Unilateral Palatal Hypoplasia: A Case Report With a Long-Term Follow-Up.

Isolated unilateral palatal hypoplasia is an extremely rare congenital disorder that usually causes velopharyngeal incompetence. We herein report a case with isolated unilateral palatal hypoplasia that was treated and followed up over nine years. No hypernasality or articulation errors were observed through the postoperative period. Here the intraoperative and postoperative findings are described.

Long-Term Follow-up With Multispecialty Management of a Giant Lymphangioma of an Infant Tongue Contributed to Reduced Complications of the Disease: A Case Report of a 21-Year Follow-up.

Background. Lymphangiomas are benign tumors of abnormal lymphatic tissue. Approximately 6% of all lymphangiomas occur on the tongue. A lymphangioma of the tongue may present as a localized or a diffused growth, which may enlarge to cause macroglossia, impaired speech, and difficulty in mastication. This article reports a 21-year follow-up of a male infant who presented with a giant tongue lymphangioma. This long-term follow-up with multidisciplinary management including partial glossectomy, sclerotherapy, and orthodontic treatment to diminish complications of the disease in adulthood.

Hemopexin as a Potential Binding Partner of Arginine-Rich Cell-Penetrating Peptides in Serum.

Serum proteins affect the in vivo fate and cellular uptake of arginine-rich cell-penetrating peptides (CPPs) and drugs delivered by CPPs. Although the binding of CPPs to serum proteins may possibly reduce their cellular uptake to some extent, it may also prolong their circulation half-life in vivo. We aimed to identify novel binding proteins of arginine-rich CPPs in serum to better understand their in vivo fate and develop more sophisticated drug delivery systems using CPPs. Isothermal titration calorimetry analysis suggests that albumin, the most abundant protein in serum, binds to d-forms of oligoarginine; however, the dissociation constants are several tens of a micromolar. Candidate proteins with the potential of binding to arginine-rich CPPs in serum were then explored using nondenaturing polyacrylamide gel electrophoresis followed by mass spectrometry analysis. Studies using fluorescence correlation spectroscopy determined hemopexin as a potential binding partner of d-forms of arginine-rich CPPs, including d-octaarginine (r 8) and the d-form of the peptide, corresponding to HIV-1 Rev (34-50), with dissociation constants of submicromolar to micromolar range. Using flow cytometry and a split-luciferase-based system, the promotion effect of hemopexin on the total cellular uptake and cytosolic localization of cargos conjugated with these CPPs was confirmed. Therefore, this study elucidated hemopexin as a potential binding partner of d-arginine-rich CPPs that may affect their in vivo fate and cellular uptake.

The anatomic classification of the anophthalmic eye socket (Types 0-V): A high-level taxonomy classification system.

Eyelid and orbital deformities caused by various defects, such as tumor resection and trauma, whether congenital or acquired, are extremely complex and atypical. Several classifications systems for these anophthalmic conditions have been developed, but none have proven suitable for determining the ideal reconstructive surgical strategy. We therefore designed a novel system known as the Anatomic Classification of the Anophthalmic Eye Socket (Types 0-V) for optimum reconstruction of anophthalmic socket deformities focusing on eyelid and orbital defects. Type 0 is an eyelid defect type, in which only the eyelid is defective; Type I is a phthisis bulbi type, in which the anatomical eyeball is preserved, but the visual function is lost; Type II is a substitution type involving filling with implant packing after evisceration or enucleation; Type III is an enucleation type involving enucleation of the ophthalmus; Type IV is an exenteration (incomplete) type involving exenteration while saving the eyelids; and Type V is an exenteration (complete) type involving exenteration including eyelid defects. Using this classification system, it will be possible to standardize reconstructive procedures of the anophthalmic socket.

Auricular Cartilage Composite Graft for Glans Reconstruction After Squamous Cell Carcinoma of the Penis.

Background. Surgical procedures for squamous cell carcinoma of the penis generally involve primary closure, partial glansectomy, skin graft, and penile amputation. Partial penile resection can result in not only unsightly deformation of the penis but also functional disorders of the urinary line as well as psychological effects due to subjective perceptions of a loss of power and masculinity. With the use of an organ-preserving procedure for functional reconstruction without compromising oncological control, this report describes a new procedure for performing functional penile reconstruction with an auricular cartilage composite graft.

Functional Reconstruction for Severe Heat Press Injury of the Proper Digits Using Immediate Preserved Subdermal Vascular Network Skin Graft: A Case Report.

The patient was a 57-year-old woman who suffered third-degree burns to the dorsal side of her left fingers (non-dominant hand) when it was caught in a press machine heated to 200°C while she was cleaning clothes. At 20 hours after the injury, the necrotic tissue was excised and covered with a preserved subdermal vascular network (PSVN) skin graft, which allowed the patient to regain a very good hand function. Even for severe heat press injuries of the hand, the combination of immediate surgical intervention, a thick skin graft with PSVN, and early rehabilitation from the first postoperative week leads to good functional and cosmetic reconstruction outcomes.

Reconstruction of extra-large severe punching hole injury in the palm: A case report.

A 48-year-old man sustained a severe punching hole injury of 8 cm in diameter on the palm of his left hand using a punching instrument (for making the bottom of drink cans), and his middle and ring fingers were almost amputated. A flow-through type immediate ALT (anterolateral thigh) flap was used to bypass the distal blood flow and a titanium plate for mandibular reconstruction and plantar glabrous skin were used to preserve the floating amputated fingers. As there has been no report of reconstruction of a punching hole in the palmar region that exceeds 8 cm in diameter, this report is novel and educational.

Giant sebaceous nevus occupying half of the head associated with sebaceous carcinoma, apocrine adenocarcinoma, and basal cell carcinoma: A case report.

We herein report a 57-year-old man afflicted with multiple malignant tumors arising from a giant sebaceous nevus on his left parieto-temporal scalp and neck. The upper eyelid was resected in all layers, and the auricle was resected as well, leaving part of the external auricular cartilage; the parotid gland area was also resected over the parotid fascia. The lost part of the left eyebrow was reconstructed using an anterior forehead skin flap, and the residual defect was covered with skin graft and expanded scalp flap. This is probably the first case report of giant sebaceous nevus associated with three malignancies: sebaceous carcinoma, apocrine adenocarcinoma, and basal cell carcinoma.

Protection of rat artery grafts from tissue damage by voltage-applied supercooling.

Supercooling preservation below 0 °C allows the storage of the transplantable sources in an unfrozen state. This can improve the safety and efficacy of storage by improving the inhibition of metabolism and organ preservation in comparison with conventional preservation at 4 °C. We have developed a supercooling technique using a voltage-applied apparatus without perfusion. We examined the preservation effects of our supercooling preservation technique in a rat model of artery transplantation. Our technique produces a supercooled state at - 2 °C with application of 1000 V. The viability of tissue cells from rat arteries was found to be higher with storage using the proposed method than that under ordinary conditions. Damage to the vascular endothelium of the femoral artery preserved by voltage-applied supercooling at - 2 °C was reduced compared to storage under ordinary conditions. Artery graft revival was successfully achieved with graft patency after supercooling preservation, and 1 week outcomes for post-transplanted grafts, including thrombosis, were better with supercooling preservation than with conventional 4 °C preservation. Supercooling artery preservation at - 2 °C with 1000 V promises to greatly prolong preservation time and improve post-transplant outcomes.

A novel technique for forehead and eyebrow reconstruction using a temporal hairline flap combined with a free forearm flap: a report of two cases.

We herein report a novel technique for managing large forehead skin defects that include the eyebrows and upper eyelid. Case 1 was of a 55-year-old woman with an eccrine carcinoma (T2N0M0) at the right forehead, resulting in a skin defect 15 cm in diameter. Case 2 was of an 81-year-old man with a malignant peripheral nerve sheath tumor (T1a N0M0) at the left forehead, resulting in a skin defect 18 cm in diameter. A pedicled temporal hairline flap and free forearm flap were combined and placed on the defect, and good eyebrows and forehead morphology was ultimately achieved.

Rare cases requiring emergency procedures while harvesting a free forearm flap: report of two cases.

The free forearm flap is considered safe to harvest and is still extremely useful for reconstruction after head and neck tumor resection. We experienced two uncommon cases, in which an emergency procedure was required during reconstructive surgery after resection of head and neck cancer. Case 1 suffered persistent hand blood flow insufficiency long after the flap was placed in the oral cavity. Case 2 had an anomalous cutaneous vein of the forearm that was a drainage vein of the flap. For risk management during free flap surgery, preparing multiple venous transplant options in advance is fundamental.

Urethral functional reconstruction using a pedicled thigh flap for urethral cutaneous fistula after vulvar necrotizing fasciitis.

The penile and scrotal skin are often resected after vulvar necrotizing fasciitis, so functional and aesthetic vulvar reconstruction is extremely challenging. With widespread and deepened infections, urethral fistulas can develop, forcing penis and scrotal amputations. In cases complicated with a urethral fistula, the wound cannot be treated by simple skin graft surgery, and complicated flap surgery is required. We verified that urethral functional reconstruction using a pedicled thigh flap is a useful technique for managing urethral cutaneous fistulas that develop after necrotizing fasciitis.

Cultured epithelial autografts for the treatment of large-to-giant congenital melanocytic nevus in 31 patients.

INTRODUCTION: Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus, and its full-thickness removal is usually difficult due to the lack of skin available for reconstruction. Curettage is an alternative approach in cases of GCMN to remove the superficial dermis above the cleavage plane with a curette in the neonatal period, and its major complications include repigmentation, retarded epithelization, and hypertrophic scar formation. In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for the treatment of congenital melanocytic nevus (CMN) that is difficult to treat with conventional methods in 2016. We have used CEA for wounds after curettage in the neonatal period or following ablation after the neonatal period in combination with laser therapies to reduce the above-mentioned complications. METHODS: In this study, we summarized all consecutive CMN patients treated using CEA from December 2016 to April 2019 and evaluated the duration required for epithelialization, incidence of hypertrophic scar, and color change in the target nevus by comparing the L∗ values one year later between the Curettage group, the non-Curettage group with initial treatment or the subsequent group. RESULTS: No significant differences were seen in the epithelization period or incidence of hypertrophic scars among the groups, but the color of the target nevus was improved significantly in the Curettage group (p < 0.01) and non-Curettage group with initial treatment (p < 0.01). CONCLUSIONS: In conclusion, CEA seems to accelerate epithelization after curettage or ablation of CMN, and this treatment could improve the color of CMN when applied initially.

The use of gauze-based negative-pressure wound therapy with Y-connector for dressing full-circumference skin grafts on both lower limbs.

Free skin grafts have long been used as an essential surgical procedure to treat skin defects due to burns, trauma or illness, requiring skin transfers from sufficient, non-marked areas. Usually, free skin grafts are covered by simple pressure dressings or tie-over dressings. However, under conditions of wide, concave or irregular wounds, graft removal has been problematic due to instability. We report a case in which gauze-based negative-pressure wound therapy using a Y-connector was indicated for the opportunity to cover both limbs with free skin grafts all around, providing successful wound care.

A Novel Treatment for Giant Congenital Melanocytic Nevi Combining Inactivated Autologous Nevus Tissue by High Hydrostatic Pressure and a Cultured Epidermal Autograft: First-in-Human, Open, Prospective Clinical Trial.

BACKGROUND: Giant congenital melanocytic nevi are large skin lesions associated with a risk of malignant transformation. The authors developed a novel treatment to reconstruct full-thickness skin defects by combining an inactivated nevus as the autologous dermis and a cultured epidermal autograft. The first-in-human trial of this treatment was performed. METHODS: Patients with melanocytic nevi that were not expected to be closed by primary closure were recruited. The full-thickness nevus of the target was removed and inactivated by high hydrostatic pressurization at 200 MPa for 10 minutes. The inactivated nevus was sutured to the original site, and a cultured epidermal autograft was grafted onto it 4 weeks later. Patients were followed for up to 52 weeks. RESULTS: Ten patients underwent reimplantation of the pressurized nevus, and one patient dropped out. The recurrence of nevus at 52 weeks was not detected by pathological diagnosis in any patients. The L* value at 52 weeks was significantly higher than that of the target nevus. One patient received skin grafting due to contracture of the reconstructed skin. The epithelized area of the reconstructed skin, as the percentage of the original target nevus, was 55.5 ± 19.4 percent at 12 weeks and 85.0 ± 32.4 percent at 52 weeks. CONCLUSIONS: The inactivated nevus caused inflammation and contracture for several months. However, no recurrence was observed, and combination therapy using an inactivated nevus with a cultured epidermal autograft may therefore be a novel treatment of giant congenital melanocytic nevi. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Reconstruction of whistling deformity using V-Y advancement flap after primary cleft lip repair.

Whistling deformity often occurs after cleft lip primary repair, marked by deficiency of vermilion tubercle. The purpose of the surgery includes improving the appearance and function of the lip. Adequate amount of vermillion tubercle is necessary to fully cover the front teeth, produce lip seal while speaking consonant sound and balance the projection of face. Many techniques are known to repair whistling deformity from fat injection to Abbe flap. In our department, we use V-Y advancement flap. At certain cases, we repeat the procedure to maximize the result. This simple and less complication technique shows stable outcome during follow up. We recommend this technique because of the non-visible scar after surgery, applicable for unilateral and bilateral cleft lip case at various age, and possible to be done under general or local anesthesia.

GALA-Modified Lipid Nanoparticles for the Targeted Delivery of Plasmid DNA to the Lungs.

This study describes the development of lipid nanoparticles (LNPs) for the efficient and selective delivery of plasmid DNA (pDNA) to the lungs. The GALA peptide was used as a ligand to target the lung endothelium and as an endosomal escape device. Transfection activity in the lungs was significantly improved when pDNA was encapsulated in double-coated LNPs. The inner coat was composed of dioleoylphsophoethanolamine and a stearylated octaarginine (STR-R8) peptide, while the outer coat was largely a cationic lipid, di-octadecenyl-trimethylammonium propane, mixed with YSK05, a pH-sensitive lipid, and cholesterol. Optimized amounts of YSK05 and GALA were used to achieve an efficient and lung-selective system. The optimized system produced a high gene expression level in the lungs (>107 RLU/mg protein) with high lung/liver and lung/spleen ratios. GALA/R8 modification and the double-coating design were indispensable for efficient gene expression in the lungs. Despite the fact that NPs prepared with 1-step or 2-step coating have the same lipid amount and composition and the same pDNA dose, the transfection activity was dramatically higher in the lungs in the case of 2-step coating. Surprisingly, 1-step or 2-step coatings had no effect on the amount of nanoparticles that were delivered to the lungs, suggesting that the double-coating strategy substantially improved the efficiency of gene expression at the intracellular level.

Ex vivo Induction of Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure.

Among promising solutions for tissue repair and wound healing, mesenchymal stem (or stromal) cells (MSCs) have been a focus of attention and have become the most clinically studied experimental cell therapy. Recent studies reported the importance of apoptosis in MSC-mediated immunomodulation, in which apoptotic MSCs (apoMSCs) were shown to be superior to living MSCs. Nowadays, high hydrostatic pressure (HHP), a physical technique that uses only fluid pressure, has been developed and applied in various bioscience fields, including biotechnology, biomaterials, and regenerative medicine, as its safe and simply operation. In the current study, we investigated the impact of HHP treatment on human bone marrow-MSC survival and proliferation. Based on the detection of executioner caspase activation, phosphatidylserine exposure, DNA fragmentation (TUNEL) and irrefutable ultrastructural morphological changes on transmission electron microscopy (TEM), our data revealed that HHP treatment induced complete apoptosis in MSCs. Notably, this technique might provide manipulated products for use in cell-based therapies as manufacturing capability expands. We hope that our findings will contribute to the improvement of MSCs or EVs in translational research development. Graphical Abstract.

Full circumference lower extremity degloving injury treated with hydrosurgical debridement and negative-pressure wound therapy with gauze wound filler for fixation of avulsed flap skin grafts.

Degloving, a skin and subcutis avulsion, is a severe traumatic injury sometimes caused by rolling wheels or machines. Although avulsed flaps are often readapted to its original site, most of these tissues become necrotic. Due to the extensive skin and soft tissue deficiency caused by necrosis, treatment becomes difficult. Skin grafts harvested from avulsed flaps may be used to treat degloving injuries, while negative pressure wound therapy (NPWT) is used to secure the grafts. Commonly used porous polyurethane foam wound fillers are difficult to set in circumferential extremity degloving injuries; gauze-based wound fillers are easier to use and cause less pain during dressing changes. We present a case of an extensive, full-circumference left lower-extremity degloving injury, treated using NPWT with gauze-based wound fillers for fixation of skin grafts harvested from avulsed flaps after hydrosurgical debridement. For complex wound geometries, gauze-based wound fillers can be easily applied for skin graft immobilization.

Hydrostatic pressure can induce apoptosis of the skin.

We previously showed that high hydrostatic pressure (HHP) treatment at 200 MPa for 10 min induced complete cell death in skin and skin tumors via necrosis. We used this technique to treat a giant congenital melanocytic nevus and reused the inactivated nevus tissue as a dermis autograft. However, skin inactivated by HHP promoted inflammation in a preclinical study using a porcine model. Therefore, in the present study, we explored the pressurization conditions that induce apoptosis of the skin, as apoptotic cells are not believed to promote inflammation, so the engraftment of inactivated skin should be improved. Using a human dermal fibroblast cell line in suspension culture, we found that HHP at 50 MPa for ≥ 36 h completely induced fibroblast cell death via apoptosis based on the morphological changes in transmission electron microscopy, reactive oxygen species elevation, caspase activation and phosphatidylserine membrane translocation. Furthermore, immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick-end labeling and cleaved caspase-3 showed most cells in the skin inactivated by pressurization to be apoptotic. Consequently, in vivo grafting of apoptosis-induced inactivated skin resulted in successful engraftment and greater dermal cellular density and macrophage infiltration than our existing method. Our finding supports an alternative approach to hydrostatic pressure application.