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George Tocu,1,2,&ast; Raul Mihailov,3,4 Cristina Serban,4,5 Bogdan Ioan Stefanescu,5,6,&ast; Dana Tutunaru,1,2 Dorel Firescu4,5,&ast; 1Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galați, Romania; 2Clinical Laboratory of Medical Analysis, Emergency County Clinical Hospital “Sf. Ap. Andrei” Galati, Galați, Romania; 3Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, Galați, Romania; 4Department of Surgery, Emergency County Clinical Hospital “Sf. Ap. Andrei” Galati, Galați, Romania; 5Department of Clinical Surgery, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, Galați, Romania; 6Department of Obstetrics and Gynecology, Emergency County Clinical Hospital “Sf. Ap. Andrei” Galati, Galați, Romania&ast;These authors contributed equally to this workCorrespondence: Raul Mihailov, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, 47 Domneasca Street, Galați, 800008, Romania, Tel +40745250391, Email raulmihailov@yahoo.com Cristina Serban, Department of Clinical Surgery, Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, 47 Domneasca Street, Galați, 800008, Romania, Tel +40728249228, Email cristina_gl86@yahoo.comBackground: Sepsis affects over 30 million people worldwide each year, causing approximately 6 million deaths. Challenges in clinical diagnosis and the need for an early diagnosis to prevent mortality due to sepsis have led to dependence on inflammatory biomarkers like Procalcitonin (PCT), C-reactive protein (CRP), and Interleukin-6 (IL-6).Objective: This study was performed to observe the contribution of inflammatory biomarkers in the diagnosis and prognosis of patients with surgical sepsis.Methods: We performed a retrospective observational study in a Clinical Emergency Hospital, which included a number of 125 patients with surgical sepsis admitted between January 2020 and December 2021. The patients were included in the study based on the Sepsis-3 definition. PCT, CRP, IL-6, Sepsis-related Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index (CCI), the time up to surgery, the days of treatment in Intensive Care Unit (ICU) and the total days of hospitalization had been statistically analyzed.Results: The mean age of all patients was 65.14 years. The mean value in all patients for PCT was 20.08 ng/mL, for CRP was 175.42 mg/l, and for IL-6 was 799.6 pg/mL. The strongest correlation between biomarkers was between CRP and IL-6 (r = 0.425; p < 0.0001). Of all biomarkers, the CRP correlated the strongest with patient outcomes (r = 0.544; p < 0.0001). The area under curve (AUC) for the mean values of the inflammatory biomarkers was calculated and the best diagnostic performance was for CRP with 0.816 (95% CI: 0.744– 0.887).Conclusion: CRP and IL-6 were the most efficient in sepsis diagnosis. The association of PCT, CRP and IL-6 has increased the range of certainty in sepsis diagnosis. CRP was the most efficient biomarker in the prognosis of sepsis.Keywords: inflammatory biomarkers, SOFA score, septic shock, surgical sepsis, postoperatively

Abstract Background Inflammation is considered to be one of the driving factors of cancer, and chronic inflammation plays a crucial role in tumor growth and metastasis. The aim of this study was to examine the predictive value of preoperative inflammatory biomarkers for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), including preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and aspartate aminotransferase-to-lymphocyte ratio (ALR), a novel inflammatory biomarker. Method This study included 198 patients with mRCC from a single center from 2006 to 2022. The optimal cut-off levels for the three biomarkers were derived using the receiver operating characteristic curve (ROC). Cox univariate and multivariate analyses were used to assess independent prognostic inflammatory biomarkers. Finally, independent prognostic inflammatory biomarkers were incorporated into the prognostic model to establish a nomogram to predict the postoperative survival of patients with mRCC. Result The area under the ROC curve for NLR, LMR, and ALR, respectively, is 0.71 (CI: 0.635–0.784), 0.68 (CI: 0.604–0.755), and 0.75 (CI: 0.680–0.819). The optimal LMR, NLR, and ALR cut-off levels as evaluated by the ROC curve were 3.836, 3.106, and 68.056, respectively. Patients with NLR and ALR higher than the cut-off level and LMR lower than the cut-off level had a significant relationship with OS. Multivariate analysis revealed that tumor necrosis, lower LMR, and higher ALR were independent risk factors for OS. In addition, a nomogram that includes independent prognostic inflammatory biomarkers can accurately predict the OS in patients with mRCC. Conclusion ALR and LMR are independent risk factors for the prognosis of individuals with mRCC. By monitoring ALR and LMR postoperatively, the prognosis of patients with mRCC can be better evaluated.

Yang Zhao,1,&ast; Jun Liu,2,&ast; Zhengping Xiong,1 Shanzhi Gu,1 Xibin Xia2 1Department of Interventional Therapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China; 2Department of Radiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanzhi Gu, Department of Interventional Therapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China, Email 171761993@qq.com Xibin Xia, Department of Radiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410006, People’s Republic of China, Email zghnxxb@163.comObjective: This retrospective study aimed to investigate whether pre-treatment inflammatory biomarkers, including the prognostic nutritional index (PNI), monocyte-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and platelet-lymphocyte ratio (PLR), could predict treatment response and prognosis in patients with hepatocellular carcinoma (HCC) receiving hepatic arterial infusion chemotherapy (HAIC) with the oxaliplatin, leucovorin, and fluorouracil (FOLFOX) regimen.Methods: Based on the cut-off values identified using the receiver-operating characteristic (ROC) curve, 124 patients with HCC who received HAIC with the FOLFOX regimen were divided into low- and high-score MLR, PLR, PNI, and SII groups. Univariate and multivariate regression analyses were performed to identify independent predictors of treatment response and progression-free survival (PFS).Results: The cut-off values were 0.569 for MLR (area under the curve [AUC]: 0.621), 177.01 for PLR (AUC: 0.554), 713.05 for SII (AUC: 0.570), and 46.85 for PNI (AUC: 0.665). Multivariate Cox regression analysis revealed that the modified albumin-bilirubin (mALBI) grade (hazard ratio [HR]: 2.027; P=0.032), high MLR (HR: 7.250; P=0.002), and low PNI (HR: 0.296; P=0.003) were independent predictors of HAIC non-response, with an AUC value of 0.746 (95% CI: 0.658– 0.833). A high MLR (HR: 1.714, 95% CI: 1.086– 2.704, P=0.021) was also an independent predictor of PFS. Kaplan–Meier analysis showed that the patients with a high MLR had shorter PFS than those with a low MLR (median PFS: 6 vs 10 months, P=0.011).Conclusion: The pre-treatment MLR and PNI were predictors of non-response in patients with HCC receiving HAIC with the FOLFOX regimen. The MLR also was an independent predictor of PFS.Keywords: hepatocellular carcinoma, inflammatory biomarkers, treatment response, hepatic arterial infusion chemotherapy, progression-free survival

The aim of this study was to evaluate the potential interplay between a carbohydrate diet and inflammation in atherosclerotic cardiovascular disease (ASCVD) development. ATTICA is a prospective observational study of 3042 adults free of cardiovascular disease (CVD) who were recruited in 2002 and followed for 20 years. Baseline data on carbohydrate intake and inflammatory biomarker levels were collected. Participants were stratified by carbohydrate intake (low vs. high: 190 g/day) and carbohydrate quality. At the 20-year follow-up in 2022, 1988 participants had complete data for CVD assessment. The overall quantity and quality of carbohydrate intake did not show a significant association with CVD incidence; inflammatory markers were positively correlated with an increased risk of CVD (p-values < 0.05). Chronic systemic inflammation seems to affect the CVD risk of participants who had a higher carbohydrate intake more substantially, as compared to those with low intake. Additionally, individuals with higher high carbohydrate/low fiber intake experienced a higher risk of inflammation-related CVD, compared to those with high carbohydrate/high fiber intake. The presented findings revealed that the effect of inflammation markers on the CVD risk is influenced both by the amount and quality of carbohydrate intake, irrespective of overall dietary habits and clinical and lifestyle characteristics.

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178–448) and 643 (502–839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42–21.00], and 15.16 [1.07–215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

Abstract Aims Inflammatory biomarkers, including CRP, the neutrophil‐to‐lymphocyte ratio (NLR), and the neutrophil‐to‐eosinophil ratio (NER), may predict outcomes in cancer. However, their value in immune checkpoint inhibitor (ICI) therapy‐associated cardiotoxicity remains elusive. We aimed to characterize the relationship of inflammatory markers with severity of ICI‐related cardiotoxicities (iRCs) and prognosis among patients with iRCs. Methods Patients who were diagnosed with iRCs between January 2019 and December 2021 were retrospectively enrolled and were dichotomized based on iRC severity into low‐grade (grade 1–2) vs. high‐grade (grade 3–4) groups. Results Forty‐seven patients were included. The median time‐to‐event from first ICI infusion to onset of iRCs was 35 days (IQR: 19.0–65.5 days). When compared with respective baseline values, cardiac biomarkers and inflammatory markers were significantly elevated at onset of iRCs. Compared with low‐grade iRCs, NER at iRC onset was significantly increased among patients with high‐grade iRCs (Group × Time, P

Abstract Background Besides impaired respiratory function and immune system, COVID-19 can affect renal function from elevated blood urea nitrogen (BUN) or serum creatinine (sCr) levels to acute kidney injury (AKI) and renal failure. This study aims to investigate the relationship between Cystatin C and other inflammatory factors with the consequences of COVID-19. Methods A total of 125 patients with confirmed Covid-19 pneumonia were recruited in this cross-sectional study from March 2021 to May 2022 at Firoozgar educational hospital in Tehran, Iran. Lymphopenia was an absolute lymphocyte count of less than 1.5 × 109/L. AKI was identified as elevated serum Cr concentration or reduced urine output. Pulmonary consequences were evaluated. Mortality was recorded in the hospital one and three months after discharge. The effect of baseline biochemical and inflammatory factors on odds of death was examined. SPSS, version 26, was used for all analyses. P-vale less than 0.05 was considered significant. Results The highest amount of co-morbidities was attributed to COPD (31%; n = 39), dyslipidemia and hypertension (27%; n = 34 for each) and diabetes (25%; n = 31). The mean baseline cystatin C level was 1.42 ± 0.93 mg/L, baseline creatinine was 1.38 ± 0.86 mg/L, and baseline NLR was 6.17 ± 4.50. Baseline cystatin C level had a direct and highly significant linear relationship with baseline creatinine level of patients (P 0.001). 34.4% (n = 43) of patients expired in the hospital, and the mean baseline cystatin C level of this group of patients was 1.58 ± 0.90 mg/L which was significantly higher than other patients (1.35 ± 0.94 mg/L, P = 0.002). Conclusion cystatin C and other inflammatory factors such as ferritin, LDH and CRP can help the physician predict the consequences of COVID-19. Timely diagnosis of these factors can help reduce the complications of COVID-19 and better treat this disease. More studies on the consequences of COVID-19 and knowing the related factors will help treat the disease as well as possible.

Abstract Background The purpose of the study was to compare the results of AI (artificial intelligence) analysis of the extent of pulmonary lesions on HRCT (high resolution computed tomography) images in COVID-19 pneumonia, with clinical data including laboratory markers of inflammation, to verify whether AI HRCT assessment can predict the clinical severity of COVID-19 pneumonia. Methods The analyzed group consisted of 388 patients with COVID-19 pneumonia, with automatically analyzed HRCT parameters of volume: AIV (absolute inflammation), AGV (absolute ground glass), ACV (absolute consolidation), PIV (percentage inflammation), PGV (percentage ground glass), PCV (percentage consolidation). Clinical data included: age, sex, admission parameters: respiratory rate, oxygen saturation, CRP (C-reactive protein), IL6 (interleukin 6), IG - immature granulocytes, WBC (white blood count), neutrophil count, lymphocyte count, serum ferritin, LDH (lactate dehydrogenase), NIH (National Institute of Health) severity score; parameters of clinical course: in-hospital death, transfer to the ICU (intensive care unit), length of hospital stay. Results The highest correlation coefficients were found for PGV, PIV, with LDH (respectively 0.65, 0.64); PIV, PGV, with oxygen saturation (respectively − 0.53, -0.52); AIV, AGV, with CRP (respectively 0.48, 0.46); AGV, AIV, with ferritin (respectively 0.46, 0.45). Patients with critical pneumonia had significantly lower oxygen saturation, and higher levels of immune-inflammatory biomarkers on admission. The radiological parameters of lung involvement proved to be strong predictors of transfer to the ICU (in particular, PGV ≥ cut-off point 29% with Odds Ratio (OR): 7.53) and in-hospital death (in particular: AIV ≥ cut-off point 831 cm3 with OR: 4.31). Conclusions Automatic analysis of HRCT images by AI may be a valuable method for predicting the severity of COVID-19 pneumonia. The radiological parameters of lung involvement correlate with laboratory markers of inflammation, and are strong predictors of transfer to the ICU and in-hospital death from COVID-19. Trial registration National Center for Research and Development CRACoV-HHS project, contract number SZPITALE-JEDNOIMIENNE/18/2020.

Abstract Background Early-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes. Methods We undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices. Results As opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species. Conclusions We confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes.

Background: Different biomarkers have been suggested as novel biomarkers of coronavirus disease 2019 (COVID-19) theragnosis. With the aim of having a better clinical management of COVID-19, we decided to determine the relationship between hematological, inflammatory, and novel biomarkers with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immunoglobulin (Ig)M and IgG antibodies. Methods: Blood samples from 127 confirmed COVID-19 patients aged 11–84 years old were collected and tested for SARS-CoV-2 IgM and IgG antibodies alongside with hematological, inflammatory, and novel biomarkers. The Spearman correlation test was utilized to analyze the correlation between these biomarkers with SARS-CoV-2 IgM and IgG antibodies. Results: The SARS-CoV-2 IgM antibody significantly correlated with erythrocyte sedimentation rate (ESR) (r = 0.329, p = 0.000), C-reactive protein (CRP) (r = 0.459, p = 0.000), interleukin (IL)-6 (r = 0.345, p = 0.000), IL-8 (r = 0.263, p = 0.003), neutrophil to lymphocyte ratio (NLR) (r = 0.182, p = 0.040), derived NLR (dNLR) (r = 0.197, p = 0.026), neutrophil to monocyte ratio (NMR) (r = 0.184, p = 0.038), and CRP to lymphocyte ratio (CLR) (r = 0.495, p = 0.000). Also, we find significant correlation between SARS-CoV-2 IgG antibody with hemoglobin (Hb) (r = −0.257, p = 0.004), hematocrit (Hct) (r = −0.227, p = 0.010), mean corpuscular Hb concentration (MCHC) (r = −0.212, p = 0.017), lymphocyte count (r = −0.211, p = 0.017), platelet count (r = 0.179, p = 0.044), ESR (r = 0.461, p = 0.000), CRP (r = 0.344, p = 0.000), IL-6 (r = 0.178, p = 0.046), IL-8 (r = 0.237, p = 0.007), platelet to lymphocyte ratio (PLR) (r = 0.295, p = 0.001), and CLR (r = 0.376, p = 0.000). Conclusion: Hematological biomarkers (Hb, Hct, MCHC, lymphocyte count, and platelet count), inflammatory biomarkers (ESR, CRP, IL-6, and IL-8), and novel biomarkers (dNLR, NLR, NMR, PLR, and CLR) are valuable indicators for clinical management of COVID-19.

Introduction: Autologous platelet-rich plasma (PRP) and hyaluronic acid (HA) are common treatments for knee osteoarthritis (OA). Several studies have demonstrated PRP as a safe and effective treatment for OA and, in some studies, produces a better outcome than HA. Objective: The primary objective of this study was to determine if HA injected with PRP would improve the efficacy of treatment of symptomatic knee OA compared to PRP alone. We hypothesized that the addition of HA would improve the efficacy of (PRP). Methods: A total of 64 participants with Kellgren-Lawrence (KL) Grades 1 to 4 knee OA were randomized into 2 groups and scheduled to receive 3-injections. Group 1 [PRP] received injections of PRP. Group 2 [HA+PRP] received the same treatment, with an additional HA injection for the first 2 injections. Both groups were blindfolded for the first 2 injections. To evaluate the efficacy of the regimen, participants completed patient reported outcome measures (PROMs). PROMs were completed prior to injections and at 1, 3, 6, 12, 18, and 24 months after the final injection. Results: Participants in both groups felt pain consistent with standard-of-care HA injection regimens with no difference in perceived pain. No infections or complications were observed. All PROM scores demonstrated improvement over baseline from 1-24 months post injections. There were no statistically significant differences between the groups. Conclusions: For the treatment of OA, PRP alone or PRP concomitantly with HA performed similarly out to 24 months. PRP in combination with HA was not superior to PRP alone.

Introduction: There is evidence showing that central nervous system TB (CNS-TB) causes meningitis, pachymeningitis, tuberculomas, and granulomas. However, the impact of pulmonary or spine TB on brain morphology and thickness is yet to be documented. TB is associated with increased levels of inflammatory biomarkers in specific brain regions. Objectives: The primary aim of this study was to compare cortical-brain volume and thickness between patients with pulmonary or spine TB and non-TB individuals and investigate the association between inflammatory biomarkers and brain volume or thickness among patients with pulmonary or spine TB. Methods: Participants ranging in age from 18 to 65 years (23 TB patients and 50 healthy controls), who were scanned using 1.5-T MRI at Jazan Hospital, were compared in terms of brain volumes and thicknesses. Brain volume and thickness were measured using FreeSurfer. Results: There were significant differences in the volumes of the bilateral and total amygdala and accumbens areas, right hippocampus and cerebellum, and CSF, and in the thickness of the right pericalcarine area between patients with pulmonary or spine TB and healthy controls. We also found significant associations between inflammatory biomarkers (CRP, WBC, and platelets) and brain volume but not thickness in patients with TB, p

Background: The central role of inflammatory progression in the development of Coronavirus disease 2019 (COVID-19), especially in severe cases, is indisputable. However, the role of some novel inflammatory biomarkers in the prognosis of COVID-19 remains controversial. Objective: To assess the effect of some novel inflammatory biomarkers in the occurrence and prognosis of COVID-19. Methods: We systematically retrieved the studies related to COVID-19 and the inflammatory biomarkers of interest. The data of each biomarker in different groups were extracted, then were categorized and pooled. The standardized mean difference was chosen as an effect size measure to compare the difference between groups. Results: A total of 90 studies with 12,059 participants were included in this study. We found higher levels of endocan, PTX3, suPAR, sRAGE, galectin-3, and monocyte distribution width (MDW) in the COVID-19 positive groups compared to the COVID-19 negative groups. No significant differences for suPAR and galectin-3 were detected between the severe group and mild/moderate group of COVID-19. In addition, the deaths usually had higher levels of PTX3, sCD14-ST, suPAR, and MDW at admission compared to the survivors. Furthermore, patients with higher levels of endocan, galectin-3, sCD14-ST, suPAR, and MDW usually developed poorer comprehensive clinical prognoses. Conclusions: In summary, this meta-analysis provides the most up-to-date and comprehensive evidence for the role of the mentioned novel inflammatory biomarkers in the prognosis of COVID-19, especially in evaluating death and other poor prognoses, with most biomarkers showing a better discriminatory ability. [ABSTRACT FROM AUTHOR]

Background: Depression affects approximately 27% of adults with chronic kidney disease (CKD) and end-stage kidney failure (ESKF). Depression in this population is associated with impaired quality of life and increased mortality. The extent of inflammation and the impact on depression in CKD/ESKF is yet to be established. Through a systematic literature review and meta-analysis, we aim to understand the relationship between depression and inflammation in CKD/ESKF patients. Methods: We searched nine electronic databases for published studies until January 2022. Titles and abstracts were screened against inclusion and exclusion criteria. Data extraction and study quality assessment was carried out independently by two reviewers. A meta-analysis was carried out where appropriate; otherwise a narrative review of studies was completed. Results: Sixty studies met our inclusion criteria and entered the review (9481 patients included in meta-analysis). Meta-analysis of cross-sectional associations revealed significantly higher levels of pro-inflammatory biomarkers; C-reactive protein; Interleukin 6 (IL-6) and tumour necrosis factor-alpha in patients with depressive symptoms (DS) compared to patients without DS. Significantly lower levels of anti-inflammatory cytokine IL-10 were found in patients with DS compared to patients without DS. Considerable heterogeneity was detected in the analysis for most inflammatory markers. Conclusion: We found evidence for an association of higher levels of pro-inflammatory and lower anti-inflammatory cytokines and DS in patients with CKD/ESKF. Clinical trials are needed to investigate whether anti-inflammatory therapies will be effective in the prevention and treatment of DS in these patients with multiple comorbidities. [ABSTRACT FROM AUTHOR]

We aim to assess small airway dysfunction, spirometry, health-related quality of life (HR-QoL), and inflammatory biomarkers between the wildland firefighters and healthy controls. Lung function including impulse oscillometry (IOS) and spirometry, HR-QoL measured by the 36-Item Short Form Survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ), high sensitivity C-Reactive Protein (hsCRP), and D-dimer were collected twice in the non-pollution period and pollution period. Gaussian regression was used for comparison all parameters between two groups. The results showed that the changes in area under reactance curve between 5 Hz and resonant frequency (AX) between the non-pollution and pollution periods in wildland firefighters was significantly higher compared to healthy controls (adjusted mean difference = 0.15 kPa/L, 95%CI;0.01, 0.28, p = 0.032). Our pilot study concluded that there was short-term effect on small airway function in wildland firefighter air pollutant exposure. However, there was no effect on spirometry, HRQoL, and inflammatory biomarkers in young wildland firefighters. Clinical Trials Registry: Study ID: TCTR20200828005 [ABSTRACT FROM AUTHOR]

Pressure Ulcers (PU) are a major burden for affected patients and healthcare providers. Current detection methods involve visual assessments of the skin by healthcare professionals. This has been shown to be subjective and unreliable, with challenges associated with identifying erythema in darker colour skin. Although there exists a number of promising non‐invasive biophysical techniques such as ultrasound, capacitance measurements, and thermography, the present study focuses on directly measuring the changes in the inflammatory status of the skin and underlying tissues. Therefore, in this study, we aim to analyse inflammatory cytokines collected through non‐invasive sampling techniques to detect early signs of skin damage. Thirty hospitalised patients presenting with Stage I PU were recruited to evaluate the inflammatory response of skin at the site of damage and an adjacent healthy control site. Sebutapes were collected over three sessions to investigate the temporal changes in the inflammatory response. The panel of cytokines investigated included high‐abundance cytokines, namely, IL‐1α and IL‐1RA, and low abundance cytokines; IL‐6, IL‐8, TNF‐α, INF‐γ, IL‐33, IL‐1β and G‐CSF. Spatial and temporal differences between sites were assessed and thresholds were used to determine the sensitivity and specificity of each biomarker. The results suggest significant (P <.05) spatial changes in the inflammatory response, with upregulation of IL‐1α, IL‐8, and G‐CSF as well as down‐regulation of IL‐1RA over the Stage I PU compared with the adjacent control site. There were no significant temporal differences between the three sessions. Selected cytokines, namely, IL‐1α, IL‐1RA, IL‐8, G‐CSF, and the ratio IL‐1α/IL‐1RA offered clear delineation in the classification of healthy and Stage‐I PU skin sites, with receiver operating characteristic curves demonstrating high sensitivity and specificity. There were limited influences of intrinsic and extrinsic factors on the biomarker response. Inflammatory markers provided a high level of discrimination between the sites presenting with Stage I PU and an adjacent healthy skin site, in a cohort of elderly inpatients. Indeed, the ratio of IL‐1α to IL‐1RA provided the highest sensitivity and specificity, indicative that inflammatory homeostasis is affected at the PU site. There was a marginal influence of intrinsic and extrinsic factors, demonstrating the localised effects of the inflammation. Further studies are required to investigate the potential of inflammatory cytokines incorporated within Point of Care technologies, to support routine clinical use. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory indicators are clinically significant in guiding diffuse large B-cell lymphoma (DLBCL) prognosis. However, which inflammatory markers are the best predictors of DLBCL prognosis is still unclear. In this study, we aimed to create a nomogram based on the best inflammatory markers and clinical indicators to predict the overall survival of patients with DLBCL. Patients and methods: We analyzed data from 423 DLBCL patients from two institutions and divided them into a training set, an internal validation set, and an external validation set (n = 228, 97, and 98, respectively). The least absolute shrinkage and selection operator and Cox regression analysis were used to develop nomograms. We assessed model fit using the Akaike information criterion and Bayesian information criterion. The concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's predictive performance and clinical net benefit and compared with the International Prognostic Index (IPI) and National Comprehensive Cancer Network (NCCN)-IPI. Results: The inclusion variables for the nomogram model were age, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase level, the systemic immune-inflammation index (SII), the prognostic nutritional index (PNI), and β-2 microglobulin (β-2 MG) level. In the training cohort, the nomogram showed better goodness of fit than the IPI and NCCN-IPI. The C-index of the nomogram (0.804, 95% CI: 0.751-0.857) outperformed the IPI (0.690, 95% CI: 0.629-0.751) and NCCN-IPI (0.691, 95% CI: 0.632-0.750). The calibration curve, ROC curve, and DCA curve analysis showed that the nomogram has satisfactory predictive power and clinical utility. Similar results were found in the validation cohort. Conclusion: The nomogram integrated with the clinical characteristics and inflammatory markers is beneficial to predict the prognosis of patients with DLBCL. [ABSTRACT FROM AUTHOR]

Intestinal ultrasound (IUS) is a non-invasive tool for monitoring Crohn's disease (CD) activity. Recently, sonographic activity scores, including the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and Simple Ultrasound Activity Score for CD (SUS-CD), were developed. This study aimed to assess their clinical application value. This retrospective study enrolled patients with CD from March 2021 to June 2022. The diagnostic performance of the ultrasound scores was evaluated using the simplified endoscopic score for CD (SES-CD). Correlations of ultrasound scores with SES-CD, CD activity index (CDAI), and inflammatory biomarkers were assessed. Inter-rater reliability was compared. In total, 140 patients were included. The IBUS-SAS for evaluating disease activity had an area under the curve (AUC) of 0.895, sensitivity of 85.4%, and specificity of 82.4% for the cut-off value of 48.7. The SUS-CD revealed an AUC of 0.835, sensitivity of 92.7%, and specificity of 64.7% for the cut-off value of 2.5. The IBUS-SAS and SUS-CD were positively correlated with SES-CD (r = 0.511 and 0.534, respectively). The scores correlated significantly with the CDAI and inflammatory biomarkers (all p < 0.01). The IBUS-SAS was more strongly correlated with CDAI (r = 0.666 vs 0.486) and C-reactive protein (r = 0.645 vs 0.434) than the SUS-CD. The intraclass correlation coefficient (ICC) of the IBUS-SAS and SUS-CD between the two sonologists was excellent (ICC = 0.96 and 0.78, respectively). Both the IBUS-SAS and SUS-CD can evaluate disease activity in CD and exhibited a significant correlation with activity indices and inflammatory biomarkers. ChiCTR2200055221 [ABSTRACT FROM AUTHOR]

Background: Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality. Methods: We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results. Results: The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002–1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045–1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028–1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001–1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003–1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018–1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression. Conclusions: In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression. [ABSTRACT FROM AUTHOR]

Treatment-resistant depression (TRD) is a challenging issue to address. Repetitive transcranial magnetic stimulation (rTMS) is commonly used but shows varying efficacy, necessitating a deeper understanding of depression physiology and rTMS mechanisms. Notably, an increasing amount of recent data has displayed the connection of TRD and its clinical outcome with chronic inflammatory processes. The current study included 19 TRD patients undergoing rTMS and 11 depressed patients responding to medication as a comparison group. We assessed therapeutic efficacy using MADRS, HAM-D-17, GAD-7, and PHQ-9 tests. Inflammatory markers, neurotrophins, and associated miRNAs were measured in patients blood serum before and during treatment. A control group of 18 healthy individuals provided baseline data. The results of our study showed significantly higher levels of pro-inflammatory interleukins-6 and − 8 in TRD patients compared to drug-responders, which also related to more severe symptoms before treatment. In addition, TRD patients, both before and during treatment, exhibited higher average blood serum concentrations of pro-inflammatory interleukin-18 and lower levels of anti-neuroinflammatory miR-146a-5p compared to healthy controls. We also observed that the expression of miR-16-5p, miR-93-5p, and especially miR-146a-5p correlated with clinical changes following rTMS. Our study confirmed that TRD patients possess a higher inflammatory status, while the anti-neuroinflammatory miR-146a-5p was demonstrated to have a considerable potential for predicting their rTMS treatment success.

Background: Inflammation is considered to be one of the driving factors of cancer, and chronic inflammation plays a crucial role in tumor growth and metastasis. The aim of this study was to examine the predictive value of preoperative inflammatory biomarkers for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), including preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and aspartate aminotransferase-to-lymphocyte ratio (ALR), a novel inflammatory biomarker. Method: This study included 198 patients with mRCC from a single center from 2006 to 2022. The optimal cut-off levels for the three biomarkers were derived using the receiver operating characteristic curve (ROC). Cox univariate and multivariate analyses were used to assess independent prognostic inflammatory biomarkers. Finally, independent prognostic inflammatory biomarkers were incorporated into the prognostic model to establish a nomogram to predict the postoperative survival of patients with mRCC. Result: The area under the ROC curve for NLR, LMR, and ALR, respectively, is 0.71 (CI: 0.635–0.784), 0.68 (CI: 0.604–0.755), and 0.75 (CI: 0.680–0.819). The optimal LMR, NLR, and ALR cut-off levels as evaluated by the ROC curve were 3.836, 3.106, and 68.056, respectively. Patients with NLR and ALR higher than the cut-off level and LMR lower than the cut-off level had a significant relationship with OS. Multivariate analysis revealed that tumor necrosis, lower LMR, and higher ALR were independent risk factors for OS. In addition, a nomogram that includes independent prognostic inflammatory biomarkers can accurately predict the OS in patients with mRCC. Conclusion: ALR and LMR are independent risk factors for the prognosis of individuals with mRCC. By monitoring ALR and LMR postoperatively, the prognosis of patients with mRCC can be better evaluated. [ABSTRACT FROM AUTHOR]

Despite a multimodal radical treatment, mortality of advanced epithelial ovarian cancer (AEOC) remains high. Host-related factors, such as systemic inflammatory response and its interplay with the immune system, remain underexplored. We hypothesized that the prognostic impact of this response could vary between patients undergoing primary debulking surgery (PDS) and those undergoing interval debulking surgery (IDS). Therefore, we evaluated the outcomes of two surgical groups of newly diagnosed AEOC patients according to the neutrophil, monocyte and platelet to lymphocyte ratios (NLR, MLR, PLR), taking median ratio values as cutoffs. In the PDS group (n = 61), low NLR and PLR subgroups showed significantly better overall survival (not reached (NR) vs. 72.7 months, 95% confidence interval [CI]: 40.9–95.2, p = 0.019; and NR vs. 56.1 months, 95% CI: 40.9–95.2, p = 0.004, respectively) than those with high values. Similar results were observed in progression free survival. NLR and PLR-high values resulted in negative prognostic factors, adjusting for residual disease, BRCA1/2 status and stage (HR 2.48, 95% CI: 1.03–5.99, p = 0.043, and HR 2.91, 95% CI: 1.11–7.64, p = 0.03, respectively). In the IDS group (n = 85), ratios were not significant prognostic factors. We conclude that NLR and PLR may have prognostic value in the PDS setting, but none in IDS, suggesting that time of surgery can modulate the prognostic impact of baseline complete blood count (CBC). [ABSTRACT FROM AUTHOR]

Background and aims: Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters. Methods: We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models. Results: APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile. Conclusion: Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD. [ABSTRACT FROM AUTHOR]

Monocytes exhibiting a pro-inflammatory phenotype play a key role in adhesion and development of atherosclerotic plaques. As an alternative to smoking, next-generation tobacco and nicotine products (NGP) are now widely used. However, little is known about their pro-inflammatory effects on monocytes. We investigated cell viability, anti-oxidant and pro-inflammatory gene and protein expression in THP-1 monocytes after exposure to aqueous smoke extracts (AqE) of a heated tobacco product (HTP), an electronic cigarette (e-cig), a conventional cigarette (3R4F) and pure nicotine (nic). Treatment with 3R4F reduced cell viability in a dose-dependent manner, whereas exposure to alternative smoking products showed no difference to control. At the highest non-lethal dose of 3R4F (20%), the following notable mRNA expression changes were observed for 3R4F, HTP, and e-cig respectively, relative to control; HMOX1 (6-fold, < 2-fold, < 2-fold), NQO1 (3.5-fold, < 2-fold, < 2-fold), CCL2 (4-fold, 3.5-fold, 2.5-fold), IL1B (4-fold, 3-fold, < 2-fold), IL8 (5-fold, 2-fold, 2-fold), TNF (2-fold, 2-fold, < 2-fold) and ICAM1 was below the 2-fold threshold for all products. With respect to protein expression, IL1B (3-fold, < 2-fold, < 2-fold) and IL8 (3.5-fold, 2-fold, 2-fold) were elevated over the 2-fold threshold, whereas CCL2, TNF, and ICAM1 were below 2-fold expression for all products. At higher doses, greater inductions were observed with all extracts; however, NGP responses were typically lower than 3R4F. In conclusion, anti-oxidative and pro-inflammatory processes were activated by all products. NGPs overall showed lower responses relative to controls than THP-1 cells exposed to 3R4F AqE. [ABSTRACT FROM AUTHOR]

We studied the association between inflammatory biomarkers and magnetic resonance imaging (MRI) visible perivascular spaces (PVS) in Framingham Heart Study participants free of stroke and dementia. PVS in the basal ganglia (BG) and centrum semiovale (CSO) were rated with validated methods and categorized based on counts. A mixed score of high PVS burden in neither, one or both regions was also evaluated. We related biomarkers representing various inflammatory mechanisms to PVS burden using multivariable ordinal logistic regression analysis accounting for vascular risk factors and other MRI markers of cerebral small vessel disease. Among 3604 participants (mean age 58±13 years, 47% males), significant associations were observed for intercellular adhesion molecule1, fibrinogen, osteoprotegerin, and P-selectin in relation to BG PVS, P-selectin for CSO PVS, and tumor necrosis factor receptor 2, osteoprotegerin and cluster of differentiation 40 ligand for mixed topography PVS. Therefore, inflammation may have a role in the pathogenesis of cerebral small vessel disease and perivascular drainage dysfunction represented by PVS, with different and shared inflammatory biomarkers depending on PVS topography. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the present study is to determine the in vivo and in silico anti-inflammatory effect of Azadirachta indica (A. indica) in carrageenan-induced rats and its blood biomarkers. A. indica (Neem) is a widely used medicinal plant across the world, especially in Pakistan. Neem leaves have been traditionally used for the synthesis of drugs and treatment of a wide variety of diseases. MATERIALS AND METHODS: In this study, sixty albino rats (160-200 g) were divided into 4 groups: control (group I), standard (group II), ethanolic and aqueous (group III and IV) at doses of 50, 100, 200 and 400 mg/kg. RESULTS: Ethanolic and aqueous extracts showed maximum inhibition in paw size at the 5th hour (400 mg/kg). Similarly, biomarkers measured, including Interleukin-6 and C-reactive protein, exhibited significant anti-inflammatory activity at the highest dose of 400 mg/kg in both experimental groups but were more distinct in the group treated with ethanolic extracts. Correlation between C-reactive protein (CRP) and inter-leukin-6 (IL-6) showed positive correlation in group III, while negative in group IV. Similarly, positive and negative correlations were observed between CRP biomarkers and paw size in group III nd IV, and the same results were also shown in the case of IL-6 and paw size. In molecular docking, the binding energy value of protein CRP and IL-1β with the identified ligands quercetin and nimbosterol showed (-8.2 kcal/mol and -7.7 kcal/ mol) the best binding affinity as compared to standard drug diclofenac with -7.0 kcal/mol binding energy respectively. CONCLUSIONS: In conclusion, in silico and in vivo analysis revealed that the extracts of A. indica leaves can be used as an effective drug to manage inflammation. [ABSTRACT FROM AUTHOR]

A systematic review protocol acts as a guide in the review process to prevent the introduction of bias, maintain transparency and allows reproducibility. Yoga intervention had been experimented on various health aspects such as physical functioning, health-related quality of life, psychosocial and emotional well-being among breast cancer populations, and the findings have been very encouraging. Studies are being performed on the effect of yoga intervention(s) at the molecular level by assessing the inflammatory cytokines and also stress hormones such as cortisol. This protocol is developed to escort in evaluating studies that have been performed on evidence-based yoga intervention at the level of cancer microenvironment, in women diagnosed with breast cancer, by assessing the inflammatory biomarkers and cortisol level, a primary stress marker, and a potent influence of inflammation. The findings will elucidate the picture of the cancer microenvironment as a result of yoga intervention. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the bidirectional correlation of sarcopenia with coronary heart disease (CHD), as well as to investigate the mediating role of cardiometabolic factors and inflammatory biomarkers, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted. Methods: Summary statistics were obtained from genome-wide association studies (GWAS). In our bidirectional two-sample MR, genetic variants associated with sarcopenia-related traits and CHD were instrumented for the estimation of bidirectional correlations. Besides, genetic variants associated with thirteen cardiometabolic factors and six inflammatory biomarkers were selected for further mediation analyses. To confirm the consistency of the results, several sensitivity analyses were carried out. Results: Genetically predicted higher appendicular lean mass (OR = 0.835, 95% CI: 0.790–0.882), left hand grip strength (OR = 0.703, 95% CI: 0.569–0.869), right hand grip strength (OR = 0.685, 95% CI: 0.555–0.844), and walking pace (OR = 0.321, 95% CI: 0.191–0.539) reduced CHD risk, while genetic predisposition to CHD did not affect any of the sarcopenia-related traits. Seven mediators were identified for the effects of appendicular lean mass on CHD, including waist-to-hip ratio, hip circumference, systolic blood pressure, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and fasting insulin. The mediation proportion ranged from 10.23% for triglycerides to 35.08% for hip circumference. Hip circumference was found to mediate the relationships between both left (mediation proportion: 24.61%) and right-hand grip strength (24.14%) and CHD, and the link between walking pace and CHD was partially mediated by waist-to-hip ratio (31.15%) and body mass index (26.66%). Conclusion: Our results showed that higher appendicular lean mass, hand grip strength, and walking pace reduced CHD risk, but the causal relationship was not bidirectional. Several mediators were found to mediate the causal pathways between sarcopenia-related traits and CHD, and intervention of these factors may be helpful in terms of CHD prevention in sarcopenia patients. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation contributes to aging and organ dysfunction in the general population, and is a particularly important determinant of morbidity and mortality among people with HIV (PWH). The effect of cannabis use on chronic inflammation is not well understood among PWH, who use cannabis more frequently than the general population. Materials and Methods: We evaluated participants in the Multicenter AIDS Cohort Study (MACS) beginning in 2004 with available data on cannabis use and inflammatory biomarkers. Associations of current cannabis use with plasma concentrations of inflammatory markers were adjusted for hepatitis C, tobacco smoking, and comorbidities. Markers were analyzed individually and in exploratory factor analysis (EFA). Results: We included 1352 men within the MACS. Twenty-seven percent of HIV-negative men, 41% of HIV viremic men, and 35% of virologically suppressed men reported cannabis use at baseline. Among cannabis users, 20-25% in all groups defined by HIV serostatus were daily users, and the same proportion reported weekly use. The remaining ∼50% of users in all groups reported monthly or less frequent use. Four biomarker groupings were identified by EFA: Factor 1: immune activation markers; Factor 2: proinflammatory cytokines; Factor 3: Th1- and Th2-promoting cytokines; and Factor 4: inflammatory chemokines. In EFA, daily users had 30% higher levels of Factor 2 biomarkers than nonusers (p=0.03); this was the only statistically significant difference by cannabis use status. Among individual markers, concentrations of IL-1β, IL-2, IL-6, and IL-8 (Factor 2); IL-10 (Factor 3); and BAFF (Factor 1) were higher (p

BackgroundAdipose tissue (AT) alterations are common in people living with human immunodeficiency virus (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immunometabolic parameters.MethodsIn a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous AT (SAT) and visceral AT (VAT) area and density in treatment-naive PLWH randomized to tenofovir-emtricitabine plus ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Linear regression models compared week 0 and week 96 levels, and 96-week changes, in SAT and VAT density (in Hounsfield units [HU]). Spearman correlations assessed relationships between AT density and immunometabolic parameters.ResultsOf the 228 participants, 89% were male and 44% were white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense week 96 SAT and VAT density correlated with higher high-density lipoprotein (HDL) cholesterol and adiponectin (r = 0.19-0.30) levels and lower interleukin 6, non-HDL cholesterol, triglyceride, leptin, and homeostatic model assessment of insulin resistance (r = -0.23 to -0.68) levels at week 96 after adjusting for baseline CD4+ T-cell count, HIV-1 RNA, and baseline AT area.ConclusionsFollowing virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances, and insulin resistance independent of AT area, suggesting that changes in AT density with ART may lead to adverse health outcomes independent of AT quantity.Clinical trials registrationNCT00851799.

Background: Smoking-related hemodynamic events may adversely influence renal function. The aim of this study was to evaluate renal impairment biomarkers among healthy people influenced by cigarette smoke. Methods and Results: In this case-control study, 90 subjects were enrolled: 60 were smokers, and 30 were non-smokers (apparently healthy control). Serum CysC was measured using a semi-automated, specific protein analyzer Mispa-i2 (Germany). Serum creatinine and MAU were assayed in the fully automated biochemistry analyzer (Mindray BS380). The mean concentration of CysC was significantly higher in cigarette smokers than in non-smokers (0.793±0.125 vs. 0.619±0.103, P=0.000). Also, the mean of MAU and serum creatinine levels were significantly higher in cigarette smokers than in non-smokers (18.33±3.41 vs. 12.70±0.517, 1.06±0.161 vs. 0.810±0.058, respectively, P=0.000 in both cases). The mean concentration of CysC and MAU was significantly greater in heavy smokers than in light smokers (P=0.000 and P=0.001, respectively). Serum CysC and MAU levels were positively correlated with the age of cigarette smokers (r=0.734 and r=0.730, respectively; P=0.000 in both cases) and the duration of smoking (r=0.773 and r=0.790, respectively; P=0.000 in both cases). Conclusion: cigarette smoking increases the specific renal biomarkers considered risk factors for renal impairment. Using such inflammatory biomarkers as diagnostic tools can be a necessary precaution in the development of chronic kidney disease caused by smoking and in the avoidance of acute renal consequences linked to cigarette smoking.

Abstract Background Carbohydrates are known as the main natural products of life activities. Results Streptomyces rochie strain OF1 isolated from a mangrove tree produced exopolysaccharide S5 (EPSS5) (14.2 gl−1) containing uronic acid 21.98% sulfate content of 11.65 mg/ml, and a viscosity of 1.35 mm2/s. while total hexose amine content was 24.72%. The high performance liquid chromatography (HPLC) analysis of mono sugars revealed that EPS was composed of manouronic acid, glucuronic acid, xylose, and fructose at a molar ratio of 1.0:0.5:1.0:2.0, respectively. It showed that the whole antioxidant activity was 92.06%. It showed antibacterial activity against Staphylococcus aureus, and E. coli, MRSA and Klebsiella pneumoniae. But, EPSS5 displayed low antifungal activity against Candida albicans. While no antifungal activity has been detected against Aspergillus niger. EPSS5 has antibiofilm action that is noticeable toward S. aureus with an inhibition ratio of biofilm up to 50%. Effect of EPS on serum levels of TNF-α and COX2 by 2 fold and 1.9 fold of EPS reduced serum levels of Tumor necrosis factor-α (TNF-α) by 38%, 12%, 49%, and Cyclooxygenase-2 (COX2) by 61%, 34%, and 62%, respectively. By affected of EPSS5 on arthritis in rats stimulated by carrageenan. Conclusions Administration of EPS ameliorated carrageen-induced elevation in inflammatory mediators; TNF-α/COX and suppressed the expressions of metalloproteinase 9 (MMP9) by 68%, 86%, and 75% correspondingly in comparison to the group of carrageenans. Then again, therapy involving a high dose only reduced MMP9 level by 57%, compared to free drug suggesting that EPSS5 is a good inhibitor of the MMP9, as it brought MMP9 back to normal levels via the signaling pathway.

Abstract Background Patients with tuberculosis (TB) and HIV often present with impairments in lung function and exercise capacity after treatment. We evaluated clinical and immunologic variables associated with a minimum clinically important difference (MCID) in the change in the 6 min walk test distance during the first 24 weeks of antiretroviral (ART) and anti-tubercular therapy. Methods Adults initiating ART and anti-TB treatment in the setting of newly-diagnosed HIV and pulmonary TB were enrolled in a prospective cohort study in South Africa. Patients underwent 6 min walk tests and spirometry at weeks 0, 4, 12, and 24 and biomarker level measurements early during treatment, at weeks 0, 4, and 12, when inflammation levels are typically elevated. Biomarkers included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2). An MCID was derived statistically, and achievement of an MCID was modeled as the outcome using logistic regression model. Results Eighty-nine patients walked an average of 393 (± standard deviation = 69) meters at baseline, which increased by an average of 9% (430 ± 70 m) at week 24. The MCID for change in walk distance was estimated as 41 m. Patients experiencing an MCID on treatment had worse lung function, lower 6 min walk test distance, higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF, and lower levels of collagen 1a at baseline. Experiencing an MCID during treatment was associated with increases in forced expiratory volume in 1-s [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.05–1.33] and increases in blood collagen 1a levels (OR = 1.31, 95%CI 1.06–1.62). Conclusions ART and TB treatment are associated with substantial improvements in 6 min walk test distance over time. Achievement of an MCID in the 6 min walk test in this study was associated with more severe disease at baseline and increases in collagen 1a levels and lung function during therapy.

Introduction: Remdesivir is currently approved for treating hospitalised patients with COVID-19. However, it is a priority to monitor its safety and effectiveness in various clinical settings. This study was undertaken to assess the impact of remdesivir on inflammatory and prognostic markers of COVID-19. Materials and Methods: A hospital-based prospective longitudinal study was conducted over two months comprising event monitoring of COVID-19 patients administered remdesivir as per standard guidelines. The demographic details, risk factors and all baseline parameters were collected. The patients were followed up for the appearance of any adverse drug reactions (ADRs) after the start of remdesivir therapy from Day 1 to discharge or death every day. Repeat Lab tests were done on days 2, 4, 6 and 10 days to assess the impact of remdesivir on inflammatory and prognostic markers of COVID-19 over time. Significant predictors of survival in the cohort were also assessed. Results: A total of 60 COVID-19 patients were administered remdesivir. The mean age of the patients was 59.2 (+13.7) years. There was a significant improvement in the serum creatinine (decreased from 0.9 to 0.7 mg/dL), lymphocyte count {decreased from 9.2 to 7.3 (109 cells/L)} and serum sodium (increased from 134.6 to 137.4) of the patients over six days after the administration of remdesivir. The significant survival predictors were multiple organ failure (P 0.046) and WBC count on Day 10 (P 0.001). Conclusion: Remdesivir administration improved the prognostic biomarker profile in COVID-19 patients.

Introduction/Objective. Ovarian carcinomas are the deadliest gynecological tumors. Despite advances in treatment options, survival rates are still not at the desired level. Since clinical signs are not typical in early-stage disease, two-thirds of patients are diagnosed late. Carbohydrate Antigen 125 (CA125) does not have sufficient sensitivity and specificity in early-stage disease and early post-relapse progression. There is a need for a simple and cost-effective marker that correlates with CA125. For this purpose, we aimed to evaluate the potential of systemic inflammatory markers’ as diagnostic aids. Methods. Patients with platinum-sensitive recurrent ovarian carcinomas were preferred because the treatment options were more diverse than the resistant group. Using retrospective data collection, 105 patients with platinum-sensitive recurrent ovarian carcinoma, admitted in the last four years were included in the study. Complete blood count data was recorded based on recurrence and progression periods. Results. When the systemic immune inflammatory index (SII) values were evaluated in combination with CA125 in terms of progression during the control visits after platinum-sensitive disease recurrence treatment, progression detection proportions increased to 97.5%, which was 82.9% when only CA125 was used. On the other hand, false positivity, which was 18.5% for CA125 alone, decreased to 2.5% when combined with SII. Furthermore, neutrophil lymphocyte ratio, white blood cells, and neutrophil values showed correlations with high CA125 values. Conclusion. The SII value could be used together with CA125 because it is easy to use, accessible, and has low cost in clinical practice, as well as to increase the accuracy rate and make precise corrections in the false positivity rate.

Abstract Background Many indigenous communities reside in biodiverse environments replete with natural food sources but show ​poor access and utilization. Methods To understand the links between indigenous food access, dietary intakes, and biomarkers, we conducted a cross-sectional study among women of the Santhal Community (n = 211) from 17 villages in the Godda district of Jharkhand, India. Survey methods included household surveys, dietary intake assessment (24 HDR) and micronutrient and inflammatory biomarkers' estimation. Results The diversity in access to foods from different natural sources expressed as Food access diversity index was low. This led to poor consumption and thus a low Minimum Dietary Diversity. The mean nutrient intake was less than the estimated average requirement for all nutrients. Women with higher dietary diversity scores had higher nutrient intakes. Thiamine and calcium intakes were significantly higher in women consuming indigenous foods than non-consumers. One-fourth of the women had elevated levels of inflammatory biomarkers. The prevalence of iron deficiency was approximately 70%. Vitamin A insufficiency (measured as retinol-binding protein) was observed in around 33.6% women, while 28.4% were deficient. Household access to natural food sources was associated with specific biomarkers. The access to kitchen garden (baari) was positively associated with retinol-binding protein levels and negatively with inflammatory biomarkers, while access to ponds was positively associated with ferritin levels. Conclusion The findings highlight the role of access to diverse natural foods resources, including indigenous foods, for improving nutrition security in indigenous communities. Nutrition and health programs promoting indigenous food sources should include the assessment of biomarkers for effective monitoring and surveillance.

Abstract Background The prognostic value of preoperative systemic inflammatory markers, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR), remains controversial in patients with intrahepatic cholangiocarcinoma (ICC). Therefore, this meta‐analysis aimed to investigate the prognostic value of preoperative NLR, PLR, and LMR in patients with ICC who underwent hepatic resection. Methods We conducted a comprehensive search of four electronic databases. Two researchers assessed the quality of the available data using the Newcastle–Ottawa Scale. We selected overall survival (OS) as the primary outcome and recurrence‐free survival (RFS) and disease‐free survival (DFS) as secondary outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were merged to evaluate the associations between inflammatory markers and ICC patient prognosis. Results Fifteen studies (18 cohorts) with 4123 cases were included in this meta‐analysis. The results revealed that a high preoperative NLR was associated with short OS and RFS (HR = 1.04, 95% CI: 1.01–1.07, and HR = 1.29, 95% CI: 1.04–1.60, respectively) in patients with ICC. However, the association between PLR or LMR and ICC prognosis was not statistically significant. In addition, the publication bias and sensitivity analyses demonstrated that the results were reliable and stable. Conclusion Our meta‐analysis revealed that preoperative NLR may be a useful prognostic predictor for patients with ICC.

Introduction: Knee osteoarthritis is a degenerative inflammatory disease affecting the entire joint and is characterised by progressive oss of cartilage and associated with pain. The tissue cells absorbs a certain wavelength of Light Amplification by Stimulated Emission of Radiation (LASER) which triggers a number of chemical responses in the cells that promote healing and reduce inflammation. Aim: To find the effect of Class IV LASER on pain and inflammation in knee osteoarthritis of older adults. Materials and Methods: This study utilised an experimental controlled design with pre and post comparison. The study was conducted from March 2023 to January 2024 at Jindal Physio Care, New Delhi, India, with the sample size of 36 subjects (18 each group). Participants were recruited based upon a predefined selection criterion. After signing the informed consent, all the subjects were randomly distributed among two groups (Group A and Group B). Outcome variables were inflammatory biomarkers Interleukins 6 (IL 6), Interleukins 1β (IL 1β), C-Reactive Protein (CRP) and Numeric Pain Rating Scale (NPRS), which were assessed in the beginning and at the end of study period of 10 weeks. Group A was given Placebo LASER along with moist heat, exercises and knee brace while Group B was given Class IV high-intensity LASER along with moist heat, exercises and knee brace. Data were analysed using the Student’s t-test and significance level was kept 95% (p<0.05). Results: There was a significant decrease in NPRS score, IL 6, IL 1β and CRP levels in both the groups at the end of the study. A substantial reduction was found in group B compared to group A (p<0.001). Conclusion: Class IV LASER treatment has been found satisfactory in alleviating pain and inflammation, which may be a promising treatment method for knee osteoarthritis. [ABSTRACT FROM AUTHOR]

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50–70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

A randomized, double-blind, and placebo-controlled study was conducted to assess the effect of dietary supplementation with high-rich docosahexaenoic acid (DHA) (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day in pediatric patients with cystic fibrosis (CF) as compared with placebo. The duration of supplementation was 12 months. A total of 22 patients were included, with 11 in the DHA group and 11 in the placebo group. The mean age was 11.7 years. The outcome variables were pulmonary function, exacerbations, sputum cellularity, inflammatory biomarkers in sputum and peripheral blood, and anthropometric variables. In the DHA group, there was a significant increase in FVC (p = 0.004) and FVE1 expressed in liters (p = 0.044) as compared with placebo, and a lower median number of exacerbations (1 vs. 2). Differences in sputum cellularity (predominantly neutrophilic), neutrophilic elastase, and sputum and serum concentrations of resolvin D1 (RvD1), interleukin (IL)-8 (IL-8), and tumor necrosis factor alpha (TNF-α) between the study groups were not found. Significant increases in weight and height were also observed among DHA-supplemented patients. The administration of the study product was safe and well tolerated. In summary, the use of a highly concentrated DHA supplement for 1 year as compared with placebo improved pulmonary function and reduced exacerbations in pediatric CF.

Anastomotic leakage (AL) remains the main cause of post-esophagectomy morbidity and mortality. Early detection can avoid sepsis and reduce morbidity and mortality. This study evaluates the diagnostic accuracy of the Nun score and its components as early detectors of AL. This single-center observational cohort study included all esophagectomies from 2010 to 2020. C-reactive protein (CRP), albumin (Alb), and white cell count (WCC) were analyzed and NUn scores were calculated. The area under the curve statistic (AUC) was used to assess their predictive accuracy. A total of 74 of the 668 patients (11%) developed an AL. CRP and the NUn-score proved to be good diagnostic accuracy tests on postoperative day (POD) 2 (CRP AUC: 0.859; NUn score AUC: 0.869) and POD 4 (CRP AUC: 0.924; NUn score AUC: 0.948). A 182 mg/L CRP cut-off on POD 4 yielded a 87% sensitivity, 88% specificity, a negative predictive value (NPV) of 98%, and a positive predictive value (PPV) of 47.7%. A NUn score cut-off > 10 resulted in 92% sensitivity, 95% specificity, 99% NPV, and 68% PPV. Albumin and WCC have limited value in the detection of post-esophagectomy AL. Elevated CRP and a high NUn score on POD 4 provide high accuracy in predicting AL after esophageal cancer surgery. Their high negative predictive value allows to select patients who can safely proceed with enhanced recovery protocols.

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes. HA35 was separately radiolabeled with 99mTc and 125I and administered to C57BL/6J mice for in vivo biodistribution imaging. In vitro studies indicated that HA35 and HA1600 similarly enhanced cell migration through HA receptor binding mechanisms, reduced the generation of NO and ROS, and upregulated gene expression profiles related to cell signaling pathways in immune cells. HA35 showed a more pronounced effect in regulating a broader range of genes in macrophages and microglia than HA1600. Upon intradermal or intravenous administration, radiolabeled HA35 rapidly accumulated in the liver, spleen, and lymph nodes. In conclusion, HA35 not only exhibits effects on cellular bioactivity comparable to those of HA1600 but also exerts biological effects on a broader range of immune cell gene expression. The findings herein offer valuable insights for further research into the therapeutic potential of HA35 in inflammation-mediated tissue injury.

The aim of this study was to evaluate the impact of non-surgical periodontal treatment (NS-PT) on periodontal parameters and inflammatory biomarkers in the concentration and level of calprotectin (CLP) in women with periodontitis and rheumatoid arthritis (RA). In this quasi-experimental study, we evaluated 30 women (mean age: 52.0 ± 5.8 years) with periodontitis and RA who had been diagnosed and treated for RA for more than 3 years and whose activity markers remained at similar values without significant reduction over three consecutive months. Patients underwent NS-PT, which included plaque control, scaling, and root planing. Serum and saliva samples, periodontal indices, RA activity markers, Disease Activity Score-28 (DAS28), the erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) and CLP contents were measured at the beginning of the study and 6 and 12 weeks after NS-PT. Parametric and nonparametric tests were used in the analysis. The mean age was 52.0 ± 5.8 years. Compared to the baseline results, all periodontal indices were significantly reduced 6 and 12 weeks after NS-PT (p < 0.001). DAS28 was also significantly reduced after 12 weeks (p < 0.0001). Similarly, the serum CLP concentration decreased 6 and 12 weeks after NS-PT (p < 0.0001). Of the patients, 100% presented lower levels of CRP and ESR (p < 0.0001). Overall, NS-PT reduced inflammation and disease activity, highlighting the importance of oral health in the control and treatment of systemic diseases such as RA and confirming that NS-PT effectively reduces periodontitis activity and plays a key role in modulating RA activity. Therefore, NS-PT should be considered as an adjunct treatment for RA.

Background: Patients with heart failure were affected severely by COVID-19. Most heart failure patients are on guideline directed medical therapy, which includes ACE inhibitors (ACEI) and ARBs. These medications were controversial at the beginning of the pandemic due to their interplay with the receptor that SARS-CoV-2 binds in the lungs. We investigated the effect that ACEI and ARB had on patients with hypertension, coronary artery disease, and heart failure. Methods: We recruited 176 patients with COVID-19 infection and cardiovascular comorbidities at the American University of Beirut Medical Center in Lebanon. Of these, 110 patients were taking ACEI or ARB and 66 were not. We collected clinical data and looked at inflammatory markers such as CRP and IL-6 and cardiac markers such as troponin T. We also reported the incidence of ARDS, sepsis, and death of each patient, and compared the 2 groups. Results: We found that patients taking ACEI and ARB had a statistically significant decrease in levels of troponin T, IL-6, and CRP compared to patients not taking these medications (p

Osteoarthritis (OA) is the most common form of arthritis resulting in joint discomfort and disability, culminating in decline in life quality. Attention has been drawn in recent years to disease-associated molecular biomarkers found in readily accessible biofluids due to low invasiveness of acquisition and their potential to detect early pathological molecular changes not observed with traditional imaging methodology. These biochemical markers of OA have been found in synovial fluid, blood, and urine. They include emerging molecular classes, such as metabolites and noncoding RNAs, as well as classical biomarkers, like inflammatory mediators and by-products of degradative processes involving articular cartilage. Although blood-based biomarkers tend to be most studied, the use of synovial fluid, a more isolated biofluid in the synovial joint, and urine as an excreted fluid containing OA biomarkers can offer valuable information on local and overall disease activity, respectively. Furthermore, larger clinical studies are required to determine relationships between biomarkers in different biofluids, and their impacts on patient measures of OA. This narrative review provides a concise overview of recent studies of OA using these four classes of biomarkers as potential biomarker for measuring disease incidence, staging, prognosis, and therapeutic intervention efficacy. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of hypercoagulability in COVID-19 patients is complex and not fully understood. Rotational thromboelastometry (ROTEM®) is a viscoelastic method that allows the definition of a patient's hemostatic profile. This study aimed to assess the relationship between ROTEM® parameters, the profile of inflammatory cytokines, and clinical outcomes in COVID-19 patients. Methods: A total of 63 participants (n = 29 symptomatic non-ICU COVID-19 patients, and n = 34 healthy controls) were prospectively included in the study. We assessed the relationship between the parameters of three ROTEM® tests (NATEM®, EXTEM®, and FIBTEM®) and levels of CRP, interleukin-8, interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor, interleukin 12p70, and clinical outcomes. Results: ROTEM® indicated hypercoagulability in COVID-19 patients in all the tests performed. The levels of all inflammatory cytokines were significantly higher in COVID-19 patients. NATEM more frequently detected hypercoagulability in COVID-19 patients compared to EXTEM. The strongest correlations with inflammatory biomarkers and CT severity score were with FIBTEM parameters. The elevated maximum clot elasticity (MCE) in FIBTEM was the strongest predictor of poor outcomes. Conclusions: Increased FIBTEM MCE may be associated with greater severity of COVID-19. Non-activated ROTEM (NATEM test) seems to be more valuable for detecting hypercoagulability in COVID-19 patients compared to the tissue factor activated test (EXTEM). [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is a prevalent gastrointestinal carcinoma and is closely linked to chronic inflammation, including both hepatic and extrahepatic inflammations. However, the genetic association between inflammatory traits and liver cancer has not been systematically investigated. In this study, we aimed to explore the potential causal associations between immune-mediated diseases, circulating inflammatory biomarkers and cytokines, and liver cancer using Mendelian randomization (MR) analysis. To our best knowledge, this is the most comprehensive MR study on this topic to date, involving more than 200 inflammatory traits. This is an important contribution to the field, as it provides insights into the potential causal inflammatory factors of liver cancer. Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using inflammatory traits as exposures and liver cancer as the outcome. The genetic summary data of both exposures and outcome were retrieved from previous genome-wide association studies (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, and weighted-mode methods, were employed to examine the genetic association between inflammatory traits and liver cancer. Nine extrahepatic immune-mediated diseases, seven circulating inflammatory biomarkers, and 187 inflammatory cytokines were analyzed in this study. The IVW method suggested that none of the nine immune-mediated diseases were associated with the risk of liver cancer, with odds ratios of 1.08 (95% CI 0.87–1.35) for asthma, 0.98 (95% CI 0.91–1.06) for rheumatoid arthritis, 1.01 (95% CI 0.96–1.07) for type 1 diabetes, 1.01 (95% CI 0.98–1.03) for psoriasis, 0.98 (95% CI 0.89–1.08) for Crohn's disease, 1.02 (95% CI 0.91–1.13) for ulcerative colitis, 0.91 (95% CI 0.74–1.11) for celiac disease, 0.93 (95% CI 0.84–1.05) for multiple sclerosis, and 1.05 (95% CI 0.97–1.13) for systemic lupus erythematosus. Similarly, no significant association was found between circulating inflammatory biomarkers and cytokines and liver cancer after correcting for multiple testing. The findings were consistent across all four MR methods used in this study. Our findings do not support a genetic association between extrahepatic inflammatory traits and liver cancer. However, larger-scale GWAS summary data and more genetic instruments are needed to confirm these findings. [ABSTRACT FROM AUTHOR]