Vergleich der präoperativen Planung mit dem postoperativen Ergebnis bei computergestützt geplanten posttraumatischen Rekonstruktionen des Mittelgesichts

Das Ziel der Arbeit ist die postoperative Implantat- und Knochensegmentposition mit der präoperativ geplanten virtuellen Position bei sekundären Rekonstruktionen des Mittelgesichtsskeletts und primären Rekonstruktionen der Orbitawände ohne Verwendung von Navigationssystemen zu vergleichen. Die erste Studie wertet die Implementierung der VSP zur sekundären Korrektur von posttraumatischen Deformitäten im Bereich des lateralen und zentralen Mittelgesichts (des Jochbeines, Jochbogens und Oberkiefers) aus. Die zweite Studie untersucht die Implementierung der VSP zur primären Rekonstruktion der inferioren und medialen Orbitawände. Die Patientenkohorte in der ersten Studie besteht aus Patienten, die von 2013 bis 2019 in der Klinik für Mund-, Kiefer- und Gesichtschirurgie der LMU München wegen zuvor nicht adäquat versorgter Frakturen im zentralen und lateralen Mittelgesichtsbereich operativ behandelt wurden. Patienten mit isolierten Orbitawand- oder Le Fort I-Frakturen wurden von der Studie ausgeschlossen. In der zweiten Studie wurden Patienten retrospektiv eingeschlossen, die von 2015 bis 2019 in der Klinik für Mund-, Kiefer- und Gesichtschirurgie der LMU München aufgrund von isolierten Orbitawandfrakturen operiert wurden. 8 Patienten wurden in die erste Studie und 27 Patienten in die zweite Studie aufgenommen. Die mediane Abweichung zwischen geplanter und definitiver Position für die PSI und die Knochensegmente wurde erstens zwischen den gesamten Modelloberflächen mittels einem geeigneten Algorithmus der Software 3-Matic und zweitens an anatomisch korrespondierenden Referenzpunkten ausgemessen, analysiert und ausgewertet. In der ersten Studie betrugen die medianen Abstände zwischen der virtuell geplanten und der postoperativen Position der PSI 2,01 mm (n = 18) gegenüber einem medianen Abstand bezüglich der Knochensegmente von 3,05 mm (n = 12). Bei Patienten, bei denen PSI verwendet wurden, war die mediane Verschiebung der Knochensegmente geringer als in der Gruppe mit vorgebogenen Platten. Darüber hinaus konnte der Jochbeinbereich mit geringerer Abweichung als der Oberkieferbereich positioniert werden. Ferner zeigte sich die Zahnbogenregion im Vergleich zur kranialen Oberkieferregion eine höhere Positionierungsgenauigkeit. In der zweiten Studie zeigten die Medianwerte für die Referenzpunktabmessungen eine größere Abweichung bei den Implantaten zur Versorgung der medialen Orbitawand, nämlich 0,79 mm. Der Wert für die Gruppe der Orbitabodenimplantate lag bei 0,45 mm. Es konnte keine Korrelation zwischen der postoperativen Diplopie und der Passgenauigkeit der Implantatposition nachgewiesen werden. Die vorliegende Arbeit zeigt erstens die Machbarkeit der Übertragung der VSP durch CAD/CAM Werkzeuge für die sekundäre Rekonstruktion komplexer posttraumatischer Restdeformitäten im Mittelgesicht, jedoch mit relativ erhöhter Ungenauigkeit, und zweitens die Möglichkeit einer genauen Umsetzung der Planungsposition bei der Rekonstruktion der inferioren und/oder medialen Orbitawand. Die in der ersten Studie beobachteten höheren Abweichungen lassen sich durch Unterschiede in der Bewertungsmethode sowie durch die Komplexität der Deformitäten, Osteotomien und chirurgischen Verfahren erklären, so dass der Einsatz von Navigationssystemen die Genauigkeit der Repositionierung weiter verbessern könnte

Miniplatten aus Titan zur Fixation von Gelenkfortsatzfrakturen des Unterkiefers: Evaluation des biomechanischen Verhaltens mittels der Finite-Elemente-Analyse

The current publications aimed first to determine which plating technique provides the most rigid fixation and the best biomechanical behavior and second, to examine how the positioning of the lambda plate affects the rigidity of fixation. To assess the rigidity of the osteosynthesis, the displacements of the condylar fragments were measured. The von Mises stresses in the osteosynthesis material were calculated to predict possible material failure in the plates and screws. In addition, the maximum principal strain in the bone was used to indicate potential bone areas that might be susceptible to bone resorption. All four plate designs (alpha, kappa, rhomboid, and trapezoidal) were tested under the same conditions: a load of 500 N simulating the maximum masticatory force of a healthy adult and a load of 135 N corresponding to the reduced masticatory force within the six postoperative weeks. According to our findings, all four plates showed adequate fixation of neck fractures at a load of 135 N with a risk for delayed screw loosening only when the trapezoidal and rhomboid plates were used. On the other hand, the plates showed significant differences when a load of 500 N was applied. Larger plates requiring more screws for fixation, such as the alpha and kappa plates, performed better than the rhomboid and trapezoidal plates, which have half the volume of the former. The alpha and kappa plates showed higher rigidity and better stress distribution in the bone. The trapezoidal plate resulted in less rigid fixation because the micromovements could lead to pseudoarthrosis. The above results may differ if the course of the fracture line or the position of the plate changes. These parameters were examined in the current study for the relatively new lambda plate, for which there is insufficient data to make any conclusions about its application. The rigidity of osteosynthesis using the lambda plate was studied for a load of 500N. According to the results of the present study, the lambda plate provided adequate rigidity only for neck fractures. In contrast, the stability of osteosynthesis was unsatisfactory for basal fractures. Furthermore, in condylar neck fractures, a more cranial placement of the plate should be pursued. Finally, if the Lambda plate is used for basal fractures, it should be combined with an additional plate under the sigmoid notch. The finite element analysis is a computational method, and results apply only to fracture patterns and osteosynthesis materials simulated with current models. The results should be validated by experimental or clinical studies

Identification of distinct SET/TAF-Iβ domains required for core histone binding and quantitative characterisation of the interaction

<p>Abstract</p> <p>Background</p> <p>The assembly of nucleosomes to higher-order chromatin structures is finely tuned by the relative affinities of histones for chaperones and nucleosomal binding sites. The myeloid leukaemia protein SET/TAF-Iβ belongs to the NAP1 family of histone chaperones and participates in several chromatin-based mechanisms, such as chromatin assembly, nucleosome reorganisation and transcriptional activation. To better understand the histone chaperone function of SET/TAF-Iβ, we designed several SET/TAF-Iβ truncations, examined their structural integrity by circular Dichroism and assessed qualitatively and quantitatively the histone binding properties of wild-type protein and mutant forms using GST-pull down experiments and fluorescence spectroscopy-based binding assays.</p> <p>Results</p> <p>Wild type SET/TAF-Iβ binds to histones H2B and H3 with K_dvalues of 2.87 and 0.15 μM, respectively. The preferential binding of SET/TAF-Iβ to histone H3 is mediated by its central region and the globular part of H3. On the contrary, the acidic C-terminal tail and the amino-terminal dimerisation domain of SET/TAF-Iβ, as well as the H3 amino-terminal tail, are dispensable for this interaction.</p> <p>Conclusion</p> <p>This type of analysis allowed us to assess the relative affinities of SET/TAF-Iβ for different histones and identify the domains of the protein required for effective histone recognition. Our findings are consistent with recent structural studies of SET/TAF-Iβ and can be valuable to understand the role of SET/TAF-Iβ in chromatin function.</p

Modulations of DNA contacts by linker histones and post-translational modifications determine the mobility and modifiability of nucleosomal H3 tails.

Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function

Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Simple Summary Occult metastasis in oral squamous cell carcinoma patients is a feared complication. However, there are barely any existing data on survival of patients suffering from occult metastasis. This study aims to compare patients with oral squamous cell carcinoma, considering survival in occult metastases and different treatment approaches. The impact of neck involvement and occult metastasis (OM) in patients with oral squamous cell carcinoma (OSCC) favors an elective neck dissection. However, there are barely any existing data on survival for patients with OM compared with patients with positive lymph nodes detected preoperatively. This study aims to compare survival curves of patients suffering from lymph nodal metastases in a preoperatively N+ neck with those suffering from OM. In addition, clinical characteristics of the primary tumor were analyzed to predict occult nodal disease. This retrospective cohort study includes patients with an OSCC treated surgically with R0 resection with or without adjuvant chemoradiotherapy between 2010 and 2016. Minimum follow-up was 60 months. Kaplan-Meier analysis was used to compare the survival between patients with and without occult metastases and patients with N+ neck to those with occult metastases. Logistic regression was used to detect potential risk factors for occult metastases. The patient cohort consisted of 226 patients. Occult metastases occurred in 16 of 226 patients. In 53 of 226 patients, neck lymph nodes were described as suspect on CT imaging but had a pN0 neck. Higher tumor grading increased the chance of occurrence of occult metastasis 2.7-fold (OR = 2.68, 95% CI: 1.07-6.7). After 12, 24, 48 and 60 months, 82.3%, 73.8%, 69% and 67% of the N0 patients, respectively, were progression free. In the group with OM occurrence, for the same periods 66.6%, 50%, 33.3% and 33.3% of the patients, respectively, were free of disease. For the same periods, respectively, 81%, 63%, 47% and 43% of the patients in the N+ group but without OM remained disease free. The predictors for progression-free survival were a positive N status (HR = 1.44, 95% CI: 1.08-1.93) and the occurrence of OM (HR = 2.33, 95% CI: 1.17-4.64). The presence of occult metastasis could lead to decreased survival and could be a burdening factor requiring treatment escalation and a more aggressive follow-up than nodal disease detected in the preoperative diagnostic imaging

Digital planning and individual implants for secondary reconstruction of midfacial deformities: A pilot study

Objective To evaluate the feasibility and accuracy of implementing three-dimensional virtual surgical planning (VSP) and subsequent transfer by additive manufactured tools in the secondary reconstruction of residual post-traumatic deformities in the midface. Methods Patients after secondary reconstruction of post-traumatic midfacial deformities were included in this case series. The metrical deviation between the virtually planned and postoperative position of patient-specific implants (PSI) and bone segments was measured at corresponding reference points. Further information collected included demographic data, post-traumatic symptoms, and type of transfer tools. Results Eight consecutive patients were enrolled in the study. In five patients, VSP with subsequent manufacturing of combined predrilling/osteotomy guides and PSI was performed. In three patients, osteotomy guides, repositioning guides, and individually prebent plates were used following VSP. The median distances between the virtually planned and the postoperative position of the PSI were 2.01 mm (n = 18) compared to a median distance concerning the bone segments of 3.05 mm (n = 12). In patients where PSI were used, the median displacement of the bone segments was lower (n = 7, median 2.77 mm) than in the group with prebent plates (n = 5, 3.28 mm). Conclusion This study demonstrated the feasibility of VSP and transfer by additive manufactured tools for the secondary reconstruction of complex residual post-traumatic deformities in the midface. However, the median deviations observed in this case series were unexpectedly high. The use of navigational systems may further improve the level of accuracy

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks