Dramatic Wound Closing Effect of a Single Application of an iBTA-Induced Autologous Biosheet on Severe Diabetic Foot Ulcers Involving the Heel Area.

INTRODUCTION: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism becomes ineffective due to the poor environment of the wound bed. Biosheets obtained using in-body tissue architecture (iBTA) are collagen-based membranous tissue created within the body and which autologously contain various growth factors and somatic stem cells including SSEA4-posituve cells. When applied to a wound, granulation formation can be promoted and epithelialization may even be achieved. Herein, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. CASES: Seven patients, from 46 to 93 years old, had large foot ulcers including in the heel area, which were failing to heal with standard wound treatment. METHODS: Two or four Biosheet-forming molds were embedded subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. RESULTS: In all cases, there were no problems with the mold's embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the embedding period. The Biosheets were simply applied to the wounds, and in all cases they adhered within one week, did not fall off, and became integrated with the wound surface. Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. CONCLUSIONS: Biosheets obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving the heel area.

A comparative study of natural variation in hemolymph glucose levels under different dietary sugar conditions in Drosophila melanogaster and D. simulans.

Physiological responses to environmental changes play important roles in adaptive evolution. In particular, homeostatic regulatory systems that maintain constant circulating glucose levels are crucial in animals. However, variation in circulating glucose levels and the genetic effects on phenotypic variation in natural populations remain to be clarified. Here, we investigated the hemolymph glucose levels in natural populations of Drosophila melanogaster and its sibling species, D. simulans, in Japan. We quantified hemolymph glucose concentrations in third instar larvae of 27 lines for each species, which were reared on either glucose-free or glucose-rich food. In both species, genetic variation was not a major component of phenotypic variation on either glucose-free or glucose-rich food. The hemolymph glucose concentrations were much higher in D. simulans than in D. melanogaster. Genetic variance was larger in D. simulans than in D. melanogaster. The observed differences between the two species may be associated with the much more recent colonization history of D. simulans populations in Japan and/or the tolerance to environmental stresses. Our findings suggest that natural selection acting on hemolymph glucose levels in D. melanogaster is different from that in D. simulans.

First-in-human results of an in-body tissue architecture-induced tissue-engineered vascular graft "Biotube" for application in distal bypass for chronic limb-threatening ischemia.

Small-diameter vascular substitutes remain necessary, especially in the absence of an available autologous vein. Using a completely autologous approach termed "in-body tissue architecture," a small-diameter, long, tissue-engineered vascular graft, a "Biotube," was developed. A below-the-knee distal bypass using the Biotube as a composite with expanded polytetrafluoroethylene grafts was performed to treat a patient with chronic limb-threatening ischemia without a venous graft available. The wound on the foot had completely healed 3 months after the bypass surgery, and limb salvage and walking without claudication were achieved. At the 1-year postoperative follow-up examination, duplex ultrasound scans demonstrated graft patency without thrombus or stenosis.

Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model.

OBJECTIVE: There is a need for small diameter vascular substitutes in the absence of available autologous material. A small diameter, long tissue engineered vascular graft was developed using a completely autologous approach called "in body tissue architecture technology (iBTA)". The aim of this pilot study was to evaluate "Biotubes", iBTA induced autologous collagenous tubes, for their potential use as small diameter vascular bypass conduits. METHODS: Biotubes (internal diameter 4 mm, length 50 cm, wall thickness 0.85 mm) were prepared by subcutaneous embedding of plastic moulds (Biotube Maker) in three goats for approximately two months. Allogenic Biotubes (length 10 cm [n = 2], 15 cm [n = 2], 22 cm [n = 2]) were bypassed to both carotid arteries by end to side anastomosis with their ligation between the anastomoses in another three goats. Residual Biotubes were examined for their mechanical properties. After four weeks, the harvested Biotubes were evaluated histologically. RESULTS: All Biotubes had sufficient pressure resistance, approximately 3000 mmHg. Although wall thickening occurred at two proximal anastomosis sites, all six grafts were patent without luminal thrombus formation, stenosis, or aneurysm deformation throughout the implantation period. Endothelial cells covered both anastomosis sites almost completely, with partial covering in the central portion of the grafts. Furthermore, α smooth muscle actin positive cells infiltrated the middle layer along almost the entire graft length. CONCLUSION: This preliminary study showed that small diameter, long, tissue engineered Biotubes could function properly as arterial bypass conduits in a large animal for one month without any abnormal change in vascular shape. Thus, small diameter, long Biotubes are potentially viable conduits, which are biocompatible and labour non-intensive, and therefore, suitable for clinical practice. Additionally, Biotubes can start the regeneration process in a short period of time.

Pre-implantation evaluation of a small-diameter, long vascular graft (Biotube®) for below-knee bypass surgery in goats.

There are no small-diameter, long artificial vascular grafts for below-knee bypass surgery in chronic limb-threatening ischemia. We have developed tissue-engineered vascular grafts called "Biotubes®" using a completely autologous approach called in-body tissue architecture (iBTA). This study aimed at pre-implantation evaluation of Biotube and its in vivo preparation device, Biotube Maker, for use in below-knee bypass surgery. Forty nine makers were subcutaneously embedded into 17 goats for predetermined periods (1, 2, or 3 months). All makers produced Biotubes as designed without inflammation over all periods, with the exception of a few cases with minor defects (success rate: 94%). Small hole formation occurred in only a few cases. All Biotubes obtained had an inner diameter of 4 mm and a length of 51 to 52 cm with a wall thickness of 594 ± 97 µm. All Biotubes did not kink when completely bent under an internal pressure of 100 mmHg and did not leak without any deformation under a water pressure of 200 mmHg. Their burst strength was 2409 ± 473 mmHg, and suture retention strength was 1.75 ± 0.27 N, regardless of the embedding period, whereas tensile strength increased from 7.5 ± 1.3 N at 1 month to 9.7 ± 2.0 N at 3 months with the embedding period. The amount of water leakage from the needle holes prepared in the Biotube wall was approximately 1/7th of that in expanded polytetrafluoroethylene vascular grafts. The Biotubes could be easily connected to each other without cutting or anastomosis leaks. They could be stored for at least 1 year at room temperature. This study confirmed that even Biotubes formed 1 month after embedding of Biotube Makers had properties comparable to arteries.

[A case of advanced gastric cancer with tumor embolus in the portal vein successfully treated with S-1 and CDDP therapy].

A 50-year-old man with advanced gastric cancer and a tumor embolus in the portal vein was referred to our hospital. We diagnosed the tumor as cStage III B (cT3, cN2, cH0, P0, M0) gastric cancer, and selected neoadjuvant S-1 (80 mg/m2) and CDDP (60 mg/m2) therapy for him. After 2 courses of chemotherapy, the embolus in the portal vein disappeared. After additional chemotherapy, the primary tumor and regional lymph node revealed a partial response (PR), and judging from the results from the barium meal study, upper GI endoscopic findings and CT scan, a total gastrectomy with lymph node dissection was performed.

[Investigation of epiphora following S-1 therapy].

We report the frequency of lacrimal passage disorder and the outcomes of treatment. This retrospective study was performed on 55 cases that were treated with S-1 for at least 1 month. We asked patients about ocular symptoms. An ophthalmic surgeon examined all patients and diagnosed lacrimal passage disorder in 6 of 55 patients (12. 5%). The mean dose of S- 1 was 10, 300 mg, and the average period to onset of lacrimal passage disorder was 5. 7 months. The causes of epiphora included occlusion/stenosis of lacrimal canaliculus, occlusion of lacrimal puncta and stenosis of nasolacrimal duct. Lacrimal surgery was performed in all 6 patients and epiphora improved. Lacrimal passage disorder may result from systemic treatment of patients with S-1. Symptoms of lacrimal passage disorder improved with early detection and treatment by insertion of a silicone tube.

[Type 4 advanced gastric cancer responding to histological complete response after neoadjuvant S-1 combined with CDDP therapy-report of a case].

A 75-year-old man with type 4 advanced gastric cancer was referred to our hospital. We diagnosed the tumor as cStage III B(cT4a, cN2, cM0)gastric cancer. We selected neoadjuvant S-1 combined with CDDP therapy for him. After 2 courses of chemotherapy, the extension of the gastric wall improved. After an additional 2 courses of chemotherapy, the primary tumor revealed a partial response(PR), judged from a barium meal study and upper GI endoscopic findings, and a total gastrectomy with lymph node dissection was performed. The pathological specimens showed no cancer cells in the gastric wall and lymph nodes, so the histological effect was judged as Grade 3.

Severe sepsis caused by Parvimonas micra identified using 16S ribosomal RNA gene sequencing following patient death.

An 83-year-old man visited an orthopedic hospital for his lower back pain. A compression fracture was noted in his second lumbar vertebra. He had taken pain medication for approximately five weeks, but the pain had worsened and he was unable to walk by himself. He was transferred to our hospital and diagnosed with lumbar spondylodiscitis, an iliopsoas abscess, gas gangrene of his left lower limb, and left massive pleural effusion. He was admitted to the intensive care unit. We drained the abscess and pleural effusion, provided continuous hemodiafiltration under ventilator control, and administered intravenous antibiotics. However, he died from sepsis and multiple organ failure three days following admission. Several days after his death, gram-positive cocci were identified in blood culture, pus from the abscess, and pleural exudate; although the causative organism could not be identified. Two weeks subsequent to his death, 16S ribosomal RNA gene sequencing identified Parvimonas micra in specimens taken from his body.

Successful treatment of a right internal mammary artery aneurysm with thoracoscopic surgery.

Internal mammary artery aneurysms are rarely detected, with only a few cases caused by physical trauma, connective tissue diseases, and vasculitis having been reported. We describe the case of a 52-year-old woman diagnosed with a right internal mammary artery aneurysm several months after experiencing a DeBakey Ⅲ acute aortic dissection. The artery had an indication of dissection that seemed to have caused the aneurysm. Thoracoscopic resection was performed, and the patient recovered with no major complications.

Clinical significance of a false lumen pathway through the arch in acute type A aortic dissection and its influence on cervical branch compromise.

OBJECTIVES: Upon onset of acute type A aortic dissection, the aortic true lumen generally becomes fixed around the supra-aortic branches in the greater curvature and Botallo's ligament in the lesser curvature of the aortic arch. Therefore, the pathways of the false lumen through the arch can be categorized as anterior, bilateral and posterior. We investigated the relationship between a false lumen pathway through the arch and cervical branch compromise, stratified by primary tear location. METHODS: Sixty-four consecutive patients with acute type A aortic dissection underwent emergency surgery at our institution between March 2005 and October 2013. Of these, 40 cases (63%) were DeBakey type I, 15 cases (23%) were type II and 9 cases (14%) were type III-D (retrograde type A). We conducted a retrospective review of preoperative computed tomographic angiography using three-dimensional image post-processing tools for 43 cases, excluding 15 cases with type II and 6 cases with type I for which preoperative digital image data were not available. RESULTS: Of the 43 cases, 14, 18 and 11 revealed anterior, bilateral and posterior pathways, respectively. Twenty-one cases (49%) showed a primary intimal tear in the ascending aorta (8 anterior, 12 bilateral and 1 posterior), 12 cases (28%) showed a primary intimal tear in the aortic arch (5 anterior, 3 bilateral and 4 posterior) and 10 cases (23%) showed a primary intimal tear in the descending aorta (1 anterior, 3 bilateral and 6 posterior). Twelve of the 14 anterior pathway cases (86%) had a total of 26 supra-aortic branch compromises, 13 of the 18 bilateral pathway cases (72%) had a total of 20 supra-aortic branch compromises, while only 4 of the 11 posterior pathway cases (36%) had a total of four supra-aortic branch compromises. None of the 11 posterior pathway cases had a dissection extending into all 3 supra-aortic branches. CONCLUSIONS: Posterior pathway cases generally showed primary tear locations in the arch or descending aorta, and cervical branch compromise was rare. Aortic dissections tended to extend into the cervical branches through the anterior side of the aortic arch. A false lumen pathway through the arch was strongly associated with cervical branch compromise in acute type A aortic dissections.

A new classification system for branch artery perfusion patterns in acute aortic dissection for examining the effects of central aortic repair.

OBJECTIVES: We developed a new classification system for branch perfusion patterns in acute aortic dissection and used it to retrospectively evaluate the perfusion status of whole aortic branches and to examine the effects of central aortic repair. METHODS: Thirty-four consecutive patients with acute type A aortic dissection underwent emergent surgery at our institution between August 2008 and December 2011. A retrospective review of pre- and postoperative computed tomographic angiography was performed. Branch perfusion patterns were categorized into three classes: Class I, dissection involving but not extending into the branch; Class II, dissection extending into the branch and Class III, dissection causing ostial avulsion. RESULTS: In cervical branches (total 169 branches), 70 branches (41%) presented with Class I patterns, 58 (34%) with Class II and none with Class III. In abdominal branches (total 135 branches), 76 branches (56%) presented with Class I patterns, 12 (9%) with Class II and 18 (13%) with Class III. In common iliac arteries (total 68 arteries), 14 arteries (21%) presented with Class I patterns, 24 (35%) with Class II and none with Class III. After repair, among 21 high-risk cervical branches, 14 branches (67%) showed improvement, 3 (14%) preserved distal perfusion supplied through the patent branch false lumen and 4 (19%) showed no improvement in high-risk perfusion pattern or worsened. Among 22 high-risk abdominal branches, 18 branches (82%) showed improvement, 3 (14%) preserved distal perfusion supplied through the patent branch or aortic false lumen and 1 (5%) showed no improvement in high-risk perfusion pattern. CONCLUSIONS: To overcome malperfusion syndromes associated with acute aortic dissection, recognition of diverse branch perfusion patterns through a universal classification system is imperative.