Discordance Rate Research Articles

The Implications of a Dermatopathologist's Report on Melanoma Diagnosis and Treatment.

An accurate and comprehensive histopathology report is essential for cutaneous melanoma management, providing critical information for accurate staging and risk estimation and determining the optimal surgical approach. In many institutions, a review of melanoma biopsy specimens by expert dermatopathologists is considered a necessary step. This study examined these reviews to determine the critical primary histopathology Breslow score in which a histopathology review would be most beneficial. Histopathology reports of patients referred to our institute between January 2011 and September 2019 were compared with our in-house review conducted by an expert dermatopathologist. The review focused on assessing fundamental histologic and clinical prognostic features. A total of 177 specimens underwent histopathology review. Significant changes in the Breslow index were identified in 103 cases (58.2%). Notably, in many of these cases (73.2%), the revised Breslow was higher than the initially reported score. Consequently, the T-stage was modified in 51 lesions (28.8%). Substantial discordance rates were observed in Tis (57%), T1b (59%), T3a (67%) and T4a (50%) classifications. The revised histopathology reports resulted in alterations to the surgical plan in 15.3% of the cases. These findings emphasize the importance of having all routine pathologies of pigmented lesions referred to a dedicated cancer center and reviewed by an experienced dermatopathologist. This recommendation is particularly crucial in instances where the histopathology review can potentially alter the diagnosis and treatment plan, such as in melanoma in situ and thinner melanomas measuring 0.6-2.2 mm in thickness. Our study highlights the significant impact of histopathology reviews in cutaneous melanoma cases. The observed changes in Breslow scores and subsequent modifications in T-stage classification underline the need for thorough evaluation by an expert dermatopathologist, especially in cases of melanoma in situ and thin melanomas. Incorporating such reviews into routine practice within dedicated cancer centers can improve diagnostic accuracy and guide appropriate treatment decisions, ultimately leading to better patient outcomes.

A pseudo-dilemma: Are we over-diagnosing and over-treating traumatic splenic intraparenchymal pseudoaneurysms?

Splenic embolization for traumatic vascular abnormalities in stable patients is a common practice. We hypothesize that modern contrast-enhanced computed tomography (CT) over diagnoses posttraumatic splenic vascular lesions, such as intraparenchymal pseudoaneurysms (PSA) that may not require embolization. We reviewed the experience at our high-volume center with endovascular management of blunt splenic injuries from January 2016 to December 2021. Multidisciplinary review was used to compared initial CT findings with subsequent angiography, analyzing management and outcomes of identified vascular lesions. Of 853 splenic injuries managed overall during the study period, 255 (29.9%) underwent angiography of the spleen at any point during hospitalization. Vascular lesions were identified on 58% of initial CTs; extravasation (12.2%) and PSA (51.0%). Angiography was performed a mean of 22 hours after admission, with 38% done within 6 hours. Embolization was performed for 90.5% (231) of patients. Among the 130 patients with PSA on initial CT, 36 (27.7%) had no visible lesion on subsequent angiogram. From the 125 individuals who did not have a PSA identified on their initial CT, 67 (54%) had a PSA seen on subsequent angiography. On postembolization CT at 48 hours to 72 hours, persistently perfused splenic PSAs were seen in 41.0% (48/117) of those with and 22.2% (2/9) without embolization. Only one of 24 (4.1%) patients with PSA on angiography observed without embolization required delayed splenectomy, whereas 6.9% (16/231) in the embolized group had splenectomy at a mean of 5.5 ± 4 days after admission. There is a high rate of discordance between CT and angiographic identification of splenic PSAs. Even when identified at angiogram and embolized, close to half will remain perfused on follow-up imaging. These findings question the use of routine angioembolization for all splenic PSAs. Therapeutic/Care Management; Level IV.

Quantitative Benefit of Inpatient Dermatology Services on Hospital Length of Stay in an Academic Hospital.

Dermatologic disease has been shown to have high rates of diagnostic and treatment discordance between dermatologists and non-specialists. Inpatient dermatology consultative services have the potential to improve patient care, but there is a paucity of data evaluating the quantitative effects of such services. This study aimed to evaluate the impact a newly established inpatient dermatology service had on quantitative patient care outcomes. This retrospective cohort study compared quantitative care measures of dermatologic inpatients during the years both pre- and post-implementation of an academic hospital's dermatology consultative service. The primary outcomes included hospitalization duration, readmission rates, and establishment of outpatient dermatologic care. The study found a 1.04-day reduction in hospital length of stay (p-value = 0.046) after the consultation service establishment. Additionally, there was a significant increase in the rate by which patients sought outpatient dermatology follow-up (6.7% versus 24.4%, p-value <0.001). No significant change in the all-cause readmission rate was identified. The reduction of hospitalization duration supports inpatient dermatology services as a viable means to provide improved patient care and reduce health systems costs. Hospitals that do not have a consulting service for cutaneous conditions provided by a dermatology specialist should strongly consider establishing such a department.

Assessment of endometrial carcinoma on biopsy as a predictor of final surgical pathology: Are we doing it right? A completed audit cycle and recommendations.

Typing and grading of endometrial carcinomas (ECs) on small biopsy specimens is crucial to determine the need for full surgical staging. Histological subtype and grade are key factors available for risk stratification before surgery. However, this can be diagnostically challenging on small biopsy specimens, especially when morphologic features are subtle or overlapping. The aims of this audit were to assess concordance of endometrial carcinomas on biopsy specimens with hysterectomy specimens and to determine if the immunohistochemistry (IHC) panel being used in our practice was adequately subtyping ECs. The audit was approved by the Clinical Effectiveness Team of the Royal College of Pathologists (UK) as meeting all the criteria and standards set out by the College. Biopsies from 67 cases of EC were compared for histological subtype and grade of endometrioid carcinoma with resection specimens. A re-audit was carried out on 59 cases after implementation of changes recommended by the initial audit. Two of 35 (6%) tumours defined as G1 on biopsy were upgraded (to G2) on final pathology, as was one of 7 (14%) G2 tumours (to G3). One of these cases had solid areas just amounting to more than 6% on resection. In the second case, a comment was made that assessment had been difficult as the specimen was suboptimally fixed, but nuclei appeared atypical. Of seven G2 biopsies, one case was upgraded to grade 3 on final pathology based on proportion of solid areas. Our data show lower rates of discordance as compared to previous studies and on re-audit, the concordance between endometrioid and nonendometrioid serous carcinoma improved with the addition of immunohistochemistry (IHC) for Phosphatase and tensin homolog (PTEN) to biopsies. PTEN IHC can complement other stains and aid in the distinction of grade 3 endometrioid carcinoma from serous carcinoma on endometrial biopsies.

Factors associated with discordance in the assessment of fibrosis stage between transient elastography and liver biopsy in NAFLD patients

Background and aimsFew studies focus on the concordance of fibrosis stage assessment between transient elastography (TE) and liver biopsy (LB) in non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the rate of discordance and factors associated with discordance in the fibrosis stage assessment between TE and LB. MethodsLB-proven NAFLD patients were enrolled retrospectively. Liver fibrosis was assessed via TE and LB based on Steatosis-Activity-Fibrosis (SAF) criteria. Cohen's kappa was used to estimate the discordance between the fibrosis stage assessment by TE and LB. Logistic regression was utilized to determine the factors associated with discordance. ResultsA total of 172 eligible patients were included. The concordance of fibrosis staging between TE and LB was moderate (kappa = 0.446, p < 0.001). The overall rate of discordance was 52.90% (91/172) and highest in the F2 stage (66.28%) and F3 stage (60.42%), moderate in the F1 stage (23.81%), and lowest in the F4 stage (0.00%). The rate of overestimation and underestimation was 23.66% and 38.71% in patients detected by M-probe, while the rate of overestimation and underestimation was 33.87% and 19.35% in patients detected by XL-probe, respectively. BMI [OR=1.494, p = 0.017] and type 2 diabetes mellitus (T2DM) (OR=4.678, p = 0.008) were significantly associated with the overestimation in fibrosis stage assessment when the M-probe was applied. ConclusionsThe discordance between TE and LB in fibrosis stage assessment was unexpectedly high and mainly observed in F1-F3 patients. BMI and T2DM were the factors associated with overestimation using the M-probe.

Discordance in TME Specimen Grading in a Prospective Phase II Multicenter Rectal Cancer Trial: Are We Overestimating the Quality of our Resections ?

To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase II trial of transanal TME. Grading of TME specimens is based on macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (C/NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described. A phase II prospective taTME trial was conducted from 2017-2022 across 11 North American centers with TME quality as primary study endpoint. QC measures included training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance prior to trial reporting. Cohen's Kappa statistic was used to assess agreement in grading. Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ=0.35 (95% CI, 0.10-0.61, P<0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre- versus post-reconciliation rates of C/NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC to NC, N=1) or major downgrade (NC/C to IC, N=4) in 5 cases overall (5%). A 14% rate of major discordance was observed in TME grading between site and central reviewers. Resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through central review of TME photographs and reconciliation of major discordances is strongly recommended.

HER2-low breast cancer: evolution of HER2 expression from primary tumor to distant metastases

BackgroundBreast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression is attracting much attention due to the breakthrough progress of novel anti-HER2 antibody-drug conjugates. HER2 expression is examined in patients with HER2-low BC and their distant metastases in this study, so as to further clarify the dynamic characteristics of HER2 low status in the process of disease progression.MethodsPatients diagnosed with HER2 low breast cancer (defined as IHC1+ or IHC2+/ISH-) between 2012 and 2021 were included in this study. We evaluated HER2 expression of primary sites and metastatic sites, compared the impact of different clinicopathological parameters on HER2 status of metastases and compared the overall survival and disease-free survival of patients with different HER2 status in metastases.ResultsNinety-eight patients were included. All HER2 IHC scores were confirmed and the consistent rate with the original pathological report was 81.1%. 27.6% of the patients showed different HER2 status in metastases. The HER2 discordance rate differed among different metastatic sites (p = 0.040). The higher the T stage of the primary BC, the higher the rate of HER2 discordance was observed (p = 0.042). For the specimen type of metastasis, HER2 discordant rate was higher in surgical specimen than biopsy (p = 0.050). No difference of HER2 discordance rate was found between HER2-1+ and HER2-2+ patients. But comparing HER2 IHC score, HER2-2+ patients were less likely to have consistent metastatic HER2 levels than HER2-1+ patients (p = 0.006). No difference in survival outcomes was observed between patients with different HER2 status in metastases.ConclusionsThere is a possibility of HER2 expression alteration in the metastases of HER2-low breast cancer. And the rate of altered HER2 low expression was different among different metastatic sites, different T stages of primary BC and specimen type of metastasis. No prognostic significance was observed.

Discordance Between Invasive and NonInvasive Oxygen Saturation in Critically Ill COVID-19 Patients.

To investigate discordance in oxy-hemoglobin saturation measured both by pulse oximetry (SpO2) and arterial blood gas (ABG, SaO2) among critically ill coronavirus disease 2019 (COVID-19(+)) patients compared to COVID-19(-) patients. Paired SpO2 and SaO2 readings were collected retrospectively from consecutive adult admissions to four critical care units in the United States between March and May 2020. The primary outcome was the rate of discordance (|SaO2-SpO2|>4%) in COVID-19(+) versus COVID-19(-) patients. The odds each cohort could have been incorrectly categorized as having a PaO2/FiO2 above or below 150 by their SpO2: Fractional inhaled oxygen ratio (pulse oximetry-derived oxyhemoglobin saturation:fraction of inspired oxygen ratio [SF]) was examined. A multivariate regression analysis assessed confounding by clinical differences between cohorts including pH, body temperature, renal replacement therapy at time of blood draw, and self-identified race. There were 263 patients (173 COVID-19(+)) included. The rate of saturation discordance between SaO2 and SpO2 in COVID-19(+) patients was higher than in COVID-19(-) patients (27.9% vs 16.7%, odds ratio [OR] 1.94, 95% confidence interval [CI]: 1.11 to 2.27). The average difference between SaO2 and SpO2 for COVID-19(+) patients was -1.24% (limits of agreement, -13.6 to 11.1) versus -0.11 [-10.3 to 10.1] for COVID-19(-) patients. COVID-19(+) patients had higher odds (OR: 2.61, 95% CI: 1.14-5.98) of having an SF that misclassified that patient as having a PaO2:FiO2 ratio above or below 150. There was not an association between discordance and the confounders of pH, body temperature, or renal replacement therapy at time of blood draw. After controlling for self-identified race, the association between COVID-19 status and discordance was lost. Pulse oximetry was discordant with ABG more often in critically ill COVID-19(+) than COVID-19(-) patients. However, these findings appear to be driven by racial differences between cohorts.

Does the Primary Surgical Approach Matter When Choosing the Approach for Revision Total Hip Arthroplasty?

BackgroundMultiple surgical approaches are used for primary total hip arthroplasty (pTHA) and revision total hip arthroplasty (rTHA). This study sought to investigate prevalence of discordance of pTHA and rTHA surgical approaches and to evaluate how approach concordance impacts postoperative outcomes. MethodsA retrospective review of patients who underwent rTHA from 2000 to 2021 was conducted at 3 large urban academic centers. Patients who had minimum 1-year follow-up post-rTHA were included and grouped based on whether they received pTHA via a posterior (PA), direct anterior (DA), or laterally based (DL) approach, and by concordance of index rTHA approach with their pTHA approach. Of the 917 patients studied, 839 (91.5%) were included in the concordant cohort and 78 (8.5%) in the discordant cohort. Patient demographics, operative characteristics, and postoperative outcomes were compared. ResultsDiscordance was most prevalent in the DA-pTHA subset (29.5%), compared to the DL-pTHA subset (14.7%) or PA-pTHA subset (3.7%). Discordance varied significantly between primary approaches among all revisions, with DA-pTHA patients having the highest discordance rate for patients revised for aseptic loosening (46.3%, P < .001), fracture (22.2%, P < .001), and dislocation (33.3%, P < .001). There were no differences between groups in dislocation rate, re-revision for infection, or re-revision for fracture. ConclusionThe results of this multicenter study showed patients who received pTHA via the DA were more likely to receive rTHA via a discordant approach compared to other primary approaches. Since approach concordance did not impact dislocation, infection, or fracture rates after rTHA, surgeons can feel reassured using a separate approach for rTHA. Level III EvidenceRetrospective Cohort Study.

Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer.

Programmed death-ligand 1 (PD-L1) expression is required for benefit from immune checkpoint inhibitors in metastatic triple negative breast cancer (TNBC). In contrast, in the neoadjuvant setting patients benefited regardless of PD-L1 expression. We hypothesized that, in stages II-III breast cancers, low levels of PD-L1 expression may be sufficient to confer sensitivity to therapy and focal expression could be missed by a biopsy. In this study, we examined intratumor spatial heterogeneity of PD-L1 protein expression in multiple biopsies from different regions of breast cancers in 57 primary breast tumors (n = 33 TNBC, n = 19 estrogen receptor-positive [ER-positive], n = 5 human epidermal receptor 2-positive [HER2 +]). E1L3N antibody was used to assess PD-L1 status and staining was scored using the combined positivity score (CPS) with PD-L1 positive defined as CPS ≥ 10. Overall, 19% (11/57) of tumors were PD-L1 positive based on positivity in at least 1 biopsy. Among TNBC, PD-L1 positivity was 27% (9/33). The discordance rate, defined as the same tumor yielding PD-L1 positive and negative samples in different regions, was 16% (n = 9) in the whole study population and 23% (n = 7) in TNBC. Cohen's kappa coefficient of agreement was 0.214 for the whole study and 0.239 for TNBC, both of which falling into a non-statistically significant fair agreement range. Among all PD-L1 positive cases, 82% (n = 9/11) had positivity in only one of the tissue assessments. These results indicate that the overall 84% concordance is driven by concordant negative results. In PD-L1 positive cancers, within-tumor heterogeneity in PD-L1 expression exists.

Comparison of PD-L1 expression and MMR status between primary and matched metastatic lesions in patients with cervical cancer.

Programmed death-ligand 1 (PD-L1) and DNA mismatch repair (MMR) are considered predictive biomarkers for immunotherapy in cervical cancer. However, their expression in primary tumors and metastases does not always match affecting the course of treatment. We investigated the consistency of their expression in primary and matched recurrent/metastatic lesions from patients with cervical cancer. Primary and matched recurrent/metastatic specimens from patients with recurrent cervical cancer (n = 194) were stained for PD-L1 and MMR (MLHI, MSH6, MSH2, and PMS2) using immunohistochemistry. The degree of consistency of PD-L1 and MMR expression in these lesions was analyzed. The inconsistency rate of PD-L1 expression in primary and recurrent/metastatic lesions was 33.0%, and it varied between the recurrence sites. Positive PD-L1 rate in primary lesions was lower (15.4%) than that in recurrent/metastatic lesions (30.4%). The discordance rate of MMR expression between primary and recurrent/metastatic lesions was 4.1%. We conclude that to use PD-L1 as a predictive biomarker for immunotherapy, analysis of both metastatic and primary lesions may be required. High consistency rate of MMR expression between primary and metastatic lesions suggests that testing primary lesions alone can be sufficient for guiding the course of therapy, thereby solving the difficulty of obtaining recurrent/metastatic specimens in clinic.

Comparison of existing methods of low-density lipoprotein cholesterol estimation in patients with type 2 diabetes mellitus.

Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). Direct LDL-C measurement is not widely performed. LDL-C is routinely calculated using the Friedewald equation (FLDL), which is inaccurate at high triglyceride (TG) or low LDL-C levels. We aimed to compare this routine method with other estimation methods in patients with type 2 diabetes mellitus (T2DM), who typically have elevated TG levels and ASCVD risk. We performed a retrospective cohort study on T2DM patients from a multi-institutional diabetes registry in Singapore from 2013 to 2020. LDL-C values estimated by the equations: FLDL, Martin/Hopkins (MLDL) and Sampson (SLDL) were compared using measures of agreement and correlation. Subgroup analysis comparing estimated LDL-C with directly measured LDL-C (DLDL) was conducted in patients from a single institution. Estimated LDL-C was considered discordant if LDL-C was <1.8mmol/L for the index equation and ≥1.8mmol/L for the comparator. A total of 154,877 patients were included in the final analysis, and 11,475 patients in the subgroup analysis. All 3 equations demonstrated strong overall correlation and goodness-of-fit. Discordance was 4.21% for FLDL-SLDL and 6.55% for FLDL-MLDL. In the subgroup analysis, discordance was 21.57% for DLDL-FLDL, 17.31% for DLDL-SLDL and 14.44% for DLDL-MLDL. All discordance rates increased at TG levels >4.5mmol/L. We demonstrated strong correlations between newer methods of LDL-C estimation, FLDL, and DLDL. At higher TG concentrations, no equation performed well. The Martin/Hopkins equation had the least discordance with DLDL, and may minimise misclassification compared with the FLDL and SLDL.

Evaluation of Local Recurrence and Diagnostic Discordance in Chondrosarcoma Patients Undergoing Preoperative Biopsy.

Preoperative biopsy of chondroid lesions has demonstrated discordance between biopsy grade and surgical resection grade. Furthermore, there is evidence to suggest risk of tumor contamination during biopsy. We evaluated our large chondrosarcoma institutional cohort to compare the rates of local recurrence based on pre-surgical biopsy, as well as other tumor characteristics and disease-related outcomes. This was a retrospective review of patients who underwent surgical resection for chondrosarcoma at our Institution between 2005 and 2020. Outcomes included rates of local recurrence, metastasis, and overall survival. No significant differences were found in local recurrence and recurrence-free survival in cases of pre-operative biopsy. Thirteen (28.2%) patients had discordance between histological grade on biopsy and resection. Seven (63.6%) patients with dedifferentiation present on final resection were not identified on biopsy. The only independent predictor of recurrence-free survival and metastasis-free survival was the presence of dedifferentiation on resection. To our knowledge, this is the first study evaluating risk of local recurrence in the setting of pre-surgical biopsy in chondrosarcoma patients. Although pre-operative biopsy may contaminate biopsy tracts, appropriate surgical planning and final resection results in no difference in local recurrence rates in this cohort. However, discordance rates between preoperative biopsy and resected specimen must be considered while determining clinical treatment.

Department Wide Validation in Digital Pathology—Experience from an Academic Teaching Hospital Using the UK Royal College of Pathologists’ Guidance

Aim: we describe our experience of validating departmental pathologists for digital pathology reporting, based on the UK Royal College of Pathologists (RCPath) “Best Practice Recommendations for Implementing Digital Pathology (DP),” at a large academic teaching hospital that scans 100% of its surgical workload. We focus on Stage 2 of validation (prospective experience) prior to full validation sign-off. Methods and results: twenty histopathologists completed Stage 1 of the validation process and subsequently completed Stage 2 validation, prospectively reporting a total of 3777 cases covering eight specialities. All cases were initially viewed on digital whole slide images (WSI) with relevant parameters checked on glass slides, and discordances were reconciled before the case was signed out. Pathologists kept an electronic log of the cases, the preferred reporting modality used, and their experiences. At the end of each validation, a summary was compiled and reviewed with a mentor. This was submitted to the DP Steering Group who assessed the scope of cases and experience before sign-off for full validation. A total of 1.3% (49/3777) of the cases had a discordance between WSI and glass slides. A total of 61% (30/49) of the discordances were categorised as a minor error in a supplementary parameter without clinical impact. The most common reasons for diagnostic discordances across specialities included identification and grading of dysplasia, assessment of tumour invasion, identification of small prognostic or diagnostic objects, interpretation of immunohistochemistry/special stains, and mitotic count assessment. Pathologists showed similar mean diagnostic confidences (on Likert scale from 0 to 7) with a mean of 6.8 on digital and 6.9 on glass slide reporting. Conclusion: we describe one of the first real-world experiences of a department-wide effort to implement, validate, and roll out digital pathology reporting by applying the RCPath Recommendations for Implementing DP. We have shown a very low rate of discordance between WSI and glass slides.

Widespread Misinterpretation of Advance Directives and Portable Orders for Life-Sustaining Treatments Threatens Patient Safety and Causes Undertreatment and Overtreatment.

Widespread Misinterpretation of Advance Directives and Portable Orders for Life-Sustaining Treatments Threatens Patient Safety and Causes Undertreatment and Overtreatment.

XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease

BackgroundXentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.MethodsThis double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors. Patients received a weekly intravenous infusion of xentuzumab (1000 mg) or placebo in combination with everolimus (10 mg/day orally) and exemestane (25 mg/day orally). The primary endpoint was progression-free survival (PFS) per independent review.ResultsA total of 103 patients were randomised and 101 were treated (n = 50 in the xentuzumab arm and n = 51 in the placebo arm). The trial was unblinded early due to high rates of discordance between independent and investigator assessment of PFS. Per independent assessment, median PFS was 12.7 (95% CI 6.8–29.3) months with xentuzumab and 11.0 (7.7–19.5) months with placebo (hazard ratio 1.19; 95% CI 0.55–2.59; p = 0.6534). Per investigator assessment, median PFS was 7.4 (6.8–9.7) months with xentuzumab and 9.2 (5.6–14.4) months with placebo (hazard ratio 1.23; 95% CI 0.69–2.20; p = 0.4800). Tolerability was similar between the arms, with diarrhoea (33.3–56.0%), fatigue (33.3–44.0%) and headache (21.6–40.0%) being the most common treatment-emergent adverse events. The incidence of grade ≥ 3 hyperglycaemia was similar between the xentuzumab (2.0%) and placebo (5.9%) arms.ConclusionsWhile this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab.Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.

Patient reported outcomes in obstructive hypertrophic cardiomyopathy undergoing myectomy: Results from SPIRIT-HCM study

BackgroundPatient reported outcomes (PRO) can assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). In symptomatic oHCM patients, we sought to study the correlation between various PROs, their association with physician reported New York Heart Association (NYHA) class and changes after surgical myectomy. MethodsWe prospectively studied 173 symptomatic oHCM patients undergoing myectomy (age 51 years, 62% men) between 3/17–6/20. PROs, including a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] c) Duke Activity Status Index [DASI] & d) European QOL score [EQ-5D], along with NYHA class, 6-min walk test (6MWT) distance and peak left ventricular outflow tract gradient (PLVOTG) were recorded at baseline and 12 month follow-up. ResultsThe median baseline PRO scores (KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D) were 50, 67, 63, 25, 50, 37, 44, 25 and 0.61, respectively; 6MWT distance was 366 m. There were significant correlations between various PROs (r-values between 0.66 and 0.92, p < 0.001), but only modest correlations with 6MWT and provokable LVOTG (r-values between 0.2 and 0.5, p < 0.01). At baseline, 35–49% patients in NYHA class II had PROs worse than median, while 30–39% patients in NYHA Class III/IV had PROs better than median. At follow-up, a 20 point improvement in KCCQ summary score was observed in 80%, 4 point improvement in DASI score in 83%, 4 point improvement in PROMIS physical score 86% and a 0.04 point improvement in EQ-5D in 85%); along with improvements in NYHA class (67% in Class I) and peak LVOTG (median 13 mmHg) and 6MWT (median distance 438 m). ConclusionsIn a prospective study of symptomatic oHCM patients, surgical myectomy significantly improved PROs, LVOT obstruction, and functional capacity, with a high correlation between various PROs. However, there was high rate of discordance between PROs and NYHA class. Study registrationClinicalTrials.gov: NCT03092843.

Use of nongynecologic cytologic-histologic correlation to identify patterns of error: An institutional experience.

Quality management practices empower cytology laboratories to deliver consistent, high-quality patient care. Monitoring of key performance indicators is one way by which laboratories can identify patterns of error and focus their improvement activities. Cytologic-histologic correlation (CHC) identifies error by retrospectively reviewing cytology cases when discordant surgical pathology diagnoses are reported. Analysis of CHC data can elucidate patterns of error and direct quality improvement initiatives. CHC data of nongynecologic cytology specimens were reviewed over a 3-year period (2018-2021). Errors were separated by anatomic site and classified as either sampling or interpretive errors. A total of 364 discordant cases were identified out of 4422 cytologic-histologic pairs (a discordant rate of 8%). The majority (272; 75%) were sampling errors, with fewer interpretive errors (92; 25%). Sampling errors were found to occur most commonly in lower urinary tract and lung. Interpretive errors were most commonly found in lower urinary tract and thyroid. Nongynecologic CHC data can be a valuable resource for cytology laboratories. By studying the types of errors, quality improvement activities can be targeted toward problem areas.

Occam's Razor: Two Arrhythmias in a Single Heart?

Occam's Razor: Two Arrhythmias in a Single Heart?

Clinical and histologic factors associated with discordance between steatosis grade derived from histology vs. MRI-PDFF in NAFLD.

Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an excellent biomarker for the non-invasive quantification of hepatic steatosis. To examine clinical and histologic factors associated with discordance between steatosis grade determined by histology and MRI-PDFF in patients with non-alcoholic fatty liver disease (NAFLD) METHODS: We included 728 patients with biopsy-proven NAFLD from UC San Diego (n = 414) and Yokohama City University (n = 314) who underwent MRI-PDFF and liver biopsy. Patients were stratified by steatosis, and matched with MRI-PDFF cut-points for each steatosis grade: 0 (MRI-PDFF < 6.4%), 1 (MRI-PDFF: 6.4%-17.4%), 2 (MRI-PDFF: 17.4%-22.1%), 3 (MRI-PDFF ≥ 22.1%). Primary outcome was major discordance defined as ≥2 steatosis grade difference determined by histology and MRI-PDFF. Mean (±SD) age and BMI were 55.3 (±13.8) years and 29.9 (±4.9) kg/m2 , respectively. The distributions of histology and MRI-PDFF-determined steatosis were 5.5% grade 0 (n = 40), 44.8% 1 (n = 326, 44.8%), 33.9% 2 (n = 247), and 15.8% 3 (n = 115) vs. 23.5% grade 0 (n = 171), 49.7% 1 (n = 362), 12.9% 2 (n = 94), and 13.9% 3 (n = 101). Major discordance rate was 6.6% (n = 48). Most cases with major discordance had greater histology-determined steatosis grade (n = 40, 88.3%), higher serum AST and liver stiffness, and greater likelihood of fibrosis ≥2, ballooning ≥1 and lobular inflammation ≥2 (all p < 0.05). Histology overestimates steatosis grade compared to MRI-PDFF. Patients with advanced NASH are likely to be upgraded on steatosis grade by histology. These data have important implications for steatosis estimation and reporting on histology in clinical practice and trials, especially in patients with stage 2 fibrosis.