Training in Vascular Microsurgery: The Ex Vivo Biological Model on Domestic Turkey Leg (Meleagris gallopavo).

There are various models for practicing microsurgical anastomoses, from synthetic to ex vivo and in vivo biological ones. In this study, we present the domestic turkey (Meleagris gallopavo) as an ex vivo biological model in the practice of surgical anastomoses. In our opinion, it represents a model that is very similar to a human one, low cost, and easy to find. In fact, our study shows that the diameters of the arteries and veins used for anastomoses (tibial artery diameter: 2.5 ±â€…0.6 mm; tibial vein diameter: 3.5 ±â€…1.2 mm) are similar to those of human arteries and veins most frequently used in microsurgical free flaps. So, we believe that this animal model is a great model for microsurgical training for doctors who approach this difficult and long to learn discipline.

Parecoxib decreases cellular growth and Bcl-2 protein levels in primary cultures of keloid fibroblasts.

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 µM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 µM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.

The Effect of Drains and Compressive Garments Versus Progressive Tensioning Sutures on Seroma Formation in Abdominoplasty: A New Perspective for Abdominoplasty Procedure?

Authors comment on the paper "The effect of drains and compressive garments versus progressive tensioning sutures on seroma formation in abdominoplasty" written by Brown et al in Aesthetic Plastic Surgery.Although the authors present interesting results on the effectiveness of progressive tensioning sutures proposed originally by Pollok and Pollok, we express some considerations about the analyzed data and patients, hoping in a new research extending these findings to include both aesthetic and post-bariatric abdominoplasty patients, evaluating the effectiveness of these sutures in varied contexts.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 Table of Contents or online Instructions to Authors www.springer.com/00266 .

Efficacy of a Novel Rigenase® and Polyhexanide (Fitostimoline® Septagel) Hydrogel Device for the Treatment of Vulvovaginitis Symptoms: Cross-Sectional Analysis of a National Survey and Prospective Observational Study.

Background and Objectives: Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey gynecologists about their habits regarding the treatments of the pathology and to evaluate the efficacy of a novel vaginal hydrogel composed of wheat extracts and polyhexanide aimed at reducing vulvovaginitis symptomatology. Materials and Methods: A cross-sectional analysis of a national survey using 155 Italian gynecologists and a prospective, open-label, observational study were carried out in 75 outpatient clinics across Italy. Pre- and postmenopausal women with suspicion of vulvovaginitis due to at least four of the following symptoms (leucoxanthorrhea, bad odor from genitalia, vulvovaginal dryness, petechiae, burning, and pruritus) while waiting for microbiological swab analysis were included and treated with one hydrogel application every 3 days for 1 week. Primary endpoint was the complete resolution of symptomatology. Results: The pre-study survey reported that, for most clinicians, local or oral treatment (65.7% and 82.8%, respectively) with antibiotics or antifungals is used very often. Therefore, we proceeded to carry out an observational study. Overall, 615 (362 of fertile age and 253 in postmenopause) women were included in this study. At the 28th follow-up examination, complete resolution of symptomatology was achieved in 578/615 (94.1%; p < 0.001) within 12.72 ± 6.55 and 13.22 ± 6.33 days for those of fertile age and in postmenopause, respectively (p = 0.342). All of the evaluated symptoms were significantly reduced after treatment (p = 0.001) without differences according to the patient's menopausal status. A slightly significant reduction in Gardnerella Vaginalis (p = 0.040) and Candida Albicans (p = 0.049) was found after treatment. No patient reported side effects, adverse reactions, or discontinued therapy. Conclusions: This pilot study showed that a hydrogel based on Rigenase® (wheat extract) and polyhexanide could be a promising treatment for the relief of vulvovaginitis symptoms. However, these results are limited by the absence of a control group. Additional comparative and randomized controlled trials between the hydrogel and other non-antibiotic devices as well as local antibiotic therapy should be performed to increase the validity of the findings.

Letter on: "Meta-analysis of the Oncological Safety of Autologous Fat Grafting After Breast Cancer on Basic Science and Clinical Studies".

Authors comment on the paper "Meta-analysis of the oncological safety of autologous fat grafting after breast cancer on basic science and clinical studies" written by Kai Wang et al in Aesthetic Plastic Surgery. Although the authors present interesting results on the safety of autologous fat graft after breast cancer and breast reconstruction, we express some considerations about the analyzed manuscript and about the safety of this procedure in specific cohort of patients having particular cancer characteristics.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 https://www.springer.com/00266 .

Multiple Foci of Basal Cell Carcinoma Arising in Rhinophyma: A Case Report and Literature Review.

Background: Rhinophyma is a benign condition caused by the excessive growth of sebaceous glands in the nasal tissue, presenting with symptoms such as nasal hypertrophy, erythema, and papules. Cases of basal cell carcinoma in rhinophyma have been reported in literature, but its etiological role remains unclear. It is uncertain whether rhinophyma is predisposed to neoplasm development or if their coexistence is coincidental. Material and Method: We conducted a literature survey to identify such cases reported over the years. Results: We identified 22 studies reporting a total of 47 cases in the literature, all involving male patients. The most common pattern of occurrence was the rapid growth of a nodular formation within the context of rhinophyma. Discussions and Conclusion: The elucidation of the association between basal cell carcinoma and rhinophyma remains challenging. The presence of multiple foci supports the theory that rhinophyma may play a role in their development, but larger studies are needed to establish a causal relationship.

Letter on: "Platelet-Rich Plasma for Treatment of Hair Loss Improves Patient-Reported Quality of Life".

Authors comment on the paper "Platelet-Rich Plasma for Treatment of Hair Loss Improves Patient-Reported Quality of Life" written by Abigail Meyers et al in Aesthetic Plastic Surgery. Although the authors present interesting results on the quality of life of patients after platelet-rich plasma, we express some considerations about the proposed composition of PRP and hoping in larger sample study.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Letter on: "Aesthetic, Quality-of-Life, and Clinical Outcomes after Inferior Pedicle Oncoplastic Reduction Mammoplasty".

Authors comment on the paper "Aesthetic, Quality of Life, and Clinical Outcomes after Inferior Pedicle Oncoplastic Reduction Mammoplasty" written by Thomas Y Xia et al. Although the authors present excellent results on Inferior Pedicle Oncoplastic Reduction Mammoplasty, we express some considerations about the proposed follow-up and hope in new research on this topic by Xia et al using his interesting data.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hyaluronic acid-based fillers in patients with autoimmune inflammatory diseases.

The use of hyaluronic acid (HA)-based aesthetic therapies is growing steadily, and according to the International Society of Aesthetic Plastic Surgery, more than 4.3 million aesthetic procedures using HA were performed in 2019, an increase of 15.7% than 2018. More people are offering these types of services, often without proper training or qualifications. Therefore, there is an increasing number of reports in the literature relating to possible adverse events, with subsequent therapeutic problems and more or less serious consequences for patients. The aim of this research is to carry out a review of the literature in order to evaluate the impact of hyaluronic acid-based fillers in patients with autoimmune inflammatory diseases, in particular scleroderma and Systemic Lupus Erythematosus (SLE). Although HA plays a central role in the inflammatory process, the use of HA-based fillers in patients with autoimmune inflammatory diseases is still controversial. HA, in fact, in inflamed tissues helps to propagate the inflammatory response and, injected in the form of a dermal filler, could potentially promote reactivation of the underlying disease. For this reason, many specialists do not perform HA-based aesthetic treatments in patients with scleroderma or SLE. However, recent scientific evidence suggests that the use of HA-based fillers in patients with scleroderma can lead to improvement of skin lesions, with satisfactory results. In the literature, there are no clinical studies that contraindicate the administration of HA-based dermal fillers in patients with inflammatory disease.

Letter on "An Original Approach to Massive Weight Loss Deformities in the Lower Thigh: A Retrospective Assessment of Results and Patients".

Authors comment on the paper "An Original Approach to Massive Weight Loss Deformities in the Lower Thigh: A Retrospective Assessment of Results and Patients" written by Dr. Pierfranco Simone et al. Although the authors present excellent results on medial tight lift, we express some considerations about the proposed follow-up and hope in new research on this topic by Dr. Simone et al. using his interesting technique.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pelvic Organ Prolapse Syndrome and Lower Urinary Tract Symptom Update: What's New?

(1) Background: This narrative review aimed to analyze the epidemiological, clinical, surgical, prognostic, and instrumental aspects of the link between pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), collecting the most recent evidence from the scientific literature. (2) Methods: We matched the terms "pelvic organ prolapse" (POP) and "lower urinary tract symptoms" (LUTS) on the following databases: Pubmed, Embase, Scopus, Google scholar, and Cochrane. We excluded case reports, systematic reviews, articles published in a language other than English, and studies focusing only on a surgical technique. (3) Results: There is a link between POP and LUTS. Bladder outlet obstruction (BOO) would increase variation in bladder structure and function, which could lead to an overactive bladder (OAB). There is no connection between the POP stage and LUTS. Prolapse surgery could modify the symptoms of OAB with improvement or healing. Post-surgical predictive factors of non-improvement of OAB or de novo onset include high BMI, neurological pathologies, age > 65 years, and the severity of symptoms; predictors of emptying disorders are neurological pathologies, BOO, perineal dysfunctions, severity of pre-surgery symptoms, and severe anterior prolapse. Urodynamics should be performed on a specific subset of patients (i.e., stress urinary incontinence, correct surgery planning), (4) Conclusions: Correction of prolapse is the primary treatment for detrusor underactivity and for patients with both POP and OAB.

SGLT2 breast expression could affect the cardiovascular performance in pre-menopausal women with fatty vs. non fatty breast via over-inflammation and sirtuins' down regulation.

OBJECTIVES: To evaluate the expression of sodium-glucose transporter 2 (SGLT2), inflammatory cytokines, and sirtuins in breast fat tissue at baseline, and serum cytokines of fatty vs. non-fatty pre-menopausal women at baseline, and at 12 months of follow-up. To correlate SGLT2/cytokines/sirtuins expression to clinical variables, and their changes (Δ) at follow-up, as intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. BACKGROUND: Pre-menopausal women with the lowest breast fat density (fatty breast) vs. higher breast fat density (non-fatty breast) are a high-risk population for cardiovascular diseases and worse prognosis. METHODS: We analyzed SGLT2/cytokines/sirtuins of excised fatty breasts of fatty vs. non-fatty pre-menopausal women. We correlated SGLT2/cytokines/sirtuins to Δ IMT, Δ LVM, Δ LVEF, and Δ MPI, and normal cardiac performance (NCP) at 1 year of follow-up. RESULTS: fatty vs. non-fatty breast over-expressed SGLT2/inflammatory cytokines, with lowest values of sirtuins (p<0.05). We found a direct correlation between SGLT2 (R2 0.745), TNFα (R2 0.262), and ΔMPI (p<0.05), and an inverse correlation between breast density (R2 -0.198), SIRT-3 (R2-0.181), and ΔMPI (p<0.05). Fatty breast (0.761, CI 95% [0.101-0.915]), SGLT2 (0.812, CI 95% [0.674-0.978]) and SIRT-3 (1.945, CI 95% [1.201-3.148]) predicted NCP at 1 year of follow-up. CONCLUSIONS: fatty vs. non-fatty breast women over-expressed SGLT2/inflammatory cytokines, and down-regulated breast sirtuins. SGLT2/inflammatory cytokines expression and inversely the tissue sirtuin 3 (tSIRT3) and breast percentage density linked to ΔMPI at 1 year of follow-up. Fatty breast and SGLT2 inversely predicted NCP; SIRT-3 increased the probability of NCP at 1 year of follow-up.

Potential role of the hydroxyl carboxylic acid receptor type 2 (HCAR2) in microglia pathophysiology: A possible cross-talk with C-X-C chemokine receptor 1 (CXCR1).

Following insults or injury, microglia cells are activated contributing to the cytotoxic response or by promoting an immune-mediated damage resolution. Microglia cells express HCA2R, a hydroxy carboxylic acid (HCA) receptor, which has been shown to mediate neuroprotective and anti-inflammatory effects. In this study we found that HCAR2 expression levels were increased in cultured rat microglia cells after Lipopolysaccharide (LPS) exposure. In a similar fashion, the treatment with MK 1903, a potent full agonist of HCAR2, increased the receptor protein levels. Moreover, HCAR2 stimulation prevented i) cells viability ii) morphological activation iii) pro/anti-inflammatory mediators production in LPS-treated cells. Likewise, HCAR2 stimulation reduced the proinflammatory mediators mRNA expression induced by neuronal chemokine fractalkine (FKN), a neuronal derived chemokine activating its unique receptor, chemokine receptor 1 (CX3CR1) on microglia surface. Interestingly, electrophysiological recordings in vivo revealed that MK1903 was able to prevent the increase of the nociceptive neurons (NS) firing activity mediated by the spinal FKN application in healthy rats. Collectively, our data demonstrate that HCAR2 is functionally expressed in microglia, by showing its capability to shift microglia toward an anti-inflammatory phenotype. Moreover, we indicated the contribute of HCAR2 in the FKN signaling and suggested a possible HCAR2/CX3CR1 functional interaction. This study paves the way for further investigations aimed at understanding the role HCAR2 as potential target in neuroinflammation-based CNS disorders. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".

Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome.

BACKGROUND: Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. METHODS: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C-) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). RESULTS: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C-), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. CONCLUSIONS: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

Systemic Beta-Hydroxybutyrate Affects BDNF and Autophagy into the Retina of Diabetic Mice.

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25−50−100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome−lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.

Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9.

Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether the changes will persist long term or are capable of resolving. This review brings together existing knowledge on both COVID-19 and pulmonary fibrosis, starting with the main key players in promoting pulmonary fibrosis, such as alveolar and endothelial cells, fibroblasts, lipofibroblasts, and macrophages. Further, we provide an overview of the main molecular mechanisms driving the fibrotic process in connection with Galactin-1, -3, -8, and -9, together with the currently approved and newly proposed clinical therapeutic solutions given for the treatment of fibrosis, based on their inhibition. The work underlines the particular pathways and processes that may be implicated in pulmonary fibrosis pathogenesis post-SARS-CoV-2 viral infection. The recent data suggest that galectin-1, -3, -8, and -9 could become valuable biomarkers for the diagnosis and prognosis of lung fibrosis post-COVID-19 and promising molecular targets for the development of new and original therapeutic tools to treat the disease.

Post-Bariatric Plastic Surgery: Abdominoplasty, the State of the Art in Body Contouring.

Due to the increased prevalence of obesity in the last decades, bariatric surgery has been on the rise in recent years. Bariatric surgery is a compelling option for weight loss in obese patients with severe obesity-related comorbidities or for whom lifestyle modifications have proven ineffective. Redundant skin following significant weight loss is a common occurrence affecting up to 96% of patients who undergo bariatric surgery, negatively impacting physical and psychosocial health and detracting from activities of daily living. Statistics of the American Society of Plastic Surgeons show that 46,577 body contouring procedures were performed after massive weight loss in the USA in a 2020 report. Abdominoplasty, a well-established cosmetic surgery procedure for improving body contour, is performed by removing excess skin and fat from the abdominal wall and thereby restoring musculofascial integrity and skin elasticity, resulting in a more ideal body shape and increasing quality of life. Although abdominoplasty is a safe procedure, it has been associated with a higher complication rate compared with other body-contouring procedures. Technologic advances over the past decade have been developed as non-invasive alternatives or adjunctive tools to surgery to enhance cosmetic results and minimize complications. New energy-based technologies may supplant invasive surgery for mild to moderate skin laxity and/or diminish the extent of surgery and resulting scars. Plastic surgeons play a significant role in improving the quality of life of patients who suffer from obesity and underwent bariatric surgery. We are deeply convinced, however, that the advancement of knowledge and research in this field will determine the introduction of new technologies and custom-made techniques. This advancement will reduce the complication rate with a rapid reintegration of the patient into the world of work and resumption of daily activities.

MED1/BDNF/TrkB pathway is involved in thalamic hemorrhage-induced pain and depression by regulating microglia.

Central post-stroke pain (CPSP) and associated depression remain poorly understood and pharmacological treatments are unsatisfactory. Recently, microglia activation was suggested to be involved in CPSP pathophysiology. The goal of this study was to investigate the effectiveness of a co-ultramicronized combination of N-palmitoylethanolamide and luteolin (PEALut) in a mouse model of thalamic hemorrhage (TH)-induced CPSP. TH was established through the collagenase-IV injection in thalamic ventral-posterolateral-nucleus. PEALut effects in CPSP-associated behaviors were evaluated during a 28-days observation period. We found that repeated administrations of co-ultra PEALut significantly reduced mechanical hypersensitivity after TH, as compared to vehicle, by reducing the early microglial activation in the perilesional site. Moreover, PEALut prevented the development of depressive-like behavior (21 days post-TH). These effects were associated with the restoration of synaptic plasticity in LEC-DG pathway and monoamines levels found impaired in TH mice. Hippocampal MED1 and TrkB expressions were significantly increased in TH compared to sham mice 21 days post-TH, whereas BDNF levels were decreased. PEALut restored MED1/TrkB/BDNF expression in mice. Remarkably, we found significant overexpression of MED1 in the human autoptic brain specimens after stroke, indicating a translational potential of our findings. These results pave the way for better-investigating depression in TH- induced CPSP, together with the involvement of MED1/TrkB/BDNF pathway, proposing PEALut as an adjuvant treatment.

Long-term neuropathic pain behaviors correlate with synaptic plasticity and limbic circuit alteration: a comparative observational study in mice.

ABSTRACT: Neuropathic pain has long-term consequences in affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. In this study, we used the spared nerve injury (SNI) model to characterize the development of sensory and aversive components of neuropathic pain and to determine their electrophysiological impact across prefrontal cortex and limbic regions. Moreover, we evaluated the regulation of several genes involved in immune response and inflammation triggered by SNI. We showed that SNI led to sensorial hypersensitivity (cold and mechanical stimuli) and depressive-like behavior lasting 12 months after nerve injury. Of interest, changes in nonemotional cognitive tasks (novel object recognition and Y maze) showed in 1-month SNI mice were not evident normal in the 12-month SNI animals. In vivo electrophysiology revealed an impaired long-term potentiation at prefrontal cortex-nucleus accumbens core pathway in both the 1-month and 12-month SNI mice. On the other hand, a reduced neural activity was recorded in the lateral entorhinal cortex-dentate gyrus pathway in the 1-month SNI mice, but not in the 12-month SNI mice. Finally, we observed the upregulation of specific genes involved in immune response in the hippocampus of 1-month SNI mice, but not in the 12-month SNI mice, suggesting a neuroinflammatory response that may contribute to the SNI phenotype. These data suggest that distinct brain circuits may drive the psychiatric components of neuropathic pain and pave the way for better investigation of the long-term consequences of peripheral nerve injury for which most of the available drugs are to date unsatisfactory.