Discordant Group Research Articles

A Participatory and Spatial Multicriteria Decision Approach to Prioritize the Allocation of Ecosystem Services to Management Units

Forest management planning can be challenging when allocating multiple ecosystem services (ESs) to management units (MUs), given the potentially conflicting management priorities of actors. We developed a methodology to spatially allocate ESs to MUs, according to the objectives of four interest groups—civil society, forest owners, market agents, and public administration. We applied a Group Multicriteria Spatial Decision Support System approach, combining (a) Multicriteria Decision Analysis to weight the decision models; (b) a focus group and a multicriteria Pareto frontier method to negotiate a consensual solution for seven ESs; and (c) the Ecosystem Management Decision Support (EMDS) system to prioritize the allocation of ESs to MUs. We report findings from an application to a joint collaborative management area (ZIF of Vale do Sousa) in northwestern Portugal. The forest owners selected wood production as the first ES allocation priority, with lower priorities for other ESs. In opposition, the civil society assigned the highest allocation priorities to biodiversity, cork, and carbon stock, with the lowest priority being assigned to wood production. The civil society had the highest mean rank of allocation priority scores. We found significant differences in priority scores between the civil society and the other three groups, highlighting the civil society and market agents as the most discordant groups. We spatially evaluated potential for conflicts among group ESs allocation priorities. The findings suggest that this approach can be helpful to decision makers, increasing the effectiveness of forest management plan implementation.

Novel biomarker panel measuring endothelial injury identifies patients at risk of coronary artery syndrome and discordance with low-density lipoprotein cholesterol.

Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS with normal LDL-C using a novel validated coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury. Five-year predicted ACS risk was calculated for 6392 persons using CADPA. Persons were classified as low (<3.5%), intermediate (3.5-<7.5%) or high (≥7.5%) CADPA risk and by LDL-C levels <130 mg/dL (low) and ≥130 mg/dL (high) and whether in the discordantly low LDL-C (but high CADPA risk) or high LDL-C (but low/intermediate CADPA risk) group. Multiple logistic regression identified risk factors and biomarkers that predicted discordance. 31% were classified as low (<3.5%), 27% at intermediate (3.5-<7.5%) and 42% were at high risk (≥7.5%). 28% of subjects were identified in the low LDL discordant risk group (LDL-C< 130 mg/dL but 5-year CADPA predicted risk ≥7.5%) and 19% in the high LDL discordant risk group (LDL-C ≥ 130 mg/dL but 5-year CADPA risk of <7.5%). Diabetes (odds ratio [OR], 2.84 [2.21-3.66]), male sex (OR, 2.83 [2.40-3.35]), family history (OR, 2.23 [1.88-2.64]) and active smoking (OR, 1.99 [1.50-2.62]) predicted low LDL risk discordance more than other risk factors (all P < 0.01). Increased serum soluble FAS, hemoglobin A1c and interleukin-16 were the biomarkers most independently associated with increased risk. Discordance between LDL-C levels and ACS risk is common. Males with diabetes and a family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify individuals that could benefit from earlier targeting of risk factor modification for the prevention of ACS.

904-P: Discordance between Youth and Parent Report of Diabetes Distress in Type 1 Diabetes (T1D): The Importance of Youth Perceptions

Diabetes Distress (DD) can be experienced differently by family members living with T1D. We examined concordance and discordance between youth and parent report of DD and the relationship with youth glycemic control, diabetes-specific family conflict and parent involvement in diabetes tasks in a sample of youth starting real-time continuous glucose monitoring (CGM). Youth (N=120, 51% male) with T1D ages 8-17 years and their parents (84% mothers) completed surveys assessing DD, family conflict and parent involvement. Previously validated cut-points of &amp;gt;41 (PAID-Peds, youth) and &amp;gt;56 (PAID-PR, parents) identified clinically significant DD. Youth/parent dyads were classified as concordant when both youth and parents scored below (Youth Low/Parent Low) or above (Youth High/Parent High) the cut-points. Youth/parent dyads were classified as discordant when youth scored below and parent scored above (Youth Low/Parent High) or youth scored above and parent scored below (Youth High/Parent Low) the cut-points. Youth had a mean±SD age of 12.7±2.7 years, T1D duration 6.1±3.6 years and A1c 8.0±0.8%; 84% were pump treated. About ¼ of youth (26%) and parents (23%) reported clinically significant DD with 62% of dyads concordant for low DD, 10% concordant for high DD and 28% discordant for DD. Concordant groups did not differ significantly from discordant groups. In the 2 discordant groups, A1c and youth-reported family conflict differed significantly; A1c: 7.5±0.9% vs. 8.3±0.7% (p=.043) and family conflict: 5.6±5.1 vs. 22.9±22.0 (p=.036) in the Youth Low/Parent High and Youth High/Parent Low groups, respectively. Parent involvement did not differ across the groups. DD can be perceived differently by youth with T1D and their parents. When youth perceive high DD and parents do not, youth appear at risk for adverse outcomes, highlighting the importance of youth perceptions. Disclosure K. Wentzell: None. M. R. Fu: None. L. K. Volkening: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. Funding National Institutes of Health (R01DK089349, K12DK094721, P30DK036836)

Recurrence score testing does not appear to benefit patients with Grade 1, progesterone receptor-positive breast cancers: An opportunity to eliminate overtreatment and decrease testing costs

BackgroundWe previously described a risk prediction model (Anne Arundel Medical Center [AAMC] model) based on pathology which may eliminate the need for recurrence score (RS) testing in select early-stage breast cancers. There is a concern that patients in discordant risk prediction groups (AAMC vs. RS) may be overtreated or undertreated if RS testing were omitted. MethodsWe queried the Surveillance, Epidemiology, and End Results (SEER) database for all breast cancer patients between 2004 and 2015. AAMC low-risk was defined as Grade 1 and progesterone receptor-positive (PR + ) tumors, while AAMC high-risk was defined as Grade 3 or estrogen-negative tumors. RS low-risk group was defined as RS < 16 and age ≤ 50 years, or RS ≤ 25 and age > 50 years. RS high-risk group was defined as RS > 25. ResultsA total of 71,212 cases were analyzed. Of these, 590 were AAMC low-risk/RS high-risk discordant, while 5,596 were AAMC high-risk/RS low-risk discordant. For AAMC low-risk/RS high-risk discordant, 10-year breast cancer-specific survival (BCSS) did not differ for patients who received adjuvant chemotherapy versus those who did not (93% chemotherapy vs. 99% unknown/no chemotherapy, p = .12). Overall survival (OS) was also comparable (92% chemotherapy vs. 91% unknown/no chemotherapy, p = .42). In the AAMC high-risk/RS low-risk discordant group, 10-year BCSS (92% chemotherapy vs. 96% unknown/no chemotherapy, p = .06) and OS (87% chemotherapy vs. 90% unknown/no chemotherapy, p = .52) did not differ between adjuvant chemotherapy and unknown/no chemotherapy groups. ConclusionsAdjuvant chemotherapy in the AAMC low-risk/RS high-risk and AAMC high-risk/RS low-risk discordant groups did not improve survival. This supports consideration of omission of RS testing in Grade 1, PR + tumors. Patients with Grade 3 tumors do benefit from RS testing.

Real-world concordance between tumor mutational burden (TMB) from blood (circulating tumor DNA) and tissue in lung cancer.

e20522 Background: Tumor mutational burden (TMB) level is associated with response to immunotherapy in lung cancer. However, tissue TMB can be difficult to obtain, as tissue samples obtained from biopsies may be insufficient. Circulating tumor DNA-based TMB has been developed in order to complement or replace tissue TMB, but there is limited real-world data on their concordance. Here, we investigate the landscape and concordance between blood and tissue TMB, along with clinical traits of the concordant and discordant groups. Methods: Tumor mutational burden (TMB) was calculated using Tempus (tissue) and Guardant Health (blood) next generation sequencing (NGS) platforms from October 2020 to January 2021. There were 33 patients who had both Tempus and Guardant TMB data. Under the assumption that tissue TMB (tTMB) correlates with blood TMB (bTMB) at a ratio of 1:1.6, the patients were divided into concordant and discordant groups. The concordant group patients had bTMB/tTMB ratios between 1.3 and 1.9. The discordant group was divided into two subgroups: over 1.9 (Group B) and less than 1.3 (Group C). Among the 33 patients, 9 patients were excluded due to their non-evaluable bTMB levels. Treatment response was evaluated using RECIST criteria. Results: Of the remaining 24 patients, 7 patients in the concordant group and 21 patients in the discordant group were analyzed according to their clinical manifestations [Blood TMB (n = 24): range [1.46, 44.01], median = 9.57], [Tissue TMB (n = 24), range [1.3, 18.4], median = 4.5]. We compared the clinical presentations (number of metastatic organs and metastatic sites) between the two discordant groups (Groups B and C). Among the 24 patients, 13% (n = 3) had small cell lung cancer, 50% (n = 12) had adenocarcinoma, and 29% (n = 7) had squamous cell lung carcinoma. Patients with higher bTMB than tTMB (Group B) had more squamous cell carcinoma cases (71%, n = 5) compared to remaining groups (Groups A and C) (29%, n = 2). Among the discordant group, 6% of the patients (n = 1) had small cell lung cancer, 47% (n = 8) had adenocarcinoma, and 35% (n = 6) had squamous cell carcinoma. Further, 58% (n = 14) of the patients had higher bTMB than tTMB levels. Among the concordant and discordant groups, tumor burden as reflected by the number of metastatic sites and metastatic lesions and the sum of the largest diameters of tumor lesions using RECIST had no significant difference (p = 0.10, 0.68, 0.54, respectively). The concordant and discordant groups showed no significant difference in objective response (33% vs. 20%, p = 0.60) or clinical benefit rate (100% vs. 60%, p = 0.33). Conclusions: The majority of the patients had higher blood TMB than tissue TMB (Group A), with a concordance rate as low as 28%. Further studies are warranted to understand the biology behind the difference between blood and tissue TMB, including intertumoral heterogeneity.

Concordance of HER2+ status by IHC/ISH and ERBB2 status by NGS in a real-world clinicogenomic database and analysis of outcomes in patients (pts) with metastatic breast cancer (mBC).

1036 Background: HER2 overexpression/amplification measured by IHC or ISH is a predictive biomarker for HER2-targeted therapies. Next-generation sequencing (NGS) can identify ERBB2 amplification (amp) and mutations. We examined clinical characteristics, NGS testing patterns, and outcomes of pts treated with 1L HER2 therapy with HER2+ mBC based on ERBB2 amp status using a real-world (RW) clinico-genomic database (CGDB). Methods: Pts with mBC (HER2+ by IHC and/or ISH) treated with 1L HER2 therapy who had undergone NGS and were treated within the Flatiron Health (FH) network were eligible. Clinical characteristics and HER2 testing results were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports and linked to genomic data from Foundation Medicine (FMI) in the nationwide (US-based), de-identified FH-FMI CGDB. Demographic, clinical and genomic characteristics were summarized and stratified by concordance between HER2+ (IHC 3+ or ISH amp+) and ERBB2amp+ status [copy number (CN) ≥ 5]. NGS testing patterns and 1L HER2 therapy were characterized and stratified by concordance status. Concordance was assessed based on contemporaneous timing of paired test specimen collection dates (FMI NGS ≤ 30 days of HER2+ status). RW overall survival (rwOS) stratified by HER2+/ ERBB2 amp concordance was estimated with Kaplan-Meier analysis and adjusted Cox proportional hazards models. Results: Among 268 eligible pts, HER2+/ ERBB2amp+ concordance was 66% (176/268); concordance among contemporaneous paired specimens was 73% (106/145). Demographic and clinical features were overall well-balanced with most pts treated at community sites [94%, (252/268)]; the discordant (HER2+/ ERBB2amp-) group (95/268) had more pts with hormone receptor positive disease (73% vs 62%). Concordance by assay type varied; IHC+ only, IHC+/ISH+, and ISH+ only agreement was 72% (95/132), 76% (26/34) and 52% (50/96), respectively. A higher proportion of discordance (35% vs 19%) was seen in pts treated at community vs. academic sites. Median rwOS was 32.9 months (IQR 25.9-38.9) among concordant (HER2+/ ERBB2amp+) and 15.5 months (IQR 8.9-30.1) among discordant (HER2+/ ERBB2amp-) pts, aHR = 0.71 [95% CI: 0.48-1.03; p = 0.073]. Conclusions: Among RW pts with HER2+ mBC receiving 1L HER2 therapy, discordance between ERBB2amp and IHC/ISH HER2 testing methods was observed. Pts with tumors HER2+ by IHC and/or ISH but negative for ERBB2amp had a trend towards worse rwOS following receipt of HER2 therapy compared to concordant cases. Contemporaneous timing of specimen collection was associated with greater concordance. Future analyses on the additive value of ERBB2 CN as a predictive marker, and assessing factors that may affect discordance such as intratumor HER2 heterogeneity, tumor content, and biopsy site are warranted.

The Clinical and Radiologic Outcomes of Patients With Different 3-Dimensional Hemivertebra Morphologies Undergoing Posterior-Only Hemivertebra Resection and Fusion

To compare the clinical and radiologic outcomes of patients with different 3-dimensional (3D) hemivertebra morphologies undergoing posterior-only hemivertebra resection and fusion. The files of patients with congenital scoliosis (CS) due to single hemivertebra undergoing posterior-only hemivertebra resection and fusion from January 2010 to January 2018 were reviewed. After evaluating the 3D computed tomography images, CS patients were divided into a unison hemivertebra group and a discordant hemivertebra group. Clinical outcomes, radiologic outcomes, and incidence of complications were compared. A total of 42 consecutive patients with CS patients due to a single hemivertebra undergoing posterior-only hemivertebra resection and fusion were included in this study. The Cobb angle of the segmental curve was significantly improved postoperatively and at the last follow-up in both groups (all P < 0.05). At both postoperation and the last follow-up, no significant differences were found in the incidence of complications, Cobb angle of the segmental curve, correction rate of the segmental curve, or other radiologic outcomes between the unison hemivertebra group and discordant hemivertebra group (all P > 0.05). Compared with the unison hemivertebra group, increased operation time (P= 0.006) and intraoperative blood loss (P= 0.037) were found in the discordant hemivertebra group. For CS patients with unison hemivertebra or discordant hemivertebra, satisfactory radiologic results were obtained by posterior-only hemivertebra resection and fusion. In terms of surgery, the radiologic outcomes of discordant hemivertebra patients were similar to those of unison hemivertebra patients, but discordant hemivertebrae could easily result in longer operation time and more intraoperative blood loss.

Relationship between Discordance of Low-Density Lipoprotein and Non-High-Density Lipoprotein Cholesterol and Risk Stratification in Acute Myocardial Infarction

Abstract Background: Sizeable proportion of patients have discordant low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (NHDL-C). It has been shown that discordance of LDL-C and NHDL-C either underestimates or overestimates coronary risk. Objective: We assessed whether this discordance has an impact on GRACE and TIMI risk scores in patients with acute myocardial infarction (AMI). Methods: We retrospectively evaluated the data of 198 consecutive patients with AMI. Fasting serum lipid profiles were recorded, GRACE and TIMI scores were calculated. Patients were divided into 3 groups according to LDL-C and NHDL-C percentiles: Discordant group: LDL-C NHDL-C (n=48). GRACE and TIMI scores, mortality and cardiovascular events (heart failure, non-fatal myocardial infarction and angina) at sixth month were compared between these three groups. Differences between these groups were analyzed with One-way ANOVA or Kruskal-Wallis rank test, and with chi-square for percentages. Also, post hoc LSD or Conover-Iman's non-parametric multiple comparison test were used. A p value NHDL-C (p=0.029 and 0.008, respectively). Cardiovascular events and mortality at sixth month were not different among groups (p=0.473 and p=0.176, respectively). Conclusion: GRACE score was higher in discordant group with LDL-C<NHDL-C, but there is no difference regarding TIMI scores between discordant and concordant groups in AMI patients.

Correlation of COVID-19 antigen test and CBNAAT results at a single tertiary care hospital in North India: an experience

Background: Nucleic acid amplification test (NAAT) is considered gold standard in the molecular diagnosis of CoV-2 infection but since it is costly, labor intensive and needs technical expertise, rapid chromatographic immunoassay for the qualitative detection of specific antigens to SARS CoV-2 have been devised. Objectives of this study was to compare the results of Antigen test and NAAT for CoV-2 infection carried out during the months of July and August 2020 by single tertiary care hospital in Lucknow, Uttar Pradesh and to determine the utility of rapid antigen test in the SARS CoV-2 diagnosis.Methods: All the patients who came to our hospital seeking admission during July 2020 and August 2020 were included in the study. A total of 1000 patients were included in this study.Results: Out of a total 1000 cases which were included in the study, 769 cases (76.9%) were found to be SARS CoV-2 negative by both antigen and CBNAAT, 100 cases (10.0%) were SARS CoV-2 positive by both antigen and CBNAAT tests. But in 131 cases (13.1%), antigen was not able to pick up the disease. It was also found that the Cycle Threshold (Ct) value for the discordant group was higher (Mean E= 28, Mean N2=33) when compared to the group where antigen was positive.Conclusions: The present study establishes the role of rapid antigen tests in contributing to the quick, point of care diagnosis of SARS CoV-2. These assays are safe, simple, and fast and can be used in local clinics and hospitals. These tests are very important for real-time patient management and infection control decision.

Histopathologic Diagnosis Discrepancies Between Preoperative Endoscopic Forceps Biopsies and Specimens Resected by Endoscopic Submucosal Dissection in Superficial Gastric Neoplasms.

The standard of practice when a superficial lesion was identified during upper GI endoscopy is to take an endoscopic forceps biopsy (EFB) of the lesion. The histopathologic findings then will determine the management plan. Endoscopic submucosal dissection (ESD) enables en-bloc resection for early neoplasms of the gastrointestinal tract and provides an adequate specimen that permits a more reliable histopathologic assessment. The objective of this study was to determine the rate of histopathologic discrepancy between EFB and specimens resected by ESD, and to identify the predisposing risk factors for this discordance. This is a retrospective study, enrolling patients with superficial gastric neoplasms that underwent EFB followed by ESD. We divided cases to concordant or discordant group according to the histopathologic diagnosis of EFB and ESD specimens. We also analyzed the features that may have influenced the occurrence of histopathologic discordance and the association between discordant samples of adenocarcinoma and neoplastic invasion to deeper layers. A total of 115 gastric ESD procedures were performed with 84 patients meeting the inclusion criteria. Histopathologic discordance between EFB and ESD specimens were observed in 35.8% of cases (30/84 lesions). The univariant-bivariant analysis and multivariate logistic regression analysis showed that histologic discordance was closely related to the size of the lesions ( P =0.028). Histopathologic discrepancy between EFB and ESD specimens may occur in approximately one-third of cases, particularly for lesions over 20 mm, which may lead to crucial delays in gastric cancer precise diagnosis and treatment.

Is VE/VCO2 Slope More Reflective of Isolated Cardiac Performance Compared to Peak VO2: A Comparison of Cardiopulmonary Stress Test Variables before and after Transplantation

<h3>Purpose</h3> Peak oxygen consumption (VO2) can be influenced by various cardiac, respiratory, pulmonary vascular, and peripheral extraction limitations. The best prognostic marker for isolated cardiac dysfunction remains unclear. This study aimed to determine whether VO2 or minute ventilation-carbon dioxide production slope (VE/VCO2) is more reflective of isolated cardiac performance by assessing pre- and post-operative outcomes of cardiopulmonary exercise testing (CPX) in heart transplant (HT) patients. <h3>Methods</h3> We conducted a single center, retrospective study of HT patients who underwent pre- and post-operative CPX (N= 16) between 2014 and 2019. CPX after-transplant was part of routine care, and all participants were healthy at the time of assessment. Patients with either discordant (N = 9) or concordant (N= 7) pre-transplant VO2 and VE/VCO2 were categorized. Patients with a ventilatory class (severity of VE/VCO2) that was at least one grade more severe than their Weber class (severity of VO2) were defined as discordant. Pre- and post-operative CPX outcomes were compared between the two groups. <h3>Results</h3> For the entire cohort, peak VO2, VE/VCO2, VO2/HR, METs, and RER were comparable pre- and post-operatively (p > 0.05 for all). Paired comparison of change in peak predicted VO2 was significant for the entire cohort (p= 0.04). It trended towards significance in the discordant group (p= 0.06) and was not significant for the concordant group (p= 0.54). The discordant group had a near normal peak predicted VO2 after HT on average 79% (68,90) while the concordant group had an abnormally low peak predicted VO2 46% (37-59) p=0.09. <h3>Conclusion</h3> Patients with VE/VCO2 values higher and out of proportion to VO2 responded more robustly after transplantation. This difference may be reflective of a more isolated cardiac limitation that is more readily correctible after transplantation.

Association of AID and MUM1 by Immunohistochemistry in Diffuse Large B-Cell Lymphoma

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with dysregulation of somatic hypermutation (SHM) and class switch recombination (CSR) have been known to contribute for its lymphomagenesis. Activation-induced cytidine deaminase (AID) enzyme plays a vital role for both processes. Multiple myeloma oncogene 1 (MUM1) is known to upregulate the AID expression in normal and pathological conditions. However, both AID and MUM1 expression association in DLBCL is still unexplored using immunohistochemistry method. We examined DLBCL samples and then retrospectively tested its correlation with clinical findings.METHODS: A retrospective cohort study with 20 cases of DLBCL biopsy tissue with AID and MUM1 antibody was conducted. The samples were then classified into concordant (AID+/MUM1+ or AID-/MUM1-) and discordant group (AID-/MUM1+). The clinicopathological comparison was performed to observe any association between immunohistochemistry expression and clinical findings.RESULTS: Among 20 samples of DLBCL, concordant expression rate of AID and MUM1 was 80% with kappa Cohen’s of 0.578 (p=0.004). A significant association was observed between AID and MUM1 expression with a prevalence ratio of 2.25 (95% CI: 1.08-4.67; p=0.008). Clinical characteristics were not significantly different between each group. Restricted mean survival time was shorter in the concordant group compared with the discordant group but statistically insignificant (21.16 vs. 22.5 months; p=0.531).CONCLUSION: The result of this study showed the association between AID and MUM1 expression in DLBCL. However, whether the association may add further molecular heterogeneity of DLBCL is still to be confirmed by expanding the study.KEYWORDS: AID, CSR, DLBCL, MUM1, SHM

FRAX score with and without bone mineral density: a comparison and factors affecting the discordance in osteoporosis treatment in Thais

The Fracture Risk Assessment Tool (FRAX) is used to calculate the 10-year probability of fracture using important clinical factors, with bone mineral density (BMD) as an optional input variable. We aimed to determine the rate of concordance between treatment recommendations of osteoporosis with 10-year probability of hip fracture calculated using FRAX scores with and without BMD and to identify relevant clinical risk factors associated with discordance. This was a cross-sectional study conducted in patients between 40 and 90 years of age who were screened for osteoporosis by BMD measurement using dual energy X-ray absorptiometry (DXA) from 2010 to 2018 at a university hospital in Thailand. A FRAX questionnaire was administered to determine demographic data and osteoporotic risk factors. FRAX scores with and without BMD were calculated for each participant using the Thai reference, and patients were categorized into either the treatment or non-treatment group based on a cut-off of 3% 10-year probability of hip fracture. When FRAX scores with and without BMD results were consistent, they were considered concordant. Otherwise, they were deemed discordant. Clinical risk factors were compared between the concordant and discordant groups. A total of 3545 participants were included in the study. The majority (83.8%) were in the concordant group. However, older age, lower BMD, and FRAX without BMD around the intervention threshold were significantly associated with discordant results. In the discordant group, FRAX with BMD suggested treatment in more participants with lower age, higher BMI, and lower BMD when compared with FRAX without BMD. FRAX scores with and without BMD yielded concordant predictions regarding the 10-year probability of hip fracture suggesting pharmacological treatment. However, this concordance declined in elderly and osteoporotic participants and in those with FRAX without BMD around intervention threshold. BMD data may be required in these populations in order to facilitate accurate risk assessment.

Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results: Incidence and Characterization in a Large, Contemporary United States Cohort.

Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeitmodestly, the prognostication.

Discordance Between Subjective and Objective Cognitive Function in Older Korean Americans.

Objectives: To examine predictors of membership in discordant groups identified by subjective and objective measures of cognitive function. Methods: Participants in the Study of Older Korean Americans (N = 2046) were classified according to their subjective cognitive ratings (excellent/very good/good vs. fair/poor) and Mini-Mental State Examination scores (normal cognition vs. cognitive impairment), yielding two discordant groups: (1) positive ratings but cognitive impairment and (2) negative ratings but normal cognition. Logistic regression models examined how the discordant group membership was associated with personal resources. Results: Among those with positive cognitive ratings, the odds of belonging to the discordant group were associated with low personal resources (advanced age and lower levels of education, acculturation, and knowledge about Alzheimer's disease). However, an opposite pattern was observed among those with negative ratings. Discussion: The pattern of discordance suggests ways to promote early detection of cognitive impairment and close the gap in cognitive health care.

Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation.

Capillary deposition of C4d is an important marker of antibody-mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen-tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood. We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p=.022). Cumulative incidence of cellular rejection at 1year was comparable (31% vs. 29%, p=.46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p=.004). Overall 1-year survival was comparable (90% vs. 96%, p=.24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p<.001). The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.

Abstract PS6-38: A comparison of oncotype DX and NHS predict to assess the benefit of adjuvant chemotherapy in patients with early breast cancer

Abstract INTRODUCTION Early breast cancer (EBC) which is hormone receptor positive, HER2 negative and 0-3 Lymph node positive, defines a Luminal subtype with an excellent outcome and the benefit of adjuvant chemotherapy in this subgroup of patients is increasingly questioned. Gene-expression profile tests have evolved to help stratify risk and to individualise treatment decisions. The 21-gene recurrence-score assay, “Oncotype DX” (ODX) is a genomic test used to quantify the likelihood of distant recurrence (Recurrence Score i.e. RS) and predict chemotherapy benefit. Although it is included in international guidelines as a tool to identify patients who could safely avoid adjuvant chemotherapy, its utility is restricted due to cost in countries with limited resources where it is not covered by insurance. The “NHS Predict” (NHSP) is a freely available online prognostic and predictive test based on cancer registry data. It utilises an algorithm based on clinical parameters and biomarker status to provide an estimate of survival as well as the potential benefit of third generation chemotherapy, hormonal and targeted therapy. The NHSP is based on “Clinical Risk (CR)” while the ODX is based on “Genomic Risk (GR)” assessment. The present study was undertaken to compare the results obtained by ODX with those obtained by NHSP so as to determine the concordance of the two tests and establish the utility of the NHSP in resource-constrained countries. PATIENTS AND METHODS Patients with early ER positive, HER2 negative, 0-3 nodes positive breast cancer, who underwent the ODX assay from January 2010 to March 2020 at a tertiary referral centre were entered into this study. Patients were stratified as per the ODX RS into Low (RS= 0-20 for ≤ 50 years, 0-25 for &amp;gt;50 years) and High (RS= &amp;gt;21 for ≤ 50 years and 26-100 for &amp;gt;50 years) risk for recurrence with absolute chemotherapy benefit (ACB) estimated to be ≤7% and &amp;gt;7% respectively at 9 years.Subsequently, the NHS Predict 2.2 tool (https://breast.predict.nhs.uk/tool ) was used to compute the absolute benefit of third generation chemotherapy for each of these patients. Relevant clinical data i.e. age, menopausal status, tumour size, grade, Ki-67, ER/PR/HER2 status, nodal status and method of detection was entered into the algorithm. The ACB at 10 years, as determined by NHSP, was stratified into Low risk≤ 7% and High risk &amp;gt;7% so as to correspond to the ACB derived from ODX. The results obtained by NHSP were compared to those of the ODX to determine the concordance between the two tests. RESULTS 104 patients were entered into the study. The mean age was 53 years (range 31-76 years), 39.4% were premenopausal and 60.5% post-menopausal. The average tumour size was 19.4mm (range 8-55mm) with 61.53% T1, 36.53% T2 and 1.92% with T3 disease.14.4% were grade 1, 66.3% grade 2, and 19.2% grade 3. 74% were lymph node negative and 14.4%, 9.6% and 0.96% had 1, 2 and 3 positive nodes respectively. On ODX evaluation, low RS was seen in 87 (83.65%), and high RS in 17(16.34%) patients. As per NHSP, 99 (95.19%) patients were classified into low CR and 5 (4.8%) into high CR. There was 82.7% (86/104) concordance between NHSP and ODX with discordance in 18 patients. Of the concordant group, 84 had low CR and GR and 2 had high CR and GR. In the discordant group 15 patients had low CR on NHSP but high GR on ODX and while 3 patients had a high CR on NHSP but ODX showed low GR. CONCLUSIONS In a group of patients with low clinical risk EBC there is high concordance between the NHSP and ODX tests. There is a subgroup of patients with discordant results in whom the ODX may identify patients who could potentially benefit with adjuvant chemotherapy. NHSP can aid decision making regarding adjuvant chemotherapy and identify patients who could potentially avoid chemotherapy in low risk early breast cancer. Citation Format: Vinay Deshmane, Anuja Raniwala. A comparison of oncotype DX and NHS predict to assess the benefit of adjuvant chemotherapy in patients with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-38.

Preoperative supine traction radiographs often result in higher Lenke classifications than supine bending radiographs in adolescent idiopathic scoliosis.

Retrospective chart and radiographic review. The purpose of this study is to determine if both traction and side-bending radiographs yield the same Lenke classification. Supine side-bending radiographs are used to evaluate curve flexibility and assign Lenke classification in Adolescent Idiopathic Scoliosis (AIS). Supine traction radiographs are another tool used by treating surgeons to gauge flexibility and appropriate levels for spinal fusion in AIS. Retrospective chart and radiographic review were performed on AIS patients that underwent a posterior spinal fusion from 2008 to 2017. Cobb angles and Lenke classifications were determined on all upright posterioanterior (PA) spine radiographs, supine traction radiographs, and four supine bending radiographs. Statistical analysis using independent t tests and chi-square tests as appropriate were compared between patients with or without discordant Lenke classifications with p value set at < 0.05 for statistical significance. 184 patients met inclusion criteria, 36 males and 148 females. The average Cobb angle for the proximal thoracic (PT) curve was 27.2°, main thoracic (MT) curve was 60.5°, and thoracolumbar/lumbar (TL/L) curve was 48.0°. Significantly less curve correction was found with supine traction radiographs compared with bending radiographs: PT (23.1° vs 18.9°, p < 0.001), MT (38.9° vs 37.9°, p = 0.015), and TL/L (25.9° vs. 18.0°, p < 0.001). Lenke Classification was found concordant in 151/184 (82.1%). Traction views in the discordant Lenke classification group demonstrated less curve correction than those in the concordant group: PT (27.4° vs. 22.1°, p = 0.011), MT (45.3° vs. 37.5°, p < 0.001), and TL/L (29.3° vs 25.1°, p = 0.019). Supine traction and supine bending radiographs provided a concordant Lenke classification 82.1% of the time. However, supine traction radiographs demonstrate less curve correction, a higher Lenke classification, and underestimated the TL/L curve correction to a greater degree. A single supine traction film is not an adequate substitute to side-bending radiographs when determining Lenke classification in patients with Adolescent Idiopathic Scoliosis. III.

Impacto de la adherencia a un algoritmo híbrido para la selección de la estrategia inicial de cruce en la intervención coronaria percutánea de oclusiones crónicas

Introduction and objectivesThe hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study. MethodsWe examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry. ResultsThe initial crossing strategy was concordant with the hybrid algorithm recommendation in 1833 interventions (44%). Patients in the concordant group had a similar age to those in the discordant group but a lower mean J-CTO score (2.0 ± 1.4 vs 2.8 ± 1.1; P < .01). The concordant group showed higher technical success with the first crossing strategy (68% vs 48%; P < .01) and higher overall technical success (88% vs 83%; P < .01) with no difference in the incidence of in-hospital major adverse events (1.8% vs 2.3%; P = .26). In multivariable analysis, after adjustment for age, prior myocardial infarction, prior PCI, prior coronary artery bypass grafting, J-CTO score, and scheduled CTO PCI, nonadherence to the hybrid algorithm was independently associated with lower technical success of the initial crossing strategy (odds ratio, 0.55; 95% confidence interval, 0.48-0.64; P < .01). ConclusionsAdherence to the hybrid algorithm for initial crossing strategy selection is associated with higher CTO PCI success but similar in-hospital major adverse cardiac events.

Selection of parathyroidectomy methods for primary hyperparathyroidism according to concordance between ultrasonography and MIBI scan results.

Determination of appropriate operative methods for primary hyperparathyroidism (PHPT) is difficult when localisation results are discordant between imaging studies. The aim of this study was to compare the efficacy of focused parathyroidectomy (FP) and bilateral neck exploration (BNE) according to the concordance in localisation results. One hundred and ninety-one patients who underwent a PHPT operation at Asan Medical Center between 2000 and 2010 were divided into two groups according to the concordance in findings between neck ultrasonography (USG) and sestamibi (MIBI) scan. Differences in clinicopathological features and surgical outcomes between the concordant (n=137) and discordant (n=54) groups were analysed. FP and BNE did not show significant differences in postoperative persistent hyperparathyroidism rates. Although intraoperative parathyroid hormone (IOPTH) monitoring was not performed in this study, the cure rates of PHPT using only USG and MIBI scans were satisfactorily high, at 98.5% in the concordant group and 96.3% in the discordant group. The cure rates of FP and Unilateral exploration in single-negative USG and MIBI scans were 100%. Multiple lesions and hyperplasia were more common in the discordant group. In cases where it is difficult to apply IOPTH, FP without IOPTH is feasible in patients showing concordant or single-negative detection on USG and MIBI scans, whereas BNE is recommended in cases of discordance or double-negative results on imaging studies, to prevent recurrence or persistent disease. Appropriate selection of parathyroidectomy methods according to the concordance in USG and MIBI scans might produce good results without any difference in recurrence.