Red Breast Syndrome and Acellular Dermal Matrix.

Increasingly popular for use in breast reconstruction, acellular dermal matrix (ADM) can provide support and protection to implants. However, use of ADM may be associated with infection and complications, including red breast syndrome (RBS). RBS is an inflammatory event that typically presents with cutaneous erythema over the domain where the ADM is surgically implanted. As ADM use increases, presumably, more cases of RBS will occur. Thus, techniques and tools to mitigate or manage RBS are needed to improve patient outcomes. Here, we describe a case where RBS was diagnosed and interestingly resolved after exchange for a different brand of dermal matrix. This surgical resolution maintained excellent reconstructive results with no recurrent erythema over a follow-up period of 7 months. Although we cannot rule out RBS due to other variables, RBS due to patient hypersensitivity to certain ADMs has been documented in the literature. In this instance, our results suggest that revision with an alternate ADM brand may serve as a potential solution.

Deeper Seated Than Skin Deep: Report of a Rare Case of Follicular Occlusion Tetrad and a Literature Review.

Follicular occlusion tetrad (FOT) is a clinical syndrome consisting of hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal cyst (PC). These entities typically occur independently, but occasionally present simultaneously comprising FOT. The four components share similar pathophysiology affecting the apocrine glands, follicular hyperkeratinization being the hallmark of each entity. Understanding shared similarities of each disease is paramount for the treatment approach as the relapsing and chronic nature of this syndrome can be burdening to patients. We present the case of a 22-year-old obese Hispanic man with a history of tobacco use who presented with worsening skin lesions. The patient developed extensive facial cystic acne 5 years before presentation, followed by left axillary hidradenitis suppurativa lesions two years before the presentation and right axillary involvement one year after. Skin manifestations then expanded to include the lower back, gluteal and perineal areas. The patient was diagnosed with FOT and despite conservative medical management, his lesions failed to improve. He ultimately underwent multiple staged excisional debridement surgeries and skin grafts. Our case underlines the presence of a syndromic association of cutaneous lesions that share a common pathogenesis and emphasizes that this entity requires a multidisciplinary approach. New biologic therapies continue to emerge and may potentially prevent the need for surgical intervention and the burden associated with it.

Population-based analysis of POT1 variants in a cutaneous melanoma case-control cohort.

Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein-telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies.

Two Cases of Autoimmune Syndrome Induced by Adjuvants (ASIA): A Multifaceted Condition Calling for a Multidisciplinary Approach.

Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. Similarly, the patient was treated with corticosteroids followed by breast implant removal with complete resolution of symptoms. The successful treatment of these patients was achieved by collaboration between rheumatology and plastic surgery, which emphasizes the need for a multidisciplinary approach in the diagnosis and management of patients with ASIA.

Clinical Outcomes of Acellular Dermal Matrix (SimpliDerm and AlloDerm Ready-to-Use) in Immediate Breast Reconstruction.

Background The use of acellular dermal matrix (ADM) for post-mastectomy reconstruction is considered by many surgeons to be an accepted component of surgical technique. Early clinical experience is described for SimpliDerm® - a novel human ADM (Aziyo Biologics, Silver Spring, USA), and AlloDerm® Ready-To-Use (RTU) - an established ADM (Allergan Medical, Irvine, USA). Methods Records were retrospectively reviewed from four sites between 2016 and 2021 of patients who underwent immediate, two-stage reconstruction with either SimpliDerm (n=38) or AlloDerm RTU (n=69) after mastectomy and were followed out to exchange to permanent implant(s), tissue expander(s) explant, or death. Results Immediate breast reconstruction with tissue expanders and ADM was performed on 107 patients (181 breasts). Overall mean patient age was 51.4 ± 12.4 years, and mean BMI was 28.0 ± 5.8 kg/m2. Significantly more patients in the SimpliDerm group were of Hispanic or Latino ethnicity (34.2% vs. 7.2%; P<.001). Reconstructions were predominantly prepectoral (82.3%). A total of 35 adverse events (AEs) occurred in 27 (25.2%) patients, with no difference in AE type, classification, or rates between ADM groups. No AEs were considered related to either ADM. The observed AE profiles and rates are similar to those published for other ADMs in immediate breast reconstruction. Conclusions There continues to be a need for additional clinically equivalent ADMs to provide physicians with more availability and options for their practice. This retrospective, multisite study describes comparable clinical outcomes with SimpliDerm and AlloDerm RTU through a median of 133.5 days (~four months) following immediate two-stage breast reconstruction.

Histologic Analysis of Sensory and Motor Axons in Branches of the Human Brachial Plexus.

BACKGROUND: The topographic distribution through histologic analysis of motor and sensory axons within peripheral nerves at the brachial plexus level is not clearly defined, as there has previously been little need to appreciate this microanatomy. A desire to better understand the topography of fascicle groups developed with the introduction of targeted muscle reinnervation. METHODS: Fourteen bilateral brachial plexus specimens from seven fresh human cadavers were harvested at the time of organ donation, and immunofluorescent staining of motor and sensory nerves with choline acetyltransferase and Neurofilament 200 was performed to determine whether a consistent somatotopic orientation exists at the brachial plexus level. RESULTS: There was significant variability in the number of fascicles at the level of the brachial plexus. Qualitative analysis of choline acetyltransferase staining demonstrated that although motor axons tended to be grouped in clusters, there were high degrees of variability in somatotopic orientation across specimens. The radial nerve demonstrated the highest number of total myelinated axons, whereas the median nerve exhibited the greatest number of motor axons. The ulnar nerve contained only 13 percent motor axons, which was significantly lower than the median, radial, and musculocutaneous nerves. CONCLUSIONS: There was no consistent somatotopic organization of motor and sensory axons of the mixed major nerves of the arm just distal to the brachial plexus, but clustering of motor axons may facilitate the splitting of nerves into primarily "motor" and "sensory" fascicles.

Microsurgical Reconstruction of the Burned Hand and Upper Extremity.

Improvements in critical care and burn victim resuscitation have led to increased survival of burned patients. Initial resuscitation, early excision of burned tissues, prevention of burn wound sepsis, and wound coverage remain mainstays of care. Many burn wounds require complex reconstruction. This is particularly important in the hand. Coverage of tendons, ligaments, joints, vessels, nerves, and bones of the hand requires healthy vascularized tissue to maintain viability and function. Local flaps or regional flaps may be within the burn zone of injury. Refined microvascular free tissue transfer techniques offer free tissue transfer as a procedure that can be safely performed.

Two-stage treatment of ischial pressure ulcers in spinal cord injury patients: Technique and outcomes over 8 years.

BACKGROUND: Despite newly introduced techniques, reconstruction of ischial pressure ulcers remains a difficult problem with high-reported failure rates. METHODS: A retrospective chart review was performed on all spinal cord injury patients who underwent ischial pressure ulcer reconstruction by the senior author (V.L.) between 2004 and 2012. The two-stage procedure consisted of debridement and bone biopsy, followed by bursectomy, partial ischiectomy, fascial release, and gluteus maximus and hamstring advancement flaps. Postoperative care included 2-week supine bed rest on an air-fluidized bed, sitting tolerance rehabilitation, and thorough behavioral training. RESULTS: Sixty-five patients (74 flaps) were identified. A 45.9% had a previous attempt at reconstruction. The median follow-up period was 622 days. Overall, 67.6% of flaps were intact at the last follow-up. Superficial and deep dehiscence rates were 16.2 and 28.4%, respectively. Seven out of 35 flaps suffered late recurrence after being well healed for more than 1 year. History of previous reconstruction was found to be associated with increased odds of superficial (OR 6.02, 95% CI 1.55-23.3) and deep dehiscence (OR 12.3, 95% CI 1.99-76.9). CONCLUSIONS: The evolution of the senior author's decades of practice has led to the development of a simpler repair, which relies on plane-by-plane release of scarred tissues to improve the mobility of muscle and skin flaps without large tissue movements, even in the setting of apparent extensive tissue loss. This technique is a reliable option, particularly for the primary ischial pressure ulcer.

Excisional wound healing is delayed in a murine model of chronic kidney disease.

BACKGROUND: Approximately 15% of the United States population suffers from chronic kidney disease (CKD), often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. METHODS: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD) 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR). RESULTS: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU) and angiogenesis (CD31), with a concurrent increase in inflammation (CD45) as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1ß, eNOS, iNOS) on qPCR. CONCLUSIONS: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

Limb transplantation and targeted reinnervation: a practical comparison.

Limb transplantation and targeted reinnervation are complimentary but very different approaches for restoring function to an upper limb amputee. This article reviews the advantages and limitations of both of these procedures, and highlights the reconstructive obstacles in the treatment of upper limb amputees.

Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior?

Murine models have provided valuable insights into the pathogenesis of both diabetes and chronic wounds. However, only a few published reports to date have investigated wound healing differences among the differing diabetic mouse models. The goal of the present study was to further define the wound healing deficiency phenotypes of streptozotocin-induced (STZ-induced), Akita, and db/db diabetic mice in comparison with a promising new polygenic strain of Type 2 diabetes (NONcNZO10) by using three specific wound models that targeted different critical processes in the pathogenesis of chronic wounds. Incisional, excisional, and ischemia/reperfusion wound models were established on mice of each strain. Wound healing parameters including tensile strength, epithelial gap, and wound necrosis were evaluated. In contrast to the other diabetic mice, the NONcNZO10 strain was found to have significant wound healing impairments in all wound healing models. Not only do the NONcNZO10 mice appear to better model human Type 2 diabetes, these provocative findings suggest that the mice may show more clinically relevant wound healing deficiencies than previous diabetic mouse models.

Homeostasis of the epidermal barrier layer: a theory of how occlusion reduces hypertrophic scarring.

The mechanism of hypertrophic scar reduction using silicone gel sheeting remains elusive. We hypothesize that the decrease in scar formation is due to occlusion and homeostasis of the barrier layer. Using an established model of hypertrophic scarring, rabbits were divided into four groups and scars were tape-stripped or occluded with Kelocote, Cavilon, or Indermil, with each rabbit serving as its own internal control. All wounds were harvested on day 28 and examined histologically to measure the scar elevation index (SEI), epithelial thickness, and cellularity. Immunohistochemistry fluorescence was used to quantify inflammation in the dermis. Transepidermal water loss (TEWL) was measured for each occlusive agent and tape stripping. Ultrastructural analysis was performed by electron microscopy. Kelocote, Cavilon, and Indermil all significantly decreased SEI when compared with controls. Each of the occlusive treatments was shown to decrease TEWL while tape stripping increased TEWL. Tape stripping significantly increased the SEI, epithelial thickness, and cellularity. Immunostaining for macrophages showed increased density of inflammatory cells in the tape-stripped scars. Under electron microscopy, the tape-stripped wounds displayed extensive inflammation and keratinocyte damage. Both unwounded skin and occlusion-treated scars did not display these characteristics. In conclusion, hypertrophic scarring was reduced regardless of occlusive method used. Furthermore, repeated disruption of the permeability barrier by tape stripping led to an increase in scarring. Ultrastructural analysis suggests that occluded wounds may be in an advanced state of wound repair. Occlusion may mediate its effects through establishing homeostasis of the epidermal barrier layer.

Essential roles for early growth response transcription factor Egr-1 in tissue fibrosis and wound healing.

The early growth response gene (Egr-1) codes for a zinc finger transcription factor that has important roles in the regulation of cell growth, differentiation, and survival. Aberrant Egr-1 expression is implicated in carcinogenesis, inflammation, atherosclerosis, and ischemic injury. We reported previously that normal fibroblasts stimulated by transforming growth factor-ss showed rapid and transient induction of Egr-1. Moreover, we observed that tissue expression of Egr-1 was elevated in patients with scleroderma, which suggests that Egr-1 may be involved in tissue repair and fibrosis. Here, we investigated matrix remodeling and wound healing in mice harboring gain of function or loss of function mutations of Egr-1. Using the model of bleomycin-induced scleroderma, we found that the early influx of inflammatory cells into the skin and lungs, and the subsequent development of fibrosis in these organs, were markedly attenuated in Egr-1 null mice. Furthermore, full-thickness incisional skin wound healing was impaired, and skin fibroblasts lacking Egr-1 showed reduced migration and myofibroblast transdifferentiation in vitro. In contrast, transgenic mice with fibroblast-specific Egr-1 overexpression showed exuberant tissue repair, with enhanced collagen accumulation and increased tensile strength of incisional wounds. Together, these results point to the fundamental role that Egr-1 plays in the regulation of transforming growth factor-ss-dependent physiological and pathological matrix remodeling.

Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model.

Bacterial biofilms have gained increasing visibility in recent years as a ubiquitous form of survival for microorganisms in myriad environments. A number of in vivo models exist for the study of biofilms in the setting of medically relevant implanted foreign bodies. Growing evidence has demonstrated the presence of bacterial biofilms in the setting of a number of chronic wound states including pressure sores, diabetic foot ulcers, and venous stasis ulcers. Here we present a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm. We established biofilms using either Staphylococcus aureus or Staphylococcus epidermidis in splinted cutaneous punch wounds created on the backs of normal C57Bl6/J mice. Wound reepithelialization was significantly delayed by bacterial biofilms. This effect was specifically dependent on the ability of the bacteria to form biofilms as demonstrated by exogenous administration of biofilm inhibiting peptides and the use of mutant Staphylococcus spp. deficient in biofilm formation. This represents the first direct evidence for the effect of bacterial biofilms on cutaneous wound healing.