Serum CRP Levels Research Articles

Value of C-reactive Protein Level to Distinguish between Ischemic and Hemorrhagic Stroke

Abstract Background Stroke is considered as a life threatening case in neurological patients. It is one of the leading causes of morbidity and mortality worldwide, as cerebrovascular accidents rank first in the frequency and importance among all neurological disease. Spontaneous ICH accounts for approximately 20% of all strokes, and it is characterized by high rates of mortality and residual disability among survivors. Aim of the Work To detect the value of serum CRP level in differentiation between ischemic and hemorrhagic stroke. Patients and Methods We conducted a prospective cross section study which included patients who were diagnosed with acute stroke through the period Jan 2021 and July 2021, we recruited 72 patients who were admitted to stroke unit of Ain shams university, they were subsequently divided based on etiology of the stroke into 2 groups: Ischemic stroke group: 36 patients and hemorrhagic stroke group: 36 patients. Results We conducted a cross section analytical study to compare the CRP level among egyptian cohort of patients (n = 72) who were diagnosed with acute ischemic (n = 36) versus hemorrhagic strokes (n = 36) who were admitted to emergency of Ain shams university, aiming to detect the value of serum CRP level in differentiation between ischemic and hemorrhagic stroke. In the present study we found that there was a statistically significant difference between the studied groups and CRP on day 0, mean CRP during Hospital Stay and CRP at discharge. Conclusion Elevated CRP levels are associated with excessive risk of ischemic stroke but not hemorrhagic stroke. The serum CRP level can be used as a predictor for ischemic stroke in the general population.

The Study of Biomarkers inSmokers Infected with Covid-19 in Basra, Iraq

Background: The COVID-19 pandemic has heightened awareness of infectious illnesses and their links to host variables and underlying disorders. Objectives: In this review, we look at current research on a possible link between smoking and COVID-19 and study the biomarker changes in patients. Material and Methods: A case-control study included 45 smoker’s patients with COVID-19 and 50 healthy subjects as a control group who visited Al-Basra Teaching Hospital and Allmwanei Hospital in Al-Basra province between October 2021 and February 2022. The age average for the study population was (25-80) years. Serum and blood levels of human CBC, ESR, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HbA1c, Troponin, Cholesterol, Triglyceride, HDL, LDL, VLDL, Creatinine, Urea, Uric acid and GFR were measured. Results: The results show all biomarkers tend to have high sensitivity and specificity for smoker COVID patients based on the ROC curve analysis: Lymphocyte, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HDL, Creatinine, Urea, and GFR. These biomarkers might be helpful in determining the kind and severity of COVID-19 in smokers. Although the data is limited to a total number of patients. Conclusion: Studying patient alterations and vital signs led to the conclusion that smoking and COVID-19 are related. It was also verified that all vital indicators had strong sensitivity and specificity for smoking COVID patients.

Assessing Active Bowel Inflammation in Crohn's Disease Using Intestinal Ultrasound: Correlation With Fecal Calprotectin.

To analyze the correlation between intestinal ultrasound (IUS) and serum and fecal biomarkers, and the characteristics of small bowel disease, for the assessment of active bowel inflammation. Patients with Crohn's disease (CD) who underwent an initial IUS examination between July 2018 and November 2022 at our institution were included retrospectively. We divided small and large bowels into seven segments, and recorded the presence of active inflammation according to following criteria: bowel wall thickness ≥ mm with ≥1 of feature of active disease on IUS. The correlations between IUS-assessed activity and serum C-reactive protein (CRP, mg/dL) and fecal calprotectin (FC, μg/g) levels were analyzed. A total of 127 patients were included (mean age: 32.42 ± 12.07, M:F = 90:37, median disease duration 6 years [0-35]). Of them, 78 showed active bowel inflammation (61.4%), with inflammation distal to the terminal ileum being the most common disease location (n = 61, 78.2%). FC and serum CRP levels were significantly correlated with the number of segments with active inflammation (rho = 0.58, 0.48), number of segments with complications (r = 0.35, 0.31), and US activity score (r = 0.62, 0.54). With FC cutoff values of 100 and 150 μg/g, the concordance rates for patients with active small bowel disease were 78.7% (26/33) and 72.7% (24/33), respectively, which were better than those for other disease locations. Disease activity determined by IUS was significantly correlated with the biomarkers, with a better concordance rate in patients with active small bowel disease than in those with other disease locations with FC cut-off values of 100 and 150 μg/g.

Elevated levels of neutrophil related chemokine citrullinated histone H3, interleukin-8 and C-reaction protein in patients with immune checkpoint inhibitor therapy: predictive biomarkers for response to treatment

BackgroundImmune checkpoint inhibitor (ICI) therapy has been used in various tumors. The biomarkers predictive of a response to ICI treatment remain unclear, and additional and combined biomarkers are urgently needed. Secreted factors related to the tumor microenvironment (TME) have been evaluated to identify novel noninvasive predictive biomarkers.MethodsWe analyzed 85 patients undergoing ICI therapy as the primary cohort. The associations between ICI response and all biomarkers were evaluated. A prediction model and a nomogram were developed and validated based on the above factors.ResultsSeventy-seven patients were enrolled in the validation cohort. In the primary cohort, the baseline serum levels of H3Cit, IL-8 and CRP were significantly higher in nonresponder patients. A model based on these three factors was developed, and the “risk score” of an ICI response was calculated with the formula: “risk score” = 3.4591×H3Cit + 2.5808×IL8 + 2.0045 ×CRP– 11.3844. The cutoff point of the “risk score” was 0.528, and patients with a “risk score” lower than 0.528 were more likely to benefit from ICI treatment (AUC: 0.937, 95% CI: 0.886–0.988, with sensitivity 80.60%, specificity 91.40%). The AUC was 0.719 (95% CI: 0.600-0.837, P = 0.001), with a sensitivity of 70.00% and specificity of 65.20% in the validation cohort.ConclusionsA model incorporating H3Cit, IL-8 and CRP has an excellent prediction ability for ICI response; thus, patients with a lower “risk score” selectively benefit from ICI treatment, which may have significant clinical implications for the early detection of an ICI response.

Integrating network analysis and pharmacokinetics to investigate the mechanisms of Danzhi Tiaozhi Decoction in metabolic-associated fatty liver disease (MAFLD)

Ethnopharmacological relevanceBased on ancient classics, Danzhi Tiaozhi Decoction has been successfully used to treat nonalcoholic fatty liver disease for decades. However, its therapeutic mechanisms remain unclear. Aim of the studyThis study aimed to investigate the effects of Danzhi Tiaozhi Decoction (DZTZD) on metabolic-associated fatty liver disease (MAFLD). Materials and methodsFirst, we identified the active ingredients of DZTZD and their potential targets in the Traditional Chinese Medicine System Pharmacology database. Using the overlapped genes, we selected the key MAFLD-associated genes, then conducted GO and KEGG pathway enrichment analyses. Furthermore, DZTZD was administered orally to rats, and their serum and liver tissues were examined for absorbed compounds using pharmacochemistry. UPLC-Q-Exactive Orbitrap/MS was used to determine the main compounds. Then, we validated the binding association of the key targets with their active compounds with AutoDock Tools and other software. Finally, the predicted hub targets were experimentally validated. ResultsWe found 254 active compounds in DZTZD corresponding to 208 targets. Sixteen key genes were identified, and the enrichment analysis revealed multiple signaling pathways, including the AGE-RAGE pathway in diabetic complications and the lipid and atherosclerosis signaling pathway. Next, 160 absorbed components and metabolites were characterized in vivo, and 53 absorbed components and metabolites were characterized in liver tissue. Thirteen parent compounds were identified, including coptisine, quercetin, luteolin, and aloe-emodin. The molecular docking data demonstrated the strongest binding between the active compounds and the core proteins. Moreover, the animal experiments showed that DZTZD decreased body weight, liver weight, lipid accumulation, and ALT, AST, CRP, FFA, IL-6, PEPCK, G6P, TG, TC, and LDL-c serum levels, and increased serum HDL-c levels compared to high-fat induced rats. Besides, the RT-PCR and Western blot showed that DZTZD inhibited the SREBP1c and FAS and increased hyperlipidemia-induced CPT-1A levels. In the high-fat group, JNK phosphorylation increased, and AKT protein phosphorylation decreased, while DZTZD reversed these effects. ConclusionBased on the pharmacological network analysis, pharmacochemistry, and experimental validation, DZTZD can potentially improve MAFLD via the JNK/AKT pathway.

Diagnostic Clues for Women with Acute Surgical Abdomen Associated with Ruptured Endometrioma.

(1) Background: An investigation of the preoperative diagnostic clues used to identify ruptured endometrioma by comparing the ruptured and unruptured states in patients who underwent laparoscopic operations due to endometrioma. (2) Methods: Patients with ruptured endometriomas (14 patients) and unruptured endometriomas (60 patients) were included, and clinical symptoms, laboratory findings, and radiological findings were analyzed. (3) Results: There were no significant differences in age, parity, last menstrual cycle days, or median size of endometrioma between two groups (group A: ruptured; group B: unruptured). The median serum level of CA 125 was 345.1 U/mL in group A and 49.8 U/mL in group B (p = 0.000). The median serum levels of CA 19-9 in group A and B were 46.0 U/mL and 19.1 U/mL, respectively (p = 0.005). The median serum level of CRP in group A was 1.2 g/dL, whereas it was 0.3 in group B (p = 0.000). ROC analysis showed that the optimal CA 125 cutoff value was 100.9 U/mL; the optimal CA 19-9 cutoff value was 27.7 U/mL; and the optimal CRP cutoff value was 1.0 g/dL. (4) Conclusions: Ruptured endometrioma can be diagnosed preoperatively using a combination of clinical symptoms, laboratory findings, and radiological findings. If a physician suspects a ruptured endometrioma, surgery should be performed to ensure optimal prognosis.

Diastolic dysfunction of ventricles in patients with calcium pyrophosphate crystal deposition disease while receiving anti-inflammatory therapy

Calcium pyrophosphate crystal deposition disease (CPPD) may be associated with developing of diastolic dysfunction (DD). To determine the variability of echocardiographic parameters in patients with CPPD receiving anti-inflammatory therapy. Twenty six patients with CPPD and osteoarthritis (OA) from 18 to 65 years old were included in the case-control study. All patients underwent echocardiography, laboratory parameters at baseline and after 6 months. Patients with CPPD received methotrexate 15 mg per week or hydroxychloroquine 200 mg once a day, or colchicine 1 mg per day. Diastolic function according to echocardiography was assessed. Diastolic dysfunction was detected in 19 patients: in 11 (42%) patients with CPPD and 8 (31%) patients with OA (p=0.39). The baseline serum CRP level was higher in the CPPD group (p=0.03), no differences were found for other indicators. Twenty-two patients with CPPD and 19 patients with OA completed the study. In patients with OA, there were no significant changes in indicators reflecting the diastolic function of ventricles. CPPD therapy with colchicine, hydroxychloroquine and methotrexate has a positive effect on indicators of diastolic ventricular function.

The relationship of fetal sex and maternal race and ethnicity with early and late pregnancy C-reactive protein and interleukin-8.

Promotion of a healthy pregnancy is dependent on a coordinated immune response that minimizes inflammation at the maternal-fetal interface. Few studies investigated the effect of fetal sex on proinflammatory biomarkers during pregnancy and whether maternal race could impact this association. We aimed to examine whether fetal sex could, independently of maternal race/ethnicity and the condition of pregnancy (normal vs. complicated), impact inflammatory markers (C-reactive protein [CRP] and interleukin-8 [IL-8] levels) in early and late pregnancy. This study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART, N=816). Maternal serum CRP and IL-8 levels were measured in early and late pregnancy (10-18 and 32-38weeks of gestation, respectively). Five hundred and twenty-eight out of 816 pregnant women who participated in the trial had available CRP and IL-8 measurements at both study time points. We examined the association of fetal sex with early and late CRP and IL-8 levels and their paired sample difference. We further investigated whether maternal race/ethnicity, pregnancy complications (i.e., preeclampsia and gestational diabetes), and early pregnancy body mass index (BMI) could affect the association between these two biomarkers and fetal sex adjusting for potential confounders. For this purpose, we used generalized linear and logistic regression models on log-normalized early and late CRP and IL-8 levels as well as their split at median to form high and low groups. Women pregnant with male fetuses (266/528=56.5%) had higher CRP levels in early to mid-pregnancy (β=.18: 95% confidence interval [CI]: CI=0.03-0.32; p=.02). Twenty-seven percent (143/528) of the study subjects were Hispanic. Hispanic African American [AA] women and women of races other than White and AA had higher levels of CRP at early to mid-pregnancy compared with White women (β=.57; 95% CI: 0.17-0.97; p<.01 and β=.27; 95% CI: 0.05-0.48; p=.02, respectively). IL-8 levels were not associated with fetal sex in early and late pregnancy (p's>.05). Other factors such as gestational diabetes and early pregnancy BMI were associated with higher CRP levels and higher CRP and IL-8 levels, respectively. Dichotomizing log-normalized cytokine levels at the median in a sensitivity analysis, women with male fetuses had lower odds of high (above-median) IL-8 levels at early pregnancy. Also, women with races other than AA and White carrying male fetuses had higher odds of having high (above-median) late-pregnancy CRP and early-pregnancy IL-8 levels (adjusted odds ratio [aOR]=3.80, 95% CI: 0.24-1.23; p=.02 and aOR=3.57; 95% CI: 0.23-1.03; p=.02, respectively). Of the pregnancy complications, women with gestational diabetes mellitus had a higher paired difference of early and late pregnancy CRP levels (β=.38; 95% CI: 0.09-0.68; p=.01), but no difference in IL-8 levels (p's>.05). No associations between the inflammatory markers and preeclampsia were found. Fetal sex is associated with CRP in early pregnancy and an association with IL-8 in early pregnancy is implied. Our study further indicates that maternal race/ethnicity could be a contributing factor in the relationship between fetal sex and inflammatory responses during pregnancy. However, the specificity and level of the contribution might vary by type of cytokine, pregnancy stage, and other confounding factors such as BMI that may impact these associations.

Physiological Effects of Calprotectin and B Cell Activating Factor in COVID-19 Patients

Objectives: This study set out to determine how Calprotectin and B cell activating factor contributes to early COVID-19 patient severity prediction.&#x0D; Methods: The study included 25 healthy controls and 52 patients with SARS-COV2 infection who were clinically diagnosed with COVID-19 illness and were between the ages of 23 and 35. The serum levels of CALP and BAFF were measured using the ELISA method. To gauge CRP levels, an immunoturbidometric assay was performed.&#x0D; Results: Variations in serum levels of CALP and BAFF were found to be statistically insignificant in the study (P=0.7109 &amp; P=0.7575, respectively). When compared to the control group (103.95±36.67 ng/mL; 403.03±1.03), COVID-19 patients had non-significantly raised levels of CALP and BAFF (106.5±4.67 ng/mL; 436.9±12.77 pg/mL, respectively). According to ROC curve analysis, the area under the receiver operating characteristics curve (AUC) for CALP and BAFF was (0.5170) and (0.5259), respectively. (r=0.6923; P=0.0001). There was a significant positive correlation between serum CALP and BAFF levels. The connection between serum CRP levels and CALP (r=0.3010; P=0.1271) and BAFF levels (r=0.2912; P=0.1406) was insignificantly positive.&#x0D; Conclusion: The current study's findings suggested that serum CALP and BAFF concentrations were increased in COVID-19 patients, suggesting that these inflammatory markers may be helpful indicators of the severity of COVID-19.

Estimation levels of CTHRC1and some cytokines in Iraqi patients with Rheumatoid Arthritis

Collagen triple helix repeat containing-1 (CTHRC1) is an essential marker for Rheumatoid Arthritis (RA), but its relationship with pro-inflammatory, anti-inflammatory, and inflammatory markers has been scantily covered in extant literature. To evaluate the level of CTHRC1 protein in the sera of 100 RA patients and 25 control and compare levels of tumour necrosis factor alpha (TNF-α), interleukin 10 (IL-10), RA disease activity (DAS28), and inflammatory factors. Higher significant serum levels of CTHRC1 (29.367 ng/ml), TNF-α (63.488 pg/ml), and IL-10 (67.1 pg/ml) were found in patient sera as compared to that in control sera (CTHRC1 = 15.732 ng/ml, TNF-α = 33.788 pg/ml, and IL-10 = 25.122 pg/ml). There was no significant correlation between the level of serum CTHRC1 and DAS28 (r = 0.046, P = 0.650), while there were positive significant correlations between the levels of serum CTHRC1 and CRP (r = 0.372, P = 0.0001), ACPA (r = 0.254, P = 0.01), TNF-α (r = 0.202, P = 0.044), and IL-10 (r = 0.260, P = 0.0001). The level of CTHRC1 (&gt; 25.385 ng/ml) in combination with the levels of CRP and ACPA provided a good indication of RA prediction with sensitivity = 71.0%, specificity = 100.0%, accuracy = 0.71%, positive predictive value (PPV) = 100.0%, and negative predictive value (NPV) = 46.3%. The study showed a significant correlation between the levels of CTHRC1 and TNF-α, and IL-10. These molecules may play a prominent role in the diagnostic and etiology of RA

#4208 CRP EXACERBATES SARS-COV-2-NUCLEOCAPSID PROTEIN-INDUCED ACUTE KIDNEY INJURY

Abstract Background and Aims COVID-19, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), is a progressive viral pneumonia with a broad spectrum of clinical manifestations involving multiple organs. Acute kidney injury (AKI) is common in COVID-19, especially the critically ill patients. Our previous study proved that kidney-specifically overexpressing SARS-CoV-2 N protein induces AKI, which become worsen in mice under ischemic condition. Clinically, CRP is a risk factor for AKI in COVID-19 patients. Recent clinical study showed that CRP Apheresis is able to effectively remove the plasma CRP and thus improve the clinical outcome in critically ill COVID-19 patients. We thus hypothesize that CRP may not only be a biomarker or risk factor, but also a potential mediator or novel therapeutic target for COVID-19 AKI. Method The role of CRP in COVID-19 AKI was investigated in a mouse model of AKI induced by ultrasound-microbubble-mediated kidney-specifically transferring SARS-CoV-2 N-expressing plasmids in CRP wide-type (WT) and Transgenic (Tg) mice. We also developed a novel therapy for SARS-CoV-2 N-induced by targeting CRP signaling with a neutralizing anti-CD32 antibody both in vivo and in vitro. Results In COVID-19 patients with AKI, serum levels of CRP were significantly elevated when compared with non-AKI group. In mice, kidney-specifically overexpressing SARS-CoV-2 N protein caused AKI including tubular necrosis and elevated levels of serum creatinine and BUN in CRP WT mice, which became more severe in CRP Tg mice. Importantly, targeting CRP-CD32 signaling with a neutralizing antibody to CD32 significantly inhibited SARS-CoV-2 N protein-induced AKI in CRP Tg mice. Mechanistically, we uncovered that CRP promoted SARS-CoV-2-N protein-induced AKI via the Smad3-p21-dependent G1 cell cycle arrest and NF-κB/p-p65-driven renal inflammation, which was blocked by anti-CD32 antibody in vivo and in vitro. Conclusion CRP is not only a biomarker or risk factor, but also a mediator in SARS-CoV-2 N protein-induced AKI. CRP signals through CD32 mediate SARS-CoV-2 N-induced AKI via mechanisms associated with the Smad3-p21-dependent G1 cell-cycle arrest and NF-κB/p-p65-driven renal inflammation. Targeting CRP-CD32 signaling may represent as a novel therapy for COVID-19-associated AKI.

#5703 COVID-19, RENAL DAMAGE AND ITS EVOLUTION IN HOSPITALISED PATIENTS IN THE FIRST WAVE OF THE PANDEMIC: EXPERIENCE OF ONE CENTRE

Abstract Background and Aims The damage that SARS Cov2 virus exerts at the renal level has been the subject of analysis in many studies. We analysed the extent of Acute Kidney Injury (AKI), possible factors involved and mortality in patients hospitalised with Covid-19 during the first wave of the pandemic. We reassessed renal function, as well as inflammatory and nutritional status of patients 18 months after admission, together with the capacity for recovery of renal function. Method Observational and retrospective study of patients admitted to the ward or intensive care unit (ICU) for Covid-19 during the month of March 2020. We defined the stage of renal damage according to the KDIGO guidelines. Among the possible risk factors associated with AKI and mortality, we analysed haematological analytical parameters (lymphopenia and plateletopenia), inflammatory markers such as CRP and ferritin, and nutritional status, vitamin D and cholesterol, among others. We evaluated ICU mortality using the Odin scale and the life expectancy at 10 years using the Charlson scale. We used the Chi-square test and Fisher's test, considering significant values p&amp;lt;0.05. Results A total of 576 patients were admitted during the study period, of whom 10.6% were admitted to the ICU (n 61). A total of 45.9% (n 28) had some degree of AKI, the most frequent being grade 2 (22.9%), followed by grade 3 (18%) and grade 1 (4.9%). Of all patients requiring admission to the ICU, 78.6% of those with AKI died. The Odin scale was significantly associated with AKI and mortality, but the Charlson scale was not. The maximum dose of Cisatracurium was significantly associated with AKI. Among the patients admitted to inpatient areas (n 515), 9.9% (n 51) had AKI and 31.4% of these patients died. In most cases the degree of renal damage was mild (82.4% grade 1 vs. 13.7% grade 2 and 3.9% grade 3). When we studied the patients who presented with AKI (n 79), we observed that CK and LDH values were significantly higher, indicating a more inflammatory state. Of the 79 patients, 48.1% (n 38) died, with significant differences in serum CRP and D-dimer levels. Of the 41 patients who survived, we conducted an 18-month follow-up study that only 36.6% (n 15) completed, with a mean age of 69.7 years, 73.3% being male and 20% with previous chronic kidney disease (CKD). At the end of follow-up 86% of them recovered renal function, according to pre-admission figures, including those patients with baseline CKD. Only 13% of the patients who completed follow-up showed a slight worsening of renal function with respect to their baseline situation. We observed differences in the values of calcium, vitamin B12 and vitamin D in the group of patients who recovered renal function compared to those who showed deterioration with respect to their situation prior to admission (p&amp;lt;0.02). Conclusion The incidence of AKI in COVID patients requiring admission to the ICU was four times higher than in patients admitted to the ward. The severity of renal damage was greater in the ICU, predominantly AKI 2-3 vs AKI 1, with mortality 2.5 times higher than in the ward. The group of patients who develop AKI have an elevation of inflammatory markers, which increases in the group of deceased patients. In ICU, the Odin scale was significantly related to AKI and mortality. - The mortality rate in the group of patients with AKI was high. Most of the patients have recovered pre-admission renal function after 18 months of follow-up, with differences in nutritional parameters such as calcium, vitamin B12 and vitamin D.

Anti-arthritic potential of ethyl acetate fraction of &lt;em&gt;Pinus roxburghii&lt;/em&gt; Sargent stem bark in Freund's complete adjuvant induced arthritis in Wistar rats

Traditional and folk medicine regularly make use of the Pinus roxburghii Sargent (Pinaceae) plant. Unfortunately, there is a lack of data on this plant's potential anti-arthritic effects.Pinus roxburghii Sargent ethyl acetate stem bark has anti-arthritic properties in Wistar rats with arthritis produced by Freund's Complete adjuvant. As a positive control, diclofenac was administered. To define the anti-arthritic activity, the influence on pain perception parameter, haematological parameters, the effect on rheumatoid factor, CRP, and serum parameters were evaluated.In this study, the ethyl acetate fraction of Pinus roxburgii Sargent was found to significantly inhibit pain perception parameters at doses of 250 and 500 mg/kg. Serum levels of RF, NO, and CRP were significantly lower in the Pinus roxburghii Sargent group compared to the disease control group. In disease-free rats, Pinus roxburghii Sargent significantly raised RBC and lowered WBC, both of which point to a suppressive effect on inflammatory mediators. The number of inflammatory cells had decreased, as seen by histopathology. Several imaging parameters, including spur formation, joint spacing, bone erosion, etc., were significantly reduced in a radiological assessment.In this study, authors noted that Pinus roxburghii Sargent had a direct effect on slowing the progression of arthritis, reducing inflammation and synovitis, and protecting arthritic joints from cartilage and bone deterioration. Stem bark extract of Pinus roxburghii Sargent has been shown to have anti-arthritic action based on clinical, biochemical, and histological analysis. Yet more research is required to pin down the precise mechanism of action.

Correlation between Serum Interleukin-33, β2-Microglobulin Levels and DS Stage in Patients with Multiple Myeloma

To investigate the correlation between serum interleukin-33 (IL-33), β2microglobulin (β2-MG) levels and Durie-Salmon (DS) stage in patients with multiple myeloma (MM). 100 MM patients admitted to the First Affiliated Hospital of Fujian Medical University from March 2019 to January 2021 were selected and divided into stage I, stage II and stage III groups according to the DS staging system. A baseline data questionnaire of patients was designed, then the relevant baseline data and laboratory test results of patients were recorded. The levels of serum IL-33 and β2-MG of all patients were detected, and the correlation between serum IL-33, β2-MG levels and DS stage of MM patients was analyzed. Among the 100 patients with MM, there were 32 cases in stage I, 39 cases in stage II and 29 cases in stage III. The levels of serum CRP and β2-MG of patients in stage III were significantly higher than those of patients in stage I and II, and the levels of serum CRP and β2-MG of patients in stage II were significantly higher than those of patients in stage I, the differences were statistically significant (P <0.05). The level of serum IL-33 of patients in stage III was significantly lower than that of patients in stage I and II, and the level of serum IL-33 of patients in stage II was significantly lower than that of patients in stage I, the differences were statistically significant (P <0.05). There was no statistical significant difference in other data between groups (P >0.05). Kendall's tau-b correlation analysis showed that the levels of serum CRP and β2-MG were positively correlated with DS stage in MM patients (r =0.534, 0.776), the level of serum IL-33 was negatively correlated with DS stage in MM patients (r =-0.759). Ordered logistic regression analysis and forest plot showed that the low level of serum IL-33 and the high level of β2-MG were the influencing factors of high DS stage in MM patients (P <0.05 ). DS stage of MM patients is closely related to the levels of serum IL-33 and β2-MG, that is, the lower the serum IL-33 level and the higher the β2-MG level, and the higher the DS stage of MM patients.

Association of biomarkers (BMs) with efficacy of adjuvant nivolumab (NIVO) vs placebo (PBO) in patients with resected stage IIB/C melanoma (CA209-76K).

9504 Background: Adjuvant NIVO significantly prolonged recurrence-free survival (RFS) over PBO in stage IIB/C melanoma in the randomized, phase III Checkmate 76K trial (HR; 95% CI: 0.42 [0.30–0.59]). For the first time, select BMs and their association with RFS were analyzed in early-stage melanoma treated with an anti-PD-1 agent. Methods: Baseline primary tumor and serum BMs were analyzed, including interferon gamma-related gene expression signature (IFNγ-sig), TMB, BRAF mutation, % intratumoral CD8+ T cells, tumor cell PD-L1 expression, and serum CRP levels. BMs were evaluated as continuous variables (high vs low levels) and dichotomized by median or prespecified cutoffs. HRs were estimated using a Cox proportional hazards model. Results: Analysis of continuous BM levels within treatment arms showed that higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with prolonged RFS with NIVO but not PBO. The same trend was observed in the dichotomized analyses. No clear association between PD-L1 expression and RFS was identified in either arm. Benefit of NIVO over PBO was seen across all BM subgroups, including by BRAFV600 mutation status. Patients with higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels showed numerically greater relative benefit with NIVO, although CIs overlapped (Table). Conclusions: Higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with longer RFS with NIVO treatment. No BMs assessed were prognostic for RFS in the PBO arm, in contrast to previous reports in melanoma. Prolonged RFS was seen in patients treated with NIVO over PBO across levels of BMs, and irrespective of BRAF mutational status. Composite analyses of BMs with clinical and histopathologic factors will be evaluated for their potential to optimize risk:benefit stratification for NIVO in this patient population. Clinical trial information: NCT04099251 . [Table: see text]

Predictive value of cell population data with Sysmex XN-series hematology analyzer for culture-proven bacteremia.

Cell population data (CPD) parameters related to neutrophils, such as fluorescent light intensity (NE-SFL) and fluorescent light distribution width index (NE-WY), have emerged as potential biomarkers for sepsis. However, the diagnostic implication in acute bacterial infection remains unclear. This study assessed the diagnostic value of NE-WY and NE-SFL for bacteremia in patients with acute bacterial infections, and those associations with other sepsis biomarkers. Patients with acute bacterial infections were enrolled in this prospective observational cohort study. For all patients, a blood sample, with at least two sets of blood cultures, were collected at the onset of infection. Microbiological evaluation included examination of the blood bacterial load using PCR. CPD was assessed using Automated Hematology analyzer Sysmex series XN-2000. Serum levels of procalcitonin (PCT), interleukin-6 (IL-6), presepsin, and CRP were also assessed. Of 93 patients with acute bacterial infection, 24 developed culture-proven bacteremia and 69 did not. NE-SFL and NE-WY were significantly higher in patients with bacteremia than in those without bacteremia (p < 0.005, respectively), and were significantly correlated with the bacterial load determined by PCR (r = 0.384 and r = 0.374, p < 0.005, respectively). To assess the diagnostic value for bacteremia, receiver operating characteristic curve analysis was used. NE-SFL and NE-WY showed an area under the curve of 0.685 and 0.708, respectively, while those of PCT, IL-6, presepsin, and CRP were 0.744, 0.778, 0.685, and 0.528, respectively. Correlation analysis showed that the levels of NE-WY and NE-SFL were strongly correlated with PCT and IL-6 levels. This study demonstrated that NE-WY and NE-SFL could predict bacteremia in a manner that may be different from that of other indicators. These findings suggest there are potential benefits of NE-WY/NE-SFL in predicting severe bacterial infections.

Comparison of Serum Levels of SIL-2R, IL-6, IL-10, TNF-α, CRP, ESR and Fibrinogen in Patients with Active and Inactive Behçet’s Disease

Behçet's disease (BD) is a chronic inflammatory illness that affects the entire body and is characterized by recurring episodes of oral aphthae, ocular and cutaneous lesions, and scrotal or vaginal ulcerations. The involvement of other organs and systems increases mortality in addition to the significant morbidity. This study involved a total of 40 participants, 20 of whom were healthy controls and 20 of whom were patients (of the 20 Behçet's patients, 12 (60%) were in the active phase and 8 (40%) were in the inactive phase). There was no therapy being given to any of the 20 patients that would have affected their cytokine levels. Only young men made up the patient and control groups because both early onset and male sex are signs of poor prognosis. The ELISA method was used to measure the levels of serum cytokines. The statistical analysis of the derived numerical values employed the Mann-Whitney U Test. We found a significant correlation between serum cytokine levels and classical acute phase markers in active Behçet’s patients. ESR (P &lt; 0,001), CRP (P &lt; 0,001), fibrinogen (P &lt; 0,001), IL-10 (P &lt; 0,001), IL-6 (P &lt; 0,001), SIL-2R (P &lt; 0,001) and TNFα (P &lt; 0,001). There was no statistically significant difference in serum levels of classical acute phase markers ESR (P = 0,746), CRP (P = 0,476) and fibrinogen (P = 0,940) when inactive Behçet’s patients and healthy controls were compared. However, serum levels of IL-10 (P &lt; 0,001), IL-6 (P = 0,001), SIL-2R (P &lt; 0,001) and TNFα (P = 0,001) were statistically different between inactive Behcet's patients and the control group. Our research shows that even in the inactive phase, serum cytokine levels of Behçet’s patients are much higher than the healthy control group. However, the levels of ESR, CRP and fibrinogen, which are classical acute phase markers, were found at normal levels in Behçet’s patients in the inactive phase. These findings show that measurement of serum interleukin levels will enable us to take preventive measures for morbidity and mortality follow-up of Behçet's patients.

Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice

AimsTo evaluate the potential of Myricetin against S.aureus induced osteomyelitis. BackgroundOsteomyelitis is infected condition of bone by micro-organisms. The mitogen-activated protein kinase (MAPK), inflammatory cytokines and Toll-like receptor-2 (TLR-2) pathway are mainly involved in osteomyelitis. Myricetin is a plant-food derived flavonoid which shows anti-inflammatory activity. ObjectiveIn the present study, we evaluated the potential of Myricetin against S.aureus induced osteomyelitis. MC3T3-E1 cells were used for in vitro studies. MethodMurine model of osteomyelitis was developed in BALB/c mice by injecting S.aureus in the medullary cavity of the femur. The mice were studied for bone destruction, anti-biofilm activity, osteoblast growth markers alkaline phosphatase (ALP), osteopontin (OCN) and collagen type-I (COLL-1) were studied by RT-PCR, ELISA analysis for levels of proinflammatory factors CRP, IL-6 and IL-1β. Expression of proteins by Western blot analysis and anti-biofilm effect by Sytox green dye fluorescence assay. Target confirmation was done by performing in silico docking analysis. ResultsMyricetin reduced bone destruction in osteomyelitis induced mice. The treatment decreased bone levels of ALP, OCN, COLL-1 and TLR2. Myricetin decreased serum levels of CRP, IL-6 and IL-1β. The treatment suppressed activation of MAPK pathway and showed anti-biofilm effect. Docking studies suggested high binding affinity of Myricetin with MAPK protein in silico, by showing lower binding energies. ConclusionMyricetin suppresses osteomyelitis by inhibiting ALP, OCN, COLL-1 via the TLR2 and MAPK pathway involving inhibition of biofilm formation. In silico studies suggested MAPK as potential binding protein for myricetin.

Host Gut-Resistome and Gut-Immune Axes are the key to Non-cholera Vibrioinfection severity in aging and heat stress

Abstract Global incidences of periodic heat waves and exposures are on the rise and that also have impacted non-cholera Vibrioabundance in coastal waters. We hypothesized that aging and a parallel heat stress (HS) may potentiate the risk of non-cholera Vibrioinfections in the host and exacerbate the pathology. To study the underlying pathological changes in possible co-exposure of HS and subsequent non-cholera Vibriochallenge, an aging mouse model was used. Mice were exposed to HS at 40°C for three hours/day for 15 days. This was followed by a Vibrio vulnificuschallenge 24 hours post HS exposure. Results showed that HS exposure decreased the diversity of the host gut microbiome and altered the relative abundance of many important taxa as assessed by Whole Meta-Genome Sequencing (WMS). Gut leaching was evident via the alteration of tight junction proteins and concomitant endotoxemia was evident. Decrease in abundance of Akkermansia muciniphila, a species well known for protection of gut barrier integrity was observed. Serum CRP levels, a clinical indicator of septicemia was elevated in the HS mice following Vibrio vulnificusinfection, over and above the Vibrio-only or HS-only group. Significant amplification of gut leaching, gastrointestinal and systemic inflammation (IL-1β, IL-6, TNF-α), T-cell senescence and altering IgA levels were also noted in the HS+ Vibriogroup. WMS also showed an altered host resistome signature and abundance of genes harboring the antimicrobial resistance to tetracycline group of antibiotics, a common antibiotic used for treatment of non-cholera Vibrioinfections. In summary, HS augmented susceptibility to non-cholera vibriosis via host variability in resistome patterns and altered gut-immune mediators. This study was supported by NIH/NIEHS Grant 1P01ES028942-01#Project 4 Toxicology awarded to Dr. S. Chatterjee.

Relationship between spontaneous excretion of lower ureter stones with stone size and serum level of C-reactive protein

Background: According to the recent studies on patients with stones in the urinary system, the CRP serum levels can be useful in predicting the possibility of success in expectant treatment and spontaneous excretion of stone and thus, selecting the appropriate patient for this treatment approach; however the studies conducted in this field are inadequate and the results obtained are slightly contradictory. The aim of this study was to investigate the relationship between spontaneous excretion of lower ureter stones with stone size and serum level of C-reactive protein. Methods: This cross-sectional study has been done on 95 patients with lower ureter stone during 2020-2021. Information including gender, age, body mass index, stone size, spontaneous excretion of stone, and CRP serum level were extracted from the files of patients. The existence of stone and its characteristics have been confirmed using ultrasound. Results: The mean CRP serum level was 8.74±‏5.06 mg/l and the frequency of spontaneous stone excretion was 72.6% (n=69). CRP serum level was significantly lower in patients with spontaneous stone excretion (7.42 vs. 12.23 mg/l and p=0.001). The cut-off point of CRP serum level was 13.5 mg/l for patients with ureter stone size of 4-7 (with 84% sensitivity and 58% specificity) and for patients with ureter stone size of 7-10, it was 12.5 mg/l (with 83% sensitivity and 56% specificity). Conclusions: The results showed that there is a significant relationship between the CRP serum levels, along with stone size with spontaneous excretion of lower ureter stones.