PRP&F/P MPs improved survival of dorsal paired pedicle skin flaps in rats.

BACKGROUND: Skin flap necrosis is a problem encountered postoperatively. The purpose of this study was to evaluate the effects of platelet-rich plasma containing fragmin/protamine microparticles (PRP&F/P MPs) on viability in a rat dorsal paired pedicle skin (DPPS) flap. MATERIALS AND METHODS: Two symmetrical adjoining rectangular flaps (8 × 2 cm each) were drawn on the rat dorsum. Two days after PRP&F/P MPs-, PRP-, F/P MPs-, and saline (control)-injections (n = 8 each), flaps were elevated as a random pattern flap without the lateral thoracic, posterior intercostal, and deep circumflex iliac vessels. The flaps were immediately sutured back and the flap survival area was measured 7 d after flap elevation. RESULTS: The flap survival rate in PRP&F/P MPs-injected groups (73.1% ± 4.2%) was significantly higher than those in PRP (64.9% ± 4.0%), F/P MPs (59.4 ± 4.5%), and control (61.2% ± 4.2%) groups. Histologic observation of the flaps showed survived thick granulation tissue and neovascularization in PRP&F/P MPs-injected groups. CONCLUSIONS: When PRP&F/P MPs are administered 2 d before the flap elevation, the improved flap survivals are observed. The pre-injection of PRP&F/P MPs may thus represent a promising treatment to prevent skin flap necrosis in reconstructive surgery.

Enhanced effect of platelet-rich plasma containing a new carrier on hair growth.

BACKGROUND: Treatments for alopecia are in high demand, but not all are safe and reliable. Dalteparin and protamine microparticles (D/P MPs) can effectively carry growth factors (GFs) in platelet-rich plasma (PRP). OBJECTIVE: To identify the effects of PRP-containing D/P MPs (PRP&D/P MPs) on hair growth. METHODS & MATERIALS: Participants were 26 volunteers with thin hair who received five local treatments of 3 mL of PRP&D/P MPs (13 participants) or PRP and saline (control, 13 participants) at 2- to 3-week intervals and were evaluated for 12 weeks. Injected areas comprised frontal or parietal sites with lanugo-like hair. Experimental and control areas were photographed. Consenting participants underwent biopsies for histologic examination. RESULTS: D/P MPs bind to various GFs contained in PRP. Significant differences were seen in hair cross-section but not in hair numbers in PRP and PRP&D/P MP injections. The addition of D/P MPs to PRP resulted in significant stimulation in hair cross-section. Microscopic findings showed thickened epithelium, proliferation of collagen fibers and fibroblasts, and increased vessels around follicles. CONCLUSION: PRP&D/P MPs and PRP facilitated hair growth but D/P MPs provided additional hair growth. The authors have indicated no significant interest with commercial supporters.

Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with hydrosheets composed of chitin/chitosan, fucoidan, and alginate as wound dressings.

To create a moist environment for rapid wound healing, a hydrosheet composed of alginate, chitin/chitosan, and fucoidan (ACF-HS) has been developed as a functional wound dressing. The aim of this study was to evaluate the accelerating effect of ACF-HS on wound healing for rat mitomycin C-treated healing-impaired wounds. Full-thickness skin defects were made on the back of rats and mitomycin C was applied onto the wound for 10 minutes to prepare a healing-impaired wound. After thoroughly washing out the mitomycin C, ACF-HS was applied to the healing-impaired wounds. The rats were later euthanized and histological sections of the wounds were prepared. The histological examinations showed significantly advanced granulation tissue and capillary formations in the healing-impaired wounds treated with ACF-HS on days 7 and 14, in comparison with that in alginate fiber (Kaltostat), hydrogel wound dressing (DuoACTIVE), and nontreatment (negative control). Furthermore, in cell culture studies, ACF-HS-absorbed serum and fibroblast growth factor-2 was found to be proliferative for fibroblasts and endothelial cells, respectively, and ACF-HS-absorbed serum was found to be chemoattractive for fibroblasts. However, our results may not be strictly comparable with general healing-impaired wound models in humans because of the cell damage by mitomycin C. In addition, more biocompatibility studies of fucoidan are essential due to the possibility of renal toxicity.

Platelet-rich plasma (PRP) promotes survival of fat-grafts in rats.

This study evaluated the effects of platelet-rich plasma (PRP) on resorption and adipocyte survival in autologous fat-graft of rats prepared with isogenous PRP. Fat grafts prepared without PRP (control group) became united to the tissue adjacent to the implantation site and were significantly resorbed from 30 days. On the other hand, fat grafts prepared with PRP (PRP group) demonstrated little resorption from 30 to 120 days and appeared pink, had a soft, supple feel, and were easily compressible. Histologic sections of grafts in the control and PRP groups at 10 days exhibited similar consolidation of the grafted tissue, which contained morphologically normal adipocytes with different degrees of granulation and capillary formation. From 20 days normal adipocytes were obviously decreased in the control group, while the PRP group demonstrated increased granulation tissue and capillary formation and good maintenance of normal adipocytes for at least 120 days.

Management of Infected Calcific Myonecrosis: A Report of 2 Cases.

Calcific myonecrosis (CM) is a rare condition in which a large calcified mass develops after trauma. Generally, CM occurs in a lower extremity, and there have been no reports of its occurrence in the upper arm. We report 2 cases of infected CM, including a rare case of CM occurrence in the arm and a typical case in the leg. Case 1: An 84-year-old woman presented with a draining sinus and a large calcified mass in the arm and axillary region. The mass involved the neurovascular bundle; thus, complete resection was impossible. We performed surgical debridement and postoperative negative-pressure wound therapy with instillation and dwell. Case 2: A 43-year-old man presented with a large calcified mass in the right leg and 2 draining sinuses. After surgical debridement, negative-pressure wound therapy was initiated. However, the wound became infected, and we performed additional debridement, followed by a split thickness skin grafting. The infection was controlled in both patients, although complete resection was not feasible. Complete resection is generally considered the optimum treatment for infected CM, but it is difficult to achieve in some patients. Negative-pressure wound therapy with instillation and dwell appears as a good option for postoperative management if complete resection of infected CM cannot be achieved.

Intramedullary fixation with bioabsorbable and osteoconductive hydroxyapatite/poly-L-lactide threaded pin in digital replantation.

In digital replantation, Kirschner wire (K-wire) fixation has commonly been used for osteosynthesis. On the other hand, K-wires are often obtrusive because of protrusion from the replanted digit. We describe a case series treated using hydroxyapatite/poly-L-lactide (HPLLA) threaded pins, which are not only bioabsorbable, but also osteoconductive, for osteosynthesis in crushed amputation or comminuted fracture, including distal phalanx amputation. Using an HPLLA threaded pin, 10 digital replantations were performed between July 2016 and April 2018. The precisely cut pin is manually pushed into the fracture site as an intramedullary nail. The pin is first pushed into the distal site, and then into the proximal site, after drilling with a K-wire of the same diameter as the pin. All amputations were crush type, and levels of amputations were Tamai zone I in three cases, zone II in two and zone III in five. Eight of the 10 digits survived. The two digits that did not survive showed venous insufficiency. Bone union of the eight digits was successfully obtained after 9-19 weeks (median 12 weeks). No adverse events occurred such as distortion of the pin, infection or foreign body reaction. The HPLLA threaded pin may be an adequate device to fix fractures in digital replantation.

Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix.

Adipose tissue-derived stromal cells (ATSCs) have recently gained widespread attention as a potential alternate source to bone marrow-derived mesenchymal stem cells with a proliferative capacity and a similar ability to undergo multilineage differentiation. In this study, we evaluated the effectiveness of freshly isolated autologous ATSCs-containing atelocollagen matrix with silicon membrane (ACMS) on wound healing of diabetic (db/db) mice. Cultured ATSCs from (db/db) mice secreted significant amounts of growth factors and cytokines, which are suitable for wound repair. Two full thickness round skin defects were made on the backs of healing-impaired db/db mice. Freshly isolated autologous ATSCs-containing ACMS or ACMS alone were applied to the wounds. Twelve mice were treated and then killed at 1 or 2 weeks (n = 6 each). Histologic sections of the wounds were prepared at each time period after treatment. Histologic examination demonstrated significantly advanced granulation tissue formation, capillary formation, and epithelialization in diabetic healing-impaired wounds treated with autologous ATSCs-containing ACMS, compared with mice treated with ACMS alone. These results suggested that transplantation of autologous ATSCs-containing ACMS significantly accelerated wound healing in diabetic healing-impaired db/db mice.

A case of mediastinitis with an exposed artificial blood vessel that was associated with right ventricular wall damage during treatment.

We report a serious case of right ventricular wall damage during mediastinitis treatment, which was successfully treated with negative-pressure wound therapy with continuous instillation (NPWT-CI).

Appropriate Use of Intravenous Unfractionated Heparin after Digital Replantation: A Randomized Controlled Trial Involving Three Groups.

BACKGROUND: The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation. METHODS: This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications. RESULTS: No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7. CONCLUSION: Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Maggot debridement therapy with a direct dressing can cause compression injuries in patients with chronic limb ischemia.

While there are no reports regarding dressing-associated iatrogenic skin ulcer as an adverse event of maggot debridement therapy (MDT), MDT is clinically used on patients with critical limb ischaemia with dermal fragility. Herein we report causes and counter measures for a case of iatrogenic skin ulcer induced by MDT dressing.

Eyelid Reconstruction Using Oral Mucosa and Ear Cartilage Strips as Sandwich Grafting.

BACKGROUND: The eyelid structure can be divided into an inner layer and an outer layer. Reconstruction of a full-thickness eyelid defect is accomplished by full-thickness composite tissue transfer or combined layered reconstruction. We present a new technique for inner layer reconstruction using ear cartilage and oral mucosa. METHODS: The oral mucosa graft is harvested from the inner side of the lower lip to fit the defect size and shape. The ear cartilage graft is harvested as a rectangular strip. The harvested mucosa is sutured to the defect margin and the cartilage strip graft is interposed to the defect. Finally, the outer layer of the defect is covered with skin flaps. Consequently, the ear cartilage graft is sandwiched between the mucosa graft and the skin flap. RESULTS: We used this technique for the reconstruction of 13 full-thickness eyelid defects of various locations, sizes, and shapes. Ten cases involved the lower eyelid, 2 cases involved the lower eyelid including the medial canthus, and 1 case involved the upper eyelid. The oral mucosa graft survived in all patients. The reconstructions were successful and there were no postoperative reports of conjunctival or corneal irritation. CONCLUSIONS: The present technique using a combination of an ear cartilage strip graft and oral mucosa graft is an easy and versatile technique for reconstruction of inner layer eyelid defects. We believe that the beneficial effects of tears, which are richly oxygenated, improved survival of the grafted mucosa.

Coronary Artery Disease in Patients with Critical Limb Ischemia Undergoing Major Amputation or Not.

BACKGROUND: Due to the increase of elderly and diabetes patients, surgeons encounter patients requiring treatment of critical limb ischemia (CLI) in the presence of systemic arteriosclerotic diseases. In this study, we retrospectively investigated the prevalence of coronary artery disease (CAD) in patients with CLI who underwent major (above-the-ankle) amputation or nonmajor amputation (below-the-ankle amputation or debridement of wound). METHODS: We retrospectively investigated 129 consecutive patients surgically managed for CLI in our institution between January 2013 and December 2015. The prevalence of CAD was defined as a cardiac treatment history or significant vascular stenosis (stenosis of > 75%). The outcomes were compared between patients who underwent major amputation (n = 36) and nonmajor amputation (n = 93). Additionally, archived record of 566 patients treated nonsurgically by percutaneous transluminal angioplasty in our institution was investigated to evaluate patients with milder peripheral artery disease. RESULTS: CAD was present in 83 patients (69%), including 82% of patients who underwent major amputation and 63% of nonmajor amputation group. The prevalence of CAD was significantly higher in the major amputation group (P = 0.042). Ejection fraction was not significantly different (P > 0.05). Among the 566 CLI patients treated by only percutaneous transluminal angioplasty, 227 (40%) had CAD, which was a significantly lower prevalence than those surgically treated (P < 0.001). CONCLUSIONS: The presence of CAD is more frequent in CLI patients who require extended surgical management of the limb than in those who do not. Evaluation of CAD and careful perioperative management are important for patients with CLI patients.

Maggot debridement therapy for a patient with critical limb ischaemia and severe cardiac dysfunction: possibility of limb salvage.

Ischaemic skin ulcer occurred on the foot of a 73-year-old man who had a history of fulminant myocarditis with severe cardiac dysfunction. We attempted wound bed preparation by maggot debridement therapy and salvaged his limb. It can be one of the adjuvant treatment strategies for critical limb ischaemia.

The Effect of Smoking on Necrosis Rate in Digital Replantation and Revascularization with Prostaglandin E1 Therapy: A Retrospective Study.

BACKGROUND: Most microsurgeons believe that smoking and severity of injury adversely affect the outcome of digital replantation surgery. As countermeasures, several pharmacologic agents have been used for the perioperative period. The purpose of this retrospective study was to examine whether the rate of necrosis is appreciably different across smokers versus nonsmokers with prostaglandin E1 therapy. METHODS: The authors' study subjects included 144 patients (184 digits) who underwent replantation or revascularization between August of 2013 and August of 2015.The primary outcome was the incidence of total necrosis after replantation surgery, and the secondary outcomes were the rate of overall necrosis, proportion of total necrosis to overall necrosis, and total success. Intravenous administration of prostaglandin E1 was performed at the rate of 120 µg/day for 7 days after surgery in all patients. These outcomes of each injury type were compared between smoking and nonsmoking groups. RESULTS: Among the 184 injured digits, the incidence of total necrosis in smokers (23 percent) was higher than that in nonsmokers (17 percent), although no significant difference was shown (p = 0.36). The adjusted odds ratio was 1.17 (95 percent CI, 0.51 to 2.69). Similarly, there was no significant difference in the secondary outcomes between the two groups. CONCLUSION: The authors' retrospective study found no significant difference in the formation or extent of necrosis after replantation or revascularization between smoking and nonsmoking groups when all patients were treated with prostaglandin E1. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Magnetic Resonance Imaging Visualizes Median Nerve Entrapment due to Radius Fracture and Allows Immediate Surgical Release.

Median nerve entrapment with forearm fracture is rare, and surgical exploration in the early stage is rarely performed. We report the case of a 19-year-old man presenting with severe pain and numbness of the thumb, index, and middle fingers and half of the ring finger along with weakness of abduction and opposition of the thumb after fracture of the radial shaft. These symptoms remained unimproved despite precise closed reduction and cast immobilization. The radius fracture was barely displaced, but complaints were increasing, particularly when the wrist and/or fingers were stretched. This suggested direct involvement of the median nerve at the fracture site, so magnetic resonance imaging (MRI) of the forearm was performed to identify any entrapment. Short tau inversion recovery MRI visualized significant deviation and entrapment of the median nerve at the fracture site. Surgical release of the entrapment was performed immediately, and complaints resolved shortly thereafter. A positive Tinel sign from the palm to the fingertips and recovery of abduction and opposition of the thumb were seen at 6 months postoperatively. This report highlights the utility of MRI for detecting median nerve entrapment at a fracture site, allowing immediate surgical release.

Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with PRP-containing fragmin/protamine microparticles (PRP&F/P MPs).

PURPOSE: The purpose of this study was to evaluate the accelerating effects of platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs) for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining) showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin C-treated rats. METHOD: Full-thickness skin defects were made on the back of rats and mitomycin C was applied on the wounds to prepare a healing-impaired wound. After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone, and PRP&F/P MPs were injected around the wounds. The rats were later euthanised and histological sections of the wounds were then prepared at indicated time periods after the treatment. RESULTS AND CONCLUSION: These results indicated the numbers of large, medium, and small capillary lumens 7 days after injection of PRP&F/P MPs were significantly higher than those after injection of PRP or F/P MPs alone. Furthermore, epithelium and granulation tissue formations were significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs 3, 7 and 14 days after injection of PRP&F/P MPs.

Novel hydrocolloid-sheet as wound dressing to stimulate healing-impaired wound healing in diabetic db/db mice.

To create a moist environment for wound healing, a hydrocolloid-sheet composed of alginate, chitin/chitosan and fucoidan (ACF-HS) has been developed as a functional wound dressing. ACF-HS gradually adsorbed medium without any maceration and the medium adsorption in vitro reached constant after 18 h. ACF-HS could effectively interact with and protect a healing-impaired wound in diabetic db/db mice, providing a good moist healing environment with exudate. Furthermore, the wound dressing could have other properties like ease of application and removal, and proper adherence. The aim of this study was to evaluate an accelerating effect of ACF-HS on wound healing for healing-impaired wounds in diabetic db/db mice. Round full-thickness skin defects (12 mm in diameter) were made on the back of db/db mice to prepare healing-impaired wounds. After applying ACF-HS to the wounds, the mice were later killed and histological sections of the wound were prepared. Histological examinations showed significantly advanced granulation tissue and capillary formations in the wounds treated with ACF-HS on days 4, 9 and 14 compared with those in commercially available hydrocolloid wound dressing and non-treatment (control). Thus, ACF-HS may serve as a new wound dressing for diabetic healing-impaired wounds.

Protective effect of prostaglandin E1 on radiation-induced proliferative inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in rats.

We examined the effects of prostaglandin E1 (PGE1) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE1 had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE1 were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE1. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE1 administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE1-administered rats were significantly lower than for those in the skin of rats which did not receive PGE1. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE1 administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE1 administrated. Thus, PGE1-administration may potentially alleviate the radiation-induced skin injury.

Stimulatory Effect of Autologous Adipose Tissue-Derived Stromal Cells in an Atelocollagen Matrix on Wound Healing in Diabetic db/db Mice.

We aimed to evaluate the effectiveness of the application of an atelocollagen matrix containing autologous adipose tissue-derived stromal cells (ASCs) on wound healing in diabetic (db/db) mice. Cultured ASCs from db/db mice and from db/+ mice secreted identical amounts of growth factors, cytokines, and type I collagen. ASCs from db/db mice proliferated at the same rate as those from db/+ mice. When DiI-labeled ASCs were applied to full-thickness round skin wounds on the backs of diabetic db/db mice, histological observation at 2 weeks showed that red fluorescent-labeled tissues were formed in the epidermis, dermis, and capillaries. Twelve db/db mice were treated with either matrix alone or matrix containing ASCs and then sacrificed at 1 or 2 weeks. A histological examination demonstrated significantly advanced granulation tissue formation, capillary formation, and epithelialization in those wounds treated with atelocollagen matrix containing ASCs, compared with wounds treated with matrix alone.

New model of radiation-induced skin ulcer in rats.

Our aim was to provide a new animal model for intractable skin ulcers in irradiated rats. Twenty-four rats were irradiated with total single radiographic irradiation doses of 10, 15, 20, and 30 Gy. The skin was observed for 6 months. In the 10-Gy group, there were no visible changes to the skin. In the 15-Gy group, epilation and depigmentation were seen about 2 weeks after irradiation. In the groups over 20-Gy, minor erosion or skin ulcers appeared in most rats. The wounds healed in the 20-Gy group, but many in the 30-Gy group could not be healed. A further 36 rats were irradiated with 20 Gy, and this was followed by the creation of cutaneous full-thickness defects at different periods. The size of the wounds was measured on days 0, 3, 5, 7, 10, and 14. Delayed wound healing was found in the irradiated groups compared with the unirradiated group (p = 0.01). There were no differences in the time of ulceration, except in the Day 7 group (p = 0.03).