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ZBTB16-associated NK cell alterations reveal shared immunometabolic signatures linking primary Sjögren's syndrome and type 1 diabetes mellitus.

BACKGROUND: Primary Sjögren's syndrome (pSS) and type 1 diabetes mellitus (T1DM) share immune-inflammatory features, yet conserved pathogenic signatures linking these autoimmune disorders remain incompletely understood. The present research sought to uncover common molecular markers and dissect the underlying immune-metabolic cross-talk underlying pSS and T1DM. METHODS: Gene expression profiles of patients with pSS and T1DM were retrieved from the Gene Expression Omnibus database, normalized, and corrected for batch effects prior to downstream analyses. Overlapping potential biomarkers were screened by integrating differential expression analysis, weighted gene co-expression network analysis and least absolute shrinkage and selection operator regression. Functional enrichment based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases was implemented to interpret gene biological properties, and a protein-protein interaction network was further established afterwards. Diagnostic performance was evaluated using receiver operating characteristic analysis. Experimental validation was conducted in non-obese diabetic (NOD) mice using quantitative PCR, immunohistochemistry, and flow cytometry. The CIBERSORT algorithm was adopted to quantify immune cell infiltration levels. RESULTS: ZBTB16 was identified as a shared hub biomarker in both pSS and T1DM and exhibited favorable diagnostic performance. Experimental validation confirmed significantly reduced ZBTB16 expression in peripheral blood mononuclear cells, salivary gland tissues, and pancreatic tissues of NOD mice. Gene Set Enrichment Analysis indicated that ZBTB16-associated signatures were enriched in mitochondrial-related processes, neuroactive ligand-receptor interactions, and ribosome-related pathways. Immune infiltration analysis revealed that resting natural killer (NK) cells were positively correlated with ZBTB16 expression in both diseases. Flow cytometric analysis further confirmed a reduced proportion of resting NK cells in peripheral blood of NOD mice, consistent with the CIBERSORT-based prediction. CONCLUSION: This study identifies ZBTB16 as a shared biomarker linking pSS and T1DM. Reduced resting NK-cell abundance was consistently observed in both computational and experimental analyses, and bioinformatic correlation analysis suggested a positive association with ZBTB16 expression. These findings provide evidence for shared molecular and immunological signatures underlying the two autoimmune disorders and support further investigation of the biological role and diagnostic value of ZBTB16 in pSS and T1DM.

Sjogren's Syndrome↗

Clinical value of vasodilator test with inhaled nitric oxide for predicting long-term response to oral vasodilators in pulmonary hypertension.

Acute vasodilator tests with prostacyclin (PGI2) or inhaled nitric oxide (iNO) are used to select patients with pulmonary arterial hypertension (PAH) who should be treated with oral vasodilators. The haemodynamic effects of PGI2 and iNO are different, and the limits for considering a vasodilator response as significant are controversial. The study was aimed to investigate the diagnostic performance of acute vasodilator testing with iNO and PGI2 in predicting the clinical outcome after 1 year treatment with oral vasodilators. Twenty-seven patients with severe PAH were studied. Nineteen patients were treated with oral vasodilators and their outcome after 1 year was qualified as favourable or unfavourable. The diagnostic performance of vasodilator tests in predicting this outcome was evaluated using receiver operating characteristics (ROC) curves. The acute effects of iNO and PGI2 on pulmonary artery pressure (PAP) were similar. By contrast, PGI2 produced more marked changes on cardiac output and pulmonary vascular resistance than iNO (P<0.05). The evolution at 1 year was favourable in 11 patients and unfavourable in 8. Patients with favourable evolution showed greater decrease of PAP with iNO than with PGI2 (P<0.05). The decrease of PAP with iNO had the greatest predictive value on the clinical outcome (area under ROC curve, 0.83). We conclude that in patients with PAH, acute vasodilator testing with iNO is preferable to PGI2 because it reflects more consistently the changes in pulmonary vascular tone. The acute decrease of PAP with iNO is the best predictor of the long-term response to oral vasodilator treatment.

Administration, Inhalation↗

Transcriptome Analysis and Experimental Validation of Palmitoylation- Related Biomarkers in Atherosclerosis.

INTRODUCTION: Protein palmitoylation contributes to membrane localisation, signal transduction, and cell-fate regulation. It is closely associated with lipid metabolic dysfunction, immune inflammation, and vascular remodelling in atherosclerosis (AS). However, key palmitoylation-related transcriptomic markers and their potential causal associations with AS remain incompletely defined. METHODS: The Gene Expression Omnibus (GEO) dataset GSE100927 was used as the training cohort, and GSE43292 was used as an external validation cohort. Differentially expressed genes were identified using limma and intersected with palmitoylation-related genes to obtain palmitoylation-related differentially expressed genes (PRDEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed using clusterProfiler. Two-sample Mendelian randomisation was used to evaluate potential causal relationships between characteristic genes and AS. Feature selection was conducted using random forest and support vector machine recursive feature elimination (SVM-RFE), and the overlapping genes selected by both methods were retained. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. A five-gene nomogram was constructed, and its clinical utility was evaluated using calibration curves and decision curve analysis (DCA). Gene set variation analysis (GSVA) was applied to compare pathway activity between high- and low-expression groups for each core gene. Single-cell analysis using Seurat and expression-based cell-cell communication analysis using CellChat were conducted with GSE159677, and upstream transcription factors were predicted using NetworkAnalyst. For in vivo validation, an AS model was established in ApoE&#x2078;/&#x2078; mice fed a high-fat diet, and aortic gene and protein expression were assessed by RT-qPCR and western blotting. RESULTS: In GSE100927, 51 PRDEGs were identified. GO and KEGG enrichment analyses highlighted pathways associated with regulation of monoatomic ion transport, sarcomere and myofibril organisation, and immune inflammation. Mendelian randomisation suggested a potential protective causal association between SLC7A7 and AS. By integrating MR with random forest and SVM-RFE feature selection, we prioritised five core genes: PLCB2, GMIP, NEXN, PLN, and SLC7A7. These genes showed good diagnostic performance in GSE43292. The resulting nomogram was well calibrated and demonstrated stable net benefit in decision curve and clinical impact curve analyses. Single-gene GSVA identified consistently activated pathways across multiple genes, including innate and adaptive immune recognition, calcium signalling and myocardial contraction/cardiomyopathy, extracellular matrix-receptor interaction, cell junction pathways, autophagy-lysosome pathways, and several metabolic programmes. At the single-cell level, PLCB2 and GMIP were predominantly expressed in T cells and macrophages, NEXN and PLN were enriched in vascular smooth muscle cells, and SLC7A7 was mainly expressed in macrophages. CellChat analysis indicated increased signals for immune-related ligand-receptor interactions. In ApoE&#x2078;/&#x2078; mice fed a high-fat diet, PLCB2, GMIP, and SLC7A7 were upregulated, whereas NEXN and PLN were downregulated; protein-level changes were concordant with the transcriptomic trends. DISCUSSION: These findings indicate that palmitoylation-related dysregulation in AS converges on immune inflammation, calcium signalling/contractile programmes, ECM remodelling, and autophagy-linked metabolism. The five-gene panel is supported by external validation, single-cell localisation to immune and vascular compartments, and concordant results in ApoE&#x2078;/&#x2078; mice. CONCLUSION: This study identified and validated five palmitoylation-related genes associated with AS. SLC7A7 showed a potential protective causal signal in MR analysis. The enriched pathway patterns linked these genes to immune inflammation, calcium signalling-contraction coupling, ECM remodelling, cell adhesion, and autophagy- associated metabolic reprogramming. The five-gene nomogram showed potential utility for diagnostic classification and decision support, nominating candidate biomarkers and pathway targets for AS molecular subtyping, diagnosis, and mechanistic investigation.

Atherosclerosis (AS)↗

Effect of contact media on the diagnostic quality of electrical resistance measurements for occlusal caries.

BACKGROUND: Electrical resistance measurements have been used for the diagnosis of occlusal caries. Both site and surface-specific techniques have been described, the latter more suited to clinical trials or epidemiological surveys. For surface-specific measurements the tooth is dried and a contact medium drawn along the fissure pattern to provide an electrical contact between a probe tip and the tooth surface. OBJECTIVES: Different contact media have been used and it was the aim of this study to investigate whether different contact media could influence the diagnostic accuracy and repeatability of surface-specific electrical resistance measurements. METHODS: Electrical resistance readings were taken on 99 molar teeth using saline, KY jelly, toothpaste or dental prophylaxis paste. Readings were repeated on 44 randomly selected teeth. The teeth were serially sectioned and visually examined to establish the deepest lesion if present. RESULTS: The Student t-test showed that there were statistically significant differences between readings taken with different contact media, with the exception of toothpaste and prophylaxis paste, where no difference was found. The strongest relationship between histology and resistance reading was achieved with KY jelly (r = 0.559). The optimum sensitivity and specificity achieved was 0.59 and 0.86, respectively (resistance cut-off 0.1 M(Omega)). ROC analysis showed that the diagnostic performance of saline was significantly inferior to the other contact media (P < 0.05). Limits of agreement were used to assess repeatability which were acceptable for all media except toothpaste. CONCLUSIONS: Differences were found between electronic resistance readings taken with different contact media. KY jelly was found to produce the best overall diagnostic performance and should be the standard material used for surface-specific measurements.

Dental Caries↗

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12&#x2011;lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12&#x2011;lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40&#xa0;ms (ST1), and 80&#xa0;ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r&#xa0;=&#xa0;0.89; V8: r&#xa0;=&#xa0;0.86; V9: r&#xa0;=&#xa0;0.83; all P&#xa0;<&#xa0;0.001). Bland-Altman analysis demonstrated minimal systematic bias (within &#xb1;0.004&#xa0;mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P&#xa0;=&#xa0;0.197). Using a 0.05&#xa0;mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12&#x2011;lead ECG.

Humans↗

Assessment of renal artery stenosis with CT angiography: usefulness of multiplanar reformation, quantitative stenosis measurements, and densitometric analysis of renal parenchymal enhancement as adjuncts to MIP film reading.

PURPOSE: Our goal was to evaluate CT angiography (CTA) in diagnosing renal artery stenosis (RAS). METHOD: Thirty-seven patients underwent digital subtraction angiography (DSA) and CTA. Visual interpretation and stenosis measurements were made from maximum intensity projection (MIP) and multiplanar reformation (MPR) laser film prints of 78 renal arteries. RESULTS: Visual reading of MIP films showed good diagnostic performance by receiver operating characteristic curve analysis, with 100% sensitivity in the assessment of > or = 50% RAS but only 42-54% specificity (overall accuracy 60-75%). The false-positive rate decreased when MIP and MPR films were read together, but the excess of false negatives among the calcified lesions disabled this diagnostic algorithm. Combining visual interpretation of MIP films with quantitative measurements yielded the best diagnostic performance: 92% sensitivity, 80% specificity, and 84% overall accuracy. Renal cortical enhancement measurements (26 patients) had 81% overall accuracy. CONCLUSION: The overall accuracy of CTA with MIP film reading can be enhanced by quantitative measurement of stenosis or reviewing MPRs.

Adult↗

Detection of caries with conventional digital imaging and tuned aperture computed tomography using CRT monitor and laptop displays.

OBJECTIVE: The purpose of this study was to compare the diagnostic performance of conventional digital images and tuned aperture computed tomography (TACT) slices in caries detection through use of cathode-ray tube monitor and laptop displays. STUDY DESIGN: Forty-two extracted posterior teeth were mounted and imaged with a direct digital radiography system. Conventional digital bitewing projections and TACT slices were acquired. Images were viewed on a high-resolution cathode-ray tube monitor and on an active-matrix laptop display. Eight observers assessed caries status of occlusal and proximal surfaces of the teeth using all combinations of image and display modality. Observers' assessments were compared with the results of histologic examination of tooth sections. Possible differences in receiver operating characteristic curve areas among displays, image modalities, observers, and surfaces were analyzed by means of analysis of variance. RESULTS: There was no statistically significant difference between the diagnostic performances provided by the cathode-ray tube monitor and laptop displays in caries detection (P = .588). In addition, the performances of digital images and TACT slices were not significantly different (P = .843). CONCLUSIONS: Modern active-matrix laptop displays provide diagnostic quality for caries detection comparable to that obtainable with cathode-ray tube monitors.

Analysis of Variance↗

Early brain natriuretic peptide increase reflects acute myocardial ischemia in patients with ongoing chest pain.

BACKGROUND: Plasma brain natriuretic peptide levels increase during acute ischemic events. In this study we tested the diagnostic performance of brain natriuretic peptide measurements in the detection of acute myocardial ischemia. METHODS: Blood brain natriuretic peptide was measured in 101 patients with ongoing chest pain but no heart failure or an ST-segment elevation myocardial infarction on arrival at the emergency department (baseline) and at 2 and 6 h later. After diagnostic testing and 1-month follow-up for ischemia, patients were classified as either ischemic or non-ischemic. RESULTS: In the ischemic group median (25th, 75th percentiles) brain natriuretic peptide values (pg/ml) were 122 (20, 349) at baseline, 116 (36, 347) at 2 h, increasing to 148 (52, 428) at 6 h (p<0.001 vs. baseline). Non-ischemic patients had 12 (5, 32) at baseline, 9 (6, 30) at 2 h, and 13 (5, 29) at 6 h (p<0.001 vs. corresponding values of the ischemic group). Receiver operator characteristic curves were constructed for brain natriuretic peptide values at baseline 2 and 6 h and for the increase of peptide levels from baseline to 6 h. All areas under curve indicated a significant diagnostic ability for the detection of ischemia. The 6-h measurement had better diagnostic performance than baseline and 2-h measurements. The subgroup of ischemic patients without myocardial necrosis also had higher brain natriuretic peptide values and could thus be discriminated from non-ischemic subjects. CONCLUSIONS: Brain natriuretic peptide values may detect acute myocardial ischemia in patients with ongoing chest pain but without ST-segment elevation, and distinguish ischemic patients from those with pain of non-ischemic origin.

Acute Disease↗

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples&#xa0;were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.&#xa0; Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans↗

[Diagnostic efficacy of fine needle aspiration biopsy in patients with thyroid nodular disease. Analysis of 510 cases].

INTRODUCTION: The prevalence of palpable thyroid nodules in the general population is 4%-7%. Although most are benign, 5% are carcinomas. This study aimed to assess the efficacy of fine needle aspiration biopsy (FNAB) of thyroid nodules to diagnose malignancy and know the benefit of repeating the FNAB in the same nodule. PATIENTS AND METHODS: A total of 510 patients (431 women and 79 men; mean age [standard deviation]: 47.6 [14.3] years) with surgery due to thyroid nodular condition between 1989 and 2002 and who had at least one FNAB prior to the surgery were studied. RESULTS: The first FNAB was benign in 312 patients (61.2%), malignant in 38 (7.5%), suspicious or indeterminate in 97 (19%) and insufficient in 63 (12.4%). Sensitivity and specificity in the first FNAB for malignancy diagnosis was 76% and 84%, respectively. Successive FNABs had a moderate concordance and significance. However, repeating the puncture did not improve diagnostic performance, since sensitive increased (84%), but specificity worsened (79%) and the area under the ROC curve was similar. In the group with suspicious or indeterminate FNAB, histology was benign in 70% and malignant in 30%. CONCLUSIONS: FNAB sensitivity and specificity for diagnosis of malignancy in thyroid nodules are high. Repetition of puncture on the same nodule does not improve diagnostic performance of the cytology. Among patients with suspicious FNAB, there is a high proportion of malignancy, which makes surgery necessary in these cases.

Adolescent↗

Translating single-cell RNA sequencing into monocyte direct leukocyte subpopulation-transcript abundance assay ratio-based biomarkers (IFI27/PSAP or IFI27/CTSS) for clinical detection of viral infection.

A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.

Humans↗

Differential diagnosis of dementia: a comparison between the expert system EVINCE and clinicians.

The diagnostic performance of the expert system EVINCE was compared with that of 85 clinicians in diagnosing 10 patients suspected of suffering from dementia. A multidisciplinary expert committee provided a standard diagnosis as reference for comparison. The results showed that the syndrome and etiologic diagnoses made by EVINCE were in very close agreement with those of the expert committee and that the diagnostic performance of EVINCE was better than that of the average clinician. The present findings indicate that expert systems, especially those within the realm of complex multidimensional medical problems, could be a valuable aid in medical practice.

Aged↗

Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-(iodine 123)-L-alpha-methyltyrosine SPECT.

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging scores with that of 3-(iodine 123)-L-alpha-methyltyrosine ((123)I-IMT) single photon emission computed tomography (SPECT) in the noninvasive grading of untreated gliomas. MATERIALS AND METHODS: The study comprised 15 patients with low-grade gliomas (grades I-II, according to World Health Organization criteria) and 33 patients with high-grade gliomas (grades III-IV). The lesions were evaluated by using an MR imaging score based on nine criteria. The (123)I-IMT uptake was quantified as the ratio between the amino acid uptake in the tumor and that in the contralateral hemisphere. To test for potentially significant differences in diagnostic performance between contrast material-enhanced MR imaging and (123)I-IMT SPECT, binormal receiver operating characteristic curves were fitted to the data and compared by using the area test. RESULTS: The accuracy of MR imaging in the noninvasive grading of untreated gliomas was higher than that of (123)I-IMT SPECT (88% vs 79%). However, the difference in diagnostic performance was not significant on the basis of findings at receiver operating characteristic analysis (P >.2). Neither MR imaging nor (123)I-IMT SPECT allowed differentiation between high-grade gliomas (grades III and IV). CONCLUSION: Although (123)I-IMT uptake is significantly higher in high-grade gliomas than in low-grade gliomas, the performance of (123)I-IMT SPECT adds little to the accuracy of determining tumor grade when MR imaging is performed.

Adult↗

Latex specific IgE: performance characteristics of the IMMULITE 2000 3gAllergy assay compared with skin testing.

BACKGROUND: In the absence of a US Food and Drug Administration (FDA)-cleared latex skin testing reagent, in vitro tests remain important for the diagnosis of latex allergy. OBJECTIVE: To evaluate the performance characteristics of IMMULITE 2000 3gAllergy (Immulite), a third-generation, FDA-cleared, continuous random-access immunoanalyzer, for the quantification of latex specific IgE. METHODS: Stored serum samples (N = 201) from patients classified as having positive or negative latex puncture skin test results were measured for latex specific IgE levels using Immulite, and these data were compared with historical results from 3 second-generation, FDA-cleared IgE antilatex assays (AlaSTAT [Ala], AutoCAP [CAP], and HY*TEC enzyme immunoassay [HT]). RESULTS: The diagnostic performances of the CAP, Ala, and Immulite assays (> or = 0.35 kU/L cutoff value) were equivalent in sensitivity and specificity (P > .05). The HT assay (> or = 0.05 kU/L cutoff value) was more sensitive and less specific (P < .05). Immulite (> or = 0.10 kU/L cutoff value) had greater sensitivity than Ala and CAP and greater specificity than HT (P < .05 for both). Diagnostic efficiency was greater for Immulite than for CAP, Ala, and HT (P < .05). CONCLUSIONS: The Immulite system is superior in diagnostic performance, especially at the 0.10 kU/L or greater cutoff level, for the diagnosis of latex allergy compared with older, second-generation assays. Immulite still misclassifies 15.5% of puncture skin test-positive individuals as negative for latex specific IgE. Compared with second-generation assays, Immulite represents a technological advance, with enhanced speed and less operator intervention.

Humans↗

Immunodiagnosis of schistosomiasis mansoni in a low endemic area in Surinam by determination of the circulating antigens CAA and CCA.

We evaluated the applicability of circulating antigen detection in serum and urine for the diagnosis of Schistosoma infections in a low endemic area. In total 389 individuals from Saramacca (Surinam) participated in the survey. Stool samples were examined using the Kato method, while circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were determined by highly specific monoclonal antibody-based ELISA's. Also schistosome specific IgM antibodies were measured by the indirect immunofluorescence assay, but the diagnostic performance of this test was found to be poor in this population. S. mansoni eggs were found in 29% of the examined cases, while CAA and CCA could be demonstrated in 23% and 17% of the serum samples and in 3% and 28% of the urine samples, respectively. Forty three percent of the study population was positive in at least one of these diagnostic assays, indicating that each individual test misses a substantial part of the subjects with an active infection. In most positive cases, intensities of infection were very low. As 204 individuals participated in all screening assays, diagnostic performance of each test was evaluated in this sub-population. The highest sensitivities were achieved with the urine-CCA assay and the parasitological examination, detecting 59 and 58 out of the 107 cases with an active infection, respectively. The serum-CAA assay detected 47 positive cases. Our results demonstrate that determination of circulating antigens, especially CCA in urine and CAA in serum, provides information additional to the parasitological examination, for the assessment of prevalence and intensity of Schistosoma infection in low endemic areas.

Adolescent↗

Validation of image quality in full-field digital mammography: is the replacement of wet by dry laser printers justified?

OBJECTIVE: Dry laser printers have replaced wet laser printers to produce hard copies of high-resolution digital images, primarily because of environmental concerns. However, no scientific research data have been published that compare the image quality of dry and wet laser printers in full-field digital mammography (FFDM). This study questions the image quality of these printers. MATERIALS AND METHODS: Objective image quality parameters of both printers were evaluated using a standardized printer test image, i.e., optical density and detectability of specific image elements (lines, curves, and shapes). Furthermore, mammograms of 129 patients with different breast tissue composition patterns were imaged with both printers. A total of 1806 subjective image quality parameters (brightness, contrast, and detail detection of anatomic structures), the detectability of breast lesions, as well as diagnostic performance according to the BI-RADS classification were evaluated. In addition, the presence of film artifacts was investigated. RESULTS: Optical density values were equal for the dry and the wet laser printer. Detection of specific image elements on the printer test image was not different. Ratings of subjective image quality parameters were equal, as were the detectability of breast lesions and the diagnostic performance. Dry laser printer images showed more artifacts (164 versus 27). However, these artifacts did not influence image quality. CONCLUSION: Based on the evidence of objective and subjective parameters, a dry laser printer equals the image quality of a wet laser printer in FFDM. Therefore, not only for reasons of environmental preference, the replacement of wet laser printers by dry laser printers in FFDM is justified.

Adult↗

Effect of heart rate on T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial. METHODS AND RESULTS: This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 +/- 0.7 microV, 1.6 +/- 1.9 microV, and 2.4 +/- 2.1 microV in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%. CONCLUSION: These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.

Cardiac Pacing, Artificial↗

Hierarchical integration of mNGS, PCR, and other conventional methods for precision TB diagnostics.

UNLABELLED: This study systematically compared the diagnostic accuracy of seven assays for detecting the Mycobacterium tuberculosis complex, including metagenomic next-generation sequencing (mNGS), droplet digital polymerase chain reaction, real-time quantitative polymerase chain reaction, EasyNAT MTC, GeneXpert MTB/RIF, interferon-gamma release assay (IGRA), and acid&#x2012;fast staining (AFS). We try to select appropriate combinations of tuberculosis (TB) detection methods for regions with varying levels of medical resources, based on sensitivity, cost-effectiveness, and operational feasibility. A retrospective analysis was conducted on 141 samples collected from patients with suspected active TB at The First Affiliated Hospital of Sun Yat-sen University between April 2022 and April 2024. Among these samples, there were 100 cases assigned to the case group and 41 cases to the control group, based on the tuberculosis diagnostic criteria. Historical data for Xpert, IGRA, and AFS were collected, and parallel experiments using mNGS, droplet digital PCR (ddPCR), real-time quantitative polymerase chain reaction (RT-qPCR), and EasyNAT were conducted on all samples. Diagnostic performance was evaluated by comparing it with the final clinical diagnoses. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic (ROC) curve analysis were conducted, along with DeLong tests for statistical comparison. Compared with the final clinical diagnosis, mNGS demonstrated the highest sensitivity (100%), followed by IGRA (79.2%), EasyNAT (79.1%), RT-qPCR (78.0%), ddPCR (75.8%), Xpert (75.3%), and AFS (16.7%). The specificity was 100% for both Xpert and AFS, followed by ddPCR (97.6%), RT-qPCR (95.1%), EasyNAT (92.7%), IGRA (72.7%), and mNGS (75.6%). ROC analysis revealed a significantly greater area under the ROC curve for mNGS (0.878) than for ddPCR (0.817, P = 0.031). DeLong tests revealed statistically significant differences in diagnostic performance between mNGS and ddPCR (P < 0.05) and between IGRA and AFS (P < 0.01). mNGS uniquely identified the pathogens involved in co-infection and quantified pathogen-specific sequencing reads. Through a comprehensive evaluation of the diagnostic efficacy, cost-effectiveness, and timeliness of tuberculosis detection methods, we propose corresponding combinations of TB testing approaches for regions with different healthcare resources. For undeveloped regions with limited resources, a combination of AFS +EasyNAT + chest X-ray is recommended. Primary care facilities may additionally employ IGRA + RT-qPCR. Intermediate-level hospitals can incorporate Xpert MTB/RIF for drug resistance testing, while tertiary hospitals or specialized centers should, on the basis of these fundamental tests, utilize mNGS for diagnosis and ddPCR for therapeutic monitoring in patients with complex mixed infections. IMPORTANCE: This study is the first to comprehensively evaluate the diagnostic efficacy, cost-effectiveness, and timeliness of seven TB detection methods in a single-center cohort. Our findings provide actionable solutions for optimizing TB diagnostics in diverse healthcare ecosystems, aligning with the WHO's End TB Strategy to ensure equitable access to rapid diagnostics.

Humans↗