OBJECTIVE: Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD) score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD score and PTP to cardiologists was superior to PTP alone in limiting testing.
METHODS: At six Danish and Swedish outpatient clinics, patients with suspected new-onset CCS were randomised to either standard diagnostic examination (SDE) with PTP, or SDE plus CAD score, and cardiologists provided with corresponding recommended diagnostic flowcharts. The primary endpoint was cumulative number of diagnostic tests at one year and key safety endpoint major adverse cardiac events (MACE).
RESULTS: In total 2008 patients (46% male, median age 63 years) were randomised from October 2019 to September 2022. When randomised to CAD score (n=1002), it was successfully measured in 94.5%. Overall, 13.5% had PTP ≤5%, and 39.5% had CAD score ≤20. Testing was deferred in 22% with no differences in diagnostic tests between groups (p for superiority =0.56). In the PTP ≤5% subgroup, the proportion with deferred testing increased from 28% to 52% (p<0.001). Overall MACE was 2.4 per 100 person-years. Non-inferiority regarding safety was established, absolute risk difference 0.4% (95% CI -1.85 to 1.06) (p for non-inferiority = 0.005). No differences were seen in angina-related health status or quality of life.
CONCLUSIONS: The implementation strategy of providing cardiologists with a CAD score alongside SDE did not reduce testing overall but indicated a possible role in patients with low CCS likelihood. Further strategies are warranted to address resistance to modifying diagnostic pathways in this patient population.

BACKGROUND: Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether increased levels of Troponin I (TnI) and C-reactive protein (CRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) is not well described. We assessed the association between 1) TnI and 2) CRP with quantified coronary plaque burden, luminal diameter stenosis, and HRP in patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred for coronary computed tomography angiography (CCTA).
METHODS: The CCTA from 1615 patients were analyzed using a semiautomatic software for coronary artery plaque characterization. Patients with high TnI (>6 ​ng/L) and high CRP (>2 ​mg/L) were identified. Associations of TnI and CRP with plaque burden, stenosis (≥50% luminal diameter stenosis on CCTA), and HRP were investigated.
RESULTS: TnI and CRP were both positively correlated with total plaque burden (TnI rs ​= ​0.14, p ​< ​0.001; CRP rs ​= ​0.08, p ​< ​0.001). In multivariate logistic regression analyses, high TnI was associated with stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p ​= ​0.034), the presence of HRP (OR 1.79, 95% CI: 1.17-2.74, p ​= ​0.008), and the subtypes of HRP; low attenuation plaque (OR 1.93, 95% CI: 1.24-3.00, p ​= ​0.003), and positive remodeling (OR 1.51, 95% CI: 1.07-2.13, p ​= ​0.018). For CRP, only stenosis and napkin ring sign correlated significantly.
CONCLUSIONS: In patients with suspected CAD, TnI and CRP are associated with HRP features. These findings may suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and affect patient management.
RESULTS:
UNASSIGNED: NCT02264717.

OBJECTIVE: The pre-test probability (PTP) model for obstructive coronary artery disease (CAD) was updated in 2019 by the European Society of Cardiology (ESC). To our knowledge, this model was never externally validated in a population with a high incidence of CAD. The aim of this study is to validate the new PTP ESC model in our population, which has a high CAD incidence, and to compare it with the previous PTP ESC model from 2013.
METHODS: We retrospectively analysed 1294 symptomatic patients with suspected CAD referred to our centre between 2015 and 2019. In all patients, the PTP score was calculated based on age, gender, and symptoms according to the ESC model from 2013 (2013-ESC-PTP) and 2019 (2019-ESC-PTP). All patients underwent invasive coronary angiography (ICA).
RESULTS: Of the 1294 patients, obstructive CAD was diagnosed in 533 patients (41.2%). The 2019-ESC-PTP model categorised significantly more patients into the low probability group (PTP < 15%) than the 2013-ESC-PTP model (39.8% vs. 5.6%, p < 0.001). Obstructive CAD prevalence was underestimated using 2019-ESC-PTP at all PTP levels (calibration intercept 1.15, calibration slope 0.96). The 2013-ESC-PTP overestimated obstructive CAD prevalence (calibration intercept -0.24, calibration slope 0.73). The discrimination measured with an area under the curve was similar for both models, indicating moderate accuracy of the models.
CONCLUSIONS: In high-risk Serbian population, both the 2013 and 2019 ESC-PTP models had moderate accuracy in diagnosing CAD, with the 2019-ESC-PTP underestimating the prevalence of CAD and the 2013-ESC-PTP overestimating it. Further studies are warranted to establish PTP models for high-risk countries.

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

The role of exercise electrocardiography (ECG) in the investigation of stable chest pain has been questioned. The American Heart Association guidelines suggest the use of exercise ECG in patients with stable chest pain and low pre-test probability (PTP) of significant coronary artery disease, while the European Society of Cardiology Guidelines does not. This retrospective observational study aimed to assess the usefulness of exercise ECG in the low-PTP population with stable chest pain. We reviewed the medical records for all outpatient exercise ECGs conducted because of stable chest pain at the Department of Medicine and Emergency, Sahlgrenska University Hospital, Mölndal, Sweden, during 2016-2018. The identified patients were categorized in low-, intermediate-, or high-risk pre-test probability of significant coronary artery disease. All low-PTP patients were followed for one year post investigation for the incidence of acute coronary syndrome and all-cause mortality. Thus, 505 patients (mean age 60 years, 56% women) with low PTP were included in the study. Only four patients (0.6%) experienced incident myocardial infarction (three patients) or all-cause mortality (one patient). The negative predictive value of exercise ECG was 99.7%, and the positive predictive value was 28.6%. In this low-PTP population, exercise ECG yields a good negative predictive value and a poor positive predictive value.

BACKGROUND: The clinical features and predictors of Clostridioides difficile infection overlap with many conditions.
OBJECTIVE: We performed a systematic review to evaluate the diagnostic utility of clinical features (clinical examination, risk factors, laboratory tests, and radiographic findings) associated with C. difficile.
METHODS: Systematic review and meta-analysis of diagnostic features for C. difficile.
METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched up to September 2021.
METHODS: Studies that reported clinical features of C. difficile, a valid reference standard test for confirming diagnosis of C. difficile, and a comparison among patients with a positive and negative test result.
METHODS: Adult and paediatric patients across diverse clinical settings.
RESULTS: Sensitivity, specificity, likelihood ratios.
UNASSIGNED: Stool nucleic acid amplification tests, enzyme immunoassays, cell cytotoxicity assay, and stool toxigenic culture.
UNASSIGNED: Rational Clinical Examination Series and Quality Assessment of Diagnostic Accuracy Studies-2.
UNASSIGNED: Univariate and bivariate analyses.
RESULTS: We screened 11 231 articles of which 40 were included, enabling the evaluation of 66 features for their diagnostic utility for C. difficile (10 clinical examination findings, 4 laboratory tests, 10 radiographic findings, prior exposure to 13 antibiotic types, and 29 clinical risk factors). Of the ten features identified on clinical examination, none were significantly clinically associated with increased likelihood of C. difficile infection. Some features that increased likelihood of C. difficile infection were stool leukocytes (LR+ 5.31, 95% CI 3.29-8.56) and hospital admission in the prior 3 months (LR+ 2.14, 95% CI 1.48-3.11). Several radiographic findings also strongly increased the likelihood of C. difficile infection like ascites (LR+ 2.91, 95% CI 1.89-4.49).
CONCLUSIONS: There is limited utility of bedside clinical examination alone in detecting C. difficile infection. Accurate diagnosis of C. difficile infection requires thoughtful clinical assessment for interpretation of microbiologic testing in all suspected cases.

A correct and prompt diagnosis of coronary artery disease (CAD) is a crucial component of disease management to reduce the risk of death and improve the quality of life in patients with CAD. Currently, the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC) guidelines recommend selecting an appropriate pre-diagnosis test for an individual patient according to the CAD probability. The purpose of this study was to develop a practical pre-test probability (PTP) for obstructive CAD in patients with chest pain using machine learning (ML); also, the performance of ML-PTP for CAD is compared to the final result of coronary angiography (CAG).
We used a database from a single-center, prospective, all-comer registry designed to reflect real-world practice since 2004. All subjects underwent invasive CAG at Korea University Guro Hospital in Seoul, South Korea. We used logistic regression algorithms, random forest (RF), supporting vector machine, and K-nearest neighbor classification for the ML models. The dataset was divided into two consecutive sets according to the registration period to validate the ML models. ML training for PTP and internal validation used the first dataset registered between 2004 and 2012 (8631 patients). The second dataset registered between 2013 and 2014 (1546 patients) was used for external validation. The primary endpoint was obstructive CAD. Obstructive CAD was defined as having a stenosis diameter of >70% on the quantitative CAG of the main epicardial coronary artery.
We derived an ML-based model consisting of three different models according to the subject used to obtain the information, such as the patient himself (dataset 1), the community\'s first medical center (dataset 2), and doctors (dataset 3). The performance range of the ML-PTP models as the non-invasive test had C-statistics of 0.795 to 0.984 compared to the result of invasive testing via CAG in patients with chest pain. The training ML-PTP models were adjusted to have 99% sensitivity for CAD so as not to miss actual CAD patients. In the testing dataset, the best accuracy of the ML-PTP model was 45.7% using dataset 1, 47.2% using dataset 2, and 92.8% using dataset 3 and the RF algorithm. The CAD prediction sensitivity was 99.0%, 99.0%, and 98.0%, respectively.
We successfully developed a high-performance model of ML-PTP for CAD which is expected to reduce the need for non-invasive tests in chest pain. However, since this PTP model is derived from data of a single medical center, multicenter verification is required to use it as a PTP recommended by the major American societies and the ESC.

UNASSIGNED: Current early risk stratification of coronary artery disease (CAD) consists of pre-test probability scoring such as the 2019 ESC guidelines on chronic coronary syndromes (ESC2019), which has low specificity and thus rule-out capacity. A newer clinical risk factor model (risk factor-weighted clinical likelihood, RF-CL) showed significantly improved rule-out capacity over the ESC2019 model. The aim of the current study was to investigate if the addition of acoustic features to the RF-CL model could improve the rule-out potential of the best performing clinical risk factor models.
UNASSIGNED: Four studies with heart sound recordings from 2222 patients were pooled and distributed into two data sets: training and test. From a feature bank of 40 acoustic features, a forward-selection technique was used to select three features that were added to the RF-CL model. Using a cutoff of 5% predicted risk of CAD, the developed acoustic-weighted clinical likelihood (A-CL) model showed significantly (P < 0.05) higher specificity of 48.6% than the RF-CL model (specificity of 41.5%) and ESC 2019 model (specificity of 6.9%) while having the same sensitivity of 84.9% as the RF-CL model. Area under the curve of the receiver operating characteristic for the three models was 72.5% for ESC2019, 76.7% for RF-CL, and 79.5% for A-CL.
UNASSIGNED: The proposed A-CL model offers significantly improved rule-out capacity over the ESC2019 model and showed better overall performance than the RF-CL model. The addition of acoustic features to the RF-CL model was shown to significantly improve early risk stratification of symptomatic patients suspected of having stable CAD.

Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]).
Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records.
The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up.
ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.

BACKGROUND: Gram staining is a classic but standard and essential procedure for the prompt selection of appropriate antibiotics in an emergency setting. Even in the era of sophisticated medicine with technically developed machinery, it is not uncommon that a classic procedure such as Gram staining is the most efficient for assisting physicians in making therapeutic decisions in a timely fashion.
METHODS: A 65-year-old Asian man with alcoholic cirrhosis complicated by esophageal varices was brought to the emergency division of Saga Medical School Hospital in early August, complaining of severe pain, redness, swelling, and purpura of the lower extremities. On physical examination he appeared in a critically ill condition suggestive of deep-seated soft tissue infection, raising a pre-test probability of streptococci, staphylococci, Vibrio sp., or Aeromonas sp. as a causative pathogen. A characteristic of his residency in an estuarine area is that raw seafood ingestion, as documented in this patient prior to the current admission, predisposes those who have a chronic liver disease to a life-threatening Vibrio vulnificus infection. Given the pathognomonic clinical features suggestive of necrotizing fasciitis, our immediate attempt was to narrow down the differential list of candidate pathogens by obtaining clinical specimens for microbiological investigation, thus inquiring about the post-test probability of the causative pathogen. The Gram stain of the small amount of discharge from the test incision of the affected lesion detected Gram-negative rods morphologically compatible with V. vulnificus. After two sets of blood culture, intravenous meropenem and minocycline were immediately administered before the patient underwent emergency surgical debridement. The next day, both blood culture and wound culture retrieved Gram-negative rods, which were subsequently identified as V. vulnificus by mass spectrometry, matrix-assisted laser desorption/ionization. The antibiotics were switched to intravenous ceftriaxone and minocycline.
CONCLUSIONS: The pre-test probability of V. vulnificus infection was further validated by on-site Gram staining in the emergency division. This case report highlights the significance of a classic procedure.