Ischemic Skin Research Articles

Terlipressin Induced Skin Ischemia: A Case Report

Terlipressin is a synthetic vasopressin analogue used in the treatment of cirrhotic patients with variceal bleeding and hepatorenal syndrome. Side effects associated with terlipressin are usually mild but some rare serious complications can also be seen. Terlipressin induced skin ischemia is one such serious complication. We report a case of 57-year-old lady, a case of chronic alcoholic liver disease presented with variceal bleeding. Patient was given bolus injection terlipressin every 4 hour and patient developed skin ischemia within 48 hours of terlipressin administration. Skin ischemic changes showed marked improvement after stoppage of terlipressin. Treating clinicians should be more vigilant about this rare adverse effect of terlipressin. Early recognition and treatment of the ischemic skin complication gives a better outcome. How to cite this article: Kumar N, Bohania N, Kumar S. Terlipressin Induced Skin Ischemia: A Case Report. J Adv Res Med 2019; 6(4): 10-12. DOI: https://doi.org/10.24321/2349.7181.201918

Effect of natural hirudin on revascularization of ischemic skin flaps in rats by Micro-CT

To investigate the effect of natural hirudin on revascularization of ischemic skin flap in rats using Micro-CT and three-dimensional (3D) reconstruction. Thirty-two Sprague Dawley rats were prepared a ischemic skin flap (8.0 cm×1.8 cm) model on the back and randomly divided into hirudin group and control group (16 rats in each group). At immediate and within 3 days after operation, the rats were treated with hypodermic injection of natural hirudin 0.3 mL (including natural hirudin 6 ATU) every day in hirudin group and the equal amount of normal saline in control group. At 6 days after operation, the survival rate of skin flap was evaluated, histological changes were observed by HE staining, and the volemia, length of blood vessels, and number of blood vessels were analyzed with Micro-CT 3D reconstruction. Both groups of rats survived to the end of the experiment without infection. Different degrees of necrosis occurred in the distal part of the skin flaps in both groups at 6 days after operation, but the flap survival rate of the hirudin group (72.11%±8.97%) was significantly higher than that of control group (58.94%±4.02%) ( t=3.280, P=0.008). Histological observation showed that the histological hierarchy of the hirudin group was clearer than that of the control group, with more microangiogenesis and less inflammatory response and inflammatory cell infiltration. Micro-CT 3D reconstruction showed that the flap vessels in the hirudin group were more and denser, and the volemia, length of blood vessels, and number of blood vessels were significantly higher than those in the control group ( P<0.05). Natural hirudin can reduce the inflammation of tissue, promote the regeneration and recanalization of blood vessels in ischemic skin flap, so as to improve the survival rate of the flap.

联合或者单独使用利伐沙班治疗青斑样血管病三例

Livedoid vasculopathy is a rare chronic ischemic necrotic skin disease caused by microvascular thrombosis in superficial vascular plexuses. Effective treatments are lacking. Efficacy of anticoagulants has been clinically proven in the treatment of this disease, but the administration route and adverse reactions limit their extensive application. The new oral factor Xa inhibitor rivaroxaban, which has many advantages, such as no need for coagulation monitoring, few adverse reactions and convenient oral administration, can be used in the prevention and treatment of thrombosis and post-thrombotic ulcers. In this article, 3 patients with livedoid vasculopathy were treated with rivaroxaban alone or in combination, and satisfactory efficacy was obtained. Key words: Skin diseases, vascular; Anticoagulants; Treatment outcome; Livedoid vasculopathy; Rivaroxaban

Effects of Ultrasound-Assisted Preconditioning on Critically Ischemic Skin Flaps: An Experimental Study

This study evaluates the effect of ultrasound-assisted preconditioning on critically ischemic flaps. Ninety-eight Sprague Dawley rats were randomly divided into eight groups. Control, surgical delay, ultrasound and sham groups were designed. Modified McFarlane flaps were raised on the back of rats, and flap survival rate was assessed on post-operative day 14 in control, ultrasound and sham groups. Bipedicled flaps were created in the surgical delay group, and 14 d after delaying, all skin flaps were elevated. Statistically, flap survival rates of all ultrasound groups were significantly higher than the control group. Plasma vascular endothelial growth factor levels were increased in all ultrasound groups. Vessel counts did not show any difference between the groups. This study shows that the preconditioning by ultrasound can be used to improve the viability of ischemic skin flaps almost at a level close to the surgical delay.

Mechanisms of the wound-healing action of native collagen type I in ischemic model full-thickness skin wounds on the example - medical devices Collost «(part I)

To study the mechanism of the native collagen type I wound-healing action of native type I collagen on the example of the medical device Collost (7% gel) in a model of the rats difficult-to-heal skin wounds. Male rats in population SD (72 individuals) surgically formed an ischemic dorsal skin flap (3×10 cm) with two full-thickness skin wounds 6 mm in diameter.The trained animals divided into 2 groups: in the experimental group, medical device Collost (gel) applied once after the operation, in the control group - a standard medical device for comparison. The dynamics of wound healing assessed, the number of M2 macrophages, myofibroblasts, vascularization and expression of the main markers of the repair process in the wound tissues and time points for assessment were: after 3, 7 and 14 days after operation using macroscopic, immunohistochemical, and molecular methods. It has been established that the mechanism of action of native collagen type I is associated with the acceleration of the appearance of «progenitorous» M2-macrophages in the wound tissues, decrease in the severity of inflammation or reduction in the duration of the inflammatory stage of the repair process, change in the expression spectrum of number of growth factors, an acceleration of neovasculogenesis. In this work, on the modern experimental model shown regenerative efficiency of a medical device based on collagen type I and described the molecular and cellular processes of wound healing when using it It has been shown that the acceleration of wound healing processes occurs when using a medical device based on native collagen type 1, it is also accompanied by a better aesthetic closure of the damaged skin area.

&amp;lt;i&amp;gt;Aloe vera&amp;lt;/i&amp;gt;—Mechanisms of Action, Uses, and Potential Uses in Plastic Surgery and Wound Healing

Aloe vera has been used for centuries for medicinal purposes. Clinical and experimental evidence indicates usefulness for skin moisturization, promoting wound healing, thermal skin injury, frostbite, and ischemic skin insults. Aloe vera has anti-inflammatory, vasodilatory, antimicrobial, and proliferative actions, which have been investigated in various experimental models and in various in vitro studies. This extensive literature review of the properties and actions of Aloe vera finds substantial evidence for the reported and also likely clinical usefulness for Aloe vera in Plastic Surgery and in wound care and wound healing. Though further clinical investigation is warranted, Aloe vera use may likely be indicated in situations where its effects could positively influence outcomes, such as wound healing, flap vascularity, and inflammatory skin pathologies.

Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats

Background: Random skin flaps are frequently applied in surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential. Here, we explored the potential of fibroblasts engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) to improve vascularization and survival of therapeutic random skin flaps. Methods: Ex vivo fibroblasts were transfected with plasmids encoding GFP, luciferase or SDF-1α modRNAs. The transfection efficiency and recombinant protein expression were assessed. Rat random skin flaps models were injected intradermally with fibroblasts transfected with modRNA in vivo. The degree of necrosis and apoptosis in skin flaps were evaluated by histological analysis. Expression of SDF-1α/CXCR4 pathway-related proteins was evaluated by western blot and immunofluorescence analyses. Findings: Our study showed that fibroblasts pre-treated with SDF-1α modRNA have the potential to salvage ischemic skin flaps. Through a detailed analysis, we revealed that a fibroblast SDF-1α modRNA combinatorial treatment dramatically reduced tissue necrosis and significantly promoted neovascularization in random skin flaps compared to that in the control and vehicle groups. Moreover, SDF-1α modRNA transcription in fibroblasts promoted activation of the SDF-1α/CXCR4 pathway, with concomitant inactivation of the MEK/ERK, PI3K/AKT and JAK2/STAT3 signaling pathways, indicating a possible correlation with cell proliferation and migration. Interpretation: Fibroblast-mediated SDF-1α modRNA expression represents a promising strategy for random skin flap regeneration. Funding Statement: This work was supported by grants from the Wenzhou Public Welfare Science and Technology Project (Y20170238), the National Natural Science Foundation of China (81401798), the Zhejiang Provincial Natural Science Foundation of China (LQ13C100001), Zhejiang Provincial Project for Medical and Health Science and Technology (2013KYA128), Shanghai Pujiang Program (18PJD031), Shanghai Collaborative Innovation Program on Translational Medicine (TM201821), the Biomedical Engineering fund of Shanghai Jiao Tong University (YG2016MS28) and fund from Shanghai Key Laboratory of Tissue Engineering. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Animal Care and Use Committee of Wenzhou Medical University (ethics code: wydw2017-0159).

Vision Loss Associated with Hyaluronic Acid Fillers: A Systematic Review of Literature.

With the global increase in the use of injectable fillers, more cases with serious adverse events such as skin ischemia and vision loss are being reported. This article aims to review the role of HA fillers, as a subgroup separate from fat graft and non-HA fillers, in causing vision loss and to elucidate various features and outcomes of post-HA filler vision loss. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to report this review. A total of 29 articles presenting 60 unique cases of post-HA filler vision loss were identified in the literature. Based on various inclusion and exclusion criteria, 26 articles with details of 44 cases were included in this study. The majority of cases were seen in women and in the 20-40years age group. The maximum number of cases was reported from Korea, followed by China. Nearly half of the cases reported after HA filler-related visual complications had partial loss of sight, hence 'partial vision loss' and 'complete vision loss' were used as differentiating descriptive terms to the degree of 'blindness.' Nearly all the cases were unilateral, with immediate onset of visual signs and symptoms. The nose, glabella, and forehead were the most commonly implicated areas, while no cases of post-HA filler vision loss were reported from lower face anatomical areas, including the chin, jawline, and lips. Partial vision loss after HA filler has a better prognosis than complete vision loss. HA filler volumes as low as 0.2ml can cause permanent, complete vision loss, which is suggestive of the embolic nature of HA filler blockage. Ophthalmic artery occlusion (OAO) and central retinal artery occlusion (CRAO) were the two most commonly involved arterial obstruction patterns followed by branch retinal artery occlusion (BRAO). BRAO is the most favorable involved arterial pattern for a chance of recovery after HA filler-related vision loss while CRAO and OAO patterns carry a very poor prognosis. Post-HA filler vision loss is nearly always of immediate onset. Partial vision loss after HA filler injection with the involvement of smaller branches of the retina, other than central retinal artery or ophthalmic artery, has more favorable visual outcomes. 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.

Overconsumption of tums, an unexpected cause of calciphylaxis in a reconstructed breast: a case report

Calciphylaxis is a rare syndrome where vascular calcifications lead to microvessel occlusion and the development of painful, ischemic skin lesions. Herein, we present a case of an otherwise healthy female with skin necrosis that developed after a nipple sparing mastectomy (NSM) who subsequently received a diagnosis of calciphylaxis with unclear etiology. A 63-year-old Caucasian female presented to our institution for care after being diagnosed with a stage IIA, triple negative inflammatory ductal carcinoma of the right breast. The patient seen in clinic 1 week after surgery and necrosis of the inferior aspect of the breast was noted with marginal blood flow below the nipple. Local wound care was continued and 10 days later, necrotic tissue was excised and sent for pathology. The pathology report returned as calciphylaxis. On subsequent discussion with the patient, she admitted to consuming approximately a bottle of tums (calcium carbonate) per day for reflux. While she was usually borderline hypercalcemic, her calcium level pre-operatively was only 10.5. We hope this report encourages surgeons to consider a diagnosis of calciphylaxis in individuals, even without obvious risk factors, with otherwise unexpected tissue necrosis.

Robot-assisted Nipple-sparing Mastectomy with Immediate Breast Reconstruction: An Initial Experience

Seeking smaller and indistinct incisions, physicians have attempted endoscopic breast surgery in breast cancer patients. Unfortunately, there are some limitations in the range of movement and visualization of the operation field. Potentially addressing these limitations, we investigated the outcomes of gas and gasless robot-assisted nipple-sparing mastectomy (RANSM) with immediate breast reconstruction (IBR). Ten patients underwent 12 RANSM with IBR between November 2016 and April 2018. Patients with tumors measuring >5 cm in diameter, tumor invasion of the skin or nipple-areolar complex, proven metastatic lymph nodes, or planned radiotherapy were excluded. Age, breast weight, diagnosis, tumor size, hormone receptor status, and operation time were retrospectively collected. Postoperative outcomes including postoperative complications and final margin status of resected were analyzed. The median total operation time and console time were 351 min (267–480 min) and 51 min (18–143 min), respectively. The learning curve presented as a cumulative sum graph showed that the console time decreased and then stabilized at the eighth case. There was no open conversion or major postoperative complication. One patient had self-resolved partial nipple ischemia, and two patients experienced partial skin ischemia. We deemed that RANSM with IBR is safe and feasible for early breast cancer, benign disease of the breast, and BRCA 1/2 mutation carriers. RANSM is an advanced surgical method with a short learning curve.

Cross Oncoplastic Breast Surgery Technique; A Good Choice for Tumors Located Far From Nipple Areola Complex

Background: Although various Oncoplastic Breast Surgery (OBS) techniques have been introduced for varied sizes of the breast and locations of tumors , surgeons are still faced with serious challenges for tumors which have developed in special anatomic part of the breast. A good instance of these challenges is the tumors located far from Nipple Areola Complex (NAC) especially in the upper inner quadrant. We aimed to assess the application of newly introduced OBS technique (Cross Technique) in these situations. Methods: The data of 95 patients who suffered from breast cancer and operated with Cross method were assessed in this prospective survey. Data was gathered regarding demographic variables, the size, location, and pathologic characteristics of tumors, patients' BMI and breast circumference and cup size. The patients were recruited to the study according to inclusion and exclusion criteria and the study protocol which was approved by the research deputy of department of surgery, Tehran University of Medical Sciences. Data was presented in a descriptive method.Results: Nighty-five patients underwent oncoplastic breast surgery using the Cross method from November 2015 to May 2018. Patients had a mean age of 48.2 ranging from 25 to 70 years. The patients had a wide range of breast circumference and cup size (70 to 95 for the breast circumference and A to E for the cup size). Clear surgical margin was obtained in 93 cases according to the permanent pathology reports. The complications were seen in 5 patients all managed conservatively (2 slight hematoma and three ischemic skin flaps). The most common histologic type was insitu and invasive ductal carcinoma (DCIS-IDC). Mean tumor size was 22.7 mm with standard deviation of 9.2mm, most of which were positive for estrogen receptor (ER)/progesterone receptor (PR). As the surgery of axilla, six lymph nodes were excised on average and 22 patients had axillary lymph node involvement.Conclusion: The Cross method is not only a reliable choice for tumors located in the UIQ, but it can also be applied safely for tumors in UOQ and upper central part of the breast, although the best application for the technique is the tumors located far from nipple areola complex.

Protective effects of icariin on dorsal random skin flap survival: An experimental study

This study was performed to examine the protective effects of icariin (ICA) on ischemic random skin flaps. A rat random-pattern skin flap model was established, and animals in the low-dose and high-dose experimental groups were administered ICA intraperitoneally at doses of 40 and 80 mg/kg, respectively, once daily for 7 days after the initial surgery. Control rats received vehicle according to the same schedule. Survival rates were observed and recorded using transparent graph paper, and flaps were obtained and stained with hematoxylin and eosin (H&E). The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the flap tissue were assessed. The blood flow volume was determined by the laser Doppler method, and tissue expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-1β, and phosphodiesterase 5 (PDE5) were scored immunohistochemically. The levels of proinflammatory cytokines, including tumor necrosis factor-α and IL-6, were determined by enzyme-linked immunosorbent assay. The main flap survival area was significantly larger in rats treated with ICA than in vehicle-treated controls. H&E staining showed an inhibitory effect of ICA on inflammation, especially at the high dose. In addition, ICA treatment was associated with decreases in the tissue MDA level, proinflammatory cytokine production, and the level of PDE5, but increases in SOD activity, blood flow volume, and the level of VEGF expression. The findings of the present study suggest that ICA is a potential therapeutic agent for random-pattern skin flap necrosis in the clinical setting.

A study of cutaneous manifestations in diabetes mellitus patients in tertiary care centre

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Diabetes is the most common metabolic disorder with increased prevalence in developing countries like India. It affects almost all organs among which skin is affected by the acute metabolic derangments as well as by chronic degenerative complications. The aims were to study the pattern of cutaneous lesions in patients with diabetes mellitus and to determine the incidence of skin manifestations specific to and associated with diabetics.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Hundred cases of diabetes mellitus with cutaneous manifestations attending skin outpatient department and other patients admitted in medical wards were included in the study.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The common skin disorders were cutaneous manifestations (67%), dermatosis more commonly associated with diabetes (36%), neuropathic and ischemic diabetic skin disease (11%).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Most common cutaneous manifestation was cutaneous infections followed by dermatosis more commonly associated with diabetes. Among cutaneous infections fungal infections were more common followed by bacterial infections. Cutaneous infections were more common in patients with poor glycaemic control and the association was found to be statistically significant.&lt;/p&gt;

Relative Tissue Oxygenation and Temperature Changes for Detecting Early Upper Extremity Skin Ischemia.

The authors' purpose was to determine whether there are reliable noninvasive methods of assessing upper extremity ischemia regardless of skin pigmentation. The authors conducted a study of healthy subjects classified based on skin pigmentation using the Fitzpatrick scale, the von Luschan color scale, and self-described race (two Hispanics, three Caucasians, and four African Americans). A surface temperature probe and a near-infrared spectroscopy monitor were placed on the posterior interosseous artery skin territory. Temporary upper limb ischemia was induced by tourniquet insufflation. Readings from both devices were taken at baseline and every 15 seconds for a total of 10 minutes of ischemia. During tourniquet insufflation, the authors found a reliable decrease in tissue oxygenation measured by near-infrared spectroscopy in all subjects and no significant change in temperature readings for any subjects. There was an average decrease of 19 percent in tissue oxygenation using near-infrared spectroscopy, with measurements on average starting at 77 percent and ending at 57 percent. There was no significant difference in the change in near-infrared spectroscopy oxygenation between participants with Fitzpatrick skin types 3, 4, and 5 or when participants were grouped into Fitzpatrick skin type less than or equal to 3 versus greater than 3, or when grouped into Fitzpatrick skin type less than or equal to 4 versus greater than 4. There was also no significant difference in participants grouped into von Luschan scores less than or equal to 20 versus greater than 20. In this healthy subjects study, near-infrared spectroscopy rapidly identified ischemia in all cases, whereas skin surface temperature did not. Near-infrared spectroscopy may be a reliable way of noninvasively monitoring for ischemia regardless of skin pigmentation degree. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, IV.

BD-2 and BD-3 increase skin flap survival in a model of ischemia and Pseudomonas aeruginosa infection

The main aim of this work was to study the usefulness of human β-defensins 2 (BD-2) and 3 (BD-3), which are part of the innate immune system, in the treatment of infected ischemic skin flaps. We investigated the effect of transducing rat ischemic skin flaps with lentiviral vectors encoding human BD-2, BD-3, or both BD-2 and BD-3, to increase flap survival in the context of a P. aeruginosa infection associated with a foreign body. The secondary endpoints assessed were: bacterial counts, and biofilm formation on the surface of the foreign body. A local ischemic environment was created by producing arterialized venous flaps in the left epigastric region of rats. Flaps were intentionally infected by placing underneath them two catheters with 105 CFU of P. aeruginosa before the surgical wounds were hermetically closed. Flap biopsies were performed 3 and 7 days post-operatively, and the specimens submitted to immunohistochemical analysis for BD-2 and BD-3, as well as to bacterial quantification. Subsequently, the catheter segments were analyzed with scanning electron microscopy (SEM). Flaps transduced with BD-2 and BD-3 showed expression of these defensins and presented increased flap survival. Rats transduced with BD-3 presented a net reduction in the number of P. aeruginosa on the surface of the foreign body and lesser biofilm formation.

Mesenchymal stem cells improve survival in ischemic diabetic random skin flap via increased angiogenesis and VEGF expression.

Random skin flaps (RSFs) are cutaneous flaps. Despite the negative impact of diabetes mellitus (DM) on RSF viability, they are commonly used in diabetic patients. In this study, we have assessed bone marrow mesenchymal stem cell (BMMSC) treatment on RSF survival, tensiometrical parameters, angiogenesis, and mast cells (MCs) count in an ischemic RSF model in rats with type 1 DM (T1DM). We induced T1DM in 30 Wistar adult male rats. The animals were assigned to three groups of 10 rats per group as follows: group 1 (control); group 2 (placebo), and group 3 (BMMSCs). A 30 × 80 mm RSF was created in each rat. On day 7, we measured the viable portion of each RSF. A sample was taken for histological and immunohistochemistry studies, fibroblasts, MCs, angiogenesis, collagen bundle density, and the presence of vascular endothelial growth factor (VEGF)+ cells. An additional sample was taken to evaluate the flap's incision strength. Treatment with BMMSCs (17.8 ± 0.37) significantly increased RSF survival compared with the control (13.3 ± 0.35) and placebo (16.1 ± 0.27) groups (one-way analysis of variance, P = .000; least significant difference, P = .000, P = .002). There was a significant improvement in angiogenesis, as confirmed by stereologic examination. Assessment of VEGF+ cells showed prominent neovascularization in BMMSC-treated RSFs compared with the control and placebo groups. Subdermal injection of BMMSC significantly increased ischemic RSF survival as a result of stimulated neovascularization in T1DM rats. Treatment of diabetic RSF with BMMSCs showed no beneficial effects in the fibroblast number and biomechanical parameters for the repair of ischemic wounds in the rat model. Treatment with BMMSCs significantly increased collagen bundle density.

Dietary nitrate protects skin flap against ischemia injury in rats via enhancing blood perfusion

Insufficient blood supply is associated with high levels of necrosis in reconstructive surgery. Restoring blood flow to undersupplied ischemic tissue is the most important impact factor determining skin flap viability. Dietary nitrate, a significant source of nitric oxide, has multiple physiological functions, including regulator of blood flow, angiogenesis, and vasodilatation. However, the effects of dietary nitrate on ischemic skin flap remain unknown. The present study evaluated whether dietary nitrate supplementation altered blood flow of ischemic skin flap in rats. Our results showed that nitrate treatment significantly enhanced ischemic tissue survival. Mechanistically, nitrate therapy significantly increased serum nitrate and nitrite levels, blood perfusion, and angiogenesis. In addition, the circulating levels of Inflammatory mediators were decreased by nitrate supplementation. In conclusion, we demonstrated that dietary nitrate supplementation protected ischemic skin flap by enhancing ischemia-induced revascularization.

Treatment of skin soft tissue embolism after hyaluronic acid injection for injection rhinoplasty in Asian patients.

The purpose of this manuscript is to investigate the treatment of skin soft tissue embolization or vascular occlusion after the injection of hyaluronic acid (HA) for Injection Rhinoplasty (IR) in Asians with a special interest in the time occurrence of the occlusion. A total of 35 cases were evaluated after receiving HA injections for IR who presented with a vascular occlusive event. They were divided into three stages based on the time to embolization. Immediate, ≤5hours; early, ≤3days; and late, >3days. There were two cases of immediate, 28 deemed early, and five late. Methods to prevent tissue necrosis are reviewed in the manuscript based on these stages. Skin color gradually recovered to normal after 11 treatments in 11 patients with mild embolization. No ischemic aggravation or skin necrosis was observed in 19 patients with moderate embolization; red scarring was seen in two and hypertrophic scar with uneven skin color in one patient. The five patients in the severe category had longer healing, more red scars, and more hypertrophic scarring. The treatment of skin soft tissue embolization or vascular occlusion after HA IR in Asians can be effected by identifying the stage and degree of embolization and treating appropriately with the outlines presented in this manuscript.

Histopathologic Review of Calcemic Uremic Arteriolopathy: A Case Series

Calcemic uremic arteriolopathy or calciphylaxis is an uncommon disorder presenting clinically as skin ischemia and necrosis, and histologically as vascular calcification and thrombosis of dermal and subdermal vasculature. This study described two Filipino females with end-stage renal disease on chronic dialysis with non-healing ulcers on the lower extremities as a result of calcification in the vessels of the dermis and subcutaneous fat with associated fat necrosis. Current understanding of its various histologic features was reviewed for proper diagnosis.

Perioperative Treatment with a Prolyl Hydroxylase Inhibitor Reduces Necrosis in a Rat Ischemic Skin Flap Model.

The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.