Vitamin D3 Improves Adipose Stromal Cell Survival and Human Fat Graft Retention in Xenograft Model.

Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex-vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide release via caspase, DAF-FM, or TMRM. Finally, forty Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with 1) Vehicle control, 2) 50ng calcitriol, 3) 50ng VD3, 4) 500ng VD3, and 5) 5000ng VD3 for 12 weeks, n=8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose escalating VD3 had significantly increased ASC viability compared to control (p<0.01). Under hypoxia, ASCs treated with 1nM VD3 had significantly greater viability than untreated and pre-treated cells (p<0.01, p<0.01) and significantly lower apoptosis-to-viability ratio (p<0.01). ASCs pre-treated with 1nM VD3 had significantly lower nitric oxide release (p<0.05) and lower mitochondrial polarization (p<0.05) compared to controls. In vivo results showed mice receiving 5000ng VD3 had significantly greater graft weight (p<0.05) and volume (p<0.05) after 12 weeks of treatment compared to controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention.

The Role of Suprapubic Superficial Fascial System Reconstruction During Repair of Adult-Acquired Buried Penis.

BACKGROUND: Adult-Acquired Buried Penis is a disorder associated with systemic obesity that confers increased risks of malignancy, sexual dysfunction, urinary abnormalities, and psychological distress. Surgical correction improves patient-reported functional and psychological outcomes and often requires collaboration between plastic and urologic surgeons. To improve postoperative cosmetic outcomes and decrease wound complications following adult-acquired buried penis repair, we performed an anatomic and histologic study of the superficial fascial layers providing support to the external male genitalia and describe our approach for fascial reconstruction. METHODS: We characterized the superficial fascial anatomy in three patients undergoing adult-acquired buried penis repair, including two patients with Wisconsin Type II disease and one patient with Wisconsin Type IV disease. Gross specimens were sent from two patients histologic analysis using H&E and elastin-specific stains to characterize the identity of the superficial fibrofatty tissue. RESULTS: In all three patients, the fundiform ligament overlying the suspensory ligament was identified, isolated, and transected for removal with the suprapubic specimen. We found that reapproximation of this ligament following transection at the time of escutcheonectomy provided significant lift to the penis and genitals via improved support of dartos fascia. Histologic analysis of the superficial fibrofatty tissue located beneath the dermis revealed histologic similarities with the superficial fascial system described previously in abdominal and breast tissue. CONCLUSIONS: Reapproximation of the fundiform ligament and superficial fascial tissue following suprapubic/lower abdominal fat pad removal during adult-acquired buried penis may improve postoperative cosmesis by reducing strain on the dermal closure. 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 http://www.springer.com/00266 .

The Future of Microsurgery: Vascularized Composite Allotransplantation and Engineering Vascularized Tissue.

Background: Microsurgical techniques have revolutionized the field of reconstructive surgery and are the mainstay for complex soft tissue reconstruction. However, their limitations have promoted the development of viable alternatives. This article seeks to explore technologies that have the potential of revolutionizing microsurgical reconstruction as it is currently known, reflect on current and future vascularized composite allotransplantation (VCA) practices, as well as describe the basic science within emerging technologies and their potential translational applications. Methods: A literature review was performed of the technologies that may represent the future of microsurgery: vascularized tissue engineering (VCA) and flap-specific tissue engineering. Results: VCA has shown great promise and has already been employed in the clinical setting (especially in face and limb transplantation). Immunosuppression, logistics, cost, and regulatory pathways remain barriers to overcome to make it freely available. Vascularized and flap-specific tissue engineering remain a laboratory reality but have the potential to supersede VCA. The capability of creating an off-the-shelf free flap matching the required tissue, size, and shape is a significant advantage. However, these technologies are still at the early stage and require significant advancement before they can be translated into the clinical setting. Conclusion: VCA, vascularized tissue engineering, and flap-specific bioengineering represent possible avenues for the evolution of current microsurgical techniques. The next decade will elucidate which of these three strategies will evolve into a tangible translational option and hopefully bring a paradigm shift of reconstructive surgery.

Fat Grafting and Regenerative Medicine in Burn Care.

Regenerative therapies such as fat grafting and Platelet Rich Plasma (PRP) have emerged as new options to tackle burn-related injuries and their long-term sequelae. Fat grafting is able to promote wound healing by regulating the inflammatory response, stimulating angiogenesis, favoring the remodeling of the extracellular matrix, and enhancing scar appearance. PRP can enhance wound healing by accelerating stages including hemostasis and re-epithelization. It can improve scar quality and complement fat grafting procedures. Their cost-effectiveness, minimal invasiveness, and promising results observed in the literature have made these tools as therapeutic candidates. The current evidence on fat grafting and PRP in acute and reconstructive burns is described and discussed in this study.

Risks and Complications Rate in Liposuction: A Systematic Review and Meta-Analysis.

Liposuction is a surgical procedure used to remove localized excess adipose tissue. According to The Aesthetic Society's latest annual report, liposuction is the most commonly performed cosmetic procedure. Despite its popularity, the existing literature lacks a unified understanding of the risks associated with liposuction. The aim of this study was to measure complications of liposuction. A systematic review and meta-analysis was reported according to PRISMA guidelines and registered on the PROSPERO database (CRD42023471626). The primary outcome was overall complication rate. The absolute risk for individual complications was also assessed. From 2957 articles, 39 studies were selected for analysis. In total, 29,368 patients were included, with a mean age of 40.62 years and mean BMI of 26.36 kg/m2. Overall, the rate of any complication was 2.62 (95% CI, 1.78-3.84). The most common complication was contour deformity, with a prevalence of 2.35% (95% CI, 1.05%-5.16%). The prevalence of hyperpigmentation was 1.49% (95% CI, 1.12%-1.99%), seroma 0.65% (95% CI, 0.33%-1.24%), hematoma 0.27% (95% CI, 0.12%-0.60%), superficial burn 0.25% (95% CI, 0.17%-0.36%), allergic reaction 0.16% (95% CI, 0.050%-0.52%), skin necrosis 0.046% (95% CI, 0.013%-0.16%), generalized edema 0.041% (95% CI, 0.0051%-0.32%), infection 0.020% (95% CI, 0.010%-0.050%), venous thromboembolism 0.017% (95% CI, 0.0060%-0.053%), and local anesthesia toxicity 0.016% (95% CI, 0.0040%-0.064%). Liposuction is a safe procedure with low complications, of which contour deformity is the most common. Raising awareness of specific risks can enhance surgical outcomes and improve patient-physician understanding.

A Bibliometric Analysis of the 50 Most Cited Articles on Body Contouring Surgery After Massive Weight Loss.

BACKGROUND: Body contouring surgery after massive weight loss has emerged a safe and reliable option to improve self-esteem, social life, work ability, physical activity, and sexual activity, and it is considered as an essential step in the multidisciplinary approach to morbid obesity. In this study, we aim to provide a comprehensive overview of the current state of literature on body contouring after massive weight loss, identifying research trends and areas for future investigation. METHODS: The Web of Science Core Collection was used to identify the 50 most cited publications on post-massive weight loss surgery. Data collected from each article included: title, journal, publication year, total citations, average citations per year, authors, study type, study topic, country, and institution of origin. RESULTS: The top 50 most-cited articles include 44 original articles and 6 review articles. The most cited article, published by Lockwood in 1991, received a total of 224 citations. The research areas included surgical outcomes and complications (n=19, 38%), psychological aspects such as body image, quality of life and desire for body contouring procedures (n=18, 36%), surgical techniques (n=11, 22%), an anatomical study (n=1, 2%), and a classification system (n=1; 2%). Plastic and Reconstructive Surgery journal published most (44%) of the papers identified. The University of Pittsburgh was the single institution that contributed the most (n=11; 22%). CONCLUSION: This bibliometric analysis provides insights and research trends for clinicians interested in body contouring after massive weight loss, facilitating the understanding and evolution of post-bariatric surgery and elucidating the rationale behind current practice. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.

BACKGROUND: Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. METHODS: Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. RESULTS: Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. CONCLUSIONS: Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.

The Effect of Fat Grafting on Scars Hyperpigmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyperpigmented scars, particularly in exposed body areas, can be difficult to conceal and may evoke psychological distress. While the precise causes of scar dyschromia are not fully understood, alterations in melanogenic activity appear to hold more significance than changes in melanocyte quantity. Current treatments encompass laser interventions. However, it is essential to consider their costs and potential complications in relation to their limited proven effectiveness. Fat grafting has gained interest as a scar modulation technique due to its regenerative properties, and its efficacy in reducing scar hyperpigmentation is currently under investigation. METHODS: A systematic review and meta-analysis was reported according to PRISMA guidelines. PubMed, Embase, and Cochrane Library databases were accessed. PROSPERO registration number is CRD42023457778. The primary outcome was a change in scar pigmentation after fat grafting. Pigmentation changes after fat grafting were calculated using the standardized mean difference (SMD) between baseline and postoperative scores according to POSAS and VSS scales. Bias assessment was conducted according to the National Institute for Health and Clinical Excellence quality assessment tool. RESULTS: A total of 8 articles meeting inclusion and exclusion criteria were identified, involving 323 patients with hyperpigmented scars treated with fat grafting. A significant difference in scar pigmentation was noted after treatment with fat grafting according to observers' ratings, with a SMD of - 1.09 [95% CI: - 1.32; - 0.85], p<0.01. The SMD for patient-reported scar pigmentation after treatment with fat grafting was - 0.99 [96% CI: - 1.31; - 0.66], p<0.01. Four studies provided objective measurements of melanin changes after fat grafting and revealed inconsistent findings compared to subjective observations. CONCLUSIONS: Fat grafting shows promise in ameliorating hyperpigmented scars based on subjective assessments, but further corroborating evidence from objective measures is required. 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 .

Clinical Practice Patterns in Abdominoplasty: 16-Year Analysis of Continuous Certification Data from the American Board of Plastic Surgery.

BACKGROUND: The authors evaluated trends in practice patterns for abdominoplasty based on a 16-year review of tracer data collected by the American Board of Plastic Surgery as part of the continuous certification process. METHODS: To facilitate comparison of an equal number of patients over time, tracer data from 2005 to 2021 were split into an early cohort (EC) (from 2005 to 2014) and a recent cohort (RC) (from 2015 to 2021). Fisher exact tests and two-sample t tests were used to compare patient demographics, surgical techniques, and complication rates. RESULTS: Data from 8990 abdominoplasties (EC, n = 4740; RC, n = 4250) were analyzed. RC abdominoplasties report a lower rate of complications (RC, 19%; EC, 22%; P < 0.001) and a lower rate of revision surgery (RC 8%; EC, 10%; P < 0.001). This has occurred despite the increased use of abdominal flap liposuction (RC, 25%; EC, 18%; P < 0.001). There has been a decline in the use of wide undermining (81% versus 75%; P < 0.001), vertical plication of the abdomen (89% versus 86%; P < 0.001), and surgical drains (93% versus 89%; P < 0.001). Abdominoplasty surgery is increasingly performed in an outpatient setting, with increased use of chemoprophylaxis for thrombosis prevention. CONCLUSIONS: Analysis of these American Board of Plastic Surgery tracer data highlights important trends in clinical practice over the past 16 years. Abdominoplasty continues to be a safe and effective procedure with similar complication and revision rates over the 16-year period.

Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Human adipose ECM alleviates radiation-induced skin fibrosis via endothelial cell-mediated M2 macrophage polarization.

Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM's potential in treating chronic-stage fibrosis.

Analyzing the Impact of Social and Psychiatric Factors in Patients Who Undergo Body Contouring Procedures.

BACKGROUND: As the prevalence of obesity increases, the number of patients seeking body contouring procedures after bariatric surgery for massive weight loss is increasing. Although the positive impact of bariatric surgery on physical and emotional health is well-described, few studies have reported on the psychosocial well-being of patients undergoing body contouring procedures. Psychosocial well-being can impact patient satisfaction and maintenance of weight loss, and is an important area to study. OBJECTIVE: The aim of this study was to characterize social and psychiatric factors of patients undergoing body contouring surgery, and to evaluate their impact on maintenance of weight loss. METHODS: A retrospective review was performed of patients who presented to a single institution for body contouring procedures between 2002 and 2018. Demographic details, medical history, psychosocial support, and operative details were collected. Univariate analysis and multinomial logistic regressions were performed with R statistical software (version 1.3.1093). RESULTS: A total of 1187 patients underwent at least 1 body contouring procedure during the study time frame. Mean BMI at presentation was 31.21 ± 10.49 kg/m2. Patients diagnosed with obesity at age 18 or older had significantly greater odds of suffering from generalized anxiety disorder (odds ratio [OR] 1.08 [95% CI, 1.02-1.15], P = .008). Patients with spousal support had 1.93 times higher odds of having maintained postbariatric weight loss at their 6-month follow-up (OR 1.93 [95% CI, 1.84-2.01], P = .028). CONCLUSIONS: Social support and age of obesity diagnosis impact psychological well-being and maintenance of weight loss following body contouring procedures.

The role of Kölliker-Fuse nucleus in breathing variability.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apneas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupneic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. Key points: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modeling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analyzing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide plausible hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Stem Cell Therapy Enriched Fat Grafting for the Reconstruction of Craniofacial Deficits.

Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting. Methods: Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months. Results: All patients had improvement in appearance. There were no serious adverse events. There was no significant difference in volume retention between the SVF-enriched and control regions overall (50.3% versus 57.3%, P = 0.269) or comparing malar regions (51.4% versus 56.7%, P = 0.494). Patient age, smoking status, obesity, and diagnosis of diabetes did not impact volume retention. Cell viability was 77.4% ± 7.3%. Cellular subpopulations were 60.1% ± 11.2% adipose derived stem cells, 12.2 ± 7.0% endothelial cells, and 9.2% ± 4.4% pericytes. A strong positive correlation was found between CD146+ CD31-pericytes and volume retention (R = 0.863, P = 0.027). Conclusions: Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.

Gnocchi Implants: An Unusual Differential Diagnosis for Breast Implant Rupture on Imaging.

Background: Although breast implant techniques have advanced considerably since the first recorded augmentation procedure in 1895, rupture remains a significant complication. Proper diagnosis is vital for patients' well-being but can sometimes prove challenging when there is no documentation of the initial procedure. Methods: This report describes a 58-year-old woman with a 30-year history of subglandular periareolar breast augmentation who was referred for bilateral implant rupture identified on computed tomography performed to monitor a breast nodule. Results: Despite classic imaging findings suggesting bilateral intracapsular implant rupture, breast implant revision surgery revealed a dense capsule containing 6 small silicone implants with no ruptures. Conclusions: This is a unique case where radiographic imaging was misleading due to an undocumented unusual breast augmentation procedure that used multiple small "gnocchi-like" silicone implants. To our knowledge, this technique has never been described until now and should be noted by the surgical and radiological community.

Sexual intercourse during pregnancy and its association with spontaneous preterm birth.

This study investigated whether sexual intercourse during pregnancy is associated with spontaneous preterm birth (SPTB). We included 77 women with SPTB and 145 women with a term birth. A total of 195 (87.8%) women had sexual intercourse during pregnancy, which was comparable between the groups. Primiparas with SPTB tended to report more often having sexual intercourse 3 - 4 times a week compared to primiparas with a term birth (8.8% vs. 0%, p =.082). We advise not to completely discourage sexual intercourse among pregnant women. Yet, high sexual intercourse frequency could be associated with SPTB.