MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells.

Angiogenesis is a critical process in repair of tissue injury that is regulated by a delicate balance between pro- and antiangiogenic factors. In disease states associated with impaired angiogenesis, we identified that miR-135a-3p is rapidly induced and serves as an antiangiogenic microRNA (miRNA) by targeting endothelial cell (EC) p38 signaling in vitro and in vivo. MiR-135a-3p overexpression significantly inhibited EC proliferation, migration, and network tube formation in matrigel, whereas miR-135-3p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3'-UTR reporter and miRNA ribonucleoprotein complex -immunoprecipitation assays, and small interfering RNA dependency studies revealed that miR-135a-3p inhibits the p38 signaling pathway in ECs by targeting huntingtin-interacting protein 1 (HIP1). Local delivery of miR-135a-3p inhibitors to wounds of diabetic db/db mice markedly increased angiogenesis, granulation tissue thickness, and wound closure rates, whereas local delivery of miR-135a-3p mimics impaired these effects. Finally, through gain- and loss-of-function studies in human skin organoids as a model of tissue injury, we demonstrated that miR-135a-3p potently modulated p38 signaling and angiogenesis in response to VEGF stimulation by targeting HIP1. These findings establish miR-135a-3p as a pivotal regulator of pathophysiological angiogenesis and tissue repair by targeting a VEGF-HIP1-p38K signaling axis, providing new targets for angiogenic therapy to promote tissue repair.-Icli, B., Wu, W., Ozdemir, D., Li, H., Haemmig, S., Liu, X., Giatsidis, G., Cheng, H. S., Avci, S. N., Kurt, M., Lee, N., Guimaraes, R. B., Manica, A., Marchini, J. F., Rynning, S. E., Risnes, I., Hollan, I., Croce, K., Orgill, D. P., Feinberg, M. W. MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells.

MicroRNA-615-5p Regulates Angiogenesis and Tissue Repair by Targeting AKT/eNOS (Protein Kinase B/Endothelial Nitric Oxide Synthase) Signaling in Endothelial Cells.

Objective- In response to tissue injury, the appropriate progression of events in angiogenesis is controlled by a careful balance between pro and antiangiogenic factors. We aimed to identify and characterize microRNAs that regulate angiogenesis in response to tissue injury. Approach and Results- We show that in response to tissue injury, microRNA-615-5p (miR-615-5p) is rapidly induced and serves as an antiangiogenic microRNA by targeting endothelial cell VEGF (vascular endothelial growth factor)-AKT (protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling in vitro and in vivo. MiR-615-5p expression is increased in wounds of diabetic db/db mice, in plasma of human subjects with acute coronary syndromes, and in plasma and skin of human subjects with diabetes mellitus. Ectopic expression of miR-615-5p markedly inhibited endothelial cell proliferation, migration, network tube formation in Matrigel, and the release of nitric oxide, whereas miR-615-5p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3' untranslated region reporter and microribonucleoprotein immunoprecipitation assays, and small interfering RNA dependency studies demonstrate that miR-615-5p inhibits the VEGF-AKT/eNOS signaling pathway in endothelial cells by targeting IGF2 (insulin-like growth factor 2) and RASSF2 (Ras-associating domain family member 2). Local delivery of miR-615-5p inhibitors, markedly increased angiogenesis, granulation tissue thickness, and wound closure rates in db/db mice, whereas miR-615-5p mimics impaired these effects. Systemic miR-615-5p neutralization improved skeletal muscle perfusion and angiogenesis after hindlimb ischemia in db/db mice. Finally, modulation of miR-615-5p expression dynamically regulated VEGF-induced AKT signaling and angiogenesis in human skin organoids as a model of tissue injury. Conclusions- These findings establish miR-615-5p as an inhibitor of VEGF-AKT/eNOS-mediated endothelial cell angiogenic responses and that manipulating miR-615-5p expression could provide a new target for angiogenic therapy in response to tissue injury. Visual Overview- An online visual overview is available for this article.

The Effect of Respiration on Breast Measurement Using Three-dimensional Breast Imaging.

BACKGROUND: Three-dimensional (3D) imaging offers new opportunities to enable objective and quantitative analysis of the breast. Unlike scanning of rigid objects, respiration may be one of the factors that can influence the measurement of breast when using 3D imaging. In this study, we aimed to investigate how the different respiratory phases affect 3D morphologic and volumetric evaluations of the breast. METHODS: We performed preoperative 3D breast imaging at the end of expiration (EE) and the end of inspiration (EI). We repeated scans on each respiratory phase, taking four scans in total (EE1, EE2 and EI1, EI2). Using Geomagic Studio 12 software, measurements from the different respiratory phases (EE1 and EI1) were compared for differences in the linear distances of breast. Breast volumetric change error (BVCE) was measured between EE1 and EE2 (R1) and between EI1 and EI2 (R2). A multilevel model was used to analyze the difference of linear-distances parameters between EE1 and EI1 and a paired sample t-test was used to analyze the difference between R1 and R2. RESULTS: Our study included 13 Chinese women (26 breasts) with a mean age of 32.6 ± 6.3 years. Compared with EI, EE showed a longer sternal notch to the level of the inframammary fold and shorter nipple to midline (p < 0.05). During EI, breast projection increased by 0.23 cm (95% CI - 0.39, - 0.08) and breast base width increased by 0.27 cm (95% CI - 0.46, - 0.09). The position of the nipple moved by 0.18 cm (95% CI - 0.34, - 0.03) laterally, 0.41 cm (95% CI 0.18, 0.64) cranially, and 0.71 cm (95% CI - 0.92, - 0.51) anteriorly. Although there was no significant difference in BVCE between EE and EI, the result seen with EE appeared to be more consistent. CONCLUSIONS: The results of this study demonstrate that there was no difference in breast volume results when patients are in the expiratory or inspiratory state during 3D breast imaging. This study, however, holds potential benefits to both surgical practice as well as the 3D imaging industry. LEVEL OF EVIDENCE IV: 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 .

Development of a large-volume human-derived adipose acellular allogenic flap by perfusion decellularization.

In reconstructive surgery, transfer of patients' tissue (autologous flaps) is routinely used to repair large soft tissue defects caused by surgery, trauma, chronic diseases, or malformations; unfortunately, this strategy is not always possible and often creates a secondary defect in the donor site of the tissue. Tissue-engineered synthetic flaps are currently unable to repair clinically-relevant, large-volume defects; allogenic flaps from cadaveric donors could provide a ready-to-use biological alternative if treated with methods to avoid the immune-rejection of the donor's cells. Here, we describe the successful decellularization of a large (> 800 cc) human-derived adipose flap through a perfusion apparatus; we demonstrate the complete removal of the immunogenic cellular components of the flap with the retention of its structural components and vascular network. Our aim is to obtain a universally compatible, off-the-shelf acellular allogenic flap that could be recellularized with cells from recipient patients to provide a tissue-engineered allogenic/autologous alternative for reconstruction of large-volume soft-tissue defects.

Reflections on a Decade of Face Transplantation.

On November 27, 2005, Isabelle Dinoire underwent the world's first partial face transplant in Amiens (France) after a dog attack had left her face severely disfigured. The abrupt surgical leap found the medical community and society unprepared to deal with the scientific, ethical, and societal implications of a surgical procedure that was striving to transition from sci-fi novels to science. Today, 10 years and over 35 transplants later, public opinion has become accustomed to the concept of "face restoration" through transplantation. However, face transplantation is far from being a safe "routine" surgery and the science behind it is still mostly unknown. Patients and multidisciplinary teams of physicians confront daily medical challenges, life-threatening risks, and personal struggle that only in part come to light. Could (or should) this be the laborious, uncertain, and high-risk trajectory of disruptive medical innovation? Over the last decade, some medical discoveries and surgical advancements in the field have been closely accompanied by partial regulatory frameworks, intense ethical discussions, and meaningful changes in social beliefs across cultures and continents. Yet, a very long way is to come and the questions we still have today greatly outweigh the answers we can offer. Here, we take the chance of the 10-year anniversary of face transplantation to reflect on the path traveled and to look forward to the challenges lying ahead.

Gene expression profiling of skeletal muscle after volumetric muscle loss.

Volumetric muscle loss (VML), usually occurring following traumatic injury, results in a composite loss of muscle mass. These injuries manifest as decreased strength and functional impairments. Clinically, these injuries often heal with fibrosis, as opposed to skeletal muscle regeneration. This study examines the healing patterns of a skeletal muscle following VML in a murine model. Eight-week old male C57BL/6J mice used in the study underwent either bilateral VML injury or cryoinjury, a widely used model known to induce skeletal muscle regeneration. Skeletal muscle was harvested at 2 and 4 weeks following injury and subjected to histological analysis. H&E staining demonstrated skeletal muscle regeneration following cryoinjury, but not VML, at either timepoint post-injury. Additionally, samples were analyzed using a wound-healing PCR array to identify differentially regulated genes of interest in VML and cryoinjury, as compared to noninjured controls. The gene array data further demonstrated prolonged inflammation and increased pro-fibrotic activity in the VML injured muscles, as compared to cryoinjury. In addition, IGF1, a known myogenic factor, was significantly decreased following VML, as compared to cryoinjury, in both ELISA and PCR. This study offers an insight into the pathophysiology of VML injury and reveals a gene profile of a nonregenerating skeletal muscle.

Adipose-derived aldehyde dehydrogenase-expressing cells promote dermal regenerative potential with collagen-glycosaminoglycan scaffold.

Aldehyde dehydrogenase (ALDH) is an enzyme that plays an important role in retinoid metabolism and highly expressed in stem cells. This study isolated ALDH-expressing cells from subcutaneous adipose tissue and investigated their potential to enhance healing in a full-thickness skin wound in rats by co-implanting them with collagen-glycosaminoglycan (c-GAG) scaffolds. ALDH-positive cells were isolated by a fluorescence-activated cell sorting technique from Lewis rat's stromal-vascular-fraction (SVF) and transplanted with c-GAG scaffolds in a rat full-thickness skin wound model. At 7 days after surgery, the microscopic appearance of c-GAG scaffolds seeded with ALDH-positive was compared with those of uncultured-SVF, and cultured-SVF adipose-derived stromal cells (ASCs). The thickness of cellular ingrowth in the ASC group (630 ± 180 µm) was significantly thicker than that in the control (390 ± 120 µm) or SVF (380 ± 140 µm) groups, but non-significantly thicker than that in the ALDH-positive group (570 ± 220 µm). The thickness of regenerated collagen layer was significantly thicker in the ALDH-positive group (160 ± 110 µm) than in the ASCs (81 ± 41 µm), the control (65 ± 24 µm), or SVF (64 ± 34 µm) groups. Immunofluorescent staining with CD31 proved that transplanted ALDH-positive cells differentiated into vascular endothelial cells in c-GAG scaffolds. Combined transplantation with c-GAG scaffolds and adipose-derived ALDH-positive cells promoted dermal regeneration, giving a possibility that ALDH-positive cells would greatly shorten the waiting period before secondary autologous skin grafting was possible.

Facial-nerve regeneration ability of a hybrid artificial nerve conduit containing uncultured adipose-derived stromal vascular fraction: An experimental study.

PURPOSE: This study investigated the potential of uncultured-stromal-vascular-fraction (SVF) cells in promoting facial nerve regeneration in a rat model. MATERIALS AND METHODS: A 7-mm nerve defect was created in the buccal branch of facial nerve in five groups of Lewis rats (total n = 30, n = 6 per group). A silicone tube, infused with syngeneic uncultured-SVF was implanted into the facial nerve defect. Groups 1-3 received 1 × 103 , 1 × 105 , and 1 × 107 cells, and regenerated nerves were examined at 13 weeks after the surgery. The findings were compared to the autograft and collagen-alone groups with facial palsy score (FPS), the number of myelinated fibers, fiber diameter, axon diameter, myelin thickness, and g ratio. RESULTS: There was no significant difference in FPS between the autograft and 1 × 105 -cell groups at 13 weeks after surgery, and FPS values of these two groups were significantly higher than those of the other three groups (P < 0.01). Axon diameter significantly increased in the 1 × 105 -cell group compared with the 1 × 103 - (P < 0.05) and 1 × 107 -cell groups (P < 0.01). Myelin thickness was found to be the highest in the autograft group, followed by the 1 × 105 -, 1 × 103 -, 1 × 107 -cell, and negative control groups, and there were significant differences among all groups (P < 0.01). CONCLUSION: The infusion of uncultured-SVF into the artificial nerve conduit promoted optimal nerve regeneration that was significantly better than nerve conduit alone. © 2016 Wiley Periodicals, Inc. Microsurgery 37:808-818, 2017.

Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.

Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

Padova Hospitale Onlus: report of a 15-year experience in surgical and medical assistance in developing countries.

Nowadays, an urgent need for global medical cooperation and assistance still bears on health care providers. Because plastic, reconstructive, and aesthetic surgery is a surgical specialty with social purposes, the humanitarian importance of the discipline is, nowadays, stronger than ever. Padova Hospitale Onlus is a nonprofit charity association with the aim to ensure sustainable medical programs, in particular in the field of plastic and reconstructive surgery. The activity of the association in fund-raising strategies, volunteer enrollment, and operative strategies has been reviewed and reported to stimulate further collaboration, emulation, and contributions. Since 1996, the association has assisted over 20,000 people during 50 missions over the 5 continents, performing more than 2000 surgical operations and almost 8000 medical examination, involving more than 320 volunteers, supplying health care material or health care facilities. Furthermore, a high rate of surgical records and of medical assistance has been performed in the last 2 years, depicting a positive rising trend of activity. However, scarce financial means, absence of a structured coordination, and/or cooperation between associations may often affect the long-term sustainability of these interventions. Thus, only an experienced and structured association may grant the required resources to sustain adequate and fruitful short-term or long-term projects for the promotion of a humanitarian cooperation as much "demand driven" as possible.

Adherence to a Healthy Lifestyle in Association With Microvascular Complications Among Adults With Type 2 Diabetes.

Importance: The association between an overall healthy lifestyle and the subsequent risk of microvascular complications among patients with diabetes remains unclear. Objective: To examine the association between adherence to a healthy lifestyle before and after diabetes diagnosis and the risk of subsequent microvascular complications among adults with diabetes. Design, Setting, and Participants: This prospective cohort study included incident patients with type 2 diabetes who were free of cardiovascular disease and cancer at the time of diabetes diagnosis and completed the diabetes supplementary questionnaires in the Nurses' Health Study (in 2000 and 2005) and the Health Professionals Follow-Up Study (in 2000, 2004, and 2008) in the US. Data were analyzed from April to August 2021. Exposures: Diet and lifestyle factors before and after diabetes diagnosis were assessed by validated questionnaires. A healthy lifestyle consisted of nonsmoking, having a healthy body weight (a body mass index of ≥18.5 or <25), engaging in moderate-to-vigorous physical activity (≥150 minutes per week), consuming a high-quality diet (top 40th percentile of the Alternative Healthy Eating Index), and moderate alcohol drinking (5-15 g/d for women and 5-30 g/d for men). Main Outcomes and Measures: Physician-diagnosed microvascular complications including diabetic neuropathy, retinopathy, nephropathy, and foot disorders were self-reported at questionnaire surveys. Results: A total of 7077 patients with type 2 diabetes were included in the cohort (4982 women in NHS and 2095 men in HPFS, mean [SD] age 61 [8.8], 94.2% White). During follow-up, 2878 patients developed microvascular complications. After multivariable adjustment, adherence to a healthy lifestyle before and after diabetes diagnosis were both associated with a lower risk of developing microvascular complications. The relative risk (RR) for participants with 4 or more low-risk lifestyle factors before diabetes diagnosis compared with zero was 0.73 (95% CI, 0.60-0.91) for any microvascular complications, 0.71 (95% CI, 0.54-0.93) for diabetic neuropathy, 0.76 (95% CI, 0.57-1.01) for diabetic retinopathy, 0.42 (95% CI, 0.23-0.79) for diabetic nephropathy, and 0.60 (95% CI, 0.35-1.00) for diabetic foot disorders. Similar results were observed for adherence to a healthy lifestyle after diabetes diagnosis, with an RR of 0.68 (95% CI, 0.55-0.83) for any microvascular complications, 0.67 (95% CI, 0.51-0.88) for diabetic neuropathy, 0.65 (95% CI, 0.48-0.86) for diabetic retinopathy, 0.57 (95% CI, 0.34-0.98) for diabetic nephropathy, and 0.62 (95% CI, 0.37-1.05) for diabetic foot disorders. In addition, greater improvement in lifestyle factors from before to after diabetes diagnosis was also significantly associated with a lower risk of neuropathy or total microvascular complications. Each increment in number of low-risk lifestyle factors was associated with a 6% (RR, 0.94; 95% CI, 0.90-0.98) lower risk for any microvascular complications and a 9% (RR, 0.91; 95% CI, 0.86-0.96) lower risk for diabetic neuropathy. Consistent results were observed when analyses were stratified by age at diabetes diagnosis, sex/cohort, or lifestyle factors before diabetes diagnosis. Conclusions and Relevance: In this cohort study, adhering to an overall healthy lifestyle was associated with a significantly lower risk of microvascular complications among individuals with diabetes. These findings suggest substantial reduction in the burden of microvascular complications associated with adopting a healthy lifestyle among patients with type 2 diabetes.

A case of squamous cell carcinoma of the scalp after several synthetic hair grafts.

UNLABELLED: In the early 1970s a novel method for hair restoration was described and gained a large following: hair implantation of artificial synthetic fibers. Though popular, the procedure faced numerous criticisms from the scientific community by the early 1980s, and several major and minor complications in a large number of patients treated were reported. However, there were no reports of any neoplasms as complications of artificial hair implantation. Thus, we report our experience with a novel case of long-term cutaneous neoplastic degeneration of an artificial hair implantation procedure in order to provide new insight on the complications related to this procedure. 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 at http://www.springer.com/00266.

In Autologous Breast Reconstruction, Frailty Is a More Accurate Predictor of Postoperative Complications: A Retrospective Cohort Analysis.

BACKGROUND: Autologous breast reconstruction has a higher postoperative complication rate in vulnerable patients. Given the high prevalence of obesity and aging, operative risk prediction is critical. Age, body mass index, and American Society of Anesthesiologists class are inaccurate predictive factors of postoperative complications. Frailty-a measure of vulnerability-was reported to be a reliable predictor of postoperative complications in multiple surgical fields. Here, we hypothesized that it would be an accurate predictor also in autologous breast reconstruction. METHODS: Patients undergoing autologous breast reconstruction (CPT code 19364) were identified using the American College of Surgeons National Surgical Quality Improvement Program database (January of 2010 to December of 2018). Frailty was calculated using the validated modified Frailty Index. Rates of wound complications, bleeding episodes, readmissions, returns to the operating room, and deep venous thromboses were compared across modified Frailty Index score, body mass index, age, and American Society of Anesthesiologists class. RESULTS: A modified Frailty Index score of 2 or greater was associated with a 22.22 percent ( p < 0.001) rate of wound complications; a 15.79 percent ( p < 0.001) rate of bleeding episodes; an 8.20 percent ( p < 0.001) rate of readmissions; a 17.19 percent ( p < 0.001) rate of return to the operating room; and a 1.81 percent ( p < 0.05) rate of deep venous thromboses. Higher body mass index, age, and American Society of Anesthesiologists class did not significantly correlate with increased rates in one or more postoperative complications. Only a high modified Frailty Index was consistently associated with significantly higher odds in all complication types. CONCLUSION: As a reliable and accurate predictor of postoperative complications in autologous breast reconstruction, frailty could be used preoperatively to counsel patients and guide surgical care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Applicant Familiarity Becomes Most Important Evaluation Factor in USMLE Step I Conversion to Pass/Fail: A Survey of Plastic Surgery Program Directors.

BACKGROUND: In 2020, Step 1 of the United States Medical Licensing Examination (USMLE) changed to a pass/fail reporting. Step 1 has been one of the main factors for both inviting applicants for interviews and for ranking in Plastic Surgery. Due to this change, we hypothesize that Step 2 CK - currently the only remaining, universal quantitative metric - will become the main factor in the residency selection process. METHODS: A survey-based cross-sectional study of United States (US) integrated plastic surgery program directors (PSPDs) investigated the factors that would assume importance following the change in the reporting pattern. RESULTS: Respondents reported that personal prior knowledge of the applicant, Letters of recommendation (LORs), Step 2 CK scores, and away rotation at the institution of interest would become the most important factors (median ratings of 5, 4.5, 4.5, 4.5, respectively on a 5-point Likert scale). Eighty-three percent of respondents were strongly dissatisfied with the conversion to pass/fail reporting. LOR's received the highest ranking (median,1; IQR,1-2) as the component used for offering away rotations after the implementation of the pass/fail reporting, followed by the applicant's medical school (median, 3; IQR, 3-4), and grades obtained during medical school (median,3; IQR,1.75-4). Standardized assessment during rotations are recommended by 67% of PSPDs. CONCLUSIONS: Future emphasis will be placed primarily on subjective metrics, including applicant familiarity. Step 2 CK, LORs, and away rotation at the institution of interest are other factors of importance. PSPDs welcome the adoption of objective assessments of patient care and medical knowledge to improve the current selection process.

NPWTi allows safe delayed free flap repair of Gustilo IIIb injuries: A prospective case series.

INTRODUCTION: Free flap lower extremity repair is associated with a high complication rate (>31%); higher rates are observed in more severe patients. In cases requiring prior systemic/local stabilization, delayed repair increases complication rate (+10% at 7 days): Negative-pressure Wound Therapy (NPWT) decreases complications but only when applied for less than 7 days. Recent limited evidence suggests that augmentation of NPWT with instillation for wound irrigation (NPWTi) might safely extend such window. This study hypothesizes that, through the combined cleansing effect of NPWT and instillation, NPWTi allows safe (low complication rate) delayed free flap repair in severe patients with Gustilo IIIb injuries (GIIIb). METHODS: A prospective case series was designed (inclusion criteria: GIIIb requiring microsurgical repair, severe patient/injury condition preventing immediate/early repair; exclusion criteria: allergy to NPWTi dressing). Patients received NPWTi (suction: 125 mmHg continuous; irrigation: NaCl 0.9%) until considered clinically ready for repair. Preoperative/postoperative complications (dehiscence, wound infection, bone non-union, osteomyelitis, flap failure) were monitored with clinical signs, imaging, and serum markers (CRP, WBC). RESULTS: Four patients (male: N = 4, female N = 1; Age: 59 [44-75] years-old) were treated. NPWTi was applied for 15.2 [9-28] days. No complication (0%) was observed preoperatively or postoperatively. Delayed repair occurred by latissimus dorsi musculocutaneous flap (N = 3), and anterolateral thigh flap (N = 2). All patients walked weight-bearing 12 [6-20] weeks after injury. CONCLUSIONS: NPWTi seems to allow safe delayed free flap repair in patients with severe lower extremity injuries unable to undergo immediate/early repair.

Hydrosurgical Debridement Allows Effective Wound Bed Preparation of Pressure Injuries: A Prospective Case Series.

BACKGROUND: Pressure injuries (PIs) are common in hospitalized patients, with incidence exceeding 50% in high-risk patients. Immobilization causes a prolonged compression of vascular networks in tissues overlying bony prominences, leading to ischemia and ulceration. Traditionally, PIs are treated with a combination of surgical debridement and reconstruction. This approach can be invasive for debilitated patients who cannot tolerate prolonged surgeries and extensive tissue resection. Hydrosurgery uses high-pressure irrigation to low-invasively debride and cleanse wounds; its use has shown positive outcomes in burn and chronic wounds care. Here, we hypothesize that hydrosurgery allows low-invasive yet effective wound bed preparation in truncal PIs. METHODS: We conducted a single-center, prospective, uncontrolled case series. Inclusion criteria for this study were presence of a truncal PI (stage III or IV) and an American Society of Anesthesiologists physical status of ≥2 (no exclusion criteria). Measured outcomes included duration of hydrosurgery, postsurgical local (dehiscence, infection, seroma) or systemic complications in the first 30 days, and PI recurrence rate (6-month follow-up). RESULTS: Seven patients (3 sacral, 2 greater trochanteric, and 2 ischial tuberosity PIs) were enrolled for this study. Average duration of hydrosurgery was 12 minutes (±3.1). No local or systemic complications were observed at a 30-day follow-up (0/7, 0%). All flaps (6/7, 86%) and graft (1/7, 14%) reconstructions successfully survived, and no PI recurrence was reported within a 6-month follow-up (0/7, 0%). CONCLUSIONS: Hydrosurgery seems to allow safe, low-invasive, and effective wound bed preparation in truncal PIs. Larger controlled trials are needed to confirm this preliminary evidence, to guide its broader adoption for improved care of high-risk patients with PIs.

Gender-specific Anatomical Distribution of Internal Pudendal Artery Perforator: A Radiographic Study for Perineal Reconstruction.

BACKGROUND: Cancer, trauma, infection, or radiation can cause perineal defects. Fasciocutaneous flaps based on perforator vessels (PV) from the internal pudendal artery (IPA) provide an ideal reconstructive option for moderate defects. We hypothesized that, due to gender differences in the pelvic-perineal region, the anatomical distribution of PV differs between genders. METHODS: Computed tomography angiographies from male and female patients without pelvic-perineal pathologies were retrospectively analyzed to study the vascular anatomy of the IPA. The number, size, type, and distribution of PV were recorded and compared between genders. Four anatomical regions were defined to describe the distribution of PV on each perineal side: anterior (A), anterior-central (AC), central-posterior (CP), and posterior (P). RESULTS: A total of 63 computed tomography angiographies were analyzed (men, 31; women, 32). Each IPA provides 2 ± 1 PV and 5 ± 2 terminal (cutaneous) branches: in both genders, 85% of PV are septocutaneous (15% musculocutaneous). In women, 70.5% of PV are located in AC, 28.2% in CP, 1.2% in A, and 0% in P: average diameter of the PV is 2.4 ± 0.3 mm. In men, 53.7% of PV are located in CP, 43.1% in AC, 3.3% in A, and 0% in P: average diameter of the PV is 2.8 ± 0.5 mm. Gender-specific differences in anatomical distribution of PV are significant (P < 0.001). CONCLUSIONS: Number, size, and type of terminal branches of PV of the IPA are consistent between genders, but their distribution is different, with women having an anterior predominance. Knowledge of gender-specific anatomy can guide preoperative planning and intraoperative dissection in flap-based perineal reconstruction.

Embryonic stem cell extracts improve wound healing in diabetic mice.

AIMS/HYPOTHESIS: Impaired wound healing significantly impacts morbidity and mortality in diabetic patients, necessitating the development of novel treatments to improve the wound healing process. We here investigated the topical use of acellular embryonic stem cell extracts (EXTs) in wound healing in diabetic db/db mice. METHODS: Wounds were induced in diabetic db/db mice, which were subsequently treated with EXTs, with 3T3 fibroblast cell line protein extracts (3T3XTs) or with saline as a control. Pathology and mechanistic assays were then performed. RESULTS: The in vivo topical administration of EXTs facilitates wound closure, contraction and re-epithelialization. Moreover, EXTs reduced the number of wound-infiltrating CD45+ inflammatory cells and increased the rate of repair and of angiogenesis as compared to controls. Interestingly, the EXT effect was partly enhanced by the use of a collagen-based biocompatible scaffold. In vivo, topical administration of EXTs increased the percentage of regulatory T cells in the wounded tissue, while in vitro EXT treatment reduced T cell-mediated IFN-γ production. Proteomic screening revealed 82 proteins differentially segregating in EXTs as compared to 3T3 extracts, with APEX1 identified as a key player for the observed immunomodulatory effect of EXTs. CONCLUSIONS: EXTs are endowed with immunoregulatory and anti-inflammatory properties; their use improves wound healing in diabetic preclinical models.