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Background: Autologous fat grafting is widely used in reconstructive, aesthetic and regenerative surgery and often requires repeated applications. Cryopreservation of lipoaspirate enables autologous fat banking and off-the-shelf availability; however, its clinical implementation is limited by freezing-induced tissue injury, regulatory requirements and uncertainties regarding the optimal preservation protocol. Glycerol is a biocompatible cryoprotective agent with promising preliminary data. Nevertheless, the optimal concentration for lipoaspirate cryopreservation remains unknown. The aim of this study was to determine the optimal glycerol concentration for preservation of adipose tissue processed according to the Cell-Enriched Lipotransfer (CELT) protocol in clinically relevant volumes under GMP-compatible conditions. Methods: Lipoaspirates from 10 patients were processed by centrifugation according to the CELT protocol and allocated into experimental groups: fresh unfrozen control, frozen samples without cryoprotectant, frozen samples with PBS, and frozen samples supplemented with glycerol in concentrations ranging from 10% to 60%. Samples were cryopreserved using a controlled freezing rate at a temperature of −80 °C for 24 h. Large-volume cryopreservation was additionally performed with the best concentration of glycerol. Post-thaw tissue quality was assessed by resazurin assay of whole tissue, stromal vascular fraction (SVF) cell live/dead counting, and resazurin assay after short-term cell culture. Results: Glycerol supplementation improved post-thaw tissue viability compared with cryopreservation without cryoprotectant or with PBS alone. An optimal concentration range between 10% and 30% glycerol was identified, with highest preservation of metabolic activity and surviving cell yield observed at 20%. Higher glycerol concentrations resulted in a marked decline in tissue quality. Cryopreservation in large volume was feasible and did not impair post-thaw viability compared with small-volume samples. Conclusions: Glycerol-based cryopreservation allows effective and GMP-compatible preservation of human lipoaspirate. An optimal glycerol concentration range was identified, enabling large-volume fat banking without compromising tissue quality. This protocol provides a clinically applicable strategy for autologous fat storage and may facilitate repeated reconstructive and regenerative treatments.

Background Syndesmotic injuries can lead to ankle instability. They are treated with syndesmotic screws or suture device. The necessity for screw removal remains a topic of debate. When removal is performed, it usually occurs 2 to 3 months post-operation. In such cases, the screw is typically visualized flouroscopically before removal. We describe an ultrasound-guided procedure for screw removal that avoids radiation exposure and has minimal infrastructural requirements. Method In this prospective cohort study, Cohort 1 included 26 screws (18 patients) that were removed under both fluoroscopic and ultrasound guidance. This allowed for the assessment of the accuracy of ultrasound compared to fluoroscopic visualization. In Cohort 2, 22 screws (17 patients) were removed solely under ultrasound guidance to evaluate the practical applicability of the method. Results A total of 35 patients were included into our study, eighteen in the first and seventeen in the second cohort respectively. In Cohort 1, the mean distance between the fluoroscopic and ultrasound measurement points of the screw heads was 2.9 mm. The mean radiation dose was 1.4 cGy/cm², and the mean operation duration was 15.2 min. Cohort 2 had a mean operative duration of 10.3 min. There were no significant differences in baseline characteristics between the groups. Radiation exposure was not present in Cohort 2. In Cohort 1, the ultrasound-guided screw localization revealed high accuracy, with the threshold < 5 mm ( p  = 0.040). We did not identify any significant predictors for the screw localization accuracy. The duration of the surgical procedure was similar in both groups. In the entire pooled cohort, a longer distance from skin to screw was associated with a longer surgery duration (ρ = 0.419, p  = 0.012). Skin-to-screw distance was found to be the only independent predictor of surgery duration ( p  = 0.009). Conclusion Ultrasound-guided localisation and removal of syndesmotic screws demonstrate comparable accuracy compared to fluoroscopy, with the additional benefits of lower infrastructural requirements and associated costs. Furthermore, this method has a similar operative time to fluoroscopy and eliminates radiation exposure, supporting its feasibility as an efficient and safe alternative for syndesmotic screw removal. Trial registration In accordance with the Declaration of Helsinki the study protocol was approved by the Ethics Review Board of the University of Regensburg, Protocol number 21-2204-101.

With a history of more than 100 years of different applications in various scientific fields, the chicken chorioallantoic membrane (CAM) assay has proven itself to be an exceptional scientific model that meets the requirements of the replacement, reduction, and refinement principle (3R principle). As one of three extraembryonic avian membranes, the CAM is responsible for fetal respiration, metabolism, and protection. The model provides a unique constellation of immunological, vascular, and extracellular properties while being affordable and reliable at the same time. It can be utilized for research purposes in cancer biology, angiogenesis, virology, and toxicology and has recently been used for biochemistry, pharmaceutical research, and stem cell biology. Stem cells and, in particular, mesenchymal stem cells derived from adipose tissue (ADSCs) are emerging subjects for novel therapeutic strategies in the fields of tissue regeneration and personalized medicine. Because of their easy accessibility, differentiation profile, immunomodulatory properties, and cytokine repertoire, ADSCs have already been established for different preclinical applications in the files mentioned above. In this review, we aim to highlight and identify some of the cross-sections for the potential utilization of the CAM model for ADSC studies with a focus on wound healing and tissue engineering, as well as oncological research, e.g., sarcomas. Hereby, the focus lies on the combination of existing evidence and experience of such intersections with a potential utilization of the CAM model for further research on ADSCs.

Background The prognosis of patients with anaplastic thyroid cancer (ATC) remains dismal. A small portion of patients experience longterm survival and need to be identified before treatment allocation. Survival scores may guide clinicians making more informed decisions about treatment options and improve the understanding of patients’ prognosis. The aim of this study was to validate two prognostic scores using an independent dataset to analyze which prognostic index is superior in discriminating survival. Methods Thirty-four patients with histologically confirmed ATC diagnosed between January 2009 and December 2019 were consecutively treated at our department and evaluated. Next generation sequencing was performed in 7 (21%) patients, but no druggable mutation was found. 50% of all patients received surgery and 56% were treated with chemoradiotherapy. The median radiation dose in equivalent dose in 2 Gy fractions (EQD2) was 50 Gy (SD:21 Gy). The study compared the discrimination of the Sugitani Prognostic Index (SPI) and the Marchand-Crety Prognostic Score (MCPS) using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 6-month survival. Results The median survival of the entire cohort was 5 months (range: 1-133). The AUC for 6-month survival was 0.85 (95% confidence interval [CI]:0.72–0.97) for SPI and 0.69 (95% CI: 0.56–0.83) for MCPS ( p  < 0.0001). Using the net reclassification index (NRI), 73% of patients were correctly reclassified using SPI instead of MCPS for 6-month survival ( p  = 0.0237). Conclusion The SPI was more accurate than the MCPS to determine patients’ life expectancies and should be recommended for clinical guidance and treatment allocation. In the last decade, comprehensive genetic profiling of actionable mutations in ATC has become vital to guide targeted therapy.

Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact of mechanical processing CELT (Cell-Enriched Lipotransfer) and CELTPLUS and electrical stimulation on the regenerative secretome of human lipoaspirates. qPCR analysis revealed that CELTPLUS processing, which incorporates mechanical intersyringe shifting, significantly doubled the gene expression of nerve growth factor (NGF) (p = 0.015), vascular endothelial growth factor (VEGF) (p = 0.02), and brain-derived neurotrophic factor (BDNF) (p = 0.04) compared to CELT-processed lipoaspirate. Protein analysis via ELISA confirmed a time-dependent secretion of NGF and VEGF over 96 h. Furthermore, 24 h electrical stimulation (2 V) significantly enhanced NGF protein release (p < 0.001). These findings demonstrate that standardized mechanical processing effectively enriches regenerative cell populations and amplifies their neurogenic and angiogenic potential. The additional modulation of growth factor secretion via electrical stimulation highlights the potential of processed adipose tissue as a functional, autologous transplant for enhanced nerve reconstruction.

We conducted a comparative study involving 39 female patients with lipedema and group-matched controls at a ratio of 1:5. The primary survey tool was the German Health Update (GEDA 2019/2020-EHIS) questionnaire, which was developed by the Robert Koch Institute (RKI), Germany. The secondary survey tool was the German Pain Questionnaire. The prevalence of hypertension (p = 0.041) and high blood lipids (p = 0.024) was lower in the lipedema group compared to the control group. General health and well-being indicators demonstrated lower overall health ratings (p < 0.001) and higher physiotherapy use in patients with lipedema (p = 0.016). Mental health assessment revealed higher depression prevalence and severity (p = 0.001), together with a lower number of close contacts (p = 0.032). Furthermore, patients with lipedema experienced higher levels of pain (p < 0.001) and more significant pain-related disability in daily activities (p < 0.001) than controls. Correlation analysis among patients with lipedema showed a positive correlation between pain severity and depressive symptoms (ρ = 0.612, p < 0.001) and a moderate positive correlation with impaired health-related quality of life (ρ = 0.418, p = 0.010). In summary, our findings highlight significant differences in health and well-being between patients with lipedema and matched controls, especially in overall, metabolic, and mental health, as well as pain perception. The findings emphasize the need for a validated lipedema-specific questionnaire and a multidisciplinary treatment approach with a combination of physical therapies, lifestyle adjustments, and psychological strategies.

Anaplastic thyroid carcinoma (ATC) is associated with a poor prognosis due to aggressive tumor growth and high treatment resistance. Hypofractionated treatment concepts may be more effective and less time consuming compared to normofractionated radiotherapy (RT). In this retrospective study, we aim to evaluate the outcome of hypofractionated regimens and perform a systematic review concerning hypofractionated RT and pooled analysis of this treatment modality. A systematic review using the MEDLINE/Pubmed and Cochrane databases was performed. Data from all eligible studies were extracted, and a pooled analysis of literature and our cohort (n = 60) was carried out to examine patient characteristics, toxicity, and outcomes of patients with ATC. As a result, median overall survival (OS) of the single center cohort was four (range 1–12) months. Survival rates at one, three, and six months were 82%, 55%, and 36%, respectively. In univariate analyses, multimodal treatment (p = 0.006) and gender (p = 0.04) were correlated with an improved OS. Six studies with a total number of 152 patients undergoing hypofractionated RT treatment were analyzed. The pooled analysis included four patient cohorts with 60 patients and showed median OS of 5.3 (range: 1–24) months. Multimodal treatment (p < 0.001) and a cumulative radiation dose ≥50 Gy in equivalent dose in 2 Gy fractions (EQD2) (p = 0.014) correlated with an improved OS. On multivariate analysis, multimodal treatment (p = 0.003, hazard ratio (HR): 0.636, 95% confidence interval (CI): 0.469–0.861) was an independent predictor for longer OS. After propensity score matching (PSM), hypofractionated RT appears to be non-inferior compared to normofractionated RT concerning OS. In conclusion, hypofractionated RT is effective with manageable toxicity. A dose escalation with ≥50 Gy (EQD2) correlated with a longer OS. Hypofractionated RT could be an integral part in multimodal treatment with a promising outcome.

Background: Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer’s growth and spread. Methods: The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer. Results: Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases. Conclusions: The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.

Metastatic anaplastic thyroid cancer is associated with a dismal prognosis. We evaluated outcome and prognostic factors in patients receiving radiation to the primary tumor in metastatic anaplastic thyroid cancer (ATC). All consecutive patients with metastatic ATC (n=20) undergoing irradiation between 2009 and 2019 for anaplastic thyroid cancer were investigated. Median survival time and median progression-free survival were 2 (range=1-22) and 2 (1-20) months. In univariate analyses, surgery, concurrent or sequential chemotherapy and higher radiation dose escalation (>39 Gy) were correlated with longer overall survival (p=0.005, p=0.018 and p=0.038), respectively. Karnofsky performance status >70% showed a trend of longer survival time (p=0.062). Limited metastatic disease, surgery and concurrent/sequential chemotherapy are correlated with longer progression-free survival times (p=0.043, p=0.024 and p=0.039), respectively. Radiation to the primary tumor in metastatic anaplastic thyroid cancer is safe and offers durable local control. Treatment intensification including concurrent or sequential chemotherapy and radiation dose escalation were associated with longer survival rates and should be considered in selected patients with metastatic disease.

Background/Objectives: Prophylactic mastectomy can significantly reduce the risk of breast cancer in patients carrying gene mutations such as BRCA1 and BRCA2. Patients who opt for breast removal are offered tailored reconstructive options based on their medical history and prior treatments, and in these often young patients with limited autologous tissue reserves, implant-based reconstruction is frequently the option of choice. Complication rates of these procedures are relatively high and account for up to 30%. Subcutaneous mastectomy with primary implant reconstruction carries risks such as hematoma, seroma, skin necrosis, necrosis of the nipple–areola complex, and wound healing issues, which may necessitate revision surgery. This university-center retrospective analysis aims to improve outcomes by identifying patient- and surgery-related risk factors associated with postoperative complications in allogenic breast reconstruction following subcutaneous mastectomy. Methods: We analyzed 61 female patients and 122 breasts who underwent primary implant-based reconstruction after skin- or nipple-sparing subcutaneous mastectomy over three years between January 2021 and December 2023. Demographic and surgical variables were systematically collected and analyzed. Results: The mean patient age was 41.5 ± 10.3 years. A total of 13% of patients were active smokers, and 1.6% had diabetes mellitus. Overall, skin flap necrosis occurred in 27.9% of patients (22.1% of breasts), wound healing disorders in 19.7% of patients, wound infections in 9.8%, and revision surgery in 18.0%. A history of pregnancy was associated with skin flap necrosis (OR 10.07, 95% CI 1.79–190.06; p = 0.032); however, this finding must be interpreted with caution due to limited statistical power and model instability. Conclusions: This investigation revealed clinically relevant patterns suggesting potential risk factors for wound healing disorders and skin necrosis. Prospective studies are planned to further substantiate these findings and to help reduce overall complication rates associated with the procedure.