Inflammatory Biomarkers C-reactive Protein Research Articles

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.

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.

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.

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.

Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients

BackgroundSarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. MethodsWe enrolled 460 HF, LVAD and HT patients. Repeated measures pre/post procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and i) New York Heart Association class; ii) pre- vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity. ResultsMedian (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32,0.05). Ln-SI decreased across worsening HF class, further declined at 1-month after LVAD and HT and rebounded over time. Ln-SI was correlated with inflammation (r=-0.28, p<0.01), and gut (r=0.28, p<0.01) and oral microbial diversity (r=0.24, p<0.01), these associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. Presence of the gut taxa Roseburia inulinivorans was associated with increased SI. ConclusionsSI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

The post-mortem use of inflammatory biomarkers C-reactive protein and procalcitonin – advantageous or impeding?

ABSTRACT Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, which can result in multi-organ failure and death due to a combination of tissue hypoperfusion, impairment of the coagulation system and oxidative stress. There is no validated gold standard for the diagnosis of sepsis, either antemortem or post-mortem. To fill the gap, other ancillary tests are performed, which may include blood cultures, immunohistochemical markers and biomarkers.

A comprehensive tool in recycling plant-waste of Gossypium barbadense L agricultural and industrial waste extracts containing gossypin and gossypol: hepatoprotective, anti-inflammatory and antioxidant effects.

Improper management of agricultural and industrial cotton wastes causes environmental pollution and worsens the climate change challenge. Green recycling of cotton could contribute to a circular economy. One of the economic values of cotton wastes lies in their bioactive components. Two types of cotton wastes-agricultural and industrial-of the species Gossypium barbadense L. Giza 95 were targeted in the current study, aiming to maximize their medicinal value and investigate the anti-inflammatory, hepatoprotective, and antioxidant activities of their phytochemical extracts. Phytochemical extraction was performed using different solvents extraction. An anti-inflammatory effect was tested in carrageenan-induced acute edema in a rat paw model. A carbon tetrachloride chronic model of liver injury was used for the assessment of hepatoprotective potential. Liver enzymes (AST and ALT), oxidative stress markers (MDA and GSH), inflammatory biomarkers (C-reactive protein), and histopathological features were investigated. As a result, ethyl acetate proved to be the solvent of best choice to extract the gossypin polyphenolics, where the extracted amount reached 14,826.2µg/g, followed by butanol (8751.4µg/g extract). The chloroform (CHCL3) fraction showed the highest amounts of gossypol (190.7µg/g extract), followed by petroleum ether. Cotton waste's composition analysis showed a wide range of components, including 33 metabolites such as gossypetin, polyphenolics, and other metabolites that possess therapeutic effects. Both chloroform extract and industrial waste extracts showed superior anti-inflammatory and hepatoprotective effects in comparison to other extracts. All tested extracts (ethyl acetate, chloroform, and industrial waste) showed proper antioxidant activities.

Dupilumab in patients with atopic dermatitis: assessing treatment response, clinical features and potential biomarkers in real-life.

Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

Abstract P103: Alterations in Sarcopenia Index Are Associated With Inflammation, Gut and Oral Microbiota Among Heart Failure, Left Ventricular Assist Device and Heart Transplant Patients

Introduction: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and associated with poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate marker of skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT) and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. Hypothesis: Sarcopenia will be associated with increased inflammation, dysbiotic microbial signatures, higher HF class, and earlier time post-HT or post LVAD. Methods: We enrolled 460 HF, LVAD and HT patients. Repeated measures pre and post procedures were obtained in a subset of LVAD and HT patients. Sarcopenia index (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression models were used to assess the relationship between SI and i) New York Heart Association class; ii) pre- vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity. Results: Median (interquartile range) ln-SI was -0.13(-0.32,0.05). Ln-SI decreased across worsening HF class, further declined within the 1-month after LVAD and HT and rebounded over time to the levels of symptomatic HF. Ln-SI demonstrated an inverse correlation with inflammation (r=-0.28, p&lt;0.0001), and a positive correlation with gut (r=0.26, p&lt;0.0001) and oral microbial diversity (r=0.24, p&lt;0.0001). Presence of the gut taxa Roseburia inulinivorans was associated with increased SI. Conclusions: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. SI levels covaried with inflammation, gut and oral microbiota in a similar fashion.

Exploring PGE2 and LXA4 Levels in Migraine Patients: The Potential of LXA4-Based Therapies.

Neurogenic inflammation plays a significant role in the pathogenesis of migraines. This study aimed to investigate the serum levels of prostaglandin E2 (PGE2), lipoxin A4 (LXA4), and other inflammatory biomarkers (C-reactive protein, fibrinogen) in migraine patients. In total, 53 migraine patients and 53 healthy controls were evaluated. Blood serum samples were collected during both attack and interictal periods and compared with the control group. In both the attack and interictal periods, PGE2 and LXA4 values were significantly lower in migraine patients compared to the control group (p < 0.001). Additionally, PGE2 values during the attack period were significantly higher than those during the interictal period (p = 0.016). Patients experiencing migraine attacks lasting ≥ 12 h had significantly lower serum PGE2 and LXA4 levels compared to those with attacks lasting < 12 h (p = 0.028 and p = 0.009, respectively). In ROC analysis, cut-off values of 332.7 pg/mL for PGE2 and 27.2 ng/mL for LXA4 were determined with 70-80% sensitivity and specificity. In conclusion, PGE2 and LXA4 levels are significantly lower in migraine patients during both interictal and attack periods. Additionally, the levels of LXA4 and PGE2 decrease more with the prolongation of migraine attack duration. Our findings provide a basis for future treatment planning.

SunGold Kiwifruit Consumption Restores Adequate to Optimal Vitamin C Status in People with a History of Severe Respiratory Infections.

Severe respiratory infections are characterised by depleted vitamin C and elevated inflammation and oxidative stress. The aim of this study was to recruit people with a history of severe respiratory infections to undergo a six-week intervention with SunGold kiwifruit to determine if this could restore adequate vitamin C status. Secondary outcomes included changes in inflammatory and oxidative stress biomarkers, self-reported fatigue and subjective mood, and the incidence, duration and severity of respiratory symptoms. The total cohort comprised 20 adults (65% female, age range 31-84 years). The participants had a low median fruit and vegetable intake of 2.3 servings/day and a correspondingly low vitamin C intake of 46 mg/day. Circulating vitamin C status was a median of 45 µmol/L and was in the hypovitaminosis range in 25% of the cohort. Following intervention with two SunGold kiwifruit/day (equivalent to ~300 mg vitamin C), there was an increase in plasma vitamin C concentrations to >60 µmol/L (p < 0.05). Approximately 20% of the participants were unable to reach adequate vitamin C status (≥50 µmol/L), possibly due to current smoking, which enhances vitamin C turnover, and a strong inverse correlation between body weight and vitamin C status (r = -0.734, p < 0.05). Following the intervention, there were indications towards decreases in the inflammatory biomarkers C-reactive protein and TNFα (p > 0.05), but no changes in oxidative stress biomarkers (F2isoprostanes, protein carbonyls). There were decreases in fatigue and depression (p < 0.05) and a lower number of individual respiratory symptoms reported during the kiwifruit intervention phase (8.5 vs. 10, p = 0.05). Overall, the consumption of two SunGold kiwifruit per day for six weeks was able to restore adequate to saturating vitamin C status in ~80% of the participants. Smokers and people with higher body weight may need larger doses and/or longer duration of supplementation. The contribution of vitamin C to reducing fatigue, depression, and number of respiratory symptoms warrants further investigation.

Personalized corticosteroid treatment of patients with severe new coronavirus infection complicated by pneumonia: a prospective comparative study

INTRODUCTION: A new coronavirus infection caused by the SARS-CoV-2 coronavirus and the associated disease COVID-19 is accompanied by a high incidence of acute respiratory distress syndrome (ARDS) and pneumonia with respiratory failure. Corticosteroids are a therapeutic treatment option. OBJECTIVE: To determine the advantage of personalized corticosteroid dosing to reduce inflammation in pneumonia in patients with comorbid diseases. MATERIALS AND METHODS: A prospective comparative study was conducted among adult patients in the Republican Clinical Infectious Hospital and the Clinical Emergency Hospital (Ufa, Republic of Bashkortostan) from May 2020 to May 2021. Patients were divided into two groups: personalized corticosteroid administration in accordance with the level of the inflammation biomarker C-reactive protein (CRP) (n = 30) compared with conventional therapy (n = 28). Measurements of CRP levels in blood samples were carried out at the time of hospitalization and then daily during the first 5 days of treatment. RESULTS: The intervention group had fewer days of respiratory support (9.4 [6.2–15.6] vs. 14.3 [7.1–21.4]; p = 0.003) and no differences in cumulative outcome (persistent dependence of respiratory support or death) and the incidence of nosocomial infection compared with the control group. Daily distribution of the biomarker CRP showed significantly lower levels on 2–4 days of treatment in the intervention group compared with the control group. CONCLUSIONS: In critically ill patients with pneumonia caused by COVID-19, and comorbid diseases, a personalized approach to the corticosteroids prescribing slightly reduced the frequency of treatment ineffectiveness and statistically significantly reduced the duration of respiratory support.

Association between polycyclic aromatic hydrocarbon exposure and liver function: The mediating roles of inflammation and oxidative stress

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects.

Influence of inflammatory factors (IL-6, CRP, NLPR, D-Dimer, LDH) on the PaO2/FiO2 ratio, in patients with severe and critical degrees of COVID-19

BACKGROUND: Several types of inflammatory biomarkers that are important in severe and critical Covid-19 infections include: levels of IL-6, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-Dimer and neutrophil-lymphocyte platelet ratio (NLRP), which are independent variables. Meanwhile, the severity of Covid-19 infection can be determined by measuring the PaO2 /FiO2 ratio. However, the relationship between the PaO2/FiO2 ratio as the dependent variable is not yet known. AIMS: To analyze the relationship between PaO2/FiO2 ratio and inflammatory biomarkers in COVID-19 patients METHOD: An analytic observational study with a retrospective, cross-sectional approach. The research sample consisted of PCR-confirmed severe and critical COVID-19 patients who were treated in the isolation room of the Ulin Hospital in Banjarmasin from August–December 2021, who met the inclusion and exclusion criteria. Data analysis used the Spearman test to see the relationship between the PaO2/FiO2 ratio and various inflammatory markers. RESULT: 52 severe and critical patients were observed according to the research flow. The number of male and female subjects (32/20) was found. The mean age was 55.38 years. The correlation test found that: there was no significant relationship between the PaO2/FiO2 ratio and IL-6 (p = 0.964), but there was a negative correlation between the PaO2/FiO2 ratio and: a).CRP (p = 0.038), b).LDH ( p&lt;0.001), c).NLPR (p = 0.013), and d). D-dimer (p&lt;0.001). The inflammatory biomarkers NLPR, LDH, and D-dimer are important independent variables for the severity of COVID-19, namely the PaO2/FiO2 ratio. CONCLUSION: There are a significant correlation between the PaO2/FiO2 ratio to measure the severity of Covid-19 and several inflammatory biomarkers CRP, LDH, NLPR and D-dimer

Effect of Curcumin gel on inflammatory and anti-inflammatory biomarkers in experimental induced periodontitis in rats: a biochemical and immunological study.

This study aimed to determine the effect of local application of curcumin gels as adjunct to scaling and root planing (SRP) on the inflammatory biomarkers matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6), C-reactive protein (CRP), and alkaline phosphatase (ALP), and the anti-inflammatory biomarker interleukin-10 (IL-10) in rats with experimentally induced periodontitis. Fifty-five adult Wistar rats with experimentally induced periodontitis were randomly divided into four groups: 15 rats received SRP + curcumin gel (CU), 15 rats received SRP + Tetracycline gel (Tet), 15 rats were treated with SRP alone, and 5 rats had experimental periodontitis without treatment (EP). Five systemically healthy rats without experimental periodontitis were used as the controls. Blood samples were collected by cardiac puncture from all groups after 2, 4, and 6 weeks of therapy. Biomarker levels determined by enzyme-linked immunosorbent assay (ELISA) and, ANOVA were used to compare the study groups. The results showed a significant increase in pro-inflammatory biomarkers and a significant decrease in anti-inflammatory biomarkers in the EP group compared with the control group (p < 0.05). The local application of curcumin or tetracycline gels resulted in a significant reduction in all inflammatory biomarkers at all periods of examination compared to the EP group. IL-10 levels gradually increased after 2 weeks, peaked at 4 weeks, and then decreased after 6 weeks, however, Tet showed statistically significant improvement compared to CU (p < 0.05). Adjunctive application of CU gel was as effective as Tet gel in the treatment of EP in rats by reducing inflammatory biomarkers and enhancing anti-inflammatory cytokines.

Deciphering salivary microbiome signature in Crohn’s disease patients with different factors contributing to dysbiosis

Crohn's disease (CD) is a chronic inflammatory bowel disease. An imbalanced microbiome (dysbiosis) can predispose to many diseases including CD. The role of oral dysbiosis in CD is poorly understood. We aimed to explore microbiome signature and dysbiosis of the salivary microbiome in CD patients, and correlate microbiota changes to the level of inflammation. Saliva samples were collected from healthy controls (HC) and CD patients (n = 40 per group). Salivary microbiome was analyzed by sequencing the entire 16S rRNA gene. Inflammatory biomarkers (C-reactive protein and calprotectin) were measured and correlated with microbiome diversity. Five dominant species were significantly enriched in CD, namely Veillonella dispar, Megasphaera stantonii, Prevotella jejuni, Dolosigranulum pigrum and Lactobacillus backii. Oral health had a significant impact on the microbiome since various significant features were cariogenic as Streptococcus mutans or periopathogenic such as Fusobacterium periodonticum. Furthermore, disease activity, duration and frequency of relapses impacted the oral microbiota. Treatment with monoclonal antibodies led to the emergence of a unique species called Simonsiella muelleri. Combining immunomodulatory agents with monoclonal antibodies significantly increased multiple pathogenic species such as Salmonella enterica, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Loss of diversity in CD was shown by multiple diversity indices. There was a significant negative correlation between gut inflammatory biomarkers (particularly calprotectin) and α-diversity, suggesting more inflammation associated with diversity loss in CD. Salivary dysbiosis was evident in CD patients, with unique microbiota signatures and perturbed species that can serve as disease biomarkers or potential targets for microbiota modulation. The interplay of various factors collectively contributed to dysbiosis, although each factor probably had a unique effect on the microbiome. The emergence of pathogenic bacteria in the oral cavity of CD patients is alarming since they can disturb gut homeostasis and induce inflammation by swallowing, or hematogenous spread of microbiota, their metabolites, or generated inflammatory mediators.

Preliminary Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of KT-333, a Targeted Protein Degrader of STAT3, in Patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia, and Solid Tumors

Background: KT-333is a first-in-class, potent, highly selective, heterobifunctional small molecule degrader of the signal transducer and activator of transcription 3 (STAT3) protein. Aberrant activation of STAT3 resulting from activating mutations or deregulated cytokine signaling underlies various malignancies including peripheral T-cell lymphomas (PTCL), cutaneous T-cell lymphoma (CTCL), and large granular lymphocytic leukemia (LGL-L). Approximately 70% of human cancers including hematological malignancies and solid tumors exhibit increased levels of phosphorylated STAT3 (pSTAT3), a biomarker of pathway activation. In non-clinical studies, treatment with KT-333 resulted in durable tumor regressions with weekly (QW) or once every two weeks IV administration in STAT3-dependent T cell lymphomas. STAT3 degradation also sensitized immunocompetent mouse models of solid and liquid cancers to anti-PD1(ASH 2021, SITC 2021). Methods: The ongoing open-label, Phase 1a/1b study is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary clinical activity of KT-333 administered as a QW IV infusion on Day 1, 8, 15 and 22 (28-day cycle) in patients (pts) with B- and T-cell lymphomas, Hodgkin's lymphoma and advanced solid tumors (ST) relapsed/refractory (R/R) to at least two prior systemic therapies and LGL-L and T-cell prolymphocytic leukemia R/R to at least one prior therapy. Cycle 1 and 2 blood samples are collected for KT-333 plasma concentrations and to measure changes in STAT3 protein expression in peripheral blood mononuclear cells (PBMCs) using targeted mass spectrometry. Whole blood RNA sequencing measures mRNA levels of STAT3 regulated targets. Plasma levels of inflammatory biomarkers are measured with Luminex. STAT3 degradation and other related biomarker changes in tumor are assessed in patients with accessible tumors. (NCT05225584). Results: As of July 10, 2023, 21 pts were treated at five dose levels (DL) in Phase 1a with a mean number of 5.8 doses. Pts included B-cell non-Hodgkin's lymphoma (n=1: DL5), Hodgkin's lymphoma (HL) (n=1: DL4), CTCL (n=3: DL1, 2 and 4), PTCL (n=1: DL2), LGL-L (n=2: DL5) and ST (n=13: DL1-4) with median age of 61 years (range 30,77) and ECOG performance status of 0 (n=7) or 1 (n=14). No DLTs and no KT-333 related serious adverse events (SAE) were reported. The most common AEs were Grade 1 and 2 and included constipation, fatigue, nausea and anemia. Best response among pts evaluable for response at data cut-off (not including CTCL or HL pts at DL4 or any DL5 pts) included one partial response after two cycles in a CTCL pt at DL2 and SD after two cycles in three ST pts treated at DL3 and DL4. PD data in blood available for DL1-4 demonstrated robust, dose-dependent, and sustained STAT3 degradation in PBMC. The mean maximum degradation of STAT3 by targeted mass spectrometry over the first two weeks in Cycle 1 by DL was (% (range; n)): DL1: 69.9% (52.6% to 84.1%; n=4), DL2: 73.5% (65.5% to 80.7%; n=3), DL3: 79.9% (72.3% to 90.4 %; n=3) and DL4: 86.6% (78.9% to 95.9 %; n=4) with absolute quantification of STAT3 peptides falling below lower limit of quantification of the assay for one pt in DL3 and two in DL4. STAT3 pathway inhibition in blood was demonstrated via transcriptional downregulation of a canonical JAK/STAT3 target, SOCS3, which correlated with changes in STAT3 protein levels. KT-333 also resulted in dose-dependent downregulation of STAT3-regulated inflammatory biomarkers C-reactive protein and serum amyloid A protein in plasma. KT-333 demonstrated linear PK with plasma exposure increasing with dose and reaching levels close to those predicted to be efficacious. Conclusion: The emerging clinical data demonstrate that KT-333 is a potent degrader of STAT3 as demonstrated in PBMCs at doses that are well tolerated. These data provide the first evidence of STAT3 targeted protein degradation in humans with associated STAT3 pathway inhibition, along with potential early signs of antitumor activity, highlighting the potential of heterobifunctional degraders for targeting previously undruggable transcription factors implicated in diseases. Based on non-clinical data and PK/PD modeling, the high levels of degradation achieved so far are expected to be clinically efficacious in STAT3-dependent malignancies. Accrual is ongoing, and analyses from additional patients will be presented at the meeting.

Inflammatory markers in serum and placenta in a randomized controlled trial of group prenatal care

Racial and socioeconomic disparities in preterm birth and small for gestational age births are growing in the United States, increasing the burden of morbidity and mortality particularly among Black women and birthing persons and their infants. Group prenatal care is one of the only interventions to show potential to reduce the disparity, but the mechanism is unclear. The goal of this project was to identify if group prenatal care, when compared with individual prenatal care, was associated with a reduction in systemic inflammation during pregnancy and a lower prevalence of inflammatory lesions in the placenta at delivery. The Psychosocial Intervention and Inflammation in Centering Study was a prospective cohort study that exclusively enrolled participants from a large randomized controlled trial of group prenatal care (the Cradle study, R01HD082311, ClinicalTrials.gov: NCT02640638) that was performed at a single site in Greenville, South Carolina, from 2016 to 2020. In the Cradle study, patients were randomized to either group prenatal care or individual prenatal care, and survey data were collected during the second and third trimesters. The Psychosocial Intervention and Inflammation in Centering Study cohort additionally provided serum samples at these 2 survey time points and permitted collection of placental biopsies for inflammatory and histologic analysis, respectively. We examined associations between group prenatal care treatment and a composite of z scored serum inflammatory biomarkers (C-reactive protein, interleukin-6, interleukin-1 receptor antagonist, interleukin-10, and tumor necrosis factor α) in both the second and third trimesters and the association with the prevalence of acute and chronic maternal placental inflammatory lesions. Analyses were conducted using the intent to treat principle, and the results were also examined by attendance of visits in the assigned treatment group (modified intent to treat and median or more number of visits) and were stratified by race and ethnicity. A total of 1256 of 1375 (92%) Cradle participants who were approached enrolled in the Psychosocial Intervention and Inflammation in Centering Study, which included 54% of all the Cradle participants. The Psychosocial Intervention and Inflammation in Centering Study cohort did not differ from the Cradle cohort by demographic or clinical characteristics. Among the 1256 Psychosocial Intervention and Inflammation in Centering Study participants, 1133 (89.6%) had placental data available for analysis. Among those, 549 were assigned to group prenatal care and 584 of 1133 were assigned to individual prenatal care. In the intent to treat and modified intent to treat cohorts, participation in group prenatal care was associated with a higher serum inflammatory score, but it was not associated with an increased prevalence of placental inflammatory lesions. In the stratified analyses, group prenatal care was associated with a higher second trimester inflammatory biomarker composite (modified intent to treat: B=1.17; P=.02; and median or more visits: B=1.24; P=.05) among Hispanic or Latine participants. Unexpectedly, group prenatal care was associated with higher maternal serum inflammation during pregnancy, especially among Hispanic or Latine participants.