Axel Ekkernkamp

Introduction: The escalating scarcity of skilled healthcare professionals is particularly pronounced within surgical specialties, where the prospect of attracting prospective medical practitioners poses formidable challenges. Throughout their academic journey, students exhibit diminishing enthusiasm and motivation to pursue careers in surgery, including trauma surgery. It is postulated that the caliber of teaching plays a pivotal role in influencing students’ subsequent specialization choices. Methods: This prospective observational study was conducted among a cohort of third-year medical students at the German University Medicine Greifswald. The methodology encompassed the utilization of a self-administered questionnaire to procure data. Results: The study encompassed 177 participants, of whom 34.7% expressed an inclination toward a career in surgery (22.7% in trauma surgery). Participants who reported a favorable impact from the examination course displayed a significantly heightened interest in clinical clerkships within trauma surgery (p < 0.001), and even expressed a contemplation of specializing in orthopedics and trauma surgery (p = 0.001). Logistic regression analysis highlighted that the convergence of practical training and positive role modeling emerged as the most influential factors augmenting the allure of trauma surgery. Conclusions: Evidently, students who gleaned substantial benefits from high-quality practical instruction in trauma surgery exhibited a significantly heightened likelihood of pursuing this domain in their future endeavors. Surgical academic institutions stand to leverage this insight in their strategic planning for attracting and retaining potential residents. Cultivating a positive affinity for trauma surgery should be instilled early in the curriculum, subsequently sustained through ongoing immersive engagement that encompasses professional as well as interpersonal dimensions.

Background/Objectives: Clavicle injuries are common and seem to be frequently subject to diagnostic misclassification. The accurate identification of clavicle fractures is essential, particularly for registry and Big Data analyses. This study aims to assess the frequency of diagnostic errors in clavicle injury classifications. Methods: This retrospective study analyzed patient data from two Level 1 trauma centers, covering the period from 2008 to 2019. Included were cases with ICD-coded diagnoses of medial, midshaft, and lateral clavicle fractures, as well as sternoclavicular and acromioclavicular joint dislocations. Radiological images were re-evaluated, and discharge summaries, radiological reports, and billing codes were examined for diagnostic accuracy. Results: A total of 1503 patients were included, accounting for 1855 initial injury diagnoses. In contrast, 1846 were detected upon review. Initially, 14.4% of cases were coded as medial clavicle fractures, whereas only 5.2% were confirmed. The misclassification rate was 82.8% for initial medial fractures (p < 0.001), 42.5% for midshaft fractures (p < 0.001), and 34.2% for lateral fractures (p < 0.001). Billing codes and discharge summaries were the most error-prone categories, with error rates of 64% and 36% of all misclassified cases, respectively. Over three-quarters of the cases with discharge summary errors also exhibited errors in other categories, while billing errors co-occurred with other category errors in just over half of the cases (p < 0.001). The likelihood of radiological diagnostic error increased with the number of imaging modalities used, from 19.7% with a single modality to 30.5% with two and 40.7% with three. Conclusions: Our findings indicate that diagnostic misclassification of clavicle fractures is common, particularly between medial and midshaft fractures, often resulting from errors in multiple categories. Further prospective studies are needed, as accurate classification is foundational for the reliable application of Big Data and AI-based analyses in clinical research.

Background: The clavicle remains one of the most fractured bones in the human body, despite the fact that little is known about the MR imaging of it and the adjacent sternoclavicular joint. This study aims to establish standardized values for the diameters of the clavicle as well as the angles of the sternoclavicular joint using whole-body MRI scans of a large and healthy population and to examine further possible correlations between diameters and angles and influencing factors like BMI, weight, height, sex, and age. Methods: This study reviewed whole-body MRI scans from the Study of Health in Pomerania (SHIP), a German population-based cross-sectional study in Mecklenburg–Western Pomerania. Descriptive statistics, as well as median-based regression models, were used to evaluate the results. Results: We could establish reference values based on a shoulder-healthy population for each clavicle parameter. Substantial differences were found for sex. Small impacts were found for height, weight, and BMI. Less to no impact was found for age. Conclusions: This study provides valuable reference values for clavicle and sternoclavicular joint-related parameters and shows the effects of epidemiological features, laying the groundwork for future studies. Further research is mandatory to determine the clinical implications of these findings.

Although Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC₂₀ and IC₅₀ were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine.

Background: The use of cold atmospheric plasma (CAP) in oncology has been intensively investigated over the past 15 years as it inhibits the growth of many tumor cells. It is known that reactive oxidative species (ROS) produced in CAP are responsible for this effect. However, to translate the use of CAP into medical practice, it is essential to know how CAP treatment affects non-malignant cells. Thus, the current in vitro study deals with the effect of CAP on human bone cancer cells and human osteoblasts. Here, identical CAP treatment regimens were applied to the malignant and non-malignant bone cells and their impact was compared. Methods: Two different human bone cancer cell types, U2-OS (osteosarcoma) and A673 (Ewing’s sarcoma), and non-malignant primary osteoblasts (HOB) were used. The CAP treatment was performed with the clinically approved kINPen MED. After CAP treatment, growth kinetics and a viability assay were performed. For detecting apoptosis, a caspase-3/7 assay and a TUNEL assay were used. Accumulated ROS was measured in cell culture medium and intracellular. To investigate the influence of CAP on cell motility, a scratch assay was carried out. Results: The CAP treatment showed strong inhibition of cell growth and viability in bone cancer cells. Apoptotic processes were enhanced in the malignant cells. Osteoblasts showed a higher potential for ROS resistance in comparison to malignant cells. There was no difference in cell motility between benign and malignant cells following CAP treatment. Conclusions: Osteoblasts show better tolerance to CAP treatment, indicated by less affected viability compared to CAP-treated bone cancer cells. This points toward the selective effect of CAP on sarcoma cells and represents a further step toward the clinical application of CAP.

(1) Background: Chondrosarcoma (CS) is a malignant primary bone tumor with a cartilaginous origin. Its slow cell division and severely restricted vascularization are responsible for its poor responsiveness to chemotherapy and radiotherapy. The decisive factor for the prognosis of CS patients is the only adequate therapy—surgical resection. Cold atmospheric pressure plasma (CAP) is emerging as a new option in anti-cancer therapy. Its effect on chondrosarcomas has been poorly investigated. (2) Methods: Two CS cell lines—SW 1353 and CAL 78—were used. Various assays, such as cell growth kinetics, glucose uptake, and metabolic activity assay, along with two different apoptosis assays were performed after CAP treatment. A radius cell migration assay was used to examine cell motility. (3) Results: Both cell lines showed different growth behavior, which was taken into account when using the assays. After CAP treatment, a reduction in metabolic activity was observed in both cell lines. The immediate effect of CAP showed a reduction in cell numbers and in influence on this cell line’s growth rate. The measurement of the glucose concentration in the cell culture medium showed an increase after CAP treatment. Live-dead cell imaging shows an increase in the proportion of dead cells over the incubation time for both cell lines. There was a significant increase in apoptotic signals after 48 h and 72 h for both cell lines in both assays. The migration assay showed that CAP treatment inhibited the motility of chondrosarcoma cells. The effects in all experiments were related to the duration of CAP exposure. (4) Conclusions: The CAP treatment of CS cells inhibits their growth, motility, and metabolism by initiating apoptotic processes.

Purpose: Severe accidents are the leading cause of long-term impairment and death in children. A common diagnostic procedure for children exposed to high-injury trauma is full-body contrast-enhanced CT (fbCT). However, the number of fbCT without detected injuries is relevant. In 2007, full-body MRI (fbMRI) was implemented as a diagnostic approach for children sustaining high-energy trauma. The aim of this cross-sectional retrospective study was to analyze fbMRI as a diagnostic tool for children after high-energy trauma focusing on feasibility, radiological findings, and limitations. Methods: Diagnostics using fbMRI (from apex of the head to the pelvis) was performed if a child was stable and suffered a high-energy trauma in a Level I Trauma Center in Germany. 105 fbMRIs in patients exposed to high-energy trauma aged ≤ 16 years were performed between January 2007 and December 2018. Four fbMRIs were excluded as conducted for reasons other than trauma. Time between arrival in the emergency department and fbMRI, additional diagnostic procedures, injuries, and non-trauma related pathologies were analyzed. Results: Mean time between arrival in the emergency department and fbMRI was 71 min (± SD 132 min). Two scans were discontinued and changed to a faster diagnostic procedure. 45% of children had additional X-rays and 11% CT scans. The MRIs showed intracranial abnormalities in 27%, extremities injuries in 26%, spinal injuries in 18%, pelvic, and thoracic injuries in 7% of the cases. Conclusion: Overall fbMRI is a diagnostic alternative for hemodynamically stable, conscious children after high-energy trauma with the advantages of a radiation-free technique. However, MRI diagnostics take longer than CT scans. Prospective studies will be needed to identify the limiting factors of fbMRIs as primary diagnostic procedure compared to CT scans. Trial registration: German Clinical Trials Register (DRKS; DRKS00017015). Level of evidence: Case series, level of evidence V.

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient’s further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study. Methods: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed. Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.

Chondrosarcoma is the second most common malign bone tumor in adults. Surgical resection of the tumor is recommended because of its resistance to clinical treatment such as chemotherapy and radiation therapy. Thus, the prognosis for patients mainly depends on sufficient surgical resection. Due to this, research on alternative therapies is needed. Cold atmospheric plasma (CAP) is an ionized gas that contains various reactive species. Previous studies have shown an anti-oncogenic potential of CAP on different cancer cell types. The current study examined the effects of treatment with CAP on two chondrosarcoma cell lines (CAL-78, SW1353). Through proliferation assay, the cell growth after CAP-treatment was determined. A strong antiproliferative effect for both cell lines was detected. By fluorescein diacetate (FDA) assay and ATP release assay, alterations in the cell membrane and associated translocation of low molecular weight particles through the cytoplasmic membrane were observed. In supernatant, the non-membrane-permeable FDA and endogenously synthesized ATP detected suggest an increased membrane permeability after CAP treatment. Similar results were shown by the dextran-uptake assay. Furthermore, fluorescence microscopic G-/F-actin assay was performed. G- and F-actin were selectively dyed, and the ratio was measured. The presented results indicate CAP-induced changes in cell membrane function and possible alterations in actin-cytoskeleton, which may contribute to the antiproliferative effects of CAP.