Gene Expression of Angiotensin-Converting Enzyme 2 Receptor in Skin and the Implications for COVID-19.

BACKGROUND: Binding to the angiotensin-converting enzyme 2 (ACE2) receptor is a critical step for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter target cells. This enzyme is expressed in many human tissues including the lungs, but no research has demonstrated that SARS-CoV-2 can infect human skin or subcutaneous fat tissue, despite the increasing number of reported skin manifestations. The aim of this study was to investigate ACE2 gene expression in skin using a public database. METHODS: A search of transcriptomic data sets from a public gene expression database to investigate ACE2 gene expression in human tissues. RESULTS: Human skin keratinocytes and basal cells express more ACE2 than lung epithelial cells. In contrast, both fibroblasts and melanocytes from human skin express less ACE2 than human lung epithelial cells. CONCLUSIONS: The high expression of ACE2 in keratinocytes and basal cells of human skin indicates that they may be directly susceptible to SARS-CoV-2 infection via the ACE2 receptor, especially in conditions of skin barrier dysfunction, and are therefore a potential target for the coronavirus.

Availability of COVID-19 Information From National Plastic Surgery Society Web Sites.

BACKGROUND: National plastic surgery society web sites are an important source of information for patients, family members, and healthcare professionals. There are currently no standardized recommendations for the information provided on web sites. The aim of this study was to assess the information available on each national plastic surgery society web site on the current pandemic of COVID-19. METHODS: A Google search was performed of United Nations member sovereign states to determine whether they had a national plastic surgery society web site and to assess its contents. The presence of COVID-19 information was recorded. Access to contact information, Facebook page, Twitter, and Instagram handles were noted. RESULTS: Thirty-five percent of sovereign states had plastic surgery society web sites. Twenty-two percent of national society web sites had a specific COVID-19 section. Fourteen (93%) of these 15 web sites had COVID-19-specific guidelines available for health care professionals. CONCLUSIONS: COVID-19 information provided by national plastic surgery society web sites is sparse. Two-thirds of national plastic surgery societies do not have a web presence. The availability of COVID-19 clinical guidelines and patient information sheets on national plastic surgery society web sites is limited. This study suggests that improvement and increase in COVID-19 information provided by many national plastic surgery society web sites are needed.

Availability of COVID-19 Information from National and International Aesthetic Surgery Society Websites.

BACKGROUND: National and international aesthetic surgery society websites are an important source of information for patients and aesthetic surgeons. The current COVID-19 pandemic represents an unprecedented global health crisis. The aim of this study was to assess the information available on national and international aesthetic surgery society websites on the current pandemic of COVID-19. METHODS: National and international aesthetic surgery society websites were assessed with regard to COVID-19 information. RESULTS: Thirty-one per cent of nations had aesthetic surgery society websites. Twenty-two per cent of national society websites had a specific COVID-19 section. Seventeen per cent of these websites had COVID-19-specific guidelines available; of these websites with guidelines, 77% had a specific COVID-19 section advising to provide only urgent or emergent care and 46% provided their sovereign state's directives to provide only urgent or emergent care. Two international aesthetic surgery society websites had COVID-19-specific guidelines, and one of the two had significant educational resources. CONCLUSION: The availability of COVID-19 clinical guidelines and patient information sheets on national plastic surgery society websites is sparse. In contrast, one international society website carefully analysed national and international recommendations and guidelines and made general recommendations for its members with regularly updated resources. This study suggests that improvement and increase in COVID-19 information provided by many national aesthetic surgery society websites may be improved by links to the ISAPS website. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Pathophysiology of coronavirus disease 2019 for wound care professionals.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus disease 2019 (COVID-19). The tissue tropism of SARS-CoV-2 includes not only the lung but also the vascular and integumentary systems. Angiotensin-converting enzyme 2 (ACE2) appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV-2 infection, including inflammatory cytokines, chemokines, the complement system, and acute phase proteins. The pathophysiologic significance of SARS-COV-2 and host immune system interaction, and COVID-19-associated coagulopathy instigating microvascular injury syndrome mediated by activation of complement pathways, and an associated procoagulant state is important for wound care professionals to understand.

Functional Outcome After Reconstruction of Traumatic Soft Tissue Defects in the Lower Half of the Leg With Distally Based Medial Hemisoleus Muscle Flaps: A Case Series and Literature Review.

BACKGROUND: Data regarding donor-site morbidity, postoperative clinical course, and functional outcome after hemisoleus muscle flap reconstruction are rare. The aim of this study was to determine the clinical and functional outcome of distally based medial hemisoleus flaps used for the reconstruction of defects in the lower half of the leg. METHODS: Data regarding 31 patients who underwent medial hemisoleus flap reconstruction between 2011 and 2017 were analyzed retrospectively. Epidemiological data and data on clinical outcomes and complications were obtained from hospital records. Functional outcome data were recorded in 14 cases. RESULTS: All soft tissue defects were secondary to trauma; 90.3% were male and 9.7% were female. Mean age was 52 years (range, 16-77 years). Mean defect size was 48 ± 9.5 cm. Flap survival was complete in 29 patients and partial in 2 patients. The maximal plantar flexion force in the ankle joint of the operated leg was 78.1% (P < 0.05) compared with the unaffected side. Strength endurance was reduced by 16.5% (P < 0.05) in the operated leg compared with the unaffected side. CONCLUSIONS: Medial hemisoleus flaps should be included in the armamentarium for reconstruction of small to middle traumatic lower leg defects. They are quick to raise and inset and provide robust coverage. Although there is an objective reduction in plantar flexion and endurance, this did not translate into functional limitations in our group of patients. To our knowledge, this represents the largest case series to date of functional outcome of distally based medial hemisoleus flap reconstruction in lower limbs.

Minimally invasive harvesting of adipofascial scapular flaps.

INTRODUCTION: Scapular flaps are a reliable system for reconstruction. Disadvantages of reconstruction with these flaps include unsightly scars at the donor site due to wound healing under excessive tension and the use of skin grafts. Minimally invasive harvesting techniques may reduce potential donor-site morbidity. There has been no report on endoscopically assisted harvesting of the scapular adipofascial flap. METHODS: Two patients with large defects are reviewed. Endoscopically assisted minimally invasive techniques for harvest of scapular adipofascial flaps were used in reconstruction of these soft-tissue defects. RESULTS: Both defects were successfully reconstructed in the primary setting without any donor-site wound complications. CONCLUSIONS: This is the first time that a scapular flap has been harvested successfully with a minimally invasive technique for reconstruction. This technique allows the use of a scapular flap as a pedicled flap or as a free flap. Minimally invasive harvest of the adipofascial scapular flap has the advantages of short incision and better cosmesis of the donor site, for scarring is minimized and the incision can be closed primarily without skin grafting therefore reducing donor-site morbidity compared with the traditional open technique.

Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas.

BACKGROUND: Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. METHODS: To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. RESULTS: The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. CONCLUSIONS: Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells.

BACKGROUND: Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. MATERIALS AND METHODS: A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8 weeks post-transplantation. RESULTS: Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. CONCLUSION: Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach.

Submental lymph node metastasis from invasive ductal breast carcinoma.

This case report presents a 52-year-old woman with a submental swelling which arose 3 years after wide local excision and axillary lymphadenectomy for breast carcinoma. Histopathological examination after excision biopsy of this lesion confirmed the presence of invasive breast carcinoma in a submental lymph node. Computed tomography of the head, neck, thorax, abdomen and pelvis demonstrated multiple brain and pulmonary metastases. Further management was palliative and the patient died 5 months later. This is the first description of a breast carcinoma metastasising to the submental region. Metastatic breast carcinoma should be considered in the differential diagnosis of head and neck lymphadenopathy in patients with previously diagnosed breast carcinoma.

Postablative reconstruction of vulvar defects with local fasciocutaneous flaps and superficial fascial system repair.

INTRODUCTION: Postablative reconstruction of vulvar defects is a difficult challenge because of the functional, locational and cosmetic importance of this region. Local flaps carry a high incidence of delayed wound healing as local flaps may redistribute but not eliminate local wound tension. Repair of the superficial fascial system may avert local complications by minimising tension to the skin and increasing the initial biomechanical strength of wound. The aim of this study was to determine the clinical outcome of local fasciocutaneous flaps used for postablative reconstruction of vulvar defects in which the superficial fascial system was repaired. METHODS: A retrospective analysis was conducted of patients with vulvar carcinoma in situ or vulvar carcinoma, who underwent ablation and immediate reconstruction with local fasciocutaneous flaps and superficial fascial system repair. Postoperative complications were recorded and clinical outcomes were evaluated. RESULTS: Twelve of the 13 flaps healed primarily. Complications included 2 superficial wound infections, both of which were treated successfully with antibiotic therapy. One flap was complicated by minor wound dehiscence, which healed with conservative treatment. DISCUSSION: Local fasciocutaneous flaps with superficial fascial system repair provide excellent design flexibility and can be designed and tailored to reconstruct postablative vulvar defects with good outcomes and minimal morbidity.

Genotoxic and cytotoxic activity of host defense peptides against human soft tissue sarcoma in an in vitro model.

Soft tissue sarcomas (STSs) are a heterogeneous group of rare, mesenchymal tumors. Treatment with common chemotherapeutic drugs is consistently associated with low response rates and high rates of adverse toxic effects. Host defense peptides (HDPs) are used as part of innate immunity, and many of them act by directly lysing the target cell membrane. Studies have demonstrated high selectivity of HDP analogs against malignant cells because of a relative abundance of negative charges in malignant cell membranes, compared to normal cells. Our aim was to assess the toxic efficacy of [D]-K(6)L(9), [D]-K(3)H(3)L(9), and Protegrin-1 against the fibrosarcoma cell line, HT1080, and primary human fibroblasts to analyze the potential of these peptides as therapeutic options against STSs. Cell proliferation of the fibrosarcoma cell line, HT1080, and human fibroblasts was determined in vitro after treatment with [D]-K(6)L(9), [D]-K(3)H(3)L(9), and Protegrin-1. Genotoxicity was examined on the basis of the mild alkali version of single-cell gel electrophoresis (comet assay). Doxorubicin, a commonly used STS chemotherapeutic agent, served as the control. The native HDP, Protegrin-1, could show a cytotoxic tendency against malignant cells, but no selectivity in genotoxic trials. The synthetic peptide, [D]-K(6)L(9), could not show any selective oncolytic activity against sarcoma cells. [D]-K(3)H(3)L(9) has shown a tendency for toxic selectivity against malignant cells. There is a potential of developing suitable oncolytic candidates with selectivity against malignant cells. [D]-K(3)H(3)L(9) showed the first promising results, but there has to be further investigation to improve the therapeutic properties of HDPs.

Management of Hand Surgery Services during the Novel Coronavirus Disease 2019 Pandemic.

Introduction The novel coronavirus disease 2019 (COVID-19) pandemic is an international public health emergency. Health systems must plan for the increasing requirements for critical care during the COVID-19 pandemic. The aim of this article is to offer strategies for hand surgeons to planning and implementing their response during the COVID-19 pandemic and in the subsequent phases to preserve health care system functioning. Materials and Methods Assessment of the principles of management related to COVID-19 management to develop pandemic preparedness and response protocols pertinent to patients, health care workers, and health systems. Results Strategies for the reorganizing hand surgery practice and a set of recommendations that should facilitate the process of rescheduling both out-patient service and surgical activities during the COVID-19 and its subsequent phases are suggested. Conclusion During the COVID-19 pandemic, management of patients requiring specialist care for hand conditions should be adapted to limit the risks associated with the virus without jeopardizing outcomes. These expedient recommendations during extraordinary circumstances are a foundation for further discussion on the topic as the COVID-19 pandemic evolves.

Examining trends in the evidence base for the treatment of burns and a quality assessment of randomised controlled trials over an 11-year period.

BACKGROUND: Previous articles assessed the evidence-base for the treatment of burns, but the latest was published in 2010, examining data up to and inclusive of 2008. The aim of this article is to examine the trend in the number of high-evidence publications over the subsequent 11-year period and quality-assess RCTs within this timeframe. MATERIALS AND METHODS: All articles published in Burns and Journal of Burn Care and Research (JBCR) were identified using PubMed Search Tools and its Single Citation Matcher function. These journals were manually screened from 01/01/2009-01/06/2020 inclusive. Additionally, a PubMed search was conducted searching for RCTs and meta-analyses in English with the MESH term burns to identify meta-analyses and RCTs in all other journals. The reporting of RCTs was assessed using a modified CONsolidated Standards of Reporting Trials (CONSORT) checklist. RESULTS: A total of 5145 articles were evaluated from Burns and JBCR, with 3230 (62.78%) from Burns and 1915 (37.22%) from JBCR. 0.012% were meta-analyses of RCTs, 0.30% were other meta-analyses, and 2.52% were initially identified as RCTs. Whilst a significant increase in the number of high-evidence publications is observed, these represent 2.83% (n = 237) of the total. An additional 95 RCTs were identified in other journals, 58 being included in quality-analysis. A total 128 RCTs were thus eligible for quality-assessment, the most popular individual topic being wound healing (n = 28; 21.88%). The most highly reported criterion was listed inclusion and exclusion criteria (n = 111; 86.72%) and the least reported criterion was allocation concealment (n = 22; 13.92%). CONCLUSIONS: This study observes a positive trend in high-evidence publications. The reporting of several CONSORT criteria in RCTs remains poor. Observation to standard reporting guidelines is advocated to improve the quality of reporting.

Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery.

BACKGROUND: Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. METHODS: In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. RESULTS: The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. CONCLUSION: The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.

Female plastic and reconstructive surgeons' personal decision making for breast cancer treatment and reconstruction.

INTRODUCTION: No original articles have been published exploring female surgeons' preferences for breast cancer treatment and reconstruction if they were to be diagnosed with breast cancer. MATERIALS AND METHODS: 107 female breast plastic and reconstructive surgeons were surveyed as to the methods of breast cancer treatment and reconstruction they would opt for if they were diagnosed with a 2 cm invasive breast carcinoma. RESULTS: 75% stated that they would opt for mastectomy rather than undergo breast conserving surgery and radiation (21%). Most (95%) of those choosing a mastectomy would opt for reconstruction. For reconstruction choices, 50% of those surveyed would have autologous breast reconstruction with abdominal tissue (38% deep inferior epigastric perforator flap; 12% transverse rectus abdominis muscle flap). 26% would choose tissue expansion with implant and 19% would opt for a latissimus dorsi flap. For those choosing tissue expansion with implant reconstruction 64% would choose a silicone implant, 9% would choose a saline implant and 27% felt either type of implant would be acceptable. For those choosing latissimus dorsi flap with implant reconstruction, 69% would choose a silicone implant, 13% would choose a saline implant and 19% felt either type of implant would be acceptable. DISCUSSION: Female surgeons offer an exclusive insight into surgical outcomes following breast cancer therapy and reconstruction. This study suggests that due to their clinical experiences they have knowledge as to outcomes and consequences of breast cancer treatment and reconstruction and their choices do not always adhere to current guidelines.

Oncolytic activities of host defense peptides.

Cancer continues to be a leading source of morbidity and mortality worldwide in spite of progress in oncolytic therapies. In addition, the incidence of cancers affecting the breast, kidney, prostate and skin among others continue to rise. Chemotherapeutic drugs are widely used in cancer treatment but have the serious drawback of nonspecific toxicity because these agents target any rapidly dividing cell without discriminating between healthy and malignant cells. In addition, many neoplasms eventually become resistant to conventional chemotherapy due to selection for multidrug-resistant variants. The limitations associated with existing chemotherapeutic drugs have stimulated the search for new oncolytic therapies. Host defense peptides (HDPs) may represent a novel family of oncolytic agents that can avoid the shortcomings of conventional chemotherapy because they exhibit selective cytotoxicity against a broad spectrum of malignant human cells, including multi-drug-resistant neoplastic cells. Oncolytic activity by HDPs is usually via necrosis due to cell membrane lysis, but some HDPs can trigger apoptosis in cancer cells via mitochondrial membrane disruption. In addition, certain HDPs are anti-angiogenic which may inhibit cancer progression. This paper reviews oncolytic HDP studies in order to address the suitability of selected HDPs as oncolytic therapies.

Negative pressure rooms and COVID-19.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 novel coronavirus disease (COVID-19), has rapidly developed into a global pandemic and public health emergency. The transmission and virulence of this new pathogen have raised concern for how best to protect healthcare professionals while effectively providing care to the infected patient requiring surgery. Although negative pressure rooms are ideal for aerosol-generating procedures, such as intubation and extubation, most operating theatres are generally maintained at a positive pressure when compared with the surrounding areas. This article compares negative and positive pressure rooms and the advantages of a negative pressure environment in optimising clinical care and minimising the exposure of patients and health care professionals to SARS-CoV-2.