Biomarkers C-reactive Protein Research Articles

Measurement of Pancreatic Stone Protein Compared with C-Reactive Protein and Procalcitonin in the Diagnosis of Sepsis in an Intensive Care Unit: A Systematic Review.

Sepsis remains a significant challenge in the intensive care unit (ICU), with prompt diagnosis and management being critical to improving patient outcomes. Biomarkers have emerged as valuable tools for identifying and predicting sepsis outcomes, with pancreatic stone protein (PSP), procalcitonin (PCT) and C-reactive protein (CRP) as three promising candidates. This systematic review aimed to analyse and compare the diagnostic accuracy of PSP, PCT and CRP regarding sepsis in the ICU. A review of the literature on the diagnostic performance of the three biomarkers was performed using PubMed Central, PubMed, ScienceDirect, Oxford Academic, SpringerLink and Cochrane Library. Data regarding the diagnostic accuracy of the three biomarkers were extracted, compared, and represented as the area under the curve (AUC) receiver operating characteristics (ROC). Three studies examining PSP, PCT and CRP biomarkers in 858 adult patients admitted to the ICU were included in this review. Compared with PCT and CRP, the PSP biomarker, with its unique applications and properties that may potentially benefit patients, doctors and hospitals, performed well and proved reliable in diagnosing sepsis in adult patients. PSP demonstrated reliability in sepsis diagnosis. Further analysis should be conducted to establish a formal, appropriate indication, as well as to determine a suspected sepsis patient's condition when testing each biomarker.

Developing Augmented Pro-SOFA and Pro-SAPS Models by Integrating Biomarkers PCT, NLR, and CRP with SOFA and SAPS-III Scores.

Sepsis, a life-threatening condition characterized by a dysregulated immune response to infection, remains a significant clinical challenge globally. This study aims to enhance the predictive accuracy of existing sepsis severity scores by developing augmented versions of the SOFA and SAPS-III models, termed Pro-SOFA and Pro-SAPS, through the integration of biomarkers procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). This prospective observational study was conducted in the medical ICU of a tertiary care hospital in southern India from August 2022 to December 2023. A total of 301 adult patients suspected or confirmed to have sepsis were assessed for eligibility, with 171 patients completing the study. Demographic and clinical data were collected; SOFA and SAPS-III scores were calculated and augmented with PCT, NLR, and CRP to develop Pro-SOFA and Pro-SAPS models. The performance of these models was evaluated using Brier scores, AUC, and net reclassification index (NRI). The augmented Pro-SOFA and Pro-SAPS models demonstrated superior predictive accuracy compared to their original counterparts. The Brier scores for Pro-SOFA and Pro-SAPS were 0.181 and 0.165, respectively, indicating better calibration than the original scores. The Pro-SAPS showed significant improvement over the original SAPS-III score (NRI = 0.50, SE = 0.14, p < 0.01). Similarly, Pro-SOFA outperformed the original SOFA (NRI = 0.49, SE = 0.13, p < 0.01). Integrating PCT, CRP, and NLR with SOFA and SAPS-III scores to develop Pro-SOFA and Pro-SAPS significantly improves the predictive accuracy for sepsis mortality and can thus potentially improve sepsis outcomes. Nandakumar A, Sudeep S, Sreemohan AC, Vijayakumar S, Sudhakaran GJ, Gutjahr G, et al. Developing Augmented Pro-SOFA and Pro-SAPS Models by Integrating Biomarkers PCT, NLR, and CRP with SOFA and SAPS-III Scores. Indian J Crit Care Med 2024;28(10):935-941.

The impact of maternal vulnerability on stress biomarkers and first-trimester growth: the Rotterdam Periconceptional Cohort (Predict Study)

Abstract STUDY QUESTION Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? SUMMARY ANSWER The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and negatively with tryptophan, while higher hair cortisol concentrations are associated with reduced first-trimester growth without mediation of tryptophan. WHAT IS KNOWN ALREADY A high degree of maternal vulnerability during the periconception period is associated with impaired first-trimester growth and pregnancy complications, with consequences for long-term health of the child and future life course. However, due to the challenges of early identification of vulnerable women, the uptake of periconception care is low in this target group. STUDY DESIGN, SIZE, DURATION Between June 2022 and June 2023, this study was conducted in a sub-cohort of 160 pregnant women participating in the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective tertiary hospital-based cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS One hundred and thirty-two women with ongoing pregnancies and available stress biomarker data were included in the analysis. Data on periconceptional social, lifestyle, and medical risk factors were collected via self-administered questionnaires, and these factors were used for the development of a composite maternal vulnerability risk score. Stress biomarkers, including stress hormones (hair cortisol and cortisone) and inflammatory and oxidative stress biomarkers (C-reactive protein, total homocysteine, and tryptophan metabolites) were determined in the first trimester of pregnancy. First-trimester growth was assessed by crown–rump length (CRL) and embryonic volume (EV) measurements at 7, 9, and 11 weeks gestation by making use of an artificial intelligence algorithm and virtual reality techniques using 3D ultrasound data sets. The associations between the maternal vulnerability risk score and stress biomarkers were identified using linear regression models, and between stress hormones and CRL- and EV-trajectories using mixed models. A mediation analysis was performed to assess the contribution of tryptophan. All associations were adjusted for potential confounders, which were identified using a data-driven approach. Several sensitivity analyses were performed to check the robustness of the findings. MAIN RESULTS AND THE ROLE OF CHANCE The maternal vulnerability risk score was positively associated with concentrations of hair cortisol and cortisone (pg/mg) (β = 0.366, 95% CI = 0.010–0.722; β = 0.897, 95% CI = 0.102–1.691, respectively), and negatively with tryptophan concentrations (µmol/L) (β = –1.637, 95% CI = –2.693 to –0.582). No associations revealed for C-reactive protein and total homocysteine. Higher hair cortisol concentrations were associated with reduced EV-trajectories (3√EV: β = –0.010, 95% CI = –0.017 to –0.002), while no associations were found with CRL-trajectories. Mediation by tryptophan was not shown. LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out, and the external validity may be limited due to the study’s single-center observational design in a tertiary hospital. WIDER IMPLICATIONS OF THE FINDINGS There is mounting evidence that a high degree of maternal vulnerability negatively affects maternal and perinatal health, and that of the future life course. The results of our study emphasize the need to identify highly vulnerable women as early as possible, at least before conception. Our findings suggest that the chronic stress response and alterations of the maternal tryptophan metabolism are involved in maternal vulnerability, affecting first-trimester growth, with potential impact on the long-term health of the offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Departments of Obstetrics and Gynecology and Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Junior Award granted by the De Snoo—van ’t Hoogerhuijs Foundation in March 2022. There are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Predicting Mortality in Sepsis: The Role of Dynamic Biomarker Changes and Clinical Scores-A Retrospective Cohort Study.

The prognostic value of baseline inflammatory markers in sepsis remains controversial, with conflicting evidence regarding their association with mortality. The dynamic changes in these markers over time might offer additional insights into disease progression and patient outcomes. This retrospective observational study included 138 patients with severe infections. The inflammatory biomarkers procalcitonin (PCT), C-reactive protein (CRP), and lactate (LAC) were measured at three time points: upon hospital admission (baseline), approximately 24-48 h after admission (second measurement; M2), and 48-72 h after admission (third measurement; M3). The primary outcome was 30-day mortality. A Mann-Whitney U test was used to compare the biomarker levels between the survivors and non-survivors. A Spearman's correlation was used to assess the relationships between the baseline parameters. A logistic regression and a receiver operating characteristic (ROC) curve analysis were employed to evaluate the prognostic value of the baseline markers and their dynamic changes. The baseline LAC and SOFA score were significantly associated with 30-day mortality. The percentage decrease in PCT, CRP, and LAC from the baseline to M3 emerged as strong predictors of survival, with the ROC curve analysis demonstrating superior discriminatory ability compared to the baseline values. CRP_Delta exhibited the highest AUC (0.903), followed by PCT_Delta (0.843) and LAC_Delta (0.703). The dynamic changes in these inflammatory biomarkers, particularly PCT, CRP, and LAC, offer valuable prognostic information beyond their baseline levels in predicting 30-day mortality in severe infections. These findings highlight the importance of monitoring biomarker trends for early risk stratification and potential treatment guidance.

Serum Procalcitonin ,Cystatin C, Kidney Injury Molecule -1 Levels in Patients with Diabetic Foot Ulcer and Relation with Chronic Kidney Disease

Objective: To evaluate the serum levels of Procalcitonin (PCT), C-Reactive Protein (CRP), Cystatin C, and Kidney Injury Molecule-1 (KIM-1) in patients with diabetic foot ulcers (DFU). Methods: This case-control study included 120 participants divided into four groups: 30 with diabetic foot ulcers (DFU), 30 with diabetic foot ulcers and chronic kidney disease (DFU &amp; CKD), 30 with diabetes mellitus (DM), and 30 healthy controls. The study was conducted from November 2023 to March 2024. Laboratory tests performed on all patients and controls included CBC, blood urea, serum creatinine, and serum CRP levels using a fully automated analyzer. PCT, Cystatin C, and KIM-1 levels were measured using the ELISA method. Results: The biomarkers PCT, CRP, and WBC showed a significant increase in the diabetic foot group and the diabetic foot with chronic kidney disease group. Additionally, there were positive correlations between PCT and CRP and Cystatin C, and between KIM-1 and Cystatin C. ROC analysis of PCT demonstrated high sensitivity and specificity (91.1% and 99%, respectively). Conclusion: Elevated Procalcitonin levels in diabetic foot patients can predict early infection even without clear clinical signs. Increased levels of Cystatin C and KIM-1 serve as good biomarkers for renal function and complications of diabetes, showing a close relationship with diabetic foot conditions.

Sex Differences in Biochemical Analyses, Cardiometabolic Risk Factors and Their Correlation with CRP in Healthy Mexican Individuals.

Few studies have been undertaken to detect the presence of cardiovascular risk factors (CRFs) in healthy populations (individuals auto-reported as healthy). These risk factors include high body mass index (BMI), high waist-to-hip ratio (WHR), high systolic and diastolic blood pressure (SBP, DBP), high uric acid and high Castelli's risk index (CRI); this last is the ratio of total cholesterol to HDL cholesterol (TC/HDL-c). In addition, the correlations between CRFs and the biomarker C-reactive protein (CRP) has not been explored in each sex. Therefore, this study aimed to determine sex differences in the abnormalities in blood and urine analyses, including CRFs and their correlation with CPR in a non-representative sample of healthy Mexican individuals. A total of 238 subjects were included, 123 (51.7%) of whom were women. The main blood alterations detected were high serum lipids, including high total cholesterol, LDL-cholesterol, triglycerides, and the CRI, which were higher in men than in women. The men's samples had a higher frequency of hypertensives and pre-hypertensives than the women's sample. The CRP showed positive significant correlations with the CRFs: BMI, WHR, SBP, DBP, uric acid, and the CRI, with a higher correlation for BMI and WHR, and most of these correlations were higher in women than in men. Additionally, all these factors showed a positive correlation among them. In conclusion, the main alterations observed in blood are related to cardiovascular risk and were reported with a higher frequency in men when compared with women. This finding can be related to the higher values of WHR in this sex; additionally, the inflammatory marker CRP was more correlated with the cardiometabolic risk factors in women than in men, which suggests a different relationship between inflammation and cardiometabolic risk factors in each sex.

Improving prognostication of pneumonia among elderly patients: usefulness of suPAR

PurposeElderly patients with suspected pneumonia represent a significant proportion of hospital admissions, which is a prognostic challenge for physicians. Our research aimed to assess the prognosis of patients with pneumonia using soluble urokinase plasminogen activator receptor (suPAR) combined with clinical data.MethodsIn a prospective observational study including 164 patients > 65 years (mean age 84.2 (+/-7.64) years) who were hospitalized for a suspicion of pneumonia, suPAR was assessed for each patient, as was the prognosis score (PSI, CURB65) and inflammatory biomarkers (C-reactive protein, procalcitonin, white blood cells). The prognostic value of the suPAR for 30-day mortality was assessed using receiver operating characteristic (ROC) curve analyses. Optimal cut-offs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index.ResultsA suPAR > 5.1 ng/mL was predictive of 30-day mortality with a sensitivity of 100% and a specificity of 40.4%. A combination of the following parameters exhibited an SE of 100% (95% CI, 100–100) for an SP value of 64.9% (95% CI, 57.6–72.2) when at least two of them were above or below the following cut-off threshold values: suPAR > 9.8 ng/mL, BMI < 29.3 kg/m2 and PSI > 106.5.ConclusionThe suPAR seems to be a promising biomarker that can be combined with the PSI and BMI to improve the prognosis of pneumonia among elderly patients. Prospective studies with larger populations are needed to confirm whether this new approach can improve patient outcomes.Trial registrationClinicalTrials.gov (NCT02467192), 27th may 2015.

Comparison of dietary inflammatory index and inflammatory biomarkers between vegetarians and omnivores in Chinese population

Most previous studies on the association between vegetarian diet and inflammation have used only one inflammatory biomarker e.g., C-reactive protein (CRP) and the findings were generally inconsistent. Therefore, we conducted a cross-sectional study to investigate the correlation between diet and inflammation in Chinese vegetarians using dietary indices and multiple inflammatory biomarkers. 279 vegetarians and omnivores of the same sex and age recruited in Shanghai, 2016. 24-h dietary review questionnaire was collected and used to calculate Dietary inflammatory index (DII) and Energy-adjusted inflammatory index (E-DII) of both groups. In addition, energy intake matched vegetarian and omnivore recipes were designed by registed dietitions and used to calculate a theoretical DII. Five serum inflammatory biomarkers CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), neutrophil–lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. We found that vegetarians had significantly lower E-DII and theoretical DII than omnivores (P < 0.001). In contrast, the raw DII of vegetarians was almost the same with that of omnivores, probably due to lower energy intake in vegetarians than in omnivores (1367.97 ± 479.75 vs. 1724.78 ± 568.13, P < 0.001). Levels of TNF-α, IL-6, NLR and PLR were significantly higher in vegetarians than in omnivores while no statistical differences were found in CRP. In conclusion, a theoretical vegetarian diet with adequate energy intake as well as a balanced dietary intake showed good anti-inflammatory effects, though this was not fully reflected in vegetarian population in the real world, probably due to insufficient energy intake in the vegetarian population.

STABILITY (Symptomatic Review during Biologic Therapy) of Inflammatory Bowel Disease Patients Receiving Infusion Therapy Improves Clinical Outcomes.

Several studies have correlate improved patient outcomes with increased physician-patient contacts, particularly in chronic diseases. Extending this approach to inflammatory bowel disease (IBD) care presents a promising means of improving outcomes. At LSU Health Shreveport (LSUHS), a new approach called "STABILITY" (Symptomatic Review during Biologic Therapy) was implemented during infusion therapy visits for IBD patients. These brief 15 min physician-patient interviews aimed to discuss the patients' current IBD-related symptoms and evaluate the need for any changes in their treatment plan. Our goal was to remove a care gap and prevent intensifying symptoms created by missed appointments and loss of contact. To analyze the effectiveness of the STABILITY approach, a retrospective chart review was conducted on 111 IBD patients (18 with ulcerative colitis, 93 with Crohn's disease) seen at LSUHS between 2011 and 2022. Since March 2019, STABILITY has been mandatory for all infusion therapy visits. The data collected included patients' demographics, lab levels for biomarkers (fecal calprotectin, C-reactive protein, and erythrocyte sedimentation rates), hospitalizations, medication changes, and diagnosis dates before and after the implementation of STABILITY. Additionally, voluntary, anonymous infusion patient satisfaction surveys post-STABILITY were used to gather patient responses. In males with IBD, disease severity and hospitalizations were reduced significantly (p = 0.004 and 0.0234, respectively). In females with IBD, disease severity and hospitalizations were also reduced significantly (p = 0.0001 and 0.0072, respectively). In patients with UC and CD, there were significant improvements in disease severity (p = 0.043 and p = 0.0001, respectively), and CD hospitalizations were also improved (p = 0.0013). In males and females with UC, disease severity was marginally and significantly reduced (p = 0.0781 and p = 0.0379, respectively). In males and females with CD, disease severity was significantly reduced (p = 0.0161 and 0.0003, respectively), and CD male and female hospitalizations were also reduced significantly (p = 0.0436 and 0.013). Analyzing of survey responses, we found that the most patients reported improved IBD symptoms (56%), gained understanding of their condition (84%) and were in favor of continuing STABILITY consultations during infusion therapy (93%). To further investigate the impact of STABILITY, we conducted a comparative analysis between IBD patients undergoing STABILITY infusion therapy and LSUHS patients solely on self-injectable biologics. Our paired data analysis showed significant improvements in disease severity in female IBD patients (1.69 ± 0.13 vs. 1.41 ± 0.12, p = 0.0001) and male IBD patients (1.58 ± 0.16 vs. 1.2 ± 0.135, p = 0.004), in UC patients (1.833 ± 0.4.2 vs. 1.444, p = 0.043), in all CD patients (1.59 ± 0.11 vs. 1.29 ± 0.01, p = 0.0001), in male CD patients (1.52 ± 0.167 vs. 1.15 ± 0.15, p = 0.016), in female CD patients (1.66 ± 0.15 vs. 1.4 ± 0.13, p = 0.0003), in female UC patients (1.82 ± 0.32 vs. 1.45 ± 0.31, p = 0.0379), and marginally in male UC patients (p = 0.0781). Similarly, hospitalizations were significantly reduced in CD patients considered in aggregate (0.21 ± 0.04 vs. 0.11 ± 0.03, p = 0.0013), in male IBD patients (0.175 ± 0.06 vs. 0.05 ± 0.035, p = 0.024), in female IBD patients (0.21 ± 0.05 vs. 0.11 ± 0.04, p = 0.0072), in male CD patients (0.18 ± 0.07 vs. 0.06 ± 0.042, p = 0.0436), and in females with CD (0.23 ± 0.06 vs. 0.13 ± 0.04, p = 0.013). Although average values for fecal calprotectin, CRP, and sedimentation rate were frequently reduced after STABILITY interviews, these data did not reach statistical significance. These preliminary findings suggest that STABILITY may be effective in maintaining low disease activity or remission in IBD patients.

Multiparametric Cardiac Magnetic Resonance Imaging to Discriminate Endomyocardial Biopsy-Proven Chronic Myocarditis From Healed Myocarditis

BackgroundDetecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis. ObjectivesThis study sought to assess the performance of cardiac magnetic resonance (CMR) for the detection of ongoing inflammation and the discrimination of chronic myocarditis from healed myocarditis. MethodsConsecutive patients with persistent symptoms (>30 days) suggestive of myocarditis were prospectively enrolled from a single tertiary center. All patients underwent a multiparametric 1.5-T CMR protocol including biventricular strain, T1/T2 mapping, and late gadolinium enhancement (LGE). Endomyocardial biopsy was chosen for the reference standard diagnosis. ResultsAmong 452 consecutive patients, 103 (median age: 50 years; 66 men) had evaluable CMR and cardiopathologic reference diagnosis: 53 (51%) with chronic lymphocytic myocarditis and 50 (49%) with healed myocarditis. T2 mapping as a single parameter showed the best accuracy in detecting chronic myocarditis, if abnormal in ≥3 segments (92%; 95% CI: 85-97), and provided the best discrimination from healed myocarditis, as defined by the area under the receiver-operating characteristic curve (0.87 [95% CI: 0.79-0.93]; P < 0.001), followed by radial peak systolic strain rate of the left ventricle (0.86) and the right ventricle (0.84); T1 mapping (0.64), extracellular volume fraction (0.62), and LGE (0.57). Specificity increased when T2 mapping was combined with elevation of either troponin or C-reactive protein. ConclusionsA multiparametric CMR protocol allows detection of ongoing myocardial inflammation and discrimination of chronic myocarditis from healed myocarditis, with segmental T2 mapping and biventricular strain analysis showing higher diagnostic accuracy compared with T1 mapping, extracellular volume fraction, and LGE. The use of biomarkers (troponin or C-reactive protein) may improve specificity.

Serum procalcitonin and C-reactive protein as indices of early sepsis and mortality in North Indian pediatric burn injuries: a prospective evaluation and literature review.

Delays in diagnosing sepsis in children afflicted with thermal injuries can result in high morbidity and mortality. Our study evaluated the role of the biomarkers Procalcitonin (PCT) and C-reactive protein (CRP) as predictors of early sepsis and mortality, respectively, in this group of patients. This was a prospective evaluation of 90 pediatric burn cases treated at a tertiary care burn center in Northern India. Patients, aged 1-16 years, presenting within 24 hours of being burned, with >10% body surface area of burn injury were included in the study. Levels of PCT and CRP were measured on days 1, 3, 5, and 7. Patients were followed until discharge, 30th post-burn day, or death, whichever occurred first. Sepsis was clinically present in 49 of 90 (54.4%) cases with a median 30% total body surface area (TBSA) of burns. Mortality was seen in 31 of 90 (34.4%) cases with a median of 35% TBSA burns. High PCT and CRP were seen in the sepsis group, particularly on days 3, 5, and 7. PCT was also significantly higher in the mortality group (days 1 and 3). While PCT was a good early predictor of sepsis and mortality in children with burns, CRP was reliable as a predictor of sepsis only. Both markers, however, can serve as adjuncts to culture sensitivity reports for diagnosing early onset sepsis and initiation of antibiotic therapy in appropriate patients.

Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this risk is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact of parenting interventions on biological markers associated with these risks is crucial for mitigating long-term health disparities. To examine the effect of 20 weeks of an internet-based parent-child interaction training (iPCIT) program on biomarkers associated with aging and chronic inflammation among preschoolers with developmental delay at 12-month follow-up. An observational secondary analysis of data from a randomized clinical trial conducted from March 17, 2016, to December 15, 2020, to assess changes in salivary DNA methylation (DNAm)-derived biomarkers following iPCIT intervention. Participants were recruited from 3 Part C early intervention sites in a large southeastern US city. Eligible participants included children recruited within 3 months of their third birthday who had a Child Behavior Checklist Externalizing Problems T score greater than 60 and provided saliva in at least 1 study wave. Data analysis was conducted May 2023 to April 2024. Participants received either iPCIT (a telehealth therapeutic intervention focused on enhancing the parent-child relationship and addressing behavioral challenges in young children) or referrals as usual. DNAm at the 12-month follow-up was assessed using the Infinium HumanMethylationEPIC Bead Chip Assay to derive biomarkers DunedinPACE, C-reactive protein (CRP), and interleukin-6 (IL-6). Analyses were intent-to-treat and used path analysis. A total of 71 children (mean [SD] age, 36.27 [0.61] months 51 male [71.8%] and 20 female [28.2%]) were analyzed, of whom 34 received iPCIT and 37 received referrals as usual. The iPCIT group had a slower pace of aging (β = 0.26; 95% CI, 0.06 to 0.50; P = .03) and less DNAm-derived CRP (β = 0.27; 95% CI, 0.05 to 0.49; P = .01) relative to the control condition at the 12-month follow-up. These associations remained significant after accounting for baseline DNAm score, child demographics, and symptom severity, and were independent of predicted buccal epithelial cell proportion for both DunedinPACE and CRP. There was no association with DNAm-derived IL-6 (β = 0.14; 95% CI, -0.08 to 0.36; P = .21). In this study of a parenting intervention, iPCIT, the association of intervention with decreased molecular markers of inflammation and biological aging suggests their potential to modify aspects of the biological embedding of stress. Understanding the systemic biological impact of such interventions offers insights into addressing health disparities and promoting resilience among vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.

Association of early dexmedetomidine exposure with brain injury biomarker levels following moderate - severe traumatic brain injury: A TRACK-TBI study

BackgroundTraumatic brain injury (TBI) triggers autonomic dysfunction and inflammatory response that can result in secondary brain injuries. Dexmedetomidine is an alpha-2 agonist that may modulate autonomic function and inflammation and has been increasingly used as a sedative agent for critically ill TBI patients. We aimed to investigate the association between early dexmedetomidine exposure and blood-based biomarker levels in moderate-to-severe TBI (msTBI). MethodsWe conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study (TRACK-TBI), which enrolled acute TBI patients prospectively across 18 United States Level 1 trauma centers between 2014–2018. Our study population focused on adults with msTBI defined by Glasgow Coma Scale score 3–12 after resuscitation, who required mechanical ventilation and sedation within the first 48 h of ICU admission. The study’s exposure was early dexmedetomidine utilization (within the first 48 h of admission). Primary outcome included brain injury biomarker levels measured from circulating blood on day 3 following injury, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and the inflammatory biomarker C-reactive protein (CRP). Secondary outcomes assessed biomarker levels on days 5 and 14. Linear mixed-effects regression modelling of the log-transformed response variable was used to analyze the association of early dexmedetomidine exposure with brain injury biomarker levels. ResultsAmong the 352 TRACK-TBI subjects that met inclusion criteria, 50 (14.2 %) were exposed to early dexmedetomidine, predominantly male (78 %), white (81 %), and non-Hispanic (81 %), with mean age of 39.8 years. Motor vehicle collisions (27 %) and falls (22 %) were common causes of injury. No significant associations were found between early dexmedetomidine exposure with day 3 brain injury biomarker levels (GFAP, ratio = 1.46, 95 % confidence interval [0.90, 2.34], P = 0.12; UCH-L1; ratio = 1.17 [0.89, 1.53], P = 0.26; NSE, ratio = 1.19 [0.92, 1.53], P = 0.19; S100B, ratio = 1.01 [0.95, 1.06], P = 0.82; hs-CRP, ratio = 1.29 [0.91, 1.83], P = 0.15). The hs-CRP level at day 14 in the dexmedetomidine group was higher than that of the non-exposure group (ratio = 1.62 [1.12, 2.35], P = 0.012). ConclusionsThere were no significant associations between early dexmedetomidine exposure and day 3 brain injury biomarkers in msTBI. Our findings suggest that early dexmedetomidine use is not correlated with either decrease or increase in brain injury biomarkers following msTBI. Further research is necessary to confirm these findings.

Melatonin mediates intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients

Background Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. Methods Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman’s correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. Results As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman’s correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = −0.19, p < .05) and LPS (r = −0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = −0.46, p < .01), LPS (r = −0.35, p < .01) and CPR (r = −0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea–hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. Conclusions Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis.

Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London. Evidence before this study: Blood RNA biomarker signatures and CRP measurements have emerged as potential triage tests for TB, but evidence is mostly limited to their performance in pulmonary TB. Microbiological diagnosis of extrapulmonary TB (EPTB) is made challenging by the need for invasive sampling to obtain tissue from the site of disease. This is compounded by lower sensitivity of confirmatory molecular tests for EPTB compared to their performance in pulmonary disease. We performed a systematic review of diagnostic accuracy studies of blood RNA biomarkers or CRP measurements for EPTB, which could mitigate the need for site-of-disease sampling for the diagnosis of TB. We searched PubMed up to 1 st August 2023, using the following criteria: "extrapulmonary [title/abstract] AND tuberculosis [title/abstract] AND biomarker [title/abstract]". Although extrapulmonary TB was included in several studies, none focused specifically on EPTB or included an adequate number of EPTB cases to provide precise estimates of test accuracy. Added value of this study: To the best of our knowledge, we report the first diagnostic accuracy study of blood RNA biomarkers and CRP for TB among people with EPTB syndromes. We examined the performance of seven previously identified blood RNA biomarkers as triage tests for TB lymphadenitis and TB pericarditis compared to a microbiology reference standard among people referred to hospital for invasive sampling in a high TB and HIV prevalence setting. Multiple blood RNA biomarkers showed comparable diagnostic accuracy to that previously reported for pulmonary TB in both EPTB disease cohorts, irrespective of HIV status. All seven blood RNA biomarkers showed superior diagnostic accuracy to CRP for both lymphadenitis and pericarditis, but failed to meet the combined >90% sensitivity and >70% specificity recommended for a blood-based diagnostic triage test by WHO. Nonetheless, in decision curve analysis, an approach of using the best performing blood RNA biomarker to trigger confirmatory microbiological testing showed superior clinical utility in clinical services seeking to reduce the number needed to test (using invasive confirmatory testing) to less than 4 for each EPTB case detected. If acceptable to undertake invasive testing in more than 4 people for each true case detected, then a test-all approach will provide greater net benefit in this TB/HIV hyperendemic setting.Implications of all the available evidence: Blood RNA biomarkers show some potential as diagnostic triage tests for TB lymphadenitis and TB pericarditis, but do not provide the level of accuracy for blood-based triage tests recommended by WHO for community-based tests. CRP has inferior diagnostic accuracy to blood RNA biomarkers and cannot be recommended for diagnostic triage among people with EPTB syndromes referred for invasive sampling.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies

BackgroundCD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies.MethodsIn this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson’s Chi-square test, t-test, Mann–Whitney U-test, Kaplan–Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression.ResultsIn this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262–15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577–5.345], P < 0.001) and severe infection (9.040 [2.256–36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy.ConclusionsCRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.

Evaluation of Salivary Biomarkers and Spirometry for Diagnosing COPD in Non-Smokers and Smokers of Polish Origin.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however, traditional diagnostic methods (based on spirometry) show limitations, prompting the search for predictive biomarkers and modern diagnostic techniques. This study explored the validation of COPD-related biomarkers (C-reactive protein, procalcitonin, neutrophil elastase, and alpha-1 antitrypsin) in saliva. A diverse cohort, including healthy non-smokers, healthy smokers, and COPD patients of Polish origin, underwent spirometry and marker analysis. The data correlated with clinical factors, revealing noteworthy relations. Firstly, salivary biomarker levels were compared with serum concentrations, demonstrating notable positive or negative correlations, depending on the factor. Further analysis within healthy individuals revealed associations between biomarker levels, spirometry, and clinical characteristics such as age, sex, and BMI. Next, COPD patients exhibited an enhanced concentration of biomarkers compared to healthy groups. Finally, the study introduced a breathing assessment survey, unveiling significant associations between self-perceived breathing and spirometric and tested parameters. Outcomes emphasized the relevance of subjective experiences in COPD research. In conclusion, this research underscored the potential of salivary biomarkers as diagnostic tools for COPD, offering a non-invasive and accessible alternative to traditional methods. The findings paved the way for improved modern diagnostic approaches.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study

BackgroundPeriprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsWe performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsCompared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688–0.823), 0.758 (95% CI: 0.687–0.821), 0.714 (95% CI: 0.639–0.781), 0.709 (95% CI: 0.634–0.777), 0.723 (95% CI: 0.649–0.789), and 0.728 (95% CI: 0.654–0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499–0.653) and 0.694 (95% CI: 0.619–0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790–0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015).ConclusionOur study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.