HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?

BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target. METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy. CONCLUSION: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.

Post-graduation career pathways: a nationwide survey among dental students in Germany.

OBJECTIVES: Oral and maxillofacial surgery (OMFS) has to compete with other specialties for the best candidates. With the upcoming change of generations (Z and Alpha) and the movement toward gender parity of dentistry, understanding changing preferences and misconceptions is essential. MATERIAL AND METHODS: An online survey was conducted by the German-Association-of-Oral-and-Maxillofacial-Surgery (DGMKG) across German dental schools. The survey collected demographic data, academic background, and career aspirations, with a focus on OMFS. The dental student survey results were compared to a survey given to OMFS Specialists. RESULTS: 637 dental students, mainly female (70%), from 30 German universities participated. 27% had defined career aspirations post-graduation, with self-employment and academia being popular choices. 67% were unsure. Specializations leaned towards restorative dentistry (41%), orthodontics (36%), and prosthodontics (31%). While 73% showed interest in surgical practices, 20% were attracted in specializing in OMFS. Of those averse to OMFS, 78% cited long training duration as the deterrent, 12% were put off by perceived unattractive working hours. Other reasons included negative undergraduate experiences, scarcity of part-time positions, and perceived inadequate earnings. CONCLUSION: Accurate data is crucial for career decisions. OMFS societies must proactively share accurate information and guide students. OMFS offers family-friendly hours, and while its training might be longer than dental specialties, it is on par with other surgical professions. CLINICAL RELEVANCE: Dental students consistently regard OMFS as commendable career path. To guarantee sustained OMFS expertise, it is imperative to nurture this interest through dedicated academic mentorship and innovative education, thereby solidifying their professional direction.

Insights into Predicting Tooth Extraction from Panoramic Dental Images: Artificial Intelligence vs. Dentists.

OBJECTIVES: Tooth extraction is one of the most frequently performed medical procedures. The indication is based on the combination of clinical and radiological examination and individual patient parameters and should be made with great care. However, determining whether a tooth should be extracted is not always a straightforward decision. Moreover, visual and cognitive pitfalls in the analysis of radiographs may lead to incorrect decisions. Artificial intelligence (AI) could be used as a decision support tool to provide a score of tooth extractability. MATERIAL AND METHODS: Using 26,956 single teeth images from 1,184 panoramic radiographs (PANs), we trained a ResNet50 network to classify teeth as either extraction-worthy or preservable. For this purpose, teeth were cropped with different margins from PANs and annotated. The usefulness of the AI-based classification as well that of dentists was evaluated on a test dataset. In addition, the explainability of the best AI model was visualized via a class activation mapping using CAMERAS. RESULTS: The ROC-AUC for the best AI model to discriminate teeth worthy of preservation was 0.901 with 2% margin on dental images. In contrast, the average ROC-AUC for dentists was only 0.797. With a 19.1% tooth extractions prevalence, the AI model's PR-AUC was 0.749, while the dentist evaluation only reached 0.589. CONCLUSION: AI models outperform dentists/specialists in predicting tooth extraction based solely on X-ray images, while the AI performance improves with increasing contextual information. CLINICAL RELEVANCE: AI could help monitor at-risk teeth and reduce errors in indications for extractions.

Development and validation of a cadaveric porcine Pseudotumor model for Oral Cancer biopsy and resection training.

OBJECTIVE: The gold standard of oral cancer (OC) treatment is diagnostic confirmation by biopsy followed by surgical treatment. However, studies have shown that dentists have difficulty performing biopsies, dental students lack knowledge about OC, and surgeons do not always maintain a safe margin during tumor resection. To address this, biopsies and resections could be trained under realistic conditions outside the patient. The aim of this study was to develop and to validate a porcine pseudotumor model of the tongue. METHODS: An interdisciplinary team reflecting various specialties involved in the oncological treatment of head and neck oncology developed a porcine pseudotumor model of the tongue in which biopsies and resections can be practiced. The refined model was validated in a final trial of 10 participants who each resected four pseudotumors on a tongue, resulting in a total of 40 resected pseudotumors. The participants (7 residents and 3 specialists) had an experience in OC treatment ranging from 0.5 to 27 years. Resection margins (minimum and maximum) were assessed macroscopically and compared beside self-assessed margins and resection time between residents and specialists. Furthermore, the model was evaluated using Likert-type questions on haptic and radiological fidelity, its usefulness as a training model, as well as its imageability using CT and ultrasound. RESULTS: The model haptically resembles OC (3.0 ± 0.5; 4-point Likert scale), can be visualized with medical imaging and macroscopically evaluated immediately after resection providing feedback. Although, participants (3.2 ± 0.4) tended to agree that they had resected the pseudotumor with an ideal safety margin (10 mm), the mean minimum resection margin was insufficient at 4.2 ± 1.2 mm (mean ± SD), comparable to reported margins in literature. Simultaneously, a maximum resection margin of 18.4 ± 6.1 mm was measured, indicating partial over-resection. Although specialists were faster at resection (p < 0.001), this had no effect on margins (p = 0.114). Overall, the model was well received by the participants, and they could see it being implemented in training (3.7 ± 0.5). CONCLUSION: The model, which is cost-effective, cryopreservable, and provides a risk-free training environment, is ideal for training in OC biopsy and resection and could be incorporated into dental, medical, or oncologic surgery curricula. Future studies should evaluate the long-term training effects using this model and its potential impact on improving patient outcomes.

Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the α1 and ß1 Subunits of Soluble Guanylyl Cyclase.

The binding of nitric oxide (NO) to heme in the ß1 subunit of soluble guanylyl cyclase (sGC) activates both the heterodimeric α1ß1 and α2ß1 isoforms of the enzyme, leading to the increased production of cGMP from GTP. In cultured human mast cells, exogenous NO is able to inhibit mast cell degranulation via NO-cGMP signaling. However, under inflammatory oxidative or nitrosative stress, sGC becomes insensitive to NO. The occurrence of mast cells in healthy and inflamed human tissues and the in vivo expression of the α1 and ß1 subunits of sGC in human mast cells during inflammation remain largely unresolved and were investigated here. Using peroxidase and double immunohistochemical incubations, no mast cells were found in healthy dental pulp, whereas the inflammation of dental pulp initiated the occurrence of several mast cells expressing the α1 and ß1 subunits of sGC. Since inflammation-induced oxidative and nitrosative stress oxidizes Fe2+ to Fe3+ in the ß1 subunit of sGC, leading to the desensitization of sGC to NO, we hypothesize that the NO- and heme-independent pharmacological activation of sGC in mast cells may be considered as a regulatory strategy for mast cell functions in inflamed human dental pulp.

Variants of arterial supply to the inferior (diaphragmatic) surface of the ventricles of the heart and the influence on age at death.

Coronary artery systems of the inferior wall of the ventricles vary considerably. Schlesinger's concept distinguishes dominance of the right or left coronary artery (LCA) or balanced type. LCA dominance has been reported to be associated with increased mortality. Early angiography studies have shown that the anterior interventricular artery (AIVA), a branch of the LCA, often continues on the inferior surface of the heart and may replace the inferior interventricular artery. Others considered an AIVA on the inferior surface of the heart a rare variant. A long AIVA is a strong predictor of death in acute anterior wall myocardial infarction. We determined coronary artery variance at the inferior surface of the ventricles in 134 dissected human hearts and analyzed a possible association between coronary artery variance and age at death. The AIVA extended to the inferior side in 64.9% of the hearts, but rarely reached the basal half of the inferior interventricular groove. Most frequently (53%), it extended into the apical two-fifths of the length of the inferior ventricular walls. An AIVA extending to the apical 40% of the length of the inferior ventricular walls may therefore be considered a common variant. In 20.1% of the hearts, a right inferior diagonal artery was also found. Statistical analysis neither revealed an association between mean AIVA length at the inferior ventricular surface and type of coronary artery dominance nor an association between AIVA length at the inferior ventricular surface or coronary artery dominance type and age at death.

The relation between tau pathology and granulovacuolar degeneration of neurons.

Neurofibrillary tangles arising from aggregated microtubule-associated protein tau occur in aged brains and are hallmarks of neurodegenerative diseases. A subset of neurons containing aggregated tau displays granulovacuolar degeneration (GVD) that is characterized by membrane-bound cytoplasmic vacuoles, each containing an electron-dense granule (GVB). Tau pathology induces GVBs in experimental models, but GVD does not generally follow tau pathology in the human brain. The entorhinal cortex, DRN, and LC are among the regions that display pathological changes of tau earliest, whereas neurons with GVBs occur first in the hippocampus and have been found in oral raphe nuclei only at the most advanced GVD stage. To date, there is no detailed report about neurons with GVD in aminergic nuclei. We studied the relation between tau pathology and GVD in field CA1 of the hippocampus, entorhinal cortex, dorsal (DRN) and median (MRN) raphe nucleus, and locus coeruleus from elderly subjects with Braak & Braak stages of tau pathology ranging from 0 to VI. Tau pathology and GVBs were visualized by means of immunolabeling and quantified. Percentages of neurons containing GVBs were significantly related to percentages of AT8-positive neurons in the regions examined. GVD and tau pathology were found together in neurons to a different extent in regions of the brain. 53.2% of AT8-immunoreactive neurons in CA1, 19.8% in layer II of the entorhinal cortex, 29.6% in the DRN, and 31.4% in the locus coeruleus contained GVBs. Age-related factors, the percentage of neurons with pretangles in a region of the brain, and the metabolism of a neuron possibly influence the prevalence of neurons with GVBs.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a 10-year experience in a burns unit.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and its more severe counterpart, toxic epidermal necrolysis (TEN), are skin hypersensitivity reactions defined by epidermal blistering and necrosis. The exact pathophysiology of SJS/TEN is yet to be deciphered, but a number of risk factors have been identified including adverse drug reactions. The diagnosis of SJS/TEN is made on a clinical basis, and treatment consists of supportive care and occasionally immunosuppressants, such as cyclosporin, high-dose intravenous immunoglobulins and/or corticosteroids. Mortality rates can reach 20-25% in adults but are reduced with early intervention. To identify optimal treatment regimens, to better understand the patient cohort affected, and to help identify key risk factors for mortality, we report our experience with the treatment and management of SJS/TEN patients. METHODS: A retrospective review of consecutive patients with SJS and/or TEN admitted to a single burns centre in Germany, between 2008 and 2018, was conducted. The primary outcomes of demographics, clinical course, treatment and patient-reported outcomes were recorded and compared with a control group of patients with burns without a diagnosis of SJS/TEN. RESULTS: A total of 23 patients with SJS/TEN met the inclusion criteria: 17 (74%) with TEN; four (17%) with SJS/TEN overlap; and two (9%) with SJS. Of the patients, 14 (61%) were female and nine (39%) were male. Patient age ranged from 32-78 years (mean: 52 years). A matched cohort of 23 patients with burns served as the control group. All patients received standard of care with a multidisciplinary team. Compared with the control group, SJS/TEN patients had higher mortality rates (n=6, 26% versus n=8, 35%, respectively). The average age of death was 69 years in SJS/TEN patients versus 63 years in control group patients. Age and SCORTEN scores were significant predictors of mortality. CONCLUSIONS: SJS and TEN are rare but extreme reactions of the skin and mucosa, associated with high disease mortality rates. This 10-year single-centre retrospective review contributes to the bank of information for reviews evaluating the management of SJS/TEN patients.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. METHOD: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens-Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999-2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. RESULTS: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. CONCLUSION: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Inflammation in the Human Periodontium Induces Downregulation of the α1- and ß1-Subunits of the sGC in Cementoclasts.

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and ß1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and ß1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and ß1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.

Molecular Mechanisms of Hair Growth and Regeneration: Current Understanding and Novel Paradigms.

Hair is a defining feature of mammals and has critical functions, including protection, production of sebum, apocrine sweat and pheromones, social and sexual interactions, thermoregulation, and provision of stem cells for skin homeostasis, regeneration, and repair. The hair follicle (HF) is considered a "mini-organ," consisting of intricate and well-organized structures which originate from HF stem and progenitor cells. Dermal papilla cells are the main components of the mesenchymal compartments in the hair bulb and are instrumental in generating signals to regulate the behavior of neighboring epithelial cells during the hair cycle. Mesenchymal-epithelial interactions within the dermal papilla niche drive HF embryonic development as well as the postnatal hair growth and regeneration cycle. This review summarizes the current understanding of HF development, repair, and regeneration, with special focus on cell signaling pathways governing these processes. In particular, we discuss emerging paradigms of molecular signaling governing the dermal papilla-epithelial cellular interactions during hair growth and maintenance and the recent progress made towards tissue engineering of human hair follicles.

ChatGPT in healthcare: A taxonomy and systematic review.

The recent release of ChatGPT, a chat bot research project/product of natural language processing (NLP) by OpenAI, stirs up a sensation among both the general public and medical professionals, amassing a phenomenally large user base in a short time. This is a typical example of the 'productization' of cutting-edge technologies, which allows the general public without a technical background to gain firsthand experience in artificial intelligence (AI), similar to the AI hype created by AlphaGo (DeepMind Technologies, UK) and self-driving cars (Google, Tesla, etc.). However, it is crucial, especially for healthcare researchers, to remain prudent amidst the hype. This work provides a systematic review of existing publications on the use of ChatGPT in healthcare, elucidating the 'status quo' of ChatGPT in medical applications, for general readers, healthcare professionals as well as NLP scientists. The large biomedical literature database PubMed is used to retrieve published works on this topic using the keyword 'ChatGPT'. An inclusion criterion and a taxonomy are further proposed to filter the search results and categorize the selected publications, respectively. It is found through the review that the current release of ChatGPT has achieved only moderate or 'passing' performance in a variety of tests, and is unreliable for actual clinical deployment, since it is not intended for clinical applications by design. We conclude that specialized NLP models trained on (bio)medical datasets still represent the right direction to pursue for critical clinical applications.

Full-thickness skin graft versus split-thickness skin graft for radial forearm free flap donor site closure: protocol for a systematic review and meta-analysis.

BACKGROUND: The radial forearm free flap (RFFF) serves as a workhorse for a variety of reconstructions. Although there are a variety of surgical techniques for donor site closure after RFFF raising, the most common techniques are closure using a split-thickness skin graft (STSG) or a full-thickness skin graft (FTSG). The closure can result in wound complications and function and aesthetic compromise of the forearm and hand. The aim of the planned systematic review and meta-analysis is to compare the wound-related, function-related and aesthetics-related outcome associated with full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) in radial forearm free flap (RFFF) donor site closure. METHODS: A systematic review and meta-analysis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed. Electronic databases and platforms (PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI)) and clinical trial registries (ClinicalTrials.gov, the German Clinical Trials Register, the ISRCTN registry, the International Clinical Trials Registry Platform) will be searched using predefined search terms until 15 January 2024. A rerun of the search will be carried out within 12 months before publication of the review. Eligible studies should report on the occurrence of donor site complications after raising an RFFF and closure of the defect. Included closure techniques are techniques that use full-thickness skin grafts and split-thickness skin grafts. Excluded techniques for closure are primary wound closure without the use of skin graft. Outcomes are considered wound-, functional-, and aesthetics-related. Studies that will be included are randomized controlled trials (RCTs) and prospective and retrospective comparative cohort studies. Case-control studies, studies without a control group, animal studies and cadaveric studies will be excluded. Screening will be performed in a blinded fashion by two reviewers per study. A third reviewer resolves discrepancies. The risk of bias in the original studies will be assessed using the ROBINS-I and RoB 2 tools. Data synthesis will be done using Review Manager (RevMan) 5.4.1. If appropriate, a meta-analysis will be conducted. Between-study variability will be assessed using the I2 index. If necessary, R will be used. The quality of evidence for outcomes will eventually be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: This study's findings may help us understand both closure techniques' complication rates and may have important implications for developing future guidelines for RFFF donor site management. If available data is limited and several questions remain unanswered, additional comparative studies will be needed. SYSTEMATIC REVIEW REGISTRATION: The protocol was developed in line with the PRISMA-P extension for protocols and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 September 2023 (registration number CRD42023351903).

Cyto R-CNN and CytoNuke Dataset: Towards reliable whole-cell segmentation in bright-field histological images.

BACKGROUND AND OBJECTIVE: Cell segmentation in bright-field histological slides is a crucial topic in medical image analysis. Having access to accurate segmentation allows researchers to examine the relationship between cellular morphology and clinical observations. Unfortunately, most segmentation methods known today are limited to nuclei and cannot segment the cytoplasm. METHODS: We present a new network architecture Cyto R-CNN that is able to accurately segment whole cells (with both the nucleus and the cytoplasm) in bright-field images. We also present a new dataset CytoNuke, consisting of multiple thousand manual annotations of head and neck squamous cell carcinoma cells. Utilizing this dataset, we compared the performance of Cyto R-CNN to other popular cell segmentation algorithms, including QuPath's built-in algorithm, StarDist, Cellpose and a multi-scale Attention Deeplabv3+. To evaluate segmentation performance, we calculated AP50, AP75 and measured 17 morphological and staining-related features for all detected cells. We compared these measurements to the gold standard of manual segmentation using the Kolmogorov-Smirnov test. RESULTS: Cyto R-CNN achieved an AP50 of 58.65% and an AP75 of 11.56% in whole-cell segmentation, outperforming all other methods (QuPath 19.46/0.91%; StarDist 45.33/2.32%; Cellpose 31.85/5.61%, Deeplabv3+ 3.97/1.01%). Cell features derived from Cyto R-CNN showed the best agreement to the gold standard (D¯=0.15) outperforming QuPath (D¯=0.22), StarDist (D¯=0.25), Cellpose (D¯=0.23) and Deeplabv3+ (D¯=0.33). CONCLUSION: Our newly proposed Cyto R-CNN architecture outperforms current algorithms in whole-cell segmentation while providing more reliable cell measurements than any other model. This could improve digital pathology workflows, potentially leading to improved diagnosis. Moreover, our published dataset can be used to develop further models in the future.

Improving detection of oral lesions: Eye tracking insights from a randomized controlled trial comparing standardized to conventional approach.

BACKGROUND: Early detection of oral cancer (OC) or its precursors is the most effective measure to improve outcome. The reasons for missing them on conventional oral examination (COE) or possible countermeasures are still unclear. METHODS: In this randomized controlled trial, we investigated the effects of standardized oral examination (SOE) compared to COE. 49 dentists, specialists, and dental students wearing an eye tracker had to detect 10 simulated oral lesions drawn into a volunteer's oral cavity. RESULTS: SOE had a higher detection rate at 85.4% sensitivity compared to 78.8% in the control (p = 0.017) due to higher completeness (p < 0.001). Detection rate correlated with examination duration (p = 0.002). CONCLUSIONS: A standardized approach can improve systematics and thereby detection rates in oral examinations. It should take at least 5 min. Perceptual and cognitive errors and improper technique cause oral lesions to be missed. Its wide implementation could be an additional strategy to enhance early detection of OC.

AIxSuture: vision-based assessment of open suturing skills.

PURPOSE: Efficient and precise surgical skills are essential in ensuring positive patient outcomes. By continuously providing real-time, data driven, and objective evaluation of surgical performance, automated skill assessment has the potential to greatly improve surgical skill training. Whereas machine learning-based surgical skill assessment is gaining traction for minimally invasive techniques, this cannot be said for open surgery skills. Open surgery generally has more degrees of freedom when compared to minimally invasive surgery, making it more difficult to interpret. In this paper, we present novel approaches for skill assessment for open surgery skills. METHODS: We analyzed a novel video dataset for open suturing training. We provide a detailed analysis of the dataset and define evaluation guidelines, using state of the art deep learning models. Furthermore, we present novel benchmarking results for surgical skill assessment in open suturing. The models are trained to classify a video into three skill levels based on the global rating score. To obtain initial results for video-based surgical skill classification, we benchmarked a temporal segment network with both an I3D and a Video Swin backbone on this dataset. RESULTS: The dataset is composed of 314 videos of approximately five minutes each. Model benchmarking results are an accuracy and F1 score of up to 75 and 72%, respectively. This is similar to the performance achieved by the individual raters, regarding inter-rater agreement and rater variability. We present the first end-to-end trained approach for skill assessment for open surgery training. CONCLUSION: We provide a thorough analysis of a new dataset as well as novel benchmarking results for surgical skill assessment. This opens the doors to new advances in skill assessment by enabling video-based skill assessment for classic surgical techniques with the potential to improve the surgical outcome of patients.

Accuracy of on-site teleoperated milling with haptic assistance.

PURPOSE: In bone surgery specialties, like orthopedics, neurosurgery, and oral and maxillofacial surgery patient safety and treatment success depends on the accurate implementation of computer-based surgical plans. Unintentional plan deviations can result in long-term functional damage to the patient. With on-site teleoperation, the surgeon operates a slave robot with a physically-decoupled master device, while being directly present at the operation site. This allows the surgeon to perform surgical tasks with robotic accuracy, while always remaining in the control loop. METHODS: In this study the master- and slave-side accuracy of an on-site teleoperated miniature cooperative robot (minaroHD) is evaluated. Master-side accuracy is investigated in a user study regarding scale factor, target feed rate, movement direction and haptic guidance stiffness. Scale factors are chosen to correspond to primarily finger, hand, and arm movements. Slave-side accuracy is investigated in autonomous milling trials regarding stepover, feed rate, movement direction, and material density. RESULTS: Master-side user input errors increase with increasing target feed rate and scale factor, and decrease with increasing haptic guidance stiffness. Resulting slave-side errors decrease with increasing scale factor and are < 0.07 mm for optimal guidance parameters. Slave-side robot position errors correlate with the feed rate but show little correlation with stepover distance. For optimal milling parameters, the 95th percentile of tracked slave-side position error is 0.086 mm with a maximal error of 0.16 mm. CONCLUSION: For optimal guidance and milling parameters, the combined error of 0.23 mm is in the range of the dura mater thickness (< 0.27 mm) or mandibular canal wall (~ 0.85 mm). This corresponds to safety margins in high-demand surgical procedures like craniotomies, laminectomies, or decortication of the jaw. However, for further clinical translation, the performance and usability of on-site teleoperated milling must be further evaluated for real-life clinical application examples with consideration of all error sources in a computer-assisted surgery workflow.

Impact of age on microvascular free flap perfusion in head and neck reconstruction.

OBJECTIVE: Aging is associated with structural and functional cardiovascular changes that may affect microvascular free flap perfusion, which is a prerequisite for flap viability and flap success. This study is aimed to investigate the impact of age on flap perfusion. STUDY DESIGN: Intraoperative and postoperative flap perfusion of 348 patients who underwent successful reconstruction with a radial free forearm flap (RFFF), anterolateral thigh flap (ALTF), or fibular free flap (FFF) was retrospectively analyzed and compared between older (>70 years) and younger patients (≤70 years) using the Mann-Whitney test and linear regression models. RESULTS: Intraoperative flap blood flow and hemoglobin concentration (55.5 arbitrary units [AU] vs 69.3 AU, P = .004; 42.5 AU vs 47.3 AU, P = .016, respectively) were reduced in ALTFs in older patients compared with younger patients. These 2 differences did not persist in multivariable testing (P = .097 and P = .323, respectively). No other differences were observed between the older and younger patients in terms of intraoperative and postoperative flap blood flow, hemoglobin concentration, and hemoglobin oxygen saturation in RFFFs, ALTFs, and FFFs (all P > .05). CONCLUSIONS: Age has no impact on microvascular free flap perfusion in RFFFs, ALTFs, and FFFs. This could contribute to the observed equal success of free flaps in older patients.

Development of machine learning and multivariable models for predicting blood transfusion in head and neck microvascular reconstruction for risk-stratified patient blood management.

BACKGROUND: Although blood transfusions have adverse consequences for microvascular head and neck reconstruction, they are frequently administered. Pre-identifying patients would allow risk-stratified patient blood management. METHODS: Development of machine learning (ML) and logistic regression (LR) models based on retrospective inclusion of 657 patients from 2011 to 2021. Internal validation and comparison with models from the literature by external validation. Development of a web application and a score chart. RESULTS: Our models achieved an area under the receiver operating characteristic curve (ROC-AUC) of up to 0.825, significantly outperforming LR models from the literature. Preoperative hemoglobin, blood volume, duration of surgery and flap type/size were strong predictors. CONCLUSIONS: The use of additional variables improves the prediction for blood transfusion, while models seems to have good generalizability due to surgical standardization and underlying physiological mechanism. The ML models developed showed comparable predictive performance to an LR model. However, ML models face legal hurdles, whereas score charts based on LR could be used after further validation.

Tolerable degree of muscle sacrifice when harvesting a vastus lateralis or myocutaneous anterolateral thigh flap.

The myocutaneous anterolateral thigh (ALT) and vastus lateralis (VL) flaps include a large muscle mass and a sufficient vascular pedicle, and they have been used for decades to reconstruct traumatic and acquired defects of the head and neck and extremities. In spite of these benefits, musculoskeletal dysfunction was reported in nearly 1 out of 20 patients at follow-up. It is unclear whether the recently proposed muscle-sparing flap-raising approach could preserve VL muscle function and whether patients at increased risk could benefit from such an approach. Therefore, we performed a predictive dynamic gait simulation based on a biological motion model with gradual weakening of the VL during a self-selected and fast walking speed to determine the compensable degree of VL muscle reduction. Muscle force, joint angle, and joint moment were measured. Our study showed that VL muscle reduction could be compensated up to a certain degree, which could explain the observed incidence of musculoskeletal dysfunction. In elderly or fragile patients, the VL muscle should not be reduced by 50% or more, which could be achieved by muscle-sparing flap-raising of the superficial partition only. In young or athletic patients, a VL muscle reduction of 10%, which corresponds to a muscle cuff, has no relevant effect. Yet, a reduction of more than 30% leads to relevant weakening of the quadriceps. Therefore, in this patient population with the need for a large portion of muscle, alternative flaps should be considered. This study can serve as the first basis for further investigations of human locomotion after flap-raising.