Preventive Paradox? Postoperative Outcomes After Risk-Reducing Mastectomy and Direct-to-Implant Breast Reconstruction.

BACKGROUND: Risk-reducing mastectomy (RRM) with direct-to-implant (DTI) breast reconstruction is becoming increasingly important in breast cancer prevention. While the oncological benefits of RRM-DTI are well documented, there is a paucity of studies investigating its perioperative safety. METHODS: The ACS-NSQIP database (2008-2022) was queried to identify all patients who underwent RRM-DTI. Outcomes of interest included 30-day occurrence of reoperation, readmission, and surgical and medical complications. Multivariate logistic regression was used to determine factors associated with postoperative complications. RESULTS: A total of 1019 patients were included, with a mean age and BMI of 42.8 ± 10.9 years and 25.7 ± 5.8 kg/m², respectively. Complications occurred in 142 (14.0%) cases, with 103 (10.1%) reoperations and 51 (5.0%) readmissions. 62 (6.3%) surgical complications were recorded, the majority of which were superficial incisional infection (n = 19; 1.9%) and organ space infections (n = 19; 1.9%). Medical complications were rare (n = 13; 1.3%). Multivariable analyses revealed that higher BMI was significantly associated with any (OR:1.06, P < .0001), surgical (OR:1.08, P < .0001), and medical complications (OR:1.08, P = .04). Patients with bleeding disorders were at a significantly higher risk of any complications (OR:5.5, P = .03), while outpatient setting (OR:1.9, P = .03) and corticosteroid use (OR:6.6, P = .01) were identified as independent predictors of surgical complications. CONCLUSION: The risk of adverse events following RRM-DTI should not be underestimated, with a 30-day complication rate of 14%. Higher BMI, bleeding disorders, outpatient setting, and corticosteroid use were identified as risk factors. These findings underscore the need for thorough preoperative risk stratification, patient counseling, and health optimization to optimize surgical outcomes.

Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study.

Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02-1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03-1.21) and those with VD (aHR 0.90; 95% CI 0.64-1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Advances in Reconstructive Robotic Microsurgery in the Extremity.

Robotic surgery has emerged as a promising technique for reconstructive procedures, offering potential advantages across various surgical fields. Following initial case reports on the use of the Symani Surgical System (Medical Microinstruments, S.p.A) for microsurgical anastomosis, the authors evaluated its full potential in extremity reconstruction. They conducted a retrospective analysis of patients with soft tissue defects of the upper and lower extremities treated between February 2022 and May 2024. Each patient underwent soft tissue reconstruction with free tissue transfer with microsurgical anastomosis performed using the Symani Surgical System. The study included 7 male patients and 1 female patient, aged between 19 and 71 years (mean age: 50.6 y). The most used recipient vessels were the anterior tibial artery and vein (37.5%). The preferred anastomotic technique was end-to-side in arterial anastomoses (6/8). All arterial anastomoses were performed using the Symani Surgical System. The mean anastomosis time was 33.2±5.8 minutes. One out of 8 patients required surgical revision outside of the anastomosis. The authors' findings suggest that using the Symani Surgical System for microanastomosis in extremity reconstruction is a safe and effective approach, leading to satisfactory outcomes in different anatomic regions. The system allows for the successful execution of various anastomosis techniques, including end-to-end and end-to-side connections, using single interrupted or running sutures, which enhances its versatility in complex reconstructive procedures. The benefits of robotic assistance in terms of precision and ergonomics are promising for the future of reconstructive microsurgery.

Senescence in Adipose-Derived Stem Cells: Biological Mechanisms and Therapeutic Challenges.

Adipose tissue-derived stem cells (ADSCs) represent a subset of the mesenchymal stem cells in every adipose compartment throughout the body. ADSCs can differentiate into various cell types, including chondrocytes, osteocytes, myocytes, and adipocytes. Moreover, they exhibit a notable potential to differentiate in vitro into cells from other germinal lineages, including endothelial cells and neurons. ADSCs have a wide range of clinical applications, from breast surgery to chronic wounds. Furthermore, they are a promising cell population for future tissue-engineering uses. Accumulating evidence indicates a decreased proliferation and differentiation potential of ADSCs with an increasing age, increasing body mass index, diabetes mellitus, metabolic syndrome, or exposure to radiotherapy. Therefore, the recent literature thoroughly investigates this cell population's senescence mechanisms and how they can hinder its possible therapeutic applications. This review will discuss the biological mechanisms and the physio-pathological causes behind ADSC senescence and how they can impact cellular functionality. Moreover, we will examine the possible strategies to invert these processes, re-establishing the full regenerative potential of this progenitor population.

Surgical Management of Breast Capsular Contracture-A Multi-institutional Data Analysis of Risk Factors for Early Complications.

BACKGROUND: Capsular contracture (CC) is a common complication following implant-based breast surgery, often requiring surgical intervention. Yet, little is known about risk factors and outcomes following CC surgery. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program database (2008-2021) to identify female patients diagnosed with CC and treated surgically. Outcomes of interest included the incidence of surgical and medical complications at 30-days, reoperations, and readmissions. Confounder-adjusted multivariable analyses were performed to establish risk factors. RESULTS: 5,057 patients with CC were identified (mean age: 55 ± 12 years and mean body mass index [BMI]: 26 ± 6 kg/m2). While 2,841 (65%) women underwent capsulectomy, capsulotomy was performed in 742 patients (15%). Implant removal and replacement were recorded in 1,160 (23%) and 315 (6.2%) cases, respectively. 319 (6.3%) patients experienced postoperative complications, with 155 (3.1%) reoperations and 99 (2.0%) readmissions. While surgical adverse events were recorded in 139 (2.7%) cases, 86 (1.7%) medical complications occurred during the 30 day follow-up. In multivariate analyses, increased BMI (OR: 1.04; p = 0.009), preoperative diagnosis of hypertension (OR: 1.48; p = 0.004), and inpatient setting (OR: 4.15; p < 0.001) were identified as risk factors of complication occurrence. CONCLUSION: Based on 14 years of multi-institutional data, we calculated a net 30 day complication rate of 6.3% after the surgical treatment of CC. We identified higher BMI, hypertension, and inpatient setting as independent risk factors of postoperative complications. Plastic surgeons may wish to integrate these findings into their perioperative workflows, thus optimizing patient counseling and determining candidates' eligibility for CC surgery. 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 .

Quality of life and satisfaction after breast augmentation: A systematic review and meta-analysis of Breast-Q patient-reported outcomes.

BACKGROUND: Breast augmentation ranks among the most popular plastic surgery procedures. Yet, reports on post-operative patient-reported quality of life (QoL) and satisfaction remain conflicting. METHODS: A systematic review was conducted following the PRISMA guidelines. Three databases were searched for eligible studies that reported pre-and/or post-operative Breast-Q™ augmentation scores for patient QoL (psychosocial, sexual, and physical well-being) and/or satisfaction. RESULTS: A total of 39 studies (53 patient cohorts and 18,322 patients) were included in the quantitative synthesis. The pairwise meta-analysis revealed significant improvements in patient-reported psychosocial (MD: +38.10) and sexual well-being (MD: +40.20) as well as satisfaction with breast (MD: +47.88) (all p < 0.00001). Physical well-being improved slightly after breast augmentation (MD: +6.97; p = 0.42). The single-arm meta-analysis yielded comparable results, with Breast-Q™ scores in psychosocial and sexual well-being as well as satisfaction with breast increasing from 37.2, 31.1, and 26.3 to 75.0, 70.6, and 72.7, respectively (all p < 0.00001). Physical well-being improved by 8.1 (75.8 pre-operatively to 83.9 post-operatively; p = 0.17). Subgroup analyses highlighted higher QoL and satisfaction following breast augmentation for purely esthetic purposes and alloplastic mammaplasty. Although patient-reported physical and sexual well-being increased in the long term, psychosocial well-being was the highest in the short term. CONCLUSION: Patient satisfaction with breast, psychosocial, and sexual well-being increased significantly after breast augmentation. In contrast, patient-reported physical well-being yielded ambivalent results, varying by mammaplasty technique and post-operative follow-up time. Plastic surgeons should be sensitized about our findings to refine eligibility criteria and gain a deeper understanding of the patients' perceived surgical experience. PROSPERO TRIAL REGISTRATION NO: CRD42023409605.

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.

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: Clinical isolates foremost of chronic wounds were exposed in vitro to dilutions of two antiseptics 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 twofold 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.

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.

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.

Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea.

BACKGROUND AND PURPOSE: Previous studies have examined the risk of stroke in patients with Parkinson disease (PD), but the incidence of PD onset among stroke patients and its risk according to severity of poststroke disabilities have scarcely been investigated. This study aims to determine whether the risk of PD is increased among stroke patients using a retrospective cohort with a large population-based database. METHODS: We used data collected by the Korean National Health Insurance Service from 2010 to 2018 and examined 307,361 stroke patients and 380,917 sex- and age-matched individuals without stroke to uncover the incidence of PD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), and the risk of PD was compared according to presence and severity of disability. RESULTS: During 4.31 years of follow-up, stroke patients had a 1.67 times higher risk of PD compared to individuals without stroke (adjusted HR = 1.67, 95% CI = 1.57-1.78). The risk of PD was greater among stroke patients with disabilities than among those without disabilities, even after adjustment for multiple covariates (adjusted HR = 1.72, 95% CI = 1.55-1.91; and adjusted HR = 1.66, 95% CI = 1.56-1.77, respectively). CONCLUSIONS: Our study demonstrated an increased risk of PD among stroke patients. Health professionals need to pay careful attention to detecting movement disorders as clues for diagnosing PD.

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.

The risk of fracture in age-related macular degeneration according to the presence of visual disability: a nationwide cohort study.

PURPOSE: To evaluate the association between age-related macular degeneration (AMD) with or without visual disability (VD) and the risk of fracture using the National Health Insurance data in South Korea. METHODS: In total, 3,894,702 individuals who had taken part in health-screening programs between January 1, 2009, and December 31, 2009, were included in the cohort and followed until December 31, 2019. The participants with VD, which could be related to the severity of AMD, were defined as those with a loss of vision or visual field defect as certified by the Korean government's Ministry of Health and Welfare. The hazard ratio was calculated for groups (control and AMD with/without VD) using the multivariable-adjusted cox regression analysis. RESULTS: In total, 466,890 participants (11.99%) were diagnosed with fractures during the study period. An increased risk of fracture was observed in individuals with AMD compared with the control (adjusted hazard ratio (aHR), 1.09, 95% confidence interval (CI), 1.06-1.11). Furthermore, among the AMD individuals, an increased risk of fracture was prominent in individuals with VD (aHR 1.17, 95% CI 1.08-1.27) than those without VD (aHR 1.08, 95% CI 1.06-1.11) compared with the reference group (control). CONCLUSIONS: AMD was associated with an increased risk of fracture even without VD. Prevention for fracture should be considered in AMD patients, especially when accompanied by VD.

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.