Integrating AI in Lipedema Management: Assessing the Efficacy of GPT-4 as a Consultation Assistant.

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI's Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4's responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4's responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Association between Donor Age and Osteogenic Potential of Human Adipose Stem Cells in Bone Tissue Engineering.

Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population, and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods.

Free Transplantation of a Tissue Engineered Bone Graft into an Irradiated, Critical-Size Femoral Defect in Rats.

Healing of large bone defects remains a challenge in reconstructive surgery, especially with impaired healing potential due to severe trauma, infection or irradiation. In vivo studies are often performed in healthy animals, which might not accurately reflect the situation in clinical cases. In the present study, we successfully combined a critical-sized femoral defect model with an ionizing radiation protocol in rats. To support bone healing, tissue-engineered constructs were transferred into the defect after ectopic preossification and prevascularization. The combination of SiHA, MSCs and BMP-2 resulted in the significant ectopic formation of bone tissue, which can easily be transferred by means of our custom-made titanium chamber. Implanted osteogenic MSCs survived in vivo for a total of 18 weeks. The use of SiHA alone did not lead to bone formation after ectopic implantation. Analysis of gene expression showed early osteoblast differentiation and a hypoxic and inflammatory environment in implanted constructs. Irradiation led to impaired bone healing, decreased vascularization and lower short-term survival of implanted cells. We conclude that our model is highly valuable for the investigation of bone healing and tissue engineering in pre-damaged tissue and that healing of bone defects can be substantially supported by combining SiHA, MSCs and BMP-2.

Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In Vivo Bone Tissue Engineering.

Alginate dialdehyde (ADA), gelatin, and nano-scaled bioactive glass (nBG) particles are being currently investigated for their potential use as three-dimensional scaffolding materials for bone tissue engineering. ADA and gelatin provide a three-dimensional scaffold with properties supporting cell adhesion and proliferation. Combined with nanocristalline BG, this composition closely mimics the mineral phase of bone. In the present study, rat bone marrow derived mesenchymal stem cells (MSCs), commonly used as an osteogenic cell source, were evaluated after encapsulation into ADA-gelatin hydrogel with and without nBG. High cell survival was found in vitro for up to 28 days with or without addition of nBG assessed by calcein staining, proving the cell-friendly encapsulation process. After subcutaneous implantation into rats, survival was assessed by DAPI/TUNEL fluorescence staining. Hematoxylin-eosin staining and immunohistochemical staining for the macrophage marker ED1 (CD68) and the endothelial cell marker lectin were used to evaluate immune reaction and vascularization. After in vivo implantation, high cell survival was found after 1 week, with a notable decrease after 4 weeks. Immune reaction was very mild, proving the biocompatibility of the material. Angiogenesis in implanted constructs was significantly improved by cell encapsulation, compared to cell-free beads, as the implanted MSCs were able to attract endothelial cells. Constructs with nBG showed higher numbers of vital MSCs and lectin positive endothelial cells, thus showing a higher degree of angiogenesis, although this difference was not significant. These results support the use of ADA/gelatin/nBG as a scaffold and of MSCs as a source of osteogenic cells for bone tissue engineering. Future studies should however improve long term cell survival and focus on differentiation potential of encapsulated cells in vivo.

Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate-Based Scaffolds.

Vascularization of bioartificial tissues can be significantly enhanced by the generation of an arteriovenous (AV) loop. Besides the surgical vascularization, the choice of the scaffold and the applied cells are indispensable cofactors. The combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem cells (MSCs) is a promising approach with regard to biocompatibility, biodegradation, as well as de novo tissue formation. In this study, we targeted the investigation of the vascularization of ADA-GEL with and in the absence of encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL microcapsules was placed in the groin of Lewis rats and an AV loop was placed into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B contained 2 × 106 DiI-labeled MSCs/mL ADA-GEL. Four weeks postoperatively, tissue formation and vascularization were investigated by histology and microcomputed tomography. We were able to prove vascularization originating from the AV loop in both groups with statistically significant more vessels in group B containing MSCs. Moreover, encapsulated MSCs promoted biodegradation of the ADA-GEL microcapsules. In the present study, we were able to demonstrate for the first time, the successful vascularization of ADA-GEL microcapsules by means of the AV loop. Furthermore, ADA-GEL displayed a good biocompatibility and encapsulation of MSCs into ADA-GEL microcapsule-enhanced vascularization as well as biodegradation.

Influence of Different Irradiation Protocols on Vascularization and Bone Formation Parameters in Rat Femora.

Aim of the present study was the establishment of an efficient and reproducible model for irradiation of rat femora as a model for impaired osteogenesis and angiogenesis. Four different irradiation protocols were compared: single irradiation of the left femur with 20 Gy and explantation after 4 or 8 weeks (group A, B) and three irradiation fractions at 3-4 days intervals with 10 Gy and explantation after 4 or 8 weeks (group C, D). The contralateral, unirradiated femur served as control. Evaluation included histology, microcomputertomography (µCT), and real-time polymerase chain reaction. Histology showed a pronounced increase of vacuoles in bone marrow after irradiation, especially after 4 weeks (group A and C), demonstrating bone marrow edema and fatty degeneration. Irradiation provoked a decrease of total cell numbers in cortical bone and of hypoxia-inducible factor 1 alpha (HIF1α)-positive cells in bone marrow. The expression of several markers (osteocalcin [OCN], runt-related transcription factor 2 [RUNX2], transforming growth factor beta 1 [TGFß1], tumor necrosis factor alpha [TNFα], vascular endothelial growth factor A [VEGFA], and HIF1α) was decreased in group A after irradiation. This might suggest a decreased metabolism after irradiation. A significant decrease in small-sized vessels was seen in µCT evaluation in group A and D. Single irradiation with 20 Gy had the most severe and reproducible impact on osteogenesis and angiogenesis after 4 weeks while being well tolerated by all animals, thus making it an excellent model for evaluation of bone healing and vascularization in irradiated tissue.