Discordant Patients Research Articles

P200 The relationship between patient and physician global assessment in patients with anti-neutrophil cytoplasmic antibody associated vasculitis

Abstract Background/Aims Patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) often have reduced health-related quality of life (HRQoL) as assessed by the SF-36 questionnaire. Global assessment provides a patient and physician’s view on the patient’s overall health and wellbeing. The aim of this project was to examine the level of agreement between the patient and physician global assessment (PtGA and PhGA) in patients with AAV. Methods Patients attending our dedicated tertiary vasculitis clinic were recruited into this prospective study. PtGA and PhGA scores, out of 100, were assessed via a visual analog scale, with higher scores representing better health. SF-36 assessed HRQoL. Discordance was defined as an absolute difference of ≥ 20 between PhGA and PtGA. Active disease was defined as a BVAS of ≥ 1. Results Ninety-seven patients (mean age 58 years, 46% male) participated. Forty-three (44%) patients had active disease. The majority (88%) were on immunosuppressive therapy with renal (79.4%), lung (42.3%) and sino-nasal (40.2%) being the most commonly involved systems. The mean (SD) PtGA and PhGA was 63.4 (22.2) and 60.8 (24.8) respectively (t = 2.63, p = 0.0049). Mean (SD) PtGA in active versus inactive disease was 59 (22.8) and 66 (21.5) respectively (t = 1.49, p = 0.07). PhGA scores were higher than PtGA in 44 patients with an overall mean difference of + 13.7 (95% confidence interval [CI] 9.97, 17.46, p < 0.001). PtGA scores were higher than PhGA in 48 patients (mean difference +17.9, 95% CI 22.6, 13.3, p < 0.001). Scores were discordant in 26 patients, with PhGA>PtGA (negatively discordant) in 10 (38%). Mean (SD) PhGA in discordant patients versus non-discordant patients was 47.5 (24.7) versus 65.7 (23.1) respectively (t = 1.71, p = 0.001). Mean (SD) age in positively discordant versus negatively discordant patients was 58.8 (17.3) versus 69.1 (8) respectively (t = 1.71, p = 0.026). The percentage of patients with active disease (n=number of patients) in positively discordant versus negatively discordant patients was 50% (n = 8) versus 30% (n = 3) respectively (p = 0.008). Bland-Altman plots showed no systematic bias as global scores increased. Conclusion Overall, physicians did not overestimate patients' global health when using the global assessment tool. Discordance rates were 26%, within which physicians were likelier to assess the patient's global health as lower than patients did themselves. Positively discordant patients (PhGA<PtGA) were likelier to have active disease and were younger on average. Disclosure A. Bhonsle: None. T. Coughlan: None. R. Graven: None. P. Bussa: None. M. Gingold: None. K. Polkinghorne: None. J. Ryan: None. A. Kitching: None.

Abstract 6610: Increasing blood volumes to detect minimal residual disease in neoadjuvant-treated early breast cancer patients

Abstract Breast cancer (BC) is the most frequent neoplasia affecting women worldwide normally detected at early stages. In this regard, early diagnosis drastically decreases mortality, however, around 20% of these patients will later relapse. This is mainly caused by undetectable molecular residual disease (MRD) not eliminated by standard primary treatments. Therefore, it is crucial to detect the after-treatment MRD to stratify the patients by their risk of relapse. Liquid biopsies have emerged as non-invasive method to obtain information about tumors and improve clinical cancer management. Regarding this, much has been hypothesized about utilizing high blood volumes to overcome the necessity of complex and resource-intensive next generation sequencing (NGS) methodologies to detect highly diluted blood tumor components in localized cancers. Herein, we employed a combined analysis of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) together with high blood volumes and single-assay droplet digital PCR (ddPCR) to detect MRD with ultra-high sensitivity. We prospectively assayed 124 samples extracted at baseline, post-neoadjuvant therapy (NAT), post-surgery and a follow-up on a six-monthly basis. A median of 76.40 mL of blood to detect CTCs and 40 mL of plasma to detect ctDNA per patient from 19 BC women were used in this study. ddPCR assays were performed with a median of 14 partitions per determination to detect ctDNA and 12 partitions for CTCs. Overall, ctDNA, CTCs and ctDNA and/or CTCs were detected in 84.21%, 66.66% and 89.47% respectively in the pre-treatment blood samples. MRD (ctDNA and/or CTCs) was detected in 73.68% of the after NAT blood samples. On the other hand, it was detected in 46.66% and 70.00% of the post-surgery and follow-up samples respectively. Post-NAT MRD was detected in 57.14% (4/7) and 83.33% (10/12) of patients with and without pathological complete response pCR respectively. To note, the discordant patients achieving pCR in tissue with detectable MRD in blood were high-risk BC. Importantly, in one of the two patients without pCR and no MRD detected, not enough sample were available to complete the analysis. The other discordant patient presented a localized disease with residual cancer burden value of 1 and no lymph nodes affected. In 1 out of 19 (5.26%) patient clinically relapsed with a positive MRD detection 6 months earlier. Applying this methodology, we observed a sensitivity of 0.004% in ctDNA detection and 0.224 CTCs per mL of blood. Overall, this novel methodology greatly improves sensitivity for ctDNA and CTCs detection in treatment-naïve early BC. In addition, MRD was successfully detected in post-treatment samples antedating clinical relapse by 6 months in one patient. This prospective study is potentially demonstrating that using high blood volumes and a single-assay ddPCR is a cost-effective strategy to monitor localized BC and predict relapses. Citation Format: Alfonso Alba-Bernal, Ana Godoy-Ortiz, María Emilia Domínguez-Recio, Begoña Jimenez-Rodriguez, María Elena Quirós-Ortega, Esperanza López-López, Guillermo Carbajosa-Antona, Jesús Peralta-Linero, Luis Vicioso, Estefanía Bellagarza-García, Guadalupe Dolores Garrido-Ruiz, Cynthia Robles-Podadera, Alicia Garrido-Aranda, María Dunia Roldán-Díaz, Jesús Velasco-Suelto, Rocío Lavado-Valenzuela, Martina Álvarez, Nuria Ribelles, Javier Pascual, Emilio Alba, Iñaki Comino-Méndez. Increasing blood volumes to detect minimal residual disease in neoadjuvant-treated early breast cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6610.

Impact of right ventricular stiffness on discordance between hemodynamic parameter and regurgitant volume in patients with pulmonary regurgitation.

Accurate detection of significant pulmonary regurgitation (PR) is critical in management of patients after right ventricular (RV) outflow reconstruction in Tetralogy of Fallot (TOF) patients, because of its influence on adverse outcomes. Although pressure half time (PHT) of PR velocity is one of the widely used echocardiographic markers of the severity, shortened PHT is suggested to be seen in conditions with increased RV stiffness with mild PR. However, little has been reported about the exact characteristics of patients showing discrepancy between PHT and PR volume in this population. Echocardiography and cardiac magnetic resonance imaging (MRI) were performed in 74 TOF patients after right ventricular outflow tract (RVOT) reconstruction [32 ± 10 years old]. PHT was measured from the continuous Doppler PR flow velocity profile and PHT < 100 ms was used as a sign of significant PR. Presence of end-diastolic RVOT forward flow was defined as RV restrictive physiology. By using phase-contrast MRI, forward and regurgitant volumes through the RVOT were measured and regurgitation fraction was calculated. Significant PR was defined as regurgitant fraction ≥ 25%. Significant PR was observed in 54 of 74 patients. While PHT < 100 ms well predicted significant PR with sensitivity of 96%, specificity of 52%, and c-index of 0.72, 10 patients showed shortened PHT despite regurgitant fraction < 25% (discordant group). Tricuspid annular plane systolic excursion and left ventricular (LV) ejection fraction were comparable between discordant group and patients showing PHT < 100 ms and regurgitant fraction ≥ 25% (concordant group). However, discordant group showed significantly smaller mid RV diameter (30.7 ± 4.5 vs. 39.2 ± 7.3mm, P < 0.001) and higher prevalence of restrictive physiology (100% vs. 42%, P < 0.01) than concordant group. When mid RV diameter ≥ 32mm and presence of restrictive physiology were added to PHT, the predictive value was significantly improved (sensitivity: 81%, specificity: 90%, and c-index: 0.89, P < 0.001 vs. PHT alone by multivariable logistic regression model). Patients with increased RV stiffness and non-enlarged right ventricle showed short PHT despite mild PR. Although it has been expected, this was the first study to demonstrate the exact characteristics of patients showing discrepancy between PHT and PR volume in TOF patients after RVOT reconstruction.

Subcutaneos Implantable Cardioverter: Defibrillator: Is the Conventional Pre-Implant Screening Enough to Assess Eligibility?

Aims: The subcutaneous implantable cardioverter-defibrillator (S-ICD) requires screening prior to implantation. Surface anatomical landmarks (SAL) guide the screening. The heart silhouette shows variations, therefore, these landmarks may differ. We aimed to determine the concordance between SAL and fluoroscopy guided screening, and analyze discordance predicting factors. Methods: We performed a conventional SAL guided screening (CS) in left and right parasternal electrode position (LPP/RPP) to candidates for S-ICD. Subsequently, we performed a fluoroscopy guided screening (FGS) according to cardiac silhouette. Screenings in which at least the result of one sensing vector did not coincide were considered “discordant”. A comparison was done between discordant vs. concordant cases. A simple binary logistic regression analysis was performed to assess the risk of being discordant individually for each of the variables. Results: The results of CS and FGS were compared in 110 patients (220 comparisons: 110 LPP and 110 RPP). 90 (40.91%) were discordant in at least one sensing vector (46 in LPP and 44 in RPP). In 3 patients (2.73%) the indication of which type of defibrillator was implanted changed according to the FGS. There were no significant differences between the discordant and concordant screening patients. Conclusion: There is a level of discordance between CS and FGS. There were no analyzed factors that were able to predict discordance between these two screening methods. It might be reasonable to perform FGS before implant.

2235. Discordance of Clinical and Microbiological Endpoints in Clinical Trials for Complicated Urinary Tract Infection (cUTI)

Abstract Background Complicated urinary tract infections (cUTI) are a clinical syndrome characterized by pyuria and a documented microbial pathogen on urine or blood culture, accompanied by local and systemic signs and symptoms, in the presence of urinary tract abnormalities or acute pyelonephritis. Current FDA guidance recommends that the primary endpoint for cUTI clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed time after therapy. In recent trials, it has been noted that while some patients have clinical resolution of symptoms, they are considered failures due to positive urine cultures. These discordant outcomes have raised questions about the utility of the microbiological endpoint. Methods We analyzed patient data from 13 phase 3 clinical trials submitted to the FDA. We focused on the microbiological modified intent-to-treat (m-MITT) population, including patients who have at least 1 bacterial pathogen known to cause cUTI and received at least one dose of study drug (N=4842). Outcomes were determined at the Test of Cure (TOC) visit 7-10 days after therapy, and the Late Follow Up (LFU) visit 3-4 weeks after therapy. Clinical and microbiological success were defined as the resolution of cUTI symptoms present at entry, with no new symptoms (clinical cure), and reduction of the pathogen at entry to ≤ 103 CFU/mL on urine culture (microbiological eradication). Results Among all included patients, 70.7% were overall successes at the TOC, exhibiting clinical and microbiological success. 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). In a multivariate logistic regression model, discordance was associated with obesity, lithiasis, use of analgesics, and receipt of carbapenem antibiotics. Discordant patients were at an increased risk for clinical failure at the LFU visit, and the risk of late clinical failure increased with longer time between the TOC and LFU visits. Conclusion Microbiological persistence at the TOC visit despite resolution of symptoms was associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component in the composite endpoint. Disclosures All Authors: No reported disclosures.

Patient-Reported Versus Physician-Assessed Health Status in Heart Failure With Reduced and Preserved Ejection Fraction From ASIAN-HF Registry.

We aimed to assess if discordance between patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ)-overall summary (os) score and physician-assessed New York Heart Association (NYHA) class is common among patients with heart failure (HF) with reduced or preserved ejection fraction, and determine its association with outcomes. A total of 4818 patients with HF were classified according to KCCQ-os score (range 0-100, dichotomized by median value 71.9 into high [good] versus low [bad]) and NYHA class (I/II [good] or III/IV [bad]) as concordant good (low NYHA class, high KCCQ-os score), concordant bad (high NYHA class, low KCCQ-os score), discordant worse NYHA class (high NYHA class, high KCCQ-os score), and discordant worse KCCQ-os score (low NYHA class, low-KCCQ-os score). The composite of HF hospitalization or death at 1 year was compared across groups. There were 2070 (43.0%) concordant good, 1099 (22.8%) concordant bad, 331 (6.9%) discordant worse NYHA class, and 1318 (27.4%) discordant worse KCCQ-os score patients. Compared with concordant good, adverse outcomes were the highest in concordant bad (HR, 2.7 [95% CI, 2.2-3.5]) followed by discordant worse KCCQ-os score (HR, 1.8 [95% CI, 1.4-2.2]) and discordant worse NYHA class (HR, 1.5 [95% CI, 1.0-2.3]); with no modification by HF phenotype (preserved versus reduced ejection fraction, Pinteraction=0.52). At 6 months, 1403 (48%) experienced clinically significant improvement in KCCQ-os score (≥5 points increase over 6 months). Patients with improved KCCQ-os at 6 months (HR, 0.65 [95% CI, 0.47-0.92]) had better outcomes and the association was not modified by HF phenotype (Pinteraction=0.40). One-third of patients with HF had discordance between patient-reported and clinician-assessed health status, largely attributable to worse patient-reported outcomes. Such discordance, particularly in those with discordantly worse KCCQ, should alert physicians to an increased risk of HF hospitalization and death, and prompt further assessment for potential drivers of worse patient-reported outcomes relative to physicians' assessment.

Primary Hyperparathyroidism: Is Image Localization Alone Sufficient to Ensure Long-Term Cure in Unifocal Disease?

Advances in imaging have facilitated precise preoperative localization and focused resection of hyperfunctional parathyroids in primary hyperparathyroidism (PHPT). Combining imaging techniques or a "dual" approach, when concordant, improves adenoma-localizing accuracy above individual modalities. This study sought to assess biochemical cure and failure rates (persistence or recurrence) of surgery directed by dual imaging alone in PHPT. This observational, single-center analysis comprised 31 patients diagnosed with PHPT and imaged with both ultrasound (USG) of theneck and sestamibi scintigraphy. The extent of surgery was based solely on inter-modality concurrence for adenoma localization; imaging-concordant patients underwent focused parathyroidectomy, whereas discordant patients necessitated neck exploration (with extent altered according to scintigraphic lesion lateralization). No intraoperative localizing adjuncts were used. Twenty-three patients had concordant imaging, of which 19 underwent focused exploration, with sensitivity and positive predictive value (PPV) for dual imaging of 100% and 95.7%, respectively. The overall sensitivity and PPV were 92.9% and 89.7% for USG aloneand 100% and 93.6% for scintigraphy, respectively. The mean age and prevalence of thyroid disease were significantly higher in the discordant group. All patients achieved postoperative normocalcemia. There were no cases of persistent or recurrent hyperparathyroidism on follow-up. In the imaging-concordant setting, focused surgery may be safely performed with the omission of other adjuncts for localization. Older age and concomitant thyroid pathology predispose to discordant imaging and are risk factors for surgical failure when attempting an image-directed approach. Neck exploration is an alternative in these patients with excellent cure rates and acceptable morbidity.

Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study

Background ContextLevel-specific lumbar bone mineral density (BMD) evaluation of a single vertebral body can provide useful surgical planning and osteoporosis management information. Previous comparative studies have primarily focused on detecting spinal osteoporosis but not at specific levels. PurposeTo compare the detection rate of lumbar osteoporosis between quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA); to explore and analyze the distribution models of QCT-derived BMD and DXA T-score at the specific levels; and to evaluate the diagnostic accuracy of level-specific BMD thresholds for the prediction of osteoporotic vertebral compression fracture (OVCF) in postmenopausal women. Study Design/SettingA comparative analysis of prospectively collected data comparing QCT-derived BMD with DXA T-score. Patient SampleA total of 296 postmenopausal women who were referred to the spine service of a single academic institution were enrolled. Outcome MeasuresQCT-derived BMD and DXA T-score at specific levels, with or without osteoporotic vertebral compression fracture. MethodsPostmenopausal women who underwent QCT and DXA within a week of admission from May 2019 to June 2022 were enrolled. The diagnostic criteria for osteoporosis recommended by the World Health Organization and the American College of Radiology were used for lumbar osteoporotic diagnosis. To evaluate differences in lumbar BMD measurements at specific levels, a threshold of T score=-2.5 and QCT-derived BMD = 80 mg/cm3 were used to categorize level-specific lumbar BMD into low and high BMD. Disagreements in BMD categorization between DXA and QCT were classified as a minor or major discordance based on the definition by Woodson. Data between QCT and DXA were visualized in a stacked bar plot and analyzed. Correlations between DXA and QCT at the specific levels were evaluated using Pearson's linear correlation and scatter plots. Curve fitting of BMD distribution, receiver operating characteristic (ROC) and area under the curve (AUC) for each single vertebral level was performed. ResultsOf the 296 patients, QCT diagnosed 61.1% as osteoporosis, 30.4% as osteopenia and 8.4% as normal. For those screened with DXA, 54.1% of the patients had osteoporosis, 29.4% had osteopenia and 16.6% had normal BMD. Diagnoses were concordant for 194 (65.5%) patients. Of the other 102 discordant patients, 5 (1.7%) were major and 97 (32.8%) were minor. Significant correlations in level-specific BMD between DXA and QCT were observed (p<.001), with Pearson's correlation coefficients ranging from 0.662 to 0.728. The correlation strength was in the order of L1 > L2 > L3 > L4. The low BMD detection rate for QCT was significantly higher than that for DXA at the L3 and L4 levels (65% vs. 47.9% and 68.1% vs 43.7, respectively, p<.001). Patients with OVCF showed significantly lower QCT-derived BMD (47.2 mg/cm3 vs. 83.2 mg/cm3, p<.001) and T-score (-3.39 vs. -1.98, p<.001) than those without OVCF. Among these patients, 82.8% (101/122) were diagnosed with osteoporosis by QCT measurement, while only 74.6% (91/122) were diagnosed by DXA. For discrimination between patients with and without OVCF, QCT-derived BMD showed better diagnosed performance (AUC range from 0.769 to 0.801) than DXA T-score (AUC range from 0.696 to 0.753). ConclusionQCT provided a more accurate evaluation of lumbar osteoporosis than DXA. The QCT-derived BMD measurements at a specific lumbar level have a high diagnostic performance for OVCF.

PO-714-07 ELECTROCARDIOGRAPHIC DISCORDANCE TO PREDICT LEFT VENTRICULAR SUMMIT VENTRICULAR ARRHYTHMIA ORIGIN

Left ventricular summit region (LVS) ventricular arrhythmias (VAs) can be challenging to eliminate with ablation (Abl) and may be confused for VAs arising from more easily accessible outflow tract (OT) areas. ECG clues are few but important to guide management. We aimed to identify novel ECG discordance patterns to predict LVS VA origin and inform catheter Abl complexity. Consecutive patients 2017-2021 undergoing Abl of LVS VAs (OT VAs with suspected intramural origin based on mapping and need for Abl from >1 sites in right (RV) or left ventricular (LV) OT or great cardiac vein/anterior interventricular vein (GCV/AIV) for VA control) were included. All inferior axis VAs were analyzed on 12-lead ECG. Discordant ECG patterns, or those in which precordial transition and lead I axis were inconsistent with RVOT or LVOT origin, were identified: 1) left bundle, right axis, precordial transition by V3 (LBRI-early), or 2) right bundle, left axis (RBLI). Concordant patterns were those with vectors consistent with either RVOT (LBRI, precordial transition >V3) or LVOT (LBLI, precordial transition V3, or RBRI) exit (Figure). Of 29 patients identified (69% male; mean age 59.0 ± 12.8 yrs; LVEF 43 ± 15%), 16 (55%) had discordant ECGs, most (14/16) with LBRI-early pattern; 13 had concordant ECGs, 3 suggesting RVOT and 10 consistent with LVOT exit. All patients required Abl from multiple anatomic sites, including LVOT in all, RVOT in 10, and GCV/AIV in 7, to effect partial or complete success in 25 (86%) patients after mean 1.9 1.2 Abls. Among discordant ECG patients, Abl at more anatomic sites was necessary to reduce VA burden (Figure). ECG discordance is a marker of ventricular arrhythmias arising from the left ventricular summit region. Identification of this novel ECG feature can improve the ability to predict the site of origin and to guide in ablation of LV summit arrhythmias.

P217 Describing the evolution of concordance/discordance between DAS28-ESR and ultrasound power Doppler synovitis in a treatment-naïve early RA cohort

Abstract Background/Aims Discordance between DAS28-ESR and ultrasound (US)-detected power Doppler synovitis (PDUS) can lead to unnecessary DMARD cycling. Using DAS28-ESR and PDUS in an early RA trial cohort, we aimed to identify and describe concordance and discordance at diagnosis and evaluate their proportional change in response to treatment. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept + methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week 24. Clinical and US assessments were completed at baseline, weeks 12/24/48. Remission was DAS28-ESR ≤2.6 and active disease was DAS28-ESR &amp;gt;2.6. PDUS presence was defined as total PDUS score ≥ 1. Active concordance was defined as active disease with PDUS while active discordance was defined as active disease without PDUS. Remission concordance was defined as remission without PDUS while remission discordance was defined as remission with PDUS. Descriptive analyses were undertaken to address the above aims. Results At baseline all patients had active disease - 67% (81/120) were concordant and 33% (39/120) were discordant. Baseline DAS28-ESR and individual components were higher in the concordant compared to discordant group. In the active concordant group, from baseline to weeks 24 and 48 respectively, 30% (24/81) and 20% (16/81) persisted, and 26% (22/81) and 38% (31/81) became remission concordant; while 30% (24/81) and 35% (28/81) shifted to active discordance at weeks 24 and 48 respectively and 14% (11/81) and 7% (6/81) became remission discordant. In the active discordant group, from baseline to weeks 24 and 48 respectively, 72% (28/39) and 49% (19/39) persisted and only one and two patients were remission discordant; while 8% (3/39) and 15% (6/39) shifted to active concordance at weeks 24 and 48 respectively and 18% (7/39) and 31% (12/39) became remission concordant. Conclusion Discordance of DAS28 is typically associated with later RA. In this report, a third of patients shifted from active concordance to discordance following DMARD treatment early in the RA pathway. Further study is needed to understand how these patients compare to those that started and persisted with active discordance, and also later discordant RA patients. Disclosure R. Shukla: None. D.A. Selby: None. P. Emery: None. D. Plant: None. M.H. Buch: None.

Determining Cause for Activated Partial Thromboplastin Time and Anti-Factor Xa Discordance in Mechanical Circulatory Support Patients on Heparin; Can Thromboelastogram Help?

<h3>Purpose</h3> Both activated partial thromboplastin time (aPTT) and anti-Xa levels are used to monitor unfractionated heparin (UFH) in mechanical circulatory support (MCS) patients. Studies have demonstrated high level of discordance between these assays, particularly in critically ill patients. Thromboelastogram (TEG) is an assay that provides a graphical representation of hemostasis, and it may aid in guiding decision-making in discordant patients. The objective of this pilot study is to identify the causes of aPTT and anti-Xa discordance and to evaluate the potential benefit of TEG in guiding MCS patient's anticoagulation management. <h3>Methods</h3> A total of 18 patients receiving UFH with consecutive discordant aPTT/anti-Xa assays between April to August 2021 underwent 27 comprehensive evaluations. For each patient concurrent aPTT and anti-Xa assay data were collected for 2 days and 1 day prior to the date of TEG (69 evaluations). Discordance was considered as a 20 second difference between measured aPTT and calculated aPTT corresponding with the anti-Xa value. Results of TEG, antithrombin (AT)3, lupus anticoagulant (LA), free plasma hemoglobin and anticoagulation therapy outcomes one-week post-TEG were also collected. Results were interpreted by a hematopathologist with expertise in hemostasis who made recommendations regarding therapy and the best assay to monitor UFH. <h3>Results</h3> A dose response curve calculated from the paired aPTT/anti-Xa data showed a high degree of variability in aPTT for an anti-Xa assay level of 0.1-0.4 IU/mL (R² = 0.07). In 29/69 (42%) of the paired values, discordance was caused by the presence of LA affecting aPTT. When evaluated in conjunction with TEG, 12/24 (50%) values were positive for LA, 5/25 (20%) values had AT3 <60%, 11/27 (37%) patients had underlying factor deficiency determined by TEG, and 0/19 (0%) values had free Hgb >100 mg/dL. There were 6/27 bleeding events (22 %): epistaxis (1), melena (3), vaginal spotting (1), and hematoma (1). <h3>Conclusion</h3> Lupus anticoagulant, factor deficiency, and warfarin administration are the main causes for aPTT and anti-Xa discordance in MCS patients on heparin. TEG, in combination with LA and AT3 can help in identifying discordance cause, assess overall hemostasis, and the most appropriate parameter to monitor heparin.

Three-dimensional QCA-based vessel fractional flow reserve (vFFR) in Heart Team decision-making: a multicentre, retrospective, cohort study

ObjectivesTo evaluate the feasibility of three-vessel three-dimensional (3D) quantitative coronary angiography (QCA)-based fractional flow reserve (FFR) computation in patients discussed within the Heart Team in whom the treatment decision was...

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients’ Prognosis With Metastatic Renal Cancer

BackgroundIn Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients.MethodsIn this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales.ResultsOur results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99).ConclusionThis study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

Discordant parameters of insulin-like growth factor 1 and growth hormone in the diagnosis and monitoring of acromegaly

Acromegaly is a rare endocrine disorder associated with multiple complications and increased mortality. Timely diagnosis and adequate treatment can bring the life expectancy of patients with acromegaly closer to the general population level. The tests for the diagnosis of acromegaly are measurement of both serum GH, and GH after oral glucose administration; serum insulin-like growth factor-1 (IGF-1). However, in clinical practice, up to 39% of patients with discordant results are found. The patients with discordant GH and IGF-1levels, are the most difficult to manage. This review discusses the prevalence of discordant GH and IGF-1 outcomes in patients with acromegaly; factors causing this discrepancy; the impact of hormone levels on treatment outcomes. Although endocrinologists are used to dealing with this discrepancy in clinical practice for many years, discordant patients'outcome remains uncertain and undefined The optimal treatment should be individually tailored for each patient, taking into account all clinical parameters.

Evaluation of HbA1c and glucose management indicator discordance in a population of children and adolescents with type 1 diabetes.

Glucose management indicator (GMI) is a useful metric for the clinical management of diabetic patients using continuous glucose monitoring (CGM). In adults, a marked discordance between HbA1c and GMI has been reported. To date, no studies have evaluated this discordance in children/adolescents with type 1 diabetes (T1D). HbA1c and real-life CGM data of the 12 weeks preceding HbA1c measurement were collected from 805 children/adolescents. The absolute difference between HbA1c and GMI was calculated for both the 12-week and 4-week periods preceding HbA1c measurement and the proportion of discordant patients was defined according to specific thresholds in the entire study population and in subjects stratified by type of CGM, insulin therapy, gender, age and puberty. Regression analyses were performed with HbA1c-GMI discordance as dependent variable and patients' characteristics as independent ones. A new GMI equation for children and adolescent was derived from the linear regression analysis between mean glucose and HbA1c. HbA1c-GMI discordance calculated on the 12-week period was <0.1, ≥0.5 and ≥1.0 in 24.8, 33.9 and 9.2% of the subjects, respectively. No significant differences in the proportion of discordant patients were found comparing patients stratified by type of CGM, insulin therapy, gender, age and puberty. GMI-HbA1c discordance was not significantly explained by age, gender, BMI, type of CGM, insulin therapy, hemoglobin, anemia and autoimmune diseases (R2 =0.012, p=0.409). HbA1c-GMI discordance calculated on the 4-week period was comparable. GMI (%) equation derived for this cohort was: 3.74 + 0.022x (mean glucose in mg/dl). GMI could be meaningfully discordant respect to HbA1c in more than a third of children/adolescents with T1D. This discrepancy should be taken into careful consideration when the two indices are directly compared in daily clinical practice.

Evaluation of the Atellica TnIH cardiac troponin I assay and assessment of biological equivalence.

We evaluated the analytical performance characteristics and the biological equivalence of the Atellica TnIH assay. Precision, detection capability, linearity, and sex specific 99th percentiles were determined de novo. Classification of patients relative to the 99th percentiles was used to assess biological equivalence. Analytical precision and detection capability of the Atellica TnIH assay is excellent with a limit of blank <1ng/L and 62.5% of women and 93% of men had results above the limit of detection. The 99th percentiles (90% CI) in women were 49ng/L (31-67) and 70ng/L (48-121) in men. An asymmetrical distribution involving 5% of results was notable. Agreement was moderate (Kappa 0.58, 95% CI 0.53-0.63) with 20% of patients discordantly classified with Atellica TnIH below and Access hsTnI above the 99th percentiles. Serial results in 195 patients demonstrated good agreement (Kappa 0.84, 95% CI 0.77-0.90). Differences greater than the assay specific reference change values (z≥±1.96) occurred in 65% (95% CI 53-76%) of 99th percentile discordant patients compared to 2.7% (p<0.001) and 76% (p=0.17) of the concordant low and high cTnI groups respectively. The 99th percentile discordant and the concordantly elevated groups are more alike with respect to their z≥±1.96 rates. This favours an overestimated Atellica TnIH 99th percentile as more likely, and we hypothesize that antibody interference resulting in asymmetric scatter of nearly 5% samples may be the underlying mechanism. Analytical accuracy and interferences in cardiac troponin assays should be investigated and resolved with high priority.

Supplementing Existing Societal Risk Models for Surgical Aortic Valve Replacement With Machine Learning for Improved Prediction.

BackgroundThis study evaluated the role of supplementing Society of Thoracic Surgeons (STS) risk models for surgical aortic valve replacement with machine learning (ML).Methods and ResultsAdults undergoing isolated surgical aortic valve replacement in the STS National Database between 2007 and 2017 were included. ML models for operative mortality and major morbidity were previously developed using extreme gradient boosting. Concordance and discordance in predicted risk between ML and STS models were defined using equal‐size tertile‐based thresholds of risk. Calibration metrics and discriminatory capability were compared between concordant and discordant patients. A total of 243 142 patients were included. Nearly all calibration metrics were improved in cases of concordance. Similarly, concordance indices improved substantially in cases of concordance for all models with the exception of deep sternal wound infection. The greatest improvements in concordant versus discordant cases were in renal failure: ML model (concordance index, 0.660 [95% CI, 0.632–0.687] discordant versus 0.808 [95% CI, 0.794–0.822] concordant) and STS model (concordance index, 0.573 [95% CI, 0.549–0.576] discordant versus 0.797 [95% CI, 0.782–0.811] concordant) (each P<0.001). Excluding deep sternal wound infection, the concordance indices ranged from 0.549 to 0.660 for discordant cases and 0.674 to 0.808 for concordant cases.ConclusionsSupplementing ML models with existing STS models for surgical aortic valve replacement may have an important role in risk prediction and should be explored further. In particular, for the roughly 25% to 50% of patients demonstrating discordance in estimated risk between ML and STS, there appears to be a substantial decline in predictive performance suggesting vulnerability of the existing models in these patient subsets.

The concordance between preoperative aspiration and intraoperative synovial fluid culture results: intraoperative synovial fluid re-cultures are necessary whether the preoperative aspiration culture is positive or not

AimsPreoperative aspiration culture and intraoperative cultures play pivotal roles in periprosthetic joint infection (PJI) diagnosis and pathogen identification. But the discordance between preoperative aspiration culture and intraoperative synovial fluid culture remains unknown. We aim to determine (1) the discordance between preoperative and intraoperative synovial fluid (SF) culture and. (2) compared to intraoperative synovial fluid cultures, the sensitivity of preoperative aspiration fluid culture. Then the following question is tried to be answered: Are intraoperative synovial fluid re-cultures necessary if the preoperative aspiration culture is positive?Materials and methodsBetween 2015 and 2019, 187 PJI patients managed with surgeries were included in this study. Compared to intraoperative synovial fluid culture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of preoperative aspiration culture were calculated. Then, the discordance between preoperative aspiration culture and intraoperative SF culture was analyzed.ResultsThe sensitivity of preoperative aspiration culture was 81.29% compared to intraoperative synovial fluid cultures. Concordance was identified in 147 PJI (78.61%) patients and culture discordance occurred in 40 patients (21.39%). In these discordant PJI patients, 24 patients (60%) were polymicrobial and no intraoperative synovial fluid culture growth was found in 16 PJI cases (40%). Preoperative monomicrobial staphylococcus results had a sensitivity of and a specificity of 80.43% and 83.16%, respectively. Preoperative polymicrobial results had the lowest sensitivity.ConclusionsThe intraoperative synovial fluid re-cultures are necessary if the preoperative aspiration culture is positive and the discordance between preoperative aspiration culture and intraoperative synovial fluid culture should be noted especially when Streptococcus spp. and more than one pathogen was revealed by preoperative aspiration culture.Level of evidence: Level III.

Examining clinical training through a bicultural lens: Experiences of genetic counseling students who identify with a racial or ethnic minority group

Biculturals are individuals who have had significant exposure to more than one culture and who possess more than one cultural frame of reference. In the United States, this term has been used to describe both immigrants and members of racial or ethnic minority groups who live within the majority white culture. Biculturals develop a distinct repertoire of social and cognitive skills and have been shown to engage in a process of cultural frame switching in response to salient cultural cues. Through a conceptual lens offered by current research on biculturalism, this article examines transcripts of focus groups we collected for a study on the clinical training experiences of genetic counseling students who identify with a racial or ethnic minority group. We conducted a constructivist grounded theory study, collecting data via 13 videoconference focus groups with 32 recent graduates of genetic counseling training programs who identify with a racial or ethnic minority group. We focus here on two of the thematic categories identified in that study related to participants’ experiences interacting with patients during supervised clinical rotations. We find three ways in which being bicultural influenced these genetic counselors’ patient interactions. First, participants described interactions with both culturally concordant and culturally discordant patients that highlighted the salience of their racial, ethnic, or cultural identity in these encounters. Second, they reported sensitivity to social nuances between and within cultures, reflecting the findings of prior research about heightened cultural awareness in biculturals. Third, they described switching cultural frames in response to their patients’ identities which, at times, created conflict between their professional and culturally concordant frameworks. The results of this study suggest that the influence of a student's racial, ethnic, or cultural identity on interactions with patients should be discussed within the supervisory relationship, and that being bicultural confers advantages in learning to provide culturally responsive care.

A Comparative Retrospective Study of Immunotherapy RANO Versus Standard RANO Criteria in Glioblastoma Patients Receiving Immune Checkpoint Inhibitor Therapy

ObjectivesReal-time assessment of treatment response in glioblastoma (GBM) patients on immune checkpoint blockade (ICB) remains challenging because inflammatory effects of therapy may mimic progressive disease, and the temporal evolution of these inflammatory findings is poorly understood. We compare GBM patient response during ICB as assessed with the Immunotherapy Response Assessment in Neuro-Oncology (iRANO) and the standard Response Assessment in Neuro-Oncology (RANO) radiological criteria.Methods49 GBM patients (seven newly diagnosed and 42 recurrent) treated with ICBs at a single institution were identified. Tumor burden was quantified on serial MR scans according to RANO criteria during ICB. Radiographic response assessment by iRANO and RANO were compared.Results82% (40/49) of patients received anti–PD-1, 16% (8/49) received anti-PD-L1, and 2% (1/49) received anti-PD-1 and anti-CTLA4 treatment. Change in tumor burden and best overall response ranged from −100 to +557% (median: +48%). 12% (6/49) of patients were classified as concordant non-progressors by both RANO and iRANO (best response: one CR, one PR, and four SD). Another12% (6/49) had discordant assessments: 15% (6/41) of RANO grade progressive disease (PD) patients had iRANO grade of progressive disease unconfirmed (PDU). The final classification of these discordant patients was pseudoprogression (PsP) in three of six, PD in two of six, and PDU in one of six who went off study before the iRANO assessment of PDU. iRANO delayed diagnosis of PD by 42 and 93 days in the two PD patients. 76% (37/49) patients were classified as concordant PD by both RANO and iRANO. 12% (6/49) of all patients were classified as PsP, starting at a median of 12 weeks (range, 4–30 weeks) after ICB initiation.ConclusionsStandard RANO and iRANO have high concordance for assessing PD in patients within 6 months of ICB initiation. iRANO was beneficial in 6% (3/49) cases later proven to be PsP, but delayed confirmation of PD by <3 months in 4% (2/49). PsP occurred in 12% of patients, starting at up to 7 months after initiation of ICB. Further study to define the utility of modified RANO compared with iRANO in ICB GBM patients is needed.