Increase In C-reactive Protein Levels Research Articles

No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis.

Elevated C-reactive protein (CRP) levels are associated with an increased risk for colorectal cancer (CRC), as well as a poor prognosis, but it remains unclear whether these associations are causal. This study examined the potential causality between CRP levels and CRC survival using 2-sample Mendelian randomization (MR). From the Korean Genome and Epidemiology Study, a genome-wide association study (n=59,605), 7 single-nucleotide polymorphisms (SNPs) related to log2-transformed CRP levels were extracted as instrumental variables for CRP levels. The associations between the genetically predicted CRP and CRC-specific and overall mortality among CRC patients (n=6,460) were evaluated by Aalen's additive hazard model. The sensitivity analysis excluded a SNP related to the blood lipid profile. During a median of 8.5 years of follow-up, among 6,460 CRC patients, 2,676 (41.4%) CRC patients died from all causes and 1,622 (25.1%) died from CRC. Genetically predicted CRP levels were not significantly associated with overall or CRC-specific mortality in CRC patients. The hazard difference per 1,000 person-years for overall and CRC-specific mortality per 2-fold increase in CRP levels was -2.92 (95% confidence interval [CI], -14.05 to 8.21) and -0.76 (95% CI, -9.61 to 8.08), respectively. These associations were consistent in a subgroup analysis according to metastasis and a sensitivity analysis excluding possible pleiotropic SNPs. Our findings do not support a causal role for genetically predisposed CRP levels in CRC survival.

C-Reactive Protein and White Blood Cell Count in Cardiogenic Shock.

This study examines the prognostic impact of C-reactive protein (CRP) and white blood cell (WBC) counts in patients with cardiogenic shock (CS). Data regarding the prognostic impact of inflammatory biomarkers in CS are scarce. All consecutive patients with CS from 2019 to 2021 admitted to a cardiac intensive care unit (ICU) were included at one institution. Laboratory measurements were retrieved from the day of admission (i.e., day 1), as well as days 2, 3, 4, and 8. The primary endpoint was 30-day all-cause mortality. Statistical analyses included univariate t-tests, Spearman's correlations, C-statistics, Kaplan-Meier, and Cox regression analyses. From a total of 240 consecutive patients admitted with CS, 55% died within 30 days. CRP levels on days 3 to 8 were associated with reliable discrimination for 30-day all-cause mortality (area under the curve (AUC): 0.623-0.754), whereas CRP on day 1 was not (AUC = 0.514). In line, CRP > 100 mg/L on day 3 (56% vs. 37%; log-rank p = 0.023; HR = 1.702; 95% CI 1.060-2.735; p = 0.028) and especially a CRP increase of at least 200% from days 1 to day 3 (51% vs. 35%; log-rank p = 0.040; HR = 1.720; 95% CI 1.006-2.943; p = 0.048) were associated with an increased risk of all-cause mortality. Furthermore, WBC on day 1 discriminated 30-day all-cause mortality (AUC = 0.605; p = 0.005) with an increased risk of all-cause mortality in patients admitted with WBC > 10 × 106/mL (59% vs. 40%; log-rank p = 0.036; HR = 1.643; 95% CI 1.010-2.671; p = 0.045). In conclusion, WBC count on admission as well as CRP levels during the course of ICU treatment were associated with 30-day all-cause mortality. Specifically, an increase of CRP levels by at least 200% from day 1 to day 3 during the course of ICU treatment was associated with an increased risk of 30-day all-cause mortality. The present study is one of the first to describe the prognostic value of inflammatory biomarkers in consecutive all-comer CS patients treated at a cardiac ICU.

Metabolic syndrome in antiphospholipid syndrome versus rheumatoid arthritis and diabetes mellitus: Association with arterial thrombosis, cardiovascular risk biomarkers, physical activity, and coronary atherosclerotic plaques.

Cardiovascular disease (CVD) is the foremost cause of morbidity and deaths in antiphospholipid syndrome (APS), driven by thrombo-inflammation and atherothrombosis mechanisms. Metabolic syndrome (MetS) is a proinflammatory and prothrombotic state characterized by increased CVD risk. We aimed to evaluate the prevalence of MetS in APS patients compared to rheumatoid arthritis (RA) and diabetes mellitus (DM) and its associations with clinical and laboratory patient characteristics and vascular ultrasound (US) markers of subclinical atherosclerosis. We included 414 patients in our study: 138 patients with APS (median age: 44.9 years, females 70%) and matched 1:1 for age and sex RA and DM subjects. Three sets of criteria were used for MetS diagnosis: Joint Interim Statement (JIS), International Diabetes Federation (IDF) and modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). The demographic, clinical and laboratory characteristics of all participants were recorded and carotid and femoral US was performed in patients with APS. Multivariate regression models were applied. Prevalence of MetS was 23.9%, 23.2%, 20.3% (based on JIS, IDF, modified NCEP-ATPIII criteria, respectively) in APS versus 17.4%, 17.4%, 13% in RA (p=0.181, p=0.231, p=0.106, respectively), and 44.2%, 44.2%, 40.6% in DM patients. In multivariate analysis, patients with systemic lupus erythematosus- related APS had an approximately 2.5-fold higher risk of MetS versus RA patients. MetS in APS was independently associated with arterial thrombosis (Odds ratio 3.5, p=0.030). Odds ratio for MetS was 1.16 for each one unit increase in C-reactive protein levels according to JIS and IDF criteria, and 1.49 and 1.47 for each one unit increase in uric acid levels using the IDF and modified NCEP-ATPIII models, respectively. APS patients with atherosclerotic carotid plaques had 4 to 6.5-fold increased risk of MetS. Odds for MetS were decreased by 26% with an increase in physical activity by one hour per week. MetS is present in approximately one-fourth of APS patients at a comparable prevalence to that observed in patients with RA. MetS in APS is associated with arterial thrombosis, cardiovascular risk biomarkers, physical activity, and subclinical atherosclerosis, supporting its role in cardiovascular risk stratification and management in APS.

A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.

C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide invitro and invivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy.

C-reactive protein as an early marker of postoperative leakage in patients after endoscopic laser assisted Zenker's diverticulotomy.

Minimally invasive endoscopic techniques are the treatment of choice for Zenker's diverticulum (ZD). Our objective was to evaluate the results and efficacy of endoscopic and open approaches, to determine whether postoperative C-reactive protein (CRP) serum levels can be used as a marker to exclude the presence of esophageal leakage, and to identify risk factors for development of postoperative leakage and complications. Patients who underwent transcervical myotomy and diverticulotomy (TMD) or endoscopic cricopharyngeal myotomy (ECM) with CO2 laser for ZD in years 2008-2021 at our department were included in this retrospective study. Of the 101 patients enrolled, 83 patients underwent ECM and 18 TMD. The procedure time of the endoscopic technique was significantly shorter compared to that of transcervical method (p < 0.001). The median time to oral intake was 6days for ECM and 10.5days in the TMD group (p < 0.001). There was a 13% (n = 11) and 16.7% (n = 3) symptomatic recurrence rate and 3.6% (n = 3) and 16.7% (n = 3) major complications rate for ECM and TMD groups, respectively. The incidence of contrast leak (CL) evaluated by postoperative swallow study was 8.9% (9 from 83 patients in the ECM group only). In patients with CL, a significant increase in CRP levels on postoperative day (POD) 2 and 3 was detected when compared to patients without CL. Endoscopic diverticulotomy with CO2 laser represents a safe and efficient treatment of ZD. Elevation of postoperative CRP serum levels over 123.8mg/L on POD2 and 98.8mg/L on POD3 may indicate presence of an esophageal leakage.

Do Laboratory Biomarkers Predict Survival In Severe Covid-19? A Cross-Sectional Study.

This study aims to compare lymphocyte count, C-reactive protein (CRP), ferritin, Lactate Dehydrogenase (LDH) and D-dimer among survivors and non-survivors of severe COVID-19. This retrospective cross-sectional analytical study included 69 patients for whom a record of the biomarkers and survival status was available. Baseline and peak values were selected for serum CRP, ferritin, LDH and D-Dimer. Baseline and trough lymphocyte counts were selected. Data were analyzed using SPSS version 21. Mean and standard deviation were used to compare the biomarkers with paired t-test. p-value <0.05 was taken as significant. The mean age of the study population was 55.5±9.1 years and 50 (72.5%) were male. Among survivors, the increase in CRP level was not significant (from 15.80±9.8 mg/dl to 17.87±8.4 mg/dl, p=0.45) while it was significant in non-survivors (from 16.68±10.90 mg/dl to 20.77±12.69 mg/dl, p=0.04). There was no significant rise in LDH levels in survivors (from 829.59±499 U/L to 1018.6±468 U/L, p=0.20) while it increased significantly in non-survivors (from 816.2±443.08 U/L to 1056.61±480.54 U/L, p=0.003). The decrease in lymphocyte count and increase in D-Dimers in both the groups was significant (p=0.001). There was no significant elevation in ferritin in both the groups (p>0.05). In severe COVID-19 patients, serum CRP and LDH can be used for risk stratification and predicting survival. Lymphopenia, increase in serum ferritin and D-dimers may not predict survival.

Analysis of the relationship between human complement components C3 &amp; C4 deficiency and C– reactive protein levels as an indicator of the increase of microbial infections

The complement system is an important component of the immune system that consists of a group of plasma proteins produced by the liver and serving a defense function. As a result, the deficiency in any of the complement system components leads to the loss of the function of the deficient protein causing a specific clinical problem or disease. For that reason, this study was designed to investigate C3 and C4 deficiencies in young patients and to inspect the possibility of using C-Reactive Protein (CRP) test and the variation of C3 and C4 concentrations in children`s blood as an indicator of the onset of infection. This study was conducted in the children hospital in Benghazi city, Libya. The blood samples were collected from 446 children in all hospital units to examine the proportion of complement deficiency among those children and C3, C4 deficiency was set as an indicator of infection occurrence. The results of this study have shown a deficiency in complement proteins C3 and C4 were in 44 (10%) samples and 2 (0.4%) samples respectively, the female candidates had a higher rate of C3 and C4 deficiency than males. In addition, the CRP levels were elevated in 167 (55.9%) cases. Furthermore, the association between the increase of CRP levels and low levels of C3 and C4 was observed in 26 (8.7%) cases and 2 (0.6%) cases. These results suggest a strong association between complement proteins C3 and C4 deficiency and an elevation of CRP levels (P-Value=0.00), which supports the concept of using such association as an indicator of microbial infection

Significance of Serum C-Reactive Protein in Assessing the Severity of Covid Illness Among Vaccinated and Non-Vaccinated Individuals

C-reactive protein (CRP) is a protein produced by the liver. CRP levels in the blood, rises when there is an inflammatory condition in the body. A CRP test determines the amount of CRP in the blood to detect inflammation caused by acute conditions or to monitor disease severity in chronic conditions. Covid – 19 is an inflammatory condition, and an increase in CRP level helps in assessing the severity of covid illness. Our aim is to compare the severity of covid illness between the vaccinated and non-vaccinated individuals by estimating the CRP level. This is a cross-sectional study that included 100 Covid positive patients who were clinically diagnosed with fever at Sree Balaji Medical College and Hospital and were randomly selected (both vaccinated and unvaccinated) for the study. The level of serum C-Reactive Protein was estimated in all covid positive patients using the latex agglutination method. Of the 100 covid positive patients, 30 were vaccinated and 70 were not, with 8 vaccinated and 63 non-vaccinated individuals hospitalized due to increased severity. Only 27% of vaccinated people had elevated CRP levels, whereas up to 90% of non-vaccinated people had elevated CRP levels, emphasizing the importance of vaccination in reducing the severity of covid-19 infection. From this study, it was concluded that it is mandatory to estimate CRP level in covid- 19 patients as it is an inflammatory marker to assess the severity of the infection in them. Consequently, it is found that vaccines play an important role in reducing the severity of covid infection (as inflammation is reduced)

No Significant Association Between Plasma Endosialin Levels and the Presence or Severity of Coronary Artery Disease.

BackgroundEndosialin, also called tumor endothelial marker-1 or CD248, is a transmembrane glycoprotein that is suggested to play a role in inflammation as well as tumor progression. Endosialin expression was also reported to be upregulated in human atherosclerotic lesions. However, no study has reported blood endosialin levels in patients with coronary artery disease (CAD).MethodsWe investigated the association between plasma endosialin levels and the presence or severity of CAD in 376 patients who underwent elective coronary angiography for suspected CAD. The severity of CAD was represented as the numbers of stenotic coronary vessels and segments.ResultsOf the 376 study patients, CAD was found in 210 patients (one-vessel disease (1-VD), n = 90; two-vessel disease (2-VD), n = 65; and three-vessel disease (3-VD), n = 55). Compared with 166 patients without CAD, 210 patients with CAD had higher C-reactive protein (CRP) levels (median 0.57 vs. 0.43 mg/L, P = 0.007). However, endosialin levels did not significantly differ between patients with and without CAD (0.91 vs. 0.92 ng/mL, P = 0.693). A stepwise increase in CRP levels was found depending on the number of > 50% stenotic vessels: 0.43 in CAD(-), 0.52 in 1-VD, 0.57 in 2-VD, and 0.58 mg/L in 3-VD (P = 0.019). No marked difference was found in endosialin levels among four groups of CAD(-), 1-VD, 2-VD, and 3-VD (0.92, 0.89, 0.98, and 0.87 ng/mL, respectively, P = 0.785). Moreover, no significant correlation was found between endosialin levels and the numbers of > 50% and > 25% stenotic segments or CRP levels. In multivariate analysis, endosialin levels were not a significant factor associated with CAD independent of atherosclerotic risk factors.ConclusionsPlasma endosialin levels in patients with CAD were found to be not higher than in those without CAD and to be not significantly associated with the presence or severity of CAD.

Relationship Between C-Reactive Protein and Respiratory Diseases in Patients with Type 2 Diabetic Retinopathy.

BackgroundThe aim of this study was to explore the relationship between C-reactive protein (CRP) and respiratory diseases in patients with diabetic retinopathy.Material/MethodsWe identified 855 patients with diabetic retinopathy who met the inclusion criteria from the “Diabetes Complications Data Set” in the National Population Health Data Center. We divided patients into 3 groups according to CRP tertiles: Q1 (<0.3 mg/dL), Q2 (0.3–0.35 mg/dL), and Q3 (>0.35 mg/dL). A multivariate logistic regression model was used to evaluate the relationship between CRP and respiratory diseases. The area under the receiver operating characteristic (ROC) curve was used to investigate the independent predictive effect of CRP on respiratory diseases.ResultsOf the 855 patients with diabetic retinopathy, 137 (16%) had respiratory diseases. Prevalence of respiratory diseases gradually increased with an increase in CRP level (P for trend=0.001). With CRP as a continuous variable in the logistic regression model adjusted for confounding factors (model 3), the odds ratio (OR) per 1 standard deviation increment of CRP was 1.25 (95% CI 1.07–1.45, P=0.004). When the lowest CRP tertile group was used as the reference group, the OR of the highest CRP tertile group was 1.99 (95% CI 1.22–1.3.26, P=0.006). Adding CRP to the risk factor model increased the area under the ROC curve (0.68 vs 0.65, P=0.017). Subgroup analysis showed that the relationship between CRP and respiratory diseases had no potential heterogeneity among subgroups.ConclusionsCRP can be used as an effective biomarker in predicting risk of respiratory diseases in patients with diabetic retinopathy.

Treatment of Septic Arthritis of the Hip Joint Using Repeated Aspirations: When Should We Operate?

The well-accepted treatment of septic arthritis of the hip joint (SAHJ) is surgical drainage of the joint, but repeated aspirations of the hip joint under sonography, have been used for over twenty years with significant success in some centers, including ours. In recent years, we identified some children who did not respond to aspirations and had to undergo arthrotomies. We were concerned that some children may have reached the operating room after a longer than ideal time. Identification of the characteristics of patients who did not respond to repeated aspirations and development of a treatment algorithm that expedites decision-making regarding the necessity of surgery. This is a single-center retrospective cohort analysis. All the patients diagnosed with SAHJ between 2007 and 2019 were identified. Patients who responded to repeated aspirations were compared to those who did not improve and required surgery. Demographic and clinical data and laboratory results were obtained from the patients' electronic medical records. Forty-eight children (88.9%) were treated successfully with repeated aspirations and six children (11.1%) did not improve after aspirations and underwent hip arthrotomies. Five out of 48 children from the aspiration group (10.4%) and 4 out of 6 from the arthrotomy group (66.7%) had chronic comorbidities (p = 0.0051). The mean duration of fever over 38.5 degrees centigrade and the length of stay were higher in the arthrotomy group (p = 0.0040, p = 0.0301, respectively). When we examined the change in C-reactive protein (CRP) levels before and after the first aspiration (Delta CRP), we found a decrease in the aspiration group and an increase in the arthrotomy group (p = 0.0044). The new algorithm which we present allows an expeditious assessment of the patient's response to the repeated aspiration method and thus prevents unnecessary surgeries for the treatment of SAHJ. Patients with chronic comorbidities, prolonged fever, and an increase in CRP level following the first aspiration, are at risk of treatment failure and should be treated with an arthrotomy. Level 4-cohort study.

CRP apheresis in acute myocardial infarction and COVID-19

Das C‑reaktive Protein (CRP) ist das bekannteste Akute-Phase-Protein. Beim Menschen gehen Entzündungen bzw. Infektionen zumeist mit einem Anstieg der CRP-Konzentration im Blut einher, weshalb dem CRP in der täglichen klinischen Routine als Biomarker eine bedeutende Rolle zukommt. Das CRP kann durch die Markierung von geschädigten Zellen die Einleitung der Phagozytose vermitteln. Diese Markierung führt zur Aktivierung des klassischen Komplementwegs (bis hin zu C4) und endet in der Elimination von Pathogenen oder reversibel geschädigten bzw. toten Körperzellen. Sinnvoll erscheint dieses bei einer äußeren Wunde des Körpers. Im Falle von „inneren Wunden“ (z. B. Herzinfarkt, Schlaganfall) induziert CRP durch Zellmarkierung jedoch eine Gewebeschädigung von potenziell regenerierbarem Gewebe mit entsprechend deletären Effekten auf Herz- und Hirnstruktur bzw. -funktion. Die beschriebene Markierung von ischämischen, aber potenziell regenerierbaren Zellen durch CRP tritt offenbar auch bei „coronavirus disease 2019“ (COVID-19) auf. Teile der Lunge werden durch intraalveoläre Ödeme und Blutungen ischämisch und parallel dazu steigt das CRP dramatisch an. Die selektive Immunadsorption von CRP aus dem Blutplasma („CRP-Apherese“) füllt die therapeutische Lücke in der derzeitigen Pharmakotherapie, mit der eine schnelle und effiziente therapeutische Absenkung einer fulminanten CRP-Belastung des menschlichen Organismus nicht möglich ist. Mit der CRP-Apherese ist es zum ersten Mal möglich, dieses pathologische Molekül in der klinischen Praxis schnell und effizient zu entfernen.

Effect of allopurinol drug use on GFR and proteinuria in patients with renal transplant recipients (ADOPTR study)

BackgroundHyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on renal functions and proteinuria in renal transplant recipients. This study aimed to investigate the effect of allopurinol treatment on renal functions in renal transplant recipients (RTR). MethodsA total of 245 patients with renal transplantation were included in this randomized, placebo-controlled study. Patients were randomized to receive either placebo (121 patients) or 300 mg/day allopurinol (124 patients). We have examined uric acid, urinary protein creatinin ratio, MDRD (the modification of diet in renal diseases) and CRP (C-reactive protein) before and 24 weeks after treatment in both group. ResultsIn the allopurinol group, the mean serum uric acid levels, eGFR (estimated glomerular filtration rate), and creatinine urinary albumin creatinin ratio (UACR) significantly improved (p < 0.001). Also uric acid level was positively correlated with the UACR (r = 0,645 p < 0.001) and negatively correlated with MDRD (r = −0,387 p < 0.05) in allopurinol treatment group. A statistically significant increase in CRP level was observed (p < 0,05) in plasebo group. Multivariate regression analysis showed that uric acid was positively correlated with UACR (r = 0,473, β = 0.021, p = 0.002) and negatively correlated with MDRD (r = −0554 β = 0.016, P = 0.001) in allopurinol treatment RTR. ConclusionUrate, a salt of uric acid, is lowered by allopurinol treatment resulting in improved eGFR and decreased proteinuria, when compared to the placebo group. Therefore, we suggest that allopurinol therapy should be part of the management of kidney transplant patients with normal kidney function. Long-term follow-up studies will be useful in revealing the effect of uric acid management on kidney functions and proteinuria.

Association between Pre-Pregnancy BMI and Inflammatory Profile Trajectories during Pregnancy and Postpartum in Brazilian Women with Periodontitis: The IMPROVE Trial.

This study aimed to explore the association between pre-pregnancy BMI and longitudinal changes in inflammatory markers from the second trimester of pregnancy to 6–8 weeks postpartum in women with periodontitis. This is a secondary exploratory analysis of 68 women who took part in a feasibility clinical trial in Rio de Janeiro, Brazil. Inflammatory markers included C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and matrix metalloproteinase-9 (MMP-9) blood concentrations at 11–22 (T0) and 30–36 gestational weeks (T1), and 6–8 weeks postpartum (T3). Longitudinal generalised linear mixed-effects models were used to identify possible associations between pre-pregnancy BMI and changes in concentrations of inflammatory markers. Pre-pregnancy excess weight (β = 4.39; 95% CI, 2.12–6.65) was significantly associated with increased CRP levels from pregnancy to postpartum. There were no significant associations between pre-pregnancy BMI and longitudinal changes in IL-6, IL-10 and MMP-9. Our findings provide evidence that a higher pre-pregnancy BMI may lead to increases in CRP levels during pregnancy in women with periodontitis, irrespective of the severity of clinical periodontal parameters. Further studies need to investigate if predictors of changes in inflammatory markers can be used as prognostic factors for gestational outcomes.

Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis

BackgroundA potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. ObjectivesTo examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. MethodsIn a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. ResultsFor all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. ConclusionTreatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. Trial registrationClinicalTrials.gov ID: NCT01446328; URL: http://www.clinicaltrials.gov/.

Prospective Study: Frequency of Ophthalmic Findings, Relationship with Inflammation Markers, and Effect on Prognosis in Patients Treated in the COVID-19 Intensive Care Unit

Objectives:To prospectively evaluate the frequency of ocular findings and inflammation markers levels in patients treated in the intensive care unit due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to determine the relationship between these parameters and mortality.Materials and Methods:We prospectively evaluated 53 patients who were treated in the intensive care unit of a pandemic hospital between January 1 and June 30, 2021 and whose SARS-CoV-2 diagnosis was confirmed by reverse transcriptase polymerase chain reaction test from nasopharyngeal swab samples. Ocular findings were evaluated together with white blood cell, neutrophil, lymphocyte count, C-reactive protein, lactate dehydrogenase and ferritin levels, and mortality rate.Results:There was no statistically significant correlation between lactate dehydrogenase, white blood cell, neutrophil, and lymphocyte count elevation and the frequency of inflammatory eye signs (p=0.308, p=0.694, p=0.535, p=0.374). In multivariate analyses, no statistically significant correlation was observed between ferritin level and the frequency of inflammatory eye findings (p=0.087). In addition, for each 1 mg/dL increase in C-reactive protein level, the detection of inflammatory eye findings decreased by 1.9% (95% confidence interval: 3.3%-0.4%; p=0.015). It was determined that 7 of 13 patients with inflammatory eye findings died and this was not statistically significant (p=0.810).Conclusion:Inflammatory examination findings of the ocular surface were detected in 13 (24.5%) of 53 patients treated in the intensive care unit for SARS-CoV-2 infection. Ocular surface examination of patients treated in the intensive care unit due to the SARS-CoV-2 epidemic is important.

Inflammation and Conception in a Prospective Time-to-Pregnancy Cohort.

Inflammation may contribute to subfertility but this has not been well-explored in large prospective cohort studies. We conducted a prospective 12-month cohort study of time to pregnancy in North Carolina, the Time to Conceive study (2010-2016). Participants were 30-44 years old, without a history of infertility (N = 727). We analyzed blood samples with a high sensitivity assay for C-reactive protein (CRP). Women reported their weight, height, and other covariates. We natural log-transformed CRP and examined it (1) linearly, after exploration using restricted cubic splines and (2) in categories based on American Heart Association criteria. We estimated fecundability ratios (FRs) with log-binomial discrete-time-to-pregnancy models. Separate models included an interaction term with body mass index (BMI). The adjusted estimated FR per natural log-unit increase in CRP level was 0.97 (confidence interval [CI] = 0.91, 1.0). The FR (CI) for high CRP (>10 mg/L) compared with low CRP (<1 mg/L) was 0.78 (0.52, 1.2). Compared with normal-weight women with low CRP, women with obesity and high CRP had lower estimated fecundability, but the confidence interval was wide (FR = 0.63; CI = 0.35, 1.1). There was no pattern in the estimated fecundability across levels of CRP within categories of BMI. There was no evidence of an association between CRP and fecundability either alone or within levels of BMI. Further studies of CRP and fecundability should include higher levels of CRP and additional markers of inflammation.

The potential role of interleukin-6, endotoxin and C-reactive protein as standard biomarkers for acute appendicitis in adults

Introduction/Objective. Acute appendicitis (AA) is by far the most frequent urgent condition in abdominal surgery and numerous biomarkers may help the physician to diagnose and even predict the severity of the disease. The objective of the paper was to determine the accuracy of C-reactive protein (CRP), interleukin-6, and endotoxin level and compare it with the diagnostic value of Alvarado score (AS) in adults surgically treated for AA. Methods. Sixty-seven patients were diagnosed with AA using AS. Prior to surgery serum levels of inflammatory biomarkers were determined and together with AS were respectively compared to the results of histopathological analysis of specimens. The patients were divided into three group according to the histopathological assessment. Results. The univariate analysis revealed that the increase of CRP level by one unit increases the probability of complicated AA (CoAA) occurrence by 1% (1.00?1.02, p &lt; 0.05). ROC curve analysis has revealed that CRP has better capacity to predict suppurative AA (SAAs)/CoAAs than catarrhal AA (CAA), with the cut-off value of 19.45. The increase of AS value by one unit produced 2.98-fold increase of the probability of CoAA occurrence (1.60?5.57, p &lt; 0.001), while positive AS value increases the probability of CoAA occurrence 24.67 times (4.94?123.12; p &lt; 0.001). ROC curve analysis demonstrated that AS may predict CoAAs better than CAAs/SAAs, with the cut-off value of 8.50. Conclusion. AS and CRP should be routinely used combined as powerful tools for the diagnosis and prediction of complicated AA.

Alterations of the Oral Microbiota Profiles in Chinese Patient With Oral Cancer.

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, of which more than 90% is squamous cell carcinoma. The incidence of oral cancer is on the rise worldwide. An imbalance between the microorganism composition and its host may lead to the occurrence of oral malignant tumors. Accumulating evidence suggests that the oral microbiota plays an important role in oral cancer; however, the association between oral microbiota and oral cancer has not yet been comprehensively studied. In this study, metagenomic sequencing was used to compare the microbial composition of three groups of samples from Chinese patients with oral cancer, patients with precancerous lesion, and normal individuals. In terms of microbiota richness, the oral microbiota of patients with precancerous lesions was richer than that of oral cancer patients and healthy controls, whereas in terms of microbiota diversity, there was little difference between the three groups. The three groups of samples exhibited statistically significant differences in microbiota composition and metabolic function at the family, genus, and species levels (P < 0.05). The differentially enriched phylum in oral cancer samples was Bacteroidetes (P < 0.05). At the genus level, the main differentially enriched taxa were Prevotella, Peptostreptococcus, Carnobacterium, and Diastella (P < 0.05). The species level was differentially enriched in Prevotella intermedia and Peptostreptococcus stomatis (p < 0.05). The prediction of microbiota function shows that oral cancer is mainly associated with coenzyme A biosynthesis, phosphopantothenic acid biosynthesis, inosine 5’-phosphate degradation, and riboflavin biosynthesis. Furthermore, the increase in C-reactive protein level in oral cancer patients was found to be closely related to P. intermedia. Overall, oral bacterial profiles showed significant differences between the oral cancer group and normal group. Hence, microbes can be employed as diagnostic markers and treatment targets for oral cancer.

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity