METHODS: This multi-institutional study examined total joint arthroplasty patients from 3 institutions. Patients fulfilling major criteria for infection as defined by Musculoskeletal Infection Society were considered infected (n = 684). Patients undergoing aseptic revision for a noninfective indication and did not show evidence of PJI or undergo reoperation within 2 years served as a noninfected control group (n = 820). The algorithm was validated on a separate cohort of 422 cases. RESULTS: The first step in evaluating PJI should include a physical examination, followed by serum C-reactive protein, erythrocyte sedimentation rate, and D-dimer. If at least one of these tests are elevated, or if high clinical suspicion exists, joint aspiration should be performed, sending the fluid for a white blood cell count, leukocyte esterase, polymorphonuclear percentage, and culture. Alpha defensin did not show added benefit as a routine diagnostic test. In inconclusive cases, intraoperative findings including gross purulence, histology, and next-generation sequencing or a single positive culture can aid in making the diagnosis. The proposed algorithm demonstrated a high sensitivity (96.9%) and specificity (99.5%). CONCLUSION: This validated, evidence-based algorithm for diagnosing PJI should guide clinicians in the workup of patients undergoing revision arthroplasty and improve clinical practice. It also has the potential to reduce cost.

Relationship of High-Density Lipoprotein-Associated Arylesterase Activity to Systolic Heart Failure in Patients with and without Type 2 Diabetes.

High-density lipoprotein (HDL) confers protection against cardiovascular disease partly attributable to its robust anti-oxidant activities, which is largely impaired in diabetic conditions. In this study, we analyzed the anti-oxidant activity of HDL, as represented by the arylesterase activity of paraoxonase 1 (PON1) in HDL particles, in 216 consecutive HF patients with (n = 79) or without (n = 137) type 2 diabetes, and age- and gender-matched 112 diabetic and 189 non-diabetic non-HF controls. We found arylesterase activity was significantly decreased in patients with than without HF, and was further decreased when comorbid with diabetes. After adjusting for conventional risk factors and apolipoprotein A-I levels, arylesterase activity remained correlated positively with left ventricular ejection fraction in diabetic (r = 0.325, P = 0.020) but not non-diabetic patients (r = 0.089, P = 0.415), and negatively with NT-proBNP and NYHA functional class in both subgroups. In regression analyses, a higher risk of HF was observed in diabetic than non-diabetic patients when having low arylesterase activities. In conclusion, our data demonstrate that impaired serum arylesterase activity in patients with HF is further reduced when comorbid with diabetes. The relationship of impaired arylesterase activity to HF is especially enhanced in diabetic patients.

What Is the Diagnostic Accuracy of Alpha-Defensin and Leukocyte Esterase Test in Periprosthetic Shoulder Infection?

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) after total shoulder arthroplasty (TSA) is challenging, especially in patients with Cutibacterium (formerly Propionibacterium) acnes infection. Despite the increasing number of patients with PJI of the shoulder, there are still no robust data regarding diagnostic tests in detecting shoulder PJI. QUESTIONS/PURPOSES: (1) What are the sensitivity, specificity, and negative- and positive-predictive values for the alpha-defensin enzyme-linked immunosorbent assay test in detecting PJI after TSA? (2) What are the diagnostic accuracies in detecting shoulder PJI for synovial alpha-defensin, leukocyte esterase Test, and serum C-reactive protein (CRP)? METHODS: All patients with painful TSA, who underwent joint aspiration to validate or exclude a PJI, between July 2015 and February 2018 were enrolled in this single-center study. Further indications for aspiration were as follows: planned revision arthroplasty, early loosening and clinical signs of infections, especially serum CRP elevation. A total of 121 patients were aspirated to exclude or verify a PJI, and 16 patients were excluded. In all, 105 patients with a mean age of 68 years (± 12 years) were included for analysis. Patients who underwent TSA were considered aseptic or septic according to the Musculoskeletal Infection Society criteria. Twenty-four patients had a PJI, and the remaining 81 patients were in the aseptic group. The microbiologic evaluation including polymicrobial infection showed C. (formerly P.) acnes in 15 patients (63%). Synovial fluid was then analyzed using microbiology cultures, alpha-defensin immunoassay, and leukocyte esterase. The specificity, sensitivity, and positive-predictive and negative-predictive values were calculated for each test. RESULTS: The overall accuracy for alpha-defensin was 91% (95% confidence interval [CI], 84.4-96); sensitivity was 75% (95% CI, 53-90), specificity was 96% (95% CI, 90-99), negative predictive value was 93% (95% CI, 85-97), and positive predictive value was 86% (95% CI, 64-97). In contrast, the overall accuracy for leukocyte esterase was 76% (95% CI, 61-88), sensitivity was 50% (95% CI, 21-79), specificity was 87% (95% CI, 69-96), positive predictive value 60% (95% CI, 26-88) and negative predictive value was 81% (95% CI, 64-93). CONCLUSIONS: Summarizing the study results, the alpha-defensin ELISA and leukocyte esterase tests had less sensitivity in detecting shoulder PJI than previously reported TKA or THA results. The quality and low amount of joint fluid is the difficult part of the diagnostic. C. (formerly P.) acnes was the most common cause of PJI. Focusing on low-grade infections, alpha-defensin has shown its advantages in diagnosing PJI regardless pathogen virulence. Since the diagnostic of a PJI is always a synopsis of findings, the alpha-defensin and leukocyte esterase test can be used as adjunct diagnostic tool in patients with painful TSA. We propose further prospective studies to improve the diagnostic and confirm the results. LEVEL OF EVIDENCE: Level III, diagnostic study.

Associations of plasma LP(a), Hcy and D-D levels with the subtype of ischemic cerebrovascular disease.

The relevance of LP(a), Hcy, and D-D in ischemic cerebrovascular disease remains undefined. This study aimed to assess the associations of plasma LP(a), Hcy and D-D levels with the subtype of ischemic cerebrovascular disease.Patients with ischemic cerebrovascular disease admitted to the Taixing People's Hospital were retrospectively enrolled from November 2017 to July 2018. Immunoturbidimetry was used to assess 119 LAA, 107 SAO, and 112 TIA patients for plasma LP(a), Hcy, and D-D levels.Plasma LP(a), Hcy, and D-D levels in the large artery atherosclerosis (LAA) group were significantly lower than those of the transient ischemic attack (TIA) group (all P < .05). LP(a), Hcy, and D-D levels were significantly reduced in the SAO group compared with the TIA group (both P < .05). The LAA and SAO groups showed comparable values for all the above parameters (P > .05).LP(a), Hcy, and D-D levels differ according to the subtype of ischemic cerebrovascular disease.