Prolonged antibiotic prophylaxis in tissue reconstruction using autologous fat grafting: Is there a benefit for wound healing?

Fat grafting is a well-established method in plastic surgery. Despite many technical advances, standardised recommendations for the use of prophylactic antibiotics in fat grafting are not available. This retrospective multicentre study aims to analyse the use of prophylactic antibiotics in fat grafting and to compare complication rates for different protocols. A retrospective medical chart review of 340 patients treated with fat grafting of the breast from January 2007 to March 2019 was performed in three plastic surgery centres. Complications, outcomes, and antibiotic regimes were analysed. The Clavien-Dindo classification was applied. All patients received perioperative antibiotic prophylaxis: 33.8% (n = 115) were treated with a single shot (group 1), 66.2% (n = 225) received a prolonged antibiotic scheme (group 2). There was no significant difference in the number of sessions (P = .475). The overall complication rate was 21.6% (n = 75), including graft resorption, fat necrosis, infection, and wound healing problems. Complication rates were not significantly different between groups. Risk factors for elevated complication rates in this specific patient group are smoking, chemotherapy, and irradiation therapy. The complication rate for lipografting of the breast is low, and it is not correlated to the antibiotic protocol. The use of prolonged prophylactic antibiotics does not lower the complication rate.

Hide-and-seek: Neurotropes Plattenepithelkarzinom der periorbitalen Region - eine Fallserie und Übersichtsarbeit aktueller Literatur.

Das Plattenepithelkarzinom ist nach dem Basalzellkarzinom das zweithäufigste Malignom der Haut und wird vorwiegend an sonnenexponierten Stellen wie der Gesichtshaut diagnostiziert. Diese meist lokal destruktiv wachsende Malignität kann durchaus auch invasives Wachstumsverhalten, wie perineurale Ausbreitungsmechanismen, aufweisen. Das Plattenepithelkarzinom der periorbitalen Region ist in bis zu 14 % der Fälle mit perineuraler Invasion assoziiert. Vor allem in diesem Bereich birgt die anatomische Nähe zu den Hirnnerven das Risiko einer Progression Richtung zentrales Nervensystem, was mit einer schlechteren Prognose assoziiert ist. Der klinisch unauffällige Charakter dieser Entität resultiert oft in einer Verzögerung der definitiven Diagnosestellung, wodurch die vollständige Resektion und anschließende Rekonstruktion erschwert werden. Eine aufmerksame klinische Evaluierung kann bereits vor Erlangen histologischer Befunde Hinweise für ein perineurales Wachstum liefern. Neben fünf herausfordernden Fällen analysiert diese Arbeit Risikofaktoren, klinische als auch histologische Merkmale und Behandlungsoptionen des periorbitalen Plattenepithelkarzinoms mit perineuraler Invasion.

Hide-and-seek: Neurotropic squamous cell carcinoma of the periorbital region - a series of five cases and review of the literature.

Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun-exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology. Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.

The Pectoralis Major Island Flap: Short Scar Modified Muscle-Sparing Harvesting Technique Improves Aesthetic Outcome in Reconstructive Head and Neck Surgery.

BACKGROUND: Pectoralis major flap reconstruction is often associated with large unappealing scars in head-neck surgery. We recently established an alternative harvesting technique that improves aesthetic outcome. OBJECTIVES: The objective of this study was to demonstrate a modified surgical technique that harvests the pectoralis major muscle as an island flap and focuses on minimizing incision lines and applying a muscle-sparing approach. METHODS: A retrospective analysis covering the period 2008-2018 was conducted. Patients who underwent pectoralis major island flap reconstruction for fistula prophylaxis after salvage laryngectomy at the Medical University of Innsbruck were included. Flap harvesting was performed subcutaneously using two small incision lines, thereby sparing the clavicular and upper sternocostal aspects of the pectoralis muscle. RESULTS: Twenty-three patients with squamous cell carcinoma of the larynx (n = 19) or pharynx (n = 4) underwent salvage laryngectomy and consecutive reconstruction using a pectoralis major island flap and our muscle-sparing technique. Mean overall operation time was 147 ± 48.6 min. The majority (70%) of patients had an uneventful course of recovery and showed satisfying aesthetic results and low donor site morbidity as compared to traditional harvesting techniques. Six (26%) patients had major complications that required surgical revision. Three (13%) cases were complicated with fistulas. CONCLUSION: The pectoralis major island flap is shown to be reliable in otolaryngeal surgery. This surgical technique minimizes scarring and preserves thoracic wall architecture by taking a less invasive approach, thereby improving aesthetic outcome and reducing overall patient morbidity.

Risk factors and complications after body-contouring surgery and the amount of stromal vascular fraction cells found in subcutaneous tissue.

Body contouring surgery following massive weight loss is often prone to complications. Subcutaneous adipose tissue is a rich source of stromal vascular fraction (SVF) cells, and moreover it plays an important role in the pathophysiology of obesity, metabolic syndrome, and wound healing. In this retrospective, single-centred appraisal, complications are examined and correlated with individual SVF numbers in abdominal subcutaneous fat tissue. We analysed whether the weight loss method affected complications. Eighty seven massive weight loss patients undergoing body contouring surgery between 2010 and 2017 were included in the study. In total, 57 cases with at least one complication were recorded (65.5%). Maximum lifetime weight was 109.6 kg (range 48-184 kg). Half of the complications (50.8%) were minor complications without the need for surgical revision. The mean number of SVF found in the resected tissue was 714 997.63 cells/g fat tissue. We found no statistical difference in complication rates dependent on cell numbers. Smoking (P = .049) and a high BMI at the time point of surgery (P = .031) led to significantly more complications. Also, a high resection weight (P = .057) showed a tendency for impaired wound healing. However, there was no difference in complication rates following body contouring procedures attributable to the method of weight loss in this study.

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue.

Human abdominal subcutaneous adipose tissue consists of two individual layers—the superficial adipose tissue (SAT) and deep adipose tissue (DAT)—separated by the Scarpa’s fascia. The present study focuses on the analysis of morphological and immunological differences of primary adipocytes, adipose-derived stem cells (ASC), and tissue-infiltrating immune cells found in SAT and DAT. Adipocytes and stromal vascular fraction (SVF) cells were isolated from human SAT and DAT specimens and phenotypically characterized by in vitro assays. Ex vivo analysis of infiltrating immune cells was performed by flow cytometry. Primary adipocytes from SAT are larger in size but did not significantly differ in cytokine levels of LEPTIN, ADIPOQ, RBP4, CHEMERIN, DEFB1, VISFATIN, MCP1, or MSCF. ASC isolated from SAT proliferated faster and exhibited a higher differentiation potential than those isolated from DAT. Flow cytometry analysis indicated no specific differences in the relative numbers of ASC, epithelial progenitor cells (EPC), or CD3⁺ T-cells, but showed higher numbers of tissue-infiltrating macrophages in SAT compared to DAT. Our findings suggest that ASC isolated from SAT have a higher regenerative potential than DAT-ASC. Moreover, spatial proximity to skin microbiota might promote macrophage infiltration in SAT.

A small 'lick' will sink a great ship: fulminant septicaemia after dog saliva wound treatment in an asplenic patient.

Capnocytophaga canimorsus is a bacterium transmitted through the saliva of dogs. An infection can cause severe sepsis with acral necrosis and is potentially fatal. Here, we report the case of a 41-year-old man who was infected through a wound that was licked by his dog. He went into septic shock with disseminated intravascular coagulation and subsequently lost both lower legs, his nose and all the fingers on both hands.

Comparison of fasciocutaneous V-Y and rotational flaps for defect coverage of sacral pressure sores: a critical single-centre appraisal.

Pressure sore rates remain high in both nursing homes as well as in hospitals. Numerous surgical options are available for defect coverage in the sacral region. However, objective data is scarce as to whether a specific flap design is superior to another. Here, we aim to compare two fasciocutaneous flap designs for sacral defect coverage: the gluteal rotation flap and the gluteal V-Y flap. All primary sacral pressure sores of grades III-IV that were being covered with gluteal fasciocutaneous rotational or V-Y flaps between January 2008 and December 2014 at our institution were analysed. A total of 41 patients received a total of 52 flaps. Of these, 18 patients received 20 gluteal rotational flaps, and 23 patients received 32 V-Y flaps. Both groups were comparable with regards to demographics, comorbidities and complications. Significantly more V-Y flaps were needed to cover smaller defects. Mean length of hospital stay was significantly prolonged when surgical revision had to be carried out. Both flap designs have proven safe and reliable for defect coverage after sacral pressure sores. Gluteal rotational flaps appear to be more useful for larger defects. Both flap designs facilitate their reuse in case of pressure sore recurrence. Complication rates appear to be comparable in both designs and to the current literature.

The posterior thigh flap for defect coverage of ischial pressure sores - a critical single-centre analysis.

The development of pressure sores is still not only an enormous economical but also a medical burden. Especially in the ischial region, the local defect coverage remains demanding as it is the main weight-bearing area in wheelchair-mobilised patients and is prone to high mobility. The purpose of our study was to report our long-time experience with the reconstruction of ischial pressure ulcers with the medially based posterior thigh flap. A retrospective analysis of all primary pressure sores grade III-IV in the ischial area, which were covered with a medially based posterior thigh flap between January 2008 and December 2014, at our department was conducted. A total of 28 patients underwent defect coverage of an ischial pressure sore with the aforementioned flap. The subgroup with complications showed a statistically significant longer hospital stay. A statistically significant correlation between age and the coincidence of comorbidities could be seen. Older patients showed significantly higher grades of pressure sores. The medially based posterior thigh flap is a safe and reliable flap design. Complication rates are comparable to other flaps. Nevertheless, in case of complications, a significantly longer duration of hospitalisation has to be taken into account.

Long-Term Results after Autologous Breast Reconstruction with DIEP versus PAP Flaps Based on Quality of Life and Aesthetic Outcome Analysis.

(1) Background: This work aimed to conduct a comparative study, providing long-term data about patient-reported outcome measures and donor site scar assessments, as well as an aesthetic evaluation of the reconstructed breasts in patients with DIEP versus PAP flap breast reconstruction. (2) Methods: This prospective, single-center, matched cohort study included a total of 36 patients after DIEP and PAP flap breast reconstruction. The evaluation was carried out using the Breast-Q and POSAS questionnaire, as well as the Breast Aesthetic Scale for cosmetic analysis, by four plastic surgeons. (3) Results: The postoperative Breast-Q evaluation revealed no significant differences between both patient groups for the categories of the physical well-being of the donor site, the physical well-being of the breast, and satisfaction with the breast. A scar evaluation of the donor site region showed equivalent results for the thigh and abdomen regions, concerning the overall opinion of the patients and the observers. There was no significant difference between both methods of reconstruction for all aspects of breast aesthetics. (4) Conclusions: Similar results for donor site morbidity, scar quality, and the aesthetic outcome of the breasts in both the DIEP and PAP patient groups have been demonstrated. Hence, in those cases suitable for both types of reconstruction, the decision can be based on factors such as patients' lifestyles, leisure activities, and preferences.

Resection of Skin Cancer Resulting in Free Vascularized Tissue Reconstruction: Always a Therapeutic Failure?

The globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient's neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n = 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

BACKGROUND: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. METHODS: We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. RESULTS: CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. CONCLUSION: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

Correction of Temporal Hollowing After Pterional Craniotomy by Autologous Fat Grafting. A Single-Center Experience.

OBJECTIVE: Aesthetic complications following neurosurgical procedures impact patient quality of life and self-perception. Postoperative temporal hollowing frequently is seen after temporal craniotomy, resulting mainly from atrophy of the temporal muscle. Autologous fat grafting is a tailorable method to correct such approach-related sequelae. We herein present our clinical patient series and discuss pearls and pitfalls of this method. METHODS: In this retrospective single-center study, correction of postoperative temporal hollowing using autologous fat grafting was performed in 16 patients. Temporal tissue thickness ratio was measured using magnetic resonance tomography images to visualize the graft. Patients, plastic surgeons, and neurosurgeons evaluated the results independently using the herein presented scale. RESULTS: The mean interval between the neurosurgical procedure and fat grafting was 62 months. A mean volume of 11.5 mL of autologous fat was injected in an average of 2.5 sessions after initial rigottomy. Temporal tissue thickness was significantly augmented at a mean of 2.2 years after the operation (mean 0.71 ± 0.25, range 0.43-1.1; P = 0.0214) as compared with the preoperative finding (mean 0.48 ± 0.1, range 0.32-0.6). Patients were more satisfied with the results than were surgeons, reflecting the significant impact of the deformity on patient self-esteem. CONCLUSIONS: Autologous fat grafting is a valuable method for correcting postoperative temporal hollowing that provides stable results, high patient and surgeon satisfaction, and can be tailored to the patient's individual needs. It should not be considered a merely aesthetic operation but an important rehabilitation step towards restoring the patient's quality of life.

Donor-Site Morbidity and Quality of Life after Autologous Breast Reconstruction with PAP versus TMG Flap.

The transverse myocutaneous gracilis (TMG) and the profunda artery perforator (PAP) flap are both safe choices for autologous breast reconstruction originating from the same donor region in the upper thigh. We aimed to compare the post-operative outcome regarding donor-site morbidity and quality of life. We included 18 patients who had undergone autologous breast reconstruction with a PAP flap (n = 27 flaps). Prospective evaluation of donor-site morbidity was performed by applying the same questionnaire that had already been established in a previous study evaluating TMG flap (n = 25 flaps) outcome, and results were compared. Comparison of the two patient groups showed equivalent results concerning patient-reported visibility of the donor-site scar and thigh symmetry. Still, the TMG group was significantly more satisfied with the scar (p = 0.015) and its position (p = 0.001). No difference was found regarding the ability to sit for prolonged periods. Donor-site wound complications were seen more frequently in the PAP group (29.6%) than in the TMG group (4.0%). Both groups expressed rather high satisfaction with their quality of life. Both flaps show minimal functional donor-site morbidity and high patient satisfaction. To minimize wound healing problems in PAP patients, thorough planning of the skin paddle is necessary.

Long-Term Outcome Analysis and Technical Refinements after Autologous Breast Reconstruction with PAP Flap: What We Have Learnt.

Introduction: The profunda artery perforator (PAP) flap represents a valuable alternative to the deep inferior epigastric artery perforator flap which, nowadays, is considered the golden standard for autologous breast reconstruction. The goal of this study was to evaluate the long-term satisfaction, functional outcomes of the donor site following PAP flap-based breast reconstruction and to present our personal learning experience along with suggestions for technique refinements. Methods: In this prospective single-center appraisal, 18 patients who underwent PAP flap-based breast reconstruction between January 2016 and November 2019 were enrolled. The Patient and Observer Scar Assessment Scale (POSAS) and the Breast-Q questionnaire were employed to evaluate the results 12 months postoperative. Data were analyzed with the Q-Score program. Complications were recorded in the medical database and classified with the Clavien-Dindo classification. Results: In the questionable time frame, 164 female patients underwent free flap breast reconstruction. Of those, 18 patients that received PAP flaps (9 bilateral) were included in this study. We recorded one flap loss because of venous failure. Most complications concerned the donor site, including hematoma, seroma, and wound healing problems. Patients' satisfaction was high at 12 months post-surgery, despite critical evaluation of the donor site scar. Conclusion: The PAP flap serves as an excellent option for breast reconstruction in patients who do not have abundant abdominal tissue. The overall clinical outcome was good and patients' evaluation showed high satisfaction after 12 months despite high complication rates. Modifications in planning and flap harvesting might improve the donor site outcome and the overall complication rate.

Simple, but effective: Nasal splinting for airway securement in free flap reconstruction following orbital exenteration.

Orbital exenteration is a disfiguring procedure that often results in free tissue transfer for reconstructive purposes. The reconstructive focus is the obliteration of dead space while sparing the nasal airway, particularly if the medial orbital wall was resected. Prolapse of transferred tissue into the nasal airway may cause breathing difficulties drastically compromising quality of life. The objective of this study was to demonstrate the effectiveness and feasibility of temporary nasal septum splints as mechanical support for transferred tissue, to prevent airway obstruction. This novel application technique was employed in three patients between 2017 and 2018. No flap loss or sino-orbital fistulas were observed. On postoperative MRI and endoscopy, a patent nasal airway was observed at all times. Temporary nasal splinting in combination with free tissue transfer proved to be a simple, but effective reconstructive option for securing the nasal airway following orbital exenteration with resection of the medial orbital wall.

Tangential Excision of Rhinophyma with the Disposable Razor Blade: Simple and Cost Efficient with Aesthetically Good Results.

Medical therapies for rhinophyma have been described but these only delay progression. Therefore, surgery is the method of choice. Plenty of modalities have been described including cold-knife surgery, electrosurgery, hydrosurgery, laser-assisted treatments, and dermabrasion. SETTINGS AND DESIGN: In this two-center study, patients' charts and photodocumentation were analyzed retrospectively. MATERIALS AND METHODS: Surgery was performed under general anesthesia with an additional local anesthesia of the affected areas of the nose. We removed the hypertrophic tissue in thin layers with a sterile disposable razor blade under constant visual control of the underlying cartilage and adnexal structures. A dressing with Mepithel and gauzes was applied. Patients presented weekly to monitor the wounds. Follow-up was 1 year. RESULTS: From 2016 to 2019, nine male patients with rhinophyma underwent surgical therapy at AGAPLESION Markus Hospital, Frankfurt am Main, Germany and at the Department of Plastic, Reconstructive and Aesthetic Surgery, Innsbruck Medical University, Austria. The mean age of the patients was 66 years. Mean time to complete re-epithelization equaled 31.5 days. No recurrences were noted within the follow-up period of 1 year. Patients' satisfaction was very high. Only one patient had hypertrophic scars at the wing of the nose and another one developed a superficial fistula without connection to the nasal cavity. CONCLUSION: To the best of our knowledge, this is the first case series describing the use of a disposable razor blade for rhinophyma treatment supporting its efficiency described in previous anecdotal publications. We can highly recommend the technique, as it is cost-efficient and simple and provides excellent aesthetic results.

Oxidant therapy improves adipogenic differentiation of adipose-derived stem cells in human wound healing.

BACKGROUND: Adipose-derived stem cells (ASC) and adipocytes are involved in numerous physiological and pathophysiological conditions, which have been extensively described in subcutaneous and visceral fat depots over the past two decades. However, much less is known about ASC and adipocytes outside classical fat tissue depots and their necessity in tissue remodeling after injury. Therefore, we investigated the etiology of adipocytes in human granulation tissue and define their possible role wound healing. METHODS: Identification of human wound tissue adipocytes was determined by immunohistochemical staining of granulation tissue sections from patients undergoing surgical debridement. Stromal cell fractions from granulation tissue and subcutaneous fat tissue were generated by collagenase type II-based protocols. Pro- and anti-inflammatory wound bed conditions were mimicked by THP1- and CD14+ monocyte-derived macrophage models in vitro. Effects of macrophage secretome on ASC differentiation and metabolism were determined by immunoblotting, flow cytometry, and microscopy assessing early and late adipocyte differentiation states. Functional rescuing experiments were conducted by lentiviral transduction of wildtype PPARG, IL1RA, and N-chlorotaurine (NCT) treatment. RESULTS: Single and clustered adipocyte populations were detected in 11 out of 13 granulation tissue specimens and single-cell suspensions from granulation tissue showed adipogenic differentiation potential. Pro-inflammatory signaling by IFNG/LPS-stimulated macrophages (M (IFNG/LPS)) inhibited the maturation of lipid droplets in differentiated ASC. In contrast, anti-inflammatory IL4/IL13-activated macrophages (M (IL4/IL13)) revealed minor effects on adipocyte development. The M (IFNG/LPS)-induced phenotype was associated with a switch from endogenous fatty acid synthesis to glycolysis-dominated cell metabolism and increased pro-inflammatory cytokine production. Impaired adipogenesis was associated with increased, but seemingly non-functional, CEBPB levels, which failed to induce downstream PPARG and CEBPA. Neither transgenic PPARG overexpression, nor inhibition of IL1B was sufficient to rescue the anti-adipogenic effects induced by IFNG/LPS-activated macrophages. Instead, macrophage co-treatment during stimulation with NCT, a mild oxidant produced by activated granulocytes present in human wounds in vivo, significantly attenuated the anti-adipogenic effects. CONCLUSIONS: In conclusion, the appearance of adipocytes in wound tissue indicates a prevailing anti-inflammatory environment that could be promoted by NCT treatment and may be associated with improved healing outcomes.