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Heart failure (HF) is usually suspected by clinical history, symptoms, physical examination, electrocardiogram findings, and natriuretic peptides’ values. However, echocardiography and other imaging techniques play an essential role in supporting HF diagnosis. Thanks to its non-invasiveness and safety, transthoracic echocardiography is the first-level technique of choice to assess myocardial structure and function, trying to establish the diagnosis of HF with reduced, mildly reduced, and preserved ejection fraction. The role of echocardiography is not limited to diagnosis but it represents a crucial tool in guiding therapeutic decision-making and monitoring response to therapy. Over the last decades, several technological advancements were made in the imaging field, aiming at better understanding the morphofunctional abnormalities occurring in cardiovascular diseases. The purpose of this review article is to summarize the incremental role of imaging techniques (in particular cardiac magnetic resonance and myocardial scintigraphy) in HF, highlighting their essential applications to HF diagnosis and management.

Introduction Three-dimensional electroanatomical mapping (3D EAM) has expanded radiofrequency catheter ablation applications in humans to almost all complex arrhythmias and has drastically reduced fluoroscopy use, yet its potential in dogs is poorly investigated. The objectives of the current study were to assess the feasibility and safety of 3D EAM of all four heart chambers, 3D EAM-guided biopsies and transseptal puncture in dogs. Animals Eight healthy purpose-bred Beagle dogs. Materials and Methods Electroanatomical mapping was performed under general anaesthesia during sinus rhythm using a 22-electrode mapping catheter. Left heart catheterisation was achieved by either retrograde transaortic access (n = 4) or transseptal puncture (n = 4). Results Successful 3D EAM of the right atrium and ventricle was achieved in all dogs at a median time of 33 (13–40) and 17 (3–52) min, respectively. Left atrial and ventricular 3D EAM was successful in six and seven dogs, at a median time of 17 (4–27) and 8 min (4–19), respectively. Complications requiring intervention occurred in one dog only and were a transient third degree atrioventricular block and pericardial effusion following transseptal puncture, which was treated by pericardiocentesis. All dogs recovered uneventfully. Fluoroscopy time was limited to a median of 7 min (0–45) and almost exclusively associated with transseptal puncture. Conclusions Three-dimensional EAM of all cardiac chambers, including mapping-guided biopsy and transseptal puncture is feasible in small dogs. Complications are similar to those reported in human patients. This suggests a potential added value of 3D EAM to conventional electrophysiology in dogs with arrhythmias.

Introdução: A Terapia de Indução Percutânea de Colágeno (TIPC) tem sido utilizada frequentemente no tratamento de cicatrizes de acne. Objetivo: Identificar os efeitos da TIPC no tratamento de cicatrizes de acne em adultos e sua combinação com outras terapias. Método: Foi realizada uma revisão sistemática, com levantamento de dados nas bases de dados PUBMED, PEDro e CENTRAL. Foram incluídos apenas estudos com delineamento de ensaios clínicos randomizados, com versão em texto completo e sem restrições de idioma ou ano de publicação. Os estudos foram analisados por meio da escala PEDro. Resultados: Foram identificados 5420 artigos nas bases de dados. Após a exclusão de 28 artigos duplicados, foram excluídos 5393 artigos pela análise dos títulos, 7 pela análise dos resumos e 12 a partir da leitura na íntegra, sendo selecionados 9 artigos para análise. A maioria dos relatórios indicou que o microagulhamento é seguro e bem tolerável para todos os pacientes, enquanto a terapia combinada mostrou melhora na aparência das cicatrizes de acne. Agentes tópicos adicionais, como o ácido tricloroacético, recebem benefícios do microagulhamento, pois aumentam a entrega de drogas através da barreira cutânea. Conclusão: O microagulhamento em conjugação com solução de jesser, laser de CO2 fracionado, PRP, injeção intradérmica de plasma de plaquetas, peeling de ácido glicólico 35% e peeling químico apresenta melhor tolerância e efetividade no tratamento de cicatrizes de acne em adultos em relação a monoterapia. No entanto, pesquisas com um melhor desenho metodológico e um tamanho de amostra maior se tornam necessárias.

The eyebrow is a complex structure of the human face, which has both functional (communication) and aesthetic aspects and contributes to a persons’ individual appearance. Ptosis of the eyebrow is a common condition, especially among the elderly and smokers. Facial appearance is disrupted by eyebrow ptosis, and in many cases, correction and treatment are needed. No specific type of browlift has been shown to be superior to another, and since there is a wide variation in treatment preference between patients, it requires an individual approach to each specific patient. This review provides an overview of the history of the browlift, non-surgical treatment and current surgical techniques available.Level of evidence: Not ratable.

Chronic inflammation in cesarean scar defect contributes to secondary infertility in women with cesarean scar syndrom; however, it remains unclear about the situation of inflammation in uterine cavity in women with cesarean scar syndrome. This ambidirectional cohort study aimed to explore the effect of inflammation in the uterine cavities of women with cesarean scar syndrome on infertility at a single university hospital. The frequency of chronic endometritis in infertile patients was retrospectively compared between the cesarean scar syndrome group and non-cesarean scar syndrome group. The frequency of endometriosis was also investigated in patients with cesarean scar syndrome who underwent laparoscopy. The level of tumor necrosis factor-α and interleukin-1β in the uterine cavity was prospectively evaluated in the cesarean scar syndrome group and in women with a history of cesarean section (control group) using an enzyme-linked immunosorbent assay. There was a significant difference in the incidence of chronic endometritis between the cesarean scar syndrome and non-cesarean scar syndrome groups (65.8% and 46.0%, respectively, p = 0.0315). Endometriosis was detected in 51 (70%) patients with laparoscopy. Tumor necrosis factor-α and interleukin-1β levels in the cesarean scar syndrome group were significantly higher than those in the control group (p = 0.0002 and p = 0.0217, respectively). Our findings suggest that one cause of secondary infertility in women with cesarean scar syndrome is embryo implantation failure-associated chronic endometritis, endometriosis, and chronic inflammation in the uterine cavity.

Background: Transcutaneous lower eyelid approaches are associated with a risk of postoperative scarring depending on the distance between the incision line and the lower eyelid margin. The lower eyelid crease of Caucasians corresponds to a ridge-shaped fold in young Asians. However, this relationship has not been sufficiently evaluated in the latter. The authors, therefore, investigated the location of the scar and the lower eyelid crease or ridge to find the optimal location for the incision line.Methods: This study included 60 out of 139 patients who underwent inferior orbital wall reconstruction through a lower eyelid skin incision between July 2019 and June 2020. According to the location of the scar, the patients were classified into three groups: group A ( ≥ 2 mm above the lower eyelid crease or ridge), group B (within the lower eyelid crease or ridge to 2 mm above the lower eyelid crease or ridge), and group C (within the lower eyelid crease or ridge to 2 mm below the lower eyelid crease or ridge). At 6 or 12 months after surgery, the Patient and Observer Scar Assessment Scale (POSAS) score was obtained, the distance between the lower eyelid margin and the scar (DMS) and the distance between the margins of the peripheral pupil and the lower eyelid (DMPE) were measured, and the occurrence of ectropion was evaluated.Results: Group B had the lowest POSAS score (A: 22.7 ± 8.0, B: 20.9 ± 2.4, C: 32.5 ± 4.1, p < 0.001). Linear regression analysis showed that the DMS was positively correlated with the POSAS score (p < 0.001) and that the risk of DMPE widening increased as the DMS decreased (p = 0.029). None of the patients had ectropion.Conclusion: When using the transcutaneous approach for inferior orbital wall reconstruction, the optimal incision site is within the lower eyelid crease or ridge to 2 mm above the lower eyelid crease or ridge.

Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.

Introduction Third-degree burns are known to affect the epidermis, dermis, hypodermis and adjacent structures, causing damage to the dermal matrix. To date, the gold standard treatment is autologous skin grafting. However, its effectiveness is limited owing to its availability and cost. Depending on the severity of the wound, the maturation of the graft can take several weeks. The cosmetic results are often unsatisfactory. Given the need to develop new therapies to improve the management and quality of life of patients, cell therapy has become a promising alternative. Objective To describe the evolution of non-grafted third-degree burns after subcutaneous application of autologous bone marrow (BM) total nucleated cells (TNCs). Case report We present the case of a 52-year-old male patient with a third-degree scald on the external surface of the left foot. Nine days after the burn, 2 ml of autologous BM TNCs were applied subcutaneously around the wound. An autologous skin graft was not performed; therefore, healing was performed with second intention. The patient had good clinical evolution without any keloid scars or complications. Conclusion Although current treatments for third-degree burns still have limitations, recent studies have shown the effectiveness of stem cells in these types of burns by allowing accelerated healing. However, further studies are required to demonstrate their efficacy and safety.

Introduction The philtral ridges form a prominent visual landmark in the upper lip. An aesthetically pleasing cleft lip repair should restore this preferably without any scars cutting across it. Although there are several scientific publications on morphology of this structure and its variations, very few studies on the Indian population have been published. Aim To study the morphology of the philtral ridges and their relationship to the columellar base in normal Indian children and its significance in cleft lip repair. Methods 115 normal healthy children from southern India aged between one and 12 years were studied based on direct observation of the relationship of the superior end of the philtral ridge to the columellar base and nasal sill. In type A, the philtral ridge terminates at the nasal sill just lateral to the columellar base, and in type B, it either reaches or fades before reaching the columellar base. All observations were performed by the first author by examining standardized two-dimensional (2D) photographs of the upper lip-nose complex. Results In this study, 74% of the subjects had the philtral column extending lateral to the columellar base. Conclusion These finding assume a significance since, in a substantial proportion of the studied population, techniques of cleft lip repair such as the rotation advancement method, place a scar that crosses the upper third of the philtral ridge which may be undesirable.

Wounds on embryonic mouse fetuses regenerate up to embryonic day (E) 13, but after E14, the pattern is lost and a visible scar remains. We hypothesized that the sonic hedgehog (Shh), which is involved in patterning during development, is involved in the regeneration of texture. Embryos of ICR mice were surgically injured at E13, E14, and E15 and analyzed for the expression of Shh. For external Shh administration, recombinant Shh-containing slow-release beads were implanted in the wounds of mice. In contrast, cyclopamine was administered to wounds of adult mice to inhibit Shh. The expression of Shh was unaltered at E13, whereas it was upregulated in the epidermis of the wound from E14 onward. Implantation of recombinant Shh-containing beads into E13 wounds inhibited skin texture regeneration. Cyclopamine treatment inhibited epithelialization and thickening of the epidermis in the wounds of adult mice. In vitro, Shh promoted proliferation and inhibited the migration of epidermal keratinocytes through the activation of cyclin D proteins. Thus, our results suggested that the expression of Shh is involved in the regeneration of texture during wound healing, especially in epidermal keratinocyte migration and division, and could inhibit skin texture regeneration after E14.

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non-gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine-induced rat model of muscle injury. Forty-eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post-surgery to examine the following: (1) inflammatory (interleukin [IL]-1β, IL-6), and transforming growth factor (TGF)-β and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL-1β, IL-6, and TGF-β expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL-1β, IL-6, and TGF-β. The paste is inexpensive and non-invasive. Thus, it may be the treatment of choice for patients with muscle damage.

Data extracted from 35 studies included in a systematic review

Study design/patients and methods A 19-year-old male was reported to have a postoperative facial trauma suture as a result of being involved in a car accident. Red light-emitting diode (LED) therapy (20 min, 96 J/cm2, 633 nm), Botulinum Toxin Type A 36 IU injection, BroadBand Light and Er:YAG laser at various stages of wound healing were applied as the sequential therapy. Results Since the correction was promptly apparent and acceptable, the treatment proved secure and efficacious for repairing wound healing. Conclusion Clinically sequential therapy has demonstrated marked improvement in our case. Scar sequential therapy may offer a new strategy for wound healing recovery.

Background: Facial Lacerations constitute an important reason for children (< 18 years) to visit emergency room. While bleeding and pain are the associated acute problems, the long term outcome in terms of a cosmetically acceptable scar is a matter of significant parental concern. The aim of the research is to study the profile of facial lacerations in children and to assess the outcome of repair. Materials and Methods: A retrospective review of children who underwent facial laceration repair between January 2018 and December 2020 was done. The deep ones underwent sutured repair in layers reinforced withtissue adhesive in operation room under intra-venous anesthesia and superficial ones in emergency room with only tissue adhesive following usual wound treatment protocol. Demographics, surgical details and outcomes were studied. All the repaired cuts were followed up at 1 year retrospectively and the cosmetic outcome was evaluated using modified stony brooke scoring system. Results: A total of 40 patients (24 males, 16 females) underwent facial laceration repair at a mean age of 4.7 years (range 1-13 years). Seventeen were deep and 23 were superficial cuts. Only1child in the superficial group with gross wound contamination at presentation developed wound infection. No dissatisfaction was reported in the deep group while parents of 4 children in the superficial group reported dissatisfaction with the final scar. Conclusion: While surface cuts can be treated with irrigations and tissue adhesive in the emergency room, the deeper cuts require layered repair aided by tissue adhesive for optimum scar outcome.

Wound healing is a complicated cascading process; disequilibrium among reparative processes leads to the formation of pathologic scars. Herein, we explored the role of mortalin in scar formation and its association with the interleukin-1α receptor using in vitro and in vivo models. To investigate the effects of mortalin, we performed an MTT cell viability assay, qRT-PCR, and Western blot analyses, in addition to immunofluorescence and immunoprecipitation studies using cultured fibroblasts. A rat incisional wound model was used to evaluate the effect of a mortalin-specific shRNA (dE1-RGD/GFP/shMot) Ad vector in scar tissue. In vitro, the mortalin-treated human dermal fibroblast displayed a significant increase in proliferation of type I collagen, α-smooth muscle actin, transforming growth factor-β, phospho-Smad2/3-complex, and NF-κB levels. Immunofluorescence staining revealed markedly increased mortalin and interleukin-1α receptor protein in keloid tissue compared to those in normal tissue, suggesting that the association between mortalin and IL-1α receptor was responsible for the fibrogenic effect. In vivo, mortalin-specific shRNA-expressing Ad vectors significantly decreased the scar size and type-I-collagen, α-SMA, and phospho-Smad2/3-complex expression in rat incisional scar tissue. Thus, dE1-RGD/GEP/shMot can inhibit the TGF-β/α-SMA axis and NF-κB signal pathways in scar formation, and blocking endogenous mortalin could be a potential therapeutic target for keloids.

RINGS is an international initiative to facilitate collaborative international effort to map all Antarctic ice-sheet margin to accurately estimate ice discharge from Antarcitca. This whitepaper is authored by the RINGS Action Group in Scientific Committee on Antarctic Research. Members of this action group is listed in the whitepaper.

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring.

Acne scars are a frequent complication with major social and psychological implications for the individual, to which attention must be paid. aiming at the timely and aggressive management of severe forms of acne, thus avoiding, as far as possible, its appearance. However, some of these patients will present this complication even with early intervention, this is due to impaired healing and the severity and duration of the inflammatory phenomenon. At a time when there are still no indisputable treatments in this area, it is necessary to seek a consensus that allows patients to provide physical and psychological relief for an irreversible sequel, even more so when it is secondary to a high incidence pathology such as acne. The main objective of this article is to review the existing valid evidence on the different treatment options and the association of these therapies to attenuate the scars caused by acne vulgaris. Literature review was used as a research methodology. In conclusion, the programming of the various parameters of the different types of therapies seems to play a definitive role in the final success of the treatment.

AIM: To investigate and evaluate healing patterns around flaps made with different side-cut angulations after femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Thirty-four patients (68 eyes) received a 90° side-cut (n=34) or a 120° side-cut flaps (n=34) made with a femtosecond laser. One day, 1wk, 1 and 3mo postoperatively, side-cut scar was evaluated under slit-lamp photography according to a new grading system (Grade 0=transparent scar, 1=faint healing opacity, and 2=evident healing opacity). In vivo corneal confocal microscopy and anterior segment optical coherence tomography (AS-OCT) were used to observe wound-healing patterns around flap margin in the two groups. Sirius Scheimpflug Analyzer was also used to analyze higher order aberrations 3mo after surgery. RESULTS: There were no significant differences in flap wound-healing patterns at each follow up between the two groups (P>0.05). Three months after surgery, the flap edge scar classified as Grade 0 had excellent apposition and rapid nerve regeneration. At 3 mm and 5 mm pupil diameters, there were significant differences in trefoil aberrations between the two groups (P0.05). CONCLUSION: Flap edge scars classified as Grade 0 have excellent apposition and rapid nerve regeneration, and 120° side-cut angle flaps induce less trefoil aberrations after FS-LASIK.

A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil‐added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil‐added groups. On histologic examination, verapamil‐added groups showed (a) reduced SEI (1.93 (1.79‐2.67) for control vs 1.34 (1.21‐1.51) for silicone only and 1.13 (1.01‐1.65) for verapamil‐added silicone), (b) fibroblast count 700.5 (599.5‐838.5) for control, 613.25 (461‐762.5) for silicone only, and 347.33 (182.5‐527) for verapamil‐added silicone), and (c) capillary formation (52 (35.5‐96.5) for control, 46 (28‐64.5) for silicone only, and 39.83(24‐70) for verapamil‐added silicone) (Kruskal‐Wallis test, P

Background/Aims: Endoscopic submucosal dissection (ESD) for gastric neoplasms is a widely performed procedure. Local recurrence is rare, but various post-ESD scars are encountered during follow-up endoscopy. Therefore, we investigated atypical scar patterns and evaluated the associated factors.Materials and Methods: Clinicopathologic and endoscopic reviews of gastric neoplasms treated with ESD from January 2009 to December 2015 were conducted. Atypical scar patterns were classified as irregular erythema, nodularity, or mucosal defect.Results: A total of 264 patients with 274 gastric neoplasms, including 201 adenomas and 73 early gastric cancers, were enrolled. The key endoscopic findings at the resection scar were defined on the basis of gross morphology as follows: irregular erythema, mucosal defect (erosion or ulcer), and nodularity. An irregular erythema scar pattern was associated with male sex, a nodularity scar pattern with smoking, and a mucosal defect scar pattern with infra-angle location (angle and antrum) and cancer. An irregular erythema with nodularity scar pattern was also associated with male sex. An irregular erythema with nodularity and mucosal defect scar pattern was associated with liver disease and chronic kidney disease.Conclusions: The atypical scar patterns after gastric ESD are associated with various clinicopathologic factors.

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases., Graphical abstract Artemisinin drugs, isolated from Artemisia, effectively prevent or treat multiple types of tissue fibrosis when administered to several preclinical animal models of varied etiologies.Image 1

BackgroundHypertrophic scars can cause pain, movement restrictions, and reduction of quality of life. Despite numerous options to tackle hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Secreted factors from peripheral blood mononuclear cells (PBMCsec) were previously described for their beneficial effects in tissue regeneration. Here, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single cell resolution (scRNAseq).MethodsMouse wounds and scars were treated with PBMCsec either intradermally or topically. Human mature scars were treated with PBMCsec ex vivo in explant cultures. All experimental settings were analyzed by single cell RNA sequencing (scRNAseq). A variety of bioinformatics approaches were used to decipher gene regulation in the scRNAseq data sets. Components of the extracellular matrix (ECM) were investigated in situ by immunofluorescence. The effect of PBMCsec on myofibroblast differentiation and elastin expression was investigated by stimulating human primary fibroblasts with TGFβ.FindingsTopical and intradermal application of PBMCsec regulated the expression of a variety of genes involved in pro-fibrotic processes and tissue remodeling. Our bioinformatics approach identified elastin as a common linchpin of antifibrotic action in both, the mouse and human experimental setting.In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast-differentiation and attenuates abundant elastin expression through non-canonical signaling inhibition. Furthermore, TGFβ-induced breakdown of elastic fibers was strongly inhibited by addition of PBMCsec.InterpretationTogether, we showed anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings, suggesting PBMCsec as a novel therapeutic option to treat skin scarring.Research in contextEvidence before this studyParacrine factors secreted from irradiated peripheral mononuclear cells (PBMCsec) show strong tissue regenerative properties in a variety of organs and are shown to enhance cutaneous wound healing. Whether PBMCsec shows anti-fibrotic properties on scar formation has not been investigated so far.Added value of this studyIn the present study, we were able to demonstrate that PBMCsec improves quality of developing and mature scars in mouse and human scar tissue. We found that PBMCsec is able to attenuate the expression of various genes, promoting scar formation and inhibit TGFβ-induced myofibroblast differentiation. Elastin and TXNIP were identified as a common linchpin of its anti-fibrotic action.Implications of all the available evidenceUsingin vivo, ex vivo, andin vitromodels and analyses on a single-cell level, our study paves the way for clinical studies evaluating the use of PBMCsec for the treatment of human cutaneous scars.

Endoscopic submucosal dissection (ESD) is considered the treatment of choice for early gastric cancer (EGC) with a negligible risk of lymph node metastasis. Locally recurrent lesions on artificial ulcer scars are difficult to manage. Predicting the risk of local recurrence after ESD is important to manage and prevent the event. We aimed to elucidate the risk factors associated with local recurrence after ESD of EGC. Between November 2008 and February 2016, consecutive patients (n = 641; mean age, 69.3 ± 9.5 years; men, 77.2%) with EGC who underwent ESD at a single tertiary referral hospital were retrospectively analyzed to evaluate the incidence and factors associated with local recurrence. Local recurrence was defined as the development of neoplastic lesions at or adjacent to the site of the post-ESD scar. En bloc and complete resection rates were 97.8% and 93.6%, respectively. The local recurrence rate after ESD was 3.1%. The mean follow-up period after ESD was 50.7 ± 32.5 months. One case of gastric cancer-related death (0.15%) was noted, wherein the patient had refused additive surgical resection after ESD for EGC with lymphatic and deep submucosal invasion. Lesion size ≥15 mm, incomplete histologic resection, undifferentiated adenocarcinoma, scar, and the absence of erythema of the surface were associated with a higher risk of local recurrence. Predicting local recurrence during regular endoscopic surveillance after ESD is important, especially in patients with a larger lesion size (≥15 mm), incomplete histologic resection, surface changes of scars, and no erythema of the surface.

Presented herein is the only case in literature with the synchronous development of endometrioid-type endometrium cancer and endometrioid carcinoma originating from the endometriosis foci in a scar tissue. A 44-year-old female patient presented with complaints of abnormal uterine bleeding, swelling at the rectus muscle level in the abdominal wall, and cyclic pain close to the old cesarean section incision scar. Pathological findings of the rectus muscle and endometrial biopsies revealed endometrioid adenocarcinoma (grades 2 and 1, respectively). Positron emission tomography, performed for primary focus investigation, revealed pathologic fluorodeoxyglucose uptake in the uterine cavity and biopsy site, consistent with residual tumor without any pathologic uptake elsewhere. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic and para-aortic lymphadenectomy, and the residual tumor in the left rectus muscle was excised. The patient was followed up for 3 years. At a postoperative follow-up in the 4th year, no relapsed tumor or metastasis was seen on imaging.

Severe anal stenosis is an unusual complication following hemorrhoidectomy but leads to severe morbidity. The treatment of severe anal stenosis is usually some type of anoplasty. We designed a heart-shaped bilateral advancement anoplasty for the correction of this condition. We carried out this operation in five patients with successful results.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Introduction Acne vulgaris is a common, chronic disease. One of the most commonly encountered complications of acne is permanent atrophic scarring. Treatment of atrophic scars includes fillers, dermabrasion, laser resurfacing, microneedling and peelings and it is often difficult to treat. In our double-blind randomized controlled trial (RCT), we investigated the synergistic effect of microneedling with the application of trichloroacetic acid, kojic acid and hydrogen peroxide in the treatment of atrophic acne scars. Aim To assess the clinical effectiveness and patients' quality-of-life (HRQoL) after three types of atrophic post-acne scar treatment, namely microneedling alone (MN) vs chemical peeling alone (CP) vs. a combination of microneedling and chemical peeling (MN + CP). Material and methods A total of 120 patients were enrolled into the study following strict inclusion/exclusion criteria and randomized into the three treatment groups - MN, CP (a combination of trichloroacetic acid, kojic acid and hydrogen peroxide), and MN + CP. According to a preapproved protocol, each patient underwent four treatment sessions, each spread 20 days apart. Both pre- and post-treatment clinical status (using the Goodman-Baron scale; two expert raters blinded to the treatment used) and patients' HRQoL (using the Dermatology Life Quality Index) were assessed. Results During the 5-month recruitment period, a total of 120 patients were approached and agreed to take part in the study (94 females - 78.3% and 26 males) (mean age of 30.14 ±3.64 years; range: 18-45 years). Only in the MN + CP group there was a statistically significant improvement according to the G-B scale post-treatment (2.87 ±0.83 vs. 2.03 ±1.16 respectively; p = 0.0005). Patients in all three treatment groups experienced a statistically significant improvement in their HRQoL post-treatment (all p's Conclusions A combination of microneedling and chemical peeling produces the best, objectively measured effects in the treatment of atrophic post-acne scars. All examined treatments, even if not producing a clinically significant treatment outcome, improve patients' HRQoL.

Background Microneedling (MN) is used for the treatment of scars, amongst other indications. Although used in Asia and the Middle East for decades, related to the supposed lack of post-procedure pigmentary alterations even in darker skin types, MN only recently gained attention in the United States as an effective, well-tolerated aesthetic treatment. Materials and methods A systematic review of the Medline database was completed using search terms "microneedle" or "microneedling" or "micro needle" or "micro needling" and "scar". Included articles were written in English and discussed the use of MN for the treatment of scars in human subjects. Results Fifty-eight studies were included for review, with a total of 1845 patients treated for acne scarring, hypertrophic or keloid scars, and those resulting from surgery, trauma, varicella or smallpox. MN and its counterpart fractional radiofrequency MN (FRF-MN) were used as monotherapy or in combination with topical, surgical or systemic modalities. MN and FRF-MN treatment resulted in clinical improvement of scar appearance from baseline. No serious adverse events occurred. Conclusion MN is a well-tolerated, minimally invasive procedure that can be used for the treatment of scars with a high level of patient satisfaction. Further clinical studies are needed to develop standardized treatment protocols.

Late gadolinium enhancement (LGE) is a widely used cardiac magnetic resonance imaging (MRI) technique to diagnose a broad range of ischemic and non-ischemic cardiomyopathies. Since its development and validation against histology already more than two decades ago, the clinical utility of LGE and its span of applications have increased considerably.In this review we will present the basic concepts of LGE imaging and its diagnostic and prognostic value, elaborate on recent developments and emerging methods, and finally discuss future prospects.Continuous developments in 3 D imaging methods, motion correction techniques, water/fat-separated imaging, dark-blood methods, and scar quantification improved the performance and further expanded the clinical utility of LGE imaging.LGE imaging is the current noninvasive reference standard for the assessment of myocardial viability. Improvements in spatial resolution, scar-to-blood contrast, and water/fat-separated imaging further strengthened its position.· LGE MRI is the reference standard for the noninvasive assessment of myocardial viability. · LGE MRI is used to diagnose a broad range of non-ischemic cardiomyopathies in everyday clinical practice.. · Improvements in spatial resolution and scar-to-blood contrast further strengthened its position. · Continuous developments improve its performance and further expand its clinical utility.· Holtackers RJ, Emrich T, Botnar RM et al. Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging: From Basic Concepts to Emerging Methods. Fortschr Röntgenstr 2022; 194: 491 - 504.Das Late-Gadolinium-Enhancement (LGE) ist eine weit verbreitete Methode in der kardialen Magnetresonanztomografie (MRT) um ein breites Spektrum an ischämischen und nicht-ischämischen Kardiomyopathien zu diagnostizieren. Die klinische Anwendung und Nutzen haben sich seit der Entwicklung und histologischen Validierung des LGE vor mehr als zwei Jahrzehnten erheblich gesteigert.In dieser Übersichtsarbeit wird das Grundprinzip der LGE-Bildgebung und der diagnostische und prognostische Wert vorgestellt, aktuelle Entwicklungen und neue Methoden erläutert und Zukunftsperspektiven diskutiert.Kontinuierliche Weiterentwicklungen bei 3D-Bildgebungsmethoden, Bewegungskorrekturtechniken, wasser-/ fettgetrennter Bildgebung, Dark-Blood-Methoden und Narbenquantifizierung haben die Leistung und den klinischen Nutzen der LGE-Bildgebung weiter verbessert.Die LGE-Bildgebung ist der aktuelle nichtinvasive Referenzstandard für die Beurteilung der Myokardvitalität. Verbesserungen bei der räumlichen Auflösung, dem Narben-Blut-Kontrast und der wasser-/fettgetrennten Bildgebung haben diese Position weiter gestärkt.· LGE-MRT ist der Referenzstandard für die nichtinvasive Beurteilung der Myokardvitalität.. · Das LGE wird in der täglichen klinischen Praxis zur Diagnose eines breiten Spektrums nicht-ischämischer Kardiomyopathien eingesetzt.. · Verbesserungen der räumlichen Auflösung und des Narben- Blut-Kontrastes haben diese Position weiter gestärkt.. · Kontinuierliche Weiterentwicklungen verbessern die Leistung und erweitern den klinischen Nutzen..

Merkel cell carcinoma (MCC) is an aggressive and uncommon primary cutaneous neuroendocrine cancer. With unknown pathogenesis, immunosuppression, ultraviolet radiation, Merkel cell polyomavirus, and arsenic exposure are the risk factors. Reported here is a rare case of MCC developing on a scar tissue.

OBJECTIVES This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact on procedural outcome and long-term prognosis.BACKGROUND The prevalence of genetic variants associated with monomorphic VT among DCM is unknown.METHODS Ninety-eight consecutive patients (age 56 +/- 15 years; 84% men, left ventricular ejection fraction [LVEF] 39 12%) referred for DCM-VT ablation were included. Patients underwent electroanatomical mapping and testing of >= 55 cardiomyopathy-related genes. Mapping data were analyzed for low-voltage areas and abnormal potentials. LP/Pv-positive (LP/Pv+) patients were compared with LP/Pv-negative (LP/Pv-) patients and followed for VT recurrence and mortality.RESULTS In 37 (38%) patients, LP/Pv were identified, most frequently LMNA (n = 11 of 37, [30%]), 17N (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2 of 37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had tower LVEF (35 + 13% vs. LP/Pv-: 42 11%; p 0.005) and were less often men (n 27 [73%] vs. n 55 [90%] p 0.03). After a median follow-up of 2.4 years (interquartile range: 0.9 to 4.4 years), 63 (64%) patients had VT recurrence (LP/Pv+: 30 of 37 [81%] vs. LP/Pv-: 33 of 61 [54%]; p = 0.007). Twenty-eight patients (29%) died (LP/Pv +: 19 of 37 [51%] vs. LP/Pv-: 9 of 61 [15%]; p CONCLUSIONS In patients with DCM-VT, a genetic cause is frequently identified. LP/Pv+ patients have a tower LVEF and more extensive VT substrates, which, in combination with disease progression, may contribute to the poor prognosis. Genetic testing in patients with DCM-VT should therefore be recommended. (C) 2020 by the American College of Cardiology Foundation.

We have analyzed the expression of key genes orchestrating tail regeneration in lizard under normal and scarring conditions after cauterization. At 1-day post-cauterization (1 dpc), the injured blastema contains degenerating epithelial and mesenchymal cells, numerous mast cells, and immune cells. At 3 and 7 dpc, a stratified wound epidermis is forming while fibrocytes give rise to a scarring connective tissue. Oncogenes such as wnt2b, egfl6, wnt6, and mycn and the tumor suppressor arhgap28 are much more expressed than other oncogenes (hmga2, rhov, fgf8, fgfr4, tert, shh) and tumor suppressors (apcdd1, p63, rb, fat2, bcl11b) in the normal blastema and at 7 dpc. Blastemas at 3 dpc feature the lowest upregulation of most genes, likely derived from damage after cauterization. Immunomodulator genes nfatc4 and lef1 are more expressed at 7 dpc than in normal blastema and 3 dpc suggesting the induction of immune response favoring scarring. Balanced over-expression of oncogenes, tumor suppressor genes, and immune modulator genes determines regulation of cell proliferation (anti-oncogenic), of movement (anti-metastatic), and immunosuppression in the normal blastema. Significant higher expression of oncogenes wnt2b and egfl6 in normal blastema and higher expression of the tumor suppressor arhgap28 in the 7 dpc blastema indicate that they are among the key/master genes that determine the regulated regeneration of the tail.

Objective: To validate a newly developed method for capturing 3-dimensional (3D) images of the nasolabial region for assessing upper lip scarring and asymmetry in surgically managed unilateral cleft lip and palate (UCLP) cases. Design: Validation study, single cohort. Materials and Methods: Eighteen surgically managed UCLP cases were recruited, the nasolabial region of each face was scanned using an intraoral scanner (IOS) to produce 3D images. The images were manually segmented to allow the calculation of surface area of the scar and upper lip asymmetry. Five professionals and 5 lay assessors subjectively evaluated the same images and graded the upper lip scarring and asymmetry at 2 separate occasions. The relationship between the subjective and objective assessments was evaluated. Results: Moderate correlation was found between subjective and objective evaluations of the upper lip scarring and total asymmetry. The captured 3D images were of good quality for the objective measurements of lip asymmetry and residual scarring. Moderate to strong correlations were detected between the 2 panels (T ranging between 0.5 and 0.9) with no significant difference ( P > .05) in the mean score of the subjectively evaluated parameters. Conclusion: The IOS is a useful tool for the capture of the nasolabial morphology. The captured 3D images are a reliable source for measuring lip asymmetry and scar surface area. The method has sufficient validity for routine clinical use and for objective outcome measures of the surgical repair of cleft lip.

Background Skin cancer is common, growing, challenging, and in need of progress in early‐stage treatment. 20 MHz high‐intensity focused ultrasound (HIFU) is new and applied to actinic keratosis (AK) and skin cancers for the first time. HIFU of lower frequency is already used in the treatment of internal cancers. Materials and Methods Eight patients with 201 AK lesions, one patient with 7 basal cell carcinomas (reoccurrences after PDT), and one patient with 7 Kaposi sarcoma lesions (4 treated with radiotherapy in the past) were given 1‐3 HIFU treatments. Twenty megahertz HIFU was dosed as 150 ms at 0.6‐1.2 J/shot applied to target lesions. Probes with different target depths were available. The preferred shot energy and focal depth in AK were 0.9 J and 1.3 mm. A “Sandwich” strategy with HIFU applied in two depths were tried in cancers. The follow‐up period was 3‐6 months. Results All AK cleared except 5, giving a cure rate of 97%. Post‐treatment lesion healed in 1‐2 weeks with no scar. VAS pain was from 1 to 8, and in any case less than experienced with previous PDT. In both basal cell carcinoma (BCC) and sarcoma, healing was confirmed by histological verification. Discussion/conclusion 20 MHz HIFU was an effective and safe treatment of AK. This new treatment, applicable to any anatomical site, has promising advantages relative to PDT and has the potential to replace or supplement PDT in future. Case‐observations indicated that HIFU can be useful in skin cancers as well.

Background/aim To evaluate the histopathological and mechanical effects of Ankaferd Blood Stopper (ABS) application on wound healing. Materials and methods A total of 24 Wistar albino rats were randomly divided into three equal groups. In each group, a 3 cm-long midline vertical skin incision was performed in the back of the rats. In Group 1, the incision was sutured primarily. In Group 2, incision was left to secondary healing. In Group 3, ABS was applied to the incision. On the 10th day, burst pressure width was measured, and rats were sacrificed. The tissue samples were examined histopathologically. Statistical analysis was conducted with IBM SPSS program. P < 0.05 was considered significant. Results The mean burst pressure widths of wound separation were 13.66 ± 0.457, 7.18 ± 2.599, and 13.66 ± 1.11 mm for Groups 1–3, respectively. The difference in burst pressure width between Groups 1 and 3 was not significant (P > 0.05) but was significant between Groups 2 and 3 (P = 0.000). The vascular proliferation median values were 1, 2, and 2, for Groups 1–3, respectively. Although the difference was significant between Groups 1 and 2 in terms of vascular proliferation score (P = 0.047), no significant difference was observed between Group 3 and others. No statistically significant difference was observed among the groups in terms of collagen score, mononuclear cell infiltration, and polymorphonuclear cell proliferation (P > 0.05). The median values of fibroblast proliferation score were 1, 2, and 3, in Groups 1–3, respectively. Fibroblast proliferation score significantly differed between Groups 1 and 3 (P = 0.003). Conclusion ABS application results in a clean wound healing that is as strong as primary repair. However, additional studies are required to evaluate the late results of increased fibroblastic activity in the early period of ABS application alone.

Summary Background Hypertrophic scars frequently follow primary closure of surgical wounds. Laser application at or shortly after suture may be associated with a reduction in scar formation, although the respective study results vary. Aim The objective was to evaluate the efficacy of early laser applied within the first six months after surgery to reduce scar formation compared to no treatment. Methods We searched the databases MEDLINE and CENTRAL on 14 January 2019 and included randomized controlled trials (RCTs). Primary outcome was the Vancouver Scar Scale (VSS). Measure of treatment effect was the mean difference from baseline. Results Seventeen relevant RCTs randomized 430 scars (413 assessed) and compared laser versus no treatment. Fourteen studies applied a split-scar and three applied a simple parallel design. Three studies with a split-scar design favored the laser group on VSS, and one study had indifferent findings. Considerable heterogeneity I2 = 86% did not justify a meta-analysis. The remaining 13 studies did not report appropriate data. Conclusion On the basis of the currently available evidence, we are uncertain whether early laser can reduce scar formation, and more high-quality research is needed for a definitive conclusion.

Root-knot nematodes (Meloidogyne spp.) infect a large number of crops including guava. We investigated a population of Meloidogyne sp. infecting guava in the Coimbatore region of Tamil Nadu, India for identification and species confirmation. Detailed morphological and morphometric observations based on second-stage juveniles, males, females, and perineal patterns showed resemblance of the isolated population with the original and subsequent descriptions of M. enterolobii. Isozyme analysis of the young egg-laying females displayed the characteristic esterase phenotype pattern similar to that of M. enterolobii. Additionally, the identity of the nematode population was further validated by M. enterolobii specific SCAR marker and ITS rDNA. Recently published reports on the occurrence and morphological descriptions of M. enterolobii from India are largely incongruent with the original and subsequent redescriptions of the species. Here, we present the most comprehensive morphology and morphometrics of an Indian population of M. enterolobii for its authentic identification.

Background. Assessment of the state of healed burn wounds after their treatment is an urgent problem at the present time. Aim of the research. To assess the condition of post-burn wounds in 1 and 6 months after the completion of treatment of II-III degree burns (according to ICD-10) in children using bioplastic collagenous material "Collost" in various forms and traditional local conservative therapy using hydrocolloid dressings. Material and methods. The condition of the healed wound was assessed at discharge, as well as after 1 and 6 months in 48 patients using modified Vancouver Scar Scale (management of burn wounds: main group - bioplastic material and hydrocolloid dressings; control group - hydrocolloid dressings). Results. The use of native collagen in the complex treatment of thermal trauma helps to reduce the relative and absolute risk after 1 and 6 months as well as to lower adverse trends from the post-burn wound. Conclusions. The obtained results suggest further investigation of the mechanism of influence of type I collagenbased drugs on the dynamics of the wound process in thermal burns, as well as the study of its effect on individual wound characteristics described by the Vancouver scar scale.

BACKGROUND: Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates. METHODS: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated. RESULTS: Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity. CONCLUSIONS: Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar. ispartof: NUCLEAR MEDICINE COMMUNICATIONS vol:43 issue:5 pages:502-509 ispartof: location:England status: published

Collagen bundle orientation (CBO) in myocardial infarct scars plays a major role in scar mechanics and complications after infarction. We aim to compare four histopathological methods for CBO measurement in myocardial scarring. Myocardial infarction was induced in 21 pigs by balloon coronary occlusion. Scar samples were obtained at 4 weeks, stained with Masson's trichrome, Picrosirius red, and Hematoxylin-Eosin (H&E), and photographed using light, polarized light microscopy, and confocal microscopy, respectively. Masson's trichrome images were also optimized to remove non-collagenous structures. Two observers measured CBO by means of a semi-automated, Fourier analysis protocol. Interrater reliability and comparability between techniques were studied by the intraclass correlation coefficient (ICC) and Bland-Altman (B&A) plots and limits of agreement. Fourier analysis showed an almost perfect interrater reliability for each technique (ICC >= 0.95, p < 0.001 in all cases). CBO showed more randomly oriented values in Masson's trichrome and worse comparability with other techniques (ICC vs. Picrosirius red: 0.79 [0.47-0.91], p = 0.001; vs. H&E-confocal: 0.70 [0.26-0.88], p = 0.005). However, optimized Masson's trichrome showed almost perfect agreement with Picrosirius red (ICC 0.84 [0.6-0.94], p < 0.001) and H&E-confocal (ICC 0.81 [0.54-0.92], p < 0.001), as well as these latter techniques between each other (ICC 0.84 [0.60-0.93], p < 0.001). In summary, a semi-automated, Fourier-based method can provide highly reproducible CBO measurements in four different histopathological techniques. Masson's trichrome tends to provide more randomly oriented CBO index values, probably due to non-specific visualization of non-collagenous structures. However, optimization of Masson's trichrome microphotographs to remove non-collagenous components provides an almost perfect comparability between this technique, Picrosirius red and H&E-confocal.

Macrophages are prominent cells in normally healing adult skin wounds, yet their exact functions and functional significance to healing outcomes remain enigmatic. Many functional attributes are ascribed to wound macrophages, including host defense and support of the proliferation of new tissue to replace that lost by injury. Indeed, the depletion of macrophages is unmistakably detrimental to normal skin healing in adult mammals. Yet in certain systems, dermal wounds seem to heal well with limited or even no functional macrophages, creating an apparent paradox regarding the function of this cell in wounds. Recent advances in our understanding of wound macrophage phenotypes, along with new information about cellular plasticity in wounds, may provide some explanation for the apparently contradictory findings and suggest new paradigms regarding macrophage function in wounds. Continued study of this remarkable cell is needed to develop effective therapeutic options to improve healing outcomes.

Background: Cardiac CT with late iodine enhancement (LIE-CT) may characterize the scarred myocardium, but the role of readers’ experience and scar pattern on LIE-CT diagnostic performance is unknown. Aim was to assess the diagnostic performance of LIE-CT according to readers’ experience, scar pattern and contrast-to-noise ratio (CNR) using late gadolinium enhancement MRI (LGE-MRI) as reference. Methods: LIE-CT and LGE-MRI images of 40 consecutive patients were analyzed. Two readers with different experience (8 and 2years) independently analyzed LIE-CT images defining the presence/absence of scar and scar CNR, segmental involvement, transmural pattern and scar etiology. The same parameters were extracted from LGE-MRI by two expert readers in consensus, blinded to the LIE-CT results. Results: Scars were identified at LGE-MRI in 29/40 patients and 141/680 segments. Scar burden at LIE-CT versus LGE-MRI correlated better for the most experienced reader than for the least experienced one (ρ = 0.954 and ρ = 0.797, p < 0.001). The most experienced reader missed scars in 2 patients and in 21/141 segments; the least experienced in 5 patients and 53/141 segments. The most experienced reader showed higher accuracy and sensitivity compared to the least experienced in per-patient (accuracy: 95% vs. 88%; sensitivity: 93% vs. 83%) and per-segment analysis (accuracy: 96% vs. 92%; sensitivity: 85% vs. 62%). Specificity was excellent (100% per-patient, 99% per-segment,) regardless of readers’ experience. Missed scars had non-ischemic pattern, low scar burden (< 6%) and lower CNR compared to ischemic scars (2.33 vs. 3.54, p = 0.005). Conclusion: LIE-CT represents an alternative to LGE-MRI, although the impact of readers’ experience on sensitivity for small non-ischemic scars should be considered.

Background aims There is currently no definitive treatment for the painful scar. Autologous adipose tissue grafting (AATG) as a treatment option for scars has become increasingly popular and there is now an abundance of evidence in the literature that supports its application. Some studies suggest that human adipose tissue is a rich source of multipotent mesenchymal stromal cells. To our knowledge, there is currently no systematic literature review to date that examines the effectiveness of AATG for reducing pain in scars. Our novel systematic review aims to examine clinical studies on the use of AATG in the treatment of the painful scar. Methods A literature search was performed using the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Medline, Cochrane library and Embase. The following key words and search terms were used: adipose stem cells, scar, pain, autologous fat grafting, scar management and neuropathic pain. Human interventional studies using autologous adipose tissue grafting for the treatment of painful scars including case series, case-control, cohort studies and randomized controlled trials were reviewed. Results A total of 387 studies were found and 18 studies from January 1990 to January 2019 were identified as relevant for the purpose of this systematic review. Two studies were evidence level V, seven were evidence level IV, six were evidence level III, two were evidence level II and one was level I. A total of 337 scars were assessed in 288 patients for improvement in pain after scar treatment using adipose tissue grafting. An improvement in the analgesic effect was recorded in 12 of the 18 studies with adipose tissue grafting. A total of 233 of the 288 treated subjects responded with reduction in pain, whereas the rest did not. We carried out a pooled analysis of the studies and observed an odds ratio of 3.94 (P = 0.00001) when comparing pain reduction to no change in pain. Conclusions We conclude that AATG is a promising and safe modality for the treatment of the painful scar. There is an abundance of low-level evidence to support its use as an alternative treatment but there is a lack of high-level evidence at present to support its standard use. Future long-term randomized controlled trials with analgesic scores as the primary outcome measures are required to assess long-term efficacy.

Endometriosis is a frequent disease in women at reproductive age and is defined as functional endometrium located other place than uterus. The abdominal wall is an uncommon site of extrapelvic endometriosis. It usually occurs in a previous surgical scar. We present a case of a 31 years old, gravida, secundipara who was admitted with painful uterine contractions and abdominal wall endometrioma. During the caesarian section we also practice the excision of endometrioma.

Background Acne is a chronic inflammatory skin disease caused by bacterial colonization that damages the pilosebaceous gland on the face and other parts of the body. It is one of the most frequent dermatologic diseases in the young population. Acne vulgaris is a devastating disease, and it has a significant impact on a patient's quality of life, influencing their self-esteem as well as their psychosocial development. This study aimed to explore the psychological symptoms associated with patients with acne, its impact on their quality of life according to their personal characteristics, and to raise the importance of observing and managing psychological symptoms during acne treatment. Methods In this cross-sectional study, data were collected through a paper questionnaire. The questionnaire was composed of two parts, the first includes data about demographics and general health while the second has details about the Dermatology Life Quality Index (DQLI); the Arabic validated version was used for data collection. Data were analyzed using SPSS version 20 (IBM Corp., Armonk, NY). Results According to the impact of acne on respondents' lives, 40.0% have no effect at all, 31.0% have small effects, 19.0% have moderate effects,9.0% have large effects, and 0.7% have extremely large effects. Conclusions Acne is a major problem that affects the quality of life of young patients. Its effect is significantly higher among less educated patients and those with a longer duration of disease.

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.

Background: While many aspects of the wound repair process are understood, there is still limited understanding about why chronic wounds develop, how we predict, diagnose and improve healing outcomes, and why some wounds heal with scarring. Identifying current gaps in knowledge, as well as areas of strengths, will inform recommendations for future research-based themes and influence the targeting of resources. Aims: This scoping review aims to (i) map current knowledge and research activities into wound healing in Australia and (ii) understand strengths and identifying research gaps in science-focused wound research in Australia. Methods: Guided by the PRISMA-ScR framework, this scoping review will include original laboratory-based science studies on wounds conducted in Australia. Records will be searched in PubMed, CINAHL and Embase from January 2010 to March 2021. All screened titles and abstracts will be independently assessed by two reviewers using Rayyan®. A third reviewer will solve any conflicts that arise. This will be followed by full text screening and in-depth analysis after resolution of conflicts. Results and dissemination: Following data extraction from the final included articles, results will be grouped according to area of research and synthesised in a narrative review. Findings will be published in a peer-reviewed journal Refereed/Peer-reviewed

Increasing evidence suggests that the BCG vaccine has non-specific effects, altering the susceptibility to non-tuberculous infections. Thus, early BCG vaccination may reduce mortality. BCG is recommended at birth but is often delayed. Vaccination opportunities are missed due to multidose vials not being opened for a few children. We will assess the effect of making BCG available at the first health-facility contact on early infant mortality and morbidity in a rural setting in Guinea-Bissau Introduction Increasing evidence suggests that the BCG vaccine has non-specific effects, altering the susceptibility to non-tuberculous infections. Thus, early BCG vaccination may reduce mortality. BCG is recommended at birth but is often delayed. Vaccination opportunities are missed due to multidose vials not being opened for a few children. We will assess the effect of making BCG available at the first health-facility contact on early infant mortality and morbidity in a rural setting in Guinea-Bissau. Methods and analysis In a cluster-randomised crossover trial, we randomise 23 health centres to two different treatment groups. In half of the health centres, BCG is provided as per current practice; in the remaining health centres, we make BCG available everyday to allow opening a vial of BCG if there is just one eligible child present. The randomisation of centres will be crossed over after 12 months and enrolment will continue for another 12 months. We will use logistic regression models with adjustment for village to assess the effect of making BCG available at the first health-facility contact. The main outcome is non-accidental mortality between day 1 and day 42 after birth. We will adjust for sex, health centre, period (before/after crossover) and level of surveillance (level 1 or level 2). Further analyses include assessment of the effect on hospital admission and a cost-effectiveness evaluation. Ethics and dissemination If BCG vaccination reduces early infant mortality, missed opportunities and delays of vaccinations expose infants in several low-income countries to unnecessary excess mortality risk. The present trial will provide information on the effect of implementing a feasible intervention, where all children receive BCG at their first health-facility contact. Consent is obtained from all pregnant women registered as part of the trial. The results of the study will be published and communicated to the National Institute of Public Health in Guinea-Bissau.

Aim Scar formation generally occurs in cutaneous wound healing in mammals, mainly caused by myofibroblast aggregations, and currently with few effective treatment options. However, the pedicle wound (about 10 cm in diameter) of the deer can initiate regenerative healing, which has been found to be achieved via paracrine factors from the internal tissues of antlers. Methods Enzymatically digested velvet antler peptides (EVAP) were prepared along with other types of antler extracts as the controls. The effects of EVAP on healing of full-thickness skin wounds were evaluated using rats in vivo, and on myofibroblast transdifferentiation tested using transforming growth factor-β1 (TGF-β1)-induced human dermal fibroblasts in vitro. Results EVAP significantly accelerated the wound healing rate, reduced scar formation, and improved the healing quality, including promoted angiogenesis, increased number of skin appendages (hair follicles and sebaceous glands) and improved the distribution pattern of collagen fibers (basket-wave like) in the healed tissue. Moreover, EVAP significantly down-regulated the expression levels of genes pro- scar formation (Col1a2 and TGF-β1), and up-regulated the expression levels of genes anti-scar formation (Col3a1 and TGF-β3), and suppressed the excessive transdifferentiation of myofibroblasts and the formation of collagen I in vivo and in vitro. Furthermore, we found these effects were highly likely achieved by inhibiting the TGF-β signaling pathway, evidenced by decreased expression levels of the related genes, including TGF-β1, Smad2, p-Smad2, α-SMA, and collagen I. Conclusions EVAP may be a promising candidate to be developed as a clinic drug for regenerative wound healing.