Artificial Intelligence-Powered Hand Surgery Consultation: GPT-4 as an Assistant in a Hand Surgery Outpatient Clinic.

PURPOSE: Exploring the integration of artificial intelligence in clinical settings, this study examined the feasibility of using Generative Pretrained Transformer 4 (GPT-4), a large language model, as a consultation assistant in a hand surgery outpatient clinic. METHODS: The study involved 10 simulated patient scenarios with common hand conditions, where GPT-4, enhanced through specific prompt engineering techniques, conducted medical history interviews, and assisted in diagnostic processes. A panel of expert hand surgeons, each board-certified in hand surgery, evaluated GPT-4's responses using a Likert Scale across five criteria with scores ranging from 1 (lowest) to 5 (highest). RESULTS: Generative Pretrained Transformer 4 achieved an average score of 4.6, reflecting good performance in documenting a medical history, as evaluated by the hand surgeons. CONCLUSIONS: These findings suggest that GPT-4 can effectively document medical histories to meet the standards of hand surgeons in a simulated environment. The findings indicate potential for future application in patient care, but the actual performance of GPT-4 in real clinical settings remains to be investigated. CLINICAL RELEVANCE: This study provides a preliminary indication that GPT-4 could be a useful consultation assistant in a hand surgery outpatient clinic, but further research is required to explore its reliability and practicality in actual practice.

Specific features of ex-obese patients significantly influence the functional cell properties of adipose-derived stromal cells.

Adipose-derived stromal cells (ADSC) are increasingly used in clinical applications due to their regenerative capabilities. However, ADSC therapies show variable results. This study analysed the effects of specific factors of ex-obese patients on ADSC functions. ADSC were harvested from abdominal tissues (N = 20) after massive weight loss. Patients were grouped according to age, sex, current and maximum body mass index (BMI), BMI difference, weight loss method, smoking and infection at the surgical site. ADSC surface markers, viability, migration, transmigration, sprouting, differentiation potential, cytokine secretion, telomere length and mtDNA copy number were analysed. All ADSC expressed CD73, CD90, CD105, while functional properties differed significantly among patients. A high BMI difference due to massive weight loss was negatively correlated with ADSC proliferation, migration and transmigration, while age, sex or weight loss method had a smaller effect. ADSC from female and younger donors and individuals after weight loss by increase of exercise and diet change had a higher activity. Telomere length, mtDNA copy number, differentiation potential and the secretome did not correlate with patient factors or cell function. Therefore, we suggest that factors such as age, sex, increase of exercise and especially weight loss should be considered for patient selection and planning of regenerative therapies.

Human adipose-derived stem cells support lymphangiogenesis in vitro by secretion of lymphangiogenic factors.

Lymphedema is a chronic progressive disease ultimately resulting in severe, disfiguring swelling and permanent changes of the affected tissues. Presently, there is no causal treatment approach of lymphedema. Therefore, most therapies are purely symptomatic. However, the recent use of stem cell-based therapies has offered new prospects for alternative treatment options. The present study was performed to investigate the effects of human adipose-derived stem cells (ADSCs) on human dermal lymphatic endothelial cells (HDLECs) in terms of basic in vitro lymphangiogenic assays (WST-8 assay, scratch assay, transmigration assay, sprouting assay, tube formation assay). The influence of ADSC-conditioned medium (ADSC-CM) on HDLECs was compared to recombinant VEGF-C, bFGF and HGF. Further ADSC-CM was characterized by protein microarray and enzyme-linked immunosorbent assay (ELISA). Although key-lymphangiogenic growth factors - like VEGF-C - could only be detected in low concentrations within the conditioned medium (CM), HDLECs were potently stimulated to proliferate, migrate and to form tube like structures by ADSC-CM. Despite concentrations more than hundredfold higher than those found in the conditioned medium, stimulation with recombinant VEGF-C, bFGF and HGF was still weaker compared to ADSC-CM. These results highlight the effectiveness of growth factors secreted by ADSC to stimulate HDLEC, potentially providing a promising new therapeutic approach for the treatment of lymphedema.

Plastic Surgery Reconstruction of Chronic/Non-Healing Wounds.

In western countries, approximately 1 % of individuals are affected by chronic wounds during their lifetime. Due to changing demographics, this incidence will likely increase in the future. Additionally, the high prevalence is accompanied by substantial treatment expenditures. Therefore, it is of global interest to find effective treatment algorithms. In this article, we present up-to-date solutions for treating chronic / difficult to heal and complex wounds by means of plastic and reconstructive surgery. We outline the principles of chronic wounds and how to perform an appropriate diagnosis. Close cooperation and interdisciplinary exchange are important for optimizing treatment. We report the principles of wound debridement and the role of negative pressure wound therapy. Moreover, we discuss the state of the art of defect reconstruction by means of skin grafting, with or without acellular dermal matrices, local tissue transfers and free tissue transfers. In very complex cases, the local macrovascular blood flow is greatly reduced and there are few, if any, recipient vessels for free flap reconstruction. We discuss the role of arteriovenous loops to overcome this problem.

Proangiogenic effects of tumor cells on endothelial progenitor cells vary with tumor type in an in vitro and in vivo rat model.

Endothelial progenitor cells (EPCs) contribute to neovascularization in tumors. However, the relationship of EPCs and tumor-induced angiogenesis still remains to be clarified. The present study aimed at investigating the influence of 4 different tumor types on angiogenic properties of EPCs in an in vitro and in vivo rat model. It could be demonstrated that in vitro proliferation, migration, and angiogenic abilities and genetic modifications of EPCs are controlled in a tumor-type-dependent manner. The proangiogenic effect of mammary carcinoma, osteosarcoma, and rhabdomyosarcoma cells was more pronounced compared to colon carcinoma cells. Coinjection of encapsulated tumor cells, especially mammary carcinoma cells, and EPCs in a rat model confirmed a contributing effect of EPCs in tumor vascularization. Cytokines secreted by tumors such as monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and TNF-related apoptosis-inducing ligand play a pivotal role in the tumor cell-EPC interaction, leading to enhanced migration and angiogenesis. With the present study, we were able to decipher possible underlying mechanisms by which EPCs are stimulated by tumor cells and contribute to tumor vascularization. The present study will contribute to a better understanding of tumor-induced vascularization, thus facilitating the development of therapeutic strategies targeting tumor-EPC interactions.-An, R., Schmid, R., Klausing, A., Robering, J. W., Weber, M., Bäuerle, T., Detsch, R., Boccaccini, A. R., Horch, R. E., Boos, A. M., Weigand, A. Proangiogenic effects of tumor cells on endothelial progenitor cells vary with tumor type in an in vitro and in vivo rat model.

The potential role of telocytes in Tissue Engineering and Regenerative Medicine.

Research and ideas for potential applications in the field of Tissue Engineering (TE) and Regenerative Medicine (RM) have been constantly increasing over recent years, basically driven by the fundamental human dream of repairing and regenerating lost tissue and organ functions. The basic idea of TE is to combine cells with putative stem cell properties with extracellular matrix components, growth factors and supporting matrices to achieve independently growing tissue. As a side effect, in the past years, more insights have been gained into cell-cell interaction and how to manipulate cell behavior. However, to date the ideal cell source has still to be found. Apart from commonly known various stem cell sources, telocytes (TC) have recently attracted increasing attention because they might play a potential role for TE and RM. It becomes increasingly evident that TC provide a regenerative potential and act in cellular communication through their network-forming telopodes. While TE in vitro experiments can be the first step, the key for elucidating their regenerative role will be the investigation of the interaction of TC with the surrounding tissue. For later clinical applications further steps have to include an upscaling process of vascularization of engineered tissue. Arteriovenous loop models to vascularize such constructs provide an ideal platform for preclinical testing of future therapeutic concepts in RM. The following review article should give an overview of what is known so far about the potential role of TC in TE and RM.

Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells.

Lymphatic metastasis is one of the main prognostic factors concerning long-term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF-C, bFGF, MSC-conditioned medium (MSC-CM) or by co-culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary-like structures was assessed by a tube formation assay on Matrigel® . The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC-CM and by co-culture with MSC. The effect of stimulation with MSC-CM was stronger compared to stimulation with the growth factors VEGF-C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF-C, bFGF and by MSC-CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.

Myogenic differentiation of primary myoblasts and mesenchymal stromal cells under serum-free conditions on PCL-collagen I-nanoscaffolds.

BACKGROUND: The creation of functional skeletal muscle via tissue engineering holds great promise without sacrificing healthy donor tissue. Different cell types have been investigated regarding their myogenic differentiation potential under the influence of various media supplemented with growth factors. Yet, most cell cultures include the use of animal sera, which raises safety concerns and might lead to variances in results. Electrospun nanoscaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability. We therefore aimed to develop a serum-free myogenic differentiation medium for the co-culture of primary myoblasts (Mb) and mesenchymal stromal cells derived from the bone marrow (BMSC) and adipose tissue (ADSC) on electrospun poly-ε-caprolacton (PCL)-collagen I-nanofibers. RESULTS: Rat Mb were co-cultured with rat BMSC (BMSC/Mb) or ADSC (ADSC/Mb) two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-nanofibers. Differentiation media contained either AIM V, AIM V and Ultroser® G, DMEM/Ham's F12 and Ultroser® G, or donor horse serum (DHS) as a conventional differentiation medium. In 2D co-culture groups, highest upregulation of myogenic markers could be induced by serum-free medium containing DMEM/Ham's F12 and Ultroser® G (group 3) after 7 days. Alpha actinin skeletal muscle 2 (ACTN2) was upregulated 3.3-fold for ADSC/Mb and 1.7-fold for BMSC/Mb after myogenic induction by group 3 serum-free medium when compared to stimulation with DHS. Myogenin (MYOG) was upregulated 5.2-fold in ADSC/Mb and 2.1-fold in BMSC/Mb. On PCL-collagen I-nanoscaffolds, ADSC showed a higher cell viability compared to BMSC in co-culture with Mb. Myosin heavy chain 2, ACTN2, and MYOG as late myogenic markers, showed higher gene expression after long term stimulation with DHS compared to serum-free stimulation, especially in BMSC/Mb co-cultures. Immunocytochemical staining with myosin heavy chain verified the presence of a contractile apparatus under both serum free and standard differentiation conditions. CONCLUSIONS: In this study, we were able to myogenically differentiate mesenchymal stromal cells with myoblasts on PCL-collagen I-nanoscaffolds in a serum-free medium. Our results show that this setting can be used for skeletal muscle tissue engineering, applicable to future clinical applications since no xenogenous substances were used.

ADSCs and adipocytes are the main producers in the autotaxin-lysophosphatidic acid axis of breast cancer and healthy mammary tissue in vitro.

BACKGROUND: Breast cancer is the most common malignancy in women affecting one out of eight females throughout their lives. Autotaxin (ATX) is upregulated in breast cancer which results in increased lysophosphatidic acid (LPA) formation within the tumor. This study's aim was to identify the role of different mammary cell populations within the ATX-LPA axis. METHODS: Epithelial-cell-adhesion-molecule-positive (EpCAM) and -negative cells from breast tumors, adipose-derived stem cells (ADSCs) of tumor-adjacent and tumor-distant mammary fat were isolated and compared to healthy ADSCs, mammary epithelial cells (HMECs), and mesenchymal cells (MES) of healthy mammary tissue (n = 4 each) and further to well-established breast (cancer) cell lines. RESULTS: mRNA expression analyses revealed that ADSCs and MES largely expressed LPA receptor 1 (LPAR1) while epithelial cells mainly expressed LPAR6. LPA 18:1 activated all the cell populations and cell lines by rise in cytosolic free calcium concentrations. MES and ADSCs expressed ATX whereas epithelial cells did not. ADSCs revealed the highest expression in ATX with a significant decline after adipogenic differentiation in healthy ADSCs, whereas ATX expression increased in ADSCs from tumor patients. Breast (cancer) cell lines did not express ATX. Transmigration of MES was stimulated by LPA whereas an inhibitory effect was observed in epithelial cells with no differences between tumors and healthy cells. Triple-negative breast cancer (TNBC) cell lines were also stimulated and the transmigration partly inhibited using the LPA receptor antagonist Ki16425. CONCLUSIONS: We here show that each mammary cell population plays a different role in the ATX-LPA axis with ADSCs and adipocytes being the main source of ATX in tumor patients in our experimental setting. Inhibitors of this axis may therefore present a valuable target for pharmacological therapies.

Reconstruction of composite defects of the scalp and neurocranium-a treatment algorithm from local flaps to combined AV loop free flap reconstruction.

BACKGROUND: Reconstruction of cranial composite defects, including all layers of the scalp and the neurocranium, poses an interdisciplinary challenge. Especially after multiple previous operations and/or radiation therapy, sufficient reconstruction is often only possible using microsurgical free flap transplantation. The aim of this study was to analyze the therapy of interdisciplinary cases with composite defects including the scalp and neurocranium. METHODS: From 2009 to 2017, 23 patients with 18 free flaps and 10 pedicled/local flaps were analyzed. First choices for free flaps were muscle flaps followed by fasciocutaneous flaps. RESULTS: Except for four patients, a stable coverage could be reached in the first operation. Three of these patients received a local scalp rotation flap in the first operation and needed an additional free flap because the local flap was no longer sufficient for coverage after wound healing deficiency or tumor relapse. The superficial temporal artery or external carotid artery served as recipient vessels. In special cases, venous grafts or an arteriovenous loop (AV loop) were used as extensions for the recipient vessels. CONCLUSIONS: In summary, an interdisciplinary approach with radical debridement of infected or necrotic tissue and the reconstruction of the dura mater are essential to reach a stable, long-lasting reconstructive result. Based on our experience, free flaps seem to be the first choice for patients after multiple previous operations and/or radiation therapy.

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue.

BACKGROUND: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. SUMMARY: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.

Management of extremely hard-to-heal extremity wounds with severe life-threatening complications.

The introduction of neoadjuvant radiotherapy has allowed limb-preserving surgical treatment in patients with extremity soft tissue sarcoma, and the overall prognosis of this approach is similar to that of limb amputation. The benefits of this treatment, however, are often accompanied with a higher risk of major complications and blood vessel damage because of radiation-induced inflammation and necrosis of the vessel wall. In particular, it is associated with the rupture of large vessels like the femoral artery and more severe complications of wounds located in the proximal lower extremity. We present a series of four patients with soft tissue sarcoma of the thigh undergoing tumour removal and reconstruction of the defect after neoadjuvant radiotherapy. The post-operative outcome depended on the total dose of radiation used as well as the closing technique of the resulting wound. Major wound complications occurred when the irradiated skin was closed directly over the resection cavity or when local skin flaps were used. In one case, severe radiation-induced life-threatening multiple bleeding events occurred, which led to multiple flap failures. Even if the skin cover is not a problem, we propose a combined interdisciplinary approach involving immediate plastic surgical transfer of healthy, well-vascularised tissue into a defect resulting from oncological resection of sarcoma of the lower extremity following neoadjuvant radiotherapy in order to avoid secondary wound breakdown and severe bleeding complications.

Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells.

BACKGROUND: There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. METHODS: A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. RESULTS: Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. CONCLUSION: Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.

The Potential Role of Telocytes for Tissue Engineering and Regenerative Medicine.

Despite recent advances in surgery, medicine and anaesthesiology as well as the development of microsurgical tissue transplantation, wear out of body parts remains a problem, and organ shortage does not allow to allocate enough donor organs for patients with vital diseases and conditions. The idea to create spare parts or spare organs from the patients own cells by combining engineering approaches to cellular and molecular medicine for th purpose of Tissue Engineering (TE) was fascinating when popularized in the early 1990ies. However clinically success was limited, mainly because of a lack in rapid vascularization of large scale TE replacement constructs useful for clinical purposes. The idea to utilize cells and cytokines to aid the human organism in gradually restoring lost tissue functions has drawn attention to the wider field of Regenerative Medicine (RM). Stem cells and putative stem cells, such as the recently discovered and meanwhile well described interstitial Telocytes, which are comprised of extremely long and thin prolongations named telopodes, may well become active players in the regenerative process. This article highlights the principles of TE and RM and the potential role of Telocytes with regard to tissue regeneration.

A novel early precursor cell population from rat bone marrow promotes angiogenesis in vitro.

BACKGROUND: Some studies demonstrated therapeutic angiogenesis attributable to the effects of endothelial progenitor cells (EPC), others have reported disappointing results. This may be due to the fact that EPC populations used in these contradictory studies were selected and defined by highly variable and differing experimental protocols. Indeed, the isolation and reliable characterization of ex vivo differentiated EPC raises considerable problems due to the fact there is no biomarker currently available to specifically identify EPC exclusively. On the other hand traditional differentiation of primary immature bone marrow cells towards the endothelial lineage is a time-consuming process of up to 5 weeks. To circumvent these shortcomings, we herein describe a facile method to isolate and enrich a primary cell population from rat bone marrow, combining differential attachment methodology with cell sorting technology. RESULTS: The combination of these techniques enabled us to obtain a pure population of early endothelial precursor cells that show homogenous upregulation of CD31 and VEGF-R2 and that are positive for CD146. These cells exhibited typical sprouting on Matrigel™. Additionally, this population displayed endothelial tube formation when resuspended in Matrigel™ as well as in fibrin glue, demonstrating its functional angiogenic capacity. Moreover, these cells stained positive for DiI-ac-LDL and FITC-UEA, two markers that are commonly considered to stain differentiating EPCs. Based upon these observations in this study we describe a novel and time-saving method for obtaining a pure endothelial precursor cell population as early as 2-3 weeks post isolation that exhibits endothelial abilities in vitro and which still might have retained its early endothelial lineage properties. CONCLUSION: The rapid isolation and the high angiogenic potential of these syngeneic cells might facilitate and accelerate the pre-vascularization of transplanted tissues and organs also in a human setting in the future.

PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat.

BACKGROUND: The Arterovenous Loop (AV Loop) model is a vascularization model in tissue engineering research, which is capable of generating a three dimensional in vivo unit with cells as well as the supporting vessels within an isolation chmaber. In our previous studies the AV loop in the isolation chamber was discovered to undergo hypoxia, characterized by Hypoxia Inducible Factor (HIF) up-regulation. The vascularization followed the increase of HIF-α temporally, while it was spatially positively correlated with the HIF-α level, as well. This study aims to prove that HIF-1a up-regulation is the stimulus for vascularization in the AV loop model. METHOD: The AV loop model in rats was created by interposing a femoral vein graft into the distal ends of the contralateral femoral artery and vein, and the loop was embeded in fibrin matrix and fixed in isolation chamber. PHD (prolyl hydroxylases) inhibitor DMOG (Dimethyloxallyl Glycine) was applied systemically in the rats in 40 mg/KG at day 0 and day 3 (DMOG-1), or in 15 mg/KG at day 8, day10 and day12 (DMOG-2). Two weeks later the specimens were explanted and underwent morphological and molecular evaluations. RESULTS: Compared to the control group, in the DMOG-2 group the HIF-1α positive rate was siginicantly raised as shown in immunohistochemistry staining, accompanied with a smaller cross section area and greater vessel density, and a HIF-1α accumulation in the kidney. The mRNA of HIF-1α and its angiogenic target gene all increased in different extends. Ki67 IHC demostrate more positive cells. There were no significant change in the DMOG-1 group. CONCLUSION: By applying DMOG systemically, HIF-1α was up-regulated at the protein level and at the mRNA level, acompanied with angiogenic target gene up-regulateion, and the vascularization was promoted correspondingly. DMOG given at lower dosage constantly after one week tends to have better effect than the group given at larger dosage in the early stage in this model, and promotes cell proliferation, as evidenced by Ki67 IHC. Thus, this study proves that HIF-1a up-regulation is the stimulus for vascularization in the AV loop model and that the process of the vessel outgrowth can be controlled in the AV Loop model utilizing this mechanism.

Factors influencing surgical care and outcome of pediatric burn injuries and the use of synthetic skin substitutes.

Burn trauma is one of the most common causes of inpatient treatment in children and is associated with severe physical and psychological consequences. Synthetic skin substitutes are designed to reduce the risk of infection, minimize wound pain, and reduce the frequency of dressing changes. However, data regarding premature detachment of these materials is scarce. The aim of this study was to identify factors associated with early detachment and subsequent consequences for surgical treatment. A retrospective analysis of 392 children with superficial and deep partial thickness burns undergoing inpatient treatment with application of a skin substitute (Suprathel®) was performed. Patient age, wound localization and progression as well as burned total body surface area (TBSA %) were investigated as possible risk factors for early detachment of wound dressings and surgical intervention. Premature material detachement was significantly associated with burn localization (p < 0.001) and correlated with burn depth progression (r = 0.23, < 0.001) and patient age (r = 0.22, < 0.001). Surgical revision after material detachment were required in 13 % of patients. Patient age and burn localization seem to increase the risk of premature material detachement. In addition, we observed increased premature detachment of Suprathel®in areas which elicited higher wound progression rates. Identifying these areas might prove pivotal in the improvement of pediatric burn trauma management.

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.

Cancer research by means of tissue engineering--is there a rationale?

Tissue engineering (TE) has evoked new hopes for the cure of organ failure and tissue loss by creating functional substitutes in the laboratory. Besides various innovations in the context of Regenerative Medicine (RM), TE also provided new technology platforms to study mechanisms of angiogenesis and tumour cell growth as well as potentially tumour cell spreading in cancer research. Recent advances in stem cell technology--including embryonic and adult stem cells and induced pluripotent stem cells--clearly show the need to better understand all relevant mechanisms to control cell growth when such techniques will be administered to patients. Such TE-Cancer research models allow us to investigate the interactions that occur when replicating physiological and pathological conditions during the initial phases of replication, morphogenesis, differentiation and growth under variable given conditions. Tissue microenvironment has been extensively studied in many areas of TE and it plays a crucial role in cell signalling and regulation of normal and malignant cell functions. This article is intended to give an overview on some of the most recent developments and possible applications of TE and RM methods with regard to the improvement of cancer research with TE platforms. The synthesis of TE with innovative methods of molecular biology and stem-cell technology may help investigate and potentially modulate principal phenomena of tumour growth and spreading, as well as tumour-related angiogenesis. In the future, these models have the potential to investigate the optimal materials, culture conditions and material structure to propagate tumour growth.

New aspects on efficient anticoagulation and antiplatelet strategies in sheep.

BACKGROUND: After addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages. RESULTS: Responses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid). CONCLUSION: High dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in sheep. Efficient anticoagulation can be ensured using sodium enoxaparin rather than dabigatran etexilate in age-dependent dosages. The findings of this study significantly contribute to the improvement of a safe and reliable prophylaxis for thromboembolic events in sheep. Applying these results in future translational experimental studies may help to avoid early dropouts due to thromboembolic events and associated unnecessary high animal numbers.