Peripheral Venous Blood Samples Research Articles

The use of venous blood gas in assessing arterial acid−base and oxygenation status – an analysis of aggregated data from multiple studies evaluating the venous to arterial conversion (v-TAC) method

ABSTRACT Background Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria. Research design and methods We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits. Results 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (−0.029 to 0.031), PCO2 −0.08 (−0.65 to 0.49) kPa, and PO2 0.04 (−1.71 to 1.78) kPa, with similar values for all sub-group analyses. Conclusion These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid−base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.

Empowerment, Pain Control, and Quality of Life Improvement in Early Triple-Negative Breast Cancer Patients through Pain Neuroscience Education: A Prospective Cohort Pilot Study Protocol (EMPOWER Trial)

The treatment of early triple-negative breast cancer (eTNBC) has improved patients’ prognosis but often leads to adverse events and sequelae affecting quality of life (QoL). Pain Neuroscience Education (PNE) is a promising non-pharmacological intervention in this field. Preliminary data have shown the beneficial effect of PNE in BC survivors. However, there are still gaps in knowledge regarding its optimal use in eTNBC. To address this issue, a prospective pilot study will enroll 30 consecutive patients diagnosed with eTNBC at IRCCS Humanitas Research Hospital. The PNE program will consist of 10 weekly sessions to be started within 4 weeks of the onset or worsening of a pain syndrome (PS). QoL, pain, and disability will be assessed before, during, at the end of, and 6 months after PNE using validated questionnaires. Peripheral venous blood samples will be taken before and at the end of PNE to evaluate inflammatory serum biomarker levels. The primary objective is to evaluate whether PNE leads to clinical improvement in QoL and pain. If successful, it will be validated in a larger multi-centric cohort, potentially leading to its widespread implementation as a standard pain management tool for eTNBC patients.

Elevated basophil count is associated with increased risk of endometriosis.

Immunological dysregulation plays a fundamental role in the inflammatory aspects of endometriosis. Circulating blood leukocytes, one of the most abundant immune cell populations in the human body, have been shown diagnostic significance in some diseases. Nevertheless, the association between peripheral blood leukocyte counts and endometriosis remains unexplored to date. We analysed two targeted study cohorts: a tertiary centre cohort (Endometriosis at Oxford University [ENDOX] study, 325 cases/177 controls) and a large-scale population study (UK Biobank [UKBB], 1537 cases/6331 controls). In both datasets, peripheral venous blood sample results were retrieved and counts of leukocyte subpopulations, including neutrophils, lymphocytes, monocytes, eosinophils and basophils analysed. Logistic regression models were used to investigate the association of leukocyte subtype alterations with endometriosis status, adjusting for confounding factors. We demonstrate that higher blood basophil level is associated with increased odds of endometriosis. This association was first discovered in the ENDOX cohort (basophils >0.04 x10^9/L: OR 1.65 [95%CI:1.06-2.57], P trend = 0.025) and replicated in the UKBB dataset (basophils >0.04 x10^9/L: OR 1.26 [95%CI:1.09-1.45], P trend = 0.001). Notably, women with basophil counts in the upper tercile had significantly increased odds of having stage III/IV endometriosis (ENDOX study: OR = 2.30, 95% CI [1.25 to 4.22], P trend = 0.007; UKBB study (OR = 1.40, 95% CI [1.07 to 1.85], P trend = 0.015). None of the other leukocyte subtypes showed an association. Our findings suggest an association between inflammatory responses and the pathogenesis of endometriosis; future studies are warranted to investigate whether the association is causal.

Molecular transmission network and drug resistance in treatment-naïve HIV-1 infected patients in the Liangshan District, China.

Objective This study aimed to investigate the molecular transmission network and drug resistance in treatment-naïve HIV-1 infected patients in the Liangshan District, China. Methods The research subjects for this study were HIV-1 infected patients who did not receive any anti-retroviral therapy (ART) in the Liangshan District between January 2022 and July 2023. Peripheral venous whole blood samples were collected from the research subjects. 2 mL blood was used for CD4+ T lymphocyte counting detection. 10 mL blood was centrifuged to separate the plasma and blood cells for quantitative detection of HIV-1 RNA and DNA and drug resistance testing of HIV-1. Results A total of 156 participants were included in this study (88 males and 68 females). The median age of the participants was 37 years old. The findings revealed a positive correlation between the HIV-1 DNA and the HIV-1 RNA levels (r=0.478, P<0.001). However, a negative correlation was observed between HIV-1 DNA levels and CD4+ T lymphocyte counts (r=-0.186, P=0.020). Of the 156 participants, 148 were successfully tested for drug resistance of HIV-1 RNA and HIV-1 DNA simultaneously. Four cases failed the HIV-1 RNA drug resistance testing, and another four failed the HIV-1 DNA drug resistance testing. The most common HIV-1 subtype was the CRF07_BC recombinant. In this study, the overall incidence of transmitted drug resistance (TDR) was 8.33%. The resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) were 7.69% and 0.64%, respectively. Additionally, 32 participants were found to have drug-resistant mutations. The primary drug-resistant mutations were K103N, V179D, E157Q, and A128T, mainly against efavirenz (EFV) and nevirapine (NVP) resistance. Conclusion The drug resistance of HIV-1 infected ART-naïve patients in the Liangshan District cannot be ignored. HIV-1 drug resistance testing is recommended before initiating ART.

Early biomarkers of disease in hypertrophic cardiomyopathy: does telomere length matter?

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Biomedical Research Institute of Murcia (IMIB-Arrixaca) Introduction Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden death in people under 35 years of age. (1) The variability of the phenotype together with its incomplete penetrance has been an obstacle to a complete understanding of the clinical spectrum and consequences of the disease. In recent years, there has been increasing interest in telomeric shortening and several authors have linked it to age-related diseases and HCM. (2, 3) Our aim was to study whether telomere length could affect the age at presentation and the severity of the HCM phenotype in genetic carriers. Methods Measurement of telomere length in circulating leukocytes (LTLc) was performed in 96 patients carrying a mutation in MYBPC3 causing HCM [58 affected (24 severely affected), 38 unaffected]. The variants included were c.2308+1G&amp;gt;A, p.Pro108Alafs*9, p.Arg891Alafs*160 and p.Glu258Lys, all considered founder mutations in our region. Peripheral venous blood samples were obtained from patients at the Inherited Heart Diseases Unit and stored at -80 ºC after informed consent had been signed by all participants. For telomere length analysis, a telomeric restriction fragment (TRF) assay was performed using the TeloTAGGGTelomereLenghtAssay kit (Roche, 12209136001) according to the manufacturer's protocol with slight modifications. Results Our results show a lower LTLc in those affected patients with a more severe HCM phenotype compared to the affected and unaffected group (p=0.023) independently of age and sex, which are two variables that affect LTLc. Similarly, a shorter telomere length was associated with greater severity of the phenotype, with patients presenting a larger left atrial size (p=0.032), septal size (p=0.023) and greater obstruction (p=0.044). The presence of atrial fibrillation (p=0.039) and sudden death (p=0.024) was also higher in patients with shorter telomeres. Conclusions Telomere length is a variable that influences the expression of the phenotype in HCM patients carrying a MYBPC3 variant. This is an observation that supports the thesis of numerous publications linking HCM and other age-related diseases, sometimes called telomeropathies,(2) to telomere shortening. It has also been linked to non-hereditary conditions(3). This fact sheds some light on the complex phenotypic variability present in HCM, raising LTL as a promising prognostic biomarker of the disease, as has already been suggested by other authors.(4, 5, 6).Workflow in the telomere legth analysisClinical associations of LTLc

Initial experience with ablation of ventricular arrhythmias using a pulsed-field system

Abstract Introduction Catheter ablation using radiofrequency (RF) current is a well-established method of treatment of ventricular arrhythmias (VA). However, RF ablation may fail to eliminate deeply located arrhythmogenic substrate. Pulsed-field (PF) is a novel energy source with a potential to create deeper lesions, especially in scar tissue. Purpose This study aims to present the data on safety and efficacy (acute outcome data) of VA ablation using PF. Methods The population consists of 15patients (5 women, age: 61 ± 19years) after previously failed RF ablation of VA. The underlying condition was nonischemic cardiomyopathy (53%), coronary artery disease (13%), and congenital heart disease (13%), respectively. No structural heart disease was present in 20% of cases. The mean left ventricular ejection fraction was 39 ± 13%. Eighty percent of patients had sustained VA, the remaining patients presented with frequent ventricular ectopy. Ablation was performed using a conventional irrigated 4-mm tip catheter in a combination with commercially available PF generator. Peripheral venous blood samples for the assessment of the plasmatic levels of high-sensitivity troponin T (hsTnT) were obtained the next day (usually 18-24hours) after the procedure. Results A mean of 17±12 PF applications (25A) per patient were delivered. In 5 patients (33%), an additional RF ablation (4±9 applications) was performed. Acute success as assessed by non-inducibility of VA or elimination of ectopic focus was achieved in all but one patient (93%). In 4 cases (27%), PF energy was applied within the great cardiac vein and subsequent coronary angiography did not reveal any abnormality. On the other hand, transient conduction system block occurred in 3 cases (20%) during PF application on the lateral LV wall remotely from the LV septum (complete AV block in one, LBBB in two patients). These events resolved in all cases within one hour. Ablation using PF did not result in excessive increase of hsTnT (657±482ng/l, with upper reference level of 14ng/l). Conclusion Initial experience with PF for the treatment of VA indicates high acute efficacy. The long-term effect is to be determined. PF applications in the ventricle may be associated with unexpected but transient conduction system damage, even when applications are performed remotely from the interventricular septum. The postprocedural increase in plasma troponin levels is only moderate.

Biochemical markers of neuro-myocardial damage after pulmonary vein isolation: the effect of different energy sources

Abstract Background Pulmonary vein isolation (PVI) by thermal energy, both radiofrequency (RF) and cryoenergy(Cryo), is associated with a significant release of myocardial and collateral neural injury markers. Damage to periatrial ganglionated plexi also results in a substantial change in cardiac autonomic regulations. On the contrary, pulsed electric field (PEF) energy tends to spare cardiac neural tissue. Purpose To quantify the impact of different ablation energy sources that are used for PVI on neuro-myocardial damage by the assessment of specific biomarkers. Methods A study enrolled 85 patients with paroxysmal atrial fibrillation who underwent PVI (age: 61 ± 12 years, 74% males). In 23 patients, RF energy was delivered by the irrigated-tip catheter, while 30 patients were ablated using a second-generation cryoballoon catheter. In 32 patients, PVI was performed using a multipolar pentaspline catheter and PEF energy. Peripheral venous blood samples for assessing the plasmatic levels of S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), high-sensitivity troponin I and T (hsTnI and hsTnT) were obtained before, immediately after the PVI, and the next day (usually 18-24 hours after the procedure). Study groups were compared regarding absolute biomarker levels and hsTnT/S100B ratio (a surrogate of cardioselectivity). Results Following successful PVI, a significant increase in plasma levels of all biomarkers was observed: DhsTnT = 1040±434 ng/L, 1731±830 ng/L and 1010±397 ng/L; DhsTnI = 1504±918 ng/L, 16464±11911 ng/L and 10789±7589 ng/L; DS100B: 0.04±0.02 mg/L, 0.03±0.04 mg/L and 0.14±0.08 mg/L; DNSE: 34±72 ng/mL, 27±53 ng/mL and 45±52 ng/mL (all with P &amp;lt;0.001) for RF, PEF and Cryo groups, respectively. A direct comparison of maximal biomarker levels between study groups is depicted in the Figure. The hsTnT/S100B ratio was 23±14, 12±6, and 6±3 in PEF, RF, and Cryo groups, respectively (ANOVA P &amp;lt;0.01), indicating that PEF was 1.9-times and 3.8-times more cardioselective than RF and Cryo, respectively. Following the PVI, the heart rate accelerated by 2±8, 13±14, and 9±11 bpm in the PEF, RF, and Cryo groups, respectively. No correlation was observed between S100B release and HR acceleration (R = 0.07, P = 0.55). Conclusion Compared to thermal energy sources, PEF energy induces more specific damage to cardiomyocytes than cardiac nerves. There was no correlation between S100B release and HR acceleration.

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

IntroductionSystemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost.MethodsTwenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2).ResultsSSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC.Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2.ConclusionsSSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies.

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Frequency of Hepatitis C in patients presented with isolated thrombocytopenia.

Objective: HCV-related thrombocytopenia poses challenges in infection and treatment. This study emphasizes screening for early thrombocytopenia as it signals hematological abnormalities, indicating bleeding tendencies and complications. Study Design: Cross-sectional Investigation. Setting: Pathology Department of Allama Iqbal Medical College and Jinnah Hospital. Period: November 2019 to November 2020. Methods: Included 180 participants with platelet counts &lt;100,000/µl, normal hemoglobin, and WBC counts. Exclusions: anemia, leucopenia, prior Hepatitis C treatment, and platelet clumps. Data on age, gender, socioeconomic status, and family history were collected. Platelet counts and HCV detection utilized peripheral smears and venous blood samples, analyzed with SPSS version 25.0. Results: In a study of 180 thrombocytopenic patients of all ages were included with mean age 32. Among 34 HCV-positive cases, 102 had a family history, with age-wise distribution: 18, 14, 2. Gender: 20 males, 14 females. HCV-positive households: 21 positive, 13 negative. Significant p-values for age groups (p=0.000), non-significant for gender (p=0.281), socioeconomic status (p=0.083), and household HCV status (p=0.505). Conclusion: A significant association exists between decreased platelet count and Hepatitis C virus, providing valuable insights for screening in clinical settings.

Link Between Daily Sunlight Exposure and Dyslipidemia Patients – A Cross-Sectional Study

Background: Earlier studies have suggested that Sunlight and vitamin D are related to cardiovascular disease (CVD), but the link between sunlight exposure and risk factors for CVD has not been adequately investigated. Dyslipidaemia is a major risk factor for CVD we aim to investigate whether sunlight exposure has an effect on dyslipidemia patients’ serum lipid profile and vitamin D. Methods: This study was carried out in apparently healthy Indian adults of both sexes, aged above 18 years and dyslipidemia patients’ from Swamy Vivekananda Medical College Hospital (SVMCH). Normal control group (healthy subjects) (n30), Dull sunlight exposure group dyslipidemia patients N30, and bright sunlight exposure group dyslipidemia patients n30, Oral supplement of Vitamin D group (n30), Obese dyslipidemia patients group (n30) before and after sunlight exposure, after overnight fasting peripheral venous blood samples were collected, and the serum was stored in -80 oC fridge. Serum levels of 25(OH) D (25- hydroxy vitamin D3) and lipid levels were analyzed by routine lab method using an Autoanalyzer. Results: We compare the bright and dull sunlight exposure dyslipidemia patients and obese groups; a significant elevation was seen in 25-(OH) D concentrations in the bright sunlight exposure group (P &lt; 0.01), and the lipid profiles TGs, TCs, LDL-C, and VLDL-C were significantly decreased (P &lt; 0.05). The HDL-C level significantly increased when compared to the dull sunlight exposure group. There was no significant change in serum Vitamin D and lipid profile level of the oral supplement vitamin D group compared with the bright sunlight exposure group. Conclusion: Our study reveals that bright sunlight exposure is beneficial and linked with the improvement of Vitamin D and lipid profile of dyslipidemia. In comparison orally supplemented Vitamin D had an adverse effect on lipid profile.

Within-individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test.

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.0) is cumbersome to administer, requiring intravenous and oral administration of cholate and six peripheral venous blood samples over 90 min. To alleviate the burden of test administration, we explored whether an oral only (DuO) version, and other simplified versions, of the test could provide reproducible measurements of liver function. DuO requires only oral dosing and two blood samples over 60 min. The simplified SHUNT test versions were SHUNT V1.1 (oral and IV dosing but four blood samples) and SHUNT V2.0 (oral and IV dosing but only two blood samples over 60 min). In this paper, we describe the reproducibility of DuO and the simplified SHUNT tests relative to that of SHUNT V1.0; equivalency is described in a separate paper. Data from two studies comprising 236 SHUNT tests in 94 subjects were analyzed retrospectively by each method. All simplified methods were highly reproducible across test parameters with intraclass correlation coefficients >0.93 for test parameters Disease Severity Index (DSI) and Hepatic Reserve. DuO and SHUNT V2.0 improved reproducibility in measuring portal-systemic shunting (SHUNT%). These simplified tests, particularly DuO and SHUNT V2.0, are easier to administer and less invasive, thus, having the potential to be more widely accepted by care providers administering the test and by patients receiving the test.

Fraccaro Syndrome (49,XXXXY): Case study in antenatal and postnatal from South Indian patients, an awareness to the human society

Aim: 49, XXXXY syndrome is a rare chromosomal abnormality with an approximate incidence of 1:85000 – 1:100000. Early diagnosis is important to improve the quality of life of patient. This study was carried out to assess the chromosomal abberations in prenatal and postnatal sample of patients through cytogenetics study. Methodology: Sex chromosomal aneuplodies were performed in both amniotic fluid and peripheral venous blood samples. Cytogenetic studies such as Karyotyping was done in in-vitro culture cells by GTG banded metaphase slides. FISH test was conducted in raw sample to rule out low grade mosaicism and DNA isolated from both the samples to rule out the gain and loss of genes by Chromosomal microarray technique. Results: The two cases performed showed aneuploidy with pentasomy sex chromosomes in Karyotyping in all the metaphase analysed and FISH test resulted with five signals in sex chromosome with four copies of X chromosomes and one copy of Y chromosome in all the cells. There was no loss of genes and only gain of genes in X chromosomes as identified in Chromosomal microarray. Interpretation: Based on the findings, antenatal screening is essential and should not be avoided for any USG findings and biochemical screening. The test should not be limited only to trisomy studies. Extensive studies should be performed to rule out the genetic disorders. Chromosomal aneuploidies can be identified by cytogenetic studies like Karyotyping, FISH and Chromosomal microarray technique. Key words: Aneuploidy, Chromosomal microarray analysis, Cytogenetics, Fraccaro syndrome, Karyotyping, Pentasomy sex chromosome

The Relationship between the Systemic Immune-Inflammation Index and Ischemia with Non-Obstructive Coronary Arteries in Patients Undergoing Coronary Angiography.

Ischemia with the non-obstructive coronary artery (INOCA) is an ischemic heart disease that mostly includes coronary microvascular dysfunction and/or epicardial coronary vasospasm due to underlying coronary vascular dysfunction and can be seen more commonly in female patients. The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a new marker that predicts adverse clinical outcomes in coronary artery disease (CAD). This study aims to investigate the relationship between INOCA and SII, a new marker associated with inflammation. A total of 424 patients (212 patients with INOCA and 212 normal controls) were included in the study. Peripheral venous blood samples were received from the entire study population prior to coronary angiography to measure SII and other hematological parameters. In our study, the value of p<0.05' was considered statistically significant. The optimal cut-off value of SII for predicting INOCA was 153.8 with a sensitivity of 44.8% and a specificity of 78.77% (Area under the curve [AUC]: 0.651 [95% CI: 0.603-0.696, p=0.0265]). Their ROC curves were compared to assess whether SII had an additional predictive value over components. The AUC value of SII was found to be significantly higher than that of lymphocyte (AUC: 0.607 [95% CI: 0.559-0.654, p = 0.0273]), neutrophil (AUC: 0.559 [95%CI: 0.511-0.607, p=0.028]) and platelet (AUC: 0.590 [95% CI: 0.541-0.637, p = 0.0276]) in INOCA patients. A high SII level was found to be independently associated with the existence of INOCA. The SII value can be used as an indicator to add to the traditional expensive methods commonly used in INOCA prediction.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing

ObjectivesRheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. MethodsThe study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. ResultsThe study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64–0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63–0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61–0.96, a balanced accuracy range of 0.46–0.94, and an AUC range of 0.46–0.94. ConclusionsThis study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Analysis of NF1 gene variants in a Chinese pedigree and a sporadic patient with Neurofibromatosis type 1

To explore the genetic basis for a Chinese pedigree and a sporadic case with Neurofibromatosis type 1 (NF1). Clinical data of the pedigree and the sporadic case were collected. Genomic DNA was extracted from peripheral venous blood samples and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. All patients from the pedigree were found to harbor a c.3251delC variant in exon 25 of the NF1 gene, whilst a c.4312_4314delGAA variant was found in exon 32 of the NF1 gene in the sporadic case. Variants of the NF1 gene may account for the occurrence of NF1 in this pedigree and sporadic case.

Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis

BackgroundWe aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data.MethodsA total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using “DESeq2” package in R language. Functional enrichment analysis was conducted using the “clusterProfiler” package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape.ResultsWe identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP.ConclusionDOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS

Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion. suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses. suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis. suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion. Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.

Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction

BackgroundAcute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). MethodsIn this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging. ResultsMedian plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. ConclusionHigh plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI.