Independent Readers Research Articles

The usefulness of QT interval measurement as a screening tool for cascade testing in asymptomatic patients at risk of long QT syndrome

Abstract Background Long QT syndrome (LQTS), an inherited arrhythmic syndrome, remains a public health concern with up to 3000 unexpected deaths in the US annually. A simple 12-lead ECG is the most easily accessible tool for initial screening. Purpose To describe the diagnostic utility of the standard QT correction techniques in 12-Lead ECGs, in a screening population of first-degree relatives of persons with LQTS of known genotype. Methods In this single centre study, data were included on consecutive patients undergoing cascade clinical and genetic testing for LQTS, who had a first degree relative with genotype-positive LQTS, from the years 2019 to 2022. Patient demographics, baseline ECG and genetic results were obtained. The QT interval was manually calculated between three independent readers using the tangent method and corrected using the 4 most commonly used formulae: Bazett (BQTc), Fridericia (FreQTc), Framingham (FraQTc) and Hodges (HQTc). The Mean QT was calculated by taking the average of four consecutive QT measurements in lead II or V5. The QT dispersion (QTd), was also calculated by using the formula: QTd = QT max – QT min. Results Data was available on 97 patients from 14 families. The mean age at screening was 44 years, and 51.5% were males. Two-thirds of patients were asymptomatic (n = 74, 76.3%). Fifteen patients had syncopal events. 72.2% (n = 70) of patients had a family history of arrhythmic death. After clinical screening and genotyping, 46.4% (n = 45) patients were gene positive for either KCNQ1 (75.5%) or KCNH2 (24.5%). Patients with prior syncope were more likely to be gene positive (72.7% vs 39.2%, p = 0.005). The 12-Lead ECG derived QTc result is listed in Table 1, with all correction modalities showing a higher corrected QT in the genotype-positive group (p <0.001). The diagnostic performance of BQTc was similar to that of the newer formulae (FreQTc, FraQTc and HQTc) when correcting for heart rate within the range of 60 – 100bpm as listed in Table 2. At a cut-off value of 440ms, BQTc formula had a sensitivity of 51% and a specificity of 84% for predicting genotype pathogenicity as listed in Table 3. The QT dispersion was higher in patients with KCNH2 compared to those with KCNQ1 (122msec, SD 30.5 vs 74.2 msec, SD 30.4, p value <0.001). Patients with KCNH2 were more likely to require an ICD (83.3% vs 16.7%, p <0.001). The mean Schwartz score in gene positive patient was 2.6 compared to 1.9 (p <0.003). Conclusion Formula correction of QT interval to heart rate had good overall diagnostic performance. Both FreQT and FraQT had high AUROC across different heart rates, though there was no statistically significant difference seen between correction formulae. The ECG remains a good preliminary screening tool method for identifying patients with increased risk LQTS in this population. Larger studies are needed to power for comparisons between QT correction methods.

Reproducibility of Cardiac Multifrequency MR Elastography in Assessing Left Ventricular Stiffness and Viscosity.

Cardiac magnetic resonance elastography (MRE) shows promise in assessing the mechanofunctional properties of the heart but faces clinical challenges, mainly synchronization with cardiac cycle, breathing, and external harmonic stimulation. To determine the reproducibility of in vivo cardiac multifrequency MRE (MMRE) for assessing diastolic left ventricular (LV) stiffness and viscosity. Prospective. This single-center study included a total of 28 participants (mean age, 56.6 ± 23.0 years; 16 male) consisting of randomly selected healthy participants (mean age, 44.6 ± 20.1 years; 9 male) and patients with aortic stenosis (mean age, 78.3 ± 3.8 years; 7 male). 3 T, 3D multifrequency MRE with a single-shot spin-echo planar imaging sequence. Each participant underwent two cardiac MMRE examinations on the same day. Full 3D wave fields were acquired in diastole at frequencies of 80, 90, and 100 Hz during a total of three breath-holds. Shear wave speed (SWS) and penetration rate (PR) were reconstructed as a surrogate for tissue stiffness and inverse viscous loss. Epicardial and endocardial ROIs were manually drawn by two independent readers to segment the LV myocardium. Shapiro-Wilk test, Bland-Altman analysis and intraclass correlation coefficient (ICC). P-value <0.05 were considered statistically significant. Bland-Altman analyses and intraclass correlation coefficients (ICC = 0.96 for myocardial stiffness and ICC = 0.93 for viscosity) indicated near-perfect test-retest repeatability among examinations on the same day. The mean SWS for scan and re-scan diastolic LV myocardium were 2.42 ± 0.24 m/s and 2.39 ± 0.23 m/s; the mean PR were 1.24 ± 0.17 m/s and 1.22 ± 0.14 m/s. Inter-reader variability showed good to excellent agreement for myocardial stiffness (ICC = 0.92) and viscosity (ICC = 0.85). Cardiac MMRE is a promising and reproducible method for noninvasive assessment of diastolic LV stiffness and viscosity. 2 TECHNICAL EFFICACY: 1.

Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy

For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6–77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Novel intravascular tantalum oxide-based contrast agent achieves improved vascular contrast enhancement and conspicuity compared to Iopamidol in an animal multiphase CT protocol

BackgroundTo assess thoracic vascular computed tomography (CT) contrast enhancement of a novel intravenous tantalum oxide nanoparticle contrast agent (carboxybetaine zwitterionic tantalum oxide, TaCZ) compared to a conventional iodinated contrast agent (Iopamidol) in a rabbit multiphase protocol.MethodsFive rabbits were scanned inside a human-torso-sized encasement on a clinical CT system at various scan delays after intravenous injection of 540 mg element (Ta or I) per kg of bodyweight of TaCZ or Iopamidol. Net contrast enhancement of various arteries and veins, as well as image noise, were measured. Randomized scan series were reviewed by three independent readers on a clinical workstation and assessed for vascular conspicuity and image artifacts on 5-point Likert scales.ResultsOverall, net vascular contrast enhancement achieved with TaCZ was superior to Iopamidol (p ≤ 0.036 with the exception of the inferior vena cava at 6 s (p = 0.131). Vascular contrast enhancement achieved with TaCZ at delays of 6 s, 40 s, and 75 s was superior to optimum achieved Iopamidol contrast enhancement at 6 s (p ≤ 0.036. Vascular conspicuity was higher for TaCZ in 269 of 300 (89.7%) arterial and 269 of 300 (89.7%) venous vessel assessments, respectively (p ≤ 0.005), with substantial inter-reader reliability (κ = 0.61; p < 0.001) and strong positive monotonic correlation between conspicuity scores and contrast enhancement measurements (ρ = 0.828; p < 0.001).ConclusionTaCZ provides absolute and relative contrast advantages compared to Iopamidol for improved visualization of thoracic arteries and veins in a multiphase CT protocol.Relevance statementThe tantalum-oxide nanoparticle is an experimental intravenous CT contrast agent with superior cardiovascular and venous contrast capacity per injected elemental mass in an animal model, providing improved maximum contrast enhancement and prolonged contrast conspicuity. Further translational research on promising high-Z and nanoparticle contrast agents is warranted.Key PointsThere have been no major advancements in intravenous CT contrast agents over decades.Iodinated CT contrast agents require optimal timing for angiography and phlebography.Tantalum-oxide demonstrated increased CT attenuation per elemental mass compared to Iopamidol.Nanoparticle contrast agent design facilitates prolonged vascular conspicuity.Graphical

Imaging Findings and MRI Patterns in a Cohort of 18q Chromosomal Abnormalities.

The abnormalities of the long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MR imaging features. We hypothesized that there would be variable but recognizable white matter and structural patterns in this cohort. In this retrospective cohort study, we included pediatric patients with a proved abnormality of 18q between 2000-2022. An age- and sex-matched control cohort was also constructed. Thirty-six cases, median MR imaging age 19.6 months (4.3-59.3), satisfied our inclusion criteria. Most were female (25, 69%, F:M ratio 2.2:1). Fifty MR imaging studies were analyzed, and 35 (70%) had delayed myelination. Two independent readers scored brain myelination with excellent interrater reliability. Three recognizable evolving MR imaging patterns with distinct age distributions and improving myelination scores were identified: Pelizaeus-Merzbacher disease-like (9.9 months, 37), intermediate (22 months, 48), and washed-out pattern (113.6 months, 53). Etiologically, MRIs were analyzed across 3 subgroups: 18q deletion (34, 69%), trisomy 18 (10, 21%), and ring chromosome 18 (5, 10%). Ring chromosome 18 had the highest myelination lag (27, P = .005) and multifocal white matter changes (P = .001). Trisomy 18 had smaller pons and cerebellar dimensions (anteposterior diameter pons, P = .002; corpus callosum vermis, P < .001; and transverse cerebellar diameter, P = .04). In this cohort of 18q chromosomal abnormalities, MR imaging revealed recognizable patterns correlating with improving brain myelination. Imaging findings appear to be on a continuum with more severe white matter abnormalities in ring chromosome 18 and greater prevalence of structural abnormalities of the pons and cerebellum in trisomy 18.

A-156 Comparison of blast and variant lymphocyte flagging between the Alinity hq from Abbott and XN-1000 from Sysmex

Abstract Background Blast cells are immature white blood cells (WBC). The presence of blasts in the peripheral blood may be associated with certain diseases such as myelodysplastic syndrome and acute myelogenous leukemia. Variant lymphocytes (i.e., reactive lymphocytes, atypical lymphocytes) are WBCs produced by the immune system in reaction to infections caused by pathogens such as Epstein-Barr virus, cytomegalovirus, etc. It is clinically useful that the automated hematology analyzer is capable of flagging these cells. In this study, the blast (shown as ‘BLAST’ on the Alinity hq and ‘Blast/Abn Lympho?’ or ‘Blast?’ on XN-1000) and variant lymphocyte (shown as ‘VAR LYM’ on the Alinity hq, and ‘Atypical Lympho?’ on XN-1000) flagging was compared between the Alinity hq from Abbott and XN-1000 from Sysmex. Alinity hq has different sensitivity settings available for BLAST and VAR LYM flagging. In this study, the default setting for Alinity hq was used. For XN-1000, the Q-Flag default setting is 100. In this study, the setting was 120 for ‘Blast/Abn Lympho’ and 100 for “Atypical lympho?’. Methods Blood specimens were tested on the Alinity hq and XN-1000 analyzers. Two smears per specimen were made manually or by the Alinity hs slide maker stainer and read by two independent readers. The specimens showing any of the following flagging were included in the analysis: ‘BLAST’ on Alinity hq, ‘VAR LYM’ on Alinity hq, ‘Blast/Abn Lympho?’ or ‘Blast?’ on XN-1000, ‘Atypical lympho?’ on XN-1000. The flagging reports of these samples from both analyzers were compared to the smear review to determine if each analyzer's blast and variant lymphocyte flagging were true positive, false positive, true negative, or false negative. Results A total of 520 specimens were tested, yielding 41 specimens for blast flagging analysis and 80 specimens for variant lymphocyte flagging analysis. Due to the scarce availability of true positive samples from the manual review, true positive and false negative rate were not compared. For blast flagging using smear results of &amp;gt;=1% or &amp;gt;=5% as the positive criterion, Alinity hq yielded a 9.8% (=4/41) false positive rate and 87.8% (=36/41) true negative rate. XN-1000 yielded a 75.6% (=31/41) false positive rate and 22.0% (=9/41) true negative rate. For variant lymphocyte flagging using smear results of &amp;gt;=5% as the positive criterion, Alinity hq yielded a 6.3% (=5/80) false positive rate and 92.5% (=74/80) true negative rate. XN-1000 yielded a 91.3% (=73/80) false positive rate and 7.5% (=6/80) true negative rate. Conclusions This study demonstrated that Alinity hq achieved a much lower false positive rate and much higher true negative rate for both blast and variant lymphocyte flagging when compared to the XN-1000. Manual blast and variant lymphocyte morphology classification is laboratory- and technician-dependent. Both analyzers allow different sensitivity/specificity levels to flag blasts and variant lymphocytes. Each individual laboratory should evaluate and choose the setting that is most suitable for their specific patient populations to obtain the desired flagging rate.

Image quality of virtual monochromatic and material density iodine images for evaluation of head and neck neoplasms using deep learning-based CT image reconstruction – A retrospective observational study

PurposeTo compare the quality of deep learning image reconstructed (DLIR) virtual monochromatic images (VMI) and material density (MD) iodine images from dual-energy computed tomography (DECT) for the evaluation of head and neck neoplasms with CT scans from a conventional single-energy protocol. MethodA total of 294 head and neck CT scans (98 VMIs operated at 60 keV, 102 MD iodine images, and 94 images from a 120 kVp single-energy CT (SECT) protocol) were retrospectively evaluated. VMIs and MD iodine images were generated using the Gemstone Spectral Imaging (GSI) mode using DLIR and metal artifact reduction (MAR) algorithms. SECT images were generated using adaptive statistical iterative reconstruction (ASIR-V). Images were scored by two independent readers on a 6-point Likert-type scale for overall image quality, vessel contrast, soft tissue contrast, noise texture, noise intensity, artifact reduction, and sharpness. ResultsSubjective overall image quality was rated as superior or excellent in 98 % of DLIR-based MD iodine images and VMIs, but only in 55 % of ASIR-V-based SECT images. For each individual quality criterion, image quality of VMIs and MD iodine images was rated as better than that of SECT images (p < 0.001 in each case). Noise texture and intensity were rated better in MD iodine images than in VMIs. ConclusionDECT using both DLIR and MAR for the generation of VMIs and MD iodine images resulted in higher subjective quality of oncologic head and neck images than ASIR-V-based SECT. Noise reduction and noise texture were best achieved with DLIR-based MD iodine images.

Differentiating primary from metastatic ovarian tumors of gastrointestinal origin by CT

PurposeTo determine differentiating CT imaging features of primary ovarian cancers from ovarian metastases of gastrointestinal origin. MethodsRetrospective study of 50 patients with new ovarian lesions on CT, half were primary ovarian cancers and half gastrointestinal metastases. Two blinded independent readers described tumor characteristics on CT (size, laterality, margin, etc.) and ancillary features (ascites, peritoneal seeding, lymphadenopathy, etc.). Patient age, sex, cancer history, and tumor marker levels for CA-125 and CEA were collected. Wilcoxon test and Pearson's chi-squared test were used for statistical analysis. Results50 patients with mean age of 62.1 years were included. Ovarian metastases were more likely to be cystic/mainly cystic (p=0.013), have smooth margins (p=0.011), and have no/mild enhancement (p<0.001). Primary ovarian lesions were associated with moderate to large volume of ascites (p=0.047) and more commonly seen with lymphadenopathy (p=0.008). Laterality was not significantly different between the two groups. CA-125 level was more commonly elevated in primary ovarian lesions (87% vs 50%, p=0.018), and with much higher values (1076.5 vs 155.1, p=0.013). CEA level was more commonly elevated in metastatic ovarian lesions (83.3% vs 15.4%, p<0.001), and with higher values (72.4 vs 2.1, p<0.001). ConclusionOvarian metastases were more frequently smooth-margined and cystic with little enhancement. Primary ovarian lesions were more commonly associated with lymphadenopathy and larger volume of ascites. Tumor markers CEA and CA-125 were more frequently elevated in metastatic and primary lesions, respectively. Cancer history was the only variable that increased the odds of metastasis and therefore it is important to always correlate with history of cancer.

Magnetic resonance defecography: Post-defecation straining detects more and maximal prolapse in the anterior and middle compartments

ObjectiveTo compare pre-defecation straining without rectal gel and post-defecation straining with the defecation phase, and to investigate their roles in evaluating pelvic organ prolapse (POP). Material & methodsMagnetic Resonance Defecography (MRD) images of 65 patients with a clinical diagnosis of POP were retrospectively reviewed by two independent readers. Measurements were taken at rest, pre-defecation straining without rectal gel, defecation, and post-defecation straining. The presence, sizes, and/or grades of cystocele, uterovaginal prolapse, widened levator hiatus, perineal descent, cul-de-sac hernia, rectocele, and rectal intussusception were evaluated and compared across the four phases. ResultsCompared to pre-defecation straining, both defecation and post-defecation straining detected more cases, larger sizes, and higher grades of prolapse in all compartments. When comparing defecation and post-defecation straining, the latter diagnosed four more cases of cystocele (80 % vs 73.9 %, p = 0.2) with larger size (−34.1 vs −29.0, p < 0.01) and higher grade (p = 0.19). Post-defecation straining also identified eight more cases of uterovaginal prolapse (89.2 % vs 73.9 %, p < 0.01) with larger size (−32.9 vs −26.4, p < 0.01) and higher grade (p < 0.01) compared to defecation. Conversely, defecation detected eight more cases of rectocele (46.2 % vs 33.9 %, p < 0.01) with larger size (9.2 vs 6.2 cm, p < 0.01) and higher grade (p = 0.26). ConclusionPost-defecation straining effectively depicts the maximal extent of prolapse in the anterior and middle compartments, and should be performed whenever there is a clinical need for a comprehensive assessment of prolapse in these compartments.

Concordance of PD-L1 Expression in Metastatic Triple-negative Breast Cancer Between the 22C3 and E1L3N Antibodies Using Combined Positive Scoring.

For patients with metastatic triple-negative breast cancer (TNBC), treatment with pembrolizumab is dependent on the accurate determination of programmed death ligand 1 (PD-L1) expression using immunohistochemistry (IHC). This study evaluated the interobserver concordance in assessing PD-L1 expression on TNBC samples using the commercial 22C3 IHC assay and an in-house assay based on the E1L3N antibody. Concordance between the 22C3 and the E1L3N IHC assays was evaluated on TNBC samples read by a commercial laboratory and a Brigham and Women's Hospital breast pathologist (BWH reader). Each slide was given a PD-L1 combined positive score (CPS) and was considered PD-L1 positive or negative based on the CPS cutoff of 10. Interobserver concordance for the assays was also evaluated on a subset of samples between 2 and 3 independent readers. On 71 samples, 2 independent readers (1 BWH reader and commercial laboratory) using E1L3N and 22C3, respectively, reached agreement on PD-L1 status (positive/negative) on 64 samples (90.1%). Using 22C3, 2 independent readers reached agreement on PD-L1 status on 30 of 36 samples (83.3%), and 3 independent readers reached agreement on 16 of 27 samples (59.3%). Using E1L3N, 2 BWH readers reached agreement on PD-L1 status on 18 of 27 samples (66.7%). Three BWH readers reached an agreement on 2 of 12 of the most challenging samples (16.7%). In conclusion, concordance between E1L3N and 22C3 testing using CPS for PD-L1 in metastatic TNBC was >90%. However, certain cases were challenging to agree upon using current threshold criteria, highlighting the need for more standardized evidence-based methods to assess PD-L1 expression.

Evaluation of apparent diffusion coefficient (ADC) with regards to reproducibility and diagnostic accuracy as well as possible significance of pre - and post - contrast acquisition and employment of different b values

PurposeOngoing efforts are focusing on optimizing diffusion-weighted imaging (DWI) as an essential part of breast MRI protocol. Our study aimed to evaluate the effect of contrast media (CM) on the apparent diffusion coefficients (ADC) acquired following current recommendations. Patient and Methods: Patients who underwent 3 T breast MRI with a histologically verified suspicious lesion were included in this IRB-approved, single-center, cross-sectional retrospective study. Breast MRI protocol included a DWI sequence with multiple b-values, which was acquired before and after CM administration. ADC maps were calculated by in-line monoexponential fitting with b-values 0 /800 and 50/800. Two independent readers (R1, R2) reviewed the images in separate sessions for b values 0/800 and 50/800, pre- and post-CM. Bland Altmann plots as well as intraclass correlation coefficients (ICCs) for inter-reader agreement, different b-values, and pre- and post-CM were calculated. Diagnostic accuracy was evaluated and compared by calculating the area under the receiver operating characteristics curve (AUC). Results: 91 lesions in 89 patients were examined (mean age 50.7 years, standard deviation 13.9). ADC values were significantly (P<0.05) lower post-CM (mean ranging from 1.28 x10−3 mm2/s to 1.30 x10−3 mm2/s) compared to pre-CM (mean ranging from 1.32 x10−3 mm2/s to 1.37 x10−3 mm2/s) for both b-values combinations (0/800 and 50/800 s/mm2). We found an almost perfect inter-reader agreement pre-/post-CM with b values 0/800 and 50/800 (ICC ranging from 0.853 to 0.939). Bland Altman plot demonstrated no systematic difference between readers. ROC analysis revealed good diagnostic performance without significant differences (P>0.05) between b values 0/800 and 50/800 s/mm2 as well as pre- and post-CM with areas under the ROC curve between 0.834 and 0.877. Conclusion: ADC values are slightly lower when acquiring b values 0/800 and post-CM. This effect does not reduce the diagnostic performance but may be relevant in case of definite cut-offs in medical decision making.

[89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial

With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89Zr-labelled monoclonal antibody ([89Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [89Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [89Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [89Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment. Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [89Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [89Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths. Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing. Telix Pharmaceuticals.

Three-Dimensional Transthoracic Echocardiography for Semiautomated Analysis of the Tricuspid Annulus: Validation and Normal Values

The expansion of tricuspid valve (TV) interventions has underscored the need for accurate and reproducible three-dimensional (3D) transthoracic echocardiographic (TTE) tools for evaluating the tricuspid annulus and for 3D normal values of this structure. The aims of this study were to develop new semi-automated software for 3D TTE analysis of the tricuspid annulus, compare its accuracy and reproducibility against those of multiplanar reconstruction (MPR) reference, and determine normative values. Three-dimensional TTE images of 113 patients with variable degrees of tricuspid regurgitation were analyzed using the new semiautomated software and conventional MPR methodology (as the reference standard), each by three independent readers. For each measured parameter, intertechnique agreement was assessed using linear regression and Bland-Altman analyses, and interreader variability using intraclass correlation coefficients and coefficients of variation. Additionally, 3D TTE data sets of 789 subjects from the WASE (World Alliance Societies of Echocardiography) study were analyzed using this new software to determine normal values for each tricuspid annular (TA) parameter. Semiautomated measurements showed excellent agreement with MPR reference values for all TA measurements: high correlations (all r values >0.8) and minimal biases. All measurements were more reproducible than with MPR: higher intraclass correlation coefficients (0.94-0.96 vs 0.82-0.90) and lower coefficients of variation (5%-12% vs 8%-18%). Sex- and age-related differences were identified in 3D normal values of most TA parameters. Dynamic analysis showed that TA parameters vary throughout the cardiac cycle, reaching minimal values at end-systole and maximum values in late diastole. Novel software for semiautomated analysis of TA geometry and dynamics provides accurate and reproducible measurements. Normal values of TA dimensions, parsed by sex and age, are reported.

Exploratory analysis of the potential disconnect between objective inflammatory response and clinical response following certolizumab pegol treatment in patients with active axial spondyloarthritis

IntroductionThis post hoc analysis evaluated the relationship between objective measures of inflammation and clinical outcomes following 12 weeks of certolizumab pegol (CZP) treatment in patients with active axial spondyloarthritis (axSpA).MethodsWe...

Assessment of interstitial lung disease in a systemic sclerosis patient cohort using photon-counting detector CT with ultra-high resolution and a 1024-pixel image matrix.

This study assessed the potential of ultra-high-resolution (UHR) and a 1024-matrix in photon-counting-detector CT (PCD-CT) for evaluating interstitial lung disease (ILD) in systemic sclerosis (SSc) patients. Sixty-six SSc patients who underwent ILD-CT screening on a first-generation PCD-CT were retrospectively included. Scans were performed in UHR mode at 100 kVp with two different matrix sizes (512x512 and 1024x1024) and reconstructed at slice thicknesses of 1.5 mm and 0.2 mm. Image noise, subjective image quality, and ILD changes (1) were evaluated on a 5-point Likert-scale by two independent readers. Interreader agreement for subjective image quality ranged from fair to almost perfect (Krippendorff-Alpha: 0.258-0.862). Overall image quality was highest for 1.5 mm/1024matrix images ((reader 1: 4 (4.4), reader 2: 5 (4.5)). Image sharpness was rated significantly better in 0.2 mm images (p < 0.001). Regarding ILD changes, 0.2 mm slice thickness outperformed 1.5 mm slice thickness significantly (p < 0.001), while there was no significant difference between the two matrix sizes. 1024 matrix size demonstrated superiority in evaluating coarse reticulations compared to 512matrix size. UHR mode with a 0.2 mm slice thickness showed enhanced image sharpness and improved visibility of ILD changes compared to standard reconstructions. This has the potential to enable the early detection of subtle disease manifestations. With the invention of PCD-CT different reconstruction algorithms need to be evaluated for specific pathologies. In our study ILD UHR mode with 0.2 mm slice thickness showed to be beneficial in the detection of parenchymal changes in patients with scleroderma.

Sensitivity and specificity of the Salzburg EEG criteria for nonconvulsive status epilepticus.

The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy. A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying "certain/possible NCSE" was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals. In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (n = 53). The criteria showed a sensitivity of 94% (95% CI: 92-96%), a specificity of 77% (95% CI: 73-81%), a positive predictive value of 34% (95% CI: 30-39%), and a negative predictive value of 99% (95% CI: 98-100%). False positives for "certain NCSE" (n = 16) included many serial seizures and stimulus-induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for "possible NCSE" (n = 79) were mainly represented by different encephalopathies and postictality. The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice.

Significant age-related differences between lower leg muscles of older and younger female subjects detected by ultrashort echo time magnetization transfer modeling.

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE-MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE-MT modeling technique is sensitive to age-related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1±6.1years old, BMI = 22.3±3.5) and 20 older (74.7±5.5years old, BMI = 26.7±5.9) female subjects were imaged using UTE sequences on a 3T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2-MM), and water T2 (T2-W) were calculated using UTE-MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE-MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2-MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2-W showed significantly higher values in the older group. The age-related differences were more pronounced for MMF (-17 to -19%) and T2-W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE-MT MRI techniques in evaluating age-related skeletal muscle changes.

High Spatial-Resolution and Acquisition-Efficiency Cardiac MR T1 Mapping Based on Radial bSSFP and a Low-Rank Tensor Constraint.

Cardiac T1 mapping is valuable for evaluating myocardial fibrosis, yet its resolution and acquisition efficiency are limited, potentially obscuring visualization of small pathologies. To develop a technique for high-resolution cardiac T1 mapping with a less-than-100-millisecond acquisition window based on radial MOdified Look-Locker Inversion recovery (MOLLI) and a calibrationless space-contrast-coil locally low-rank tensor (SCC-LLRT) constrained reconstruction. Prospective. Sixteen healthy subjects (age 25 ± 3 years, 44% females) and 12 patients with suspected cardiomyopathy (age 57 ± 15 years, 42% females), NiCl2-agar phantom. 3-T, standard MOLLI, radial MOLLI, inversion-recovery spin-echo, late gadolinium enhancement. SCC-LLRT was compared to a conventional locally low-rank (LLR) method through simulations using Normalized Root-Mean-Square Error (NRMSE) and Structural Similarity Index Measure (SSIM). Radial MOLLI was compared to standard MOLLI across phantom, healthy subjects, and patients. Three independent readers subjectively evaluated the quality of T1 maps using a 5-point scale (5 = best). Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient analysis, linear regression, Bland-Altman analysis. P < 0.05 was considered statistically significant. In simulations, SCC-LLRT demonstrated a significant improvement in NRMSE and SSIM compared to LLR. In phantom, both radial MOLLI and standard MOLLI provided consistent T1 estimates across different heart rates. In healthy subjects, radial MOLLI exhibited a significantly lower mean T1 (1115 ± 39 msec vs. 1155 ± 36 msec), similar T1 SD (74 ± 14 msec vs. 67 ± 23 msec, P = 0.20), and similar T1 reproducibility (28 ± 18 msec vs. 22 ± 15 msec, P = 0.34) compared to standard MOLLI. In patients, the proposed method significantly improved the sharpness of myocardial boundaries (4.50 ± 0.65 vs. 3.25 ± 0.43), the conspicuity of papillary muscles and fine structures (4.33 ± 0.74 vs. 3.33 ± 0.47), and artifacts (4.75 ± 0.43 vs. 3.83 ± 0.55). The reconstruction time for a single slice was 5.2 hours. The proposed method enables high-resolution cardiac T1 mapping with a short acquisition window and improved image quality. 1 TECHNICAL EFFICACY: Stage 1.

Radiological signs of stone impaction add no value in predicting spontaneous stone passage

Stone size and location are key factors in predicting spontaneous stone passage (SSP), but little attention has been paid to the influence of radiological signs of stone impaction (RSSI). This research aims to determine whether RSSI, alongside stone size, can predict SSP and to evaluate the consistency of ureteral wall thickness (UWT) measurements among observers. In this retrospective study, 160 patients with a single upper or middle ureteral stone on acute non-enhanced computed tomography (NCCT) were analysed. Patient data were collected from medical records. Measurements of RSSI, including UWT, ureteral diameters, and average attenuation above and below the stone, were taken on NCCT by four independent readers blind to the outcomes. The cohort consisted of 70% males with an average age of 51 ± 15. SSP occurred in 61% of patients over 20 weeks. The median stone length was 5.7 mm (IQR: 4.5–7.3) and was significantly shorter in patients who passed their stones at short- (4.6 vs. 7.1, p < 0.001) and long-term (4.8 vs. 7.1, p < 0.001) follow-up. For stone length, the area under the receiver operating characteristic curve (AUC) for predicting SSP was 0.90 (CI 0.84–0.96) and only increased to 0.91 (CI 0.85–0.95) when adding ureteral diameters and UWT. Ureteral attenuation did not predict SSP (AUC < 0.5). Interobserver variability for UWT was moderate, with ± 2.0 mm multi-reader limits of agreement (LOA). The results suggest that RSSI do not enhance the predictive value of stone size for SSP. UWT measurements exhibit moderate reliability with significant interobserver variability.

Macaque liver substrate for evaluating dense fine speckled-like patterns on HEp2010 cells

Antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) is instrumental in the evaluation of systemic autoimmune diseases (SADs). The dense fine speckled (DFS) ANA staining predominantly associates with anti-DFS70, an autoantibody that is thought to exclude the presence of SAD. However, the DFS pattern may mask the presence of other ANA patterns that may be clinically relevant. Our laboratory uses the HEp2010 substrate which contains both HEp2 and liver substates. The aim of this study was to determine whether negative liver nucleus immunofluorescence could exclude the presence of antibodies to extractable nuclear antigens (ENA) in sera with DFS-like patterns. One hundred consecutive sera samples suspicious for DFS pattern, along with 15 sera of control patterns (positive metaphase bars) were included in the study. Each sample was examined separately on HEp2010 (Euroimmun) and liver by two independent readers. Anti-DFS70 was assessed by line and chemiluminescent immunoassays. DFS-like sera were more likely to be liver nucleus-negative compared with control sera. Of the liver-negative sera, 61/64 (95.3%) were deemed anti-ENA negative. Using the liver substrate in the evaluation of anti-ENA had a sensitivity of 90.0% and a negative predictive value of 95.4%. In our cohort, concurrent evaluation of sera with the liver substrate helped rule out the presence of other anti-ENA. This technique may be a safeguard for DFS-like ANA patterns that may mask underlying anti-ENA on IIF.