Discrepant Cases Research Articles

Analysis of microsatellite instability in endometroid carcinoma with deficient mismatch repair

Objective: To analyze the microsatellite instability (MSI) status in endometrioid endometrial carcinoma (EEC) with deficient mismatch repair (dMMR) and to explore the concordance between MSI next generation sequencing (NGS)/PCR and MMR immunohistochemistry (IHC) results. Methods: Sixty dMMR EEC cases by IHC from November 2017 to February 2019 were selected in the Department of Pathology, Peking Union Medical College Hospital. Two pathologists reviewed the IHC results. The MSI status and the germline/somatic mutational status of MMR genes were analyzed by NGS. MLH1 promoter methylation status was determined by methylation-specific PCR (MSP) in cases with MLH1 protein deficiency. In cases with discrepant results between MMR IHC and MSI NGS, the MSI status was detected again by PCR, and the reasons for the discrepancy were discussed with gene mutation and MLH1 promoter methylation results. Results: Among 60 dMMR EEC specimens, 3 samples were re-assigned as proficient mismatch repair (pMMR) after pathological review, and identified as MSS by NGS. Another 3 dMMR cases showed MSI-uncertainty (MSI-U) by NGS due to insufficient tumor content. In the remaining 54 cases, the concordance between MMR IHC and MSI NGS was 87% (47/54). The seven discrepant cases was further analyzed: in 5 discrepant cases with MLH1/PMS2 protein loss, one case did not have enough samples for detection, one case was MSI-H, and the remaining three cases were MSS by PCR. All these 5 cases with MLH1/PMS2 protein loss showed the MLH1 promoter hypermethylation, two of which also had a somatic mutation in the MSH2 gene. The two discrepant cases with MSH6 protein loss were both MSS by PCR, one of which was considered to have Lynch syndrome with germline mutation in MSH6 gene. Conclusions: Although the overwhelming majority of dMMR EEC cases by IHC shows MSI-H by NGS/PCR, there are uncommon discrepant dMMR EEC cases with MSS. They are mostly found in cases with MLH1/PMS2 protein loss caused by MLH1 promoter hypermethylation and rarely related to Lynch syndrome. Both MMR IHC and MSI NGS/PCR tests have their advantages and disadvantages, complimentary to each other.

Selective pathological examination following hip arthroplasty: A retrospective cohort study

BackgroundPathological examination of the femoral head after hip arthroplasty is often performed routinely. The cost-effectiveness of the examination with regard to identifying clinically relevant diagnoses has been a point of discussion. To date, recommendations on performing pathological examination based on patient characteristics, disease history or radiographic findings are scarce. The aim of this study was to gain insight in when to select a patient for pathological examination of the femoral head by means of the following research questions: “How many clinically relevant diagnoses does selective pathological examination identify?” “Which factors contribute to selection of the femoral head for conducting pathological examination?” “What are the costs of selective pathological examination for identifying clinically relevant diagnoses?” HypothesisSelective pathological examination of the femoral head results in higher ratios of identified clinically relevant diagnoses against substantially lower costs. MethodsA retrospective cohort study was performed over the period of 2010–2015. All pathological reports were collected from our hospital and screened for resected femoral heads after primary total hip arthroplasty (THA) or primary hemiarthroplasty (HA). The coherence between preoperative diagnosis and postoperative pathological diagnosis was defined as concordant, discrepant or discordant. The aim was to perform logistic regression analysis. ResultsIn total, 164 patients were included of 3998 hip arthroplasties performed during the study period with a mean age of 74±12.3 years including 54 (33%) male and 110 (67%) female of whom 112 (68%) underwent THA and 52 (32%) HA. A discrepancy in diagnosis was found in nine patients (6%) and discordance in three patients (2%). The most frequently reported reasons to perform pathological examination were malignancy in medical history n=86 (53%), avascular necrosis n=22 (13%), bone abnormality perioperatively n=19 (11%) and pathological fracture n=13 (8%). The factors that identified the unexpected clinically relevant diagnoses were pathological fracture (3 cases out of 13), bone abnormality perioperatively (2 out of 19), abnormalities on preoperative radiographs (1 out of 9) and to a lesser extent malignancy in history (2 out of 86). With costs of pathological examination of approximately €163 per femoral head, performed in 164 patients, the total costs of pathological examination resulted in €26,732. The cost per discrepant case (n=9) was €2970 and the cost per discordant case (n=3) was €8910. ConclusionSelective pathological examination of the femoral head following hip arthroplasty results in higher ratios of discrepant and discordant cases against substantially lower costs. Factors that identify clinically relevant diagnoses are pathological fracture, perioperative bone abnormality, abnormalities on preoperative radiographs and to a lesser extent malignancy in history. Level of evidenceIII; retrospective cohort study.

Performance Evaluation of the Newly Developed In Vitro Rapid Diagnostic Test for Detecting OXA-48-Like, KPC-, NDM-, VIM- and IMP-Type Carbapenemases: The RESIST-5 O.K.N.V.I. Multiplex Lateral Flow Assay.

The objective of this study was to evaluate the performance of the RESIST-5 O.K.N.V.I. assay for identifying these five common domestic carbapenemases among a large number of clinical isolates in South Korea. A total of 268 non-duplicated clinical isolates of gram-negative bacilli were included in this study as follows: 258 carbapenemase-producing (CP) strains (OXA-48-like, KPC, NDM, VIM, IMP, GES, OXA-23 and two or more carbapenemase producers) and 10 non-CP carbapenem-resistant Enterobacterales (non-CP CREs). Overall sensitivity and specificity were 98.4% and 100%, respectively. In addition, all non-targeted carbapenemase producers including GES and OXA-23 producers and non-CP CREs were correctly identified as negative results. There were only four discrepant cases in which three VIM carbapenemase producers and one NDM carbapenemase producer were not detected. The RESIST-5 O.K.N.V.I. assay as an in vitro diagnostic test for detecting five common carbapenemases provided rapid and accurate results in a short time, indicating that this method could provide an innovative solution for early detection, resulting in appropriate antimicrobial treatment in the clinical field.

Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches

OBJECTIVEThis study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging–Alzheimer's Association (NIA-AA) criteria versus 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIGNCross-sectional examination of baseline data from the Prevention of Alzheimer's dementia (AD) using Cognitive remediation and transcranial direct current stimulation in Mild Cognitive Impairment (MCI) and Depression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. SETTINGFive geriatric psychiatry and memory clinics located at academic hospitals affiliated with the Department of Psychiatry, University of Toronto. PARTICIPANTSOlder adults (N = 431) with a history of major depressive disorder (MDD) in remission, MCI, or both. MEASUREMENTSMain outcome was a comparison of NIA-AA diagnostic rates of MCI or dementia versus DSM-5 rates of mild or major neurocognitive disorder. Secondary analyses examined demographic, race, gender, premorbid intellectual ability, psychosocial, health-related, and genetic predictors of discrepancy between DSM-5 and NIA-AA diagnoses. RESULTSThere were 103 (23.8%) discrepant cases, with most (91; 88.3%) of these discrepant cases reflecting more impairment with the detailed neuropsychological testing and NIA-AA criteria. Discrepancies were more likely in individuals with a history of MDD or who had at least one ApoE4 allele. CONCLUSIONThe NIA-AA criteria, in conjunction with comprehensive neuropsychological testing, identified a greater prevalence of cognitive impairment than DSM-5 criteria, in conjunction with the Montreal Cognitive Assessment. Detailed neuropsychological evaluations are recommended for older adults who have a history of MDD or a genetic vulnerability to dementia.

Assessment of lymphovascular invasion in early stage endometrial carcinoma -a retrospective study

IntroductionEndometrial carcinoma is associated with several known prognostic factors. Recently, lymphovascular invasion (LVI) has gained a prominent position in the risk assessment of early endometrioid endometrial carcinoma, in identifying patients who can benefit from adjuvant radiation therapy. This study aims to assess LVI in early-stage endometrioid endometrial carcinoma accurately with emphasis on its extent /grading. We also propose a few local recommendations for improving LVI reproducibility in endometrial carcinoma to guide future studies.MethodsThe duration of this retrospective study was 2 years. Early-stage I (Ia and Ib), and grade 1 and 2 endometrioid endometrial carcinomas were included. 03 reviewers independently recorded their findings on H&E stained slides. LVI was graded as none, focal and substantial. In discordant cases, immunohistochemical stain CD 31 was used.All the data was entered in the statistical software SPSS version 26 and analyzed for frequencies. The relationships between various histological parameters assessed and the degree of reproducibility for LVI amongst various observers were also determined.ResultsOut of a total of 70 cases of endometrioid carcinoma diagnosed on hysterectomy specimen, only 32 met our inclusion criteria. The rate of LVI positivity was 6.3 %, 34.4 %, and 37.5 % respectively for reviewers 1, 2, and 3. The degree of reproducibility in LVI assessment and LVI grading was significant amongst reviewers 2 and 3. Also, a significant association was drawn between tumor grade and LVI.ConclusionDespite limitations in our study we recommend including both LVI assessment and grading in routine reporting formats locally. By adding a second reviewer in LVI assessment and using CD31 in discrepant cases LVI positivity can be significantly increased.

Evaluation of a fully closed real time PCR platform for the detection of SARS-CoV-2 in nasopharyngeal swabs: a pilot study

AimsTo date, reverse transcriptase PCR (RT-PCR) on nasopharyngeal swabs is the ‘gold standard’ approach for the diagnosis of COVID-19. The need to develop easy to use, rapid, robust and with...

Does Retrograde Femoral Nailing through a Normal Physis Impair Growth? An Experimental Porcine Model.

Materials and methodsThe study was carried out using an experimental porcine model. Eleven juvenile female porcines were randomized for insertion of a retrograde femoral nail in one limb. The other limb acted as a control. The animals were housed for 8 weeks before the nail was removed and housed for 8 additional weeks, that is, 16 weeks in total. Growth was assessed by interphyseal distance on 3D magnetic resonance imaging (MRI) after 16 weeks and the operated limb was compared to the non-operated limb. Histomorphometric analysis of the physeal canal was performed.ResultsNo difference in longitudinal growth was observed when comparing the operated femur to the non-operated femur using MRI after 16 weeks. No osseous tissue crossing the physis was observed on MRI or histology. The empty canal in the physis after nail removal was filled with fibrous tissue 16 weeks after primary surgery.ConclusionGrowth was not impaired and no bone bridges were seen on MRI or histology 16 weeks after insertion and later removal of the retrograde femoral nail.Clinical significanceThe insertion of a retrograde intramedullary femoral nail centrally through the physis and later removal might be safe, however, long-term follow-up is needed.Aim and objectiveThe insertion of an intramedullary nail may be beneficial in certain cases of leg length discrepancy (LLD) in children. However, it is unknown if the physeal injury due to the surgery may cause bone bridge formation and thereby growth arrest after removal. This study aimed to assess longitudinal interphyseal growth 16 weeks after insertion and later removal of a retrograde femoral nail passing through the physis. Moreover, to analyse the tissue forming in the empty physeal canal after removal of the nail.How to cite this articleAbood AA, Rahbek O, Olesen ML, et al. Does Retrograde Femoral Nailing through a Normal Physis Impair Growth? An Experimental Porcine Model. Strategies Trauma Limb Reconstr 2021;16(1):8–13.

“It’s a Lot Less Hassle and a Lot More Fun”: Factors That Sustain Teachers’ Enthusiasm for and Ability to Deliver Sport Education

Purposes: (a) To describe how more experienced and expert teachers interpreted and delivered sport education (SE) during their careers and (b) to discover and describe factors within their occupational socialization that sustained the teachers’ enthusiasm for and ability to deliver SE. Method: Participants were nine teachers. Primary data sources were formal interviews. Secondary supporting sources were documents and film. They were analyzed by employing standard interpretive methods. Credibility and trustworthiness were established through a search for discrepant and negative cases and member checking. Findings: At different times in their careers, the teachers delivered SE in one of four ways: watered down, through a cafeteria approach, the full version, and the full+ version. A number of factors from their acculturation, professional socialization, and organizational socialization enabled the teachers to deliver the full+ version or led to them delivering other versions of the model. Conclusions: The findings allow us to make practical suggestions for preservice and inservice teacher education that may help university faculty facilitate the teaching of SE.

Negligible therapeutic impact, false-positives, overdiagnosis and lead-time are the reasons why radiographs bring more harm than benefits in the caries diagnosis of preschool children

BackgroundTo evaluate the clinical course and interventions required during two years of follow-up of dental surfaces of deciduous molars diagnosed, and consequently treated, by two different strategies: diagnosis made by clinical examination alone or associated with radiographs.MethodsThis is a secondary analysis of a two-arm randomized clinical trial with parallel groups related to the diagnostic strategy for caries detection in preschool children. 216 children (3–6 years old) were followed-up for two years. All dental surfaces were diagnosed by visual inspection and later, through radiographic assessment. Baseline treatment was made in accordance with the results obtained by visual inspection performed alone or combined with radiographic method, considering the allocated group. Dental surfaces with no restoration needs, or those restored at the beginning of the study were followed-up for two years. The treatment decision was made according to the allocated group. The outcome was the occurrence of failure (a new caries lesion or a restoration replacement) during the follow-up.Results4383 proximal and occlusal surfaces of deciduous molars in 216 preschool children were diagnosed and treated according to the abovementioned diagnostic strategies and followed-up for 24 months. The assessment of radiographs made change the initial decision reached by visual inspection in about 30% of the surfaces when all types of interventions were considered. However, most disagreements occurred for initial lesions, where radiographs tended to underestimate them. Discordances between methods occurred in less than 5% of all surfaces when considered lesions requiring operative treatment. For discrepancy cases, the placed interventions guided by following the radiographic results did not present less failures against those made following only visual inspection. As a matter of fact, the use of radiographs in the diagnostic strategy for caries detection in children brought more harms than benefits due to the occurrence of false-positives, overdiagnosis and lead-time bias.ConclusionsSimultaneous association of visual inspection and radiographic assessment for caries detection in preschool children causes more harms than benefits, and therefore, visual inspection should be conducted alone in the regular clinical practice.Trial registration Clinicaltrials.gov platform: NCT02078453, registered on 5th March 2014.

Differences Between CT-Perfusion and Biphasic Contrast-enhanced CT for Detection and Characterization of Hepatocellular Carcinoma: Potential Explanations for Discrepant Cases.

To compare the diagnostic value of liver perfusion computed tomography (PCT) and biphasic contrast-enhanced CT (bpCECT) for detection and characterization of hepatocellular carcinoma (HCC), and to identify potential causes for inter-modal discrepancies. In this retrospective study, 162 cases with a total of 325 HCC-typical lesions were evaluated using both PCT and bpCECT (mean time between examinations=15 days, range=0-13 days). HCC diagnosis was performed by multi-modality imaging including lesion growth at follow-up. For PCT, a total acquisition time of 40 s (26 measurements) each 1.5 s using 80 kV and 100 mAs, as well as 50 ml iodine contrast agent (at 5 ml/s) covering the entire liver was used. Mean arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic arterial index (HPI) for both tumor and non-involved liver parenchyma; mean blood flow, blood volume and k-trans for tumor were quantified. Tumor localization, and size were registered. bpCECT consisted of unenhanced, arterial (30-33 s delay), and portal-venous (70-75 s) phases performed using 120 kV, 200-250 mAs, thin-slice reformates (<1 mm), 100 ml contrast agent (at 3 ml/s) followed by 50 ml saline flush. Finally, we divided the results according to detection by PCT only (i.e. missed by pbCECT), and by both PCT and pbCECT. PCT detected 272 lesions compared to 217 with bpCECT only. HCCs in liver segments 4 and 5 were significantly better detected by PCT (p<0.005). Furthermore, PCT detected significantly smaller HCCs than did bpCECT (p<0.001). Lesions detected by both methods had significantly higher mean ALP (p=0.03) and HPI (p=0.02), and lower mean PVP (p=0.01). Tumor blood flow, blood volume and k-trans proved not to be significant for lesion detection. The mean ALP, HPI, and PVP in inconspicuous cirrhotic liver were also not significant for lesion detection. The PVP(tumor)/HPI(liver) ratio of detected lesions was significantly higher for PCT alone (p=0.04). Pretreated, still vital lesions were better detected by bpCECT. Detection of smaller HCC lesions, lesions located in liver segments 4 and 5, as well as lesions presenting lower ALP and HPI, and higher PVP(tumor)/HPI(liver) ratio was better using both methods, emphasizing the important role of PCT.

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies of the Korean population and performance characteristics of HLA typing by next-generation sequencing.

Human leukocyte antigen (HLA) identification at the allelic level is important for haematopoietic stem cell transplantation (HSCT). Next-generation sequencing (NGS) resolves ambiguous alleles by determining the phase of the polymorphisms. The aim of this study was to validate the software for HLA-SBT (sequence-based typing), assess Korean allele frequency, and characterise the performance of NGS-HLA typing. From the 2009 to 2016 registry, 1293 unrelated healthy donors with a complete dataset of previously characterised HLA-A, -B, -C, and -DRB1 loci were selected and assessed for frequency, haplotype inference, and relative linkage disequilibrium. For performance characteristics of NGS-HLA, alleles included in 1293 cases and ambiguous or alleles assigned as new by SBT-HLA software, or unassigned alleles were included. A total of 91 and 41 quality control samples resulted in 1056 alleles (132 samples × 4 loci × 2 diploid) for analysis. The GenDx NGSgo kit was used for NGS-HLA typing using the Illumina MiSeq platform. A panel of 132 samples covered 231 alleles, including 53 HLA-A, 80 HLA-B, 43 HLA-C, and 55 HLA-DRB1 by HLA-SBT typing. Comparison of SBT-HLA and NGS-HLA typing showed 99.7% (1053/1056) concordance and discrepant cases were resolved by manual evaluation. Typing by NGS resulted in 67 HLA-A, 112 HLA-B, 71 HLA-C, and 72 HLA-DRB1 alleles. A total of 132 ambiguous, 4 new, and 1 unassigned alleles by HLA-SBT were resolved by NGS-HLA typing. NGS-HLA typing provided robust and conclusive results without ambiguities, and its implementation could support HSCT in clinical settings.

Spectrum, Risk Factors, and Outcomes of Neurological and Psychiatric Complications of COVID-19: A UK-Wide Cross-Sectional Surveillance Study

Background: SARS-CoV2 is associated with neurological and psychiatric complications including cerebrovascular events, encephalopathy and peripheral nerve disease. Detailed clinical data, including factors associated with recovery, is lacking, hampering prediction modelling and targeted therapeutic interventions. We studied COVID-associated neurological and psychiatric complications, to investigate the key clinical features, including those associated with outcome.Methods: This UK-wide cross-sectional surveillance study of neurological and psychiatric complications of COVID-19 in adult hospitalised patients captured detailed data on demographics/risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions, based on criteria adopted by the World Health Organisation, were used, with cross-specialty independent adjudication for discrepant cases. Patients meeting multiple clinical case definitions were identified. Cases of stroke were compared to normative data during the equivalent time-period prior to the pandemic. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome.Findings: 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy not meeting delirium criteria; and peripheral nerve-disorders (41, 15%). 27% of cerebrovascular events occurred in patients 60 years old, the younger patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and more frequently had systemic thrombotic events. Nevertheless, in both younger and older stroke cases there was an association with conventional, modifiable, cerebrovascular risk factors. The timing of neurological presentation varied between disease groups. In 34 cases (13%), clinical case definitions overlapped, and these cases were more likely to require intensive care and ventilation. Regardless of clinical case definition, older age, a higher pre-COVID-19 frailty score, and a high admission white cell count independently associated with a poor outcome. Limited recovery was most common for those with cerebrovascular events. Interpretation: COVID-19 is associated with a broad spectrum of presentations throughout the nervous system, at varied time points relative to respiratory disease. Outcomes vary between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of age and frailty. A severe encephalopathy occurs after COVID-19 and is associated with requiring intensive care and ventilation. COVID-19 is associated with large and multi-vessel stroke in young people, often with non-CNS thrombotic disease and requires further study. Nevertheless, conventional, modifiable risk factors were associated with stroke, even in younger people, suggesting the potential for public health intervention for this and future pandemics. These clinical data should be combined with blood and neuroimaging biomarkers so that patients can be stratified to targeted existing or novel therapeutics.

Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies.

Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR)2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

Overnight attending radiologist coverage decreases imaging-related emergency department recalls by at least 90.

Benefits of overnight attending radiologist final reports are debated, often stating low resident discrepancy rates, usually assessed retrospectively. The objective of this study was to assess the impact of overnight final reporting on the recall rates for patients in the emergency department (ED) receiving overnight imaging. Retrospective matched cohorts of two separate years prior (prior-16 and prior-17) and 1year after (post-18) introduction of overnight attending radiologist final reporting. Patients receiving imaging between 22:00 and 07:00h and returned to ED within 48h of initial visit discharge were electronically identified. String matching identified return visits possibly related to imaging completed on first visit. Identified return visit notes were scored by three observers individually. Unclear and discrepant cases were resolved by consensus meeting, using full patient charts where needed. Incidences were provided and logistic regression analysis defined if coverage model was a predictor for recall. Odds ratios were calculated. ED patient count with imaging completed overnight in prior-16 was 9200, in prior-17 was 9543, and in post-18 was 9992. The number of overnight imaging studies performed was respectively 13,883, 14,463, and 15,112. Imaging-related ED recalls were respectively 54, 61, and 7, a decrease with the new coverage model of 89% to true and at least 90% of expected recalls.Logistic regression demonstrated that coverage model was a significant predictor of ED recalls with chi-square of 59.86 and p< 0.001, an R2 of 0.03 (Hosmer and Lemeshow). Compared to post-18, ED patients had an odds ratio of 8.42 (prior-16) and 9.18 (prior-17) to be called back to ED. Overnight final reporting significantly decreases ED recalls for patients receiving diagnostic imaging overnight. While numbers are low even prior to rollout, the number should be minimized wherever possible to diminish patient anxiety and discomfort, reduce ED overcrowding and expedite definitive management. Section 1: What is already known on this subject • Radiology resident preliminary report discrepancy rates are low. • Overnight attending radiologist coverage is a model increasingly applied in academic and large non-academic centers. • Patient recalls to the ED are a burden to the patient and impact patient throughput in (over)crowded EDs. Section 2: What this study adds • First study to look at the impact of overnight attending final reports on the recall rate for ED patients with overnight imaging performed. • While absolute numbers are low, there is a significant decrease in patients returning to ED for imaging related issues after introducing overnight attending coverage. • Resident autonomy can be preserved and training enhanced while increasing patient safety and comfort.

Post-mortem confirmation of fetal brain abnormalities: challenges highlighted by the MERIDIAN cohort study.

To assess and analyse the concordance between post-mortem findings and inutero magnetic resonance imaging (iuMRI) in the MERIDIAN (MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero) cohort. Prospective cohort study. Fetal medicine units in the UK. Pregnant women with a diagnosis of fetal brain abnormality identified on ultrasound at 18weeks of gestation or later. All pregnancies from the MERIDIAN study that resulted in a abortion were included and the rate of uptake and success of post-mortem examinations were calculated. In the cases in which diagnostic information about the fetal brain was obtained by post-mortem, the results were compared with the diagnoses from iuMRI. Outcome reference diagnosis from post-mortem examination. A total of 155 from 823 pregnancies (19%) ended in a termination of pregnancy and 71 (46%) had post-mortem brain examinations, 62 of which were diagnostically adequate. Hence, the overall rate of successful post-mortem investigation was 40%, and for those cases there was a concordance rate of 84% between iuMRI and post-mortem examination. Detailed information is provided when the results of the post-mortem examination and the iuMRI study differed. We have shown tissue-validation of radiological diagnosis is hampered by a low rate of post-mortem studies in fetuses aborted with brain abnormalities, a situation further compounded by a 12% rate of autopsy being technically unsuccessful. The agreement between iuMRI and post-mortem findings is high, but our analysis of the discrepant cases provides valuable clues for improving how we provide information for parents. TWEETABLE ABSTRACT: iuMRI should be considered a reliable indicator of fetal brain abnormalities when post-mortem is not performed.

Evaluation of a new semi-automated Hydragel 11 von Willebrand factor multimers assay kit for routine use.

BackgroundAccurate diagnosis and classification of von Willebrand disease (VWD) are essential for optimal management. The von Willebrand factor multimers analysis (VWF:MM) is an integral part of the diagnostic process in the phenotypic classification, especially in discrepant cases. The aim of this study was to evaluate the performance of a new Hydragel 11VWF multimer assay (H11VW).MethodsAnalytical performance characteristics such as repeatability (intra-assay variability, in gel between track variation), reproducibility (inter-assay variability, between gel variation), sensitivity, EQA performance and differences between two commercially available VWF:MM kits (H5VW and H11VW) were analysed in healthy volunteers' plasmas using in-house prepared reference plasma.ResultsRepeatability and reproducibility results of H11VW demonstrated acceptable and equivalent performance with previously verified H5VW. Participation in EQA was successful. No statistically significant difference was detected between H5VW and H11VW kits for different fractions of multimers: LMWM p=0.807; IMWM p=0.183; HMWM p=0.774.ConclusionsH11VW demonstrated acceptable analytical performance characteristics. H11VW kit conveniently offers a more significant number of samples on a single gel. H5VW and H11VW kits can be used in daily practice interchangeably.

Phase II Trial of Proton Therapy vs. Photon IMRT for GBM: Secondary Analysis Comparison of Progression Free Survival between RANO vs. Clinical Assessment

BackgroundThis secondary image analysis of a randomized trial of proton radiotherapy (PT) versus photon intensity-modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment versus Response Assessment in Neuro-Oncology (RANO).MethodsEligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. “Clinical progression” was based on a clinical radiology report of progression and/or change in treatment for progression.ResultsOf 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (range: 9.4–14.7) months; 10.8 months IMRT versus 11.2 months PT (P = .14). Median RANO-PFS was 8.2 (range: 6.9, 12): 8.9 months IMRT versus 6.6 months PT (P = .24). RANO-PFS was significantly shorter than clinical PFS overall (P = .001) and for both the IMRT (P = .01) and PT (P = .04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria.ConclusionsBased on this secondary analysis of a trial of PT versus IMRT for glioblastoma, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.

Verification and Validation of Digital Pathology (Whole Slide Imaging) for Primary Histopathological Diagnosis: All Wales Experience

Aims: The study is aimed to verify Aperio AT2 scanner for reporting on the digital pathology platform (DP) and to validate the cohort of pathologists in the interpretation of DP for routine diagnostic histopathological services in Wales, United Kingdom. Materials, Methods and Results: This was a large multicenter study involving seven hospitals across Wales and unique with 22 (largest number) pathologists participating. 7491 slides from 3001 cases were scanned on Leica Aperio AT2 scanner and reported on digital workstations with Leica software of e-slide manager. A senior pathology fellow compared DP reports with authorized reports on glass slide (GS). A panel of expert pathologists reviewed the discrepant cases under multiheader microscope to establish ground truth. 2745 out of 3001 (91%) cases showed complete concordance between DP and GS reports. Two hundred and fifty-six cases showed discrepancies in diagnosis, of which 170 (5.6%) were deemed of no clinical significance by the review panel. There were 86 (2.9%) clinically significant discrepancies in the diagnosis between DP and GS. The concordance was raised to 97.1% after discounting clinically insignificant discrepancies. Ground truth lay with DP in 28 out of 86 clinically significant discrepancies and with GS in 58 cases. Sensitivity of DP was 98.07% (confidence interval [CI] 97.57–98.56%); for GS was 99.07% (CI 98.72–99.41%). Conclusions: We concluded that Leica Aperio AT2 scanner produces adequate quality of images for routine histopathologic diagnosis. Pathologists were able to diagnose in DP with good concordance as with GS. Strengths and Limitations of this Study: Strengths of this study - This was a prospective blind study. Different pathologists reported digital and glass arms at different times giving an ambience of real-time reporting. There was standardized use of software and hardware across Wales. A strong managerial support from efficiency through the technology group was a key factor for the implementation of the study. Limitations: This study did not include Cytopathology and in situ hybridization slides. Difficulty in achieving surgical pathology practise standardization across the whole country contributed to intra-observer variations.

689. Nasal versus Nasopharyngeal Sample Collection for Diagnostic Nucleic Acid Amplification Testing for Influenza A, Influenza B, and Respiratory Syncytial Viruses

BackgroundNucleic acid amplification testing (NAAT) for influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) is a standard component of diagnosis of infections with these pathogens. At our institution, current standard of practice is to collect nasopharyngeal (NP) samples for such NAAT. In an effort to provide clinicians and patients a simpler, more comfortable sample collection option, we evaluated the use of nasal samples for NAAT, compared to NP samples.MethodsBoth nasal and NP specimens were collected from each of 58 patients seen in our emergency department (January – March 2020). NP samples were collected using minitip FLOQswabs; nasal samples were collected using regular or minitip FLOQswabs. Nasal and NP samples were processed using the same protocol and tested for influenza viruses and RSV using the Cepheid GeneXpert (Xpress Flu/RSV) platform.ResultsIn total, 20 NP samples tested negative for virus and 38 tested positive (16 IAV-positive, 14 IBV-positive, 8 RSV-positive). There were 3 cases (5% of total cases) in which qualitative (positive/negative) results from the corresponding nasal samples were not in agreement with results derived from NP samples. These were considered false-negative results; one such discrepancy was resolved upon re-testing the same samples. Overall positive percent agreement between nasal- and NP-derived results was 92% (35/38), and negative percent agreement was 100% (20/20). Among samples testing positive for virus by both NP and nasal sampling methods, we found that the average cycle threshold (Ct) value for IAV detection was 5.1 cycles (n = 16, SEM = 0.83) higher for nasal samples than for NP samples. The average Ct for IBV detection was 3.3 cycles (n = 12, SEM = 1.87) higher for nasal than for NP samples. The average Ct for RSV detection was 1.9 cycles (n = 7, SEM = 1.57) higher for nasal than for NP samples.ConclusionThese results suggest that recovery of viral RNA from nasal samples is lower than that from nasopharyngeal samples, particularly for influenza viruses. This decreased detection of viral RNA from nasal samples may explain the false-negative results seen in our discrepant cases. These data suggest that a decrease in recovery of viral RNA by nasal sampling may translate to decreased diagnostic accuracy.Disclosures All Authors: No reported disclosures

Sub muscular bridge plating for pediatric femur fractures – Review of 12 patients

Introduction: The treatment of paediatric femoral fractures has been evolving from nonoperative modalities to operative intervention, especially in older children. Different methods of fixation include flexible intramedullary nailing, modified locked intramedullary nailing, external fixation, open compression plating, and sub muscular bridge plating. Treatment of complex paediatric femur diaphyseal fractures is difficult by conventional methods. External ?xation can lead to malalignment and refractures, casting is difficult for polytrauma patients and larger children, elastic nails do not provide adequate stability to unstable fractures and metaphyseal areas, and lateral trochanteric entry rigid nails are unsuitable for very proximal and distal fragments and are ideal for older children for the want of larger medullary canal. Sub muscular bridge plating has emerged as a viable alternative procedure. We present our results of sub muscular bridge plating in 12 patients. Materials and Methods: We retrospectively reviewed 12 patients with pediatric diaphyseal femoral fractures treated with SBP from 2014 to 2016. The average age was 9 years with follow up of 1yr. Results: All the children had complete union and could return to full activity. Two patients had superficial infections. There were no cases of significant malalignment or leg length discrepancy. Implant removal was performed in 8 patients without complications. Conclusion: We find sub muscular plating of paediatric femoral fractures to be an effective and reliable procedure. SBP is a minimally invasive technique that allows early mobilization with minimal complications. Keywords: Paediatric femur fractures, Submuscular plating.