BACKGROUND: The Finnish treatment guidelines for sore throat were updated in June 2020. The aim of this study was to determine how the publication of these guidelines affected the treatment of pediatric patients, particularly through the use of the Centor criteria, C-reactive protein tests, and microbiological testing in the diagnosis of Group A β-hemolytic streptococci tonsillitis.
METHODS: We conducted a retrospective single-center before-and-after cohort study in Finland from 2019 to 2022. We included all patients who visited the pediatric emergency department and were diagnosed with tonsillitis or pharyngitis.
RESULTS: We included 246 patients who were admitted before the guidelines were updated and 219 patients after. Only two patients in the after group had a Centor score reported in their patient records. Rapid antigen tests were administered to 231 patients (93.9%) before the update and 202 patients (92.2%) after (proportion difference of 1.7%, CI -3.0-6.6%). C-reactive protein was taken from 193 patients (78.5%) before the update and 189 patients (86.3%) after (proportion difference of 7.8%, CI 0.1-14.7%).
CONCLUSIONS: Centor scores were not used as recommended in the guidelines and did not impact the use of microbiological or C-reactive protein testing. More education and examining the preconceptions of health care personnel is required to implement the updated treatment guidelines in clinical practice.

OBJECTIVE: This study investigated whether adherence to the overall lifestyle recommendations in the American Cancer Society (ACS) guidelines on nutrition and physical activity for cancer survivors was associated with inflammation in breast cancer survivors.
METHODS: The study included 409 women who had undergone breast cancer surgery at least 1 year before enrollment. A generalized linear model was used to estimate the least square means and 95% confidence intervals of plasma levels of inflammatory markers according to lifestyle factors defined in terms of adherence to the ACS guidelines.
RESULTS: Higher overall adherence scores were associated with lower levels of high-sensitivity C-reactive protein (hs-CRP) (p for trend=0.015) and higher levels of adiponectin (p for trend=0.009). Similar significant associations of hs-CRP (p for trend= 0.004) and adiponectin (p for trend=0.010) levels were observed with the score for the body mass index (BMI) component of the adherence score. A higher diet component score was associated with a higher adiponectin level (p for trend=0.020), but there was no significant association for the physical activity component score.
CONCLUSIONS: The present study\'s findings suggest that maintaining a healthy lifestyle according to the ACS guidelines was associated with beneficial effects on inflammatory marker levels, especially hs-CRP and adiponectin, among breast cancer survivors. Among the 3 components of lifestyle guidelines, the BMI component exhibited the most similar tendency to the overall adherence score in relation to inflammatory indicators. Further prospective and intervention studies are needed to investigate longitudinal associations between lifestyle factors and inflammatory markers among breast cancer survivors.

BACKGROUND: Early laparoscopic cholecystectomy (ELC) is the standard treatment for acute cholecystitis (AC). However, predicting the difficulty of this procedure remains challenging. The present study aimed to develop an improved prediction model for surgical difficulty during ELC, surpassing the current Tokyo Guidelines 2018 (TG18) grading system.
METHODS: We analyzed data from 201 consecutive patients who underwent ELC for AC between 2019 and 2021. Surgical difficulty was defined as the failure to achieve the critical view of safety (non-CVS). We developed a scoring system by conducting multivariate analysis on demographics, symptoms, laboratory data, and radiographic findings. The predictive accuracy of our scoring system was compared to that of the TG18 grading system (Grade I vs. Grade II/III).
RESULTS: Through multivariate logistic regression analysis, a novel scoring system was formulated. This system incorporated preoperative C-reactive protein (CRP) values (≥5: 1 pt, ≥10: 2 pts, ≥15: 3 pts) and TG18 grading score (duration >72 h: 1 pt, image criteria for Grade II AC: 1 pt). Our model, a cutoff score of ≥3, exhibited a significantly elevated area under the curve (AUC) of 0.721 compared to the TG18 grading system alone (AUC 0.609) (p = 0.001).
CONCLUSIONS: Combining preoperative CRP values with TG18 grading criteria can enhance the accuracy of predicting intraoperative difficulty in ELC for AC.

Biomarkers are used frequently for evaluation and monitoring of patients with Crohn\'s disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD.
A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn\'s Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice.
The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 μg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence.
In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

OBJECTIVE: To assess the usefulness of the EP31-A-IR guideline published by the Clinical and Laboratory Standards Institute (CLSI) to perform the periodic verification of results\' comparability between several analyzers.
METHODS: Twenty-four biochemistry parameters that could be measured in different analyzers were included: albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, calcium, chloride, C-reactive protein, creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, total bilirubin, total cholesterol, total protein, triglycerides, urea and uric acid. In accordance with the EP31-A-IR guideline: (1) Patient samples were selected considering the concentration or activity of interest. (2) Acceptance criteria were established specifically for each concentration or activity level. A quality specification based on biological variation or on state of the art was selected, considering the analytical performance of the available technology. (3) Maximum allowable differences (MAD) between analyzers were calculated. (4) Measurements were performed as stated in appendix B of the guideline. (5) Maximum differences between analyzers were calculated. Results were considered comparable when the maximum difference was less than or equal to the MAD.
RESULTS: For the 24 parameters evaluated, any difference between analyzers exceeded the MAD.
CONCLUSIONS: The EP31-A-IR guideline proved to be useful for periodic verification of results\' comparability. However, it must be considered that, to be practicable, it may require to adjust the acceptance criteria in accordance to the analytical performance of the available technology; as well as the number of analytical measurements conforming to the laboratory resources.

This study evaluated the predictive value of different laboratory indicators for the severity of acute cholangitis (AC) according to the 2018 Tokyo Guidelines.
We enrolled consecutive patients with a diagnosis of AC from June 2016 to May 2021. Serum procalcitonin (PCT) and C-reactive protein (CRP) levels, white blood cell counts, the neutrophil-lymphocyte ratio, and the platelet-lymphocyte ratio (PLR) were compared according to the severity of AC.
In total, 293 patients were enrolled in this study (mild, n = 172; moderate, n = 68; severe, n = 53). In receiver operating characteristic analyses, CRP was the best biomarker for differentiating mild and moderate AC (area under the curve [AUC] 0.66, 95% confidence interval [CI] 0.58-0.74). PCT was the best biomarker for differentiating mild and severe AC (AUC 0.80, 95% CI 0.74-0.86). Blood culture was performed in 117 patients (39.93%), 53 of whom (45.30%) had positive results. Regarding blood culture positivity, PLR was most predictive (AUC 0.85, 95% CI 0.78-0.92).
PCT can be used as a reliable predictor of severe AC. CRP was most predictive of moderate AC, whereas PLR was most predictive of blood culture positivity.

Crohn\'s disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn\'s.
We conducted a retrospective study of patients with Crohn\'s after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test.
Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019).
Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.

The Joint Committee for Traceability in Laboratory Medicine (JCTLM) currently lists the secondary commutable certified reference material (CRM) ERM DA-474/IFCC (DA-474) \"C-Reactive Protein in Human Serum\" and two generic immunoassay-based method principles as the basis for implementing the metrological traceability of C-reactive protein (CRP) measurements by end-user measurement procedures used by medical laboratories. The current metrological traceability has produced well harmonized results for clinical samples among different end-user measurement procedures. New higher-order pure substance and secondary commutable CRMs have been nominated for listing by the JCTLM. However, the data supporting performance of these new candidate CRMs, including use of new mass spectrometry based candidate reference measurement procedures (RMPs), was not clear regarding the influence that introducing these new CRMs would have on the current well harmonized results achieved with the existing metrological traceability to DA-474. The clinically relevant CRP measurand in blood serum or plasma is a pentamer of identical subunits, which adds complexity to the application of higher-order CRMs and RMPs. The JCTLM convened a workshop in December 2022 to review the appropriate implementation of metrological traceability of CRP measurements. The workshop consensus was that the extent-of-equivalence data must include considerations about the impact of a new CRM when used for its intended purpose in the calibration hierarchies of existing end-user measuring systems; and that a new RMP must compare results with another existing well validated candidate RMP or with a globally available end-user measurement system.

Background and Objectives: Acute cholecystitis (AC) is a common surgical emergency. Recent evidence suggests that serum procalcitonin (PCT) is superior to leukocytosis and serum C-reactive protein in the diagnosis and severity stratification of acute infections. This review evaluates the role of PCT in AC diagnosis, severity stratification, and management. Materials and Methods: PubMed, Embase, and Scopus were searched from inception till 21 August 2022 for studies reporting the role of PCT in AC. A qualitative analysis of the existing literature was conducted. Results: Five articles, including 688 patients, were included. PCT ≤ 0.52 ng/mL had fair discriminative ability (Area under the curve (AUC) 0.721, p < 0.001) to differentiate Grade 1 from Grade 2-3 AC, and PCT > 0.8 ng/mL had good discriminatory ability to differentiate Grade 3 from 1-2 AC (AUC 0.813, p < 0.001). PCT cut-off ≥ 1.50 ng/mL predicted difficult laparoscopic cholecystectomy (sensitivity 91.3%, specificity 76.8%). The incidence of open conversion was higher with PCT ≥ 1 ng/mL (32.4% vs. 14.6%, p = 0.013). A PCT value of >0.09 ng/mL could predict major complications (defined as open conversion, mechanical ventilation, and death). Conclusions: Current evidence is plagued by the heterogeneity of small sample studies. Though PCT has some role in assessing severity and predicting difficult cholecystectomy, and postoperative complications in AC patients, more evidence is necessary to validate its use.

Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition.
This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept.
There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers.
This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological \'wear and tear\' and a further biomarker (PEF) that could usefully be included in future data collection.