Diagnostic accuracy of urinary antigen tests for legionellosis: A systematic review and meta-analysis

BackgroundUrinary antigen tests (UATs) have been used for the early detection of legionellosis and have demonstrated moderate sensitivity and high specificity. However, the most recent systematic review and meta-analysis published in 2009 evaluated the accuracy of UATs; since then, UAT accuracy may have changed owing to advances and developments in UAT technology and epidemiological changes in the frequency of Legionella species that cause legionellosis. Therefore, this systematic review and meta-analysis aimed to update the accuracy of UATs for legionellosis among patients with suspected pneumonia.MethodsOverall, 1326 studies were screened, 21 of which fulfilled the eligibility criteria for quality assessment and meta-analysis. Data from 5772 patients, including 1368 (23.7%) with the target condition (i.e., suspected legionellosis), were included in the analysis. The overall quality of the included studies, which was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear.ResultsThe calculated pooled sensitivity and specificity were 0.79 (95% confidence interval [CI], 0.71–0.85) and 1.00 (95% CI, 0.99–1.00), respectively. Subpopulation analysis revealed that the accuracy of UATs for sensitivity and specificity for Legionella pneumophilia serogroup 1 was 0.86 (95% CI, 0.78–0.91) and 1.00 (95% CI, 0.99–1.00), respectively.ConclusionsThis study demonstrated that the sensitivity and specificity of UATs were moderate and high, respectively, which is comparable to the results reported in 2009. Therefore, UATs may be a useful method for the early detection of legionellosis caused by Legionella pneumophila serogroup 1.Clinical trial registrationThe review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000041080).     

Evaluation of olfactory dysfunction to estimate the presence of eosinophilic chronic rhinosinusitis in patients with asthma

BackgroundEosinophilic chronic rhinosinusitis (ECRS) is often complicated by asthma and can be difficult to diagnose. This study aimed to clarify the usefulness of the self-administered odor questionnaire (SAOQ) and visual analog scale (VAS) to identify olfactory disorders in patients with asthma.MethodsThis retrospective study was conducted on patients with asthma who were referred to the Otolaryngology clinic between May and September 2018. The treatment step of asthma, asthma control test (ACT), pulmonary function test, peripheral blood eosinophils, and fractional exhaled nitric oxide (FeNO) were analyzed. ECRS was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study score. Olfactory dysfunction was evaluated using the SAOQ and VAS for olfactory disorders.ResultsThe study included 56 patients (18 males and 38 females), who were divided into two groups; those with ECRS (n = 18) and those without ECRS (n = 38). Age, sex, treatment step, ACT score, and pulmonary function were not significantly different between the groups. The ECRS group had a significantly higher FeNO value (89.1 ppb vs. 39.1 ppb) and a significantly lower SAOQ score (40.1% vs. 96.1%). The area under the receiver operating characteristic curve for the efficacy of ECRS diagnosis was 0.88, 0.889, 0.799, and 0.757 for SAOQ, VAS, blood eosinophil count, and FeNO, respectively.ConclusionThe SAOQ and VAS scores were useful tools that presented similar results to the blood eosinophil count and FeNO, and may help to improve the diagnosis of ECRS in patients with asthma.     

Clinical Deployment of Explainable Artificial Intelligence of SPECT for Diagnosis of Coronary Artery Disease

BackgroundExplainable artificial intelligence (AI) can be integrated within standard clinical software to facilitate the acceptance of the diagnostic findings during clinical interpretation.ObjectivesThis study sought to develop and evaluate a novel, general purpose, explainable deep learning model (coronary artery disease–deep learning [CAD-DL]) for the detection of obstructive CAD following single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).MethodsA total of 3,578 patients with suspected CAD undergoing SPECT MPI and invasive coronary angiography within a 6-month interval from 9 centers were studied. CAD-DL computes the probability of obstructive CAD from stress myocardial perfusion, wall motion, and wall thickening maps, as well as left ventricular volumes, age, and sex. Myocardial regions contributing to the CAD-DL prediction are highlighted to explain the findings to the physician. A clinical prototype was integrated using a standard clinical workstation. Diagnostic performance by CAD-DL was compared to automated quantitative total perfusion deficit (TPD) and reader diagnosis.ResultsIn total, 2,247 patients (63%) had obstructive CAD. In 10-fold repeated testing, the area under the receiver-operating characteristic curve (AUC) (95% CI) was higher according to CAD-DL (AUC: 0.83 [95% CI: 0.82-0.85]) than stress TPD (AUC: 0.78 [95% CI: 0.77-0.80]) or reader diagnosis (AUC: 0.71 [95% CI: 0.69-0.72]; P < 0.0001 for both). In external testing, the AUC in 555 patients was higher according to CAD-DL (AUC: 0.80 [95% CI: 0.76-0.84]) than stress TPD (AUC: 0.73 [95% CI: 0.69-0.77]) or reader diagnosis (AUC: 0.65 [95% CI: 0.61-0.69]; P < 0.001 for all). The present model can be integrated within standard clinical software and generates results rapidly (<12 seconds on a standard clinical workstation) and therefore could readily be incorporated into a typical clinical workflow.ConclusionsThe deep-learning model significantly surpasses the diagnostic accuracy of standard quantitative analysis and clinical visual reading for MPI. Explainable artificial intelligence can be integrated within standard clinical software to facilitate acceptance of artificial intelligence diagnosis of CAD following MPI.     

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease

ObjectivesIn this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundCT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies.MethodsAt 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics.ResultsICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively.ConclusionsDynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795)     

Early Diagnosis of Myocardial Infarction With Point-of-Care High-Sensitivity Cardiac Troponin I

BackgroundUntil now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms.ObjectivesThis study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI).MethodsThis study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue–specific 0/1-h algorithm.ResultsMI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication.ConclusionsThe POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587)     

Lactated Ringer's vs normal saline for acute pancreatitis: An updated systematic review and meta-analysis

IntroductionRecent studies have evaluated and compared the efficacy of normal saline (NS) and lactated Ringer's (LR) in reducing the severity of acute pancreatitis (AP) and improving outcomes such as length of stay, the occurrence of the systemic inflammatory response syndrome (SIRS), ICU admission and mortality. We performed an updated systematic review and meta-analysis of the available studies to assess the impact of these fluids on outcomes secondary to AP.MethodsWe systematically searched the following databases: PubMed/Medline, Embase, Cochrane, and Web of Science through February 8th, 2021 to include randomized controlled trials (RCTs) and cohort studies. Random effects model using DerSimonian-Laird approach was employed and risk ratios (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated for binary and continuous outcomes, respectively.Results6 studies (4 RCTs and 2 cohort studies) with 549 (230 in LR and 319 in NS) were included. The overall mortality (RR: 0.73, CI: 0.31–1.69) and SIRS at 24 h (RR: 0.69, CI: 0.32–1.51) was not significantly different. The overall ICU admission was lower in LR group compared to NS group (RR: 0.43, CI: 0.22–0.84). Subgroup analysis of RCTs demonstrated lower length of hospital stay for LR group compared to NS group (MD: 0.77 days, CI: 1.44 –0.09 days).ConclusionOur study demonstrated that LR improved outcomes (ICU admission and length of stay) in patients with AP compared to NS. There was no difference in rate of SIRS development and mortality between LR and NS treatments.     

Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

BackgroundWe recently reported that severe asthma patients with frequent exacerbations showed high blood eosinophil counts (Eo) and fractions of exhaled nitric oxide (FeNO) compared with non-exacerbators. However, we did not determine exact cutoff values related to exacerbation. The aim of this study was to determine the cutoff values of Eo and FeNO that could be related to the exacerbation of severe asthma. We also aimed to confirm the clinical utility of Th2 markers related to exacerbation.MethodsThis study included 105 severe asthma patients who completed a three-year follow-up of a severe asthma cohort study, including smokers. Three Th2 markers were selected, viz., Eo, FeNO, and positive atopic status. Regarding Eo and FeNO, we determined the cutoff values for the definition of “positive” Th2 features using receiver operating characteristic curve analyses, based on the comparisons between frequent exacerbators and other patients.ResultsThe cutoff values for positive Th2 features were Eo ≥ 250 cells/μL and FeNO ≥31 ppb. Sixteen patients (15.2%) had no Th2 features, 40 (38.1%) had one, 25 (23.8%) had two, and 24 (22.9%) had three. A high number of positive Th2 features was significantly associated with exacerbation frequencies over three years (p < 0.05). Similarly, compared to patients with one or no Th2 features, those with three Th2 features had a significantly higher probability of having more than one exacerbation (p < 0.05).ConclusionsThe cutoff values determined in the current analysis were good predictors of future exacerbations in severe asthma patients.     

Diagnostic Accuracy of Cardiovascular Magnetic Resonance for Cardiac Transplant Rejection: A Meta-Analysis

ObjectivesThe aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection.BackgroundEndomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection.MethodsPubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling–based summary receiver-operating characteristic curves were calculated.ResultsOf 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling–based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values <0.001 for T1, ECV, and LGE vs T2).ConclusionsT2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.     

Automated Analysis of Doppler Echocardiographic Videos as a Screening Tool for Valvular Heart Diseases

ObjectivesThis study sought to develop a deep learning (DL) framework to automatically analyze echocardiographic videos for the presence of valvular heart diseases (VHDs).BackgroundAlthough advances in DL have been applied to the interpretation of echocardiograms, such techniques have not been reported for interpretation of color Doppler videos for diagnosing VHDs.MethodsThe authors developed a 3-stage DL framework for automatic screening of echocardiographic videos for mitral stenosis (MS), mitral regurgitation (MR), aortic stenosis (AS), and aortic regurgitation (AR) that classifies echocardiographic views, detects the presence of VHDs, and, when present, quantifies key metrics related to VHD severities. The algorithm was trained (n = 1,335), validated (n = 311), and tested (n = 434) using retrospectively selected studies from 5 hospitals. A prospectively collected set of 1,374 consecutive echocardiograms served as a real-world test data set.ResultsDisease classification accuracy was high, with areas under the curve of 0.99 (95% CI: 0.97-0.99) for MS; 0.88 (95% CI: 0.86-0.90) for MR; 0.97 (95% CI: 0.95-0.99) for AS; and 0.90 (95% CI: 0.88-0.92) for AR in the prospective test data set. The limits of agreement (LOA) between the DL algorithm and physician estimates of metrics of valve lesion severities compared to the LOAs between 2 experienced physicians spanned from ?0.60 to 0.77 cm² vs ?0.48 to 0.44 cm² for MV area; from ?0.27 to 0.25 vs ?0.23 to 0.08 for MR jet area/left atrial area; from ?0.86 to 0.52 m/s vs ?0.48 to 0.54 m/s for peak aortic valve blood flow velocity (V_max); from ?10.6 to 9.5 mm Hg vs ?10.2 to 4.9 mm Hg for average peak aortic valve gradient; and from ?0.39 to 0.32 vs ?0.31 to 0.32 for AR jet width/left ventricular outflow tract diameter.ConclusionsThe proposed deep learning algorithm has the potential to automate and increase efficiency of the clinical workflow for screening echocardiographic images for the presence of VHDs and for quantifying metrics of disease severity.     

Uric acid and blood pressure in NHANES dated from 2009 to 2018: A cross-sectional research

Background and aimThis study aimed to explore the association between uric acid (UA) and blood pressure (BP), included systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP).Methods and resultsA cross-sectional study with 22,478 individuals aged from 12 to 80 years (11,443 males and 11,035 females) from the National Health and Nutrition Examination Survey (NHANES) was performed. Multiple linear regression analysis was applied to explore the relationship between UA and BP, Stratified analysis and interaction were performed based on gender, race, age, body mass index (BMI), and alcohol consumption. Significantly positively associations were presented in SBP(β, 0.84 [95% CI, 0.67, 1.00]), DBP(β, 0.23 [95% CI, 0.11, 0.36]), and MAP (β, 0.43 [95% CI, 0.31, 0.55]). The associations were much more stronger between UA and SBP in females (β, 1.04 [95% CI, 0.78, 1.30], p for interaction 0.0003), black group (β, 1.17 [95% CI, 0.77, 1.56], p for interaction 0.0296), age (≥45) group (β, 1.03 [95% CI, 0.68, 1.39], p for interaction <0.0001) and drinking group (β, 0.98 [95% CI, 0.75, 1.21], p for interaction <0.0001). The significant interactions were found between UA and DBP in gender and alcohol consumption (all p for interaction <0.05). In terms of MAP, the significant interactions were found in race, age, and alcohol consumption (all p for interaction <0.05).ConclusionsA significantly positively association was found between UA and BP, including SBP, DBP, and MAP.     

Cell-free DNA promoter hypermethylation as a diagnostic marker for pancreatic ductal adenocarcinoma – An external validation study

BackgroundWe recently identified a diagnostic prediction model based on promoter hypermethylation of eight selected genes in plasma cell-free (cf) DNA, which showed promising results as a diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to validate this biomarker profile in an external patient cohort and examine any additional effect of serum CA 19-9.MethodsPatients with PDAC (n = 346, stage I-IV) and chronic pancreatitis (n = 25) were included. Methylation-specific PCR of a 28-gene panel was performed on serum cfDNA samples. The previously developed diagnostic prediction model (age>65 years, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) was validated alone and in combination with serum CA 19-9 in this external patient cohort.ResultsPatients with PDAC had a higher number of hypermethylated genes (mean 8.11, 95% CI 7.70–8.52) than patients with chronic pancreatitis (mean 5.60, 95% CI 4.42–6.78, p = 0.011). Validation of the diagnostic prediction model yielded an AUC of 0.77 (95% CI 0.69–0.84). The combination of serum CA 19-9 and our test had an AUC of 0.93 (95% CI 0.89–0.96) in the primary study and 0.85 (95% CI 0.79–0.91) in the validation study.ConclusionIn this validation study, PDAC was associated with a higher number of hypermethylated genes in serum cfDNA than chronic pancreatitis. Our diagnostic test was superior to the predictive value of serum CA 19-9 alone in both the primary and the validation study. The combination of our test with CA 19-9 may serve as a clinically useful diagnostic biomarker for PDAC.     

Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

ObjectivesThe aim of this study was to assess the diagnostic performances of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion.BackgroundPPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of ¹⁸F-FDG PET/CT remains poorly studied in PPVE.MethodsA retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent ¹⁸F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of ¹⁸F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study.ResultsA total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). ¹⁸F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE.ConclusionsUsing ¹⁸F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.     

Detection of Hypertrophic Cardiomyopathy Using a Convolutional Neural Network-Enabled Electrocardiogram

BackgroundHypertrophic cardiomyopathy (HCM) is an uncommon but important cause of sudden cardiac death.ObjectivesThis study sought to develop an artificial intelligence approach for the detection of HCM based on 12-lead electrocardiography (ECG).MethodsA convolutional neural network (CNN) was trained and validated using digital 12-lead ECG from 2,448 patients with a verified HCM diagnosis and 51,153 non-HCM age- and sex-matched control subjects. The ability of the CNN to detect HCM was then tested on a different dataset of 612 HCM and 12,788 control subjects.ResultsIn the combined datasets, mean age was 54.8 ± 15.9 years for the HCM group and 57.5 ± 15.5 years for the control group. After training and validation, the area under the curve (AUC) of the CNN in the validation dataset was 0.95 (95% confidence interval [CI]: 0.94 to 0.97) at the optimal probability threshold of 11% for having HCM. When applying this probability threshold to the testing dataset, the CNN’s AUC was 0.96 (95% CI: 0.95 to 0.96) with sensitivity 87% and specificity 90%. In subgroup analyses, the AUC was 0.95 (95% CI: 0.94 to 0.97) among patients with left ventricular hypertrophy by ECG criteria and 0.95 (95% CI: 0.90 to 1.00) among patients with a normal ECG. The model performed particularly well in younger patients (sensitivity 95%, specificity 92%). In patients with HCM with and without sarcomeric mutations, the model-derived median probabilities for having HCM were 97% and 96%, respectively.ConclusionsECG-based detection of HCM by an artificial intelligence algorithm can be achieved with high diagnostic performance, particularly in younger patients. This model requires further refinement and external validation, but it may hold promise for HCM screening.     

Factors associated with the development of oral allergy syndrome: A retrospective questionnaire survey of Japanese university students

BackgroundOral allergy syndrome (OAS) is an IgE-mediated food allergy. Ingestion of causative antigens leads to the development of local symptoms such as numbness of the oral mucosa in most cases and anaphylaxis in a few cases. The prevalence of OAS including in healthy people has not been investigated. Thus, we conducted a questionnaire survey of Japanese university students.MethodsWe conducted a cross-sectional study of 2688 first-year students using a questionnaire survey in marksheet format and examined the epidemiological characteristics of OAS.ResultsOnly 2.7% of students were aware of the term “oral allergy syndrome”. A total of 143 (5.3%) students had OAS. There were significant associations between OAS and other allergic diseases including allergic rhinitis (AR) (OR: 3.8, 95% CI: 2.7–5.5), atopic dermatitis (AD) (OR: 4.6, 95%CI: 3.3–6.6), and bronchial asthma (BA) (OR: 3.0, 95%CI: 2.0–4.5). The onset age of OAS showed bimodal peaks at 0 and 10 years, and the latter peak coincided with the peak onset age of AR.ConclusionsAwareness of OAS was low in our study, which will make it difficult to treat properly and prevent its development. This survey confirmed the association between OAS and other allergic diseases, especially AR, which suggests that OAS is involved in the allergic march. A novel finding was that sensitization to antigens for OAS occurred around the same time as sensitization to antigens for AR. These results will help medical professionals diagnose OAS and develop lifestyle guidelines to prevent OAS-related symptoms such as anaphylaxis.     

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Background & AimsPatients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.MethodsWe performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months).ResultsBased on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02).ConclusionsIn patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.     

Stress-Only Adenosine CMR Improves Diagnostic Yield in Stable Symptomatic Patients With Coronary Artery Calcium

ObjectivesThis study assessed whether adenosine stress-only perfusion cardiac magnetic resonance (CMR) following a positive coronary artery calcium (CAC) score improved the diagnostic yield of invasive coronary angiography (CAG) in patients with stable chest pain. The study also established the association between positive CAC scores and stress-induced myocardial ischemia.BackgroundThe diagnostic yield of catheterization among patients with suspected coronary artery disease (CAD) is low. Improved patient selection and diagnostic testing are necessary. The CAC score can minimize unnecessary diagnostic testing, and in low-risk patients, normal CMR results have a high negative predictive value. Less comprehensive protocols may be sufficient to guide further work-up.MethodsA total of 642 consecutive patients (mean age: 63 years; 50% women) with stable chest pain and CAC scores of >0 who were referred for CMR were enrolled. Patients with a perfusion defect were subsequently examined by CAG. Patients were followed up for 1 year. Outcome was obstructive CAD.ResultsObstructive CAD was present in 12% of patients. For CAD diagnosis, the sensitivity of adenosine CMR was 90.9% (95% confidence interval [CI]: 88.7 to 93.1), specificity was 98.7% (95% CI: 97.9 to 99.6), positive predictive value was 92.0% (95% CI: 89.8 to 94.1), and negative predictive value was 98.6% (95% CI: 97.6 to 99.5). A CAC score between 0.1 and 100 without typical angina was associated with obstructive CAD in only 3% of patients. Patients with nonanginal chest pain and a CAC score ≥400 had obstructive CAD (16%).ConclusionsStress-only adenosine CMR had high diagnostic accuracy and served as an efficient gatekeeper to CAG in stable patients with a CAC score >0. Patients with CAC scores between 0.1 and 100 could be deferred from further testing in the absence of clinical features that suggested high risk. However, in patients with CAC score ≥400, functional testing should be indicated, regardless of the type of chest pain.     

Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure

BackgroundMore data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required.ObjectivesThe purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history.MethodsIn the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted.ResultsAt baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19).ConclusionsBased on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048)     

Statins and risk of thromboembolism: A meta-regression to disentangle the efficacy-to-effectiveness gap using observational and trial evidence

Background and aimsMeta-analyses of randomised controlled trials (RCTs) and observational studies indicate a lower risk of venous thromboembolism (VTE) associated with statin treatment. We aimed to compare the effect of statin therapy in these two settings and to identify and quantify potential factors to explain statin efficacy and effectiveness.Methods and resultsWe electronically searched on December 11th, 2018, articles reporting on first VTE events in RCTs (statin vs placebo) and in observational studies (participants exposed vs non-exposed to statin). We performed Knapp-Hartung random-effect meta-analyses to calculate pooled relative risks (RRs) of VTE events associated with statin treatment, separately for RCTs and observational studies; and estimated the ratio of the relative risk (RRR) comparing RCTs and observational studies using meta-regressions, progressively adjusted for study-level characteristics. Twenty-one RCTs (115,107 participants; 959 events) and 8 observational studies (2,898,096 participants; 19,671 events) were included. Pooled RRs for RCTs and observational studies were 0.82 (95% confidence interval (CI): 0.67–1.00; I² 19.2%) and 0.60 (95% CI: 0.42–0.86; I² 86.3%), respectively. In meta-regressions, the unadjusted RRR indicated a nonsignificant 23% smaller benefit in RCTs (RRR 0.77; 95% CI: 0.52–1.13); accounting for age, sex, geographical region, and duration of follow-up, there was a sensible change of the RRR which resulted 0.30 (95% CI: 0.13–0.68).ConclusionDifferences in the characteristics between patients included in RCTs and those in observational studies may account for the differential effect of statins in preventing VTE in the two settings.