What makes D-dimer assays suspicious-heterophilic antibodies?

BACKGROUND: Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article. METHODS: Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature. RESULTS: The D-dimer values were normal (0.49 and 0.15 µg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody. CONCLUSIONS: The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.

Genetic variability in stroke patients: CYP2C19 polymorphisms unraveled.

OBJECTIVE: To study the distribution characteristics of CYP2C19 polymorphisms in patients suffering from stroke in Han Chinese patients. METHOD: PCR and DNA microarray chip technology were used to detect the CYP2C19 genotype of 549 patients with stroke, and the genotype, allele frequency and metabolic type of patients with different sexes, ages and types of infarctions and the independent risk factors for clopidogrel resistance were analyzed. RESULTS: Six genotypes were detected in these 549 patients. A total of 233 (42.44%) patients had the heterozygous allele *1/*2, which was the most prevalent, followed by the homozygous wild-type allele *1/*1 (191, 34.79%). A total of 30 (5.46%) patients possessed the heterozygous allele *1/*3, and 65 (11.84%) patients had the homozygous mutant allele *2/*2. Twenty-nine (5.28%) patients had the compound heterozygous mutant allele *2/*3, and only 1 patient had the homozygous mutant allele *3/*3. The distribution of genotypes, alleles, and metabolic types did not change significantly (P > 0.05) by sex, age, or type of stroke. In addition, no independent risk factors for clopidogrel resistance were found in this analysis. CONCLUSION: The distribution of CYP2C19 genotypes, allele frequencies, and metabolic types in patients with stroke in Han Chinese patients were not correlated with sex, age, or infarction type. The possibilities of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia and high blood pressure were not statistically associated with CYP2C19 genotypes. CYP2C19 gene polymorphism detection is recommended for patients who are available, and during treatment, the CYP2C19 genotype can be used to guide personalized precise medication use in patients with stroke.

Multimodal detection and analysis of microplastics in human thrombi from multiple anatomically distinct sites.

BACKGROUND: Microplastic (MP) pollution has emerged as a significant environmental concern worldwide. While extensive research has focused on their presence in marine organisms and ecosystems, their potential impact on human health, particularly on the circulatory system, remains understudied. This project aimed to identify and quantify the mass concentrations, polymer types, and physical properties of MPs in human thrombi surgically retrieved from both arterial and venous systems at three anatomically distinct sites, namely, cerebral arteries in the brain, coronary arteries in the heart, and deep veins in the lower extremities. Furthermore, this study aimed to investigate the potential association between the levels of MPs and disease severity. METHODS: Thrombus samples were collected from 30 patients who underwent thrombectomy procedures due to ischaemic stroke (IS), myocardial infarction (MI), or deep vein thrombosis (DVT). Pyrolysis-gas chromatography mass spectrometry (Py-GC/MS) was employed to identify and quantify the mass concentrations of the MPs. Laser direct infrared (LDIR) spectroscopy and scanning electron microscopy (SEM) were used to analyse the physical properties of the MPs. Demographic and clinical information were also examined. A rigorous quality control system was used to eliminate potential environmental contamination. FINDINGS: MPs were detected by Py-GC/MS in 80% (24/30) of the thrombi obtained from patients with IS, MI, or DVT, with median concentrations of 61.75 µg/g, 141.80 µg/g, and 69.62 µg/g, respectively. Among the 10 target types of MP polymers, polyamide 66 (PA66), polyvinyl chloride (PVC), and polyethylene (PE) were identified. Further analyses suggested that higher concentrations of MPs may be associated with greater disease severity (adjusted ß = 7.72, 95% CI: 2.01-13.43, p < 0.05). The level of D-dimer in the MP-detected group was significantly higher than that in the MP-undetected group (8.3 ± 1.5 µg/L vs 6.6 ± 0.5 µg/L, p < 0.001). Additionally, LDIR analysis showed that PE was dominant among the 15 types of identified MPs, accounting for 53.6% of all MPs, with a mean diameter of 35.6 µm. The shapes of the polymers detected using LDIR and SEM were found to be heterogeneous. INTERPRETATION: This study presents both qualitative and quantitative evidence of the presence of MPs, and their mass concentrations, polymer types, and physical properties in thrombotic diseases through the use of multimodal detection methods. Higher concentrations of MPs may be associated with increased disease severity. Future research with a larger sample size is urgently needed to identify the sources of exposure and validate the observed trends in the study. FUNDING: This study was funded by the SUMC Scientific Research Initiation Grant (SRIG, No. 009-510858038), Postdoctoral Research Initiation Grant (No. 202205230031-3), and the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (No. 2020LKSFG02C).

Cystatin C predicts the risk of incident cerebrovascular disease in the elderly: A meta-analysis on survival date studies.

BACKGROUND: Stroke is the third leading cause of global year of life lost in all-age and second-ranked cause of disability adjusted life years in middle-aged and elder population. Therefore, it is critical to study the relationship between vascular-related risk factors and cerebrovascular diseases. Several cross-sectional studies have shown that Cystatin C (Cys C) is an independent risk factor for cerebrovascular diseases and levels of Cys C are significantly higher in stroke patients than in healthy individuals. In this meta-analysis, we introduce a Cox proportional hazards model to evaluate the causality between Cys C and the risk of cerebrovascular accident in the elderly. METHODS: We searched PubMed, EMBASE, the Web of Science, and the Cochrane Library from 1985 to 2019 for studies on the relationship between serum Cys C and incidence stroke with Cox proportional hazards models. We conducted a subgroup analysis of the selected studies to determine a connection between atherosclerosis and stroke. Finally, 7 research studies, including 26,768 patients without a history of cerebrovascular, were studied. RESULTS: After comparing the maximum and minimum Cys C levels, the hazard ratio for all types of stroke, including ischemic and hemorrhagic stroke, was 1.18 (95% confidence interval 1.04-1.31) with moderate heterogeneity (I2 = 43.0%; P = .119) in a fixed-effect model after pooled adjustment for other potential risk factors. In the subgroup analysis, the hazard ratio and 95% confidence interval for Cys C stratified by atherosclerosis was 1.85 (0.97-2.72). As shown in Egger linear regression test, there was no distinct publication bias (P = .153). CONCLUSION: Increased serum Cys C is significantly associated with future stroke events in the elderly, especially in patients with carotid atherosclerosis. Thus, serum levels of Cys C could serve as a predicted biomarker for stroke attack.

Neutrophil-lymphocyte ratio predicts the outcome of intracerebral hemorrhage: A meta-analysis.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is increasingly recognized as a systemic inflammation factor. It has been used as a predictor for clinical outcomes in cancers. However, its relationship with intracerebral hemorrhage (ICH) is still disputed. We sought to evaluate the prognostic role of NLR in ICH. METHODS: We searched PubMed, Cochrane Library, Medline, and EMBASE for potentially relevant articles from inception to April 8, 2018. Efficacy outcomes included major disability at 90 days, short-term mortality or in-hospital mortality. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled to assess the association between NLR and ICH. RESULTS: A total of 7 trials with 2176 patients were included in this meta-analysis. It revealed that higher NLR had a higher risk of major disability at 90 days (OR: 2.20; 95% CI: 1.27-3.81) and higher mortality at short-term (OR: 1.31; 95% CI: 1.02-1.68) in ICH; without statistically significant association with in-hospital mortality (OR: 1.02; 95% CI: 0.91-1.15). CONCLUSIONS: Our meta-analysis proved that high NLR was a predictor of major disability and mortality at short term in ICH patients, but not a predictor of in-hospital mortality.

Prognostic factors associated with survival in patients with anaplastic oligodendroglioma.

Anaplastic oligodendroglioma is a rare disease with an inadequately understood prognosis. The aim of this study was to investigate factors associated with survival outcome in anaplastic oligodendroglioma patients. A population-based cohort study was conducted based on the Surveillance, Epidemiology, and End Results program. In total, 1899 patients with a histological diagnosis of anaplastic oligodendroglioma from 1973 to 2015 were included. Mean age at diagnosis was 49.2 years, and 56.19% were male. In our study, 62.40% of patients were married, and 87.05% were white. Most patients (90.42%) were diagnosed with anaplastic oligodendroglioma as their first malignant primary tumor, but 9.58% had a diagnosis of at least one other primary malignancy; 87.89% of patients had received cancer-directed surgery. Patients receiving surgery had a better prognosis for overall survival compared to those not receiving surgery after propensity score matching analysis (p<0.05). The overall 1-, 3-, 5-, and 10-year survival of anaplastic oligodendroglioma was 78.7%, 60%, 50.2%, and 36.2%, respectively. Kaplan-Meier analysis indicated that age, marital status, presence of multiple primary malignancies, and surgical treatment were associated with overall survival, whereas sex and race were not. Moreover, age at diagnosis of 52 years was calculated as an optimal cutoff value to distinguish better and worse overall survival. Multivariate Cox proportional hazard analysis indicated that older age (OR 1.040, 95%CI1.035-1.045), single patients (OR 1.293, 95%CI 1.103-1.515), and presence of multiple primary malignancies (OR 1.501, 95%CI 1.238-1.820) were significantly associated with worse overall survival, whereas surgery (OR 0.584, 95%CI 0.494-0.689) was associated with better overall survival. A nomogram predicting 5-, and 10-year survival probability for anaplastic oligodendroglioma was constructed based on these variables. In conclusion, age, marital status, presence of multiple primary malignancies, and surgical treatment were associated with survival of anaplastic oligodendroglioma.

Prevalence of hyperuricemia among the Chinese population of the southeast coastal region and association with single nucleotide polymorphisms in urate­anion exchanger genes: SLC22A12, ABCG2 and SLC2A9.

Genome­wide association studies identified that a series of genes, including solute carrier family (SLC) 2 member 9 (SLC2A9), SLC 22 member 12 (SLC22A12) and ATP­binding cassette sub­family G member 2 (ABCG2) polymorphisms were associated with serum uric acid (SUA) levels in the present study. High incidence rates of hyperuricemia were reported in the Chinese population of the southeast coastal region; however, no evidence has confirmed the genetic association with SUA levels in this region. The present study aimed to investigate the association between uric acid levels and hyperuricemia, and genotypes of the Chinese population of the southeast coastal region. In the present study, a total of 1,056 healthy patients attending routine checkups were employed to investigate the incidence of hyperuricemia; 300 subjects were then randomly selected from the 1,056 patients for the identification of genetic polymorphisms of SLC2A9rs11722228, SLC22A12rs893006 and ABCG2rs2231142 via high­resolution melting. The present study reported that the incidence rate of hyperuricemia was 32.6% (42.5% in males and 22.7% in females, respectively). The prevalence of ABCG2rs2231142 polymorphisms (CC, CA and AA) was 44.4, 44.8 and 11.8%, respectively; SLC2A9rs11722228 polymorphisms (CC, CT and TT) were reported to be 49.3, 40.3 and 10.3%, respectively. Additionally, SLC22A12rs893006 polymorphisms (CC, CT and TT) were determined to be 57.2, 38.7 and 4.1%, respectively. The SUA levels were observed to be statistically different among each investigated genotype of ABCG2rs2231142 (P=0.047). The A allele was significantly associated with an increased risk of hyperuricemia (odds ratio=2.405 and 1.133 for CA and AA, respectively). The present study reported that high incidence rates of hyperuricemia in the Chinese population of the southeast coastal region may be closely associated with the variants of ABCG2rs2231142. Whether polymorphisms of SLC2A9rs11722228 and SLC22A12rs893006 are involved in hyperuricemia require further investigation.

Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials.

BACKGROUND: Intravenous glucocorticoids are recommended for multiple sclerosis (MS). However, they can be inconvenient and expensive. Due to their convenience and low cost, oral glucocorticoids may be an alternative treatment. Recently, several studies have shown that there is no difference in efficacy and safety between oral methylprednisolone (oMP) and intravenous methylprednisolone (ivMP). OBJECTIVES: We sought to assess the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses in this meta-analysis. METHODS: Randomized controlled trials (RCTs) evaluating the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane Library, Medline, EMBASE and China Biology Medicine until October 25, 2016, without language restrictions. The proportion of patients who had improved by day 28 was chosen as the efficacy outcome. We chose the risk ratio (RR) to analyze each trial with the 95% confidence interval (95% CI). We also used the fixed-effects model (Mantel-Haenszel approach) to calculate the pooled relative effect estimates. RESULTS: A total of 5 trials were identified, which included 369 patients. The results of our meta-analysis revealed that no significant difference existed in relapse improvement at day 28 between oMP and ivMP (RR 0.96, 95% CI 0.84 to 1.10). No evidence of heterogeneity existed among the trials (P = 0.45, I2 = 0%). Both treatments were equally safe and well tolerated except that insomnia was more likely to occur in the oMP group compared to the ivMP group. CONCLUSION: Our meta-analysis reveals strong evidence that oMP is not inferior to ivMP in increasing the proportion of patients experiencing clinical improvement at day 28. In addition, both routes of administration are equally well tolerated and safe. These findings suggest that we may be able to replace ivMP with oMP to treat MS relapses.

Effects of biovar I and biovar II of ureaplasma urealyticum on sperm parameters, lipid peroxidation, and deoxyribonucleic acid damage in male infertility.

OBJECTIVE: To reveal the impact of 2 biovars of Ureaplasma urealyticum on the sperm of infertile men by producing reactive oxygen species (ROS). METHODS: A total of 223 infertile and 146 fertile men were recruited into the study. Standard semen analysis was performed. Culturing and real-time polymerase chain reaction were used to identify biovars of U urealyticum in the semen. Semen ROS, malondialdehyde, and total superoxide dismutase levels were measured. Sperm nuclear deoxyribonucleic acid (DNA) damage was assessed of by sperm chromatin structure assay and single-cell gel electrophoresis. RESULTS: Biovar II infection was more frequent in infertile men (P=.036). When compared with uninfected individuals, biovar II-infected men displayed decreases in spermatozoa concentration (P=.041); biovar II and mix-infected men displayed decreases in total motility (P=.015; P=.014, respectively) and increase in leukocyte counts (P=.004; P=.003, respectively). Except for total superoxide dismutase level, indicators for peroxide including ROS level, malondialdehyde level, DNA fragmentation index and high DNA stainable in sperm chromatin structure assay, and tail moment in single-cell gel electrophoresis exhibited the significant differences between both infected groups vs the uninfected group (P<05). CONCLUSION: Compared with biovar I, biovar II is more likely to cause male infertility. Increased leukocyte counts, ROS level elevation, and subsequent spermatozoa membrane and DNA damage may be involved in this pathogenesis.