HOW USEFUL IS ELASTOGRAPHY IN THE FOLLOW-UP OF ACHILLES TENDON REPAIR?

Introduction: In addition to conservative modalities in the treatment of Achilles tendon injuries, open, percutaneous and minimally invasive semi-open techniques, as well as biological open surgical repair methods are used as surgical options. Compression elastography is one of the methods used for the follow-up of treatment in Achilles tendon injuries. Methods: 23 patients were included in our study between July 2013 and June 2014, as long as they had at least 4 years of follow-up. In the final control, the intact side and the operated side were both examined and compared. The variables were the American Orthopedic Foot and Ankle Score (AOFAS) which is measured as a functional score considering plantar flexion and dorsiflexion; calf circumference; Achilles tendon anteroposterior (AP) diameter; and elastographic examination. Results: The strain ratio value and AP diameter of the patients was significantly higher on the operated side than on the non-operated side (p 0.05). No correlation was observed between strain ratio and AOFAS (p: 0,995). Conclusion: Elastography is not a useful technique to evaluate functional results on long-term tendon healing. Level of Evidence III; Retrospective comparative study. © 2022. Acta Ortopedica Brasileira. All Rights Reserved.Thanks to Prof. Dr. Ebru Yeşildağ for consultation of study plannin

Behaviour and knowledge skill levels of orthopedic surgeons about radiation safety and fluoroscopy use: A survey analysis

Objective: The aim of this study was to evaluate the behaviour and knowledge skill levels of Turkish orthopedic surgeons about fluoroscopy usage and radiation safety. Methods: The questionnaire, consisting of nineteen questions, was sent to orthopaedic surgeons and requested by a total of 323 surgeons online. The questions were about personal information, training and behaviours related to radiation and fluoroscopy usage, and the use of protective equipment. Results: A total of 277 individuals completed the questionnaire. The answers of 180 surgeons whose working duration was more than 1 year and also who participated in at least one fluoroscopy requiring operation per week, were analysed. 22 (12%) participants answered that they were trained on fluoroscopy usage. Sixty people (33.3%) reported that they did not use any protective equipment regularly. The most commonly used protection methods were lead aprons 123 (68.3%). Thyroid protectors were used by 92 participants (52.1%). There was no significant difference between the groups when comparing the use of protective equipment according to the academic title. Only 19 (10.6%) of the surgeons noted that they used dosimeter regularly, and 15 (83.3%) of them reported that they controlled their dosimeters. Conclusion: In this study, Orthopedic surgeons were found not to be adequately trained about use and risks of fluoroscopy and also not to be equipped about methods for preventing radiation damage. © 2019 Turkish Association of Orthopaedics and Traumatolog

Optimizing panel-based tumor mutational burden (TMB) measurement.

Panel sequencing based estimates of tumor mutational burden (psTMB) are increasingly replacing whole exome sequencing (WES) tumor mutational burden as predictive biomarker of immune checkpoint blockade (ICB). A mathematical law describing psTMB variability was derived using a random mutation model and complemented by the contributions of non-randomly mutated real-world cancer genomes and intratumoral heterogeneity through simulations in publicly available datasets. The coefficient of variation (CV) of psTMB decreased inversely proportional with the square root of the panel size and the square root of the TMB level. In silico simulations of all major commercially available panels in the TCGA pan-cancer cohort confirmed the validity of this mathematical law and demonstrated that the CV was 35% for TMB = 10 muts/Mbp for the largest panels of size 1.1-1.4 Mbp. Accordingly, misclassification rates (gold standard: WES) to separate 'TMBhigh' from 'TMBlow' using a cut-point of 199 mutations were 10%-12% in TCGA-LUAD and 17%-19% in TCGA-LUSC. A novel three-tier psTMB classification scheme which accounts for the likelihood of misclassification is proposed. Simulations in two WES datasets of immunotherapy treated patients revealed that small gene panels were poor predictors of ICB response. Moreover, we noted substantial intratumoral variance of psTMB scores in the TRACERx 100 cohort and identified indel burden as independent marker complementing missense mutation burden. A universal mathematical law describes accuracy limitations inherent to psTMB, which result in substantial misclassification rates. This scenario can be controlled by two measures: (i) a panel design that is based on the mathematical law described in this article: halving the CV requires a fourfold increase in panel size, (ii) a novel three-tier TMB classification scheme. Moreover, inclusion of indel burden can complement TMB reports. This work has substantial implications for panel design, TMB testing, clinical trials and patient management

Conventional and semi-automatic histopathological analysis of tumor cell content for multigene sequencing of lung adenocarcinoma.

Targeted genetic profiling of tissue samples is paramount to detect druggable genetic aberrations in patients with non-squamous non-small cell lung cancer (NSCLC). Accurate upfront estimation of tumor cell content (TCC) is a crucial pre-analytical step for reliable testing and to avoid false-negative results. As of now, TCC is usually estimated on hematoxylin-eosin (H&E) stained tissue sections by a pathologist, a methodology that may be prone to substantial intra- and interobserver variability. Here we the investigate suitability of digital pathology for TCC estimation in a clinical setting by evaluating the concordance between semi-automatic and conventional TCC quantification. TCC was analyzed in 120 H&E and thyroid transcription factor 1 (TTF-1) stained high-resolution images by 19 participants with different levels of pathological expertise as well as by applying two semi-automatic digital pathology image analysis tools (HALO and QuPath). Agreement of TCC estimations [intra-class correlation coefficients (ICC)] between the two software tools (H&E: 0.87; TTF-1: 0.93) was higher compared to that between conventional observers (0.48; 0.47). Digital TCC estimations were in good agreement with the average of human TCC estimations (0.78; 0.96). Conventional TCC estimators tended to overestimate TCC, especially in H&E stainings, in tumors with solid patterns and in tumors with an actual TCC close to 50%. Our results determine factors that influence TCC estimation. Computer-assisted analysis can improve the accuracy of TCC estimates prior to molecular diagnostic workflows. In addition, we provide a free web application to support self-training and quality improvement initiatives at other institutions

The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions

Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce. Patients and methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases. Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, asymptotic to 7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p 1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants. Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival. (C) 2022 Elsevier Ltd. All rights reserved

Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe

Background: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). Materials and methods: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. Results: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. Conclusions: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe