Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells.

INTRODUCTION: Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA. MATERIALS AND METHODS: Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways. RESULTS: Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control. CONCLUSION: LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antiseptic management of critical wounds: differential bacterial response upon exposure to antiseptics and first insights into antiseptic/phage interactions - experimental studies.

BACKGROUND: With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice. MATERIALS AND METHODS: We exposed clinical isolates foremost of chronic wounds in vitro to dilutions of two antisepctics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating. RESULTS: Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus. Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a two-fold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA, opgH and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation. CONCLUSION: Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment which may be particularly beneficial for the management of critical wounds.

Risk of Heart Disease in Patients With Amputation: A Nationwide Cohort Study in South Korea.

BACKGROUND: Amputation confers disabilities upon patients and is linked to substantial morbidity and death attributed to heart disease. While some studies have focused on traumatic amputees in veterans, few studies have focused on traumatic amputees within the general population. Therefore, the present study aimed to assess the risk of heart disease in patients with traumatic amputation with disability within the general population using a large-scale nationwide population-based cohort. METHODS AND RESULTS: We used data from the Korean National Health Insurance System. A total of 22 950 participants with amputation were selected with 1:3 age, sex-matched controls between 2010 and 2018. We used Cox proportional hazard models to calculate the risk of myocardial infarction, heart failure, and atrial fibrillation among amputees. Participants with amputation had a higher risk of myocardial infarction (adjusted hazard ratio [aHR], 1.30 [95% CI, 1.14-1.47]), heart failure (aHR, 1.27 [95% CI, 1.17-1.38]), and atrial fibrillation (aHR, 1.17 [95% CI, 1.03-1.33]). The risks of myocardial infarction and heart failure were further increased by the presence of disability (aHR, 1.43 [95% CI, 1.04-1.95]; and aHR, 1.38 [95% CI, 1.13-1.67], respectively). CONCLUSIONS: We demonstrate an increased risk of myocardial infarction, heart failure, and atrial fibrillation among individuals with amputation, and the risk further increased in those with disabilities. Clinicians should pay attention to the increased risk for heart disease in patients with amputation.

Diabetes severity and the risk of depression: A nationwide population-based study.

BACKGROUND: In consideration of the substantial occurrence rates of diabetes mellitus (DM) and depression, it is imperative to identify patients with DM who are at an elevated risk of developing depression. Accordingly, this study aimed to examine whether the risk of depression escalated proportionally with the severity of diabetes. METHODS: 2,067,017 adults diagnosed with type 2 DM, with the exception of those diagnosed with depression either before or within one year of the index date, were identified from a nationwide population-based cohort in Korea. Severity scores for DM were established based on various factors, including insulin use, DM duration of at least 5 years, use of three or more oral hypoglycemic agents, the presence of chronic kidney disease (CKD), cardiovascular diseases (CVD), or diabetic retinopathy. Each of these attributes was assigned a score of one point for diabetes severity, and their cumulative sum was defined as a diabetes severity score, ranging from 0 to 6. RESULTS: During a median follow-up of 6.2 years, 407,047 cases of major depression were identified. Each component contributing to the DM severity score was significantly associated with an increased risk of depression (all P-values <0.001), with insulin use and the presence of CVD demonstrating the most significant correlation with depression risk. As the DM severity score increased, the risk of depression was observed to significantly escalate (P for trend <0.001). After adjusting for potential confounding variables, the hazard ratios (95% confidence intervals) of depression were 1.15 (1.14-1.16) in 1 point, 1.28 (1.27-1.29) in 2 points, 1.45 (1.43-1.47) in 3 points, 1.70 (1.67-1.73) in 4 points, 1.91 (1.84-1.98) in 5 points, and 2.01 (1.79-2.26) in 6 points, respectively. CONCLUSION: The results of this study indicate that diabetes severity is positively associated with an elevated risk of developing major depression. Based on these findings, it is feasible to consider targeting depression screening efforts towards individuals with higher diabetes severity scores.

Isolated and combined breast augmentation in transgender patients: Multi-institutional insights into early outcomes and risk factors.

BACKGROUND: The increasing demand for gender-affirming surgery (GAS) in transgender and gender-diverse healthcare highlights the importance of breast augmentation surgery (BAS) for transfeminine patients. Despite its significance, there is a lack of research on postoperative outcomes of BAS. METHODS: We analyzed the multi-institutional American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) (2008-2021) database to identify female transgender individuals (TGIs) who underwent BAS surgery, both isolated and combined with concurrent GAS procedures. We evaluated 30-day outcomes, including the incidence of mortality, reoperation, readmission as well as surgical and medical complication occurrence. RESULTS: Of 1699 female TGIs, 92% underwent isolated BAS and 7.7% underwent combined BAS. The mean age and body mass index (BMI) were 36 ± 12 years and 27 ± 6.6 kg/m2, respectively. Isolated BAS showed a 2.8% complication rate, while combined BAS had a higher rate with 9.1%. Specifically, all complications occurred in patients undergoing BAS with concurrent genitourinary surgery (n = 85; 14%), whereas no adverse events were recorded after combined BAS and facial feminization (n = 19) or chondrolaryngoplasty (n = 19). In patients seeking combined BAS, advanced age (p = 0.05) and nicotine abuse (p = 0.004) were identified as risk factors predisposing to adverse events, whereas American Society of Anesthesiology class 1 was found to be protective (p = 0.02). CONCLUSIONS: Isolated BAS in TGIs demonstrates a positive safety profile. Combined surgeries, particularly with genitourinary procedures, pose higher risks. Identifying risk factors such as smoking and advanced age is crucial for patient selection and surgical planning. These findings can aid in refining patient eligibility and inform surgical decision-making for BAS.

Cumulative exposure to hypertriglyceridemia and risk of type 2 diabetes in young adults.

AIM: This study aimed to examine whether cumulative exposure to hypertriglyceridemia is associated with an increased risk of developing type 2 diabetes in young adults. METHODS: The study included 1,840,251 participants aged 20-39 years who had undergonefourconsecutiveannualhealth checkups and had no history of type 2 diabetes. Participants werecategorized into five groups (exposure score 0-4) based on the frequencies of hypertriglyceridemia diagnosis over a four-year period. The primary outcome was newly diagnosed type 2 diabetes. Exploratory analyses were performed for the different subgroups. RESULTS: During a follow-up period of 6.53 years, 40,286 participants developed type 2 diabetes. The cumulative incidence of type 2 diabetes significantly increased with higher exposure scores for hypertriglyceridemia (log-rank test, P < 0.001). The multivariable-adjusted hazard ratios for incident diabetes were 1.674 (95 % CI, 1.619, 1.732), 2.192 (95 % CI, 2.117, 2.269), 2.637 (95 % CI, 2.548, 2.73), and 3.715 (95 % CI, 3.6, 3.834) for participants with scores of 1-4, respectively, compared with those with an exposure score of 0. CONCLUSIONS: In this large-scale prospective cohort study of young adults, cumulative exposure to hypertriglyceridemia was significantly associated with an increased risk of type 2 diabetes, independent of lifestyle-related factors.

Thromboembolic events in burn patients: An analysis of risk factors and different anticoagulants.

BACKGROUND: Burn patients are in a state of activated coagulation, putting them at risk for thromboembolic events. Additionally, certain patient-related factors are associated with an increased risk of thrombus formation. This study aimed to evaluate the incidence of thromboembolic events and identify potential risk factors, including patient characteristics, surgical treatment, anticoagulation strategies, and laboratory parameters. METHODS: A single-centre retrospective cohort study was conducted on all patients with burns treated between 2002 and 2020. Medical reports of patients with and without thromboembolic events were descriptively analysed. The association of time to thromboembolic events with total body surface area (TBSA) was assessed by cause-specific Cox models adjusted for different covariates. The association of time to thromboembolic events with type and dosage of anticoagulants was assessed using a cause-specific Cox proportional hazards model with time-dependent covariates, applied to a matched subset of patients. RESULTS: The incidence of thromboembolic events was 8.1% in a cohort of 642 patients. We found a statistically significant increase in the hazard for thromboembolic events by a factor of 1.02 (95% CI 1.00 to 1.03; P ≤ 0.05) per percent increase in TBSA. We identified former alcohol abuse (HR=2.54, CI 1.33 to 4.84, P = 0.005) and higher body mass index (HR=1.06, 95% CI 1.00 to 1.12, P = 0.046) as potential risk factors for the development of thromboembolic events. We further noted inadequate median anti-Factor-X activity levels and elevated C-reactive protein and procalcitonin levels at the time of the event. CONCLUSION: Our results showed a moderate risk of thromboembolic events among burn patients, underlining the importance of close monitoring with regard to thrombus formation. In particular, patients with higher TBSA, alcohol abuse and BMI may be evaluated more regularly for thromboembolic events. Anti-Factor-X activity levels should be determined regularly and therapy should be adjusted if necessary.

Risk of Depression according to Cumulative Exposure to a Low-Household Income Status in Individuals with Type 2 Diabetes Mellitus: A Nationwide Population- Based Study.

BACKGRUOUND: We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). METHODS: For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). RESULTS: During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. CONCLUSION: Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

GPR55 inhibits the pro-adipogenic activity of anandamide in human adipose stromal cells.

The endocannabinoid anandamide (AEA) stimulates adipogenesis via the cannabinoid receptor CB1 in adipose stromal cells (ASCs). However, AEA interacts also with nonclassical cannabinoid receptors, including transient receptor potential cation channel (TRPV)1 and G protein-coupled receptor (GPR)55. Their roles in AEA mediated adipogenesis of human ASCs have not been investigated. We examined the receptor-expressions by immunostaining on human ASCs and tested their functionality by measuring the expression of immediate early genes (IEGs) related to the transcription factor-complex AP-1 upon exposition to receptor agonists. Cells were stimulated with increasing concentrations of specific ligands to investigate the effects on ASC viability (proliferation and metabolic activity), secretory activity, and AEA mediated differentiation. ASCs expressed both receptors, and their activation suppressed IEG expression. TRPV1 did not affect viability or cytokine secretion. GPR55 decreased proliferation, and it inhibited the release of hepatocyte growth factor. Blocking GPR55 increased the pro-adipogenic activity of AEA. These data suggest that GPR55 functions as negative regulator of cannabinoid mediated pro-adipogenic capacity in ASCs.

Racial disparities in surgical outcomes after mastectomy in 223 000 female breast cancer patients: a retrospective cohort study.

BACKGROUND: Breast cancer mortality and treatment differ across racial groups. It remains unclear whether such disparities are also reflected in perioperative outcomes of breast cancer patients undergoing mastectomy. STUDY DESIGN: The authors reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2021) to identify female patients who underwent mastectomy for oncological purposes. The outcomes were stratified by five racial groups (white, Black/African American, Asian, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) and included 30-day mortality, reoperation, readmission, surgical and medical complications, and non-home discharge. RESULTS: The study population included 222 947 patients, 68% ( n =151 522) of whom were white, 11% ( n =23 987) Black/African American, 5% ( n =11 217) Asian, 0.5% ( n =1198) American Indian/Alaska Native, and 0.5% ( n =1018) Native Hawaiian/Pacific Islander. While 136 690 (61%) patients underwent partial mastectomy, 54 490 (24%) and 31 767 (14%) women received simple and radical mastectomy, respectively. Overall, adverse events occurred in 17 222 (7.7%) patients, the largest portion of which were surgical complications ( n =7246; 3.3%). Multivariable analysis revealed that being of Asian race was protective against perioperative complications [odds ratio (OR)=0.71; P <0.001], whereas American Indian/Alaska Native women were most vulnerable to the complication occurrence (OR=1.41; P <0.001). Black/African American patients had a significantly lower risk of medical (OR=0.59; P <0.001) and surgical complications (OR=0.60; P <0.001) after partial and radical mastectomy, respectively, their likelihood of readmission (OR=1.14; P =0.045) following partial mastectomy was significantly increased. CONCLUSION: The authors identified American Indian/Alaska Native women as particularly vulnerable to complications following mastectomy. Asian patients experienced the lowest rate of complications in the perioperative period. The authors' analyses revealed comparable confounder-adjusted outcomes following partial and complete mastectomy between Black and white races. Their findings call for care equalization in the field of breast cancer surgery.

Lambda Repair: A Novel Repair Technique for Chronic Boutonnière Deformity.

SUMMARY: Correction of a boutonnière deformity is one of the most demanding challenges in hand surgery. Surgical interventions are usually considered when functional use of the finger cannot be obtained after intense hand therapy. The authors introduce their newly described lambda (λ) repair, which is an easy-to-learn, straightforward surgical technique. The method involves an end-to-side tenorrhaphy of the lateral bands, resembling the Greek λ. Patients who underwent a lambda repair were retrospectively evaluated with preoperative and postoperative measurements of proximal interphalangeal (PIP) joint movement. Four patients (two male, two female; median age, 35.5 years) with a median follow-up period of 9.1 months were included. Three patients underwent lambda repairs for isolated boutonnière deformities, and one patient received a vascularized free toe transfer combined with a lambda repair. The preoperative average PIP joint extension lag or deficit was 28.75 degrees and could be reduced to 15 degrees. Preoperative average PIP joint active flexion was 60 degrees, which was improved to 88.75 degrees. No complications were observed. The lambda repair is a new tool in the reconstruction of boutonnière deformity, further expanding the armamentarium of hand surgeons.

The Combination of Mechanically Isolated Stromal Vascular Fraction and Fibrin Hydrogel: A Processing Protocol.

The regenerative potential of adipose-derived stromal cells (ASCs) has gained significant attention in regenerative and translational research. In the past, the extraction of these cells from adipose tissue required a multistep enzyme-based process, resulting in a heterogenous cell mix consisting of ACSs and other cells, which are jointly termed the stromal vascular fraction (SVF). More recently introduced mechanical SVF (mSVF) isolation protocols are less time-consuming and bypass regulatory concerns. We recently proposed a protocol that generates mSVF rich in stromal cells based on a combination of emulsification and centrifugation. One current issue in mSVF application for wound therapy application is the lack of a scaffold providing protection from mechanical manipulation and desiccation. Fibrin hydrogels have been shown to be a useful adjunct in cell transfer for wound healing purposes in the past. In the work herein, we delineate the preparation steps of an mSVF-fibrin hydrogel construct as a novel approach for translational research and clinical application.

Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice.

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm2). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-ß1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future.

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

Basic Principles in the Management of Acute Burn Injuries in Adults.

INTRODUCTION: This review outlines an overview of up-to-date, stage-appropriate treatment methods for burn injuries as practiced at the National Burn Center of the University Hospital Zurich. It intends to provide practitioners with recommendations for the management of acute minor to severe burn injuries based on scientific evidence as well as the long-term experience of the Burn Center. The focus is on a practical guideline and various options including novel, innovative conceptual approaches.

Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair.

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation.

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study.

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.

Outcome of Facial Burn Injuries Treated by a Nanofibrous Temporary Epidermal Layer.

BACKGROUND: The face is commonly affected in thermal injuries, with a demand for proper recognition and the correct choice of treatment to guarantee optimal aesthetic and functional outcomes. It is highly vascularized and often heals conservatively, highlighting the particular relevance of conservative treatment modalities, many of which require daily re-applications or dressing changes, which can be painful and tedious for both the patient and the healthcare providers. Motivated by encouraging results of a novel temporary nanofibrous epidermal layer, we herein present a case series of this technology in a case series of patients suffering from facial burns and treated in our Burn Center. PATIENTS AND METHODS: Patients with superficial partial-thickness facial burns and mixed pattern burns, which were treated with SpinCare™, an electrospun nanofibrous temporary epidermal layer, between 2019 and 2021, at our institution were analyzed retrospectively. The Manchester scar scale (MSS) and numeric rating scale (NRS) were used for scar, pain, and outcome evaluation at different time points by five independent board-certified plastic surgeons with profound experience in burn surgery. RESULTS: Ten patients (m = 9; f = 1) were treated and evaluated retrospectively. The mean age was 38.8 ± years (SD ± 17.85). The mean healing time was 6.4 days (SD ± 1.56). The mean follow-up was 16.4 months (SD ± 11.33). The mean MSS score was 5.06 (SD ± 1.31), and the mean NRS Score for pain was significantly reduced from initially 7 to 0.875 upon application (mean (pre-application) 7 ± 0.7 and (application) 0.875 ± 1.26; p ≤ 0.0001). Patients reported a NRS score of 10 in terms of functional and cosmetic outcomes at their final follow-up appointment. No adverse effects were observed. CONCLUSIONS: The application of a nanofibrous temporary epidermal layer such as SpinCare™ represents a relatively easy-to-use, well-tolerated, and effective alternative for the treatment of partial-thickness facial burns.

Arterial Embolism After Facial Fat Grafting: A Systematic Literature Review.

BACKGROUND: While autologous fat grafting of the face is considered a generally safe procedure, severe complications such as arterial embolism (AE) have been reported. OBJECTIVE: To summarize data on injection-related visual compromise, stroke, and death caused by arterial embolism after facial fat transplantation. MATERIALS AND METHODS: Plastic surgery societies were contacted for reports on AE after autologous facial fat injection. In addition, a systematic literature review was performed. Data extracted included study design, injection site/technique, symptoms, management, outcome, and etiology. RESULTS: 61 patients with a mean age of 33.56 ± 11.45 years were reported. Injections targeted the glabella or multiple facial regions (both n = 16/61, 26.2%) most commonly, followed by injections in the temples (n = 10/61, 16.4%) and the forehead (n = 9/61, 14.8%). The mean volume injected was 21.5 ± 21.5 ml. Visual symptoms were described most frequently (n = 24/58, 41.4%) followed by neurological symptoms (n = 20/58, 34.5%), or both (n = 13/58, 22.4%). Ophthalmic artery (OA, n = 26/60, 43.3%), anterior or middle cerebral artery (CA, n = 11/60, 18.3%) or both (n = 14/60, 23.3%) were most frequently occluded. Outcome analysis revealed permanent vision loss in all patients with OA occlusion (n = 26/26, 100%), neurological impairment in most patients with CA occlusion (n = 8/10, 80%), and vision loss in most patients suffering from both OA and CA occlusion (n = 7/11, 63.6%). Six patients died following embolisms. CONCLUSIONS: AE causes severe complications such as blindness, stroke, and death. Due to a lack of high-quality data, no evidence-based treatment algorithms exist. To increase patient safety, a database collecting cases and complications should be established. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Angiopoietin-2/Angiopoietin-1 ratio increases early in burn patients and predicts mortality.

BACKGROUND: Angiopoietin-2 (Angpt-2) is involved in the pathogenesis of the capillary leak syndrome in sepsis and has been shown to be associated with worse outcomes in diverse critical illnesses. It is however unclear whether Angpt-2 plays a similar role in severely burned patients during the early phase characterized by massive capillary leakage. Our aim was to analyze the Angiopoietin-2/Angiopoietin-1 ratio (Angpt-2/Angpt-1 ratio) over the first two days in critically ill burn patients and examine its association with survival and further clinical parameters. METHODS: Adult burn patients with a total burn surface area (TBSA) ≥ 20% treated in the burn intensive care unit (ICU) of the University Hospital of Zurich, Switzerland, were included. Serum samples were collected prospectively and serum Angpt-1 and Angpt-2 were measured by enzyme-linked immunosorbent assay (ELISA) over the first two days after burn insult and stratified according to survival status, TBSA and the abbreviated burn severity index (ABSI). Due to hemodilution in the initial resuscitation phase, the Angpt-2/Angpt-1 ratio was normalized to albumin. RESULTS: Fifty-six patients were included with a median age of 51.5 years. Overall mortality was 14.3% (8/56 patients). The total amount of infused crystalloids was 12́902 ml (IQR 9́362-16́770 ml) at 24 h and 18́461 ml (IQR 13́024-23́766 ml) at 48 h. The amount of substituted albumin was 20 g (IQR 10-50 g) at 24 h and 50 g (IQR 20-60 g) at 48 h. The albumin-corrected Angpt-2/Angpt-1 ratios increased over the first 48 h after the burn insult (d0: 0.5 pg*l/ml*g [IQR 0.24 - 0.80 pg*l/ml*g]; d1: 0.83 pg*l/ml*g [IQR 0.29 - 1.98 pg*l/ml*g]; d2: 1.76 pg*l/ml*g [IQR 0.70 - 3.23 pg*l/ml*g]; p < 0.001) and were significantly higher in eventual ICU non-survivors (p = 0.005), in patients with a higher TBSA (p = 0.001) and in patients with a higher ABSI (p = 0.001). CONCLUSIONS: In analogy to the pathological host response in sepsis, the Angpt-2/Angpt-1 ratio steadily increases in the first two days in critically ill burn patients, suggesting a putative involvement in the pathogenesis of capillary leakage in burns. A higher Angpt-2/Angpt-1 ratio is associated with mortality, total burn surface area and burn scores.