Discordance Rate Research Articles

PATH-08. MOLECULAR DIVERGENCE RATES DIFFER BETWEEN BRAIN METASTASES AND EXTRACRANIAL DISEASE SITES ACROSS PRIMARY TUMOR HISTOLOGIES

Abstract Genomic alterations and molecular subgroups between extracranial disease sites and brain metastases often differ, yet the prevalence and clinical significance of divergent evolution in brain metastases is not fully understood. This study examined genomic alterations and molecular subgroup divergence rates between matched brain metastases and extracranial disease sites. A retrospective, two-center study was conducted on patients who underwent resection of brain metastases between 2014-2022 with clinical and matched genomic data and/or molecular markers available. The overall cohort comprised 256 patients with matched tumors from multiple cancer types, most commonly from breast (n=108, 42.2%), melanoma (n=83, 32.4%), and NSCLC (n=43, 16.8%). Targeted next-generation sequencing of over 500 oncogenes was performed on resected tumors as part of clinical care (n=41 patients with matched specimens). Molecular subgroups for breast, melanoma, and non-small cell lung cancer were also assessed by immunohistochemistry to evaluate rates of molecular subgroup discordance between sites. Subgroup discordance by immunohistochemistry was observed most frequently across breast cancer (22.2%, n=24/108) with loss of the estrogen receptor (ER) and progesterone receptor (PR) and gain of HER2 most frequently observed within brain metastases. Molecular subgroup discordance was rare within melanoma (7.3%, n=6/82) and NSCLC (14.0%, n=6/43) patients. When evaluating oncogenomic alterations from targeted DNA sequencing in 41 patients with matched specimens, 80.5% (33/41) of brain metastases demonstrated a unique oncogene alteration profile compared to an extracranial disease site. Fourteen patients (34.1%) had a gain of at least 1 targetable alteration within a brain metastasis that was not observed in an extracranial disease site. Brain metastases demonstrated high rates of genomic divergence compared to primary and extracranial metastatic disease sites. This data supports obtaining brain metastasis tissue and conducting molecular profiling of this tissue to help select optimal CNS penetrant systemic therapies for each patient.

A machine learning-based analysis for the definition of an optimal renal biopsy for kidney cancer

ObjectiveRenal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports. Materials and methodsWithin a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results. ResultsOverall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required. ConclusionsThe discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold. Patients summaryRTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately.

Use of Laryngeal Ultrasound to Observe Laryngeal Movements During Noninvasive Ventilation in Healthy Volunteers.

Transnasal fiberoptic laryngoscopy (TFL) has revealed that laryngeal obstruction can hamper assisted ventilation. TFL may be considered invasive, and laryngeal ultrasound (US) could be a noninvasive alternative. The objective of this study was to investigate the feasibility of using laryngeal US to study laryngeal movements in healthy adult volunteers undergoing noninvasive ventilation (NIV) and to compare the observations with those of simultaneous TFL. In this cross-sectional study, 30 participants (19 females, age 22-65 y) underwent simultaneous video-recorded TFL and laryngeal US, breathing with and without NIV. Laryngeal US was repeated for anterior and both lateral approaches; the last 5 breaths from each assessment were analyzed. The participants rated discomfort using a numeric rating scale (NRS) from 0 (no discomfort)-10 (worst). Two blinded raters separately described and scored the TFL and laryngeal US recordings, and the findings were subsequently compared. The last 10 laryngeal US recordings were tested for interrater reliability. All participants were successfully assessed using the anterior and both lateral laryngeal US approaches during NIV. Both techniques were well tolerated; 5/30 scored 0 on NRS for TFL and 22/30 for laryngeal US. The visualization rate for all recorded breaths was 99.1% for TFL compared to 81.7% for laryngeal US; overall concordance rate was 84.6%. The discordance rate for the TFL versus laryngeal US observations was 11.1% for vocal fold movements and 11.7% for aryepiglottic fold movements. Interrater reliability showed substantial agreement (0.71). Laryngeal US emerged as a feasible method to describe laryngeal movements during NIV, providing high-quality observations and high concordance with TFL.

The discrepancy of somatic BRCA1/2 pathogenic variants from two different platforms in epithelial ovarian, fallopian tube, and peritoneal cancer

The somatic BRCA1 or BRCA2 Pathogenic Variant (PV)/Likely PV (LPV) from Next Generation Sequencing (NGS) is the most important biomarker for PARP inhibitor use and maintenance-targeted therapies. A discrepancy in the detection rates of BRCA1 and BRCA2 PV/LPV was identified among the NGS platforms. The objective of this study was to compare the somatic BRCA results from two distinct platforms using the same cohort and to identify the causes of these differences. Patients with epithelial ovarian cancer who concurrently underwent tumor NGS using two different platforms between January 2022 and June 2023 were included in this study. The two platforms used were in-house tumor NGS (Illumina NextSeq 550Dx, SureSelectXT library kit, and datasets from 1000 Genomes, ESP6500, ExAC, and ClinVar) and GreenPlan homologous recombination deficiency (HRD) test (Illumina NextSeq 550Dx, customized Twist Bioscience library kit, and datasets from COSMIC and OncoKB). The results of somatic mutations in BRCA1 and BRCA2 were compared between the two platforms. Of the 118 patients, 11.9% (n = 14) exhibited a discordant interpretation of BRCA1 or BRCA2 between the two platforms. Eleven patients (9.3%) exhibited negative results in the in-house platform but positive results (eight seven as PV of BRCA1, one as PV of BRCA2, one as LPV of BRCA1, and two as LPV of BRCA2) in the GreenPlan HRD test, while three patients (2.6%) had positive BRCA pathogenic variants (two as PV of BRCA1 [c.3340G > T, c.5152 + 3 A > C], one as LPV of BRCA2 [c.8174G > T], and one as LPV of BRCA1 [c.5017_5019delCAC]) in the in-house platform but a negative result in the GreenPlan HRD test. The discordance rate of somatic BRCA1 or BRCA2 mutations from different platforms was approximately 12%. In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed.

Diastolic hyperemia-free ratio for the assessment of intermediate coronary artery stenosis in patients with hemodialysis

Abstract Background Diastolic hyperemia-free Ratio (DFR) is new resting index and uses a pragmatic definition by including areas below the average aortic pressure with negative slope. Hemodialysis (HD) exhibits left ventricular hypertrophy and impaired microcirculation. The relationship between DFR and fractional flow reserve (FFR) in the patients with HD has not been yet investigated. Purpose We aimed to compare the rate of physiological discordance between HD patients and non-HD patients, and to elucidate the best DFR cut-off value predicting less than 0.80 of FFR in HD patients. Methods We enrolled 761 consecutive patients (1033 vessels) who underwent both DFR and FFR in the intermediate coronary artery stenosis between July 2020 and December 2023 in our hospital. The cutoff values of DFR 0.89 or less and FFR 0.80 or less were used for the study. We compared the DFR values with FFR values between HD group and Non-HD group. Results HD group consisted of 110 patients and Non-HD group consisted of 651 patients. A good correlation between DFR and FFR was observed in HD group (R=0.780 ; p < 0.0001) and Non-HD group (R=0.770 ; p < 0.0001). The rate of physiological discordance between HD group and non-HD group was each 31.3% and 20.5% (p < 0.01). Receiver operating characteristic curve showed that a suitable cut off value of DFR for equivalent FFR value of 0.80 was 0.84 in HD group and 0.89 in Non-HD group, respectively (Figure). Conclusion In the patients with HD, DFR may overestimate intermediate coronary artery stenosis and the suitable cut off value was 0.84.2024 ESC HD DFR Figure

Gap between estimated cardiovascular risk and individual risk perception: a survey from a cardiovascular prevention center.

Abstract Background Cardiovascular risk scores represent a great achievement of preventive cardiology, since they allow to stratify individual risk. The recently updated European Society of Cardiology Scores offer an accurate cardiovascular risk estimation. However, a gap between perceived and calculated risk may strongly interfere in healthy lifestyle changes as well as in cardioprotective drugs adherence. Purpose: The aim of the present study was to evaluate and quantify the above-mentioned gap. Methods A cohort of subjects referred to our Cardiovascular Prevention Center were included in the present study. Cardiologists assessed each tradional and emerging risk factor in terms of presence or absence, severity, distance from target, and the cardiovascular risk was calculated using appropriate ESC scores. Each subject filled out a questionnaire in which they were asked to declare their perceived cardiovascular risk and to report, among all the traditional and emerging cardiovascular risk factors, which ones they believed to have greater impact on their individual risk. Results 366 consecutive subject were included, 70% in primary prevention and 30% with atherosclerotic cardiovascular disease, mean age was 65 years, male gender was prevalent (57%), arterial hypertension (AHT) was found in 78,7% (43,4% uncontrolled), dyslipidaemia in 91,5% (87,5% not at target), diabetes in 18,6%, smokers were 12,9% and 24,4% had obesity. Among emerging risk factors, sedentary lifestyle was found in 63%, while 18% reported regular aerobic physical activity, mediterranean diet adherence was found in 26% and moderate-to-severe perceived anxiety in 23%, depression in 17% and stress in 66%. 6,6% had low risk cardiovascular risk, 16,1% intermediate, 38,0% high and 39,3% very high. A concordance between estimated and perceived risk was found in 18,9% while a discordance in 81,1%; 93,3% underestimate their risk, while 6,7% only overestimate it (figure 1A). A significant higher rate of discordance was found with the progressive increase of the risk (p<0.0001). Different perceived cardiovascular risk among each estimated classes of risk was shown in figure 1B and figure 2; of note only 11% of high risk and 8% of very high risk were concordant in their risk perception. In particular, elderly (p<0.001), male (p<0.001), subjects with AHT (p=0.001) and dyslipidaemia (p=0.02) showed higher rate of underestimation while younger (p<0.001), female (p<0.001) as well as anxiety (p=0.047) and depressed (p=0.010) had higher rate of overestimation. Conclusions A high rate of subject underestimate its cardiovascular risk; the higher the risk, the higher the gap between perceived and estimated risk. This risk gap represents a "risk within the risk". for these reasons it is necessary to increase all efforts towards a more effective health education in the field of cardiovascular prevention in order to reinforce patients awareness and physician-patient alliance.Figure 1Figure 2

Modeling microbial growth based on time-dependent kinetic mechanisms of digestion and passage in the ruminoreticulum

The original Cornell Net Carbohydrate and Protein System (CNCPS) model, which was developed in 1992 and revised in 2004, included a rumen submodel with a set of equations that were algebraically programmed in a spreadsheet to predict bacterial N flow to the caudal tract of cattle. In this study, we propose a modification to the original CNCPS rumen submodel based on mathematical concepts that simulate the flow paths of solids and liquid in the rumen, which are known to be essential factors affecting rumen fermentation and microbial growth. This modification allows the quantification of the impact of aging mechanisms on the availability of both soluble and insoluble substrates for microbial growth in the rumen. Additionally, a correction has been proposed on peptide uptake by rumen bacteria. Literature data were used to evaluate the model adequacy of CNCPS versions 1992 and 2004, along with the proposed model, to determine their ability to predict bacterial N flow. The proposed model more accurately predicted the variable of interest, but there was an overall underprediction bias. Despite the rightful critics of the ability of mechanistic models to predict microbial crude protein flow from the rumen, the 1992 and 2004 versions of the CNCPS and the proposed modifications implemented within the CNCPS framework led to predictions that agreed with observational data at a discordance rate of 0.05, tolerance probabilities <0.001 for versions 1992 and 2004, and a tolerance probability equal to 0.13 for the proposed model given a sample size n=39. Therefore, the proposed modifications might improve the ability of CNCPS-based models to predict the bacterial N flow from the rumen, thereby resulting in improved predictive performance compared to the original CNCPS model. Thus, it seems that models built on time-dependent kinetics of food particles and fluid are more fitting than steady-state ones to predict bacterial N flow to the caudal tract.

Reliability, reproducibility, and potential pitfalls of the O-RADS scoring with non-dynamic MRI.

The O-RADS scoring has been proposed to standardize the reporting of adnexal lesions using magnetic resonance imaging (MRI). To assess intra- and inter-observer agreement of the O-RADS scoring using non-dynamic MRI and its agreement with pathologic diagnosis, and to provide the pitfalls in the scoring based on discordant ratings. Adnexal lesions that were diagnosed using non-dynamic MRI at two centers were scored using O-RADS. Intra- and inter-observer agreements were assessed using kappa statistics. Cross-tabulations were made for intra- and inter-observer ratings and for O-RADS scores and pathological findings. Intra- and inter-observer agreements were assessed for 404 lesions in 339 patients who were admitted to center 1. Intra-observer agreement was almost perfect (97.8%, kappa = 0.963) and inter-observer agreement was substantial (83.2%, kappa = 0.730). The combined data from center 1 and center 2 included 496 patients; of them, 295 (59.5%) were operated. There was no borderline or malignant pathology for the lesions with O-RADS 1 or 2. Of those with an O-RADS score of 3, 3 (4.1%) lesions were borderline and none were malignant. The O-RADS scoring in discriminating borderline/malignant lesions from benign lesions was outstanding (area under the ROC curve 0.950, 95% CI = 0.923-0.971). Sensitivity, specificity, positive, and negative predictive values of O-RADS 4/5 lesions for borderline/malignant lesions were 96.2%, 87.1%, 72.8%, and 98.4%, respectively. The O-RADS scoring using non-dynamic MRI is a reproducible method and has good discrimination for borderline/malignant lesions. Potential factors that may lead to discordant ratings are provided here.

Comparison of clinicopathological characteristics, efficacy of neoadjuvant therapy, and prognosis in HER2-low and HER2-ultralow breast cancer

BackgroundThis study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers.MethodsConsecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level.ResultsOut of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER (p < 0.001), PR (p < 0.001), and AR (p = 0.004), along with a greater prevalence of the luminal subtype (p < 0.001). The HER2-ultralow group also demonstrated a higher prevalence of lymph node metastasis compared to the HER2-null group (p = 0.026). Varied rates of pathologic complete response (pCR) were observed among the three subgroups: HER2-null, HER2-ultralow, and HER2-low, with rates of 35.71%, 22.03%, and 12.56%, respectively. Only the HER2-low subgroup exhibited a significant difference compared to HER2-null (p = 0.001). Despite variations in pCR rates, the three subgroups exhibited comparable disease-free survival (DFS) (p = 0.571). Importantly, we found HER2-low patients with better treatment response (RCB-0/I) exhibited significantly better DFS than those with significant residual disease (RCB-II/III) (P = 0.036). The overall rate of HER2 immunohistochemical score discordance was 45.24%, mostly driven by the conversion between HER2-0 and HER2-low phenotype. Notably, 32.19% of cases initially classified as HER2-0 phenotype on baseline biopsy were later reclassified as HER2-low after neoadjuvant therapy, and it is noteworthy that 22 out of these cases (78.57%) originally had an HER2-ultralow status in the pretreatment biopsy sample.ConclusionsOur results demonstrate the distinct clinicopathological features of HER2-low and HER2-ultralow breast tumors and confirm that RCB is an effective predictor of prognosis in HER2-low populations for the first time. Notably, our findings demonstrate high instability in both HER2-low and HER2-ultralow expression from the primary baseline biopsy to residual disease after NAT. Furthermore, this study is the first to investigate the clinicopathological feature and the effectiveness of NAT for HER2-ultralow breast cancer.

Dissemination and outcome reporting bias in clinical malaria intervention trials: a cross-sectional analysis

BackgroundDissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research.MethodsAll malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated.ResultsA total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes.ConclusionsNon-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias.

Rate of Diagnostic Change in Surgical Pathology Reports after Mandatory Intradepartmental Peer Review in a Tertiary Hospital in the Philippines: A Retrospective Study.

There is a mandatory intradepartmental peer review algorithm in the University of the Philippines - Philippine General Hospital (UP-PGH) Department of Laboratories wherein specific cases are required to be reviewed by another pathologist before the release of results. The main objective of this study was to determine the rate of diagnostic change in surgical pathology reports after undergoing the said review. All surgical pathology cases which underwent the review from 2015 to 2018 were retrieved from the records of the Section of Surgical Pathology. The cases were classified as concordant or discordant. A case was considered concordant if the reviewing pathologist had agreed with the primary pathologist's diagnosis. A case was considered discordant if the reviewing pathologist had disagreed with the primary pathologist's diagnosis. Out of 5,377 cases included in this study, there were 5,209 concordant cases and 168 discordant cases, with the rate of discordance computed to be 3.1%. Out of the 168 discordant cases, 107 were revised for diagnostic change. Rate of diagnostic change was computed to be 2.0% (107 out of 5,377 cases for review). The most common criterion satisfied for meriting a mandatory review is being under the category of biopsies or cytology cases with malignant or borderline diagnoses (49.4%). The most common category of diagnostic change is change in immunohistochemistry recommendations (24.3%). Most of the discordant cases and cases revised for diagnostic change fall under the categories of gastrointestinal, gynecology, and head & neck pathology. The low rate of diagnostic change in our institution might be attributed to good diagnostic accuracy. However, it is also possible that reviewing pathologists tended to agree with the diagnosis made by their colleagues because of the element of peer pressure. Data from the study may imply that special courses/ lectures or institutional standard practice guidelines on interpreting biopsy and cytology cases as well as on the utility of immunohistochemistry studies, especially those focused on gastrointestinal, gynecology, and head & neck pathology are needed by the pathologists and the doctors training to become pathologists in our institution.

A Quality Improvement Study to Evaluate Discordance Rates of Low-Grade Squamous Intraepithelial Lesion on Cervical Pap Smears with Histopathologic Correlation

A Quality Improvement Study to Evaluate Discordance Rates of Low-Grade Squamous Intraepithelial Lesion on Cervical Pap Smears with Histopathologic Correlation

Unveiling the complexity of rifampicin drug susceptibility testing in Mycobacterium tuberculosis: comparative analysis with next-generation sequencing.

Introduction. The discordance between phenotypic and molecular methods of rifampicin (RIF) drug susceptibility testing (DST) in Mycobacterium tuberculosis poses a significant challenge, potentially resulting in misdiagnosis and inappropriate treatment.Hypothesis/gap statement. A comparison of RIF phenotypic and molecular methods for DST, including whole genome sequencing (WGS), may provide a better understanding of resistance mechanisms.Aim. This study aims to compare RIF DST in M. tuberculosis using two phenotypic and molecular methods including the GeneXpert RIF Assay (GX) and WGS for better understanding.Methodology. The study evaluated two phenotypic liquid medium methods [Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT)], one targeted molecular method (GX), and one WGS method. Moreover, mutational frequency in ponA1 and ponA2 was also screened in the current and previous RIF resistance M. tuberculosis genomic isolates to find their compensatory role.Results. A total of 25 RIF-resistant isolates, including nine from treatment failures and relapse cases with both discordant and concordant DST results on LJ, MGIT and GX, were subjected to WGS. The phenotypic DST results indicated that 11 isolates (44%) were susceptible on LJ and MGIT but resistant on GX. These isolates exhibited multiple mutations in rpoB, including Thr444>Ala, Leu430>Pro, Leu430>Arg, Asp435>Gly, His445>Asn and Asn438>Lys. Conversely, four isolates that were susceptible on GX and MGIT but resistant on LJ were wild type for rpoB in WGS. However, these isolates possessed several novel mutations in the PonA1 gene, including a 10 nt insertion and two nonsynonymous mutations (Ala394>Ser, Pro631>Ser), as well as one nonsynonymous mutation (Pro780>Arg) in PonA2. The discordance rate of RIF DST is higher on MGIT than on LJ and GX when compared to WGS. These discordances in the Delhi/CAS lineages were primarily associated with failure and relapse cases.Conclusion. The WGS of RIF resistance is relatively expensive, but it may be considered for isolates with discordant DST results on MGIT, LJ and GX to ensure accurate diagnosis and appropriate treatment options.

Anti-phosphohistone H3 (PHH3) as a proliferation marker to assess mitotic activity and to grade neuroendocrine neoplasms of hepatopancreaticobiliary (HPB) system.

The world health organization (WHO) classification of neuroendocrine neoplasms (NENs, i.e. neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs)) of the gastrointestinal system involves grading of these tumors by mitotic count (i.e. H and E mitotic index or Haematoxylin and Eosin mitotic index [HE-MI] and Mindbomb E3 ubiquitin protein ligase 1 labelling index (MIB1-LI) into Grade 1 (G1), Grade 2 (G2), or Grade 3 (G3). However, the assessment of HE-MI and MIB1-LI is hindered by several factors that contribute to discordance between these two grading methods. Clinical data demonstrate the dependency of prognosis on grade. The objective of this study was to compare the grading of NENs of the hepatopancreatobiliary (HPB) system using Anti-phosphohistone H3 mitotic index (i.e. PHH3-MI), HE-MI and MIB1-LI. In a cohort of 140 NENs selected from January 2011 to August 2019, the concordance and correlation between HE-MI, MIB1-LI and PHH3-MI grading methods were analysed using Cohen's weighted kappa (κ) statistics and Spearman's correlation (ρ), respectively. Receiver operating characteristic (ROC) curve and cut-off analyses were done to determine optimal PHH3-MI cut-off values to grade NENs. The rates of discordance between HE-MI vs. MIB1-LI, PHH3-MI vs. MIB1-LI and PHH3-MI vs. HE-MI were 52% (κ =0.416), 29% (κ =0.64) and 41% (κ =0.508), respectively. There was a significant correlation between the grading methods. PHH3-MI had good overall sensitivity and specificity at cut-offs 2 and 17 in distinguishing between G1 vs. G2, and G2 vs. G3 tumors, respectively. PHH3 immunolabeling allowed for quick and easy identification of mitotic figures (MF). It had the highest concordance with MIB1-LI. At cut-off values of 2 and 17, there was good overall sensitivity and specificity. The interobserver agreement was excellent.

HER2 status results in an unstable switch from primary to recurrent breast cancer.

Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression. We included patients who were HER2-2+ of primary or rebiopsy tumor samples, to evaluate the evolution of HER2-2+ expression. In the cohort with a total of 159 patients with HER2-2+ expression in either primary tumor or locoregional/distant metastasis samples, 44.0% had HER2-2+ in primary tumor and 88.8% in recurrent disease. Among patients with primary and recurrent HER2-2+ breast cancers, 18.5% and 15.2% of the patients, respectively, had HER2 gene amplification via ISH. The overall rate of discordance in HER2 IHC results was 67.1%. Among primary HER2-2+ patients, 74.6% were maintained in the HER2-2+ cohort at the recurrence. The discordance was mostly driven by patients switching from HER2-2+ to HER2-1+ (64.7%). Among HER2-2+ recurrent patients, discordance in the IHC results was mostly driven by switching from HER2-0 to HER2-2+ (47.1%). When HER2-low was added to the analysis, the overall rate of HER2 discordance was 40.4%. The proportion of patients with discordant HER2 expression was significantly greater among HR-positive patients than negative patients (44.1% vs. 21.7%, p=0.062). HER2 expression in primary and recurrent breast cancer samples was highly unstable. Discordance was more frequently observed in the HR-positive population.

Hypersensitivity Pneumonitis on Thin-Section Chest CT Scans: Diagnostic Performance of the ATS/JRS/ALAT versus ACCP Imaging Guidelines.

Purpose To compare the diagnostic performance of the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) versus the American College of Chest Physicians (ACCP) imaging classifications for hypersensitivity pneumonitis (HP). Materials and Methods Patients in the institutional review board-approved Interstitial Lung Disease (ILD) registry referred for multidisciplinary discussion (MDD) at the authors' institution (January 1, 2006-April 1, 2021) were included in this retrospective study when ILD was diagnosed at MDD. MDD diagnoses included HP, connective tissue disease-ILD, and idiopathic pulmonary fibrosis. Retrospective review of thin-section CT images was performed in consensus by two cardiothoracic radiologists blinded to the diagnosis. Diagnostic patterns were determined for thin-section CT images using both classifications. Discordance rates were determined. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were assessed using MDD diagnosis as the reference standard. Results A total of 297 patients were included in the study: 200 (67%) with HP, 49 (16%) with connective tissue disease-ILD, and 48 (16%) with idiopathic pulmonary fibrosis at MDD. The discordance rate between the two classifications was 21%. Assuming low HP prevalence (10%), ATS/JRS/ALAT classification outperformed ACCP classification, with greater accuracy (92.3% vs 87.6%) and greater positive predictive value (60.7% vs 42.9%). Assuming high prevalence (50%), accuracy and negative predictive value were superior using ACCP classification (81.7% vs 79.7% and 77.7% vs 72.6%, respectively), and positive predictive value was superior using ATS/JRS/ALAT classification (93.3% vs 87.1%). Conclusion Accuracy of the ATS/JRS/ALAT and ACCP HP classifications was greater in settings with low and high HP prevalence, respectively. Diagnostic performance of both classifications was discordant in a minority of cases. Keywords: CT, Thorax, Hypersensitivity Pneumonitis, Interstitial Lung Disease Supplemental material is available for this article. © RSNA, 2024.

Correlation Between Oncotype Dx Recurrence Score and PREDICT Estimates in Early Breast Cancer: A Single Institution Experience.

Oncotype Dx Recurrence Score (RS) is prognostic and predictive of chemotherapy benefit in women with node-negative and node-positive in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Nevertheless, its direct cost may be inhibitive. This study assesses the correlation between the RS and the free online PREDICT tools' estimations of adjuvant chemotherapy benefit. A retrospective review of the electronic medical records of 112 patients with tumors tested for the RS and the PREDICT tool was used to estimate survival benefits. The correlation between RS and PREDICT estimations was analyzed using Spearman rank and McNemar tests. The median age of patients was 53 (95% CI, 50 to 55) years, with most patients having negative axillary lymph nodes (78%). While the absolute value for RS showed significant positive correlations with adjuvant chemotherapy's benefit as estimated by PREDICT, no significant correlations were found between the two methods in the percentage of chemotherapy gain. Notably, discordance rates between 48% and 67% between RS-based risk assignments and those based on PREDICT estimates were significant across the study population and subgroups. Only one disease recurrence and one breast cancer-related death were documented over a median follow-up of 23.5 (95% CI, 19.8 to 27.2) months. Our findings highlight a significant discordance between RS and PREDICT tools in predicting the benefits of adjuvant chemotherapy in patients with HR+, HER2- early breast cancer. While both tools aim to personalize cancer treatment, their discordance varies, suggesting that PREDICT could not substitute RS to predict adjuvant chemotherapy benefits regardless of patient risk classification. Further studies are needed to explore these relationships and optimize precision medicine approaches in breast cancer management.

Hospital Rating Organizations' Quality and Patient Safety Scores: Analysis of Result Discrepancies.

In the USA, multiple organizations rate hospitals based on quality and patient safety data, but few studies have analyzed and compared the rating results. Compare the results of different US hospital-rating organizations. Observational data analysis of US acute care hospital ratings. Four rating organizations: Hospital Compare® (HC), Healthgrades® (HG), The Leapfrog Group® (Leapfrog), and US News and World Report® (USN). We analyzed the level of concordance (similar ranking), discordance (difference of 1 or more rankings), and severe discordance (difference of two or more rankings), as well as differences and correlations between the scores. From Feb 1 to Oct 3, 2023, we analyzed data from 2,384 hospitals. In Leapfrog, there were 688 hospitals (29%) with Grade A, 652 (27.3%) with B, 885 (37.1%) with C, 153 (6.4%) with D, and 6 (0.3%) with F. For HC, 333 hospitals (14%) had five stars, 676 (28.4%) four, 695 (29.2%) three, 502 (21.4%) two, and 171 (7.2%) one-star. In ratings between HC and Leapfrog, discordance was 70%, and severe discordance was 25.1%. USN ranked 469 hospitals (19.7%). Within the USN-ranked hospital group, there was a 62% discordance and 19.8% severe discordance between HC and Leapfrog. The analysis of orthopedic procedures from HG and USN showed discordance ranging from 48 to 61.2%. The rating organizations' reported metrics were highly discordant. A hospital's ranking by one organization frequently did not correspond to a similar ranking by another. The methodology and included timeline and patient population can help explain the differences. However, the discordant ratings may confuse patients and customers.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection

Introduction and objectivesPostchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery.Patients and methodsFrom a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy.ResultsAll patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%.ConclusionThe data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

Discordant Prenatal Cell-Free DNA Screening vs. Diagnostic Results of Sex Chromosome Aneuploidies: Implications for Newborn Screening and Genetic Counseling.

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling.