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Introduction
Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis.
Methods
To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics investigating somatic and germline variants, copy-number alteration (CNA), and different complex biomarkers. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. In addition, all raw data were re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability.
Results
The mean positive percentage agreement (PPA) of somatic variant calling was 76% and positive predictive value (PPV) 89% compared a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88% for all and 97% for clinically relevant variants. CNA calls were concordant for 82% of genomic regions. Calls of homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94%, 93%, and 93% respectively. Variability of CNAs and complex biomarkers did not increase considerably using the central pipeline and was hence attributed to wet-lab differences.
Conclusion
Continuous optimization of bioinformatic workflows and participating in round robin tests are recommend.
Minimally invasive cerclage at the tibia using a modified Goetze technique: an anatomical study
(2024)
Introduction
An undislocated fracture of the posterior malleolus is a common concomitant injury in tibial shaft spiral fractures. Nevertheless, these accompanying injuries cannot always be reliably assessed using conventional X-rays. Thus, the aim of the study is to evaluate how often a fracture of the posterior malleolus occurs with tibial shaft fractures (AO:42A/B/C and AO:43A) and which factors—identifiable in conventional X-rays—are predictive.
Methods
Retrospective evaluation of X-ray and CT images revealed a total of 103 patients with low-energy tibial shaft fractures without direct joint involvement. Proximal fractures and fractures involving the knee were excluded. Basic data on injury, the trauma mechanism, the path of the fracture, bony avulsions of the posterior syndesmosis and the procedures performed were evaluated.
Results
Thirty-nine fractures were located in the middle third of the tibia, 64 in the distal third. In 65 cases, a spiral fracture (simple or wedge fracture) was found. In 31/103 fractures, an additional osseous avulsion of the posterior syndesmosis could be detected, 5 (16.1%) of them were not recognized preoperatively due to an absence of CT imaging. In three of these patients, a fracture of the posterior malleolus was only recognized postoperatively, and an additional surgery was necessary. The spiral fractures were classified in the a.p. X-ray according to their path from lateral proximal to medial distal (Type A) or from medial proximal to lateral distal (Type B).
A Pearson chi-square test and Fisher’s exact test showed a highly significant accumulation of accompanying posterior malleolus fractures for type A fractures (p = 0.001), regardless of the location of the fracture. In addition, the fractures with involvement of the posterior malleolus had a significantly higher proportion in the fractures of the distal third (p = 0.003).
There was no statistically significant relationship between the height of the fracture and the path of the fracture (type A or B). These two factors seem to be independent factors for participation of the posterior malleolus.
Conclusion
In 40.6% of the tibial shaft fractures in the distal third, in 56.9% of the type A spiral fractures and in 67.6% of the type A fractures in the distal third, the ankle joint is involved with bony avulsion of the posterior syndesmosis, which is not always recognized in conventional X-rays. To avoid complications such as additional operations, instability and post-traumatic arthrosis, we recommend preoperative imaging of the ankle using CT for these fractures.
Level of evidence
III, retrospective cohort study.
Trail registration number
DRKS00024536.
Cerclagen stellen in der heutigen operativen Versorgung von Knochenbrüchen ein gängiges Zusatztool dar, dennoch werden sie von vielen Chirurgen kritisch gesehen oder sogar abgelehnt. Gerade in der Behandlung von subtrochantären Femurfrakturen oder periprothetischen Femurfrakturen sind sie zusätzlich zu Marknagel- oder Plattenosteosynthesen etabliert. Für die Versorgung von Tibiaschaftfrakturen konnte ein minimalinvasives Operationsverfahren für moderne Kabelcerclagen beschrieben werden, das additiv zur Standardosteosynthese durchgeführt wird und somit die Stabilität des Gesamtkonstrukts deutlich erhöht. Zur Beurteilung des Verfahrens hinsichtlich seines Komplikationsprofils erfolgte die retrospektive Betrachtung des auf diese Weise versorgten Patientengut am Universitätsklinikum Augsburg sowie eine anatomische Studie an humanen Unterschenkelkadavern. Im Rahmen der anatomischen Studie wurde zum ersten Mal gezeigt, welche Strukturen in welchem Abschnitt des Unterschenkels durch dieses minimalinvasive Verfahren gefährdet sind verletzt oder zwischen Tibia und Kabelcerclage eingefasst zu werden. Diese sind in der proximalen Hälfte Arteria et Vena tibialis posterior sowie in der distalen Hälfte Arteria et Vena tibialis anterior, Nervus peroneus profundus und die Sehne des Musculus tibialis posterior. In der Betrachtung der klinischen Ergebnisse konnte ermittelt werden, dass die Anwendung dieser additiven Operationstechnik ohne erhöhte Rate an Gefäß-, Nerven- und Sehnenläsionen sowie Wundinfektionen einhergeht. Das Verfahren stellt einen Mehrwert für den Patienten ohne Erhöhung des Komplikationsprofils im Vergleich zu den etablierten Verfahren dar.
Purpose
Supplemental cerclage wiring at the distal tibia has shown to improve the mechanical stabilization of the fracture. However, its clinical use remains controversial partly because of concerns about implant loosening as well as frictional or constrictive interference between the cerclage and cortical surface. The aim of this study was to investigate in a distal tibia fracture model possible loosening of the cerclage and interference with the bone surface.
Methods
Fourteen distal tibia oblique fractures (AO/OTA 42-A2) in seven human and synthetic bone samples, respectively were treated by plate osteosynthesis with supplemental cerclage wiring. The samples were subjected to 50,000 load cycles under combined axial and torsional loads. Angular and axial displacement were continuously monitored to identify possible cerclage loosening cerclage. Potential incision of the cerclage was inspected visually and on CT scans.
Results
Angular displacement was significantly influenced by the bone material (p ≤ 0.001) and type of osteosynthesis (p ≤ 0.001), while axial displacement was only influenced by the type of osteosynthesis (p ≤ 0.001). Lowest displacements were found in samples with plate and cable cerclage. Cerclage stability was maintained throughout the entire test period of 50,000 load cycles for human and synthetic samples. CT images revealed notches from the cerclage clamping mechanism but no incisions of the cable itself.
Conclusion
In an oblique distal tibia fracture model, loosening of the cable cerclage was not detected. Full weight-bearing cyclic loads resulted in slight imprints of the cerclage crimp in both, human and synthetic samples. Following the surgical guidelines for careful cerclage installation, a supplemental cable cerclage has the potential to significantly increase the construct stability.
