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.

Neurotized profunda artery perforator flap for subtotal tongue reconstruction - Prospective case series.

BACKGROUND: Total or subtotal glossectomy defects cause significant functional deficits in swallowing and speech and subsequently impair patients' quality of life (QOL). Recently, the profunda artery perforator (PAP) flap has emerged as a potential alternative for reconstructing extensive glossectomy defects. While previous studies assessing recovery of neurotized anterolateral thigh (ALT) flaps in head and neck reconstruction reported superior sensory recovery, improved swallow function, and improved overall patient satisfaction in patients with neurotized flaps vs. non-neurotized ALT flap reconstruction, PAP flap neurotization has not been described and systematically assessed in head and neck patients. METHODS: Six patients underwent subtotal tongue reconstruction with neurotized PAP flaps at the authors' institution from May 2022 until August 2023. A branch of the posterior femoral cutaneous nerve of the PAP flap was coaptated to the lingual nerve. Two-point discrimination, Semmes-Weinstein monofilament, pain, and temperature assessments were conducted at 3, 6, and 12 months postoperatively on the neo-tongue. The MD Anderson speech and deglutition scales and the EORTC-QLQ-H&N35 were used to record functional outcomes and QOL. RESULTS: The mean age was 69 ± 4 years, and the mean body mass index was 25 ± 7 kg/m2. Neo-tongue median 2-point discrimination at the tip improved from >10 mm at 3 months to 6 mm at 12 months. All patients had protective pain and temperature perception at the neo-tongue tip at the 6-month follow-up. Speech and swallowing functions were similar at the 12-month follow-up to data on neurotized ALT flaps from literature. No neuropathic pain was reported at the donor site at the 6-month follow-up. CONCLUSIONS: This is the first case series of PAP flap neurotization in head and neck patients, suggesting potential functional advantages with minimal donor-site morbidity. LEVEL OF EVIDENCE: V Case Series.

Impact of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: Limited data exist regarding the effect of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction. However, an adequate free flap volume is an important predictor of functional and patient-reported outcomes in head and neck reconstruction. METHODS: A systematic review of Medline, Embase, and the Cochrane Central Register of Controlled Trials was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 6710 abstracts were screened, and 36 full-text papers were reviewed. Nineteen studies met the inclusion criteria and were used to extract data for this analysis. RESULTS: A meta-analysis of 14 two-arm studies comparing the impact of adjuvant radiotherapy versus no adjuvant radiotherapy was performed. The main analysis revealed that 6 months postoperatively, irradiated flaps showed a significant reduction of volume (average, 9.4%) compared to nonirradiated flaps. The average interpolated pooled flap volumes 6 months postoperatively were 76.4% in irradiated flaps and 81.8% in nonirradiated flaps. After a median postoperative follow-up of 12 months, the total flap volume was 62.6% for irradiated flaps and 76% for nonirradiated flaps. Four studies reported that chemotherapy had no significant impact on free flap volume. CONCLUSIONS: Compared to nonirradiated flaps, irradiated flaps were significantly reduced in volume (range, 5% to 15.5%). Clinicians should take this into account when planning the surgical reconstruction of head and neck defects. Conducting large-scale prospective studies with standardized protocols and well-defined follow-up measurements could contribute to defining the ideal, personalized free flap volume for optimal function and patient-reported outcomes.

Coagulation side effects of enzymatic debridement in burned patients.

OBJECTIVES: Bromelain-based enzymatic debridement has emerged as a valuable option to the standard surgical intervention for debridement in burn injuries. Adverse effects on coagulation parameters after enzymatic debridement have been described. The purpose of this study was to compare the effect of enzymatic and surgical debridement on coagulation. METHODS: Between 03/2017 and 02/2021 patients with burn injuries with a total body surface area (TBSA) ≥ 1% were included in the study. Patients were categorized into two groups: the surgically debrided group and the enzymatically debrided group. Coagulation parameters were assessed daily for the first seven days of hospitalization. RESULTS: In total 132 patients with a mean TBSA of 17% were included in this study, of which 66 received enzymatic debridement and 66 received regular surgical-debridement. Patients receiving enzymatic debridement presented significantly higher factor-V concentration values over the first seven days after admission (p = <0.01). Regarding coagulation parameters, we found no difference in INR-, aPTT-, fibrinogen-, factor-XIII- and thrombocyte-concentrations over the first seven days (p = >0.05). CONCLUSION: Enzymatic debridement in burned patients does not appear to increase the risk of coagulation abnormalities compared with the regular surgical approach.

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.

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.

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.

Impact of Adjuvant Radiotherapy on Free Flap Volume in Autologous Breast Reconstruction: A Scoping Review.

In autologous breast reconstruction, a sufficient flap volume is fundamental to restore breast shape and ensure an aesthetic outcome. After mastectomy, postoperative irradiation is regularly indicated in the oncological treatment algorithm. When administering radiation therapy after autologous reconstruction, the tissue transferred is inherently irradiated. Although there is evidence that points to a reduction in flap volume after adjuvant radiotherapy, the data have been contradicting and inconclusive. To address this anecdotal evidence, we performed a scoping review of the current literature that addresses the effect of radiotherapy on breast flap volume. Six two-armed studies, comprising a total of 462 patients, reported on the effect of adjuvant radiotherapy on free flap volume changes. Of those, two studies found a significant negative impact of radiotherapy on free flap volume, while the other four studies did not. Reported flap volume changes ranged from no change to a reduction of 26.2%, measured up to two years postoperatively. The selected studies contain varying patient numbers, follow-up timepoints, types of flaps, and measuring methods, contributing to a relatively high heterogeneity. While we present some evidence suggesting a significant impact of adjuvant radiotherapy on breast flap volume, future studies are needed to further investigate this potential correlation.

Perioperative targeted temperature management of severely burned patients by means of an oesophageal temperature probe.

BACKGROUND: Hypothermia in severely burned patients is associated with a significant increase in morbidity and mortality. The use of an oesophageal heat exchanger tube (EHT) can improve perioperative body temperatures in severely burned patients. The aim of this study was to investigate the intraoperative warming effect of oesophageal heat transfer in severe burn patients. METHODS: Single-centre retrospective study performed at the Burns Centre of the University Hospital Zurich. Between January 2020 and May 2021 perioperative temperature management with EHT was explored in burned patients with a total body surface area (TBSA) larger than 30%. Data from patients, who received perioperative temperature management by EHT, were compared to data from the same patients during interventions performed under standard temperature management matching for length and type of intervention. RESULTS: A total of 30 interventions (15 with and 15 without EHT) in 10 patients were analysed. Patient were 38 [26-48] years of age, presented with severe burns covering a median of 50 [42-64] % TBSA and were characterized by an ABSI of 10 [8-12] points. When receiving EHT management patients experienced warming at 0.07 °C per minute (4.2 °C/h) compared to a temperature loss of - 0.03 °C per minute (1.8 °C/h) when only receiving standard temperature management (p < 0.0001). No adverse or serious adverse events were reported. CONCLUSION: The use of an oesophageal heat transfer device was effective and safe in providing perioperative warming to severely burned patients when compared to a standard temperature management protocol. By employing an EHT as primary temperature management device perioperative hypothermia in severely burned patients can possibly be averted, potentially leading to reduced hypothermia-associated complications.