Associations of polycyclic aromatic hydrocarbons exposure with serum uric acid and hyperuricemia in US adults: The role of systemic inflammation.

The associations of polycyclic aromatic hydrocarbon (PAH) exposure with serum uric acid (SUA) or hyperuricemia have been rarely assessed. We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations. A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy­PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein (CRP), a biomarker of systemic inflammation, in such associations. Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene (2-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2&3-hydroxyphenanthrene (2&3-OHPh) and total hydroxyphenanthrene (ΣOHPh) was associated with a 1.68 (95% confidence interval (CI): 0.19 to 3.17), 2.46 (0.78 to 4.13), 3.34 (1.59 to 5.09), and 2.99 (1.23 to 4.75) µmol/L increase in SUA, and a 8% (odds ratio (OR): 1.08, 1.02 to 1.15), 9% (OR: 1.09, 1.02 to 1.18), 13% (OR: 1.13, 1.05 to 1.22), and 12% (OR: 1.12, 95% CI: 1.03, 1.21) increase in hyperuricemia, respectively. Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia, with 2&3-OHPh showing the highest weight (components weights: 0.83 and 0.78, respectively). The CRP mediated 11.47% and 10.44% of the associations of ΣOHPh and 2&3-OHPh with SUA and mediated 8.60% and 8.62% in associations of ΣOHPh and 2&3-OHPh with hyperuricemia, respectively. In conclusion, internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults, and CRP played a mediating role in the associations.

A Prospective Observational Study to Assess the Neutrophil-to-Lymphocyte Ratio (NLR) and C-reactive Protein-to-Albumin Ratio (CAR) in Predicting Morbidity and Mortality Among Patients Undergoing Emergency Abdominal Surgery.

Background Emergency abdominal surgeries pose significant challenges, especially in the Indian population, due to comorbidities, delayed presentations, and limited resources. Accurately predicting morbidity and mortality is crucial for timely interventions and improved patient care. The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) have shown potential as prognostic markers, balancing inflammation and nutritional status. Aim The study aims to evaluate the predictive efficacy of NLR and CAR with regard to postoperative morbidity and mortality in patients undergoing emergency abdominal surgery, thereby contributing to better risk stratification and management strategies. Patients and methods A prospective observational study was conducted in a tertiary teaching hospital in northern Karnataka from August 2022 to June 2024, involving 102 patients undergoing emergency abdominal surgeries. The sample size (71) was calculated using G*Power software, targeting a 95% power with a 5% significance level. The inclusion criterion was patients aged over 18 years undergoing emergency abdominal surgeries; those who were immunocompromised, on steroid therapy, having malignancies, undergoing radiotherapy, or having chronic liver diseases were excluded from the study. Patients coming into the surgical inpatient department (IPD) with an acute abdomen requiring emergency abdominal surgeries as an emergency were preoperatively assessed using complete blood count (CBC), CRP, and serum albumin tests. NLR and CAR were evaluated preoperatively and at 24 and 48 hours postoperatively. The outcome measures included surgical site infection rates, hospital stay duration, and outcome in the form of recovery or death. SPSS version 20 was used for statistical analyses. Results The study included 102 patients whose mean age was 43.7 ± 18.9 years; 74 of the participants (72.5%) were male. The most common procedures were exploratory laparotomy (64 patients; 62.7%) and appendicectomy (32 patients; 31.4%). A significant increase in CAR levels was observed on postoperative days 1 and 2 compared to baseline (p < 0.05). Preoperative NLR ≥ 8 was significantly associated with higher mortality (65% vs. 50%, p < 0.01). Preoperative albumin > 3.2 g/dL was associated with better outcomes (recovery in 54 patients; 65.9%) compared to < 3.2 g/dL (15 patients; 75% mortality). This study showed that NLR and CAR are valuable predictors of postoperative outcomes, with CAR indicating the risk for surgical site infections (SSI) and NLR predicting mortality. Conclusion The preoperative NLR had a significant association with mortality among the patients. Hence the NLR can be a good marker for the worst outcome and CAR during the postoperative period can be considered as a marker to detect the risk of SSI. NLR and CAR are simple, inexpensive tests readily available from routine blood investigations. The utility of NLR and CAR as valuable prognostic markers in the perioperative assessment of patients undergoing emergency abdominal surgery could enhance the prediction of patient outcomes and guide more effective management strategies to improve patient outcomes in high-risk emergency abdominal surgery.

Sex-specific associations between levels of high-sensitivity C-reactive protein and severity of depression: retrospective cross-sectional analysis of inpatients in China.

BACKGROUND: We aimed to clarify the controversial relationship between levels of high-sensitivity C-reactive protein (hs-CRP) and severity of depression in men and women. METHODS: Medical records were retrospectively analyzed for 1,236 inpatients at our medical center who were diagnosed with depression at discharge between January 2018 and August 2022. Depression severity was assessed during hospitalization using the 24-item Hamilton Depression Rating Scale. Potential associations between severity scores and hs-CRP levels were explored using multivariate linear regression as well as smooth curve fitting to detect non-linear patterns. RESULTS: In male patients, hs-CRP levels between 2.00 mg/L and 10.00 mg/L showed a non-linear association with depression severity overall (fully adjusted ß = 1.69, 95% CI 0.65 to 2.72), as well as with severity of specific symptoms such as hopelessness, sluggishness, and cognitive disturbance. In female patients, hs-CRP levels showed a linear association with severity of cognitive disturbance (fully adjusted ß = 0.07, 95% CI 0.01 to 0.12). These results remained significant after adjusting for age, body mass index, diabetes, hypertension, history of drinking, history of smoking, and estradiol levels. DISCUSSION: Levels of hs-CRP show sex-specific associations with depression severity, particularly levels between 2.00 and 10.00 mg/L in men. These findings may help develop personalized anti-inflammatory treatments for depression, particularly for men with hs-CRP levels of 2.00-10.00 mg/L.

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

BACKGROUND: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. METHODS: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. RESULTS: Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. CONCLUSIONS: In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. REGISTRATION: ClinicalTrials.gov Identifier: NCT01000701.

C-Reactive Protein Is Not the Driver Factor in Ulcerative Colitis.

Purpose: C-reactive protein (CRP) functions as a nonspecific marker in various inflammatory disorders, particularly in evaluating the efficacy of pharmacological treatments in patients with ulcerative colitis. The existing body of evidence does not offer adequate support for the direct implication of CRP in modulating the advancement of ulcerative colitis. Methods: Our study employed a rigorous mouse model. An ulcerative colitis mouse model was established by subjecting CRP-deficient mice to dextran sulfate sodium (DSS) treatment. The phenotype of the mice, which encompassed parameters such as body weight, colon length, and spleen weight, was meticulously evaluated. Additionally, various physiological and biochemical indicators were assessed, including colon histopathology, expression levels of inflammatory factors, and staining of the intestinal mucus layer. Results: The absence of CRP did not significantly affect the phenotype, physiological characteristics, and biochemical indices in a mouse model of ulcerative colitis compared to mice with wild-type CRP. Additionally, eliminating intestinal bacteria flora interference through antibiotic treatment revealed that mice lacking CRP did not demonstrate any notable variations in the ulcerative colitis model. Meanwhile, the survival rate of mice lacking CRP did not exhibit a statistically significant difference compared to wild-type mice. Conclusion: The results of our study suggest that CRP may not directly mediate ulcerative colitis. Instead, it is more likely to be a bystander that is present alongside with elevated inflammatory factors. Further investigation is warranted to determine the precise role of CRP in humans, given the significant limitations associated with the use of mouse models.

Conditional associations of sex steroid hormones with C-reactive protein levels in American children and adolescents: evidence from NHANES 2015-2016.

Background: The relationship between sex steroid hormones and high-sensitivity C-reactive protein(hs-CRP) levels in American children and adolescents is understudied. This research will examine this association. Methods: The study conducted a data analysis from the National Health and Nutrition Examination Survey (NHANES) 2015-2016, adjusting multiple linear regression models with R 4.2.2 and EmpowerStats. A total of 1,768 children and adolescents were surveyed. Data collection involved measurements of serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG) and hs-CRP. Results: With the increase in testosterone, a brief rise (ß=0.082, P=0.047) followed by an overall decline (ß=-0.028, P=0.023) in hs-CRP was observed in the Male Prepubertal population, while a continuous decline (ß=-0.002, P<0.05) was seen in the Male Pubertal group. A positive correlation (ß=0.047, P<0.05) was found between testosterone and hs-CRP in the Female Prepubertal population, whereas no significant association (ß=0.002, P>0.05) was detected in the Female Pubertal group. A significant inverse correlation was observed between estradiol and hs-CRP solely in the Female Pubertal group (ß=-0.002, P<0.05), while no association was found in other populations. An inverse relationship between SHBG and hs-CRP was consistently noted across all groups: Male Prepubertal, Male Pubertal, Female Prepubertal, and Female Pubertal. Conclusions: The association between sex steroid hormones and high-sensitivity C-reactive protein (hs-CRP) levels among American children and adolescents is conditional and influenced by multiple factors.

Predictive Factors for the Development of Gallbladder Necrosis.

Introduction Acute cholecystitis is a common complication of gallstone disease. Likewise, gallbladder necrosis is a complication of cholecystitis associated with higher risks of morbidity and mortality. Identification of risk factors which portend to gallbladder necrosis is key in prioritizing the management of higher-risk patients. This study aimed to identify such factors that predict the development of gallbladder necrosis. Method A retrospective review of all patients undergoing emergency cholecystectomy in a tertiary hospital over a two-year period was performed. Gallbladder necrosis was diagnosed on histopathological examination of operative specimens. Multivariable logistic regression was performed to determine risk factors for gallbladder necrosis. Results A total of 163 patients underwent acute cholecystectomy and 43 (26%) had proven gallbladder necrosis. Multivariable analysis demonstrated that elevated white cell count (WCC) (OR 1.122, 95%CI 1.031-1.221, p=0.007), elevated C-reactive protein (CRP) (OR 1.004, 95%CI 1.001-1.008, p=0.022) and positive smoking status (OR 5.724, 95%CI 1.323-24.754, p=0.020) were independently predictive of gallbladder necrosis. Notably, advancing age, elevated BMI, diabetes mellitus or American Society of Anesthesiologists (ASA) grade were not found to be associated with developing necrosis. Conclusion Patients at risk of gallbladder necrosis include those with higher WCC, CRP, and active smokers. Given the increased potential complications, these risk factors should be identified early in the management of those admitted with gallstone disease to ensure such patients receive aggressive medical therapy alongside timely and guided surgical intervention.

Comparison of Biomarkers of Oxidative Stress, Inflammation, and Endothelial Function Among Vegetarians and Non-vegetarians of Vijayapura, India: A Pilot Study.

BACKGROUND: The known impact of diet on the pathophysiology of various chronic diseases and the current dietary transition in the country make it essential to assess the influence of dietary patterns specific to this region on inflammation, oxidative stress, and endothelial functions. OBJECTIVE: This study compared oxidative stress, inflammation, and endothelial functions among vegetarians and non-vegetarians in Vijayapura, Karnataka, India. METHODS: The present cross-sectional comparative study involved apparently healthy vegetarians (n=35) and non-vegetarians (n=35) aged 20-40. The anthropometric measurements like height (cm) and weight (kg) were recorded, and the BMI was calculated. The physiological parameters like systolic and diastolic blood pressure and pulse rate were recorded. Serum high-sensitivity C-reactive protein (hs-CRP), serum malondialdehyde (MDA), and serum nitric oxide (NO) were estimated as markers of inflammation, oxidative stress, and endothelial function, respectively. Statistical analysis was done using SPSS Statistics version 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). RESULTS: The average age of vegetarians and non-vegetarians was 25.22 ± 7.63 years and 25.60 ± 5.64 years, respectively. Anthropometric and physiological parameters were comparable between the two groups. However, there was a trend for higher mean body weight among non-vegetarians (53.94± 6.73 vs. 57.22±7.18) with a marginal non-statistically significant p-value (p=0.052). Vegetarians showed significantly higher serum MDA levels than non-vegetarians (2.14 (0.93-2.91) vs. 0.64 (0.35-1.32); p=0.000), while hs-CRP (vegetarians - 0.01 (0.005-0.034) vs. non-vegetarians - 0.03 (0.01-0.04); p=0.18) and serum NO levels (vegetarians - 6.72 (5.46-8.39) vs. non-vegetarians - 5.43 (2.87-9.16); p=0.215) were similar in both groups. CONCLUSION: The results were intriguing and contrasting, as serum MDA is remarkably higher among vegetarians than non-vegetarians, pointing toward greater oxidative stress among the former and possibly indicating a dietary imbalance among vegetarians, which needs further exploration.

Evaluating Personalized Add-On Ayurveda Therapy in Oxygen-Dependent Diabetic COVID-19 Patients: A 60-Day Study of Symptoms, Inflammation, and Radiological Changes.

Background Effective management of both acute and post-acute sequelae of SARS-CoV-2 is essential, particularly for type 2 diabetes mellitus (T2DM) patients, who are at increased risk of severe pro-inflammatory responses and complications. Persistent symptoms and residual lung and cardiovascular damage in post-coronavirus disease (COVID-19) individuals highlight the need for comprehensive long-term treatment strategies. Conventional treatments, including Remdesivir and glucocorticoids, have limitations, suggesting that further investigation into Ayurvedic therapies could be beneficial, though controlled trials are currently limited. Objectives Evaluate the effectiveness and safety of Ayurveda with the standard of care (SOC) versus SOC in improving symptoms, moderating immune responses (interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and radiological outcomes in oxygen-dependent, high-risk, non-vaccinated type 2 diabetes COVID-19 patients over 60 days, and thus addressing their heightened vulnerability to severe infections. Methods A controlled trial with 50 diabetic COVID-19 patients, aged 18-80, with an NLR of >= 4, primarily on Remdesivir, was assigned to Group 1 (Add-on Ayurveda+SOC, n=30) or Group 2 (SOC, n=20) based on their voluntary choice with follow-up on days 14, 28, and 60. Parametric outcomes in group analysis were assessed with robust regression and non-parametric outcomes with Cochran-Mantel-Haenszel, log-rank test, and chi-square tests at 95% confidence interval (CI). Results Group 1 exhibited statistically significant improvements in fever, cough, diarrhea, as well as NLR, IL-6, and CRP by 14 days, and in anosmia, loss of taste, shortness of breath, general weakness, and headache by 60 days. Though the sample size is small, notable improvements can be seen in troponin levels in Group 1 at 28 and 60 days. High-resolution computer tomography COVID-19 reporting and data system (HRCT CO-RADS) scores improved more slowly in Group 2 than in Group 1. Survival rates were 96.4% for Group 1 and 90% for Group 2. Numbers were too small for reliable comparisons at 60 days.  Conclusion The add-on Ayurveda group showed a better symptomatic response, and faster normalization in inflammatory markers, including IL-6 and NLR by 14 days, and cardiac markers by 28 days. Minimal clinical and no laboratory adverse events were observed. This study supports the need for a randomized, double-blind trial.

The High-Sensitivity C-Reactive Protein to High-Density Lipoprotein Cholesterol Ratio and the Risk of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention.

Background: The high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (CHR) is a novel biomarker associated with coronary artery disease (CAD) risk. This study aimed to analyze the relationship between CHR and contrast-induced acute kidney injury (CI-AKI). Methods: This retrospective cross-sectional research included 10,917 individuals who underwent PCI. CI-AKI was diagnosed using the Kidney Disease: Improving Global Outcomes (KIDIGO) standard. Univariate and multivariable logistic regression analyses were conducted to examine the association between CHR and CI-AKI, followed by a receiver operating characteristic (ROC) curve of participants to assess the clinical diagnostic performance of CHR on CI-AKI. Results: A total of 1037 patients (9.50%) developed CI-AKI after PCI. The age of individuals averaged 64.1 ± 11.1 years old, with 2511 females (23.0%). A multivariate logistic regression study revealed that higher CHR levels were linked to higher CI-AKI incidence rates ([Q4 vs. Q1]: odds ratio (OR) = 1.89, 95% confidence interval (CI) [1.42 to 2.54], p < 0.001). A restricted cubic spline analysis revealed a linear association between CHR and CI-AKI. ROC analysis indicated that CHR was an excellent predictor of CI-AKI (area under ROC curve = 0.606, 95% CI [0.588 to 0.624]). Conclusions: A high CHR level is strongly associated with increased CI-AKI incidence, suggesting that CHR may be an independent risk factor for CI-AKI. Clinical Trial registration: NCT05050877. https://clinicaltrials.gov/study/NCT05050877?tab=results.

Inflammation scores based on C-reactive protein and albumin predict mortality in hospitalized older patients independent of the admission diagnosis.

Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Predictors of the severity of the course of COVID-19: demographic factors, clinical signs and laboratory markers.

Introduction. The Coronavirus Disease 2019 (COVID-19) pandemic has had a significant impact on global healthcare, with high mortality and severe complications remaining a major concern. Understanding the predictors of COVID-19 severity may improve patient management and outcomes. While considerable research has focused on the pathogenesis of the virus and vaccine development, the identification of reliable demographic, clinical and laboratory predictors of severe disease remains critical.Hypothesis. Specific demographic factors, clinical signs and laboratory markers can reliably predict the severity of COVID-19. A comprehensive analysis integrating these predictors could provide a more accurate prognosis and guide timely interventions.Aim. The aim of this study is to identify and evaluate the demographic, clinical and laboratory factors that can serve as reliable predictors of severe COVID-19, thereby aiding in the prediction and prevention of adverse outcomes.Methodology. The methods of analysis, synthesis, generalization and descriptive statistics were used to achieve this objective.Results. The analysis showed that demographic factors such as age over 60 and male sex are significant predictors of severe COVID-19. Clinical predictors include respiratory symptoms, especially dyspnoea, and comorbidities such as hypertension, coronary artery disease, chronic obstructive pulmonary disease, respiratory failure, asthma, diabetes mellitus and obesity. Laboratory markers with high prognostic value include elevated levels of C-reactive protein, interleukin-6, ferritin, neutrophil/lymphocyte ratio, d-dimer, aspartate aminotransferase enzyme and decreased lymphocyte count.Conclusion. The study concludes that a holistic approach incorporating demographic, clinical and laboratory data is essential to accurately predict the severity of COVID-19. This integrated model may significantly improve patient prognosis by facilitating early identification of high-risk individuals and allowing timely, targeted interventions. The results highlight the importance of comprehensive patient assessment in managing and mitigating the impact of COVID-19.

Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews.

Background: Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus. Methods: The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses. Results: We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specificity for influenza or respiratory syncytial virus varied considerably across the different types of tests. Tests involving nucleic acid amplification techniques (either single pathogen or multiplex tests) had the highest diagnostic accuracy for influenza (sensitivity 91-99.8%, specificity 96.8-99.4%). Limitations: Most of the evidence was considered low or very low certainty when assessed with GRADE, due to imprecision in effect estimates, the potential for bias and the inclusion of participants outside the scope of this review (children, or people in hospital). Future work: Currently evidence is insufficient to support routine use of point-of-care tests in primary and emergency care. Further work must establish whether the introduction of point-of-care tests adds value, or simply increases healthcare costs. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159948.

Respiratory infections are a common cause of illness. Currently, healthcare professionals use clinical experience to decide whether an infection is caused by a virus or bacteria, and whether antibiotics are needed. However, this is not always easy to establish. We tried to identify the effectiveness of rapid tests (with results in under 45 minutes) at distinguishing between viral and bacterial respiratory infections. We identified and summarised all the existing reviews and studies in this area. We looked at many different tests which aim to distinguish between bacterial and viral causes of respiratory infections. In particular, we assessed: individual symptoms and signs (such as the presence of cough, or a fever) combinations of symptoms and signs (the presence or absence of multiple symptoms) various 'biomarker' tests (blood tests for evidence that the body has used its defence mechanisms) We also looked at specific tests for flu and respiratory syncytial virus, which are common causes of viral infection. The reviews we found showed symptoms and signs were not able to identify bacterial infections in people accurately. The accuracy of biomarker tests was slightly better, particularly when multiple markers were used. The accuracy of rapid tests for flu and respiratory syncytial virus varied; the most accurate tests were those that detect viral genetic material. We also found studies showing that genetic tests that identify many viruses at once (multiplex tests) were very accurate. However, most of the evidence we identified was not robust. There were concerns about the conduct of some of the studies. In some cases there was uncertainty whether a test was really accurate enough to be useful. Therefore there is still doubt about whether any of these tests will be useful additions to current clinical care.

Associations between C-reactive protein and individual symptoms of depression in a lower-middle income country.

BACKGROUND: Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). AIMS: We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. METHOD: This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms. RESULTS: High plasma CRP (≥3 mg/L) was detected in 87% (n = 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16-5.25), early morning waking (odds ratio 2.65, 95% CI 1.29-6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39-21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14-0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14-0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation. CONCLUSIONS: The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.

Evaluating the effects of dietary patterns on circulating C-reactive protein levels in the general adult population: an umbrella review of meta-analyses of interventional and observational studies.

Adopting a healthy dietary pattern may be an initial step in combating inflammation-related chronic diseases; however, a comprehensive synthesis evaluating current evidence is lacking. This umbrella review aimed to summarise the current evidence on the effects of dietary patterns on circulating C-reactive protein (CRP) levels in adults. We conducted an exhaustive search of the Pubmed, Scopus and Epistemonikos databases, spanning from their inception to November 2023, to identify systematic reviews and meta-analyses across all study designs. Subsequently, we employed a random-effects model to recompute the pooled mean difference. Methodological quality was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist, and evidence certainty was categorised as non-significant, weak, suggestive, highly suggestive or convincing (PROSPERO: CRD42023484917). We included twenty-seven articles with thirty meta-analyses of seven dietary patterns, fifteen of which (50 %) exhibited high methodological quality. The summary effects of randomised controlled trials (RCT) found that the Mediterranean diet was the most effective in reducing circulating CRP levels, followed by Vegetarian/Vegan and Energy-restricted diets, though the evidence was of weak quality. In contrast, Intermittent Fasting, Ketogenic, Nordic and Paleolithic diets did not show an inverse correlation with circulating CRP levels. Some results from combined interventional and observational studies, as well as solely observational studies, also agreed with these findings. These dietary patterns show the potential in reducing CRP levels in adults, yet the lack of high-quality evidence suggests future studies may alter the summary estimates. Therefore, further well-conducted studies are warranted.

Systemic Inflammatory Indicators and Risk of Incident Metabolically Unhealthy Phenotype.

Objective: This retrospective cohort study was designed to evaluate the association between eight systemic inflammation indicators at baseline and the metabolically unhealthy (MU) phenotype after two years of follow-up. Methods: Participants were defined as metabolically healthy (MH) if they met 0-2 of the criteria and metabolically unhealthy (MU) if they met ≥ 3 of the criteria. A many of 4175 subjects aged 20-80 years with a metabolically healthy (MH) phenotype at baseline were enrolled in the study. We compared the clinical characteristics between women and men enrolled at baseline according to the metabolic phenotype at follow-up. The associations between baseline inflammation indicators and MU status at follow-up were evaluated using logistic regression analysis. Results: 922 (22.08%) developed new-onset MU symptoms during follow-up. Logistic regression analysis found that most inflammation indicators were significantly associated with MU phenotype at follow-up, aside from the LMR and SII. After adjusting for potential confounders, only the correlations between CRP level, neutrophil count, and MU phenotype reached significance. In comparison to the control group with a CRP of <0.50 mg/L, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.61 (1.25-2.09), 1.49 (1.15-1.94), and 1.68 (1.30-2.18) for individuals with CRP levels of 0.50-0.90 mg/L, 0.91-1.72 mg/L, and above 1.72 mg/L, respectively. In the population with a neutrophil count <5.00 ×109 cells/L, the neutrophil count correlated positively and significantly with the MU phenotype. In comparison to the control group with a neutrophil count of <2.75 × 109 cells/L, the ORs and 95% CIs were 1.65 (1.30-2.09) in the population with neutrophil count >4.17 × 109 cells/L. Conclusion: CRP and neutrophil counts positively correlated with the risk of MU phenotype in Chinese subjects. These composite inflammatory markers (NLR, PLR, LMR, and SII) provide limited advantages for predicting MU risks compared to CRP.

Effect of inflammatory factors on myocardial infarction.

BACKGROUND: Cohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear. METHODS AND RESULTS: By utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.00-1.17; p = 0.04). C-reactive protein levels correlated positively with MI. No associations were observed with IL-1 beta, IL-6, IL-18, procalcitonin, TNF-α, total white cell count, or neutrophil percentage of white cells. Neutrophil count and C-reactive protein were inversely associated with lactate dehydrogenase: neutrophil cell count (OR 0.95; 95% CI, 0.93-0.98; p < 0.01) and C-reactive protein (OR 0.96; 95% CI, 0.92-1.00; p = 0.02). No associations of MI with myoglobin, troponin I, and creatine kinase-MB levels were found. CONCLUSIONS: This two-sample MR analysis revealed a causal positive association of MI with neutrophil count, C-reactive protein level, and the myocardial injury marker lactate dehydrogenase. These results indicate that monitoring C-reactive protein and neutrophil counts may be useful in management of MI patients.

Early warning model to detect anastomotic leakage following colon surgery: a clinical observational study.

Purpose: We aimed to develop a predictive tool for anastomotic leakage (AL) following colon cancer surgery by combining a clinical early warning score (EWS) with the C-reactive protein (CRP) level. Methods: The records of 1,855 patients who underwent colon cancer surgery at the Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018, with or without AL, were retrospectively reviewed. EWS and CRP levels were assessed daily from the first postoperative day until discharge. AL was defined as an anastomotic defect observed at reoperation, the presence of feculent fluid in a pelvic drain, or evidence of AL on computed tomography. The tool incorporated postoperative EWS and CRP levels for the accurate early detection of AL. Results: From postoperative days 3 to 7, the mean CRP level exceeded 200 mg/L in patients with AL and was under 200 mg/L in those without AL (P<0.05). From postoperative days 1 to 5, the mean EWS among patients with leakage exceeded 2, while scores were below 2 among those without leakage (P<0.05). Receiver operating characteristic curve analysis identified postoperative day 3 as the most predictive of early leakage, with cutoff values of 2.4 for EWS and 180 mg/L for CRP; this yielded an area under the curve of 0.87 (sensitivity, 90%; specificity, 70%). Conclusion: We propose using an EWS of 2.4 and a CRP level of 180 mg/L on postoperative day 3 following colon surgery with anastomosis as threshold values to prompt investigation and treatment of AL.

An evolutionarily conserved function of C-reactive protein is to prevent the formation of amyloid fibrils.

C-reactive protein (CRP) binds to phosphocholine (PCh)-containing substances and subsequently activates the complement system to eliminate the ligand. The PCh-binding function of CRP has been conserved throughout evolution from arthropods to humans. Human CRP, in its structurally altered conformation at acidic pH, also binds to amyloid-ß (Aß) and prevents the formation of Aß fibrils. It is unknown whether the Aß-binding function of CRP has also been evolutionarily conserved. The aim of this study was to determine whether CRP isolated from American horseshoe crab Limulus polyphemus was also anti-amyloidogenic and whether this function required structural alteration of Limulus CRP (Li-CRP). Two CRP species Li-CRP-I and Li-CRP-II were purified from hemolymph by employing PCh-affinity chromatography and phosphoethanolamine-affinity chromatography, respectively. Both Li-CRP-I and Li-CRP-II bound to immobilized Aß at physiological pH. Unlike human CRP, Li-CRP did not require any changes in its overall structure to bind to Aß. Both Li-CRP-I and Li-CRP-II bound to Aß in the fluid phase also and prevented the fibrillation of Aß. Additionally, ion-exchange chromatography of purified Li-CRP indicated that a variety of Li-CRP molecules of different subunit compositions were present in Limulus hemolymph, raising the possibility that the presence of various Li-CRP species in hemolymph facilitates the recognition of a range of proteins with differing amyloidogenicity. We conclude that the binding of CRP to Aß is an ancient function of CRP. In invertebrates, the Aß-binding function of CRP can protect the host from toxicity caused by amyloidogenic and pathogenic proteins. In humans, the Aß-binding function of CRP can protect against inflammatory diseases in which the host proteins are ectopically deposited on either host cells or foreign cells in an inflammatory milieu since immobilized proteins may expose Aß-like structures after deposition at places where they are not supposed to be.