Discordance Rate Research Articles

Abstract PO3-03-05: Clinical outcomes in early-stage TNBC according to HER2-low status

Abstract Background: Clinical outcomes according to HER2 immunohistochemistry (IHC) in patients with early-stage HER2-negative breast cancer have differed across studies. For early-stage TNBC (eTNBC), less representation of this subtype in cohorts studied to date has limited interpretation of results. We sought to evaluate outcomes according to HER2 IHC in a multi-institutional cohort of patients (pts) with eTNBC who received neoadjuvant therapy (NAT). Methods: Pts diagnosed with stage I-III TNBC (including HR-low; ER and PR < 10%) who received NAT and underwent surgery between 1/1/16-6/30/19 were identified across three institutional prospective databases. HER2 was defined as low (1+ or 2+/ISH non-amplified) or HER2-0 according to local testing at diagnosis. Pathological complete response (pCR) was defined as no residual invasive disease in breast and axilla. Multivariable logistic regression was used to compare pCR rates (HER2-low vs HER2-0) adjusting for age at diagnosis, race, anatomic clinical stage, germline BRCA1/2 (gBRCA), histology, HR status and receipt of anthracycline and taxane NAT. Recurrence-free (RFS), distant recurrence-free (DRFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios. Results: A total of 978 pts were identified of which 388 (39.7%) had HER2-low and 590 (60.3%) had HER2-0 tumors at diagnosis. Median age was 50.3 (range: 21.0-83.4) yrs. 174 (17.8%) pts had HR-low tumors. 142 (14.5%) pts had a known gBRCA mutation. 790 pts (80.8%) received anthracycline- and taxane NAT. No significant differences were observed in age, race, gBRCA, histology, HR status (low vs negative), clinical tumor size, or type of NAT between HER2-low and HER2-0 groups. Clinical nodal positivity was higher in HER2-low (55.2%) vs HER2-0 (46.6%), p=0.011. No significant difference in pCR was observed between HER2-low (32.0%) and HER2-0 (32.7%) groups, adjusted p=0.928. Among pts with residual disease (RD) post-NAT with HER2 IHC also available in the RD sample, 244/363 (67.2%) had concordant HER2 status. 70/225 (31.1%) of HER2-0 tumors at diagnosis had IHC expression post-NAT (66 HER2-low, 4 HER2-positive); 48/138 (34.8%) of HER2-low tumors at diagnosis were HER2-0 post-NAT. At a median follow-up of 3.1 yrs, RFS did not significantly differ between HER2-low vs HER2-0 pts with pCR (p=0.368) or in those with RD post-NAT (p=0.573). Similarly, DRFS did not differ according to HER2 category for pts with pCR (p=0.509) or RD (p=0.812), nor did OS for pts with pCR (p=0.514) or RD (p=0.285) (Table 1). Conclusion: In a large cohort of pts with eTNBC treated with NAT, HER2-low status was not associated with pCR or survival after adjusting for clinical factors. High rate of discordance in HER2 IHC between diagnostic and RD post-NAT was observed, highlighting the importance of repeat IHC testing in serial samples given the development of antibody drug conjugates for HER2-low breast cancer. Table 1. RFS, DRFS and OS by HER2 expression Citation Format: Ana Garrido-Castro, Danielle Brandes Zakon, Qingchun Jin, Michael Grimm, Akshara Singareeka Raghavendra, Melissa Hughes, Mathew Cherian, Julie Vincuilla, Tonia Parker, Paolo Tarantino, Elizabeth Mittendorf, Tari King, Vicente Valero, Debu Tripathy, Bhuvaneswari Ramaswamy, Sara Tolaney, Nabihah Tayob, Nancy Lin, Daniel Stover, Carlos Barcenas. Clinical outcomes in early-stage TNBC according to HER2-low status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-05.

Abstract PO3-03-11: Receptor discordance after neoadjuvant chemotherapy with pembrolizumab in early-stage triple-negative breast cancer

Abstract Background: Discordance in hormone receptor (HR) and/or HER2 status between matched primary tumors and residual specimens following neoadjuvant therapy is a known phenomenon. In the neoadjuvant setting, systemic treatment is primarily informed by the HR and HER2 status from the diagnostic biopsy. Current guidelines recommend additional adjuvant capecitabine and/or pembrolizumab and/or olaparib for patients with triple-negative breast cancer (TNBC) after neoadjuvant systemic therapy if residual disease is present at the time of surgery. Discordance in biomarker status between the initial diagnosis and residual cancer may impact postoperative systemic therapy recommendations. This study aims to investigate the discordance rate in HR and HER2 status after neoadjuvant chemotherapy (NAC) plus pembrolizumab in early-stage TNBC. Furthermore, given the emerging data in support of novel antibody-drug conjugates (ADCs) for HER2-low breast cancer, the prevalence of HER2-low disease following standard-of-care neoadjuvant therapy may have critical clinical importance. Methods: We performed a single-institution, retrospective study of early-stage TNBC patients diagnosed between February 1st, 2020 and December 1st, 2022 who were treated with neoadjuvant chemotherapy and pembrolizumab. Patients who had not undergone definitive surgery were excluded. Demographic information, clinical and pathologic characteristics, and treatment data were collected from an institutional database. Pathologic complete response (pCR) was defined as ypT0/Tis and ypN0. HR and HER2 status before and after neoadjuvant therapy were collected. This study was approved by an Institutional Review Board. Results: Among the 94 patients included the median age was 55 years (IQR 47.0-61.8). The majority of patients had invasive ductal carcinomas (90.4%), were clinical T2 stage (68.1%), and node negative (55.3%). On the core tumor biopsy, estrogen receptor (ER) was < 1% in 90 (95.7%) patients and 1-10% in 4 (4.3%) of patients. Progesterone receptor (PR) was < 1% in 91 (96.8%) of patients and 1-10% in 3 (3.2%) of patients. HER2 was 0 by IHC in 49 (52.1%) patients, 1+ in 30 (31.9%) patients, 2+ in 11 (11.7%) patients, and not performed in 4 (4.3%) patients. A pCR (ypT0/Tis ypN0) was achieved in 60 (63.8%) of the 94 patients. In the 34 patients with residual disease, 29 patients had ER status evaluated at the time of surgery. Of these patients, 4 had tumors with ER < 1% at baseline but >5% at surgery. 28 patients with residual disease had PR evaluated at the time of surgery. Of these patients, all had tumors with PR < 1% at the time of surgery. 28 patients had residual tumors with HER2 status evaluated at the time of surgery (table). Of these patients, 18 (64.3%) tumor specimens were HER2-ultra-low, 9 (32.1%) were HER2-low-positive, and 1 (3.6%) was HER2-positive. Conclusion: Receptor discordance from the time of initial biopsy to residual disease can occur in patients with early-stage TNBC treated with NAC with pembro. As additional systemic therapy is indicated in patients who do not achieve pCR, accurate tumor marker status is critical. This study highlights the potential impact of reassessment of HR and HER2 status on the surgical tumor specimen. Clinical trials that tailor adjuvant therapy recommendations based on residual biomarker analyses may further improve outcomes for women with high risk TNBC. Table. Discordance in HER2 Status Between Primary Tumor and Residual Specimen Citation Format: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer. Receptor discordance after neoadjuvant chemotherapy with pembrolizumab in early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-11.

Abstract PO2-02-07: Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study

Abstract Background: The definition of human epidermal growth factor receptor-2(HER2) low was proposed with the development of T-DXd, a novel antibody-drug conjugate (ADCs) targeting HER2 in the field of breast cancer (BC) treatments. However, whether HER2 low is a distinct subgroup is still an ongoing debate with mixed results. Current retrospective studies focused on HER2 low concentrated more on metastatic BC, less was known in early BC. The retrospective study was conducted based on HER2 low early BC to comprehensively analyze its clinicopathological features and prognostic roles compared with HER2 IHC0. Methods: This single institution retrospective study enrolled 999 early stage (stage I through III) HER2 negative invasive BC patients diagnosed at Chinese PLA General Hospital from January 2010 to December 2015. Tumors with HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay were defined as HER2 low. Clinicopathological characteristics s and survival outcomes including disease-free survival (DFS) and overall survival (OS) were compared between HER2 IHC0 and HER2 low groups. The correlations between HER2 expression and estrogen receptor (ER) status were determined by Mantel-Haenszel χ2 test. Cohen’s kappa coefficient (k) was adopted to evaluate the concordance between HER2 expression on primary tumors and matched biopsies. Results: 999 patients were eligible for inclusion criteria, among which the percentages of HER2 low in the whole cohort, HR positive group and HR negative group were 83.6%, 86.54%, 72.14% respectively. It was observed the presence of a significant higher proportion of ER level > 10% (p < 0.001), PgR positive (p < 0.001) and more patients who received endocrine therapy (p = 0.002). In HR positive group, clinicopathological features were balanced between HER2 IHC0 and HER2 low. In HR negative group, HER2 low manifested a higher proportion of invasive ductal type (p = 0.016) compared with HER2 IHC0. Survival analysis showed a significantly longer OS in HER2 low BC than HER2 IHC0. (HR: 0.458, 95%CI: 0.262-0.800, p = 0.0005). Nevertheless, the independent role was not reached in DFS. When stratified by HR status, patients with HER2 low in HR positive group demonstrated a longer OS than HER2 IHC0 (HR: 0.55, 95%CI: 0.273-1.105, p = 0.0385). The same trend was observed in HR negative group (HR: 0.385, 95%CI: 0.158-0.939, p = 0.0132). Neither the HR positive group nor the HR negative group achieved significant DFS. Besides, a positive correlation was observed between ER status and the rate of HER2 low (Mantel-Haenszel c2 test, p < 0.001, Pearson’s R = 0.159, P < 0.001). No regularity of survival differences between HER2 IHC0 and HER2 low was found in each ER level in the exploratory study. Finally, 119 patients who developed relapsed or metastatic disease were identified, with the most prevalent metastatic site being bone (31.1%), following by lung (16.80%) and lymph node (13.44%). Among 52 patients with matched biopsy samples, dynamic changes of HER2 IHC status were confirmed in both primary and relapsed statuses, with an discordance rate of 28.84% (K = 0.194, 95%CI: 0.168-0.219). conclusion: HER2 low expression breast cancer may not be regarded as a unique BC group in this real-world population due to similar clinicopathological features and prognostic roles especially in hormone-receptor positive cases. ER level was positively correlated with the rate of HER2 low population. Overall, whether HER2 low is a distinct subgroup remains to be supported and validated by more data both in clinical and molecular levels. Key words: HER2 low; Breast cancer; Clinicopathological Features; Prognosis; Molecular type Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study Citation Format: Ziqing Kong, Weihong Zhao. Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-07.

Abstract PO4-07-12: Concordance of Breast ultrasound (US) and breast Magnetic resonance imaging (MRI) for local (tumor size and node involvement) staging in patients with breast cancer before neoadjuvant chemotherapy treatment (NACT)

Abstract Introduction Breast cancer is the main cause of cancer-related deaths in Colombia, with many patients diagnosed with locally advanced (LABC) or metastatic disease. In the locally advanced setting, the use of NACT offers the opportunity of downstage BC and allows to adjust therapy based on the response, but, considering emerging therapies available in LACB as immunotherapy in triple negative BC (TNBC), dual HER2 blockade in HER2 positive BC or adjuvant iCDK 4/6 in luminal BC the importance of accurate pre NACT staging has become critical, we aim to explore the concordance of US and MRI as a method of BC staging in the NACT setting. Methods: EVA (Evidence – Verification – Analysis) is a prospective institutional multi-tumor registry that aims to gather demographic, clinical, and genomic variables from patients treated at Fundación CTIC, in Bogota Colombia, based on this registry, we recover the data from the patients that were treated with NACT and were staged with a US and an MRI before the initiation of treatment, dis concordance between the two methods was establish if a different Tumor size (change from T2 to T3 for example), a different node stage (chance from N2 to N2) or the discordant detection of multifocal disease, a descriptive analysis were performed. Results: 30 Patients were included in the analysis, The mean age was 51,7 years (28 – 79), 15/30 patients were ER of PgR positive BC, 11/30 HER2 positive BC (7/11 HER2 positive and 4/11 Luminal B HER2 positive) and 4/30 were TBNC. 28/30 patients were ductal carcinoma, with 1/30 lobular carcinoma and 1/30 medullary carcinoma. Mean ADC in luminal A-like BC was 0,9, 0,66 (0,4 – 0,9) in luminal-B HER2 negative BC, 0,77 (0,4 – 0,9) in HER2 positive BC, and 0,83 (0,7 – 0,9) in TNBC Concordance between US and MRI was only seen in 14/30 patients. The causes of discordance were Tumor size on 9/16 (change from T2 to T3 or evidence of pectoral muscle involvement), node staging on 11/16 (8/11 patients were node down staged based on MRI image), and evidence of multifocal disease not seen in the US on 2/16. Conclusion: Considering the high discordance rate between US and MRI, and the implications of accurate staging before NACT, we think that MRI should be considered as a routine evaluation before NACT. This is a small sample so a larger cohort would be needed for confirmation of this observation, based on the design of EVA, we expect to further evaluate the significance and uses in the NACT setting. Citation Format: Aura Pareja, Sergio Cervera, Maria Bravo, Sandra Franco, Jose Caicedo, William Mantilla. Concordance of Breast ultrasound (US) and breast Magnetic resonance imaging (MRI) for local (tumor size and node involvement) staging in patients with breast cancer before neoadjuvant chemotherapy treatment (NACT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-12.

Abstract PO5-06-05: DISCORDANCE BETWEEN HORMONE RECEPTORS AND HER2 STATUS IN BREAST CANCER PATIENTS RELAPSE

Abstract Introduction: Breast cancer (BC) is a heterogeneous disease, and during its progression, the tumor phenotype can undergo changes that are often associated with a poor prognosis. In this study, we aim to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression between primary and recurrent/metastatic lesions. Methods: This study is a retrospective analysis of 132 non-advanced breast cancer patients who experienced confirmed recurrence/metastasis at the Instituto Nacional de Enfermedades Neoplasicas between 2011 and 2022. Descriptive analysis was conducted to assess the expressions of ER, PgR, HER-2, and Ki-67 in primary and metastatic breast cancer, as well as clinical variables. Normality tests, including Kolmogorov-Smirnov and Shapiro-Wilk, were performed. The paired samples Wilcoxon test was used to determine significant differences between primary and recurrent/metastatic tumors. Additionally, Spearman's rank correlation coefficient was employed to evaluate the relationships of expression discordance. Results: Fifty-nine percent of patients presented locoregional recurrence, while 41% presented visceral metastasis. In the primary tumor, ER and PR expression were found in 63.6% and 55.3% of cases, respectively. HER2 status was determined as 0 (36.3%), +1 (22%), +2 (14.4%), +3 (26.5%), and not determined (0.8%) by IHC. For the recurrent/metastatic tumor, ER and PR expression were found in 59% and 34% of cases, respectively. HER2 status was determined as 0 (27.3%), +1 (19.7%), +2 (25%), +3 (25%), and not determined (3%). The median Ki-67 levels were 37% in the primary tumor and 40% in the recurrent/metastatic tumor. Significant differences were found for ER (p=0.014), PR (p< 0.001), and HER2 (p=0.019), but not for Ki-67 percentage (p=0.139). The discordance rates of ER, PR, HER2, and Ki-67 expression were 27.9%, 47.7%, and 26.3%, respectively. Conclussions: Discordance in hormone receptor expression between primary and recurrent/metastatic tumors is a common phenomenon, with ER showing a discordance rate of 27.9% and PR showing a higher rate of 47.7%. HER2 status also displayed significant discordance, with a 26.3% rate of discordant expression between primary and recurrent/metastatic tumors. The findings from this study emphasize the dynamic nature of breast cancer and the importance of comprehensive evaluation of biomarker expression in both primary and recurrent/metastatic tumors, to choose the best treatment options. Citation Format: Katia Roque, Iris Otoya, Natalia Valdivieso, Zaida Morante, Hugo Fuentes, Silvia Neciosup, Henry Gómez, Jorge Cotito, Gonzalo Ziegler, Estefania Peña, Tatiana Vidaurre, Ramon Andrade de Mello, Carlos Castañeda. DISCORDANCE BETWEEN HORMONE RECEPTORS AND HER2 STATUS IN BREAST CANCER PATIENTS RELAPSE [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-05.

Manual Evaluation of Record Linkage Algorithm Performance in Four Real-World Datasets.

Patient data are fragmented across multiple repositories, yielding suboptimal and costly care. Record linkage algorithms are widely accepted solutions for improving completeness of patient records. However, studies often fail to fully describe their linkage techniques. Further, while many frameworks evaluate record linkage methods, few focus on producing gold standard datasets. This highlights a need to assess these frameworks and their real-world performance. We use real-world datasets and expand upon previous frameworks to evaluate a consistent approach to the manual review of gold standard datasets and measure its impact on algorithm performance. We applied the framework, which includes elements for data description, reviewer training and adjudication, and software and reviewer descriptions, to four datasets. Record pairs were formed and between 15,000 and 16,500 records were randomly sampled from these pairs. After training, two reviewers determined match status for each record pair. If reviewers disagreed, a third reviewer was used for final adjudication. Between the four datasets, the percent discordant rate ranged from 1.8 to 13.6%. While reviewers' discordance rate typically ranged between 1 and 5%, one exhibited a 59% discordance rate, showing the importance of the third reviewer. The original analysis was compared with three sensitivity analyses. The original analysis most often exhibited the highest predictive values compared with the sensitivity analyses. Reviewers vary in their assessment of a gold standard, which can lead to variances in estimates for matching performance. Our analysis demonstrates how a multireviewer process can be applied to create gold standards, identify reviewer discrepancies, and evaluate algorithm performance.

Development and validation of a GT-seq panel for genetic monitoring in a threatened species using minimally invasive sampling.

Minimally invasive samples are often the best option for collecting genetic material from species of conservation concern, but they perform poorly in many genomic sequencing methods due to their tendency to yield low DNA quality and quantity. Genotyping-in-thousands by sequencing (GT-seq) is a powerful amplicon sequencing method that can genotype large numbers of variable-quality samples at a standardized set of single nucleotide polymorphism (SNP) loci. Here, we develop, optimize, and validate a GT-seq panel for the federally threatened northern Idaho ground squirrel (Urocitellus brunneus) to provide a standardized approach for future genetic monitoring and assessment of recovery goals using minimally invasive samples. The optimized panel consists of 224 neutral and 81 putatively adaptive SNPs. DNA collected from buccal swabs from 2016 to 2020 had 73% genotyping success, while samples collected from hair from 2002 to 2006 had little to no DNA remaining and did not genotype successfully. We evaluated our GT-seq panel by measuring genotype discordance rates compared to RADseq and whole-genome sequencing. GT-seq and other sequencing methods had similar population diversity and F ST estimates, but GT-seq consistently called more heterozygotes than expected, resulting in negative F IS values at the population level. Genetic ancestry assignment was consistent when estimated with different sequencing methods and numbers of loci. Our GT-seq panel is an effective and efficient genotyping tool that will aid in the monitoring and recovery of this threatened species, and our results provide insights for applying GT-seq for minimally invasive DNA sampling techniques in other rare animals.

Outcomes of a Multisite Mentored Implementation Approach to Promoting Goals of Care Conversations

ContextThe Preference-Aligned Communication and Treatment (PACT) Project is a multisite quality improvement effort that has been shown to increase the frequency of goals of care (GOC) conversations in hospitalized patients with serious illness. ObjectivesTo evaluate the effect of PACT on goal-discordant care and resource utilization. MethodsHospitals enrolled in a multiyear mentored implementation quality improvement initiative to facilitate GOC conversations for seriously ill hospitalized patients. The primary outcome was the percentage of patients with care discordant with stated preferences, assessed by comparing documented wishes to Medicare claims data for patients who were admitted to intervention units and died over the study period. Secondary outcomes evaluated end-of-life resource utilization by comparing Medicare claims data for intervention patients with propensity score-matched controls. ResultsIn the 9 hospitals included in the study, 1347 intervention group patients were compared to 4019 in the control group. Rates of discordance between wishes and care were generally low in the intervention group. Compared to the control group, patients in the intervention group had lower costs (−976.05 dollars, P = 0.010), were less likely to be admitted to the ICU (OR 0.9, P = 0.005), less likely to be on a ventilator or undergo CPR or cardioversion, more likely to enroll in hospice (OR 1.81, P < 0.001) and had a longer hospice stay (3.35 more days, P = 0.041). ConclusionA multisite mentored implementation quality improvement intervention for seriously ill hospitalized patients resulted in care aligned with goals and decreased resource utilization at the end of life.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status

BackgroundHuman epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody–drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status.MethodsThis retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed.ResultsThe overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion.ConclusionsIncorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study

BackgroundThe role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (μQFR) as the reference. MethodsCPET and μQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting μQFR ≤ 0.8. ResultsThe optimal cutoff value of O2-pulse slope ratio for predicting μQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505–0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and μQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and μQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and μQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01–0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47–64.82, p = 0.018). ConclusionOur findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Commercial Synovial Antigen Testing is Inferior to Traditional Culture for the Diagnosis of Periprosthetic Joint Infection in Patients Undergoing Revision Total Knee Arthroplasty

BackgroundDespite its limitations, a culture remains the “gold standard” for pathogen identification in patients who have periprosthetic joint infection (PJI). Recently, a synovial fluid antigen test has been introduced by a commercial entity. The purpose of this multicenter study was to determine the accuracy of the antigen test in the diagnosis of PJI. MethodsThis retrospective study identified 613 patients undergoing revision total knee arthroplasty who had undergone preoperative synovial fluid analysis. A PJI was defined using the 2018 International Consensus Meeting (ICM) criteria. Patients who had an extended period (> 180 days) from aspiration to revision procedure (n = 62), those presenting within 90 days of their index arthroplasty procedure (n = 17), and patients who had an inconclusive ICM score (n = 8) were excluded. Using receiver operator characteristic curve analyses, we examined the utility of the microbial identification (MID) antigen test and any positive culture (either preoperative or intraoperative) in the diagnosis of PJI. ResultsA total of 526 patients were included. Of these, 125 (23.8%) were ICM positive and 401 (76.2%) were ICM negative. Culture demonstrated an area under the curve (AUC) of 0.864, sensitivity of 75.2%, and specificity of 97.5%. On the other hand, the MID test exhibited an AUC of 0.802, sensitivity of 61.6%, and specificity of 98.8%. The AUC of culture was significantly higher than that of the MID test (P = .037). The MID test was positive in 41.9% of culture-negative PJI cases. We also observed a high rate of discordance (29.7%) when both culture and the MID test were positive in the ICM-positive group. ConclusionsSynovial fluid antigen testing does not provide additional clinical benefit when compared to traditional cultures for the diagnosis of PJI. The antigen test had low sensitivity in the diagnosis of PJI and a relatively high rate of discordance with culture. Level of EvidenceLevel III.

Discrepancies in Gleason score between needle core biopsy and radical prostatectomy specimens with correlation between clinical and pathological staging.

The studies have shown that GS given after assessment of the entire prostate gland on the radical prostatectomy specimen may differ from GS given after examination of a small sample from needle core biopsy. We conducted this study to assess discrepancies in the Gleason score between NCB and RP specimens and to find out the correlation between the clinical stage and pathological stage. The study included 174 patients with carcinoma prostate which underwent robotic-assisted radical prostatectomy (RARP). Pre-operative Gleason score was determined on 12-core biopsy samples under trans-rectal ultrasound (TRUS) guidance. The Gleason score obtained from the radical prostatectomy specimen was compared with that of the NCB Gleason score to find out differences. The preoperative Gleason score (GS) ranges from 6 to 9 with a mean GS of 6.97 ± 1.02. The post-operative GS ranges between 6 and 10 with mean and GS of 7.5 ± 1.10. On the pre-operative assessment of biopsy specimens, 70 (43.2%) patients had a GS of 6, while 44 patients had a GS of 7 (27.1%) and 48 (29.8%) patients had a GS of more than 7. On the postoperative assessment of specimens, 31 (19.1%) patients had post-operative GS of 6, while 66 (41%) patients had GS of 7 and 74 (41.1%) patients had GS of more than 7. When pre-operative GS and post-operative GS were compared, no changes were observed in the GS of 79 patients, whereas 83 patients showed the difference in GS, with 75 patients showing up-gradation and eight patients marked as down-graded. concordance between biopsy and the pathology results directly affects the prognosis of the patient. The results of our study demonstrated the rate of discordance between Gleason scores obtained from transrectal prostate biopsy and RP surgical specimens. This rate brings into question the accuracy of the chosen treatment.

Advances in testing for human papillomavirus -mediated head and neck cancer.

New evidence has recently emerged regarding the utility and benefits of dual p16 INKa (p16) and Human papillomavirus (HPV) status testing when determining the diagnosis and prognosis of patients with oropharyngeal cancer. HPV RNA polymerase chain reaction (PCR) is the most accurate diagnostic test. The other assays (HPV DNA PCR, HPV DNA/RNA in-situ hybridization (ISH) and p16) applied to formalin fixed tumour tissue have varying but high sensitivities and specificities. Dual p16 and HPV testing identifies discordant (p16+/HPV- or p16-/HPV+) results in 9.2% of cases, who have significantly poorer prognoses than p16+/HPV+, particularly in smokers. The proportion of discordant cases varies by region, and appears to be highest in regions with lowest attributable (p16+/HPV+) fractions. Dual testing improves prognostication for oropharyngeal cancer cases by identifying discordant cases and improving the prognostic power of the Tumour Node Metastasis (TNM) classification, especially in regions with high discordant rates. Dual testing is essential when considering patients for clinical trials of treatment de-escalation, and may be important when counselling patients on prognosis, especially in regions with high discordant rates and in smokers.

Finger cuff versus invasive and noninvasive arterial pressure measurement in pregnant patients with obesity.

Pregnant patients with obesity may have compromised noninvasive blood pressure (NIBP) measurement. We assessed the accuracy and trending ability of the ClearSight™ finger cuff (FC) with invasive arterial monitoring (INV) and arm NIBP, in obese patients having cesarean delivery. Participants were aged ≥18 years, ≥34 weeks gestation, and body mass index (BMI) ≥ 40 kg m-2. FC, INV, and NIBP measurements were obtained across 5-min intervals. The primary outcome was agreement of FC measurements with those of the reference standard INV, using modified Bland-Altman plots. Secondary outcomes included comparisons between FC and NIBP and NIBP versus INV, with four-quadrant plots performed to report discordance rates and evaluate trending ability. Twenty-three participants had a median (IQR) BMI of 45 kg m-2 (44-48). When comparing FC and INV the mean bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 16 mmHg (17, -17.3 to 49.3 mmHg), for diastolic blood pressure (DBP) -0.2 mmHg (10.5, -20.7 to 20.3), and for mean arterial pressure (MAP) 5.2 mmHg (11.1, -16.6 to 27.0 mmHg). Discordance occurred in 54 (26%) pairs for SBP, 41 (23%) for DBP, and 41 (21.7%) for MAP. Error grid analysis showed 92.1% of SBP readings in Zone A (no-risk zone). When comparing NIBP and INV, the mean bias (95% limits of agreement) for SBP was 13.0 mmHg (16.7, -19.7 to 29.3), for DBP 5.9 mmHg (11.9, -17.4 to 42.0), and for MAP 8.2 mmHg (11.9, -15.2 to 31.6). Discordance occurred in SBP (84 of 209, 40.2%), DBP (74 of 187, 39.6%), and MAP (63 of 191, 33.0%). The FC and NIBP techniques were not adequately in agreement with INV. Trending capability was better for FC than NIBP. Clinically important differences may occur in the setting of the perfusion-dependent fetus.

Concordance Rate of Radiological Stage With Post-Operative Pathological Stage In Breast Cancer

Objective: To assess the concordance between the radiological and post-operative pathological stages in invasive breast carcinoma. Study Design: Cross-validation study Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan, from Jan to Jul 2020. Methodology: A total of 160 females aged 20-80 years with confirmed diagnosis of breast cancer underwent upfront modified radical mastectomy along with axillary node dissection were included in the study. Demographic and clinic pathological findings of all the patients were reported in pre-designed proforma. Stage concordance was labelled as a patient assigned to the same stage radiologically and pathologically. Results: The mean age of the 160 patients was 47.22±10.51 years. The relationship between radiological and pathological staging was weak (r=0.383) but statistically significant (p=0.001). The tumor stage on radiological and pathological assessment was similar in 60 cases (37.3%). Radiologic assessment overestimated the stage in 75 cases (46.6%) and underestimated it in 26 cases (16.1%). The overall concordance between radiological and pathological staging was 18.8% (p=0.001). Conclusion: Among patients with breast cancer, a high rate of discordance was observed between the radiological and pathological stages. The high odds of discordance are therefore important to plan treatment.

A National School Health Campaign in Lebanon on Children Aged between 3 and 12 Years Old: Concordance Level between Parents' Reports and Medical Visit Findings about Physical and Mental Health.

A school's commitment to promoting health extends beyond students' efforts to encompass parental involvement and must recognize the critical role of parents in enhancing overall student well-being. This study, conducted in 27 schools across Lebanon, assessed parents' awareness of their children's physical and mental health. A school health campaign involved direct medical interventions on 7184 students, followed by phone interviews with 3880 parents to compare their responses with the medical findings. Discordances ranged from extreme mismatches (≥50%) to mild mismatches (<15%), with notable disparities in incomplete vaccination (67.8%), BMI (59%), and mental health indicators (expressions of sadness (69.1%), loneliness (61.0%), and anxiety (53.4%)). Factors such as school type, child's age, governorate, family income, parents' occupation, education level, and marital status significantly influenced discordance rates. Notably, mental health aspects exhibited higher disparities, emphasizing the need for improved communication between parents, physicians, and children. Bridging these gaps could empower parents with better knowledge, fostering environments conducive to lifelong healthy behaviors in children. The study underscores the urgency for enhanced communication strategies to bridge discrepancies and ensure a more comprehensive understanding of children's physical and mental well-being.

Optimization of intraoperative lumpectomy specimen labeling

BackgroundAccurate lumpectomy specimen orientation is critical as incorrect orientation may result in excision of the wrong lumpectomy margin. Our goal was to determine if specimen orientation achieved by labeling three surfaces is superior to two. MethodsThis was a prospective single-institution study including 22 breast surgical oncologists. Intraoperative labeling of either two or three surfaces of the lumpectomy specimen was based on surgeon preference. The specimen was delivered to Pathology where it was oriented by the pathology team and the surgeon then determined if the specimen was correctly oriented or if re-orientation was required. Surgeons subsequently recorded orientation technique and if re-orientation was required. Specimen weight, patient age, and BMI were recorded. Fisher’s exact test and two-sample Wilcoxon rank-sum test were used to determine p-values. ResultsOf 268 specimens, 40 (14.9%) required re-orientation. Labeling specimens on three surfaces was superior to two (22 of 195 (11.2%) versus 18 of 73 (24.6%), p = 0.01). Specimens requiring re-orientation were more likely to be heavier (36 g vs. 24 g, p = 0.02). In multivariable analysis, labeling specimens on three surfaces resulted in a 70% reduction in discordance rates between the surgeon and pathology team (OR 0.3, p = 0.001). Using mean weight of lumpectomy specimens, specimens >33 g were more likely to require reorientation (OR 2.8, p = 0.004). Age and BMI did not impact the need for re-orientation. ConclusionLumpectomy specimen labeling using three surfaces was superior to two. Surgeons should routinely orient their specimens on three or more surfaces to decrease discordance rates.

Compliance with new drug use and the effect of discrepant drug susceptibility testing on MDR/RR-TB treatment.

BACKGROUND: Following the WHO???s announcement in 2018, the use of new drugs was recommended for all patients with multidrug-resistant TB (MDR-TB) in Korea. This study aimed to evaluate adherence to new anti-TB drug regimens and implementation of molecular drug susceptibility testing (mDST) in Korea.METHODS: Nationwide, 560 patients were reported as having MDR-TB in 2021. The implementation of mDST and new anti-TB drug use were analysed. The discrepancy between mDST and phenotypic DST (pDST) results and their implications on the use of new anti-TB drugs were also analysed. The use of novel anti-TB drugs has been approved by the National TB Expert Committee.RESULTS: The non-adherence rate in MDR-TB patients was 14.3%. The mDST implementation rate was 96.1%. Of the 459 patients who underwent both mDST and pDST, the discordance rate for rifampicin (RIF) resistance was 22.6% (n = 104), of which 72.1% (n = 75) were resistant on mDST but susceptible on pDST. The discrepancy in mDST and pDST results related to RIF resistance was found to be the main cause of non-adherence to new drug regimen.CONCLUSION: Comprehensive training on how to interpret conflicting results between mDST and pDST could enhance the utilisation of new drugs in the treatment of MDR/RIF-resistant TB.

Impact of stroke volume assessment by three-dimensional transesophageal echocardiography on the classification of low-gradient aortic stenosis.

Accurate assessment of flow status is crucial in low-gradient aortic stenosis (AS). However, the clinical implication of three-dimensional transesophageal echocardiography (3DTEE) on flow status evaluation remains unclear. This study aimed to investigate the assessment of flow status using 3D TEE in low-gradient AS patients. We retrospectively reviewed patients diagnosed with low-gradient AS and preserved ejection fraction at our institution between 2019 and 2022. Patients were categorized into low-flow/low-gradient (LF-LG) AS or normal-flow/low-gradient (NF-LG) AS based on two-dimensional transthoracic echocardiography (2DTTE). We compared the left ventricular outflow tract (LVOT) geometry between the two groups and reclassified them using stroke volume index (SVi) obtained by 3DTEE. Among 173 patients (105 with LF-LG AS and 68 with NF-LG AS), 54 propensity-matched pairs of patients were analyzed. 3DTEE-derived ellipticity index of LVOT was significantly higher in LF-LG AS patients compared to NF-LG AS patients (p = 0.012). We assessed the discordance in flow status classification between SVi2DTTE and SVi3DTEE in both groups using a cutoff value of 35ml/m2. The LF-LG AS group exhibited a significantly higher discordance rate compared to the NF-LG AS group, with rates of 50% and 2%, respectively. The optimal cutoff values of SVi3DTEE for identifying low flow status, based on 2DTTE-derived cutoff values, were determined to be 43ml/m2. LVOT ellipticity in low-gradient AS patients varies depending on flow status, and this difference contributes to discrepancies between SVi3DTEE and SVi2DTTE, particularly in LF-LG AS patients. Utilizing SVi3DTEE is valuable for accurately assessing flow status.

Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.