Transcutaneous oximetry values in chronic ulcer patients during Hyperbaric treatment at 1.4 ATA compared to 2 ATA.

Chronic wounds have a significant impact on a patient's quality of life. Different pathologies, such as poor blood supply and tissue breakdown, may lead to inadequate oxygenation of the wound. Hyperbaric oxygen (HBO2) is a widely used treatment for an increasing number of medical practices. A new so-called "hyperbaric treatment" trend has emerged. The use of low-pressure, soft-sided, or inflatable chambers represents a growing trend in hyperbaric medicine. Used in professional settings as well as directly marketed to individuals for home use, they are promoted as equivalent to clinical hyperbaric treatments provided in medical centers. However, these chambers are pressurized to 1.3 atmospheres absolute (ATA) on either air or with an oxygen concentrator, both generate oxygen partial pressures well below those used in approved hyperbaric centers for UHMS-approved indications. A total of 130 consecutive patients with chronic ulcers where tested. TcPO2 was measured near the ulcer area while the patient was breathing 100% O2 at 1.4 ATA for five and 10 minutes. The average TcPO2 at 1.4 ATA after 10 minutes of O2 breathing was 161 mmHg (1-601 mmHg, standard deviation 137.91), compared to 333 mmHg in 2 ATA (1-914±232.56), p < 0.001. Each electrode tested was also statistically significant, both after five minutes of O2 breathing and after 10 minutes. We have not found evidence supporting the claim that 1.4 ATA treatment can benefit a chronic ulcer patient. The field of HBO2 is constantly evolving. We have discovered new ways to treat previously incurable ailments. Nevertheless, it is important to note that new horizons must be examined scientifically, supported by evidence-based data. The actual effect of 1.4 ATA on many ailments is yet to be determined.

Autologous Th2-polarized lymphocytes induce atopic dermatitis lesions in non-atopic human skin xenotransplants.

BACKGROUND: The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo. METHODS: Healthy human skin from non-atopic donors was transplanted onto SCID/beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption. RESULTS: Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress. CONCLUSIONS: This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.

Implant-based Breast Reconstruction Infections: The Importance of Recognizing Local Pathogens.

BACKGROUND: Implant-based breast reconstruction (IBR) is the most common method of reconstruction for breast cancer. Bacterial infection is a well-known risk with reported rates ranging from 1% to 43%. The most common pathogens of breast implant infection described in the literature are Staphylococcus aureus, Staphylococcus epidermidis, and coagulase-negative staphylococci. However, the prevalence of other pathogens and their antibiotic sensitivity profile differs profoundly in different parts of the world. OBJECTIVES: To review the current literature and protocols with respect to our region and to determine a more accurate antibiotic protocol aimed at our specific local pathogens. METHODS: A retrospective review was conducted of all cases of clinically infected implant-based breast reconstruction in our institution from June 2013 to June 2019, as well as review of microbiologic data from around the world based on current literature. RESULTS: A total of 28 patients representing 28 clinically infected implant-based breast reconstruction were identified during the studied period. Thirteen patients (46.4%) had a positive bacterial culture growth, with P. aeruginosa being the most common microorganism identified (46.1%). Review of international microbiological data demonstrated significant variation at different places and time periods. CONCLUSIONS: Microbiological data in cases of infected breast reconstructions should be collected and analyzed in every medical center and updated every few years due to the variations observed. These data will help to adjust the optimal empirical antibiotic regimens given to patients presenting with infections after breast reconstruction.

Closure of Long Surgical Incisions with Hemostatic Tissue Adhesive in a Porcine Skin Model.

OBJECTIVE: Skin adhesives offer many advantages over traditional wound-closure devices. Recently, the current research group reported on tissue adhesives composed of natural polymers (gelatin and alginate), which are biocompatible with mechanical properties suitable for tissue adhesion. The objective of the present study was to conduct clinical and histologic assessment of this hemostatic bioadhesive in the healing of long skin incisions (≥4 cm) in comparison with traditional and commercially available methods. METHODS: Researchers created 24 long incisions on the ventral side of two domestic pigs to compare four different treatment modalities: two topical bioadhesives based on gelatin and alginate combined with the hemostatic agent kaolin, nylon sutures, and commercial tissue adhesive N-butyl-2-cyanoacrylate. The bioadhesive compounds were spread on the incision surface and then mixed either manually or with a double-headed syringe. After 14 days, clinical and histologic measurements were performed to evaluate the healing phase of the wounds. RESULTS: The bioadhesive formulation that contained a relatively low crosslinker concentration demonstrated superior results to the formulation that contained a standard crosslinker concentration. However, no significant statistical differences were observed compared with the control incisions (sutures and commercial adhesive N-butyl-2-cyanoacrylate). This was verified by immunohistochemical analysis for epithelial integrity and scar formation as well as by clinical assessment. CONCLUSIONS: This newly developed bioadhesive demonstrated suitable properties for the closure of long incisions in a porcine skin model.

[MELANOMA INCIDENCE, IMMIGRATION AND ORIGIN].

BACKGROUND: Melanoma is a malignant tumor of melanocytes, whose prevalence has been increasing in recent decades. Early diagnosis allows removal of the tumor prior to the metastatic stage and may lead to a complete recovery. OBJECTIVES: To compare melanoma incidence among different epidemiological groups in northern Israel, and to assess the impact of migration on the increase in incidence of the disease. METHODS: A retrospective review was conducted of the medical records of all patients diagnosed with melanoma and treated in the Plastic Surgery Department at the Rambam Health Care Campus in 2016. Demographic data of 130 patients and tumor characteristics were collected and analyzed. RESULTS: European and American immigrants were found to carry an increased risk for melanoma compared to African and Asian immigrants. Increased melanoma risk was also found among a large subset of European immigrants from the former Soviet Union. This sub-group accounted for 32% of study group patients, while they only comprise 9% of the population (p <0.05). Most melanoma tumors in this sub-group were found in upper and lower extremities (60%). Disease was diagnosed at a younger age compared to the other European immigrants (p <0.05), with a trend towards a more advanced disease than the rest of the patients. CONCLUSIONS: Study findings imply an increased melanoma risk in immigrants from the former Soviet Union. Raising awareness of this population to preventative measures and the importance of early diagnosis may reduce morbidity and mortality caused by the disease. Further research is needed to determine whether routine screening tests should be applied to this population.

[MERKEL CELL CARCINOMA: A RETROSPECTIVE STUDY].

BACKGROUND: Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Though rare, in recent decades its prevalence has increased, and its incidence has tripled. OBJECTIVES: To describe a cohort of MCC patients treated at a referral center in northern Israel, and to compare their characteristics and course of illness to cases reported in the literature. METHODS: A retrospective review of 18 MCC patients treated in the Plastic Surgery Department at the Rambam Health Care Campus between the years 2011-2016. Patient demographics, medical history, histological findings, systemic involvement, adjuvant therapy, recurrence and survival rates parameters were collected and analyzed. RESULTS: Study group patients were predominantly elderly, mostly men, and mainly Caucasian. A few were immunocompromised. Melanoma and MCC are known to be linked, and indeed, about a quarter of the patients suffered previously from melanoma. Diabetes, although not described as an MCC risk factor, has accounted for about 50% of cases, more than 5 times its prevalence in the general population. Tumor and metastases distribution were similar to the literature. Metastases were found in about 20% of cases at diagnosis. In one third of the patients, lymph nodes were already involved during surgery, with recurrence rates of 50%, and 40% mortality in five years. CONCLUSIONS: Study results, for the first time, imply that there might be an association between diabetes and MCC. A link that could explain the rise of MCC incidence in recent decades. In addition, treatment guidelines were defined for metastatic disease which include the novel immunotherapy as a central component in treatment; hopefully, to improve patients' prognosis in this life-threatening disease.

Instantaneous depolarization of T cells via dopamine receptors, and inhibition of activated T cells of Psoriasis patients and inflamed human skin, by D1-like receptor agonist: Fenoldopam.

Activated T cells are pathological in various autoimmune and inflammatory diseases including Psoriasis, and also in graft rejection and graft-versus-host-disease. In these pathological conditions, selective silencing of activated T cells through physiological receptors they express remains a clinical challenge. In our previous studies we found that activation of dopamine receptors (DRs) in resting human T cells activates these cells, and induces by itself many beneficial T cell functions. In this study, we found that normal human T cells express all types of DRs, and that expression of D1R, D4R and D5R increases profoundly after T cell receptor (TCR) activation. Interestingly, DR agonists shift the membrane potential (Vm ) of both resting and activated human T cells, and induces instantaneous T cell depolarization within 15 seconds only. Thus, activation of DRs in T cells depolarize these immune cells, alike activation of DRs in neural cells. The skin of Psoriasis patients contains 20-fold more D1R+ T cells than healthy human skin. In line with that, 25-fold more D1R+ T cells are present in Psoriasis humanized mouse model. Highly selective D1-like receptor agonists, primarily Fenoldopam (Corlopam) - a D1-like receptor agonist and a drug used in hypertension, induced the following suppressive effects on activated T cells of Psoriasis patients: reduced chemotactic migration towards the chemokine SDF-1/CXCL12; reduced dramatically the secretion of eight cytokines: tumor necrosis factor-α, interferon-γ, interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-8 and IL-10; and reduced three T cell activation proteins/markers: CD69, CD28 and IL-2. Next, we invented a novel topical/dermal Fenoldopam formulation, allowing it to be spread on, and providing prolonged and regulated release in, diseased skin. Our novel topical/dermal Fenoldopam: reduced secretion of the eight cytokines by activated human T cells; reduced IL-1ß and IL-6 secretion by human lipopolysaccharide-inflamed skin; eliminated preferentially >90% of live and large/proliferating human T cells. Together, our findings show for the first time that both resting and activated T cells are depolarized instantaneously via DRs, and that targeting D1-like receptors in activated T cells and inflamed human skin by Fenoldopam, in Psoriasis, and potentially in other T cell-mediated diseases, could be therapeutic. Validation in vivo is required.

[A CASE REPORT OF THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) IN A BREAST CANCER PATIENT].

INTRODUCTION: A 49-year-old patient with a genetic expression of BRCA1, was admitted for a bilateral mastectomy and immediate reconstruction with tissue expander, following left breast malignancy (post-lumpectomy and radiation in the same breast). After the operation there were signs of infection in the left breast, for which she was treated with antibiotics. A few days later, mild neurological signs appeared, which resulted in an extensive investigation, and the next day a seizure occurred. Concurrent with the onset of clinical signs, thrombocytopenia and anemia appeared, accompanied by cell fractures in peripheral blood surface and decreased ADAMTS13 activity. The combination of the signs and symptoms led to the diagnosis of thrombotic thrombocytopenic purpura (TTP), probably caused by the antibiotic treatment, and the patient began treatment with plasma-parasites and steroids with a resolution of the findings. It is important to be aware of this entity, because of the disastrous consequences of misdiagnosis and therapeutic failure.

iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata.

Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10. Moreover, in pre-established humanized mouse AA lesions, hair regrowth is promoted by α-GalCer treatment through a process requiring both effector-memory iNKT cells, which can interact directly with CD8+/NKG2D+ T cells, and IL-10. This provides the first in vivo evidence in a humanized model of autoimmune disease that iNKT10 cells are key disease-protective lymphocytes. Since these regulatory NKT cells can both prevent the development of AA lesions and promote hair re-growth in established AA lesions, targeting iNKT10 cells may have preventive and therapeutic potential also in other autoimmune disorders related to AA.

Pneumonia Risk in Urgently Intubated Burn Patients.

BACKGROUND: Pneumonia is a major cause of morbidity and mortality in burn patients with inhalation injuries. An increased risk of pneumonia has been demonstrated in trauma and burn patients urgently intubated in the field vs. emergency departments (EDs). OBJECTIVES: To compare intubation setting (field vs. ED) and subsequent development of pneumonia in burn patients and to evaluate the indication for urgent intubation outside the hospital setting. METHODS: A retrospective medical records review was conducted on all intubated patients presenting with thermal (study group, 118 patients) or trauma (control group A, 74 patients) injuries and admitted to the intensive care unit of a level I trauma and burn center at a single institution during a 15 year period. Control group B (50 patients) included non-intubated facial burn patients hospitalized in the plastic surgery department. RESULTS: Field intubation was less frequent (37% field vs. 63% ED), although it was more frequent in larger burns (total body surface area > 50%; 43% field vs. 27% ED). More field intubated patients developed pneumonia during hospitalization (65% field vs. 36% ED [burns]; 81% field vs. 45% ED [multi-trauma]; 2% non-intubated, P < 0.05), with a significantly higher all-cause mortality (49% field vs. 24% ED, P < 0.05) and dramatically lower rates of extubation within 3 days (7% field vs. 27% ED, P < 0.05). CONCLUSIONS: Field intubation is associated with a higher risk of subsequent development of pneumonia in burn and multi-trauma patients and should be applied with caution, only when airway patency is at immediate risk.

Do Wound Cultures Give Information About the Microbiology of Blood Cultures in Severe Burn Patients?

BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis are among the most common infection complications occurring in severe burn patients. This study was designed to evaluate the relationship between the burn wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal wound and blood isolates from severe burn patients hospitalized in the burn unit and intensive care unit was obtained from medical records retrieved retrospectively from a computerized, hospital-wide database over a 13-year period. All data were recorded in relation to the Ryan score. RESULTS: Of 195 severe burn patients, 88 had at least 1 BSI episode. Transmission of the same pathogen from wound to blood was documented in 30% of the patients, with a rising BSI frequency as the Ryan score increased. There were a total of 263 bacteremic episodes in 88 study patients, 44% of blood isolates were documented previously in wound cultures, and transmission of the same pathogen from wound to blood was noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be broad spectrum and should rely on the susceptibility of the organisms from recent cultures of the burn wound surface, until the blood cultures results are completed.

Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus.

Developing a new drug is expensive: the cost of going from bench to bedside is about $US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits. Recombinant erythropoietin (EPO) is a potential candidate for repurposing because the results of numerous studies have shown that systemic and topical EPO is therapeutically beneficial when it is administered to healthy and diabetic animals with acute and chronic skin wounds and burns. Moreover, the molecular mechanisms of EPO's actions have been elucidated: EPO acts on those nonhematopoietic cells which are involved in the innate immune response where it promotes cellular proliferation and differentiation, exerts its cytoprotective actions, and inhibits apoptosis. In this review, the mechanism of EPO's action in skin wound healing is reviewed, and its potential for treating acute and chronic skin wounds and stimulating tissue regeneration in diabetic patients is discussed.

Spincare System Demonstrates Safety and Efficacy in Treating Partial-Thickness Burns.

Partial-thickness burns are the most common form of burns, affecting the dermis and possibly resulting in scarring and infection. The Spincare System is a new device that uses electrospinning technology to create a temporary skin-like matrix that can be applied to wounds. This study evaluated the performance, safety, and efficacy of Spincare in treating superficial to partial-thickness burns not considered for surgery. A prospective single-arm, open-label, multicenter study was conducted in 3 adult burn units across Israel. Forty-four patients with superficial to intermediate burns of up to 10% of TBSA were enrolled. Spincare was applied to the wounds, and follow-up visits were performed on days 7, 14, and 21 and months 3 and 6 posttreatment. Thirty-one patients with 36 wounds completed the day 21 visit. The mean wound healing area on day 21 was 97.26 ± 9.41%, and the mean healing time was 12.8 ± 4.3 days. Only one moderate adverse event was observed concerning the treatment, and it is important to acknowledge the potential progression of this hypertrophic scar into a keloid. This study demonstrated that Spincare is a safe and effective device for treating superficial to intermediate partial-thickness burns. Spincare achieved rapid and complete wound healing with a low incidence of adverse events.

Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata.

Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease.

Burns During Coronavirus Disease 19 Lockdown: a Multi-Center Retrospective Study in Israel.

The coronavirus disease 2019 (COVID-19) pandemic forced many countries into lockdowns to limit the spread of infection. Israel's containment measures included school closures, mobility restrictions, and workforce reductions. Our study evaluated the effect of COVID-19 on the occurrence and patterns of burn injuries. The study data was obtained via retrospective chart review of burn patients treated between March 15, 2020 and April 30, 2020, namely the period of strict national lockdown. This data was compared against data from paralleling periods between 2017 and 2019. A total of 686 patients were treated for burn injuries in the two study periods. Age group analysis revealed an increased ratio of pediatric patients aged 0-3 years during the lockdown (55.91% vs 40.79%, P = .002). In contrast, there were fewer patients presenting with burn injuries in the 7-16 and 17-29 age groups (9.66% vs 3.15%, P = .017; 16.46% vs 7.09%, P = .007, respectively). During both study periods, scald injuries were the most common burn etiology and burn injuries occurred most often at home. This predominance was further pronounced during the lockdown (71.65% vs 58.68%, P = .007; 90.55% vs 74.60%, P = .0001, respectively). The lockdown period underlined the danger faced by pediatric patients in their household environment. This danger was possibly compounded by an improper level of adult supervision as parents transitioned to remote work. These findings can educate us about factors that render burn injuries more likely not only during lockdowns, but also during regular times, thus shaping the development of burn prevention practices.

Human organ rejuvenation by VEGF-A: Lessons from the skin.

Transplanting aged human skin onto young SCID/beige mice morphologically rejuvenates the xenotransplants. This is accompanied by angiogenesis, epidermal repigmentation, and substantial improvements in key aging-associated biomarkers, including ß-galactosidase, p16ink4a, SIRT1, PGC1α, collagen 17A, and MMP1. Angiogenesis- and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIF1A, are most up-regulated in rejuvenated human skin. This rejuvenation cascade, which can be prevented by VEGF-A-neutralizing antibodies, appears to be initiated by murine VEGF-A, which then up-regulates VEGF-A expression/secretion within aged human skin. While intradermally injected VEGF-loaded nanoparticles suffice to induce a molecular rejuvenation signature in aged human skin on old mice, VEGF-A treatment improves key aging parameters also in isolated, organ-cultured aged human skin, i.e., in the absence of functional skin vasculature, neural, or murine host inputs. This identifies VEGF-A as the first pharmacologically pliable master pathway for human organ rejuvenation in vivo and demonstrates the potential of our humanized mouse model for clinically relevant aging research.

Hidden in plain sight: the (other) danger of COVID-19.

The Novel Coronavirus disease (COVID-19) first emerged in Wuhan province, China, in late November 2019 and changed public healthcare perception. It has caused a significant decline in attendance to outpatient clinics. However, other diseases have not stopped, including malignant melanoma. Survey of the number of visits to plastic surgery outpatient clinic during the first lockdown in Israel concerning malignant melanoma was compared to the same months in the previous years. We assessed the number of visits to the oncology department during 2020 compared to the number of visits and treatment protocols for malignant melanoma. During the first lockdown, the attendance at the plastic surgery outpatient clinic and ambulatory surgery decreased significantly (P = 0.002), both in excisions of suspected malignant melanoma and malignant melanoma follow-ups (P = 0.019 and P = 0.035, respectively). The last third of 2020 (from September to December) had shown a significant rise in new protocols commenced (P < 0.001). This rise in the final third of the year was not noted in 2018 or 2019. These data clearly show the rise in advanced and metastatic malignant melanoma cases due to refraining from medical follow-ups and treatments during the COVID-19 pandemic. Diseases other than COVID-19 have not vanished, and continue to treat those diseases. Ignoring malignant melanoma treatment because of COVID-19 and vice-versa will not benefit our patients.