Serum Biomarkers Research Articles

Interleukin-1 family cytokines and soluble receptors in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL-1 family (IL-1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL-1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL-1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL-18 and free IL-18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL-1Ra, IL-1R2 and ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4. Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL-1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL-18 as novel serum biomarker of active disease.

Kawasaki Disease: An update on Genetics and Pathophysiology.

Kawasaki disease (KD), a systemic vasculitic condition predominantly affecting children, remains a significant challenge in pediatric health care. First identified in 1967, KD is now recognized as the primary cause of pediatric ischemic heart disease in developed countries. This review provides a comprehensive update of KD, focusing on biomarkers, pathophysiology, and genetic associations. KD's clinical manifestation, including symptoms such as persistent fever and mucocutaneous changes, often overlaps with other pediatric conditions, complicating its diagnosis. This ambiguity, especially in cases of incomplete KD, highlights the critical need for specific biomarkers and more precise diagnostic methods. Recent studies have made promising advancements in identifying serum biomarkers and microRNAs, contributing to the development of rapid diagnostic tools. However, these are yet to be fully integrated into clinical practice. The article focuses on the pathophysiological aspects of KD, highlighting the potential for targeted therapies and personalized medicine approaches based on genetic predispositions. Collaborative efforts in global research and raising public awareness about KD are emphasized as key strategies for improving its management. This review presents the current understanding of KD while pointing out the gaps and future directions in research and clinical care. The ultimate goal is to enhance diagnostic accuracy, optimize treatment strategies, and improve patient outcomes, thereby addressing the complexities of this enigmatic and potentially life-threatening condition in pediatric medicine.

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain

Background/objectivesDebilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study. MethodsThe Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay. ResultsAt enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFβ1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings. ConclusionsThe positive association between TGFβ1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFβ1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target.

Potential Diagnostic Role of Serum Fibroblast Growth Factor-19 in Hepatocellular Carcinoma.

A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC. This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19. The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity. FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using thewell-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response. In this single-arm retrospective study,we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment. Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001). Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.

Routine ante-natal screening using maternal risk factors and biomarkers for preeclampsia in 11-13+6 weeks of gestation.

Prediction of preeclampsia in first trimester can lead to early initiation of preventative measures, as well as timely therapeutic intervention, that will prevent the maternal and perinatal morbidity and mortality. This study, prediction of preeclampsia at 11-13+6 weeks of gestation, was conducted by using serum placental growth factor (PlGF), serum pregnancy associated plasma protein - A (PAPP-A), uterine artery Doppler indices, and mean arterial pressure (MAP), in low-risk pregnant women. It is an observational longitudinal prospective study. Pregnant women with singleton pregnancies of gestational age 11-13+6 weeks were recruited. MAP, bilateral uterine artery Doppler indices, serum PAPP-A, and PlGF were measured. The follow-up of the patients was regularly done till termination of pregnancy and incidence of preeclampsia were noted. Qualitative variables were compared using Chi-square/Fisher exact test, and sensitivity and specificity of each test were analyzed. Among 139 women, 27 (19%) developed preeclampsia, out of which 10 had early preeclampsia and 17 developed late preeclampsia. By combining all the parameters, the sensitivity in detecting early preeclampsia was found to be 70% and for late preeclampsia cases, 64.7%. The sensitivity of all the parameters in predicting cases of preeclampsia in general is 66.7%, specificity is 74.1%, PPV is 38.3%, and NPV is 72%. The maternal biomarkers serum PAPP-A, serum PlGF, uterine artery PI, MAP have sensitivity of 70% in detecting early preeclampsia cases and for late preeclampsia cases, 64.71%, in first trimester and it will help in early initiation of preventative measures as well as timely therapeutic intervention.

A self-driven microfluidic immunosensor for rapid separation, enrichment, and detection of biomarkers in serum.

Biomarkers and their concentration levels are critical indicators of metabolomics for clinical applications. Rapid and sensitive analysis methods are essential for realizing timely and efficient quantitation of those significant biomarkers. In this work, a self-driven microfluidic immunosensor was developed for rapid all-in-one separation, enrichment, and detection of biomarkers. This immunosensor was constructed from a cyclic olefin copolymer (COC) channel layer and a polydimethylsiloxane (PDMS) sensing layer. The COC channel layer was modified through protein adsorption, immobilization, and remaining active site blocking. The obtained hydrophilic microchannels not only reduce the nonspecific adsorption, but also provide stable capillary-driven flow generation with linear velocities up to 20mm/s for aqueous solution auto-injection. The PDMS sensing layer was modified using capture antibodies to accomplish affinity recognition of target biomarkers. Procalcitonin (PCT) and serum amyloid A (SAA) were selected as model biomarkers in the feasibility study on applying the self-driven microfluidic immunosensor to bioassay. The limits of detection of PCT and SAA were 7.9ng/L and 7.6μg/L, respectively. Moreover, the whole process can be accomplished within 60min with excellent selectivity and reproducibility. In clinical serum sample analysis, satisfactory recoveries were achieved for PCT and SAA in the ranges of 85.0-103.0% and 95.5-106.0%, respectively, with relative standard deviations less than 5.3%. The method accuracy was further confirmed by the results of commercial immunoassay kits. This simple and easily operated immunosensor provides a rapid and sensitive biomarker analysis tool, and promotes the further development of automated and easy-to-use microfluidic immunoassays.

The Levels of Biomarkers Interleukin 1 (IL-1) and Brain-Derived Neurotrophic Factor (BDNF) in Non-Invasive Conventional Rehabilitation and Robotic Rehabilitation Among Brain Injury Patients: A Narrative Review.

Acquired brain injury (ABI) is becoming increasingly common in Malaysia as a result of a rise in both strokes and accidents. The present review aims to explore the levels of serum inflammatory markers of interleukin-1 (IL-1) and brain-derived neurotrophic factor (BDNF) following conventional and robotic rehabilitation regimes among ABI patients and the association between serum biomarkers with the Medical Research Council (MRC) scale for muscle strength. Online databases, namely ScienceDirect, PubMed, and Google Scholar were utilized by using search terms such as 'Definition of brain injury', 'Epidemiology of brain injury', 'Interleukin-1 in stroke', 'BDNF in stroke', 'Interleukin-1 in traumatic brain injury', 'BDNF in traumatic brain injury', 'Interleukin-1 level and robotic rehabilitation', 'BDNF and robotic rehabilitation', 'Interleukin-1 level and neurorehabilitation', and 'BDNF and neurorehabilitation'. All types of articles with different levels of evidence were included along with other relevant review articles. Articles that were not in English and were not available in the full text were excluded. The review identifies similar and no significant improvement in the treatment between conventional rehabilitation and robotic rehabilitation concerning serum biomarkers IL-1and BDNF. This review also identifies that muscle strength and endurance training improved the levelof serum BDNF in brain injury patients. Therefore, this review provides evidence of the levels of IL-1 and BDNF in non-invasiveconventionalrehabilitation and robotic rehabilitation among brain injury patients, as well as their relation with the MRC scale, to give a good functional outcome that will enhance the quality of life of these groups of individuals.

MiR-21, miR-29a, and miR-106b: serum and tissue biomarkers with diagnostic potential in metastatic testicular cancer

The imperative need for sensitive and precise tools is underscored in cancer diagnostics, with biomarkers playing a pivotal role in facilitating early detection and tumor diagnosis. Despite their classical pathological classification, testicular tumors lack valuable markers, emphasizing the necessity to identify and apply serum tumor markers in clinical management. Unfortunately, existing biomarkers exhibit limited sensitivities and specificities. Recent years have witnessed the discovery of novel RNA molecules, presenting a potential breakthrough as diagnostic tools and promising biomarkers. This report presents compelling evidence supporting the detection of early testicular cancer by applying a set of nine microRNAs (miRNAs), establishing them as valuable serum biomarkers for diagnosis. We developed a standardized serum-based measurement protocol and conducted comprehensive statistical analyses on the dataset to underscore the diagnostic accuracy of the miRNA pool. Notably, with a sensitivity exceeding 93%, miR-21, miR-29a, and miR-106b surpass classical serum tumor markers in the context of testicular cancer. Specifically, these miRNAs are poised to enhance clinical decision-making in testicular cancer detection and hold the potential for assessing tumor growth in monitoring chemotherapy outcomes.

Pilot study to assess the early cardiac safety of carbon ion radiotherapy for intra- and para-cardiac tumours.

Modern photon radiotherapy effectively spares cardiac structures more than previous volumetric approaches. Still, it is related to non-negligible cardiac toxicity due to the low-dose bath of surrounding normal tissues. However, the dosimetric advantages of particle radiotherapy make it apromising treatment for para- and intra-cardiac tumours. In the current short report, we evaluate the cardiac safety profile of carbon ion radiotherapy (CIRT) for radioresistant intra- and para-cardiac malignancies in areal-world setting. We retrospectively analysed serum biomarkers (TnI, CRP and NT-proBNP), echocardiographic, and both 12-lead and 24-hour Holter electrocardiogram (ECG) data of consecutive patients with radioresistant intra- and para-cardiac tumours irradiated with CIRT between June 2019 and September 2022. In the CIRT planning optimization process, to minimize the delivered doses, we contoured and gave ahigh priority to the cardiac substructures. Weekly re-evaluative 4D computed tomography scans were carried out throughout the treatment. Atotal of 16patients with intra- and para-cardiac localizations of radioresistant tumours were treated up to atotal dose of 70.4 Gy relative biological effectiveness (RBE) and amean heart dose of 2.41 Gy(RBE). We did not record any significant variation of the analysed serum biomarkers after CIRT nor significant changes of echocardiographic features, biventricular strain, or 12-lead and 24-hour Holter ECG parameters during 6months of follow-up. Our pilot study suggests that carbon ion radiotherapy is apromising radiation technique capable of sparing off-target side effects at the cardiac level. Alarger cohort, long-term follow-up and further prospective studies are needed to confirm these findings.

Biopsychosocial predictors of rapid weight gain from birth to 6 months.

Childhood obesity remains a public health crisis and identification of unique prenatal and early infancy predictors of obesity risk are critically needed. We test a comprehensive biopsychosocial model of the predictors of rapid weight gain (RWG) in the first 6 months of life. Two hundred and ninety nine pregnant women and their infants participated. Maternal prenatal psychobiological risk (PPBR) was assessed during the third trimester via maternal anthropometrics, serum biomarkers (insulin, leptin, adiponectin), and maternal report of pregnancy complications, substance use, mental health and stress. Infant stress reactivity was measured at 2 months (cortisol output, resting RSA, observed irritability, negative emotionality). At 2 and 6 months, maternal self-report of obesogenic feeding practices and observed maternal sensitivity during three tasks were collected. RWG was classified based on change in weight-for-age z scores from birth to 6 months (>0.67 SD). Obesogenic feeding practices predicted greater likelihood of RWG, β = 0.30, p = .0.01, independent of other predictors and covariates. Obesogenic feeding practices was the only proposed intervening mechanism that produced a significant indirect effect of PPBR on RWG, b = 0.05, S.E. = 0.04, 95% CI [0.002, 0.15], β = 0.06. Identifying proclivity towards obesogenic feeding practices and providing support to reduce these behaviours may enhance childhood obesity prevention efforts.

Electrolytes as predictors of fibro fatigue scores in Long-COVID patients.

The complex effects of Long-COVID, a syndrome marked by enduring symptoms after COVID-19 infection, with an emphasis on patients' differing degrees of fibro fatigue (FF). Electrolyte disturbances may affect the severity of FF and may be used as a predictive tool for severe FF in Long-COVID patients. The aim is to use the electrolyte levels for prediction of the Long-COVID patients with high FF levels. The electrolyte levels, calcium, and magnesium, as well as albumin and C-reactive protein levels were measured in 120 Long-COVID patients and 60 controls. FF scale was used for scoring the fatigue severity in all subjects. Patients were divided into high-FF (FF score>25) and moderate-FF group (FF score<25). FF is the major effector on the serum biomarker levels. High-FF group had older people, longer disease durations, lower SpO2, higher CRP, and higher peak temperatures than the control group. High-FF group has a significant decrease in serum total and ionized calcium compared with the controls and low-FF group. After controlling the cofounders, the major factor controlling the levels of the measured biomarkers is the FF value (Partial η2 = 0.468). The ROC-AUC analysis showed that the peak body temperature, Low-SpO2, high-CRP, and low electrolytes can predict the high-FF in a patient with Long-COVID with a moderate sensitivity and specificities (61.6-70%). Long-COVID patients have an elevation in FF score. The decline in electrolytes can predict the severity of FF with moderate sensitivities and specificities.

Lymphocyte-to-monocyte, platelet-to-albumin and platelet-to-lymphocyte ratios as prognostic biomarkers for neoadjuvant treatment response in rectal cancer patients

IntroductionSystemic inflammatory response (SIR) indicators are an emerging category of serum biomarkers with significant potential as prognostic and predictive factors in various types of cancers The primary focus of our study was to determine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), platelet-to-albumin ratio (PLR) and platelet-to-albumin ratio (PAR) in evaluating the response to neoadjuvant treatment for patients with rectal cancer. Materials and methodsWe included 99 consecutive patients with rectal cancer which were admitted for surgery in our institution after completing a standard neoadjuvant radio-chemotherapy regimen. Several hematologic parameters, including LMR, PAR and PLR, were calculated by collecting and analyzing blood samples preoperatively. Cases were divided into groups using ROC curve analysis to determine optimal cutoff values for each of the investigated parameters. Treatment response was assessed through histopathological analysis of the resected specimens. ResultsPLR values over 215.2 were correlated with the presence of lymph node metastasis. A similar correlation was observed between PAR values over 41.89 and lymph node positivity. A significant correlation was observed between the presence of tumor budding on histopathological analysis and high-PAR values. A statistically significant correlation between a high PLR and a good response to neoadjuvant treatment was determined. ConclusionsHigh PLR values may be associated with a more favorable treatment response to neoadjuvant radio-chemotherapy. A high PAR may be associated with unfavorable histopathological characteristics. Further studies on these readily available biomarkers are required in order to validate their clinical utility.

Integrating untargeted and targeted LC-MS-based metabolomics to identify the serum metabolite biomarkers for tuberculosis.

Given the limitations of untargeted metabolomics in precise metabolite quantification, our current research employed a novel approach by integrating untargeted and targeted metabolomics utilizing ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) to analyze the metabolic profile and potential biomarkers for tuberculosis (TB). A cohort of 36 TB patients and 36 healthy controls (HC) was enlisted to obtain serum samples. Multivariate pattern recognition and univariate statistical analysis were employed to screen and elucidate the differential metabolites, whereas dot plots and receiver operating characteristic (ROC) curves were established for the identification of potential biomarkers of TB. The results indicated a distinct differentiation between the two groups, identifying 99 metabolites associated with five primary metabolic pathways in relation to TB. Of these, 19 metabolites exhibited high levels of sensitivity and specificity, as evidenced by the area under curve values approaching 1. Following targeted quantitative analysis, three potential metabolites, namely, L-asparagine, L-glutamic acid, and arachidonic acid, were demonstrated excellent discriminatory ability as evidenced by the results of the ROC curve, dot plots, and random forest model. Particularly noteworthy was the enhanced diagnostic efficacy of the combination of these three metabolites compared to singular biomarkers, suggesting their potential utility as serum biomarkers for TB diagnosis.

A Systematic Review of the Key Predictors of Progression and Mortality of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis (RA). Identifying patients at risk of progression and death is crucial for improving RA-ILD management and outcomes. This paper explores current evidence on prognostic factors in RA-ILD. We conducted a systematic literature review to examine the impact of clinical, radiological, and histological factors on lung function decline and the survival of RA-ILD patients. We searched electronic databases, including Medline and EMBASE, from inception to date. The incidence and prognosis of predictors were qualitatively analyzed, and univariate results were combined when feasible. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Out of 2217 records, 48 studies were eligible. These studies reported various prognostic factors, including demographic variables, clinical risk factors, serum markers, and preexisting treatments. Lung function declined over time in 1225 subjects, with significant variability in smoking history and radiological/pathological UIP patterns. Severe lung fibrosis and abnormal pulmonary function tests (PFTs) were key univariate prognostic indicators, while age at initial presentation, RA disease activity, predicted DLCO percentage, and UIP pattern were the most reliable multivariate risk factors for ILD progression. Age, male gender, disease duration, RA activity, acute phase reactants, and specific serum biomarkers (Krebs vin den Lungen 6, surfactant protein D, and interleukin 6) were significantly associated with all-cause mortality. RA-ILD is a severe complication of RA characterized by significant prognostic variability. Key prognostic factors include extensive fibrosis observed on imaging, a marked decline in lung function, high RA disease activity, and specific biomarkers. These factors can guide treatment strategies and improve patient outcomes.

Nuclear-Magnetic-Resonance-Spectroscopy-Derived Serum Biomarkers of Metabolic Vulnerability Are Associated with Disability and Neurodegeneration in Multiple Sclerosis.

Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration. Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing-remitting, and 91 progressive MS patients. The spectra were analyzed to obtain concentrations of lipoprotein sub-classes, glycated acute-phase proteins, and small-molecule metabolites, including leucine, valine, isoleucine, alanine, and citrate. Composite indices for inflammatory vulnerability, metabolic malnutrition, and metabolic vulnerability were computed. MS disability was measured on the Expanded Disability Status Scale. MRI measures of lesions and whole-brain and tissue-specific volumes were acquired. Valine, leucine, isoleucine, alanine, the Inflammatory Vulnerability Index, the Metabolic Malnutrition Index, and the Metabolic Vulnerability Index differed between healthy control and MS groups in regression analyses adjusted for age, sex, and body mass index. The Expanded Disability Status Scale was associated with small HDL particle levels, inflammatory vulnerability, and metabolic vulnerability. Timed ambulation was associated with inflammatory vulnerability and metabolic vulnerability. Greater metabolic vulnerability and inflammatory vulnerability were associated with lower gray matter, deep gray matter volumes, and greater lateral ventricle volume. Serum-biomarker-derived indices of inflammatory and metabolic vulnerability are associated with disability and neurodegeneration in MS.

Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study

BackgroundEndometrial cancer is the most common gynecological malignancy; however, there is no useful blood diagnostic biomarker. This study aimed to determine the utility of tissue factor pathway inhibitor 2 (TFPI2), a biomarker of ovarian cancer, as a diagnostic marker for endometrial cancer.MethodsWe examined serum TFPI2 levels in patients with endometrial cancer (n = 328) compared to those in healthy controls (n = 65) and evaluated the performance of serum TFPI2 levels as a diagnostic marker. We investigated the clinicopathological characteristics of patients with TFPI2-negative and TFPI2-positive endometrial cancer. Using immunohistochemistry (IHC), we examined TFPI2 expression in tumor tissues of 105 patients with type II endometrial carcinoma and evaluated the correlation between serum and tissue TFPI2 positivity.ResultsPatients with endometrial cancer had significantly higher serum TFPI2 levels than controls (196.7 pg/mL vs. 83.3 pg/mL; p < 0.001). The sensitivity and specificity were 54.3% and 95.4%, respectively (cutoff value, 191 pg/mL). Serum TFPI2 levels were significantly elevated along with the stage progression (stage I, 189.6 pg/mL; stage III, 230.9 pg/mL; stage IV, 312.5 pg/mL; p < 0.001). Patients with high-risk histology showed significantly elevated serum TFPI2 levels than those with low-risk histology (220.8 pg/mL vs. 187.7 pg/mL; p < 0.001). The positivity rate for TFPI2 was the highest among tumor markers, including CA125, CA19-9, and CEA. Serum TFPI2 and CA125 levels were almost independent (r = 0.203, p < 0.001), and the combined sensitivity increased to 58.8%. The 5-year survival rate was significantly worse in TFPI2-positive patients (≥ 191 pg/mL, n = 178) than in TFPI2-negative patients (< 191 pg/mL, n = 150) (hazard ratio, 8.22; 95% confidence interval, 2.49–27.1; p < 0.001). TFPI2 immunostaining revealed that 37.1% (39/105) of the samples were positive for TFPI2, with an IHC score of > 0. There was no significant difference in the immunostaining score according to histological type. Serum TFPI2 levels and immunostaining score showed poor agreement (kappa coefficient, -0.039).ConclusionsThe serum TFPI2 level is a promising marker for diagnosing and predicting the prognosis of endometrial cancer. No correlation exists between serum and tissue TFPI2 levels. Further multicenter clinical trials are needed to test the utility of TFPI2 as a diagnostic marker.

The significance of plasma biomarkers in predicting heart failure among patients with acute myocardial infarction

Background: Acute myocardial infarction (AMI) is characterized by high mortality and disability rates. Timely and effective revascularization has saved the lives of many patients. However, some patients develop complications such as heart failure (HF) following myocardial infarction, which significantly affects their quality of life and may even be life-threatening. Therefore, the search for effective biomarkers to predict the occurrence of HF after AMI, along with early prevention and treatment strategies, will greatly improve clinical outcomes for patients with post-myocardial infarction HF Methods: A total of 170 patients with acute myocardial infarction (AMI) were enrolled in this study, including 44 patients with post-AMI heart failure (HF) and 126 patients with post-AMI non-HF. We measured the serum biomarkers NT-proBNP, cTNT, PLR, NLR, and GDF-15 in all patients using enzyme-linked immunosorbent assay (ELISA). Subsequently, we performed t-tests to assess the predictive value of these biomarkers for post-AMI heart failure (HF). Results: In the group of HF patients, cTNT, NT-proBNP, GDF-15 and NLR was significantly higher than in the group without HF, but PLR was not .The AUC of NLR to predict HF after AMI was 0.632 (95%CI:0.542-0.723), P=0.010, with a cut-off value of (3.86×109)/L , GDF-15 was 0.661 (95%CI0.560-0.763), P=0.002, with a cut-off value of 1.35 ng/mL, and NT-proBNP was 0.82 (95%CI0.723-0.876), P&lt;0.001, with a cut-off value of 1444 pg/mL. Conclusions: In five biomarkers, there is predictive value in NT-proBNP , NLR, GDF-15 for patients with HF after AMI .