Conventional Markers Research Articles

Novel electric predictors of lethal arrhythmic event in patients with hypertrophic cardiomyopathy

Abstract Background Little is known regarding the association between electrical markers and lethal arrhythmic events (LAE) in patients with hypertrophic cardiomyopathy (HCM). This study aimed to identify the electrical predictors of LAE in adult patients with HCM. Methods This study was a retrospective analysis of patients with HCM at a single center from 1998 to 2021. LAE was defined as a composite outcome of (1) sustained ventricular arrhythmia, (2) aborted sudden cardiac death (SCD), (3) implantable cardioverter defibrillator (ICD) implantation, and (4) appropriate ICD shock. A 12-lead electrocardiography was performed at the time of diagnosis. Results A total of 611 patients with HCM were analyzed, and 48 (7.8%) experienced LAE. Patients who experienced LAE were diagnosed at a younger age and more frequently had history of ventricular arrhythmia, new-onset atrial fibrillation (AF) or non-sustained ventricular tachycardia. New-onset AF, an increase in the QTc interval, and the absence of massive LVH were associated with LAE risk. In addition to conventional markers of HCM Risk-SCD, consideration of the QTc interval and massive LVH on electrocardiography improved the prediction of LAE (area under curve 0.682 to 0.740). Further inclusion of new-onset AF, history of ventricular arrhythmia, HCM type, and left ventricular mass index improved the predictability to 0.867. Conclusion An increase in the QTc interval, the absence of a massive LVH pattern on electrocardiography (ECG), and new-onset AF were independently associated with an increased risk of LAE. Comprehensive stratification using electrical markers improves the prediction of LAE when combined with conventional markers.

The added value of deep learning to submaximal exercise electrocardiogram for the 10-year prediction of major adverse cardiovascular and cerebrovascular events

Abstract Background The added value of exercise ECG data to traditional risk factors in predicting cardiovascular events remains unclear. Deep learning of ECG signals has demonstrated state-of-the-art performance in detecting subtle abnormalities indicative of cardiovascular disease. We investigated whether deep learning analysis of exercise ECGs could improve the prediction of major cardiovascular and cerebrovascular events (MACCE) with respect to established risk models in a large population-based cohort. Purpose To assess the added value of submaximal exercise ECG measurements to established cardiovascular risk prediction models. Methods We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We created two deep neural network ECG risk scores: one derived from conventional ECG parameters, measured at rest, peak exercise and late-stage recovery, and another based on the complete ECG (Q-ECG). We assessed the added value of conventional ECG parameters and Q-ECG risk scores to the UK's current prediction algorithm (QRISK3). We estimate the association between ECG parameters and MACCE, using Cox Proportional hazard models, following adjustment for traditional risk factors. All models were internally validated via 5-fold cross-validation and 1000 bootstrap iterations. Predictive performance was evaluated using Harrel's C-index, Net Reclassification Index (NRI) and net benefit. Findings: Incident MACCE was reported in 4,082 (9.9%) individuals in the study population and 3,463(9.7%) individuals with valid ECG parameters over a median follow-up period of 12.5 years. We found combined conventional ECG and Q-ECG scores were independently associated with MACCE, following adjustment for multiple testing: adjusted hazard ratio [HZ] = 1.76 (95% CI:1.63-1.91); HZ = 1.14 (95% CI:1.10-1.18), respectively, per standard deviation increase. Both conventional ECG parameters and Q-ECG were predictive of MACCE, independent of clinical risk factors, C-index = 0.64 (95%CI 0.63-0.65); net benefit = 0.09(95% CI 0.07 - 0.11) and C-index = 0.56 (95% CI 0.55-0.57); net benefit = 0.07(95% CI 0.05 - 0.09). ECG measurement's modestly improved model discrimination over the bassline QRISK3 risk score when combined with QRISK3 risk factors for conventional markers and Q-ECG score, respectively; ΔC-index 0.03 (95% CI: 0.02 – 0.04) and ΔC-index 0.03 (95% CI: 0.02 – 0.03); However, we observed no significant improvements in classification at the current recommended threshold of 10%. Conclusion In individuals without a history of prior cardiovascular disease, ECG measures independently predict the risk of MACCE. When combined with QRISK3, neural-network-derived ECG risk scores marginally improve cardiovascular risk prediction over QRISK3.

An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification

BackgroundThe triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.MethodsUsing least-square regression analysis, the following eLDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95. LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632).ResultseLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG > 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29–1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.ConclusionsLike LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.

New tumor markers for testicular cancer - in the here and now and in the future

Germ cell tumors of the testis are the most common tumor entities in young men. Since the introduction of platinum-based chemotherapy in the 1970s, most patients can be cured despite the aggressiveness of germ cell tumors. Optimal serum tumor markers are required for diagnostics, therapy monitoring and aftercare, and these are subject to high requirements. The conventional testicular tumor markers human chorionic gonadotropin (hCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) only meet these requirements with insufficient sensitivity (30-70%). The markers investigated in recent decades, such as PLAP, CEA and NSE, have not become established. Currently, miRNA-371 is being researched in particular. Reliable findings are available for initial staging with significantly better specificities of miRNA-371 compared to conventional tumor markers. Further prospective studies are being conducted for other possible clinical applications, such as follow-up care, therapy monitoring or residual tumors, in order to investigate the revolutionary potential of miRNA-371 in these areas as well. Research is also currently being conducted on circulating tumor cells (CTCs) and cell-free DNA (cfNA) in various areas of application. With regard to germ cell tumors of the testis, however, these analyses are still in their infancy, but it is hoped that this will provide a further sufficient opportunity to use serum tumor markers.

Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response. We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay. ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone. Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.

PAX5 and CD70 are expressed in thymic carcinoma but not in atypical thymoma (WHO type B3 thymoma): an immunohistochemical analysis of 60 cases

AimsThymic carcinoma and atypical thymoma (WHO type B3 thymoma) are unusual tumours the separation of which may be challenging in small biopsies. Both tumours consist of epithelioid tumour cells that...

Unveiling Genetic Diversity Among Bacterial Isolates Using SCoT Markers.

This study aimed to unveil the genetic diversity among 47 bacterial isolates from various species using start codon targeted (SCoT) markers. Six SCoT primers yielded 219 reproducible bands, with 89.04% exhibiting polymorphism. The amplification process generated 28 to 50 fragments per primer, with an average of 36.50. Genetic diversity was quantified using polymorphic information content (PIC) values ranging from 0.11 to 0.14, with SCoT32 showing the highest PIC (0.14) and SCoT23 the lowest (0.11). The resolving power (RP) index, used to assess primer discriminatory power, varied significantly, with SCoT23 demonstrating the highest RP (6.00) and SCoT29 the lowest (4.51). Comparative analysis with conventional markers like M13 and (GTG)5 revealed that certain SCoT primers exhibited superior PIC values, which indicates enhanced utility for interspecies differentiation. The high discrimination level achieved by SCoT primers underscores their effectiveness in genetic differentiation and biodiversity assessment within bacterial populations. This research highlights SCoT markers as powerful tools for microbial genetic studies, which offers valuable insights into bacterial diversity and provides a robust methodological framework for future investigations aimed at elucidating genetic variation and improving species identification. The application of SCoT markers represents a significant advancement in molecular techniques for bacterial characterization and phylogenetic analysis, demonstrating their potential to enhance our understanding of microbial genetics and evolution.

Oxidative stress: fundamentals and advances in quantification techniques.

Oxidative species, generated endogenously via metabolism or from exogenous sources, play crucial roles in the body. At low levels, these species support immune functions by participating in phagocytosis. They also aid in cellular signaling and contribute to vasomodulation. However, when the levels of oxidative species exceed the body's antioxidant capacity to neutralize them, oxidative stress occurs. This stress can damage cellular macromolecules such as lipids, DNA, RNA, and proteins, driving the pathogenesis of diseases and aging through the progressive deterioration of physiological functions and cellular structures. Therefore, the body's ability to manage oxidative stress and maintain it at optimal levels is essential for overall health. Understanding the fundamentals of oxidative stress, along with its reliable quantification, can enable consistency and comparability in clinical practice across various diseases. While direct quantification of oxidant species in the body would be ideal for assessing oxidative stress, it is not feasible due to their high reactivity, short half-life, and the challenges of quantification using conventional techniques. Alternatively, quantifying lipid peroxidation, damage products of nucleic acids and proteins, as well as endogenous and exogenous antioxidants, serves as appropriate markers for indicating the degree of oxidative stress in the body. Along with the conventional oxidative stress markers, this review also discusses the role of novel markers, focusing on their biological samples and detection techniques. Effective quantification of oxidative stress may enhance the understanding of this phenomenon, aiding in the maintenance of cellular integrity, prevention of age-associated diseases, and promotion of longevity.

B-082 Clinical Investigation of Rods and Rings Pattern in Anti-Nuclear Antibody Test in Korean Patients

Abstract Background In the mid-2000s, a novel pattern in antinuclear antibody (ANA) testing was reported. Indirect immunofluorescence assays on HEp-2 cells, conducted with sera from patients with Hepatitis C virus (HCV) infection, revealed cytoplasmic structures in the form of rods and rings (RR). These structures typically displayed rod lengths of 3-10μm and ring diameters of 2-5μm. Inosine monophosphate dehydrogenase (IMPDH) was identified as the primary component of the RR structures. Research on the administration of interferon/ribavirin (IFN/RBV) showed that ribavirin, an IMPDH inhibitor, induced RR formation in over 95% of cells. Additionally, RR patterns were reported in patients receiving other IMPDH inhibitors such as mycophenolic acid and azathioprine. While cytidine triphosphate synthase 1 (CTPS1) was suggested to be associated with RR structures, there were no reported cases in patients. Interestingly, patients receiving methotrexate, which does not directly inhibit IMPDH but hinders GTP biosynthesis, also exhibited RR structures. To explore the clinical implications of specimens showing RR patterns, a study was conducted to investigate the actual clinical scenarios associated with these findings. Methods This is a retrospective study conducted at a single center, covering the period from January 2022 to December 2023, focusing on the results of ANA testing. The ANA tests were performed using HEp-2 cells (FLUORO HEPANA TEST, MBL, Nagoya, Japan) on slides manufactured with AP 16 IF Plus (das, Palombara Sabina, RM, Italy). ANA results were obtained through qualitative testing, ranging from 1+ to 4+, or quantitative testing based on dilutions ranging from 1:40 to 1:640, depending on clinical requirements. Results Out of the 7,648 ANA test results, the RR pattern was observed in 40 cases (0.5%). Among these, 2.5% had a history of HCV infection with IFN/RBV treatment, and an additional 2.5% had concurrent use of IMPDH inhibitors. There were no reported cases of medication history related to the synthetic pathway of nucleic acids, including CTPS1. Cases where RR patterns coexisted with autoimmune diseases accounted for 35%, infections for 25%, and other inflammatory conditions for 22.5%. RR patterns reported with an intensity of 3+ or at dilutions of 1:160 or higher constituted 27.5%. Among cases displaying strong fluorescence, 45% were associated with infections, 18% with autoimmune conditions, and another 18% with unexplained inflammatory causes. In the overall sample, elevated CRP or ESR was noted in 54.5% of cases with infections, autoimmune diseases, or other inflammatory conditions. Among samples with intense intensity, 55.5% showed elevated CRP or ESR when inflammatory conditions were present. Conclusions The majority of cases exhibiting the RR pattern showed no history of exposure to IMPDH inhibitors or drugs affecting the nucleic acid synthetic pathway. A high proportion of cases clinically diagnosed with inflammation showed a concurrent RR pattern, with only approximately half of them demonstrating elevated CRP or ESR levels. This study suggests the possibility of identifying inflammatory responses not captured by conventional acute inflammation markers through the RR pattern observed in ANA testing.

Are Red Blood Cell Distribution Width and Platelet Count Useful for Diagnosing Periprosthetic Joint Infection in Patients Undergoing Re-Revision Arthroplasty.

Accurate and prompt identification of periprosthetic joint infections (PJIs) is critical prior to re-revision arthroplasty to ensure optimal surgical outcomes. Among routinely measured blood indices, red blood cell distribution width (RDW) and platelet count (PLT) have shown strong correlations with infection presence. This study aimed to assess the utility of RDW and PLT for diagnosing PJI in patients scheduled for re-revision arthroplasty. This retrospective research encompassed all patients who underwent re-revision hip or knee arthroplasty at our institution from 2008 to 2022. Participants were categorized into either the PJI (n = 41) or the non-PJI (n = 47) group following the guidelines established in the 2013 International Consensus Meeting on PJI. In this analysis, RDW and PLT counts were evaluated alongside conventional inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The efficacy of these diagnostics was evaluated by the area under the receiver operating characteristic (ROC) curve ([area under the curve AUC]). RDW demonstrated a modest AUC of 0.678 with sensitivity at 61.0% and specificity at 71.7%, using a threshold of 14.5%. PLT was on par with ESR, showing an AUC of 0.773, and both sensitivity and specificity around 73% at a threshold of 201 × 109/L. CRP presented the highest diagnostic accuracy with an AUC of 0.815, achieving a sensitivity of 82.9% and specificity of 73.9% at a 6.9 mg/L threshold, surpassing ESR's AUC of 0.754. None of the biomarkers, individually or combined, outperformed CRP alone (p > 0.05). In the context of re-revision arthroplasty, RDW and PLT demonstrate limited efficacy as diagnostic biomarkers for PJI. However, CRP retains its reliability as a biomarker when the diagnostic threshold is appropriately recalibrated.

Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Histopathological correlations of CT-based radiomics imaging biomarkers in native kidney biopsy

BackgroundKidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade.MethodsWe included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI).ResultsOverall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75–0.99) and 0.74 (95% CI 0.52–0.93) for total parenchymal and cortical ROI features, respectively.ConclusionSignificant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis.

Extensive transcriptome data providing great efficacy in genetic research and adaptive gene discovery: a case study of Elymus sibiricus L. (Poaceae, Triticeae).

Genetic markers play a central role in understanding genetic diversity, speciation, evolutionary processes, and how species respond to environmental stresses. However, conventional molecular markers are less effective when studying polyploid species with large genomes. In this study, we compared gene expression levels in 101 accessions of Elymus sibiricus, a widely distributed allotetraploid forage species across the Eurasian continent. A total of 20,273 high quality transcriptomic SNPs were identified. In addition, 72,344 evolutionary information loci of these accessions of E. sibiricus were identified using genome skimming data in conjunction with the assembled composite genome. The population structure results suggest that transcriptome SNPs were more effective than SNPs derived from genome skimming data in revealing the population structure of E. sibiricus from different locations, and also outperformed gene expression levels. Compared with transcriptome SNPs, the investigation of population-specifically-expressed genes (PSEGs) using expression levels revealed a larger number of locally adapted genes mainly involved in the ion response process in the Sichuan, Inner Mongolia, and Xizang geographical groups. Furthermore, we performed the weighted gene co-expression network analysis (WGCNA) and successfully identified potential regulators of PSEGs. Therefore, for species lacking genomic information, the use of transcriptome SNPs is an efficient approach to perform population structure analysis. In addition, analyzing genes under selection through nucleotide diversity and genetic differentiation index analysis based on transcriptome SNPs, and exploring PSEG through expression levels is an effective method for analyzing locally adaptive genes.

Serum exosomal miR-200c is a potential diagnostic biomarker for breast cancer

Background Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in BC serum exosomes and its diagnostic value. Methodology miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7, MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves. Results We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without BC disease and could be used as an early diagnostic marker for BC disease. Conclusion Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.

Estimation of Serum Malondialdehyde (a Marker of Oxidative Stress) as a Predictive Biomarker for the Severity of Coronary Artery Disease (CAD) and Cardiovascular Outcomes.

Background Coronary artery disease (CAD) is influenced by oxidative stress, which is a critical yet often overlooked factor in disease progression. While traditional biomarkers such as cholesterol levels and blood pressure are commonly used, they do not fully capture oxidative damage. Malondialdehyde (MDA), a byproduct of lipid peroxidation, offers additional insights into oxidative stress and CAD severity. Unlike conventional markers, such as low-density lipoprotein (LDL) cholesterol, which primarily reflects lipid levels, and high-sensitivity C-reactive protein (hs-CRP), which indicates inflammation, MDA directly measures oxidative damage. This makes MDA a potentially valuable complement to these traditional biomarkers, providing a more nuanced understanding of CAD risk. Despite its potential, the role of MDA in clinical assessments remains underexplored. This study aims to address this gap by evaluating MDA's effectiveness as a complementary biomarker, enhancing the assessment of CAD risk and progression beyond what is provided by existing markers. Objective This study aims to assess serum MDA levels in relation to CAD severity to explore its potential as a non-invasive biomarker for disease progression and cardiovascular outcomes. Methodology This cross-sectional study was conducted at the Department of Cardiology, Mardan Medical Complex Teaching Hospital, Pakistan, from June 2023 to May 2024. Patients were divided into different groups with varying severity of CAD. The one-way ANOVA was used to assess differences among groups, and Pearson's correlation coefficient explored relationships between MDA and all study variables. Simple linear regression analyzed associations between MDA levels, patient groups, and other variables, controlling for covariates. MDA's potential as a predictive biomarker was assessed through ROC curve analysis, with statistical significance set at a p-value < 0.05. Results A total of 133 patients were included in the study, categorized based on CAD severity into mild (n=71), moderate (n=39), and severe (n=23) groups. Serum MDA levels significantly increased with the severity of CAD. Specifically, MDA levels were 116.61 ± 41.95in the mild group, 253.45 ± 180.29in the moderate group, and peaked at 459.91 ± 149.80in the severe group. The differences in MDA levels among these groups were statistically significant (p < 0.01), supporting the association between higher MDA levels and increased CAD severity. Factors such as BMI, heart rate, blood pressure, and smoking status also significantly influenced MDA levels. Receiver operating characteristic (ROC) curve analysis demonstrated high diagnostic accuracy of MDA for assessing CAD severity, with area under the curve (AUC) values of 0.81 for moderate and 0.94 for severe CAD. Comorbid conditions such as diabetes mellitus were associated with elevated MDA levels. Conclusion Elevated serum MDA serves as a reliable, non-invasive biomarker for predicting CAD severity, with potential applications in clinical risk assessment and management strategies. By identifying patients with elevated oxidative stress early, clinicians can implement timely interventions, potentially slowing disease progression and improving outcomes.

Evaluating RB1 and p53 as diagnostic markers in treatment-related neuroendocrine prostate cancer through immunohistochemistry and genomic analysis of RB1 and TP53.

The diagnosis of treatment-related neuroendocrine prostate cancer (t-NEPC) often involves a pathological assessment and immunohistochemistry (IHC) for neuroendocrine markers. Genomic alterations in RB1 and TP53 are frequently observed in NEPC and are believed to play a crucial role in the transformation of adenocarcinoma to NEPC. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of patients with t-NEPC to better understand their prognosis and diagnostic utility. This retrospective study reviewed the records of patients diagnosed with t-NEPC at Kobe University Hospital between October 2018 and December 2022. Clinical data, including age, serum neuroendocrine marker levels, and treatment history, were collected. IHC was performed for conventional neuroendocrine markers (synaptophysin, chromogranin A, and CD56) and RB1 and p53 expression. Next-generation sequencing (NGS) was conducted using FoundationOne® CDx to identify mutations in RB1 and TP53. This study included 20 patients with t-NEPC. The median time from ADT initiation to development was 42.8 months. IHC revealed RB1 loss in 75% of cases and p53 abnormalities in 75% of cases. NGS identified RB1 mutations in 55% and TP53 mutations in 75% of cases. The concordance between NGS and IHC results was high, with 70% (14/20) agreement for RB1/RB1 and 80% (16/20) for p53/TP53. The immunostaining and genomic analysis of RB1/RB1 and p53/TP53 showed abnormal findings for the four negative cases for conventional neuroendocrine markers. This study indicated high concordance between IHC and NGS findings for RB1/RB1 and p53/TP53 in t-NEPC. We provide a comprehensive benchmark of NGS performance compared with IHC, and these findings may help increase the diagnostic sensitivity of t-NEPC.

Non-Conventional Prognostic Markers in Life-Threatening COVID-19 Cases-When Less Is More.

Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio-NLR; platelet/lymphocyte ratio-PLR) and conventional markers (C-reactive protein-CRP; procalcitonin-PCT; interleukin-6-IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR's accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes.

Ex-Vivo Human-Sized Organ Machine Perfusion: A Systematic Review on the Added Value of Medical Imaging for Organ Condition Assessment.

Machine perfused ex-vivo organs offer an excellent experimental platform, e.g., for studying organ physiology and for conducting pre-clinical trials for drug delivery. One main challenge in machine perfusion is the accurate assessment of organ condition. Assessment is often performed using viability markers, i.e., lactate concentrations and blood gas analysis. Nonetheless, existing markers for condition assessment can be inconclusive, and novel assessment methods remain of interest. Over the last decades, several imaging modalities have given unique insights into the assessment of organ condition. A systematic review was conducted according to accepted guidelines to evaluate these medical imaging methods, focussed on literature that use machine perfused human-sized organs, that determine organ condition with medical imaging. A total of 18 out of 1,465 studies were included that reported organ condition results in perfused hearts, kidneys, and livers, using both conventional viability markers and medical imaging. Laser speckle imaging, ultrasound, computed tomography, and magnetic resonance imaging were used to identify local ischemic regions and quantify intra-organ perfusion. A detailed investigation of metabolic activity was achieved using 31P magnetic resonance imaging and near-infrared spectroscopy. The current review shows that medical imaging is a powerful tool to assess organ condition.

A Study of Tpeak-Tend/QT Interval Ratio in Predicting Heart Failure in ST-Elevation Myocardial Infarction and Its Correlation With N-terminal Pro B-type Natriuretic Peptide (NT-proBNP).

Background Acute ST-elevation myocardial infarction (STEMI) is the most common cause of mortality across the world. The electrocardiogram (ECG) Tpeak-Tend/QT interval appears to be a measure of the left ventricle's transmural dispersion of repolarization (TDR). Prolongation of this time could indicate adverse cardiac events like heart failure, arrhythmias, etc. Heart failure is a clinical syndrome that includes signs and symptoms such as peripheral edema and high jugular vein pressure. N-terminal pro B-type natriuretic peptide (NT-proBNP) is an effective predictor of left ventricular function and also helps in predicting the disease prognosis. Elevated levels of NT-proBNP are seen in many cases of left ventricular dysfunction. This study aims to evaluate the predictive utility of the Tpeak-Tend/QT interval ratio in predicting major adverse cardiac events (MACEs), such as heart failure, by examining the Tend/QT interval ratio values with NT-proBNP in STEMI. Methodology This cross-sectional study was conducted at a tertiary hospital between April 2024 and June 2024. It included STEMI patients, excluding those with non-STEMI (NSTEMI), valvular heart diseases, bundle branch block, or pacemakers. The patients with a Tpeak-Tend/QT ratio < 0.3 were included in group A, and the Tpeak-Tend/QT ratio > 0.3 in group B. They were monitored for MACE-like heart failure during hospitalization and were compared with a study of the Tpeak-Tend/QT interval ratio in predicting heart failure in STEMI and its correlation with NT-proBNP levels. Results In this study, out of 45 patients, male predominance was observed, with 35 (78%) being men and 10 (22%) being women. In group A, the most common age group was 60-70 years, with 16 (51%) patients; in Group B, it was 50-60 years, with six (42.8%) patients. Out of 31 patients in group A, 25 were male, and six were female. In group B, out of 14 patients, 10 were male, and four were female. In this study, out of the 45 patients included, 12 (85%) among 14 patients who had MACEs like heart failure had a Tpeak-Tend/QT interval ratio of more than 0.3, and their measured NT-proBNP levels were also more than 900 pg/mL, thus showing a statistically significant association between Tpeak-Tend/QT interval ratio and NT-proBNP. Conclusion The present study showed an increased Tpeak-Tend/QT interval ratio and NT-proBNP in patients who developed heart failure in STEMI. As ECG is a readily available and affordable tool, the Tpeak-Tend/QT interval ratio can be used along with conventional markers like NT-proBNP to predict MACE in patients with STEMI.

MicroRNA-532-3p Modulates Colorectal Cancer Cell Proliferation and Invasion via Suppression of FOXM1.

Colorectal cancer (CRC) is a heterogeneous disease and classified into various subtypes, among which transcriptional alterations result in CRC progression, metastasis, and drug resistance. Forkhead-box M1 (FOXM1) is a proliferation-associated transcription factor which is overexpressed in CRC and the mechanisms of FOXM1 regulation have been under investigation. Previously, we showed that FOXM1 binds to promoters of certain microRNAs. Database mining led to several microRNAs that might interact with FOXM1 3'UTR. The interactions between shortlisted microRNAs and FOXM1 3'UTR were quantitated by a dual-luciferase reporter assay. MicroRNA-532-3p interacted with the 3'UTR of the FOXM1 mRNA transcript most efficiently. MicroRNA-532-3p was ectopically overexpressed in colorectal cancer (CRC) cell lines, leading to reduced transcript and protein levels of FOXM1 and cyclin B1, a direct transcriptional target of FOXM1. Further, a clonogenic assay was conducted in overexpressed miR-532-3p CRC cells that revealed a decline in the ability of cells to form colonies and a reduction in migratory and invading potential. These alterations were reinforced at molecular levels by the altered transcript and protein levels of the conventional EMT markers E-cadherin and vimentin. Overall, this study identifies the regulation of FOXM1 by microRNA-532-3p via its interaction with FOXM1 3'UTR, resulting in the suppression of proliferation, migration, and invasion, suggesting its role as a tumor suppressor in CRC.