Concentrations Of Inflammatory Biomarkers Research Articles

Unveiling the Role of PAR 1: A Crucial Link with Inflammation in Diabetic Subjects with COVID-19.

Inflammation is a distinguished clinical manifestation of COVID-19 and type 2 diabetes mellitus (T2DM), often associated with inflammatory dysfunctions, insulin resistance, metabolic dysregulation, and other complications. The present study aims to test the hypothesis that serum concentrations of PAR-1 levels differ between COVID-19 diabetic patients (T2DM) and non-diabetic COVID-19 patients and determine their association with different biochemical parameters and inflammatory biomarkers. T2DM patients with COVID-19 (n = 50) with glycated hemoglobin (HbA1c) levels of (9.23 ± 1.66) and non-diabetic COVID-19 patients (n = 50) with HbA1c levels (4.39 ± 0.57) were recruited in this study. The serum PAR-1 levels (ELISA method) were determined in both groups and correlated with parameters such as age, BMI, inflammatory markers including CRP, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), D-dimer, homocysteine, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Demographic variables such as BMI (29.21 ± 3.52 vs. controls 21.30 ± 2.11) and HbA1c (9.23 ± 1.66 vs. controls 4.39 ± 0.57) were found to be statistically elevated in COVID-19 T2DM patients compared to non-diabetic COVID-19 patients. The concentrations of several inflammatory biomarkers and PAR-1 were remarkably increased in the COVID-19 T2DM group when compared with the non-diabetic COVID-19 group. The univariate analysis revealed that increased serum PAR-1 estimations were positively correlated with enhanced HbA1c, BMI, inflammatory cytokines, D-dimer, homocysteine, and NT-proBNP. The findings in the current study suggest that increased levels of serum PAR-1 in the bloodstream could potentially serve as an independent biomarker of inflammation in COVID-19 patients with T2DM.

Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores

BackgroundSepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.MethodsPediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning.ResultsTwenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00–1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005).ConclusionsSpecific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.

Relationship between biomarkers of autophagy and inflammation in acute period of ischemic stroke

Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia, spanning early injury and tissue repair. According to recent experimental data, autophagy is involved in the regulation of neuroinflammation, influencing the outcome of the acute period of ischemic stroke (IS).Objective. To evaluate the relationship between autophagy biomarkers and inflammation indicators in the dynamics of the acute period of atherothrombotic IS.Materials and methods. 112 patients in the acute period of newly developed atherothrombotic IS and 56 donors (control group) were examined. Patients underwent dynamic clinical and neurological examination on the 1st, 7th and 14th days from the onset of the disease (magnetic resonance imaging, testing using the NIHSS scale, modified Rankin scale). At the same time intervals, blood was drawn for testing. The number of active autophagosomes in peripheral blood was assessed by flow cytometry using a specific Cyto-ID dye. The serum concentrations of proinflammatory cytokines IL‑1β, IL‑8, IL‑18 (interleukins‑1β, -8, -18), TNFα (tumor necrosis factor-α), autophagy biomarkers Beclin‑1, LC 3 and p62 were determined by enzyme-linked immunosorbent assay analysis. C-reactive protein was assessed by a highly sensitive immunoturbidimetric method.Results. A statistically significant increase in the studied parameters was revealed compared to the control group. The maximum increase in inflammation biomarkers was observed on the 1st day, and the maximum increase in key indicators of autophagy (LC 3, Beclin‑1, Cyto-ID) – on the 7th day after the development of ischemia. A direct relationship was established between the level of autophagy and the concentration of inflammatory biomarkers (CRP, IL‑1β, IL‑18, TNF-α) on the 1st and 7th days of acute IS.Conclusions. The identified correlations indicate the participation of activated autophagy in the regulation of post-ischemic neuroinflammation and its involvement in ischemic brain damage in the early stages of the acute period of IS (days 1–7). The results obtained confirm the literature data on the influence of autophagy on the outcome of the acute period of the disease.

Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.

Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine.

Canine gastric dilatation volvulus (GDV) is characterized by tissue ischemia, reperfusion, and systemic inflammation. Evidence exists that lidocaine exerts anti-inflammatory properties and potentially improves outcome. Prospective, randomized observational cohort study in client-owned dogs with GDV. The primary objective of the study was the determination of pro- and anti-inflammatory biomarker concentrations in dogs with GDV with and without intravenous (IV) lidocaine therapy. The second objective was the evaluation of side effects of lidocaine. Of 35 dogs included in the study, 20 dogs were assigned to receive lidocaine (LIDO) (2 mg/kg initially, followed by a continuous infusion at a rate of 50 μg/kg/min over 24 h) and 15 dogs not to receive lidocaine (NO-LIDO). Plasma concentrations of cytokines interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma, keratinocyte chemotactic-like, monocyte chemotactic protein, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, T0), immediately after surgery (T1), at 24 h (T24), and at 48 h (T48) post-surgery. No significant differences in concentrations of any cytokines were found between the LIDO- and the NO-LIDO group. Significant lower CRP concentrations (median [range]) were found in dogs with lidocaine compared to dogs without at T24 (97.5 pg/mL [46.3-161.7] vs. 127.9 pg/mL [26.9-182.0]; p = 0.046) and T48 (73.7 pg/mL [18.4-169.4] vs. 116.3 pg/mL [71.4-176.8]; p = 0.002). Dogs receiving lidocaine exhibited significantly impaired mentation, a prolonged period of anorexia, and longer hospitalization compared to dogs without lidocaine. Lidocaine administration had no impact on the plasma levels of cytokines during the 48-h study period, but significantly lower CRP concentrations were found at T24 and T48. Lidocaine's potential side effects require careful decision making regarding its use.

Diagnostic and Prognostic Predictors for the Success of Pulpotomy in Permanent Mature Posterior Teeth with Moderate to Severe Pulpitis: A Scoping Review

A partial or complete pulpotomy is a type of vital pulp therapy (VPT) that aims to remove the inflamed, infected pulp, leaving behind healthy, vital pulp that is capable of healing. VPT has gained renewed popularity as a treatment option in permanent mature posterior teeth with irreversible, moderate to severe pulpitis; its high success rates matching that of root canal treatment (RCT). There is currently no consensus regarding diagnostic and prognostic predictors of success of pulpotomies for managing such cases. Therefore, we conducted a scoping review to identify and analyze how these factors affect the outcome of treatment. A literature search using the PRISMA guidelines was undertaken using PubMed and Scopus on 7 July 2023. A total of 22 studies met the inclusion criteria and were qualitatively analyzed by two reviewers. The following diagnostic and prognostic factors were recognized and discussed; presenting signs and symptoms, periapical diagnosis, bleeding time, indicators of inflammation (bleeding time, concentration of inflammatory biomarkers), patient age and medical status, the depth, activity and location of caries, and restorative factors. Based on the studies assessed, there is limited evidence to support their prognostic value. Further research is necessary to identify solid predictors of outcome.

Dynamic changes in inflammatory responses and 3-year clinical outcomes of XINSORB scaffolds in coronary stenting

BackgroundInflammation is known to play a crucial role in the development of coronary atherosclerosis and vascular healing after stenting. This study aimed to investigate the dynamic changes in inflammatory responses between XINSORB and TIVOLI scaffolds and their correlation with 3-year clinical outcomes. MethodA total of 140 patients in the XINSORB group and 42 patients in the TIVOLI group were included in this prospective, single-center study, conducted in Shanghai tenth People's Hospital. Blood samples were collected at baseline, 24 h, 6 months, and 12 months after stent implantation to measure high sensitivity C-reactive protein (hsCRP), fibrinogen (FBG), white blood cell count (WBC), tumor necrosis factor (TNF), and interleukin-6 (IL-6). Receiver-operating characteristic curves and proportional hazards models were generated to evaluate the relationship between 24-h postoperative inflammatory indicators and 3-year patient-oriented composite endpoints (POCE). ResultThe levels of hsCRP, FBG, WBC, TNF, and IL-6 reached their peak levels 24 h after stenting and then gradually decreased to levels comparable to baseline at 6 and 12 months. During the 3-year follow-up, 11.4 % of the XINSORB cohort and 9.5 % of the TIVOLI cohort experienced POCE (P = 0.948). High levels of hsCRP and IL-6 24 h after the procedure were associated with clinical endpoints, and the combination of these two biomarkers improved the predictive ability of prognosis. ConclusionsThere were no significant differences between the changes in the concentration of inflammatory biomarkers after XINSORB stents or drug-eluting stent implantation. Reduction in postoperative inflammatory levels may decrease the occurrence of clinical outcomes. This study provides insights into the dynamic changes of inflammatory responses and their correlation with clinical outcomes, which could have implications for the management of patients undergoing coronary stenting. Trial registrationThe study has been registered on the official website of the China Clinical Trial Registry (ChiCTR1800014966).

Adherence to Healthy and Sustainable Dietary Patterns and Long-Term Chronic Inflammation: Data from the EPIC-Potsdam Cohort

ObjectivesWe explored the prospective associations between adherence to a priori chosen dietary patterns, including EAT-Lancet (EAT-L) and Mediterranean (tMDS) diet with long-term inflammatory responses in a German population sample.Design and SettingProspective cohort study.ParticipantsA subsample of 636 predominantly healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who were on average 51-years old at baseline.MeasurementsData was collected repeatedly between 1994/1998–2013. At baseline (1994/1998) and 6.8-years later (2001/2005), EAT-L and tMDS scores were derived from available food frequency questionnaires. Stable high, stable low, increasing, and decreasing adherence to EAT-L and tMDS were defined as scoring above/below baseline median at baseline and 6.8-years later. Long-term chronic inflammation was assessed based on the average values of repeated measurements of two inflammatory biomarkers - chemerin and high-sensitivity C-reactive protein (hs-CRP) - in plasma samples collected between 2010/2012 and 2013. Multivariable linear regression analysis adjusted for socio-demographic and lifestyle factors at baseline and in 2010/2012 was used to assess the association between diet adherence and long-term hs-CRP and chemerin concentrations.ResultsStable high or increasing adherence to EAT-L diet compared to stable low adherence was associated with slight reduction of long-term chemerin concentrations on the long run (stable high: −4.4%; increasing: −4.0%), not reaching statistical significance. Increasing adherence to tMDS compared to stable low adherence was also associated with a minor reduction in chemerin concentrations (−3.6%). Decreasing adherence to tMDS compared stable high adherence was associated with 2.7% higher chemerin. The associations were even less pronounced when hs-CRP was used as an outcome.ConclusionsAdherence to healthy and sustainable dietary patterns defined using existing definitions for EAT-L and tMDS were associated with minor and not statistically significant reduction in the concentrations of inflammatory biomarkers on the long run. More research is needed to explore whether following these diets may represent a suitable approach for targeted prevention in the general population.

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory cytokines are produced when immune system imbalances are driven by genetic and environmental triggers. Vinpocetine (VNP), a man-made analogue of the compound vincamine found in the dwarf periwinkle herb, has robust anti-inflammatory, immunomodulatory, and anti-oxidative effects; alleviates the epidermal penetration of immune cells, such as eosinophils and neutrophils; and abolishes the generation of pro-inflammatory molecules. ObjectiveThis study was aimed at exploring the effects of long-term topical VNP, both alone and co-administered with clobetasol propionate, in an imiquimod-induced mouse model of psoriasiform dermatitis. MethodsThe study protocol consisted of 48 Swiss albino mice, randomly divided into six groups of eight mice each. In group I, petroleum jelly was administered daily for 8 days. In group II, imiquimod was administered topically at 62.5 mg daily for 8 days. In groups III, VI, V, and VI, 0.05% clobetasol propionate, 1% VNP, 3% VNP, and 3% VNP plus 0.05% clobetasol were administered topically for an additional 8 days after the induction, thus resulting in a total trial length of 16 days. ResultsTopical VNP at various doses alleviated the severity of imiquimod-induced psoriatic lesions—including erythema, silvery-white scaling, and thickening—and reversed the histopathological abnormalities. Moreover, imiquimod-exposed animals treated with VNP showed markedly diminished concentrations of inflammatory biomarkers, including tumour necrosis factor-α, interleukin (IL)-8, IL-17A, IL-23, IL-37, nuclear factor-kappa B (NF-κB), and transforming growth factor-β1. ConclusionThis research provides new evidence that VNP, alone and in combination with clobetasol, may serve as a potential adjuvant for long-term management of autoimmune and autoinflammatory skin diseases, particularly psoriasis, by attenuating psoriatic lesion severity, suppressing cytokine generation, and limiting NF-κB-mediated inflammation.

Prenatal exposure to perfluoroalkyl substances and inflammatory biomarker concentrations.

We analyzed data from 1411 participants, recruited between 2008 and 2011, in the Maternal-Infant Research on Environmental Chemicals study. Our primary outcome was a composite inflammatory index derived by summing the z-scores of eight proinflammatory biomarkers. Using multivariable linear regression models, we quantified associations between each PFAS and the inflammatory index and individual biomarkers. We quantified the effects of the PFAS mixture using weighted quantile sum regression, and evaluated effect modification using product terms and sex-stratified models. Each doubling of PFOA and PFHxS was associated with a 0.38 (95% CI, 0.09, 0.67) and 0.21 (95% CI, 0.01, 0.41) SD increase in the proinflammatory index, respectively. A one-quartile increase in the PFAS mixture was associated with a 0.40 (95% CI, 0.09, 0.71) SD increase in the proinflammatory index. In individual models, we observed positive associations between PFAS and concentrations of monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and matrix metalloproteinases-9; however, the magnitude and precision varied according to the specific PFAS. Sex-specific findings were identified in few PFAS-biomarker associations. PFOA, PFOS, and PFHxS, individually and as a mixture, were positively associated with proinflammatory biomarkers during pregnancy.

Heart failure in erythrodermic psoriasis: a retrospective study of 225 patients.

Erythrodermic psoriasis (EP) is a severe form of psoriasis that affects multiple organs, including the cardiovascular system. However, few studies have focused on this condition.This study is aimed to assess the prevalence and factors associated with heart failure in EP patient, and to the measure the serum concentrations of fibroblast growth factor 23 (FGF23), a potential predictor of chronic heart failure. We retrospectively studied patients with EP hospitalized at Peking Union Medical College Hospital between January 2005 to October 2021. The prevalence of heart failure and associated factors was measured. In addition, peripheral blood samples were collected from 17 patients and matched with samples from eight healthy controls, and their serum concentrations of FGF23 were measured by ELISA. We studied 225 patients with EP, with a male: female ratio of 2.7:1 and a mean age of 47.6 ± 16.7 years. Twenty-five (11.1%) participants were diagnosed with heart failure during their hospital stay. The patients with EP and heart failure were older (58.2 years vs. 46.2 years, p = 0.001); had a higher prevalence of a history of coronary heart disease (32.0% vs. 21.5%, p < 0.001), fever (48.0% vs. 23.0%, p = 0.007), infection (56.0% vs. 35.5%, p = 0.046); higher hsCRP concentration (43.2 mg/L vs. 8.2 mg/L, p = 0.005); and higher prevalence of anemia (60.0% vs. 22.0%, p < 0.001), hypoalbuminemia (64.0% vs. 42.0%, p = 0.037), and hyperlipidemia (40.0% vs. 20.0%, p = 0.023) than those without heart failure. The serum FGF23 concentration was significantly higher in patients with EP than controls (493.1 pg/ml vs. 277.8 pg/ml, p = 0.027), and was significantly lower after treatment (395.7 pg/ml vs. 463.1 pg/ml, p = 0.022). Clinicians should be aware of the risk of heart failure in patients with EP, and especially those of advanced age and with a history of coronary heart disease, severe systemic symptoms, high concentrations of inflammatory biomarkers, and poor nutritional status.

Raman Spectroscopy Profiling of Splenic T-Cells in Sepsis and Endotoxemia in Mice.

Sepsis is a life-threatening condition that results from an overwhelming and disproportionate host response to an infection. Currently, the quality and extent of the immune response are evaluated based on clinical symptoms and the concentration of inflammatory biomarkers released or expressed by the immune cells. However, the host response toward sepsis is heterogeneous, and the roles of the individual immune cell types have not been fully conceptualized. During sepsis, the spleen plays a vital role in pathogen clearance, such as bacteria by an antibody response, macrophage bactericidal capacity, and bacterial endotoxin detoxification. This study uses Raman spectroscopy to understand the splenic T-lymphocyte compartment profile changes during bona fide bacterial sepsis versus hyperinflammatory endotoxemia. The Raman spectral analysis showed marked changes in splenocytes of mice subjected to septic peritonitis principally in the DNA region, with minor changes in the amino acids and lipoprotein areas, indicating significant transcriptomic activity during sepsis. Furthermore, splenocytes from mice exposed to endotoxic shock by injection of a high dose of lipopolysaccharide showed significant changes in the protein and lipid profiles, albeit with interindividual variations in inflammation severity. In summary, this study provided experimental evidence for the applicability and informative value of Raman spectroscopy for profiling the immune response in a complex, systemic infection scenario. Importantly, changes within the acute phase of inflammation onset (24 h) were reliably detected, lending support to the concept of early treatment and severity control by extracorporeal Raman profiling of immunocyte signatures.

Poster 126: Chronic ACL Injury Patients Have Lower Levels of Pro-Inflammatory Biomarkers in their Synovial Fluid and Worse ACLOAS Score at the Time of Surgery Than Those with Acute ACL Injury: A Cohort Study

Objectives: The relationship between structural abnormalities and inflammatory changes in the synovial fluid following ACL injury has not been well defined. The purpose of this study is to compare MRI findings and concentration of inflammatory biomarkers in the synovial fluid (SF) of acute and chronic anterior cruciate ligament (ACL) injury patients. Methods: Patients undergoing surgery for ACL injury from October 2011 to December 2021 were included in a database of patients who had SF samples collected at the time of surgery. From this cohort, 82 patients with acute ACL injury and 28 patients with chronic ACL injury were identified. All patients underwent a preoperative MRI examination of the knee and SF was aspirated from the operative knee prior to the surgical incision and concentrations of inflammatory biomarkers were quantified. MRI examinations were reviewed by a fellowship-trained musculoskeletal radiologist to assess radiographic features of acute and chronic knee injury using the validated ACLOAS system. Nonparametric tests were used to compare demographic factors, MRI findings, clinical symptoms, and SF inflammatory biomarkers between acute versus chronic ACL injury patients. A generalized linear model was used to assess the relationship of each SF biomarker with the ACLOAs subscores. Results: For acute ACL injury patients, mean time from injury to MRI and injury to surgery was 14 ± 35 days and 49 ± 38 days, respectively. The mean time from injury to MRI and injury to surgery was 3.2 ± 3.7 years and 3.4 ± 3.8 years, respectively, for those with chronic ACL injury. There were no significant demographic differences between groups; age (acute: 31.62 ± 8.02 years, chronic: 33.70 ± 10.60 years, p=0.130), sex (acute: 51.2% males, chronic: 57.1%, p=0.588), or body mass index (acute: 5.5 ± 4.4 kg/mm2, chronic: 25.3 ± 3.6 kg/mm2, p=0.931). Acute ACL injury patients had higher bone marrow edema severity scores (p&lt;0.001), Hoffa’s synovitis score (p=0.002), and effusion severity scores (p&lt;0.001). Chronic ACL injury patients had higher cartilage degeneration severity scores (p&lt;0.001), prevalence of meniscus tears (p=0.003), and meniscus tear severity scores (p&lt;0.001). Acute ACL injury patients had significantly higher synovial fluid levels of IL-6 (p=0.032), VEGF (p=0.002), TIMP1 (p&lt;0.001), IL1-RA (p=0.003), and MMP3 (p&lt;0.001) than chronic ACL injury patients. The generalized linear model revealed that after adjusting for age, sex, BMI, and time from injury to surgery, increased VEGF (p=0.003) and MMP3 (p=0.012) were associated with higher effusion score. MMP-3 was associated with a higher bone marrow edema score (p=0.034), and RANTES was associated with both a higher meniscus severity score (p=0.027) and increased cartilage lesions in the chronic ACL injury cohort. Conclusions: The findings from this study suggest that despite having more severe cartilage degeneration and a higher prevalence of meniscus pathology, chronic ACL injury patients had lower levels of synovial fluid inflammatory biomarkers at time of surgery compared to acute ACL injury patients. Additionally, we found that in chronic injuries, RANTES was associated with worse ACLOAS cartilage scores.

Poster 121: Association Between MRI Findings in ACL Injury and Subacute Synovial Fluid Inflammatory Biomarker Levels at the Time Of Surgery

Objectives: To Investigate the association between MRI findings following anterior cruciate ligament (ACL) injury and synovial fluid biomarker profile at the time of surgery Methods: Patients undergoing surgery for ACL injury from October 2011 to December 2021 were included in a database of subjects who had synovial fluid samples collected at the time of surgery. From this cohort, 82 subjects with acute ACL injury were retrospectively selected who met the following inclusion criteria: no history of prior knee trauma to suggest chronic ACL injury, history of acute non- contact knee injury, MRI examination of the knee performed within 3 weeks of knee injury, subsequent knee surgery performed between 4 and 12 weeks of knee injury, and no additional ligament tear requiring surgical treatment. All subjects underwent a preoperative MRI examination of the knee using multi-planar, multi-contrast fast spin-echo sequences. Synovial fluid was aspirated from the operative knee prior to surgical incision. Concentrations of inflammatory biomarkers including regulation on activation normal T cell expressed and secreted (RANTES), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tissue inhibitor matrix metalloproteinase 1 (TIMP1), interleukin 1 receptor agonist (IL1-RA) and matrix metalloproteinase 3 (MMP-3) were measured. The MRI examinations of all subjects were reviewed by a fellowship trained musculoskeletal radiologist to assess the presence and severity of various MRI features of acute and chronic knee injury using the validated Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) system. Nonparametric Wilcoxon tests and Fisher’s exact test were used to compare demographic factors, MRI findings, clinical symptoms, and synovial fluid inflammatory biomarkers between clusters. K-means cluster analysis was used to identify 2 distinct clusters of subjects with acute ACL injury based on biomarkers concentrations in synovial fluid. Results: The mean age of the cohort was 31.6 ± 8 years, average body mass index (BMI) was 25.5 ± 4.4 kg/m2. There 42.7% (n=35) of the cohort was female and 85.4% (n=70) were non-smokers. Two distinct clusters were identified: cluster 1 included 45 subjects and was marked by older subjects (33.2 ± 9.1 years, p=.038) with lower levels of all inflammatory synovial fluid biomarkers. Cluster 2 included 37 subjects and was marked by younger patients (29.7 ± 6.1 years, p=.038) with a more pro-inflammatory synovial fluid biomarker profile, higher ACLOAS Hoffa’s synovitis score (p=.001), and a higher incidence of subchondral bone fractures (54%, p=.002). There were no differences between clusters in time from injury to surgery (p=), BMI (p=.141), or ACLOAS meniscus (p=.086), cartilage (p=.730), or effusion scores (p=.202) Conclusions: Given the variable outcomes seen following ACL reconstruction (ACLR) surgery, a better understanding of the pathophysiology following ACL injury is needed. This study found distinct cluster of patients who exhibited a higher inflammatory reaction at the time of surgery as well as more severe findings on preoperative MRI. These findings could be used to identified clinical parameters associated with more inflammation at the time of surgery and their effect on clinical outcomes of ACLR.

Central and Peripheral Inflammation in Mild Cognitive Impairment in the Context of Alzheimer's Disease.

Mild cognitive impairment (MCI) is characterized by an abnormal decline in mental and cognitive function compared with normal cognitive aging. It is an underlying condition of Alzheimer's disease (AD), an irreversible neurodegenerative disease. In recent years, neuroinflammation has been investigated as a new leading target that contributes to MCI progression into AD. Understanding the mechanism underlying inflammatory processes involved in the early onset of the disease could help find a safe and effective way to diagnose and treat patients. In this article, we assessed over twenty different blood and cerebrospinal fluid (CSF) inflammatory biomarker concentrations with immunoassay methods in patients with MCI (mild cognitive impairment), non-impaired control (NIC), and serum healthy control (HC). We performed group comparisons and analyzed in-group correlations between the biomarkers. We included 107 participants (mean age: 64.7 ± 7.8, women: 58.9%). CSF osteopontin and YKL-40 were significantly increased in the MCI group, whereas serum C-reactive protein and interleukin-6 were significantly higher (p < 0.001) in the NIC group compared with the MCI and HC groups. Stronger correlations between interleukin-1β and inflammasome markers were observed in the serum of the MCI group. We confirmed specific inflammatory activation in the central nervous system and interleukin-1β pathway upregulation in the serum of the MCI cohort.

Meta-analysis of serological biomarkers at hospital admission for the likelihood of developing delirium during hospitalization.

Identifying biomarkers that, at hospital admission, predict subsequent delirium will help to focus our clinical efforts on prevention and management. The study aimed to investigate biomarkers at hospital admission that may be associated with delirium during hospitalization. A librarian at the Fraser Health Authority Health Sciences Library performed searches from 28 June 2021 to 9 July 2021, using the following sources: Medline, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, and the Database of Abstracts of Reviews and Effects. The inclusion criteria were articles in English that investigated the link between serum concentration of biomarkers at hospital admission and delirium during hospitalization. Exclusion criteria were single case reports, case series, comments, editorials, letters to the editor, articles that were not relevant to the review objective, and articles concerning pediatrics. After excluding duplicates, 55 studies were included. This meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Independent extraction, with the consensus of multiple reviewers, was used to determine the final studies included. The weight and heterogeneity of the manuscripts were calculated using inverse covariance with a random-effects model. Differences in mean serum concentration of biomarkers at hospital admission between patients who did and did not develop delirium during hospitalization. Our search found evidence that patients who developed delirium during hospitalization had, at hospital admission, significantly greater concentrations of certain inflammatory biomarkers and one blood-brain barrier leakage marker than patients who did not develop delirium during hospitalization (differences in the mean: cortisol: 3.36 ng/ml, p < 0.0001; CRP: 41.39 mg/L, p < 0.00001; IL-6: 24.05 pg/ml, p < 0.00001; S100β 0.07 ng/ml, p < 0.00001). These differences were independent of other confounding variables such as the patient's severity of illness. A significantly lower serum concentration, at hospital admission, of acetylcholinesterase (difference in the means -0.86 U/ml, p = 0.004) was also associated with an increased vulnerability to developing delirium during hospitalization. Our meta-analysis supports the hypothesis that patients with hypothalamic-pituitary axis dysfunction, increased blood-brain barrier permeability, and chronic overload of the cholinergic system, at hospital admission, are more vulnerable to developing delirium during hospitalization.

Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial.

Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease, as well as the risk of death. Simple markers of progression are much needed to identify those at highest risk for poor outcome. This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT). This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4 <50cells/μL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes. Of all 269 participants, 76.2% (n=205) were anaemic, and 31.2% (n=84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3.59, 95% CI: 1.32-9.76, p=0.012) and death (aOR: 3.63, 95% CI: 1.07-12.33, p=0.039). Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. The presence of moderate/severe anaemia pre-ART was independently associated with the development of TB and death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes. National Institutes of Health.

ВЗАИМОСВЯЗЬ ТИПА ЛИЧНОСТИ D И НАРУШЕНИЯ ФУНКЦИИ ЭНДОТЕЛИЯ У ПАЦИЕНТОВ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА

Introduction. Major psychosocial risk factors for acute myocardial infarction include depression, anxiety (various anxiety syndromes and disorders), pessimistic D personality type, work and family stress, anger/hostility, lack of social support, and low socioeconomic status. There are few studies evaluating the association between psychological factors and myocardial infarction. Aim. The aim of the study was to study the relationship of personality type D with the development of endothelial dysfunction in patients with acute myocardial infarction. Material and methods. The study included 158 patients, mean age 58.2±2.5 years, who were admitted to the hospital for ST-segment elevation myocardial infarction. The diagnosis was established according to the clinical guidelines of the Russian Society of Cardiology, 2020. In addition to the traditional clinical and instrumental examination, on the 3rd–7th day after the development of myocardial infarction, patients underwent an assessment of plasma concentrations of inflammatory biomarkers and psychological testing using anxiety and depression rating scales. In the group of patients, individuals with and without personality type D were identified. Results and discussion. Personality type D was found in 29.1% of patients with acute myocardial infarction. Patients with personality type D were significantly younger, employed and married, had a higher body mass index and a significantly greater hereditary burden of arterial hypertension. In patients with personality type D, the values of pro-inflammatory markers were statistically significantly different from the comparison group, which indicates the intensity of subclinical inflammation and cytokine imbalance. Personality type D was significantly associated with total inflammation score and total endothelial dysfunction score. Significant differences were found in the ratio of patients with depressive conditions in subgroups of patients with personality type D. The values of echocardiographic parameters were also associated with the presence of personality type D. Conclusion. Personality type D was associated with impaired endothelial function in men with acute myocardial infarction, they were more likely to have depressive disorders. An adverse effect of personality type D on the cardiovascular system in patients with myocardial infarction was revealed.

Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies

It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies. To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies. This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022. TEs identified by K-means clustering of plasma biomarkers collected at hospital arrival. An association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS. A total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001). Results of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes.

Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation.

Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions-Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.