Development of a cellular assay as a personalized model for testing chronic wound therapeutics.

Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.

The Vascularized Fibula as Salvage Procedure in Extremity Reconstruction: A Retrospective Analysis of Time to Heal and Possible Confounders.

The vascularized fibula transfer is a well-established technique for extremity reconstruction, but operative planning and patient selection remains crucial. Although recently developed techniques for bone reconstruction, such as bone segment transfer, are becoming increasingly popular, bone defects may still require vascularized bone grafts under certain circumstances. In this study, 41 cases, 28 (68%) men and 13 (32%) women (median age: 40 years), were retrospectively analyzed. Therapy-specific data (flap vascularity [free vs. pedicled] size in cm and configuration [single- vs. double-barrel], mode of fixation [internal/external]) and potential risk factors were ascertained. Indications for reconstruction were osteomyelitis at host site (n = 23, 55%), pseudarthrosis (n = 8, 20%), congenital deformity (n = 6, 15%), traumatic defect, and giant cell tumor of the bone (n = 2, 5% each). Complete healing occurred in 34 (83%) patients after a median time of 6 months. Confounders for prolonged healing were female gender (p = 0.002), reconstruction in the lower limb (p = 0.011), smoking (p = 0.049), and the use of an external fixator (p = 0.009). Six (15%) patients required secondary limb amputation due to reconstruction failure, and one patient had persistent pseudarthrosis at last follow-up. The only risk factor for amputation assessed via logistic regression analysis was preexisting PAOD (peripheral artery occlusive disease; p = 0.008) The free fibula is a reliable tool for extremity reconstruction in various cases, but time to full osseous integration may exceed six months. Patients should be encouraged to cease smoking as it is a modifiable risk factor.

Management of Severe Burn Wounds Colonized With Multi-resistant Pseudomonas aeruginosa and Fusarium Using Marine Omega3 Wound Matrix in a Female Victim of War.

War-related burns are common injuries, also among the civilian population. Additional trauma such as fractures or shrapnel wounds may add significant morbidity. Burn injuries in war zones are furthermore frequently undertreated and hence prone to complications. We report a case of a young female victim of war, whose severely infected burn wounds could be successfully healed using a combination of targeted antimicrobial therapy, wound conditioning using decellularized fish skin, and subsequent skin grafting.

Undergraduate Skills Training in Pandemic Times: Where Is the Future of Medical Education?

BACKGROUND: The COVID-19 pandemic forced medical programs to rapidly switch to remote teaching from scratch, impacting hands-on skills training. This study compared the efficacy of a hybrid online format to a regular in-person session for a mandatory surgical skills class. METHODS: Third-year undergraduate medical students attending the surgical skills class in the winter semester of 2020/21 at the Medical University of Graz were randomly assigned to either the hybrid or in-person class, depending on their course schedule and government regulations. The hybrid class involved online videos, one-on-one peer tutoring, and an Objective Structured Clinical Examination (OSCE). Pre- and post-class self-assessments were conducted to evaluate their theoretical and practical knowledge of a single interrupted suture. RESULTS: The study included 85 students in the regular in-person class and 50 in the hybrid class. A pre-class assessment revealed higher self-assessments in the hybrid class for theoretical and practical knowledge, but a post-class assessment showed no significant difference. The advantages and disadvantages of both modalities were identified, providing valuable insights for future curriculum development. CONCLUSIONS: Both teaching modes were effective for undergraduate surgical skills training. This study recommends implementing positive aspects of both the hybrid and in-person formats while recognizing their respective limitations.

Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders.

Skin wound healing is essential to health and survival. Consequently, high amounts of research effort have been put into investigating the cellular and molecular components involved in the wound healing process. The use of animal experiments has contributed greatly to the knowledge of wound healing, skin diseases, and the exploration of treatment options. However, in addition to ethical concerns, anatomical and physiological inter-species differences often influence the translatability of animal-based studies. Human in vitro skin models, which include essential cellular and structural components for wound healing analyses, would improve the translatability of results and reduce animal experiments during the preclinical evaluation of novel therapy approaches. In this review, we summarize in vitro approaches, which are used to study wound healing as well as wound healing-pathologies such as chronic wounds, keloids, and hypertrophic scars in a human setting.

Does Electrical Stimulation through Nerve Conduits Improve Peripheral Nerve Regeneration?-A Systematic Review.

BACKGROUND: Peripheral nerve injuries affect over 2% of trauma patients and can lead to severe functional impairment and permanent disability. Autologous nerve transplantation is still the gold standard in the reconstruction of nerve defects. For small defects, conduits can be considered for bridging. Lately, the combined use of conduits and electrical stimulation has gained attention in the treatment of peripheral nerve injury. This review aimed to present the currently available data on this topic. METHODS: PubMed, Embase, Medline and the Cochrane Library were searched for studies on electrical stimulation through nerve conduits for nerve defects in in vivo studies. RESULTS: Fifteen studies fit the inclusion criteria. All of them reported on the application of nerve conduits combined with stimulation for sciatic nerve gaps in rats. Functional, electrophysiological and histological evaluations showed improved nerve regeneration after electrical stimulation. High variation was observed in the treatment protocols. CONCLUSION: Electrically stimulated conduits could improve peripheral nerve regeneration in rat models. The combined application of nerve guidance conduits and electrical stimulation shows promising results and should be further evaluated under standardized conditions.

BMI and Revision Surgery for Abdominoplasties: Complication Definitions Revisited Using the Clavien-Dindo Classification.

After body contouring surgery of the lower trunk (CSLT), the definition, rate (4%-70%), and documentation of complications vary. Objectives: We analyzed the effect of risk factors on the outcome based on the Clavien-Dindo classification (CDC) after CSLT surgery and polled postoperative satisfaction among patients. Methods: All patients undergoing CSLT from 2001 to 2016 were included and were classified according to the CDC for postoperative events. Statistical analysis included proportional odds logistic regression analysis. We polled patients to grade their satisfaction with the postoperative result and whether they would have the operation performed again. Results: A total of 265 patients were included: 60 (22.6%), 25 (9.4%), 28 (10.6%), and 21 (7.9%) were in CDC grades I, II, IIIa, and IIIb, respectively. A high preoperative body mass index significantly increased the odds for a postoperative event requiring revision surgery under general anesthesia (CDC grade IIIb, odds ratio 0.93, 95% confidence interval 0.89-0.97, P = 0.001). One-hundred twenty-eight patients (48.3%) participated in the poll: 101 (78.9%) were either happy or content with the postoperative results, and 117 (91.4%) would have the procedure performed again, including all nine patients with CDC grade IIIb. Conclusions: Our results confirm that a high body mass index is a statistically significant risk factor for requiring major revision surgery after CSLT. Despite being a complication prone intervention, postoperative satisfaction after CSLT was ranked favorably in our sample. We recommend that the CDC be used in all surgical specialties to evaluate complications and permit future comparability of pooled data.

Introducing the "SIMline"-A Simulation Course in the Management of Severe Burns as a Tool in Undergraduate Medical Education.

Background: Management of burn injuries presents a complex and challenging situation for medical staff, especially for inexperienced young doctors. However, training on how to treat burn victims in the clinical setting is rarely taught in undergraduate medical classes. We have created the "SIMline", a simulation training program explicitly designed for coaching medical students in burn management. Methods: A total of 43 students participated in the "SIMline" course, which took place at the training facility at the Medical University of Graz, between 2018 and 2019. The course provided theoretical classes, practical exercises, and a full-scale care process simulation training. The learning progress of the students was monitored via a formative integrated test. Results: Students showed great progress throughout the course of the "SIMline" program, as their test scores improved by an average of 88%. The passing rate was 0% at the first exam (prior to course) as compared to 87% at the final exam, taken after the training. Conclusions: Comprehensive practical training programs in burn care are underrepresented in medical education. The "SIMline" course presents a novel and effective approach in training medical students in burn management. However, follow-up evaluation is necessary to confirm long-term educational benefits.

Suction Drain Volume following Axillary Lymph Node Dissection for Melanoma-When to Remove Drains? A Retrospective Cohort Study.

Postoperative complications such as seroma formation and wound-site infection occur following completion axillary lymph node dissection (ALND) for melanoma. We analyzed the impact of time-to-drain removal and drainage volume on seroma formation after ALND. We retrospectively analyzed data from 118 patients after completion ALND for melanoma. Primary endpoints were daily amount of drainage volume, seroma formation and time-to-drain removal. Secondary endpoints included patient-related, disease-specific and perioperative parameters as well as the number of histologically analyzed lymph nodes and surgical complications graded by the Clavien−Dindo classification (CDCL). Statistical analyses were performed using logistic regression models. Drain removal around the 8th postoperative day was statistically associated with a lower risk for the occurrence of seroma formation (p < 0.001). Patients with an increased drainage volume during the early postoperative days were more prone to develop seroma after drain removal. With 49% (CDCL I and II), most complications were managed conservatively, while only 5.9% (CDCL III) required revision surgery (CDCL overall: 55.9%). ALND is a safe procedure with a low rate of severe CDCL III type of complications. To decrease seroma evacuation, our results imply that drains should be removed around the 8th postoperative day to reduce the risk of infection, readmission or prolonged hospitalization.

In Vivo Models for Hypertrophic Scars-A Systematic Review.

Backgroundand Objectives: Hypertrophic scars following surgeries or burns present a serious concern for many patients because these scars not only lead to an aesthetical but also to a functional and psychological burden. Treatment of hypertrophic scars is challenging because despite various treatment options, a low level of evidence hinders preference of any specific treatment plan. To properly identify new therapeutic approaches, the use of in vivo models remains indispensable. A gold standard for hypertrophic scars has not been established to date. This review aims at giving a comprehensive overview of the available in vivo models. Materials and Methods: PubMed and CINAHL were queried for currently existing models. Results: Models with mice, rats, rabbits, pigs, guinea pigs and dogs are used in hypertrophic scar research. Rodent models provide the advantage of ready availability and low costs, but the number of scars per animal is limited due to their relatively small body surface, leading to a high number of test animals which should be avoided according to the 3Rs. Multiple scars per animal can be created in the guinea pig and rabbit ear model; but like other rodent models, these models exhibit low transferability to human conditions. Pig models show a good transferability, but are cost-intensive and require adequate housing facilities. Further, it is not clear if a currently available pig model can deliver clinical and histological features of human hypertrophic scars concurrently. Conclusions: None of the analyzed animal models can be clearly recommended as a standard model in hypertrophic scar research because the particular research question must be considered to elect a suitable model.

The Impact of Prolonged Inflammation on Wound Healing.

The treatment of chronic wounds still challenges modern medicine because of these wounds' heterogenic pathophysiology. Processes such as inflammation, ischemia and bacterial infection play major roles in the progression of a chronic wound. In recent years, preclinical wound models have been used to understand the underlying processes of chronic wound formation. However, the wound models used to investigate chronic wounds often lack translatability from preclinical models to patients, and often do not take exaggerated inflammation into consideration. Therefore, we aimed to investigate prolonged inflammation in a porcine wound model by using resiquimod, a TLR7 and TLR8 agonist. Pigs received full thickness excisional wounds, where resiquimod was applied daily for 6 days, and untreated wounds served as controls. Dressing change, visual documentation and wound scoring were performed daily. Biopsies were collected for histological as well as gene expression analysis. Resiquimod application on full thickness wounds induced a visible inflammation of wounds, resulting in delayed wound healing compared to non-treated control wounds. Gene expression analysis revealed high levels of IL6, MMP1 and CD68 expression after resiquimod application, and histological analysis showed increased immune cell infiltration. By using resiquimod, we were able to show that prolonged inflammation delayed wound healing, which is often observed in chronic wounds in patients. The model we used shows the importance of inflammation in wound healing and gives an insight into the progression of chronic wounds.