C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma

BackgroundC-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.MethodsSerum CRP levels of 329 HCC patients were detected before resection. Paired paraffin-embedded tumor samples were used to quantify immune cell populations, such as CD11b+ myeloid cells, CD68+ macrophages (Mφs), CD15+ neutrophils, CD8+ T cells, and CD206+, CD204+, CD163+ and CD169+ Mφs, by immunohistochemistry. Enrichment scores for 34 types of immune cells based on transcriptome data from 24 HCC samples were calculated by xCell. Overall survival of patients was analyzed using the Kaplan-Meier method.ResultsSerum CRP levels were correlated with liver functions and tumor stages in patients with HCC. The densities of CD68+ tumor-associated macrophages (TAMs) and CD15+ tumor-associated neutrophils (TANs) were significantly higher in patients with elevated serum CRP levels than in those with low CRP levels (both p < 0.0001). Further analysis of TAM subtypes revealed that serum CRP levels were associated with CD204+ and CD163+ Mφ densities (p < 0.0001 and p = 0.0003, respectively). Moreover, transcriptome data showed that CRP expression was associated with the expression of myeloid cell infiltration-related genes in HCC tumors. The combination of serum CRP with TAMs or TANs in both the nontumor and intratumor regions could represent a powerful criterion for predicting patient prognoses.ConclusionSerum CRP could serve as an indicator of an immunosuppressive TME in HCC, which could be of potential clinical application for treatment strategies targeting the TME.

Serum Inflammatory Factors and Oxidative Stress Factors Are Associated With Increased Risk of Frailty and Cognitive Frailty in Patients With Cerebral Small Vessel Disease

Objective: To study the correlation between serum inflammatory factors, oxidative stress factors and frailty, and cognitive frailty in patients with cerebral small vessel disease (CSVD).Methods: A total of 281 patients with CSVD were selected from Tianjin Huanhu Hospital and Inner Mongolia People's Hospital from March 2019 to March 2021. CSVD was diagnosed by MRI. The FRAIL scale was used to evaluate the frailty of patients. Patients with CSVD with frailty and MMSE score <27 were considered to have cognitive frailty. Patients with non-cognitive frailty were included in the control group. The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate the cognitive function of patients with CSVD. The serum interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase 3 (MMP-3), superoxide dismutase (SOD), and malondialdehyde (MDA) of patients with CSVD were detected. The correlation between blood inflammatory factors and oxidative stress factors with the frailty and cognitive frailty patients of CSVD were analyzed. Univariate and multivariate logistic regression were used to analyze the correlation between cognitive frailty and CSVD.Results: Among the patients with CSVD selected in this study, female patients and older patients had a higher proportion of frailty (p < 0.001). In the Frail group, MoCA score and MMSE score were significantly lower than in the Pre-Frail and Robust groups, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores were significantly higher than the Pre-Frail and Robust groups, and the differences were statistically significant (p < 0.05). Serum CRP, IL-6, TNF-α, MMP-3, and MDA levels in the Frail group were higher, but SOD levels were lower. The levels of serum CRP, IL-6, TNF-α, MMP-3, and MDA in patients with CSVD in the Cognitive Frailty group were significantly higher than those of the Control group, while the levels of SOD were significantly lower than those of the Control group, and the differences were significant (p < 0.001). The results of univariate and multivariate logistic regression analysis showed that CRP, TNF-α, MMP-3, and MDA levels were associated with cognitive frailty in patients with CSVD (p < 0.05).Conclusion: The increase of serum CRP, TNF-α, MMP-3, and MDA levels are significantly related to the increased risk of frailty and cognitive frailty in patients with CSVD.

Preoperative serum C-reactive protein concentration can be used to detect gallbladder rupture in dogs with gallbladder mucocele

OBJECTIVE To determine whether serum C-reactive protein (CRP) concentration could be used to detect gallbladder rupture (GBR) prior to surgery in dogs undergoing cholecystectomy for treatment of gallbladder mucocele (GBM). ANIMALS 45 dogs that underwent cholecystectomy because of GBM at a companion animal referral hospital from 2017 to 2020. PROCEDURES Electronic medical records were reviewed, and dogs were included if serum CRP concentration had been measured within 24 hours prior to cholecystectomy. Dogs were grouped as to whether the gallbladder was found to be ruptured or intact during surgery. Accuracy of using preoperative CRP concentration to predict GBR was compared with accuracy of abdominal ultrasonography and other preoperative blood tests. RESULTS GBR was present in 15 dogs at the time of surgery. Median preoperative CRP concentration was significantly higher in dogs with GBR (15.1 mg/dL; interquartile range, 7.4 to 16.8 mg/dL) than in dogs with an intact gallbladder (2.65 mg/dL; interquartile range, 0.97 to 13.4 mg/dL). Sensitivity, specificity, and accuracy of using preoperative CRP concentration to predict GBR were 100%, 67%, and 78%, respectively. CLINICAL RELEVANCE Measurement of preoperative CRP concentration provided excellent sensitivity and moderate specificity for detection of GBR in dogs undergoing cholecystectomy because of GBM. Accuracy of using preoperative CRP concentration for detection of GBR was not superior to the accuracy of preoperative abdominal ultrasonography. However, when CRP concentration was combined with results of ultrasonography, the sensitivity, specificity, and accuracy for detection of GBR were 100%, 93%, and 96%, respectively.

An observational study of salivary C-reactive protein as a potential novel non-invasive biomarker of neonatal sepsis

Objectives: Serial C-reactive protein (CRP) monitoring helps to rule out and prognosticate sepsis. Small blood volumes in neonates make it difficult for repeated blood draws for serial CRP monitoring. Hence, the need of the hour is a non-invasive method such as CRP estimation in saliva. This study aims to correlate salivary CRP with serum CRP levels and establish the potential clinical utility of salivary CRP in diagnosing neonatal sepsis. Materials and Methods: Twenty-three consecutive neonates diagnosed with clinically suspected sepsis and admitted to the NICU were the study subjects. Demographics such as gestational age and weight at birth, sex and detailed clinical features, and comorbidities were noted. Blood samples for CRP estimation and blood culture were collected as soon as clinical suspicion of sepsis arose. Saliva samples were collected for CRP estimation within 1 h of blood sample collection. The saliva was collected in a 2 mL syringe using low suction. Salivary and serum CRP were estimated by the particle enhanced immunoturbidimetric assay. Results: In our study, the CRP levels in saliva correlated moderately well with CRP levels in serum (Spearman correlation coefficient r = 0.582, P = 0.004). The sensitivity and specificity of salivary CRP to predict a serum level of ≥10 mg/L were observed to be 0.75 and 0.93, respectively. Conclusion: Our study shows the promise of salivary CRP as a potential clinically meaningful biomarker of neonatal sepsis and warrants the need for larger studies to validate the utility of salivary CRP to serially monitor neonatal sepsis.

Pre- and Perioperative Inflammatory Biomarkers in Older Patients Resected for Localized Colorectal Cancer: Associations with Complications and Prognosis

The association between pre- and perioperative inflammatory biomarkers, major complications, and survival rates after resection of colorectal cancer (CRC) in older patients is largely unknown. The aim was to investigate age-dependent differences in these associations. Serum CRP, IL-6, and YKL-40 were measured preoperatively and on the first and second day after resection of CRC (stages I–III) in 210 older (≥70 years) and 191 younger patients (<70 years). The results from the complications was presented as an odds ratio (OR, with a 95% confidence interval (CI)) with logistic regression. Results from the mortality rates were presented as a hazard ratio (HR, with a 95% CI) using Cox proportional hazards regression. The preoperative inflammatory biomarkers were higher in the older vs. the younger patients. The risk of complications was increased in older patients with a high preoperative CRP (OR = 1.25, 95% CI 1.03–1.53), IL-6 (OR = 1.57, 95% CI 1.18–2.08), and YKL-40 (OR = 1.66, 95% CI 1.20–2.28), but not in younger patients. Mortality was higher in younger patients with high preoperative YKL-40 (HR = 1.66, 95% CI 1.06–2.60). This was not found in older patients. Elevated preoperative inflammatory biomarkers among older patients were associated with an increased risk of complications, but not mortality. Preoperative inflammatory biomarkers may be useful in assessing the risk of a complicated surgical course in older patients with CRC.

The effect of therapy on subclinical atherosclerosis of the carotid arteries in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis (pilot study)

Endothelial dysfunction associated with chronic microcrystalline inflammation plays a role in the progression of atherosclerosis in calcium pyrophosphate crystal deposition diseases (CPPD).The aim of the study was to assess the dynamics of the development of atherosclerosis based on changes in the thickness of the intima-media complex (ICIM) of the carotid arteries (CA) in patients with CPPD receiving long-term anti-inflammatory therapy (colchicine, methotrexate, hydroxychloroquine).Materials and methods. 26 patients with CPPD and 26 patients with osteoarthritis aged over 18 years old were included. Exclusion criteria: age >65 years; presence of cardiovascular diseases. The blood lipid spectrum, hs-CRP level, anthropometric parameters were determined for all, and Doppler ultrasound ultrasonography of the carotid arteries (CA) was performed. Patients were followed up for not <6 months, assessed ICIM CA at 1 visit, then patients with CPPD, at the discretion of the attending physician, were prescribed methotrexate at a dose of 15 mg per week, hydroxychloroquine 200 mg 1 time per day or colchicine 0.5 mg 2 times a day. Patients could take NSAIDs if they were in pain. The SCORE index has been calculated for everyone.Results. Initially, ICIM values did not differ in patients with CPPD and OA. Initially, ICIM>0.9 mm were detected in 11 of 22 (50%) patients with CPPD and in OA in 8 of 19 (42%) (p=0.39). In dynamics, patients with CPPD revealed a decrease in the number of patients with ICIM>0.9 mm from 42 to 18%. At the same time, in 8 patients with CPPD, ICIM>0.9 mm was combined with a CRP level >0.2 mg/l. Out of 22 patients with CPPD, 14 (64%) patients showed a decrease in the mean values of ICIM, in 2 (9%) patients - an increase, in 5 patients the mean values of ICIM did not change. After 6 months of therapy, out of 11 patients with CPPD with ICIM >0.9 mm, after 6 months of therapy, in 7 cases there was a decrease in the indicator less than the specified value, in 5 of them a decrease in serum CRP level <2 mg/l was recorded. In patients with CPPD, the serum CRP level significantly decreased; in patients with OA, it did not change. Out of 19 patients with OA, 9 (47%) patients showed an increase in the mean ICIM over time, while the rest did not change. In those treated with hydroxychloroquine, a decrease in the mean ICIM parameters was observed in 5 out of 6 (83%) patients, colchicine - in 6 out of 9 (67%) patients, methotrexate - in 4 out of 7 (57%) patients.With CPPD, the result of therapy with colchicine, methotrexate and hydroxychloroquine in relation to the development of the initial signs of atherosclerosis according to Doppler ultrasound ultrasonography of CA can be realized based on the presence of chronic inflammation.

Comparison of Clinical Features and Inflammatory Markers between Kawasaki Disease Shock Syndrome and Kawasaki Disease without Shock: A Meta-Analysis

Since the shock is not a common symptom of KD, it is often misdiagnosed at the beginning of the pathogenesis of KDSS. The language searched was only Chinese and English. Data from the articles were screened and extracted for meta-analysis using Stata16.0 software. A total of 9 cohort studies, including 1231 patients, were included in this meta-analysis. The results of meta-analysis showed that the age of the children in the KDSS group was higher than that in the KD group without shock, and the difference was statistically significant (SMD = 1.15, 95% CI (0.52, 1.78), P < 0.05 ); the CRP content in the KDSS group was higher than that in the KD group without shock, and the difference was statistically significant (SMD = 1.99, 95% CI (0.72, 3.26), P < 0.05 ); the albumin content in the KDSS group was lower than that in the KD group without shock, and the difference was statistically significant (SMD = −1.26, 95% CI (−1.85,−0.67), P < 0.05 ); the AST content in the KDSS group was higher than that in the KD group without shock, and the difference was statistically significant (WMD = 25.95, 95% CI (15.14, 36.75), P < 0.05 ); the difference had statistical significance (RR = 3.50, 95% CI (2.30, 5.32), P < 0.05 ); meta-analysis results of type of KD, fever duration, WBC count, ESR, ALT, and other outcome measures showed that there was no significant difference between KDSS and KD without shock ( P > 0.05 ). Compared with KD without shock, children with KDSS are older and have a higher incidence of coronary artery disease, serum CRP, and AST, but albumin is lower than KD without shock. According to these characteristics, it may be helpful for the early identification of KDSS.

Differential Serum and Urine CRP, IP-10, and TRAIL Levels in Pediatric Urinary Tract Infection

Background: It is estimated that clinical evaluation and urinalysis are unable to diagnose &gt;10% of urinary tract infections (UTI) in young children. TNF-related apoptosis induced ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP) exhibit differential expression in the blood in response to bacterial vs. viral infection. We assessed if the urinary and serum levels of these host biomarkers discriminate UTI, nephronia, and response to antibiotic treatment.Methods: Hospitalized febrile children aged &lt;18 years with suspected UTI based on abnormal urinalysis were recruited prospectively between 2016 and 2018; also, non-febrile controls were recruited. Following urine culture results and hospitalization course, participants were divided into three groups based on AAP criteria and expert adjudication: UTI, viral infection, and indeterminate.Results: Seventy-three children were enrolled, 61 with suspected UTI and 12 non-febrile controls. Of the 61 with suspected UTI, 40 were adjudicated as UTI, 10 viral infection, and 11 as indeterminate. Urinary CRP and IP-10 levels were significantly higher in the UTI group (p ≤ 0.05). Urinary CRP differentiated UTI from non-bacterial etiology in children under and over 3 months of age, with AUCs 0.98 (95% CI: 0.93–1.00) and 0.82 (0.68–0.95), respectively. Similarly, urinary IP-10 discriminated with AUCs of 0.80 (0.59–1.00) and 0.90 (0.80–1.00), respectively. Serum CRP and IP-10 levels were significantly higher in UTI cases with nephronia (p ≤ 0.03). UTI-induced changes in the levels of urinary and serum biomarkers resolved during recovery.Conclusions: CRP, IP-10, and TRAIL represent biomarkers with potential to aid the clinician in diagnosis and management of UTI.

Microbiology and Outcomes of Institutionalized Patients With Stroke-Associated Pneumonia: An Observational Cohort Study

Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies and were inconsistent.Purpose: To determine the microbiology and outcomes of SAP in the lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV).Methods: In this observational study, included patients were divided into SAP and non-SAP based on a comprehensive analysis of symptom, imaging, and laboratory results. Baseline characteristics, clinical characteristics, microbiology, and outcomes were recorded and evaluated.Results: Of 200 patients, 42.5% developed SAP after the onset of stroke, and they had a lower proportion of non-smokers (p = 0.002), lower GCS score (p &lt; 0.001), higher serum CRP (p &lt; 0.001) at ICU admission, and a higher proportion of males (p &lt; 0.001) and hypertension (p = 0.039) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78.8%), followed by Gram-positive aerobic cocci (29.4%). The main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogenes, Serratia marcescens, and Burkholderia cepacia. SAP prolonged length of MV (p &lt; 0.001), duration of ICU stay (p &lt; 0.001) and hospital stay (p = 0.027), shortened MV-free days by 28 (p &lt; 0.001), and caused elevated vasopressor application (p = 0.001) and 60-day mortality (p = 0.001). Logistic regression analysis suggested that patients with coma (p &lt; 0.001) have a higher risk of developing SAP.Conclusion: The microbiology of SAP is similar to early phase of HAP and VAP. SAP prolongs the duration of MV and length of ICU and hospital stays, but also markedly increases 60-day mortality.

What are the best diagnostic tests for diagnosing bacterial arthritis of a native joint?

Aims This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint? Methods We performed a search of PubMed, Embase, and Cochrane libraries for relevant studies published between January 1980 and April 2020. Of 3,209 identified studies, we included 27 after full screening. Sensitivity, specificity, area under the curve, and Youden index of diagnostic tests were extracted from included studies. We grouped test characteristics per diagnostic modality. We extracted the definitions used to establish a definitive diagnosis of bacterial arthritis of a native joint per study. Results Overall, 28 unique diagnostic tests for diagnosing bacterial arthritis of a native joint were identified. The following five tests were deemed most useful: serum ESR (sensitivity: 34% to 100%, specificity: 23% to 93%), serum CRP (sensitivity: 58% to 100%, specificity: 0% to 96%), serum procalcitonin (sensitivity: 0% to 100%, specificity: 68% to 100%), the proportion of synovial polymorphonuclear cells (sensitivity: 42% to 100%, specificity: 54% to 94%), and the gram stain of synovial fluid (sensitivity: 27% to 81%, specificity: 99% to 100%). Conclusion Diagnostic methods with relatively high sensitivities, such as serum CRP, ESR, and synovial polymorphonuclear cells, are useful for screening. Diagnostic methods with a relatively high specificity, such as serum procalcitonin and synovial fluid gram stain, are useful for establishing a diagnosis of bacterial arthritis. This review helps to interpret the value of various diagnostic tests for diagnosing bacterial arthritis of a native joint in clinical practice. Cite this article: Bone Joint J 2021;103-B(12):1745–1753.