Abstract Background: Burns are a major public health problem. They often require intensive care and long periods of hospitalization. In Tehran, about 5% of all hospitalized injuries are burns. There are no published long-term epidemiological studies regarding burn injuries of adults in Iran. Objective: To identify risk factors for burn injuries and provide a starting point for the establishment of an effective prevention plan. Methods: We analyzed the demographic, etiological, and clinical data of 1860 burn patients admitted to a major acute care hospital in Tehran between March 2010 and April 2011. Data were obtained from the registry recorded in Shahid Motahari Trauma Hospital and evaluated using a chi-square test. Results: Males were more than twice as likely to be burn patients than females (72.0% vs. 28.0%). Second and third-degree burns with a body surface area of 21%-30% constituted the highest injury reported (75.3%). The most common causes of the recorded burns were natural gas, gasoline (42%) and open fire (10.2%). Unintentional burns were reported in 85% of the cases, and 15% of the burn victims were suicide-related incidents; mainly among women. In 75% of suicide attempts, women set themselves on fire to commit suicide. The mean duration of hospitalization was 25 days and the mortality rate was 10.7%. Mean age of reported deaths was 38.6 years; with a mean of 30 years among women and 51.5 years among men. Conclusion: The group at highest risk was young men 21-30 years old. However, an astonishing finding was that 75% of suicidal-related incidents involved women setting themselves on fire. Those with the highest mortality rate were victims of burns with gas, gasoline, and kerosene; with a mean age of 30 years of death among women.
Persistent Sweet syndrome in a patient with history of myelofibrosis thought to be in remission post-hematopoietic stem cell transplantation leads to diagnosis of molecular relapse of myelofibrosis. The authors declare no conflicts of interest.
Lack of matrix deposition is one of the main factors that complicates the healing process of wounds. The aim of this study was to test the efficacy and safety of a liquid dermal scaffold, referred to as MeshFill (MF) that can fill the complex network of tunnels and cavities which are usually found in chronic wounds and hence improve the healing process. We evaluated in vitro and in vivo properties of a novel liquid dermal scaffold in a delayed murine full-thickness wound model. We also compared this scaffold with two commercially available granular collagen-based products (GCBP). Liquid dermal scaffold accelerated wound closure significantly compared with no-treated control and collagen-based injectable composites in a delayed splinted wound model. When we compared cellular composition and count between MF, no treatment and GCBP at the histology level, it was found that MF was the most analogous and consistent with the normal anatomy of the skin. These findings were matched with the clinical outcome observation. The flowable in situ forming scaffold is liquid at cold temperature and gels after application to the wound site. Therefore, it would conform to the topography of the wound when liquid and provides adequate tensile strength when solidified. This patient-ready gelling dermal scaffold also contains the nutritional ingredients and therefore supports cell growth. Applying an injectable liquid scaffold that can fill wound gaps and generate a matrix to promote keratinocytes and fibroblasts migration, can result in improvement of the healing process of complex wounds.
The use of autologous meshed grafts saves lives of patients with large burn injuries. However, ungrafted areas remain open with a high chance of infection, fluid and heat loss and formation of devastating fishnet-like irregular scars. To overcome these difficulties, here, we formulated a shelf ready multifunctional powdered re-constituteable liquid skin substitute referred as to MeshFill to fill up void burn areas in a meshed graft. Prior to its use in a clinical setting, in this study, the functionality of filling up non-contractile splinted wounds with MeshFill on wound closer, epithelialization and healing quality was examined. A total of 32 punch wounds (6mm) were generated on the back of 8 mice (4 wounds/ mouse) and they were splinted to prevent contraction. Half of these wounds received nothing (Untreated control) and another half were filled up with MeshFill (MF). Mepitel was used as wound coverage to prevent adhesion and non-adhesive gauze was sutured over the Mepitel dressing. Wounds were daily monitored for healing, dressing and photographed on Day 7 and 14 post application. On day 7 and 14, mice were terminated and wound areas were harvested and stained for infiltrated immune cells (CD45+ cells), tissue histology and cellularity. The results showed a significantly faster epithelialization and wound closure of splinted wounds received MeshFill as compared to those of control. The findings further showed an early appearance and clearance of infiltrated immune cells (CD45+ cells) in treated wounds as compared to control indicating that the inflammation phase was shifted to early time points of healing process. The results demonstrated that the use of in situ forming scaffold accelerates wound closure and shifting the inflammation phase to an earlier time points in a delayed splinted wound model in mice. Proving the functionality of our novel liquid skin substitute in splinted wounds will set the stage for its use in a clinical setting in which void areas of autologous meshed graft can be filled up and improve the healing quality of burn injuries. Proving the functionality of our novel liquid skin substitute in splinted wounds will set the stage for its use in a clinical setting in which void areas of autologous meshed graft can be filled up and improve the healing quality of burn injuries.
Background and Objective: Despite the effectiveness of skin autotransplantation, the high degree of immunogenicity of the skin precludes the use of allografts and systemic immunosuppression is generally inappropriate for isolated skin grafts. Indoleamine 2,3 dioxygenase (IDO) is a potent immunoregulatory factor with allo- and autoimmune suppression and tolerance induction properties. This study examines the potential use of locally expressed IDO to prolong the allogeneic skin graft take in a mouse model. Approach: Syngeneic-fibroblasts were transfected with noncompetent IDO viral vector and the level of Kynurenine (Kyn) in conditioned medium was measured as an index for IDO activity. Either 1 or 3 × 106 IDO-fibroblasts were introduced intra/hypo-dermally to the mouse skin. The expression, localization, and functionality of IDO were then evaluated. The cell-injected areas were harvested and grafted on the back of allogeneic mice. The graft survival, immune-cells infiltration, and interaction with dendritic cells were evaluated. Results: The results showed a significant improvement in allogeneic graft take injected with 1 × 106 IDO-fibroblasts (18.4 ± 3.3 days) compared with control (12.2 ± 1.9 days). This duration increased to 35.4 ± 4.7 days in grafts injected with 3 × 106 IDO-expressing cells. This observation might be due to a significantly lower T cells infiltration within the IDO-grafts. Further, the result of a flow cytometric analysis showed that the expression of PD-L1/PD-L2 on CD11c+/eFluor+ cells in the regional lymph nodes of injected skin areas was significantly higher in IDO groups compared with control. Conclusion: These data suggest that allogeneic skin graft survival outcome can be prolonged significantly by local overexpression of IDO without any systemic effect.
Skin transplantation provides an excellent potential model to investigate the immunology of allograft rejection and tolerance induction. Despite the theoretical ease of performing skin transplantation, as well as the potential of directly observing the reaction to the transplanted tissue, the poor reliability of skin transplantation in the mouse has largely precluded the use of this model. Furthermore, there is controversy regarding the most appropriate skin graft donor site due to poor success of back skin transplantation, as compared with the thinner ear or tail skin. This study demonstrates a reliable method to successfully perform skin grafts in a mouse model, as well as the clinical and histologic outcome of syngeneic grafts. A total of 287 grafts were performed (in 126 mice) utilizing donor skin from the ear, tail or back. No graft failure or postoperative mortality was observed. Comparison of this technique with two previously established protocols of skin transplantation (5.0 absorbable Suture + tissue glue technique and no-suture technique) demonstrates the significant improvement in the engraftment success of the new technique. In summary, a new technique for murine skin grafting demonstrates improved reliability across donor site locations and strains, increasing the potential for investigating interventions to alter the rejection process.
Storiform collagenoma is a rare mesenchymal skin tumor that is composed of thickened collagen bundles arranged in a characteristic storiform pattern with a relatively hypocellular CD34-positive spindle cell component. Storiform collagenoma is most often sporadic, but multiple lesions can occur in Cowden syndrome, which is characterized by germline alterations in PTEN (phosphatase and tensin homolog) on chromosome 10. Here, we investigated the molecular pathogenesis of storiform collagenoma using a targeted next-generation DNA sequencing platform, including 5 sporadic cases and one case associated with Cowden syndrome. Recurrent PTEN alterations were identified in all cases, with biallelic PTEN inactivation observed in the case associated with Cowden syndrome and one sporadic case. Unexpectedly, we also identified recurrent activating mutations in the platelet-derived growth factor receptor beta ( PDGFRB ) gene. This included a missense substitution in the D5 Ig-like domain of PDGFRB in the Cowden syndrome-associated case. In addition, we report missense alterations in the juxtamembrane domain of PDGFRB in 4 of 5 (80%) sporadic cases, including mutations that have been previously described in sporadic myofibroma and myopericytoma. Therefore, we confirm the neoplastic nature of storiform collagenoma, we expand the spectrum of reported PDGFRB alterations in mesenchymal tumors and we suggest a possible collaborative role for PTEN and PDGFRB in the pathogenesis of storiform collagenoma.
Wound repair and regeneration is a multidisciplinary field of research with considerable value to the treatment of deep and large burn injuries. These injuries lack an appropriate tissue scaffold and pro-healing cells making them difficult to heal. An alternative to the often limited autologous skin is a therapy that would restore the essential matrix and cellular components for rapid healing. Over the last decade, mesenchymal stem cells have become the focus of research in regenerative medicine owing to their ability to provide the essential building blocks for skin regeneration. Herein, we utilize a validated method of wound splinting in a delayed-healing murine model to investigate the pro-healing effects of adipose-derived stem cells (ASCs) in a novel dermal matrix in the healing of complex wounds. To ensure ASC survival within the gel matrix, cells were incubated with the matrix for 14 days prior to in-vivo studies. Viability was tested at days 3,7 and 14. With ethics approval, full-thickness 8 mm diameter excisional wounds were created and splinted on the dorsum of genetically diabetic mice. Eighteen animals were randomized into 3 groups: 1) occlusive dressing only (control), 2) gel, 3) gel + ASCs. Wounds were photographed at days 0, 7, 10, 14 and wound area was calculated using Image J Software. Histologic samples were examined for architecture and collagen content. Capillary formation was quantified using immunofluorescence. GFP labelling of ASCs was used to track the fate of these cells within the wound. The gel matrix supported the survival of ASCs. In-vivo testing showed that treatment groups had accelerated epithelialization. Wounds treated with gel + ASCs had a significant reduction in wound size after Day 10 (p<0.001). Histology showed earlier re-epithelialization in both treatment groups. GFP staining showed co-localization of ASCs with capillaries. There was an increased number of capillaries in the wound site for groups treated with ASCs compared to control (p <0.001). ASCs are a viable source of pro-healing cells in deep wounds. The cell populated matrix accelerated wound healing, decreased wound size and increased capillary formation in a delayed-healing murine model. The dermal gel matrix combined with ASCs is a feasible treatment strategy for complex or large burn wounds. The dermal gel matrix component has since been shown to be non-toxic to human cells. The protocol can be modified for human use by using autologous ASCs.
