Journal of Circulating Biomarkers最新文献

Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS).

Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI.

Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters.

Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy.

Methods: Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood.

Results: The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53, and BRCA2 locus.

Conclusions: The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.

Purpose: Due to a lack of effective antiviral treatment, several vaccines have been put forth to curb SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and to reduce the mortality and morbidity rate by eliciting a protective immune response, primarily through virus-neutralizing antibodies specific for SARS-CoV-2 spike protein. This longitudinal study was designed to evaluate the vaccine effectiveness and immune response following the administration of adenoviral vaccine, COVISHIELD, in Indian population who were previously uninfected with SARS-CoV-2 and to reveal the effect of various sociodemographic, inflammatory and biochemical factors on antibody response.

Methods: Briefly, the total immunoglobulin G (IgG) against SARS-CoV-2 spike and nucleocapsid protein along with the immunological markers were estimated by chemiluminescent microparticle immunoassay (CMIA) technology. Biochemical parameters were estimated by spectrometry.

Results: A total of 348 subjects received two doses of COVISHIELD (224 males, 124 females). The mean age of the study subjects was 42.03 ± 13.54 years. Although both the doses of COVISHIELD against SARS-CoV-2 spike protein induced a robust immune response that lasted for months in all the subjects, the total IgG titer against SARS-CoV-2 spike protein was found significantly higher in subjects ≥50 years of age, and those with obesity, elevated triglycerides and elevated lactate dehydrogenase levels.

Conclusions: There is a definite effect of age and biochemical factors on the immunogenicity of COVISHIELD. An understanding of these factors could not only impact the design of vaccines and help improve vaccine immunogenicity and efficacy but also assist in decisions on vaccination schedules, in order to combat this deadly pandemic.

Delayed cerebral ischemia (DCI) substantially contributes to disability and death in subarachnoid hemorrhage (SAH) patients; however, its pathophysiology is incompletely understood and diagnostic and therapeutic strategies are lacking. Biomarkers may help to elucidate the pathophysiology, optimize early diagnosis, or provide treatment targets. We systematically searched PubMed and Embase on October 13, 2021, for studies that evaluated at least one laboratory biomarker in patients with DCI, using the most up-to-date definition of DCI as proposed by a panel of experts in 2010. Quality of studies was assessed using the Newcastle-Ottawa Scale or Cochrane Collaboration's risk of bias assessment tool. Biomarkers of clinical and radiological DCI were analyzed separately. Results were meta-analyzed if possible, otherwise narratively reviewed. Biomarkers were classified as significant, inconclusive, or nonsignificant. We defined validated biomarkers as those with significant results in meta-analyses, or in at least two studies using similar methodologies within the same time interval after SAH. The search yielded 209 articles with 724 different biomarkers; 166 studies evaluated 646 biomarkers of clinical DCI, of which 141 were significant and 7 were validated biomarkers (haptoglobulin 2-1 and 2-2, ADAMTS13, vWF, NLR, P-selectin, F2-isoprostane); 78 studies evaluated 165 biomarkers of radiological DCI, of which 63 were significant and 1 was a validated biomarker (LPR). Hence, this review provides a selection of seven biomarkers of clinical DCI and one biomarker of radiological DCI as most promising biomarkers of DCI. Future research should focus on determining the exact predictive, diagnostic, and therapeutic potentials of these biomarkers.

Background: Hepatocellular carcinoma (HCC) is a lethal cancer. Two biomarkers were used for HCC diagnosis including alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II or antagonist (PIVKA-II). However, data on biomarkers and HCC diagnosis are not consistent. This study aimed to evaluate if PIVKA-II, AFP, or a combination of both biomarkers had the best diagnostic properties for HCC.

Methods: This was a prospective study and enrolled patients 18 years or over with a high risk for HCC. AFP and PIVKA-II levels were calculated for HCC diagnosis. Diagnostic properties of both biomarkers were reported with sensitivity, specificity, and a receiver operating characteristic (ROC) curve.

Results: There were 260 patients with high risk for HCC in this cohort. Of those, 219 patients were diagnosed with HCC: confirmed by biopsy in 7 patients (2.69%) and by imaging in the others. Median values of AFP and PIVKA-II were 56 ng/mL and 348 mAU/mL, respectively. PIVKA-II level of 40 mAU/mL had sensitivity of 80.80%, while AFP of 10 ng/mL had sensitivity of 75.80%. A combination of PIVKA-II at 100 mAU/mL or over and AFP of 11 ng/mL gave sensitivity of 60.30%. The ROC curve of PIVKA-II plus AFP was significantly higher than the AFP alone (0.855 vs. 0.796; p = 0.027), but not significantly different from the PIVKA-II alone (0.855 vs. 0.832; p = 0.130).

Conclusion: PIVKA-II may have more diagnostic yield for HCC compared with AFP. It can be used alone without a combination with AFP.

Introduction: The Parsortix^® PC1 system, Food and Drug Administration (FDA) cleared for use in metastatic breast cancer (MBC) patients, is an epitope-independent microfluidic device for the capture and harvest of circulating tumor cells from whole blood based on cell size and deformability. This report details the analytical characterization of linearity, detection limit, precision, and reproducibility for this device.

Methods: System performance was determined using K₂-EDTA blood samples collected from self-declared healthy female volunteers (HVs) and MBC patients spiked with prelabeled cultured breast cancer cell lines (SKBR3, MCF7, or Hs578T). Samples were processed on Parsortix^® PC1 systems and captured cells were harvested and enumerated.

Results: The system captured and harvested live SKBR3, MCF7, and Hs578T cells and fixed SKBR3 cells linearly between 2 and ~100 cells, with average harvest rates of 69%, 73%, 79%, and 90%, respectively. To harvest ≥1 cell ≥95% of the time, the system required 3, 5 or 4 live SKBR3, MCF7 or Hs578T cells, respectively. Average harvest rates from precision studies using 5, 10, and ~50 live cells spiked into blood for each cell line ranged from 63.5% to 76.2%, with repeatability and reproducibility percent coefficient of variation (%CV) estimates ranging from 12.3% to 32.4% and 13.3% to 34.1%, respectively. Average harvest rates using ~20 fixed SKBR3 cells spiked into HV and MBC patient blood samples were 75.0% ± 16.1% (%CV = 22.3%) and 68.4% ± 14.3% (%CV = 21.1%), respectively.

Conclusions: These evaluations demonstrate the Parsortix^® PC1 system linearly and reproducibly harvests tumor cells from blood over a range of 1 to ~100 cells.