Discrepant Cases Research Articles

Discrepancy between post-treatment infarct volume and 90-day outcome in the ESCAPE randomized controlled trial.

Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better. We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome. We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24-48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24-48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between "discrepant cases" - those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV - and "non-discrepant cases". Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome. Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement (p = 0.39, p = 0.81, respectively, for PIV ≤ 7 mL/mRS ≥ 3). Pre-treatment factors independently associated with small-PIV/mRS ≥ 3 included older age (p = 0.010), cancer, and vascular risk-factors; post-treatment factors included 48-h NIHSS (p = 0.007) and post-stroke complications (p = 0.026). Absence of vascular risk-factors (p = 0.004), CT-based lentiform nucleus sparing (p = 0.002), lower 24-hour NIHSS (p = 0.001), and absence of complications (p = 0.013) were associated with large-PIV/mRS ≤ 2. Sensitivity analyses yielded similar results. Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care. https://clinicaltrials.gov/ct2/show/NCT01778335.

Follow-up study on transphyseal ACL reconstruction in Irish adolescents with no cases of leg length discrepancy or angular deformity.

The rate of ACL injury in adolescents has been rising in recent years. Surgical options include transphyseal and physeal-sparing ACL reconstruction. In this study, we performed a transphyseal ACL reconstruction and followed up patients to assess functional outcomes and to assess for growth disturbance. There were 22 patients seen at follow-up between the age of 12 and 16. Skeletal age assessment was performed using an MRI atlas with an average skeletal age of 14.7 (range 12-16). The mean follow-up time was 36months (range 14-63months). Clinical examination was performed to assess for leg length discrepancy, and leg length radiographs were used to assess for angular deformity. Patients' post-surgery functionality was assessed with the IKDC score and the Tegner Lysholm score. The mean IKDC and Lysholm scores at follow-up were found to be 91 and 94, respectively. The median Tegner score prior to injury was 8.5 and postoperatively was 7.5. There were no cases of leg length discrepancy found on clinical examination, and there were no cases of significant angular deformity. Four patients ruptured again and went on to have repeat ACL reconstruction. Midterm results at an average follow-up of 3years after the surgery showed good functional outcomes using the transphyseal ACL reconstruction technique with good return to activity. There were no cases of leg length discrepancy or angular deformity. Transphyseal ACL reconstruction is a viable method of treatment for adolescent ACL tears.

Evaluation of the fully automated Idylla EGFR Mutation Assay in Chinese patients with lung adenocarcinoma.

e21716 Background: Epidermal growth factor receptor ( EGFR) mutation testing is nowadays an essential part of lung adenocarcinoma diagnosis. Its rapid detection is of utmost significance in order to ensure that patients receive timely and appropriate treatment. However, the current techniques for EGFR examination in China, ARMS-PCR and NGS, often take 3~7 days to deliver the final results. In contrast, the fully automated Idylla EGFR assay could detect 51 EGFR mutations directly from formalin-fixed, paraffin-embedded (FFPE) samples within 2.5 hours with < 2 minutes of hands-on time. The test has proven both accurate and robust among Caucasian lung adenocarcinoma patients but has never been clinically validated in Chinese patients. Methods: FFPE samples were retrospectively collected from 94 lung adenocarcinoma patients followed by EGFR testing using the Idylla system. Seventy-eight samples were also previously assessed with ARMS-PCR, 9 with NGS and 7 with both. In case of discordance, repeat testing was performed on the same tissue block with a third method. The sensitivity and specificity of the Idylla EGFR assay were evaluated against ARMS-PCR or NGS. Mutations beyond the scope of detection by the Idylla EGFR assay were not included in the analyses. Results: Of the 94 tumors enrolled, 77 were stage I-II. The Idylla system was consistent with ARMS-PCR or NGS for the EGFR mutational profiles of 92 tumors: 80 positive and 12 negative. Among the 2 cases of discrepancy, one was wild-type using Idylla but were found to harbor G719X/S768I using ARMS-PCR (and confirmed by NGS), while the other one carried L858R according to Idylla, as confirmed by ARMS-PCR, but was discovered to have an additional mutation L861Q using NGS. The Idylla EGFR test had a sensitivity of 97.6%, a specificity of 100% and an overall concordance of 97.9%. Conclusions: The Idylla system provides a rapid, accurate and user-friendly solution to EGFR characterization, especially in time-sensitive scenarios where special expertise and staff training could be a challenge.

A retrospective evaluation of PD-L1 expression on primary non-small cell lung cancer (NSCLC) samples and associated involved hilar or mediastinal lymph nodes (N1 or N2) (REPLICA).

9044 Background: Little is known about the PD-L1 expression in early stage NSCLC as well as the possible heterogeneity of PD-L1 expression in different sites. This study provides information on both PD-L1 expression in stage II and III NSCLC and the relationship between PD-L1 expression in the primary site (lung) and metastatic lymph nodes (LNs) N1 and/or N2. Methods: Samples (primary tumor and N1/N2) from 500 patients who underwent lung resection and lymphadenectomy for NSCLC without prior treatments were collected and analyzed for PD-L1 expression using the 22C3 pharmdx Agilent assay. The tumor proportion score (TPS) is documented for each sample according to the following categories: PD-L1: < 1%, 1-49%, ≥ 50%. PD-L1 stained slides were reviewed by two pathologists independently; for discrepant cases the two pathologists reviewed the stains jointly and the consensus score used for the data analysis. Agreement between the two pathologists was assessed by overall agreement and kappa statistic. The association between PD-L1 expression in the primary tumor and lymph node was assessed by cross-tabulation. Results: A total of 456 tumors and involved LNs were included in the analysis. Pathologist one assessed 435 primary tumor and LN pairs and pathologist 2 assessed 453 tumor and LNs pairs. The overall agreement between pathologists on PD-L1 expression in primary tumor samples was 77%; K = 0.59 (95% CI 0.57 – 0.63) and in LNs 83%; k = 0.62 (95% CI 0.56 – 0.70). Primary tumors showed PD-L1 < 1% in 235/422 (55,6%), PD-L1 1-49% in 146/422 (34,6%) and PD-L1 > = 50% in 41/422 (9.8%). 77% (327/422) showed no heterogeneity in PD-L1 expression between the primary tumor and involved LNs. In tumors with PD-L1 < 1% expression, 94% of the LNs showed PD-L1 < 1% expression and less than 1% showed PD-L1 > = 50%, 6% of the LNs showed PD-L1 1-49%. When the primary tumor was PD-L1 > = 50% nearly half (46%) of the involved LNs showed the same degree of PD-L1 positivity and 10% of them showed PD-L1 < 1%; 44% of the LNs showed PD-L1 1-49%. When the primary tumor showed 1-49% PD-L1 staining, 60% of the LNs showed the same staining pattern, 36% showed PD-L1 < 1% and only 4% showed PD-L1 > = 50% expression. Conclusions: In stage II and III NSCLC, half of the primary tumors show negative PD-L1 expression. Discrepant PD-L1 expression between primary tumors and LN metastases was seen in 23% of the cases, and when present, PD-L1 expression in LN tumors tended to be lower than that in primary tumors.

Bone scintigraphy and PET-CT: A necessary alliance for bone metastasis detection in breast cancer?

e13070 Background: Bone is one of the main sites of breast cancer metastasis. Staging of this kind of disease spread can be performed in locally advanced cases with PET-CT in conjunction with Bone Scintigraphy. The purpose of this work is to compare the efficiency of bone metastasis detection between PET-CT and bone scintigraphy. Methods: Prospective analysis of locally advanced breast cancer patients treated in a Comprehensive Cancer Center between 2014 and 2019 that performed PET-CT and Bone Scintigraphy in the staging. Interval between the two exams could not exceed 2 months. Clinical and pathological characteristics of the disease were collected from electronic files and independently clinical images reports were considered to evaluate the ability of each imaging modalities to identify bone disease. In discrepancy cases a re-analysis of the images by two independent nuclear physicians was performed to validate the findings. Results: We analyzed 204 cases. The majority of them had ductal carcinomas (72.5%), cT2/3 (70%), cN1/2(61.8%) and G2/3 (94.6%), luminal B- like, HER2 positive disease (49.2%). In this cohort, bone metastasis was documented in 52 (25.5%) patients. PET-CT presented 97.0% of accuracy, surpassing the 94.1% presented by Bone Scintigraphy. The latter failed to correctly detect bone metastasis in 11 (5.4%) patients and only outperformed PET-CT in 3 (1.5%) patients. The main difference between the two modalities was the non-detection of cranium lesions in PET-CT images. Conclusions: PET-CT showed higher efficiency in bone metastasis detection than Bone Scintigraphy, probably because it detects lytic lesions. The non-detection of cranium ones can be harmful and so modifications in the image acquisition are required to improve the quality of PET-CT, avoiding other exams in bone staging.

Cyclical Synchronization of the Czech Republic and the Euro Area: A Case of Structural Discrepancies in a Time-Frequency Domain

ABSTRACT The paper investigates the cyclical synchronization of the Czech Republic with the euro area and compares it to the synchronization of Germany and Austria (the benchmark). We employed a wavelet coherence analysis with four macroeconomic variables and monthly data from 1995 to 2019. Our results suggest that the Czech Republic suffers from significant structural disparities in synchronization at high frequencies. The country is related to most of the euro area countries only indirectly. Additionally, both benchmark countries are well synchronized with the euro area at almost all frequencies, except Austria in the manufacturing sector.

The impact of 2018 ASCO-CAP HER2 testing guidelines on breast cancer HER2 results. An audit of 2132 consecutive cases evaluated by immunohistochemistry and in situ hybridization.

The 2018 iteration of the ASCO-CAP HER2 testing guidelines proposes significant changes with an emphasis on the integration of concurrent immunohistochemistry (IHC) and in situ hybridization (ISH). We wished to evaluate the impact of these changes on clinical practice. Between Jan 2012 to Feb 2017, 2132 consecutive invasive breast carcinomas were evaluated with IHC and ISH for HER2. The sample tested was the breast primary or axillary nodes in all but 57 (2.7%) distant metastases. For 1824 cases with both dual-probe ISH and IHC results, the ISH subgroup was 1: 299 (16.4%), 2: 19 (1.0%), 1.0%, 3: 6 (0.3%), 4: 48 (2.6%) and 5: 1452 (79.6%). Ultimately 21% of group 2 and 4 cases and 80% of group 4 cases were positive. The change in HER2 status between the 2018 vs 2013 was: amplified in 323 (15.2%) vs 15.5%; not amplified in 1804 (84.6%) vs 82.2%; equivocal in 0 vs 2.3% previously. In 22 of 2127 cases (1.03%) the 2013 and 2018 results were discordant, all in groups 2-4. The discrepant cases included 15 of 331 (4.5%) of 2013 amplified cancers, now negative (all in groups 2 or 3) and 7 of 1796 (0.4%) 2013 nonamplified cases, now positive (all in group 4). Because of routine testing with both IHC and ISH, we found 6 of 1147 (0.52%) IHC negative (0 or 1+) cases were amplified by ISH. Further, 19 of 289 (6.6%) of IHC 3+ cases were nonamplified by ISH, circumstances not covered by these guidelines. In summary at the population level, the 2018 ASCO-CAP guidelines have a 99% agreement with the 2013 results. A major advantage is the abolishment of the clinically problematic equivocal category. Routine performance of both IHC and ISH uncovers a small proportion of cancers whose HER2 status is not addressed by these guidelines.

Evaluating the quality of WAAS availability control algorithm under geomagnetic storm conditions

Introduction: The Wide Area Augmentation System (WAAS) is vulnerable to false alarms about the violation of the required navigation parameter availability under geomagnetic disturbances. As a consequence, the system operation efficiency might decrease because of a mismatch between the output of the control system and the actual quality of the navigation-time support. Purpose: Comparative analysis of the actual quality of navigation-and-time support for GPS users and the output information of the system for monitoring the availability of the required WAAS navigation parameters under a moderate magnetic storm and with technical failures during the operation of separate segments of GPS and WAAS systems. Results: Location errors were calculated for 82 reference stations in the USA equipped with GPS navigation receivers. The calculations used the geometric ranges of visible navigation satellites and the corresponding real values of the ionospheric range-measurement error determined by the method of two-frequency measurements. Based on the same data and through the use of the conventional standard WAAS availability control algorithm, the user protection levels were calculated in the horizontal and vertical planes. The results of these calculations are presented as a time graph of WAAS operating area coverage percentage, which was compared with the respective graphs presented in the official WAAS work reports. It is established that there are cases of significant discrepancy between the forecasts about the availability of the required navigation parameters according to the WAAS data and the real quality of positioning in the operating area of this system. There are discrepancies in the results of calculations of protection levels in the horizontal and vertical planes obtained from official reports on the operation of the system and in calculations based on the geometric range and real ionospheric range-measurement error. Practical relevance: Recommendations are proposed in order to reconsider the development of a navigation parameter availability control for wide-area augmentation systems, splitting the calculation into “locally dependent” and “globally dependent” components of differential corrections of range-measurement errors. It will reduce the likelihood of false alarms or dangerous inconsistencies in information within the system.

Evaluation of the training program for p16/ Ki-67 dual immunocytochemical staining interpretation for laboratory staff without experience in cervical cytology and immunocytochemistry.

Backgroundp16/Ki-67 dual immunocytochemical staining (DS) is considered easy to interpret if evaluators are properly trained, however, there is no consensus on what constitutes proper training. In the present study we evaluated a protocol for teaching DS evaluation on students inexperienced in cervical cytology.MethodsInitial training on 40 DS conventional smears was provided by a senior cytotechnologist experienced in such evaluation. Afterwards, two students evaluated 118 cases. Additional training consisted mainly of discussing discrepant cases from the first evaluation and was followed by evaluation of new 383 cases. Agreement and accuracy of students’ results were compared among the participants and to the results of the reference after both evaluations. We also noted time needed for evaluation of one slide as well as intra-observer variability of the teacher’s results.ResultsAt the end of the study, agreement between students and reference was higher compared to those after initial training (overall percent agreement [OPA] 81.4% for each student, kappa 0.512 and 0.527 vs. OPA 78.3% and 87.2%, kappa 0.556 and 0.713, respectively). However, accuracy results differed between the two students. After initial training sensitivity was 4.3% points and 2.9% points higher, respectively compared to the reference, while specificity was 30.6% points and 24.4% points lower, respectively, compared to the reference. At the end of the study, the sensitivity reached by one student was the same as that of the reference, while it was 2.6% points lower for the other student. There was a statistically significant difference in specificity between one student and the reference and also between students (16.7 and 15.1% points). Towards the end of the study, one student needed 5.2 min for evaluating one slide while the other needed 8.2 min. The intra-observer variability of the senior cytotechnologist was in the range of “very good” in both arms of the study.ConclusionsIn teaching DS evaluation, the students’ progress has to be monitored using several criteria like agreement, accuracy and time needed for evaluating one slide. The monitoring process has to continue for a while after students reach satisfactory results in order to assure a continuous good performance. Monitoring of teacher’s performance is also advisable.

Determination of high-risk HPV status of head and neck squamous cell carcinoma using the Roche cobas HPV test on cytologic specimens and acellular supernatant fluid.

High-risk human papillomavirus-positive (hrHPV+) oropharyngeal squamous cell carcinomas comprise a subset of head and neck squamous cell carcinomas (HNSCCs) with a distinct biology and prognosis. Commonly, the diagnosis of HNSCC is rendered on fine-needle aspiration (FNA). Because cell blocks may be insufficient for determining HPV status using microscopy-based techniques, the ability of liquid-based assays was examined in the current study. The performance of the Roche cobas 4800 platform was evaluated on the FNA material from the cell pellet and corresponding cell-free supernatant fluid specimens of primary and metastatic HNSCCs. These results were compared with the p16 immunostain result from the histologic material obtained from the same patient. Discrepant cases were adjudicated using hrHPV RNA in situ hybridization. A total of 41 samples (23 primary tumors and 18 lymph node metastases) were acquired from 34 patients with HNSCC. Primary tumors included the oropharynx (20 samples), oral cavity (13 samples), larynx (3 samples), and skin (3 samples). In 2 cases, a primary tumor could not be identified. Twenty-three samples (56%) were found to be p16 positive by immunohistochemistry. Twenty-two samples were found to be positive on cobas hrHPV testing from both cell pellet and cell-free supernatant fluid. Two cell-free supernatant fluid specimens yielded indeterminate cobas results. At the time additional hrHPV RNA in situ hybridization analysis was performed, one cobas-positive cell pellet was deemed to be a false-positive result. The sensitivity of the cobas assay was 100% for pellet material and cell-free supernatant fluid, with specificities of 94.7% and 100%, respectively. cobas hrHPV testing of HNSCC specimens demonstrated high concordance with p16 immunohistochemistry on the corresponding cell block and/or tissue specimen. Using the cell-free supernatant fluid in this platform could provide accurate HPV results while conserving material for cytomorphologic analyses.

Discrepancies between positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography in a cohort of oncological patients.

This study aims to evaluate discrepant findings between positron emission tomography/magnetic resonance imaging (PET/MRI) and positron emission tomography/computed tomography (PET/CT) in a cohort of oncological patients and to undertake a phantom study to assess the potential for extended PET acquisitions to lead to false-positive findings on PET/MRI. Discrepant findings from a series of 106 patients undergoing same-day 18 F-fluorodeoxyglucose (FDG)-PET/CT and PET/MRI were reviewed. Phantom studies explored the potential for PET acquisition time to contribute to discrepancy. There were 14 discrepant cases, 5 (35.7%) of which related to PET/MRI acquisitions that had been extended to 10min. Three of these five cases proved to be falsely positive. Phantom studies showed greater contrast recovery and signal to noise ratio for 10-min PET/MRI acquisitions compared to 2-min acquisitions using PET/CT. There were no discrepancies when PET/CT showed disseminated disease (P=0.036). Extended PET/MRI acquisitions used to accommodate multiple MRI sequences may be associated with false-positive findings compared to PET/CT. PET/MRI is more likely to have incremental value when the prior probability for disseminated disease is low.

Blood Group Discrepancies at a Regional Blood Center

Background: Blood group testing is an important part of supplying safe blood components in blood transfusion centers. Blood group discrepancy develops when reactions in forward grouping do not correspond with reverse grouping or if the preceding and recent results do not match. This study aimed to evaluate ABO blood group discrepancies among blood donors of Yazd, Iran. Materials and Methods: In this cross-sectional study, data of blood donors were obtained from the integrated database of Yazd Blood Transfusion Center during a period of eight years (2010 - 2017). Tube testing was used for determining the ABO blood groups. A serological workup was performed for diagnosis and determination of the discrepancy. Confirmation of the results was accomplished by the reference laboratory of immunohematology. Results: Blood group discrepancies were detected in 130 (0.04%) out of 322,222 donations. Technical/Clerical errors leading to ABO discrepancy were noticed in 12 (9.3%) cases. The most frequent cause of ABO discrepancies in forward grouping was subgroups of A Antigen (44.6%) and in reverse grouping was cold autoantibody (23.9%). There were 11 (8.4%) cases with alloantibodies. Two blood donors with rare Bombay phenotype and p blood group were also identified. Conclusion : For minimizing Technical/Clerical errors, accurate blood donor or sample identification programs should be implemented. All cases of blood group discrepancies should be carefully investigated, and blood donors should be informed appropriately.

An eight year review of intraoperative frozen section diagnoses and its limitations

Background: Frozen section consultation (FS) is an integral part of surgical pathology to aid surgical colleagues in making an intraoperative management decision. This audit reviews the performance of FS diagnoses in a tertiary teaching hospital. Objective: To perform an 8-year retrospective review analysing the concordance rate of FS compared with the final diagnosis on paraffin-embedded sections. Methods: 2013 cases were received for FS from 1 January 2011 to 31 December 2018, comprising 3503 specimens. The patient’s age, sex, specimen type, indication of the FS and the year performed were recorded. The diagnoses between FS and paraffin section were compared, especially for the discrepant cases. Results: Of the 3503 specimens, 3288 results were concordant (93.86%). The major discordances occurred in 66 incidences (1.88%), the minor discordances in 68 specimens (1.94%) and the diagnoses were deferred in 81 cases (2.31%). Further analyses were performed on the major discordances. The true diagnostic error was seen in 26 specimens. Twenty-one incidences were due to undersampling, 17 specimens as a result of technical error and 2 specimens were difficult cases requiring specialist referral. Conclusion: This audit addresses the diagnostic performance of intraoperative consultation and explores ways to minimise error when utilising this method.

Role of whole-body MRI for treatment response assessment in multiple myeloma: comparison between clinical response and imaging response

BackgroundWhole-body MRI (WB-MRI) including diffusion-weighted image (DWI) have been widely used in patients with multiple myeloma. However, evidence for the value of WB-MRI in the evaluation of treatment response remains sparse. Therefore, we evaluated the role of WB-MRI in the response assessment.MethodsIn our WB-MRI registry, we searched multiple myeloma patients treated with chemotherapy who underwent both baseline and follow-up WB-MRI scans. Clinical responses were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using IMWG criteria. Using RECIST 1.1, MD Anderson (MDA) criteria, and MDA-DWI criteria, imaging responses on WB-MRI were rated as CR, PR, SD, or PD by two radiologists independently. Then, discrepancy cases were resolved by consensus. Weighted Kappa analysis was performed to evaluate agreement between the imaging and clinical responses. The diagnostic accuracy of image responses in the evaluation of clinical CR, objective response (CR and PR), and PD was calculated.ResultsForty-two eligible patients were included. There was moderate agreement between imaging and clinical responses (κ = 0.54 for RECIST 1.1, κ = 0.58 for MDA criteria, κ = 0.69 for MDA-DWI criteria). WB-MRI showed excellent diagnostic accuracy in assessment of clinical PD (sensitivity 88.9%, specificity 94.7%, positive predictive value [PPV] 84.2%, negative predictive value [NPV] 96.4% in all three imaging criteria). By contrast, WB-MRI showed low accuracy in assessment of clinical CR (sensitivity 4.5%, specificity 98.1%, PPV 50.0%, NPV 71.2% in all three imaging criteria). As to the clinical objective response, the diagnostic accuracy was higher in MDA-DWI criteria than RECIST 1.1 and MDA criteria (sensitivity/specificity/PPV/NPV, 84.2%/94.4%/98.0%/65.4, 54.4%/100%/100%/40.9, and 61.4%/94.4%/97.2%/43.6%, respectively).ConclusionsIn the imaging response assessment of multiple myeloma, WB-MRI showed excellent performance in the evaluation of PD, but not in the assessment of CR or objective response. When adding DWI to imaging response criteria, diagnostic accuracy for objective response was improved and agreement between imaging and clinical responses was increased.

Transphyseal anterior cruciate ligament reconstruction using living parental donor hamstring graft: excellent clinical results at 2 years in a cohort of 100 patients

To determine outcomes of transphyseal ACL reconstruction using a living parental hamstring tendon allograft in a consecutive series of 100 children. One hundred consecutive juveniles undergoing ACL reconstruction with a living parental hamstring allograft were recruited prospectively and reviewed 2years after ACL reconstruction with IKDC Knee Ligament Evaluation, and KT1000 instrumented laxity testing. Skeletally immature participants obtained annual radiographs until skeletal maturity, and long leg alignment radiographs at 2years. Radiographic Posterior tibial slope was recorded. Of 100 juveniles, the median age was 14years (range 8-16) and 68% male. At surgery, 30 juveniles were graded Tanner 1 or 2, 21 were Tanner 3 and 49 were Tanner 4 or 5. There were no cases of iatrogenic physeal injury or leg length discrepancy on long leg radiographs at 2years, despite a median increase in height of 8cm. Twelve patients had an ACL graft rupture and 9 had a contralateral ACL injury. Of those without further ACL injury, 82% returned to competitive sports, IKDC ligament evaluation was normal in 52% and nearly normal in 48%. The median side to side difference on manual maximum testing with the KT1000 was 2mm (range - 1 to 5). A radiographic PTS of 12° or more was observed in 49%. ACL reconstruction in the juvenile with living parental hamstring tendon allograft is a viable procedure associated with excellent clinical stability, patient-reported outcomes and return to sport over 2years. Further ACL injury to the reconstructed and the contralateral knee remains a significant risk, with identical prevalence observed between the reconstructed and contralateral ACL between 12 and 24months after surgery. III (Cohort Study).

Discrepancy analysis comparing molecular and histology diagnoses in kidney transplant biopsies.

Discrepancy analysis comparing two diagnostic platforms offers potential insights into both without assuming either is always correct. Having optimized the Molecular Microscope Diagnostic System (MMDx) in renal transplant biopsies, we studied discrepancies within MMDx (reports and sign-out comments) and between MMDx and histology. Interpathologist discrepancies have been documented previously and were not assessed. Discrepancy cases were classified as "clear" (eg, antibody-mediated rejection [ABMR] vs T cell-mediated rejection [TCMR]), "boundary" (eg, ABMR vs possible ABMR), or "mixed" (eg, Mixed vs ABMR). MMDx report scores showed 99% correlations; sign-out interpretations showed 7% variation between observers, all located around boundaries. Histology disagreed with MMDx in 37% of biopsies, including 315 clear discrepancies, all with implications for therapy. Discrepancies were distributed widely in all histology diagnoses but increased in some scenarios; for example, histology TCMR contained 14% MMDx ABMR and 20% MMDx no rejection. MMDx usually gave unambiguous diagnoses in cases with ambiguous histology, for example, borderline and transplant glomerulopathy. Histology lesions or features associated with more frequent discrepancies (eg, tubulitis, arteritis, and polyomavirus nephropathy) were not associated with increased MMDx uncertainty, indicating that MMDx can clarify biopsies with histologic ambiguity. The patterns of histology-MMDx discrepancies highlight specific histology diagnoses in which MMDx assessment should be considered for guiding therapy.

Gleason score 5 + 3 = 8 (grade group 4) prostate cancer—a rare occurrence with contemporary grading

Grade Group (GG) 4 prostate cancer includes Gleason scores (GS) 3 + 5 = 8, 4 + 4 = 8, and 5 + 3 = 8. Some studies without pathology re-review of historical cohorts proposed that the presence of pattern 5 worsens prognosis compared to GS 4 + 4 = 8 cancer. We assessed how often historically graded GS 5 + 3 = 8 cancers retain this grade with contemporary grading recommendations. Sixteen prostate biopsies and 24 radical prostatectomies (RP) reported from 2005 to 2019 as GS 5 + 3 = 8 were re-reviewed and graded according to contemporary recommendations. In discrepant cases, an attempt was made to explain the different grading. One (6%) biopsy and 3 (12%) RPs remained GS 5 + 3 = 8 (GG4) after re-review. Two (12%) biopsies remained GG4 but were re-graded as GS 3 + 5 = 8 and 1 (4%) RP was reclassified as GS 4 + 4 = 8 (GG4). Eight (50%) biopsies and 15 (64%) RPs were upgraded to Gleason scores 9-10 (GG5). Five (32%) biopsies and 1 (4%) RPs were downgraded to Gleason score 7 (GG2 and 3). One (4%) RP showed GS 3 + 3 = 6 (GG1) cancer. Data from 2013-current from the 3 institutions were available to assess the incidence of GS 5 + 3 = 8 following re-review of the cases. Out of 14 359 biopsies with cancer and 6727 radical prostatectomy specimens, only 1 case (0.007%) and no cases (0%) were graded as GS 5 + 3 = 8, respectively. Reasons for grading discrepancies included: 1) assigning an overall common grade to separate needle cores or tumor nodules; 2) inclusion of <5% lower grade pattern into grading; and 3) misinterpretation of variant histology and patterns. Challenging patterns were poorly-formed glands, signet ring cell-like features, atrophic carcinoma, ductal carcinoma, and mucinous fibroplasia. GS 5 + 3 = 8 (GG4) cancer is very rare with contemporary grading. The reliability of conclusions from retrospective databases regarding the clinical significance of this grade combination without slide re-review is questionable.

Discriminant haplotypes of avirulence genes of Phytophthora sojae lead to a molecular assay to predict phenotypes.

The soybean–Phytophthora sojae interaction operates on a gene‐for‐gene relationship, where the product of a resistance gene (Rps) in the host recognizes that of an avirulence gene (Avr) in the pathogen to generate an incompatible reaction. To exploit this form of resistance, one must match with precision the appropriate Rps gene with the corresponding Avr gene. Currently, this association is evaluated by phenotyping assays that are labour‐intensive and often imprecise. To circumvent this limitation, we sought to develop a molecular assay that would reveal the avirulence allele of the seven main Avr genes (Avr1a, Avr1b, Avr1c, Avr1d, Avr1k, Avr3a, and Avr6) in order to diagnose with precision the pathotypes of P. sojae isolates. For this purpose, we analysed the genomic regions of these Avr genes in 31 recently sequenced isolates with different virulence profiles and identified discriminant mutations between avirulence and virulence alleles. Specific primers were designed to generate amplicons of a distinct size, and polymerase chain reaction conditions were optimized in a final assay of two parallel runs. When tested on the 31 isolates of known virulence, the assay accurately revealed all avirulence alleles. The test was further assessed and compared to a phenotyping assay on 25 isolates of unknown virulence. The two assays matched in 97% (170/175) of the interactions studied. Interestingly, the sole cases of discrepancy were obtained with Avr3a, which suggests a possible imperfect interaction with Rps3a. This molecular assay offers a powerful and reliable tool to exploit and study with greater precision soybean resistance against P. sojae.

Inter-hospital and intra-hospital transfer of critically ill patients: results of a questionnaire survey

Transfer of critically ill patients is often a forced but necessary measure. The article presents data from a multicenter study of the Russian Federation of anaesthesiologists and reanimatologists (RFAR), on the current state of problems in intra-hospital and inter-hospital transportation of critically ill patients. The aim of this study was to interview physicians in the intensive care and intensive care units about the problems that arise during the transfer of intensive care patients. To identify problematic issues that arose among doctors of specialists in the process of in-hospital transportation and inter-hospital transportation, a survey was conducted in medical centers from four federal districts of the Russian Federation. The data is presented in the form of relative frequencies and graphical visualization (histograms and diagrams). The study involved 538 doctors of specialists of the intensive care unit and intensive care unit. As a result, it was revealed that 88 % of the respondents faced complications during the transportation of patients in their practical work. The most common causes of complications are associated with medical aspects in 38.6 % of cases and technical reasons (equipment failure, etc.) in 35.1 % of cases, to the least extent these are organizational problems (26.3 %). The main problems with in-hospital transportation and inter-hospital transportation: insufficient provision of modern transport equipment, as well as the lack of medical transport boxes. There are cases of discrepancy between preliminary and real information about the patient’s condition. The absence of regulatory documents, standardized protocols and algorithms for the transportation of resuscitation patients was stated by 27 % of the surveyed doctors. Most of the surveyed doctors of specialists (61 %) do not use in their practice any assessment of the risks and portability of patients. 90 % of the respondents answered that they do not consider themselves legally protected in the event of adverse events during transportation. Inadequate equipment with transport equipment, lack of regulatory documents, as well as inconsistencies in medical information about the patient’s condition create a risk for the safe and efficient transportation of resuscitation patients, and medical personnel cannot consider themselves legally protected. These areas are important targets for investigation and the development of interventions to improve patient safety.

Surgically-assisted rapid maxillary expansion (SARME): indications, planning and treatment of severe maxillary deficiency in an adult patient.

ABSTRACTIntroduction: Maxillary deficiency, also called transverse deficiency of the maxilla, may be associated with posterior crossbite, as well as with other functional changes, particularly respiratory. In adult patients, because of bone maturation and the midpalatal suture fusion, rapid maxillary expansion has to be combined with a previous surgical procedure to release the areas of resistance of the maxilla. This procedure is known as surgically-assisted rapid maxillary expansion (SARME). Objective: This study discusses the indications, characteristics and effects of SARME, and presents a clinical case of transverse and sagittal skeletal maxillary discrepancy treated using SARME and orthodontic camouflage.