Discrepant Cases Research Articles

Abstract 4259: Identification of anti-neoplastic therapy given before initial visit at a referral center using natural language processing applied to medical oncology initial consultation notes

Abstract Anticancer therapy changes tumor physiology and genomics, making it a key variable in cancer studies. Although antineoplastics given at a single institution may be available in research-ready format, treatment at external institutions prior to receiving care at academic medical centers, common among patients at these centers, is often only described in free-text clinical notes, necessitating manual curation for downstream analysis. To overcome this bottleneck, we trained and validated natural language processing (NLP) models using initial consult notes to identify whether patients had received treatment at external institutions and studied the impact of these putative treatments on tumor genomics. Training data were derived from the AACR Project GENIE Biopharma Collaborative (BPC) for 2,663 patients at Memorial Sloan Kettering (MSK) across four cancer types. For each patient, we selected initial visits with medical and radiation oncologists based on an a priori note prioritization scheme and determined “ground-truth” prior external medications based on manually curated BPC administration records, whitelisting MSK-given medications. We trained logistic regression and clinical longformer models to identify external treatment receipt and evaluated model performance with 5-fold cross-validation. The clinical longformer model performed best across evaluation metrics, with an average area under the receiver operating characteristic curve of 0.972, macro-averaged precision/recall of 0.854/0.902 and macro-averaged F1 score of 0.876. Re-review of discrepant cases suggested that 75% of “false positives” may be due to curation error. We used our model to infer treatment status in a pan-cancer cohort with tumor genomic profiling using our institutional sequencing platform. Out of 48,447 patients, 11,900 were predicted to have received external treatment. Patients with putative external treatment had higher alteration frequencies in resistance-related genes than untreated patients and comparable to known pre-treated patients, including ESR1 in patients with breast cancer, AR in patients with prostate cancer, and EGFR T790M in patients with EGFR-mutated non-small cell lung cancer. Patients with putative external treatments, similar to known pre-treated patients, had shorter survival compared to treatment-naïve patients of the same cancer type. NLP can abstract external treatment status from clinical notes. When applied at scale, our model could help mitigate confounding variables and identify relationships between clinicogenomic variables and anticancer therapy. Citation Format: Thinh N. Tran, Karl B. Pichotta, Si-Yang Liu, Christopher Fong, Anisha Luthra, Brooke Mastrogiacomo, Steven Maron, Deborah Schrag, Sohrab P. Shah, Pedram Razavi, Bob T. Li, Gregory J. Riely, Nikolaus Schultz, Justin Jee. Identification of anti-neoplastic therapy given before initial visit at a referral center using natural language processing applied to medical oncology initial consultation notes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4259.

Diagnostic performance of Idylla MSI test in colorectal cancer biopsies

Universal testing for microsatellite instability (MSI) is recommended in colorectal cancer (CRC) to screen for Lynch syndrome and to guide optimal treatment and follow-up of the patients. Especially in neoadjuvant setting, where immuno-oncological treatments have recently shown excellent responses, identification of MSI status at biopsy is a prerequisite. Idylla MSI test offers a rapid and automated test to assess MSI-status from formalin-fixed paraffin-embedded tumor tissue sections. In this study, we compared the performance of the Idylla MSI test to mismatch repair (MMR) protein immunohistochemistry (IHC) using 117 CRC biopsies with previously known deficient MMR status. The concordance between Idylla and IHC was 99.0% (95/96) for biopsies with the recommended ≥ 20% tumor cell content. Further, 85.7% (18/21) of suboptimal CRC biopsy specimens (tumor cell content 5–15%) were diagnosed as MSI. Overall, we identified four discrepant cases of which three had tumor cell content less than 20%, explaining the discordant result. Our study shows that the Idylla MSI test offers a competent tool for MSI screening in CRC biopsy specimens.

Abstract P1-10-11: Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes

Abstract BACKGROUND: The role of multi-lumen catheter devices in the delivery of high dose rate (HDR) brachytherapy for adjuvant accelerated partial breast irradiation (APBI) for women with DCIS or early-stage breast cancer has been well established. In vivo dosimetry (IVD) using optically stimulating luminescence dosimeters (OSLD) is a feasible way to detect applicator instability that may cause translational and rotational inaccuracies during HDR brachytherapy delivery. Herein, we evaluate the accuracy and effectiveness of IVD to improve patient outcomes following APBI brachytherapy using the Strut Adjusted Volume Irradiation (SAVI) device. METHODS: Single-institution cohort study piloting the use of OSLD on the patient’s skin during HDR brachytherapy APBI to assess the estimated maximum skin dose (skin Dmax) and the achievable accuracy of OSLD for skin Dmax measurements. Women treated with SAVI-based APBI between November 1, 2018 and October 1, 2021 were eligible to enroll in our study. All patients met the American Society for Radiation Oncology “suitable” or “cautionary” criteria and were treated according to the American Brachytherapy Society consensus treatment planning guidelines. A SAVI preplan was created to estimate the probable point of skin Dmax. During CT simulation, a radiopaque marker was placed on the skin for visualization during treatment planning. Correction factors were applied to account for the OSLD tissue-air interface that is not present in the TG-43 expected dose calculations. Measured and calculated IVD doses were analyzed to assess agreement and cause for discrepancies found. Breast phantom IVD measurements repeated seven times with two independent dose points were analyzed to assess the best accuracy achievable under ideal conditions. RESULTS: We enrolled 41 patients with an average age of 68 years. Table 1 details the brachytherapy treatment delivery and dosimetry data. Higher skin Dmax as a percentage of the radiation prescription was associated with the occurrence of breast volume loss noted on subsequent clinical breast exams (OR 1.84 per each 5% increase in skin Dmax; 95% CI 1.21 – 3.32; p=0.016). The graphically estimated skin Dmax threshold was 80% with all cases of noted breast volume loss occurring above this threshold. The overall level of achievable IVD accuracy was ±3.32% based on breast phantom measurements. Under ideal conditions, all measurements were in the ±7% range. Three of 14 phantom measurement exceeded the 6% discrepancy range. Clinical IVD measurements detected 5 true positive cases (12.2% of cohort) that required intervention due to rotations in the SAVI applicator. For a ±7% tolerance criteria, 90.2% of the patients tested passed IVD. Of the eight patients that failed at the 7% level, IVD detected 3 OSLD placement errors, 2 rotational discrepancy cases, and 1 large air-gap at the point of measurement. CONCLUSIONS: Accuracy and reproducibility are imperative tenets of HDR brachytherapy APBI. IVD utilizing OSLD is an effective method for detecting treatment set-up and delivery errors for patients receiving SAVI-based APBI with dose accuracy within ±3.32%. Errors requiring intervention due to SAVI device rotation were detected in 12.2% of our cohort, and these errors would have likely gone undetected without IVD. Using OSLD as IVD to measure skin Dmax doses that may increase the risk of breast cosmetic defects should be investigated further. Table 1. Brachytherapy treatment delivery and dosimetry data. *PTV-Eval is a uniform 10 mm expansion on the CTV with exclusion of PTV within 5 mm of skin or chest wall. +Percent dose discrepancy refers to difference in dose between APBI plan calculations and IVD measurements. Citation Format: Tyler Gutschenritter, Afua Yorke, Nayak Polissar, Nirnaya Miljacic, Janice Kim, Lori Young. Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-11.

FIGURATIVE MEANINGS OF ORNITHONYMS IN RUSSIAN AND GEORGIAN

The purpose of this work is to identify, describe and compare the figurative semantics of ornithonyms in the Russian and Georgian languages. Russian Russian and Georgian linguocultures have not been the subject of special consideration and the comparison of ornithonyms with a figurative meaning is relevant and useful in teaching Russian as a foreign language. The following research methods were used: analysis of dictionary definitions of ornithonyms in Russian and Georgian languages; The method of continuous sampling, analytical, descriptive, classification, and comparative methods The contrastive analysis of Russian and Georgian ornithonyms used in a figurative sense showed both cases of coincidence, complete or partial, and cases of discrepancy in values.

Digital morphology and complete remote reporting capabilities by scientists and haematologists – a review

Aim: To establish a workflow for full remote reporting of blood films by laboratory haematologists. Methods: A review of a fully digital morphology workflow by a scientist and haematologist was undertaken as an audit to determine the ability of digital morphology to be utilised as a complete workflow process without the aid of a glass slide to assist with authorising referred cases requiring haematologists review. Over 100 slides were first reviewed by a haematology scientist and referred for haematologist examination on the basis of established laboratory referral criteria. These referred films were first analysed by a haematologist via the digital morphology platform. All cases were then analysed by traditional microscopy from the glass slide. Cases were assessed for reliability and concordance of the digital morphology platform to standard glass slide analysis. Cases not concordant between the digital platform and glass slide review were reassessed by an extended scan function of the digital morphology platform and concordance and reliability were again assessed and recorded. Results: One hundred and nineteen cases were assessed by both methods. There was concordance for 102 cases. The discrepant cases were discordant due to missing platelet clumping in two cases, one case missed low number myelocytes on film and the remainder of the cases were discordant due to discrepancies in assessing red cell morphology. Following the review of the extended scan file for each discordant case all 17 discordant cases were able to be assigned as concordant. Conclusion: A digital morphology workflow is a feasible alternative to standard glass slide review for FBC film cases requiring a haematologist review. The addition of the extended scan function allowed all cases to be assigned as concordant between digital morphology platform and glass slide review. This is a promising technology which will allow quicker remote authorisation of cases requiring haematologist intervention for blood film review. This approach provides flexibility in work arrangements and also offers increased access for rural and remote laboratories to centralised specialist expertise in a timely manner.

The Molecular Diagnosis Might Be Clinically Useful in Discrepant Kidney Allograft Biopsy Findings: An Analysis of Clinical Outcomes.

The Molecular Microscope Diagnostic System (MMDx) may overcome histology shortcomings. Previous studies have simply examined discrepant findings but have not attempted to determine clinical endpoints. To measure performance, clinical outcomes are strongly required. This single-center cohort study described discrepancies between MMDx and histology from 51 kidney transplant recipients (KTRs) and analyzed 72 indication biopsies, including 21 follow-up biopsies. Clinical performance was assessed by a combined endpoint of graft failure, rejection on follow-up biopsy, de novo donor-specific antibody, and improvement of kidney allograft function upon antirejection treatment. MMDx agreed in 33 (65%) and differed in 18 (35%) of 51 KTRs. Most discrepancies occurred in biopsies called no rejection by MMDx and rejection by histology (15/24, 63%). In contrast, in biopsies called rejection by MMDx, 3 were classified as no rejection by histology (3/27, 11%). Discrepant findings between MMDx and histology occurred following delayed graft function and MMDx from biopsies with a low percentage of cortex. Among 15 biopsies classified as no rejection by MMDx but rejection by histology, the clinical course suggested no rejection in 9 cases. Six KTRs reached the endpoint, showing predominant t ≥ 2 lesions. The most often occurring discrepancy is rejection by histology but no rejection by MMDx. As more KTRs do not meet the combined endpoint for rejection, MMDx might be clinically useful in these discrepant cases. Although strong histological findings have priority in indicating the treatment, clinical implementation of MMDx could strengthen treatment strategies.

Prediction of presence of fastidious bacteria by the Fully Automated Urine Particle Analyzer UF-1000i in the case of ineffective antimicrobial therapy for urinary tract infection

IntroductionRecent studies have reported associations between fastidious bacteria that are difficult to grow and isolate in conventional urine culture conditions and urinary tract infections (UTIs). Because the Fully Automated Urine Particle Analyzer UF-1000i (hereinafter referred to as “UF-1000i”) detects fastidious bacteria without being affected by culture conditions, owing to its flow cytometry-based principle, we evaluated the robustness of UF-1000i detection using clinical urine samples from patients with UTIs following ineffective antimicrobial therapy. MethodsA total of 150 patients diagnosed with UTIs were enrolled, and their laboratory findings were analyzed, focusing on the discrepancy in bacterial numbers between UF-1000i and conventional culture at each antimicrobial therapy effectiveness classification. In addition, gene identification was conducted by molecular analysis using 16S ribosomal RNA gene sequencing and next-generation sequencing (NGS) to elucidate the reason for the presence of fastidious bacteria in these samples. ResultsThe ineffective therapy cases showed more than 100-fold discrepancy in bacterial counts, with a higher proportion (30.8%) than effective therapy cases without secondary administration (5.7%) between the bacterial counts in UF-1000i and conventional culture methods. The presence rates of fastidious bacteria were 100% and 66.7% in discrepant cases of ineffective and effective without secondary administrations, respectively. ConclusionThis study suggests that discrepancies in bacterial numbers between the conventional culture method and UF-1000i measurement at the primary visit can predict the presence of fastidious bacteria, especially in cases of ineffective antimicrobial therapy.

Impact of a change to a novel chemiluminescent immunoassay for measuring plasma aldosterone on the diagnosis of primary aldosteronism.

In Japan, the standard method for measuring plasma aldosterone concentration (PAC) for primary aldosteronism (PA) diagnosis was changed from radioimmunoassay (RIA) to a novel chemiluminescent enzyme immunoassay (CLEIA). The purpose of this study is to simulate the possible impact of the change on PA diagnosis. This retrospective study assessed 2,289 PA patients. PACs measured by conventional RIA were transformed to estimated PACs (CLEIA) as follows: RIA (pg/mL) = 1.174 × CLEIA (pg/mL) + 42.3. We applied the estimated PAC (CLEIA) to the conventional cut-off of aldosterone-to-renin activity ratio ≥200 for screening and captopril challenge test (CCT) and PAC ≥60 pg/mL for saline infusion test (SIT). Application of the estimated PAC to screening and confirmatory tests decreased the number of PA diagnoses by 36% (743/2,065) on CCT and 52% (578/1,104) on SIT (discrepant cases). Among the discrepant cases, 87% (548/628) of CCT and 87% (452/522) of SIT were bilateral on adrenal venous sampling (AVS). Surgically treatable aldosterone-producing adenomas (APAs) were observed in 6% (36/579) and 5% (23/472) of discrepant cases on CCT and SIT, respectively; most were characterized by hypokalemia and/or adrenal nodule on CT imaging. Application of the PAC measured by the novel CLEIA to conventional cut-offs decreases the number of PA diagnoses. Although most discrepant cases were bilateral on AVS, there are some APA cases that were characterized by hypokalemia and/or adrenal tumor on CT. Further studies which evaluate PACs measured by both RIA and CLEIA for each patient are needed to identify new cut-offs for PAC measured by CLEIA.

Experimental estimation of liquid phase concentration in aerosol jet

Rapid-mixed models are a key tool in the numerical solution of aerosol flow evaporation problems. Despite the fact that these models are mainly based on analytical arguments, they have shown fairly good reproducibility in practice. However, with the advent of the DNS results, cases of discrepancies with the classical theory of droplet evaporation began to be discovered, which require an experimental study of the problem. The present paper shows an experimental method for estimating the concentration of the liquid phase in aerosol flows based on digital video processing.

Resolving discrepancies in forward and reverse ABO blood group typing

Background/Aim: There is a need of investigation of high frequency of the cases of ABO discrepancy revealed by forward and reverse typing. The aim of the study was to reveal optimal methods for detection of weak subgroups of group A and B antigens on erythrocytes. Methods: Sixteen persons with A blood group and anti-B antibody adsorbing ability (weak Bel, Bm and B3 antigens), 5 persons with B blood group and anti-A antibody adsorbing ability (weak Ax antigen) and 2 persons with O blood group and anti-B antibody adsorbing ability (weak Bel antigen) were investigated as the cases of type II-III of ABO discrepancy and weak B antigen. Liquid chromatography, agglutination, inhibition of agglutination and adsorption reactions at 4 °C and 37 °C with prolonged incubation (12 hours) were used in the study. Results: The persons with A blood group revealed by forward typing at 4 °C and O blood group detected by reverse typing at 37 °C showed the ability of the erythrocytes to adsorb anti-B antibody. The persons with B blood group revealed by forward typing with presence of anti-B antibodies reactive at 37 °C showed the ability of erythrocytes to adsorb anti-A antibody. Prolonged incubation at reverse typing, adsorption-elution tests, inhibition of haemagglutination and liquid chromatography were used to define blood group specificity. Conclusion: Prolonged incubation during reverse typing at 4 °C and 37 °C, adsorption at 4 °C, heat elution and liquid chromatography might help to detect blood group type in cases of type II-III of ABO discrepancy.

The use of Vsee videoconferencing for live telepathology in Rwanda, a potential solution for resource-limited area.

The shortage of pathologists is a worldwide problem that is more severe in Africa. One of the solutions is the use of telepathology (TP); however, most of the TP systems are expensive and unaffordable in many developing countries. At the University Teaching Hospital of Kigali, Rwanda, we assessed the possibility of combining commonly available laboratory tools into a system that can be used for diagnostic TP using Vsee videoconferencing. Using an Olympus microscope (with a camera) operated by a laboratory technologist, histologic images were transmitted to a computer whose screen was shared, using Vsee, with a remotely located pathologist who made the diagnoses. Sixty consecutive small biopsies (≤6 glass slides) from different tissues were examined to make a diagnosis using live Vsee-based videoconferencing TP. Vsee-based diagnoses were compared to pre-existing light microscopy-based diagnoses. Percent agreement and unweighted Cohen's kappa coefficient of the agreement were calculated. For agreement between conventional microscopy-based and Vsee-based diagnoses, we found an unweighted Cohen's kappa of 0.77 ± 0.07SE with a 95% CI of 0.62-0.91. The perfect percent agreement was 76.6% (46 of 60). Agreement with minor discrepancy was 15% (9 of 60). There were 2 cases of major discrepancy (3.30%). We were unable to make a diagnosis in 3 cases (5%) because of poor image quality related to the instantaneous internet connectivity problems. This system provided promising results. However, additional studies to assess other parameters which can affect its performance are needed before this system can be considered an alternative method of providing TP services in resource-limited settings.

Diagnostic Test Accuracy of Lung Ultrasound for Acute Chest Syndrome in Sickle Cell Disease: A Systematic Review and Meta-analysis

Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure. What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography? Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment. From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97%of cases in patients aged≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95%CI, 0.68-0.98) and the summary specificity was 0.89 (95%CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95%CI, 0.94-0.97). LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.

On applying the lackadaisical quantum walk algorithm to search for multiple solutions on grids

Quantum computing promises to improve the information processing power to levels unreachable by classical computation. Quantum walks are heading the development of quantum algorithms for searching information on graphs more efficiently than their classical counterparts. A quantum-walk-based algorithm standing out in the literature is the lackadaisical quantum walk. The lackadaisical quantum walk is an algorithm developed to search graph structures whose vertices have a self-loop of weight l. This paper addresses several issues related to applying the lackadaisical quantum walk to search for multiple solutions on grids successfully. Firstly, we show that only one of the two stopping conditions found in the literature is suitable for simulations. In the most discrepant case shown here, a stopping condition is prematurely satisfied at the step T=288 with a success probability Pr=0.593276, while the suitable condition captures the actual amplification that occurred until T=409 with Pr=0.878178. We also demonstrate that the final success probability depends on both the space density of solutions and the relative distance between solutions. For instance, we show here that decreases in the density of solutions can even take a success probability of 0.849178 to 0.961896. In contrast, increases in the relative distances can even take a success probability of 0.871665 to 0.940301. Furthermore, this work generalizes the lackadaisical quantum walk to search for multiple solutions on grids of arbitrary dimensions. In addition, we propose an optimal adjustment of the self-loop weight l for such d-dimensional grids. It turns out other fits of l found in the literature are particular cases. Our experiments demonstrate that successful searches for multiple solutions with higher than two dimensions are possible by achieving success probabilities such as 0.999979, with the value of l proposed here, where it would be 0.637346, with the value of l proposed in previous works. Finally, we observe a two-to-one relation between the steps of the lackadaisical quantum walk and Grover’s algorithm, which requires modifications in the stopping condition. That modified stopping condition can escape intermediary fluctuations that would produce premature stops at T=6 with Pr=0.000878 where the system can evolve until T=354 with Pr=0.99999, as an example that we show here. In conclusion, this work deals with practical issues one should consider when applying the lackadaisical quantum walk, besides expanding the technique to a broader range of search problems.

A case of discrepancy between three ERA tests in a woman with repeated implantation failure complicated by chronic endometritis

BackgroundEndometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests.Case reportA 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture.ConclusionBecause the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs.

Exploratory evaluation of 18F‐MK‐6240 tau PET positivity in TANGO phase 2 clinical trial of gosuranemab (BIIB092) in Mild Cognitive Impairment and mild Alzheimer’s disease

AbstractBackgroundTANGO was a randomized, placebo‐controlled, phase 2 study evaluating gosuranemab, an investigational anti‐tau antibody, for potential treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease. We explored the feasibility and validity of assessing 18F‐MK‐6240 tau PET positivity in post hoc exploratory analyses, to inform evaluation of treatment effect in future clinical trials.MethodTANGO enrolled 654 individuals aged 50‐80 years, diagnosed with MCI due to Alzheimer’s disease or mild Alzheimer’s disease, positive for amyloid pathology. 357 participants enrolled in an optional 18F‐MK‐6240 tau PET substudy. Two expert neuroradiologists read each baseline scan as visually tau positive (Tau+) or negative (Tau‐); discrepant cases were resolved by consensus. Exploratory regional SUVR quantitative thresholds (>2 standard deviations from the mean) were derived on an external 18F‐MK‐6240 sample of N=103 elderly, cognitively unimpaired, amyloid negative adults. TANGO baseline tau PET scans were classified as quantitatively Tau+ if SUVR was above a threshold in composite regions for Braak I‐II (SUVR >1.22) and/or Braak III‐IV (SUVR > 1.29). Baseline demographics and clinical characteristics were compared between the Tau+ and Tau‐ groups and concordance between the two tau positivity approaches (visual read vs. quantitative SUVR thresholds) was assessed.Results85%‐90% of the TANGO tau PET substudy population was Tau+ at baseline using quantitative or visual read approaches, respectively. Interrater agreement for the two visual readers was high (97%). Agreement between the visual read and quantitative methods was also high (93%). Tau+ and Tau‐ groups overlapped in their baseline clinical and demographic characteristics, but the Tau+ group trended toward indicators of more advanced disease at baseline (e.g. worse clinical scores).ConclusionsBased on this study of patients diagnosed with MCI due to AD and mild Alzheimer’s disease, patients who are amyloid positive also have a high probability of having tau pathology as measured by either visual read or quantitative assessment. These exploratory analyses suggest the criteria for 18F‐MK‐6240 tau PET positivity using either visual read or SUVR quantitative thresholds are feasible and valid and provides opportunities to incorporate evaluation of 18F‐MK‐6240 tau positivity into clinical trials.

Potential Limitations in the Clinical Adoption of 3-GEP Pigmented Lesion Assay for Melanoma Triage by Dermatologists and Advanced Practice Practitioners.

Background A pigmented lesion assay (PLA) is used to non-invasively detect the presence of three genes associated with melanoma (LINC00518, PRAME, and TERT) using adhesive patch testing and has the potential to reduce unnecessary biopsies. However, few studies have evaluated the clinical applicability of PLA testing and its potential limitations in real-world practice. We aim to identify possible barriers that inhibit the clinical utility of PLA testing by dermatologists. Methods Retrospective case-control study analyzing the PLA testing by two pigmented-lesion specialists that underwent PLA testing as part of clinical management. Data was collected from April 2021 to April 2022 from an academic tertiary-level center. Results The total cohort consists of 472 lesions. Genetic analysis failure for LINC00518 and PRAME occurred in 12.5% of cases and in 70.9% of cases for TERT. In 38.5% of cases, PLA results were discrepant with histopathology. The additional time associated with PLA use independent from the patient's visit was 15 min on average. Conclusion The high proportion of non-actionable results and discrepant cases highlights potential barriers to the widespread adoption of PLA testing. The high proportion of genetic analysis failure seen for TERT and limited influence on the proposed risk suggests TERT does not offer significant clinical value.

Effects of tension band plating on coronal plane alignment of lower extremities in children treated for idiopathic limb length discrepancy.

One of the most common treatment methods for moderate limb length discrepancy in children is growth modulation using tension band plating. Coronal plane deformities after tension band plating for limb length discrepancy have been documented as an important complication in articles involving heterogeneous groups consisted of both idiopathic cases and patients with pathological physes. The aim of the study was to determine the rate of coronal plane deformities after treatment of a homogeneous group of idiopathic limb length discrepancy cases with tension band plating and to compare screw constructs of medial and lateral plates. Patient files were retrospectively reviewed for amount of limb length discrepancy, anatomical femorotibial angle, mechanical lateral distal femoral angle, mechanical medial proximal tibial angle, and inter-screw angles of each plate on both sides of the tibiae and femora. Measurements at each follow-up period were compared to each other. A total of 26 patient files (37 bones) were included to the study. The mean age was 10.5 years. The mean limb length discrepancy was 27.5 mm. Implants were removed after mean 34.5 months. The mean follow-up period was 58.5 months. There was no significant difference in inter-screw angle on each side of the bones at the time of implantation and in lower limb alignments during follow-up. Treatment of mild-to-moderate idiopathic limb length discrepancy with tension band plating in children was found to be safe against any coronal plane deformity during follow-up until skeletal maturity. Level IV.

Discordant Amyloid Status Diagnosis in Alzheimer's Disease.

Early and accurate Alzheimer's disease (AD) diagnosis has evolved in recent years by the use of specific methods for detecting its histopathological features in concrete cases. Currently, biomarkers in cerebrospinal fluid (CSF) and imaging techniques (amyloid PET) are the most used specific methods. However, some results between both methods are discrepant. Therefore, an evaluation of these discrepant cases is required. The aim of this work is to analyze the characteristics of cases showing discrepancies between methods for detecting amyloid pathology. Patients from the Neurology Department of La Fe Hospital (n = 82) were diagnosed using both methods (CSF biomarkers and amyloid-PET). Statistical analyses were performed using logistic regression, and sex and age were included as covariables. Additionally, results of standard neuropsychological evaluations were taken into account in our analyses. The comparison between CSF biomarker (Aβ42) and amyloid PET results showed that around 18% of cases were discrepant-mainly CFS-negative and PET-positive cases had CSF levels close to the cut-off point. In addition, a correlation between the episodic memory test and CSF biomarkers levels was observed. However, the same results were not obtained for other neuropsychological domains. In general, CSF- and PET-discrepant cases showed altered episodic memory in around 66% of cases, while 33% showed normal performance. In common clinical practice at tertiary memory centers, result discrepancies between tests of amyloid status are far more common than expected. However, episodic memory tests remain an important support method for AD diagnosis, especially in cases with discrepant results between amyloid PET and CSF biomarkers.

Dissecting Diagnostic Discrepancies between Intraoperative and Permanent Head and Neck Pathology Sections at a Large University Medical Center

Abstract Introduction/Objective Accurate correlation between intraoperative frozen section (FS) and subsequent permanent section (PS) diagnoses is essential for quality patient care. Intraoperative FS is used for confirmation of diagnoses and margin status (MS) evaluation in head and neck (H&N) pathology. Reported FS-PS discrepancy rates for H&N cases range between 1.42% to 1.80%, mostly due to sampling and interpretation errors. We sought to review our experience with FS and concordant PS from H&N pathology cases diagnosed at a high volume, university medical center. Methods/Case Report Correlation was performed between intraoperative FS and paraffin-embedded PS of H&N surgical resections between January 2019 to December 2021. FS-PS discrepancies were classified due to “sampling” or “interpretation”. Recurrence rates based on a 2 year follow up period of 2019 cases was also recorded. Results (if a Case Study enter NA) 2337 H&N cases yielded 11108 intraoperative FS diagnoses. FS-PS correlation identified 142 (1.27%) discrepancies. Of these, 85 (60%) were for MS control, comprised of 45 (53%) due to “sampling” and 40 (47%) to “interpretation”. FS slides generally represented a single top section taken from the tissue, with “sampling” discrepancies due to discordant diagnoses identified on a deeper cut of tissue on the PS slides. Common “interpretative” discrepancies included overlooking high-grade dysplasia. For patients diagnosed in 2019, we found that 6% of discrepant cases of locoregional disease over a 2 year follow up period were due to inadequate margin control. Conclusion Our institutional intraoperative FS-PS discrepancy rate for H&N pathology cases is 1.27%, and within the national quality standards. Our FS-PS discrepancy rate for H&N cases related to MS control were mostly due to “sampling". Intraoperative review of deeper cuts of FS tissue and in service instruction for pathologists regarding intraoperative reporting of high-grade dysplasia will be the subject of a prospective study for potential improvement of “sampling” and “interpretative” discrepancies, respectively. Future studies hope to minimize the cases of locoregional occurence due to inadequate margin status.

Intraoperative Communications Between Pathologists and Surgeons: Do We Understand Each Other?

Clear communication between pathologists and surgeons during intraoperative consultations is critical for optimal patient care. To examine the concordance of intraoperative diagnoses recorded in pathology reports to surgeon-dictated operative notes and assess the impact of an intervention on the discrepancy rates. Discrepancies between the intended communication by pathologists and the interpretation by surgeons were characterized as minor with no crucial clinical impact, and major with the potential of altering patient management. After analysis, a corrective intervention was implemented with education, information sharing, and a change in protocol, and a comparative analysis was conducted. We examined 223 surgical cases with 578 intraoperative consultations. In 23% (51) of the cases, the intraoperative diagnosis was not recorded in the operative reports. We found minor discrepancies in 34% (59) and major discrepancies in 2% (3) of the remaining cases. Deferrals accounted for 24% (14 of 59) of the minor and 33% (1 of 3) of the major discrepancies. Among the discrepant cases, 56% (35 of 62) were multipart cases, including all major discrepancies. Following intervention, no major discrepancies were found in 101 cases with 186 intraoperative interpretations. The cases with no operative documentation reports decreased from 23% to 16% (16 of 101). Minor discrepancies were found in 11% (9 of 85) of the cases, indicating significant improvement (P < .001). Intraoperative diagnoses can be miscommunicated and/or misinterpreted, possibly impacting intraoperative management, particularly in multipart cases and those involving deferrals. This study highlights the importance of auditing intraoperative communications and addressing the findings through a local intervention.