Similar Specificity Research Articles

Clinical Utility of a CT-based AI Prognostic Model for Segmentectomy in Non-Small Cell Lung Cancer.

Background Currently, no tool exists for risk stratification in patients undergoing segmentectomy for non-small cell lung cancer (NSCLC). Purpose To develop and validate a deep learning (DL) prognostic model using preoperative CT scans and clinical and radiologic information for risk stratification in patients with clinical stage IA NSCLC undergoing segmentectomy. Materials and Methods In this single-center retrospective study, transfer learning of a pretrained model was performed for survival prediction in patients with clinical stage IA NSCLC who underwent lobectomy from January 2008 to March 2017. The internal set was divided into training, validation, and testing sets based on the assignments from the pretraining set. The model was tested on an independent test set of patients with clinical stage IA NSCLC who underwent segmentectomy from January 2010 to December 2017. Its prognostic performance was analyzed using the time-dependent area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for freedom from recurrence (FFR) at 2 and 4 years and lung cancer-specific survival and overall survival at 4 and 6 years. The model sensitivity and specificity were compared with those of the Japan Clinical Oncology Group (JCOG) eligibility criteria for sublobar resection. Results The pretraining set included 1756 patients. Transfer learning was performed in an internal set of 730 patients (median age, 63 years [IQR, 56-70 years]; 366 male), and the segmentectomy test set included 222 patients (median age, 65 years [IQR, 58-71 years]; 114 male). The model performance for 2-year FFR was as follows: AUC, 0.86 (95% CI: 0.76, 0.96); sensitivity, 87.4% (7.17 of 8.21 patients; 95% CI: 59.4, 100); and specificity, 66.7% (136 of 204 patients; 95% CI: 60.2, 72.8). The model showed higher sensitivity for FFR than the JCOG criteria (87.4% vs 37.6% [3.08 of 8.21 patients], P = .02), with similar specificity. Conclusion The CT-based DL model identified patients at high risk among those with clinical stage IA NSCLC who underwent segmentectomy, outperforming the JCOG criteria. © RSNA, 2024 Supplemental material is available for this article.

Development and Validation of a Genotypic Assay to Quantify CXCR4- and CCR5-Tropic Human Immunodeficiency Virus Type-1 (HIV-1) Populations and a Comparison to Trofile®.

HIV-1 typically infects cells via the CD4 receptor and CCR5 or CXCR4 co-receptors. Maraviroc is a CCR5-specific viral entry inhibitor; knowledge of viral co-receptor specificity is important prior to usage. We developed and validated an economical V3-env Illumina-based assay to detect and quantify the frequency of viruses utilizing each co-receptor. Plasma from 54 HIV+ participants (subtype B) was tested. The viral template cDNA was generated from plasma RNA with unique molecular identifiers (UMIs). The sequences were aligned and collapsed by the UMIs with a custom bioinformatics pipeline. Co-receptor usage, determined by codon analysis and online phenotype predictors PSSM and Geno2pheno, were compared to existing Trofile® data. The cost of V3-UMI was tallied. The sequences interpreted by Geno2pheno using the most conservative cut-off, a 2% false-positive-rate (FPR), predicted CXCR4 usage with the greatest sensitivity (76%) and specificity (100%); PSSM and codon analysis had similar sensitivity and lower specificity. Discordant Trofile® and genotypic results were more common when participants had specimens from different dates analyzed by either assay. V3-UMI reagents cost USD$62/specimen. A batch of ≤20 specimens required 5 h of technical time across 1.5 days. V3-UMI predicts HIV tropism at a sensitivity and specificity similar to those of Trofile®, is relatively inexpensive, and could be performed by most central laboratories. The adoption of V3-UMI could expand HIV drug therapeutic options in lower-resource settings that currently do not have access to phenotypic HIV tropism testing.

Abstract 1881: Screening of Rac1 and Cdc42 inhibitors as anti-metastatic compounds

Abstract Metastasis is responsible for >90% of cancer-related deaths and is a key cause of failure of cancer therapy. The development of effective targeted therapy to prevent and treat metastasis has been challenging. Homologous Rho GTPases Rac and Cdc42 are viable metastasis targets because they have a crucial role in the signaling pathways that regulate cell survival, proliferation, and migration, so dysregulation of these proteins leads to cancer progression and metastasis of diverse cancer types. Therefore, targeting these regulatory proteins results in anticancer and antimetastatic activity, as observed with our dual Rac/Cdc42 inhibitor, MBQ-167, in triple-negative breast cancer. MBQ-167 has an IC50 of ~100nM for Rac and Cdc42 activation inhibition and a GI50 of 130nM. MBQ-167 inhibits the binding of guanine nucleotides to Rac and Cdc42 with similar efficacy. The purpose of this study was to identify MBQ-167 derivatives with similar or greater efficacy and specificity, with a range of inhibitory mechanisms, that may be specific to the different guanine nucleotide exchange factors expressed in distinct cancer cell types. Currently, over 30 different compounds with potential Rac1 and Cdc42 inhibitory activity are being evaluated. So far, some of the evaluated compounds have shown comparable GI50 values to MBQ-167 in metastatic breast cancer cell lines. From this screening, CPV-337 was selected as a compound with a GI50 of ~55nM and ~70% Rac activation inhibition at 50nM, therefore being 2X more effective than our leading compound MBQ-167. However, evaluation of CPV-337 in the viability of the MCF-10 non-tumorigenic epithelial cell line demonstrated a GI50 of ~63nM, which is similar to that of breast cancer cells. Therefore, CPV-337 may have cytotoxic effects on breast cancer. We are continuing to screen the library of MBQ-167 derivatives in breast, pancreatic, lung, and prostate cancer cell lines. Citation Format: Jessica Colón González, María C. Santa María Fuentes, Cornelis Vlaar, Suranganie Dharmawardhane. Screening of Rac1 and Cdc42 inhibitors as anti-metastatic compounds [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1881.

Detection of pathogenic Leptospira with rapid extraction followed by recombinase polymerase amplification (RPA) and quantitative polymerase chain reaction (qPCR) assay-A comprehensive study from Sri Lanka.

Leptospirosis is the most widespread zoonosis in the world. The disease is more prevalent in tropical regions where the majority of developing countries are located. Leptospirosis is considered a protean manifestation zoonosis with severity of the disease ranging from a mild febrile illness to a severe and life-threatening illness. Clinical symptoms of leptospirosis overlap with other tropical febrile illnesses. Early, rapid, and definitive diagnosis is important for effective patient management. Since Polymerase Chain Reaction (PCR)-based assays are not readily available in most clinical settings, there is a need for an affordable, simple, and rapid diagnostic test. Quantitative PCR (qPCR) and Recombinase Polymerase Amplification (RPA) were implemented at the Faculty of Medicine, University of Kelaniya, and a prospective study to evaluate RPA for diagnosis of acute phase of leptospirosis was conducted. Results indicate that RPA and qPCR were positive in 81% (98/121) of the total positive and acute clinical samples. Of the 81 positive MAT confirmed patients 60 (74%) and 53 (65%) were positive with qPCR and RPA respectively. Retrospective evaluation revealed a high diagnostic accuracy (sensitivity-70% and specificity-87%) of RPA compared to MAT as the reference gold standard. Results further suggest that there is no significant difference between the two assays, qPCR and RPA-SwiftX (P = 0.40). Laboratory procedures for the extraction and detection by qPCR in the laboratory have been optimized to obtain results within 6 hours. However, the RPA-SwiftX method under field conditions took 35 minutes. The RPA-SwiftX method could replace the qPCR which shows similar sensitivity and specificity. Therefore, RPA established under the current study presents a powerful tool for the early and rapid diagnosis of leptospirosis at point-of-care.

An ELISA Using Synthetic Mycolic Acid-Based Antigens with DIVA Potential for Diagnosing Johne's Disease in Cattle.

Ante-mortem diagnosis of Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is normally achieved through faecal culture, PCR, or serological tests, but agreement as to which samples are positive for Johne's disease is often poor and sensitivities are low, particularly in early-stage infections. The potential solution: Mycobacterial cells contain very complex characteristic mixtures of mycolic acid derivatives that elicit antibodies during infection; this has been used to detect infections in humans. Here, we explore its application in providing an assay differentiating infected from vaccinated animals (DIVA assay) for Johne's disease in cattle. Antibody responses to different classes of mycolic acid derivatives were measured using ELISA for serum from cattle positive for MAP by both faecal PCR and commercial serum ELISA, or just by PCR, and from animals from herds with no history of Johne's disease, bovine tuberculosis reactors, BCG-vaccinated, BCG-vaccinated and M. bovis-infected, and Gudair-vaccinated animals. The best-performing antigens, ZAM295 and ST123-the latter a molecule present in the cells of MAP but not of Mycobacterium bovis-achieved a sensitivity of 75% and 62.5%, respectively, for serum from animals positive by both faecal PCR and a commercial MAP serum ELISA, at a specificity of 94% compared to 80 no-history negatives. Combining the results of separate assays with two antigens (ST123 and JRRR121) increased the sensitivity/specificity to 75/97.5%. At the same cut-offs, animals vaccinated with Gudair or BCG vaccines and bTB reactors showed a similar specificity. The specificity in BCG-vaccinated but M. bovis-infected animals dropped to 85%. Combining the results of two antigens gave a sensitivity/specificity of 37.5/97.5% for the full set of 80 PCR-positive samples, detecting 30 positives compared 16 for IDEXX. Serum ELISA using synthetic lipids distinguishes effectively between MAP-negative cattle samples and those positive by both PCR and a commercial MAP serodiagnostic, without interference by Gudair or BCG vaccination. It identified almost twice as many PCR positives as the commercial serodiagnostic, offering the possibility of earlier detection of infection.

Prediction of severity of dengue infection in children based on hepatic involvement.

To assess the spectrum of hepatic involvement in children with dengue fever (DF) and prediction of severity of dengue infection by early detection of elevated liver enzymes. This prospective observational study was conducted at a tertiary care hospital from June 2019 to September 2019. Children admitted with DF were included. Severity of DF was graded as dengue without warning sign (DNWS), with warning sign (DWS), and severe dengue fever (SDF) according to WHO criteria. Liver injury (LI) was defined as alanine aminotransferase (ALT) more than upper limit of normal irrespective of sex. Of 190 children (male, 109) with DF, 60 had DNWS, 49 had DWS, and 81 had SDF. A total of 100 children (52.6%) had LI. The distribution of hepatic involvement spectrum involves hepatomegaly (26.3%), hepatic tenderness (25.2%), features of acute liver failure (1.5%), raised level of ALT (52.6%), raised level of aspartateaminotransferase (AST) (65.8%), prolonged prothrombin time (7.3%), and reduced level of serum albumin (44.7%) in children. Of them, 5.8% and 6.8% of children had >tenfold increase in ALT and AST values. The degree of liver function derangement significantly (P < 0.05) increased with DF severity. In our study, ALT at 422 IU/L (10 times upper limit of normal [ULN]) and AST 689 IU/L (17 times ULN) had similar sensitivity and specificity as WHO recommended cutoff of 1000 IU/L (25 times of ULN) to detect SDF. ALT ≥10 times and AST ≥17 times of ULN are as sensitive as ≥25 times (as recommended by WHO) to detect SDF.

A comparison study of 68gallium-prostate-specific membrane antigen positron emission tomography-computed tomography and multiparametric magnetic resonance imaging for locoregional staging of prostate cancer.

Prostate cancer (PCa) is the most common malignancy in men aged 50 years and older and the second cause of cancer death among men. Accurate staging of PCa preoperatively is of high importance for treatment decisions and patient management. Conventional imaging modalities (ultrasound, computed tomography [CT], and magnetic resonance imaging) are inaccurate for the staging of PCa. Newer modality multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan show promising results for the staging of PCa. Only fewer studies are available for comparison of these modalities with histopathology as reference. The objective of our study is to evaluate the diagnostic accuracy of independent 68gallium PSMA (68Ga-PSMA) PET-CT compared with mpMRI for preoperative staging of PCa, using histopathology as the reference standard. From August 2021 to December 2022, 30 patients of biopsy-proven PCa were prospectively enrolled as per eligibility criteria. Preoperatively, 68Ga-PSMA PET scan and mpMRI were done in all the patients. Extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node metastasis (LNM) were investigated separately. Subsequently, the patients underwent robotic-assisted radical prostatectomy with bilateral pelvic lymph node dissection. mpMRI prostate was more sensitive (66.66%) but less specific than PSMA PET-CT (55.55%) for ECE. mpMRI and PSMA PET-CT both had similar sensitivity (83.3%) and specificity (87.5%) for SVI. PSMA PET-CT was more sensitive (85.71%) and specific (95.6%) than mpMRI prostate (62.5% and 91.30%, respectively) for LNM. PSMA PET-CT is more specific for the detection of ECE and more sensitive and specific for the detection of LNM than mpMRI, and similar for the detection of SVI. mpMRI provides only local staging, while PSMA PET-CT provides information about local, regional, and distal staging. Overall, PSMA PET-CT is superior to mpMRI for locoregional staging of PCa.

A new and promiscuous α/β hydrolase from Acinetobacter tandoii DSM 14970 T inactivates the mycotoxin ochratoxin A

The presence of ochratoxin A (OTA) in food and feed represents a serious concern since it raises severe health implications. Bacterial strains of the Acinetobacter genus hydrolyse the amide bond of OTA yielding non-toxic OTα and L-β-phenylalanine; in particular, the carboxypeptidase PJ15_1540 from Acinetobacter sp. neg1 has been identified as an OTA-degrading enzyme. Here, we describe the ability to transform OTA of cell-free protein extracts from Acinetobacter tandoii DSM 14970 T, a strain isolated from sludge plants, and also report on the finding of a new and promiscuous α/β hydrolase (ABH), with close homologs highly distributed within the Acinetobacter genus. ABH from A. tandoii (AtABH) exhibited amidase activity against OTA and OTB mycotoxins, as well as against several carboxypeptidase substrates. The predicted structure of AtABH reveals an α/β hydrolase core composed of a parallel, six-stranded β-sheet, with a large cap domain similar to the marine esterase EprEst. Further biochemical analyses of AtABH reveal that it is an efficient esterase with a similar specificity profile as EprEst. Molecular docking studies rendered a consistent OTA-binding mode. We proposed a potential procedure for preparing new OTA-degrading enzymes starting from promiscuous α/β hydrolases based on our results.Key points• AtABH is a promiscuous αβ hydrolase with both esterase and amidohydrolase activities• AtABH hydrolyses the amide bond of ochratoxin A rendering nontoxic OTα• Promiscuous αβ hydrolases are a possible source of new OTA-degrading enzymes

Systematic review and meta-analysis of diagnostic test accuracy of ST-segment elevation for acute coronary occlusion

ObjectiveTo evaluate the diagnostic sensitivity and specificity of ST-segment elevation on a 12‑lead ECG in detecting ACO across any coronary artery, challenging the current STEMI-NSTEMI paradigm. MethodsStudies from MEDLINE and Scopus (2012−2023) comparing ECG findings with coronary angiograms were systematically reviewed and analyzed following PRISMA-DTA guidelines. QUADAS-2 assessed the risk of bias. Study selectionStudies included focused on AMI patients and provided data enabling the construction of contingency tables for sensitivity and specificity calculation, excluding those with non-ACS conditions, outdated STEMI criteria, or a specific focus on bundle branch blocks or other complex diagnoses. Data were extracted systematically and pooled test accuracy estimates were computed using MetaDTA software, employing bivariate analyses for within- and between-study variation. The primary outcomes measured were the sensitivity and specificity of ST-segment elevation in detecting ACO. ResultsThree studies with 23,704 participants were included. The pooled sensitivity of ST-segment elevation for detecting ACO was 43.6% (95% CI: 34.7%–52.9%), indicating that over half of ACO cases may not exhibit ST-segment elevation. The specificity was 96.5% (95% CI: 91.2%–98.7%). Additional analysis using the OMI-NOMI strategy showed improved sensitivity (78.1%, 95% CI: 62.7%–88.3%) while maintaining similar specificity (94.4%, 95% CI: 88.6%–97.3%). ConclusionThe findings reveal a significant diagnostic gap in the current STEMI-NSTEMI paradigm, with over half of ACO cases potentially lacking ST-segment elevation. The OMI-NOMI strategy could offer an improved diagnostic approach. The high heterogeneity and limited number of studies necessitate cautious interpretation and further research in diverse settings.

Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

Distance examination of livestock with drones - an effective method for assessing health and welfare.

Distance examination is an important part of veterinary investigation into ruminant herd health and welfare. The Department of Primary Industries and Regional Development (DPIRD) explored the use of drones to conduct assessments of the health and welfare status of sheep and cattle. Three methods of distance examination were compared comprising observations; from a vehicle, a "micro" category drone and a "very small" category drone. The disturbance and behavioural reactions caused by the methods were compared. Assessments of adverse health and welfare conditions by each method were compared to observations made at yarding. The preferred method was the use of the very small drone which had the best sensitivity for detection of conditions potentially associated with adverse health or welfare and the best optics at a distance that did not disturb the animals. The optics of the very small drone enabled distance examination without disturbance in both cattle and sheep. Cattle were more sensitive to the presence of the drones than sheep. The micro drone was unable to approach cattle close enough to allow undisturbed distance examination. All methods had similar specificity, however, sensitivity varied markedly. The very small drone had the best sensitivity 86% which was statistically greater than the micro drone (44%, P = 0.05) and better than the vehicle observations, which had sensitivity of 77% (not statistically significant). The selection of an appropriate drone model is essential for accurate distance examination. Distance examination of livestock with drones of suitable optic quality and resolution represents an effective method for assessing animal health and welfare.

Performance of BD Onclarity HPV assay on FLOQSwabs vaginal self-samples.

Human papillomavirus (HPV) testing on self-collected vaginal samples has been shown to improve women's participation to cervical cancer screening programs, particularly in regions with limited access to health care. Nevertheless, the introduction of self-sampling in cervical cancer screening programs requires prior clinical validation of the HPV assay in combination with a self-sample collection device, including also the laboratory workflow and automation required for high-throughput testing in screening. In this study, the performance of BD Onclarity HPV on FLOQSwab-collected vaginal self-samples has been compared to clinician-taken liquid-based cytology samples, to detect high-grade cervical intraepithelial neoplasia using two high-throughput platforms, BD Viper LT and BD COR. The study findings have shown a similar performance of BD Onclarity on testing self-collected samples, confirming the validation of the proposed pre-analytical and analytical protocols for their use in cervical cancer screening programs based on self-collected vaginal samples.

Increased Attenuation of Intestinal Contents at CT Indicates Bowel Necrosis in Closed-Loop Small Bowel Obstruction.

Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.

Abstract WP190: Comparison of Collateral Score to ASPECTS to Exclude "Very Large" Infarct Core Volumes in Anterior Circulation Large Vessel Occlusion Strokes at 0-24 Hours

Purpose: ASPECTS&lt;3 was an explicit exclusion criterion in the SELECT2 trial to exclude "very large" infarcts (&gt;100mL) for reperfusion using endovascular thrombectomy (EVT). While specific, ASPECTS&lt;3 may be too insensitive of a threshold on noncontrast CT at 0-24 hours (especially 0-6 hours). We aim to determine if CTA based Collateral Score (CS) can be a more sensitive surrogate marker for infarct core volume (ICV)&gt;100mL while maintaining similar specificity to ASPECTS. Methods: Retrospective analysis included consecutive stroke patients arriving within 24 hours of onset, with intracranial ICA and/or M1 occlusion on CTA, and had concurrent CT perfusion. RAPID AI software estimated ICV using the rCBF&lt;30% threshold. CS was scored on CTA using the method of Tan et al on a 4-point scale for % collaterals compared to contralateral side: 0 none, 1 &gt;0 but &lt;50%, 2 &gt;=50 but &lt;100%, and 3 100%. ROC curve analysis was used to find the optimal CS cutpoint with high specificity for ICV&gt;100mL. Sensitivity and specificity of that CS threshold vs ASPECTS&lt;3 were compared using the N-1 chi square test. Results: 164 patients were included with median (IQR) age of 74 (66-84), NIHSS of 20 (12-25), and time of onset-to-CT of 4 hours (2-7.5). The LVOs were 17 ICA (10.4%), 108 M1 (65.9%), and 39 both (23.8%), with median ICV of 12mL (0-45). 16 patients had ICV&gt;100mL (9.8%) with median of 136mL (105-172). Using ASPECTS&lt;3 identified only 1 of these (ICV of 118mL at 18.5 hours), sensitivity of 6.3% (95% CI: 0.16-30.2%), with no false positives, specificity of 100% (95% CI: 97.6-100%). ROC analysis for CS showed AUC=0.818 (p&lt;0.001), with maximal specificity at CS=0 (no visible collaterals). Using CS=0 identified 6 of these infarcts, sensitivity of 37.5% [95% CI: 15.2-64.6%], with 2 false positives, specificity of 98.7% [95% CI: 95.2-99.8%]. The 2 false positives were ICV of 97mL at 2 hours and 96mL at 3 hours. The improved sensitivity of CS=0 over ASPECTS&lt;3 was significant (p=0.036) while the difference in specificity was not (p=0.144). Conclusion: In our cohort of LVOs, CS=0 was a more sensitive surrogate marker for ICV&gt;100mL compared to ASPECTS&lt;3 while maintaining near 100% specificity. If confirmed in future prospective studies, CS=0 has the potential to further streamline patient selection for EVT.

Mean ADC values and arterial phase hyperintensity discriminate small (≤ 3cm) well-differentiated hepatocellular carcinoma from dysplastic nodule.

This research endeavor sought to distinguish small (≤ 3cm) well-differentiated hepatocellular carcinoma (WD-HCC) from dysplastic nodules (DN) by employing traditional imaging features and mean apparent diffusion coefficient (mADC) values derived from diffusion-weighted imaging (DWI). In this retrospective analysis, we assessed a cohort of ninety patients with confirmed dysplastic nodules (DNs) (n = 71) or well-differentiated hepatocellular carcinoma (WD-HCC) (n = 41) who had undergone dynamic contrast-enhanced magnetic resonance imaging between March 2018 and June 2021. Multivariable logistic regression analyses were executed to pinpoint characteristics that can effectively differentiate histologic grades. A region-of-interest (ROI) encompassing all lesion voxels was delineated on each slice containing the mass in the ADC map. Subsequently, the whole-lesion mean ADC (mADC) were computed from these delineations. A receiver operating characteristic (ROC) curve was generated to assess the discriminatory efficacy of the mADC values in distinguishing between WD-HCC and DN. Among the histopathological types from benign to malignant, mADC showed a significant decrease (P < 0.001). The mADCs were effective in distinguishing WD-HCC from DN [AUC, 0.903 (95% CI 0.849-0.958)]. The best cutoffs for theYoudenindexwere 0.0012mm2/s for mADC, with moderate sensitivity (70.7%) and high specificity (94.4%). MRI features including hyperintensity at arterial phase (odds ratio, 21.2; P = 0.009), mADC < 0.0012mm2/s (odds ratio, 52.2; P < 0.001) were independent predictors for WD-HCC at multivariable analysis. The AUC value of hyperintensity at arterial phase was 0.857 (95% CI 0.786-0.928). The composite diagnostic criterion of arterial hyperintensity + mADC < 0.0012mm2/s showed good performance [AUC, 0.926 (95% CI 0.878-0.975)], displaying increased sensitivity compared to individual assessments involving arterial hyperintensity (P = 0.013), mADC < 0.0012mm2/s (P = 0.004), or LR-5 (P < 0.001), with similar specificity compared to LR-5 (P = 0.193). DN and WD-HCC displayed contrasting diffusion characteristics, attainable to distinguish with satisfactory accuracy. The utilization of arterial phase hyperintensity and mADC < 0.0012 on MRI facilitated the differentiation of WD-HCC from DN.

Bilateral External Torque CT Reliably Detects Syndesmotic Lesions in an Experimental Cadaveric Study.

If tibiofibular syndesmotic injury is undetected, chronic instability may lead to persistent pain and osteoarthritis. So far, no reliable diagnostic method has been available. The primary objectives of this study were to determine whether defined lesions of the syndesmosis can be correlated with specific tibiofibular joint displacements caused by external rotational torque and to compare the performance of bilateral external torque computed tomography (BET-CT) and arthroscopy. Secondary objectives included an evaluation of the reliability of CT measurements and the suitability of the healthy contralateral ankle as a reference. Seven pairs of healthy, cadaveric lower legs were tested and assigned to 2 groups: (1) supination-external rotation (SER) and (2) pronation-external rotation (PER). In the intact state and after each surgical step, an ankle arthroscopy and 3 CT scans were performed. During the scans, the specimens were placed in an external torque device with 2.5, 5.0, and 7.5 Nm of torque applied. The arthroscopic and CT parameters showed significant correlations in all pairwise comparisons. The receiver operating characteristic (ROC) curve analyses yielded the best prediction of syndesmotic instability with the anterior tibiofibular distance on CT, with a sensitivity of 84.1% and a specificity of 95.2% (area under the curve [AUC], 94.8%; 95% confidence interval [CI], 0.916 to 0.979; p < 0.0001) and with the middle tibiofibular distance on arthroscopy, with a sensitivity of 76.2% and specificity of 92.3% (AUC, 91.2%; 95% CI, 0.837 to 0.987; p < 0.0001). Higher torque amounts increased the rate of true-positive results. BET-CT reliably detects experimental syndesmotic rotational instability, compared with the healthy side, with greater sensitivity and similar specificity compared with the arthroscopic lateral hook test. Translation of these experimental findings to clinical practice remains to be established. Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Diagnostic performance with and without artificial intelligence assistance in real-world screening mammography

PurposeTo evaluate artificial intelligence-based computer-aided diagnosis (AI-CAD) for screening mammography, we analyzed the diagnostic performance of radiologists by providing and withholding AI-CAD results alternatively every month. MethodsThis retrospective study was approved by the institutional review board with a waiver for informed consent. Between August 2020 and May 2022, 1819 consecutive women (mean age 50.8 ± 9.4 years) with 2061 screening mammography and ultrasound performed on the same day in a single institution were included. Radiologists interpreted screening mammography in clinical practice with AI-CAD results being provided or withheld alternatively by month. The AI-CAD results were retrospectively obtained for analysis even when withheld from radiologists. The diagnostic performances of radiologists and stand-alone AI-CAD were compared and the performances of radiologists with and without AI-CAD assistance were also compared by cancer detection rate, recall rate, sensitivity, specificity, accuracy and area under the receiver-operating-characteristics curve (AUC). ResultsTwenty-nine breast cancer patients and 1790 women without cancers were included. Diagnostic performances of the radiologists did not significantly differ with and without AI-CAD assistance. Radiologists with AI-CAD assistance showed the same sensitivity (76.5%) and similar specificity (92.3% vs 93.8%), AUC (0.844 vs 0.851), and recall rates (8.8% vs. 7.4%) compared to standalone AI-CAD. Radiologists without AI-CAD assistance showed lower specificity (91.9% vs 94.6%) and accuracy (91.5% vs 94.1%) and higher recall rates (8.6% vs 5.9%, all p < 0.05) compared to stand-alone AI-CAD. ConclusionRadiologists showed no significant difference in diagnostic performance when both screening mammography and ultrasound were performed with or without AI-CAD assistance for mammography. However, without AI-CAD assistance, radiologists showed lower specificity and accuracy and higher recall rates compared to stand-alone AI-CAD.

Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Immunohistochemistry Can Be a Useful Ancillary Tool to Identify Perivascular Epithelioid Cell Tumor

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa mimics, were analyzed using GPNMB and cathepsin K immunohistochemistry. GPNMB expression was seen in all PEComas and alveolar soft part sarcomas with the majority showing diffuse and moderate-to-strong labeling, whereas other sarcomas were negative or showed focal labeling. When a cutoff of diffuse and at least moderate staining was used, GPNMB demonstrated 95% sensitivity and 97% specificity in distinguishing PEComas from leiomyosarcoma, well-differentiated/dedifferentiated liposarcomas, and undifferentiated pleomorphic sarcomas. Cathepsin K with a cutoff of any labeling had lower sensitivity (78%) and similar specificity (94%) to GPNMB. This study highlights GPNMB as a highly sensitive marker for PEComas and suggests its potential use as an ancillary tool within a panel of markers for accurate classification of these tumors.

A deep neural network for MRI spinal inflammation in axial spondyloarthritis.

To develop a deep neural network for the detection of inflammatory spine in short tau inversion recovery (STIR) sequence of magnetic resonance imaging (MRI) on patients with axial spondyloarthritis (axSpA). A total 330 patients with axSpA were recruited. STIR MRI of the whole spine and clinical data were obtained. Regions of interests (ROIs) were drawn outlining the active inflammatory lesion consisting of bone marrow edema (BME). Spinal inflammation was defined by the presence of an active inflammatory lesion on the STIR sequence. The 'fake-color' images were constructed. Images from 270 and 60 patients were randomly separated into the training/validation and testing sets, respectively. Deep neural network was developed using attention UNet. The neural network performance was compared to the image interpretation by a radiologist blinded to the ground truth. Active inflammatory lesions were identified in 2891 MR images and were absent in 14,590 MR images. The sensitivity and specificity of the derived deep neural network were 0.80 ± 0.03 and 0.88 ± 0.02, respectively. The Dice coefficient of the true positive lesions was 0.55 ± 0.02. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the deep neural network was 0.87 ± 0.02. The performance of the developed deep neural network was comparable to the interpretation of a radiologist with similar sensitivity and specificity. The developed deep neural network showed similar sensitivity and specificity to a radiologist with four years of experience. The results indicated that the network can provide a reliable and straightforward way of interpreting spinal MRI. The use of this deep neural network has the potential to expand the use of spinal MRI in managing axSpA.

The salivary microbiome as a diagnostic biomarker of periodontitis: a 16S multi-batch study before and after the removal of batch effects.

Microbiome-based clinical applications that improve diagnosis related to oral health are of great interest to precision dentistry. Predictive studies on the salivary microbiome are scarce and of low methodological quality (low sample sizes, lack of biological heterogeneity, and absence of a validation process). None of them evaluates the impact of confounding factors as batch effects (BEs). This is the first 16S multi-batch study to analyze the salivary microbiome at the amplicon sequence variant (ASV) level in terms of differential abundance and machine learning models. This is done in periodontally healthy and periodontitis patients before and after removing BEs. Saliva was collected from 124 patients (50 healthy, 74 periodontitis) in our setting. Sequencing of the V3-V4 16S rRNA gene region was performed in Illumina MiSeq. In parallel, searches were conducted on four databases to identify previous Illumina V3-V4 sequencing studies on the salivary microbiome. Investigations that met predefined criteria were included in the analysis, and the own and external sequences were processed using the same bioinformatics protocol. The statistical analysis was performed in the R-Bioconductor environment. The elimination of BEs reduced the number of ASVs with differential abundance between the groups by approximately one-third (Before=265; After=190). Before removing BEs, the model constructed using all study samples (796) comprised 16 ASVs (0.16%) and had an area under the curve (AUC) of 0.944, sensitivity of 90.73%, and specificity of 87.16%. The model built using two-thirds of the specimens (training=531) comprised 35 ASVs (0.36%) and had an AUC of 0.955, sensitivity of 86.54%, and specificity of 90.06% after being validated in the remaining one-third (test=265). After removing BEs, the models required more ASVs (all samples=200-2.03%; training=100-1.01%) to obtain slightly lower AUC (all=0.935; test=0.947), lower sensitivity (all=81.79%; test=78.85%), and similar specificity (all=91.51%; test=90.68%). The removal of BEs controls false positive ASVs in the differential abundance analysis. However, their elimination implies a significantly larger number of predictor taxa to achieve optimal performance, creating less robust classifiers. As all the provided models can accurately discriminate health from periodontitis, implying good/excellent sensitivities/specificities, the salivary microbiome demonstrates potential clinical applicability as a precision diagnostic tool for periodontitis.