Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

Japanese clinical practice guidelines for vascular anomalies 2017.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Sclerotherapy for Venous Malformations of the Pharynx or the Tongue Base Without Tracheostomy: Treatment Protocol With Intubation and Outcomes.

Venous malformations (VMs) occurring in the tongue base or pharynx are rare, but can cause airway obstruction. Considering the potential issues or morbidity related to surgical resection in the tongue or pharynx region, sclerotherapy is often preferred. We perform sclerotherapy for such lesions without conducting tracheotomy, but keep patients intubated for a certain period. Outcomes of sclerotherapy, and benefits and cautions related with our protocol were investigated.Our subjects were 10 cases in 9 patients who underwent sclerotherapy for VMs of the tongue base (6 patients) or pharynx (3 patients) from 2008 to 2017. One patient underwent treatment sessions twice. The sclerosants used were absolute ethanol (ET) (3 cases), 5% ethanolamine oleate (EO) (4 cases), or both ET and 5%EO (3 cases).In 5 of 9 patients, postoperative MRI was performed, which revealed lesion volume reduction by 12% to 47%. The intubation period varied according to the sclerosant used: ET, 5 to 11 days; 5% EO, 2 to 12 days; and combination of ET and 5% EO, 8 days. Postoperative complications included fever of unknown (n = 2), acute psychosis (n = 3), vocal cord paralysis (n = 2), and bradycardia induced from the use of a sedative agent (n = 1). One patient complained of mild transient swallowing difficulty that lasted for a month postoperatively.Although our method mandatorily requires careful postoperative management in an ICU, including sedation with anesthetic agents and artificial respiration by intubation for a certain period of time, no serious complications or post-therapeutic morbidities occurred.

Risk Factors for Macroscopic Haemoglobinuria After Sclerotherapy Using Ethanolamine Oleate for Venous Malformations.

OBJECTIVES: Sclerotherapy is an essential component of the treatment for venous malformations, and ethanolamine oleate (EO) is known as a useful sclerosing agent. However, macroscopic haemoglobinuria (MH) and subsequent renal impairment are severe complications after sclerotherapy using EO. The present study aimed to clarify the MH risk factors for better peri-operative management of venous malformations. METHODS: Data collected during 130 procedures involving 94 patients who were undergoing sclerotherapy using EO for venous malformation were retrospectively analysed. Pre-operative and operative variables, including sex, age, pre-operative body mass index, location, depth, type of lesion, size, number of procedures, type of drainage vein, ratio of sclerosant to air, and injected total dose of 5% EO per body weight (BW), were examined. Univariable analysis and multivariable logistic regression were performed to determine the possible risk factors for MH. RESULTS: Following sclerotherapy, MH occurred in 27.7% of patients, but no patient developed post-operative renal impairment because of aggressive hydration and haptoglobin administration. On univariable analysis, diffuse lesion, lesion size ≥50 cm2, and total injected dose of 5% EO ≥ 0.18 mL/kg were found to be the MH risk factors. Multivariable logistic regression analysis identified a total injected dose of 5% EO ≥ 0.18 mL/kg as the significant independent factor contributing to MH risk. CONCLUSIONS: Macroscopic haemoglobinuria is a reversible complication if immediate and appropriate interventions with aggressive hydration and haptoglobin administration are performed; therefore, it should be closely monitored following sclerotherapy, especially when using 5% EO ≥ 0.18 mL/kg.

Soft Tissue Reconstruction and Facial Reanimation With Bilateral Latissimus Dorsi Flaps After Extensive Resection of Head and Neck Arteriovenous Malformation: A Case Report.

We report a rare case of a 37-year-old man who presented with a huge arteriovenous malformation in the head and neck region. After resection, the 30 × 25 cm defect was reconstructed with a preexpanded musculocutaneous latissimus dorsi flap. The facial nerve had to be sacrificed during the resection, and smile reanimation was restored in a second operation with the contralateral latissimus muscle flap. A 15-cm length of thoracodorsal nerve was dissected and was anastomosed to the contralateral zygomatic branch in a single stage. He recovered well without any significant complications. At 6 years follow-up, there was no further growth of the arteriovenous malformation, and he had a spontaneous smile.

Implantation of Thickened Artificial Bone for Reduction of Dead Space and Prevention of Infection Between Implant and Dura in Secondary Reconstruction of the Skull.

For the treatment of skull defect compensation after neurosurgery, a customized artificial bone is often employed owing to its toughness and the relative ease of producing cosmetically good result. However, implants are vulnerable to infection and removal of implant is sometimes necessary. Several other treatment options such as autologous bone graft or free flap are likely to be considered for the secondary reconstruction to avoid reinfection; however, reimplantation of artificial bone is beneficial for the patients, being not concerned with donor site morbidity. The authors consider one of risk factors of infection of artificial bone as dead space between the implant and dura. To attain reduction of the dead space, we have employed thickened artificial bone.Between 2010 and 2014, 6 patients underwent implantation of thickened artificial bone for the secondary reconstruction.First, the infected artificial material was removed with proper debridement. More than 3 months after the closure of the infected wound, tissue expander was inserted beneath the surrounding scalp to ensure the coverage of subsequently implanted artificial bone without skin tension. The thickened artificial bone was designed from the computed tomography findings so as not to leave any dead space between the implant and dura. After optimal expansion of the scalp, the artificial bone was implanted.Postoperative courses were uneventful and the appearance of the cranial vault was satisfactory in all patients.The authors consider the use of the thickened artificial bone is easier and more suitable for patients having a skull defect, particularly in secondary reconstruction.

Successful retrograde arterial inflow through a muscular branch in a free anterolateral thigh chimeric flap transfer.

In this report, we present a case in which a free anterolateral thigh (ALT) flap was transferred for head and neck reconstruction after oropharyngeal cancer ablation, and a retrograde arterial inflow was used to salvage the flap when the main arterial pedicle showed usual repeated spasms. The flap was raised as a chimera flap comprising a fasciocutaneous flap and a vastus lateralis muscle flap. After reperfusion, the pedicle artery exhibited spasms repeatedly and vascular flow was unstable. Therefore, we performed arterial supercharge. In the distal portion of the muscle flap, a small arterial branch was dissected as a reverse-flow arterial pedicle. The recipient artery was also a retrograde limb of the superior thyroid artery. The flap survived; however, postoperative ultrasonographic echo evaluation revealed that the spastic descending branch of the lateral circumflex femoral artery was obstructed and that the reverse-flow muscular perforator alone nourished the whole flap. In free ALT flap transfer, a small perforator level artery was able to nourish a flap, even in a retrograde manner. Moreover, when the vasculature of the free flap is unstable, retrograde arterial supply to a small perforator can be an option to save the flap transfer.

Induction of ovulation in Xenopus without hCG injection: the effect of adding steroids into the aquatic environment.

BACKGROUND: The African clawed frog, Xenopus laevis, is widely used in studies of oogenesis, meiotic cell cycle and early embryonic development. However, in order to perform such studies, eggs are normally collected after the injection of hCG into the dorsal lymph sac of fully-grown female frogs following pre-injection of PMSF. Although this protocol is established and used as standard laboratory approach, there are some concerns over whether the injections could cause the transmission of deleterious microorganisms. Moreover, these injection protocols require a competent skilled worker to carry out the procedure efficiently. METHODS: Recently, we established a novel method to induce fish ovulation by simply adding the natural maturation-inducing hormone of teleosts, 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-DHP), into the surrounding water. In the present study, we demonstrate how we can induce ovulation in frogs using the same methodology. RESULTS: In frogs, progesterone was effective in the induction of oocyte maturation in vitro. We then examined the ability of progesterone to induce ovulation in frogs. However treatment of frogs with progesterone alone only occasionally induced ovulation in vivo. The number of oocytes and the frequency of ovulation were significantly lower than that induced by hCG-injection. Thus, conditions were improved by using a combination of progesterone with estradiol and by pre-treating frogs with low concentrations of progesterone or estradiol. Finally, we established an efficient means of inducing ovulation in frogs which involved pre-treatment of frogs with salt solution followed by a mixture of estradiol and progesterone at high concentration. The frequency and numbers of oocytes obtained were identical to those resulting from PMSG-hCG induction. Fertilization rate of eggs ovulated by the new treatment method was comparable to eggs obtained by hCG-injection and juveniles developed normally. CONCLUSIONS: To conclude, we have successfully developed a novel method to induce ovulation in frogs but without the need for a potentially harmful injection strategy.

Japanese clinical practice guidelines for vascular anomalies 2017.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Japanese Clinical Practice Guidelines for Vascular Anomalies 2017.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQ) were decided based on the important clinical issues. For document retrieval, key words for published work searches were set for each CQ, and work published from 1980 to the end of September 2014 was searched in PubMed, Cochrane Library and Japana Centra Revuo Medicina databases. The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System technique. A total of 33 CQ were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Clinical outcomes and recipient vessel selection for free flap transfer following arteriovenous malformation resection.

BACKGROUND: Arteriovenous malformation (AVM) is a rare vascular lesion that is difficult to treat. Radical surgical resection followed by free flap transfer is currently one of the preferred treatments, and this study aimed to assess the selection of recipient vessels and clinical outcomes for free flap transfer after AVM resection to establish better surgical management. METHODS: Data from 22 consecutive patients who underwent free flap transfer after AVM resection were retrospectively reviewed. Of these, AVMs were located at the head and neck of 11 patients and at the extremities of another 11 patients. The first choice for a recipient vessel was a normal artery or vein. However, in the absence of suitable alternatives, the feeding arteries or drainage veins were employed as recipient vessels. Patient backgrounds and postoperative outcomes were evaluated. RESULTS: Two patients required double flap transfer to cover the defects. Hence, a total of 24 flaps were transferred. A normal artery could be used in all cases of head and neck lesions, whereas a feeding artery was used in all cases of extremity lesions. On the other hand, a normal vein could be used in all cases as the recipient vein. No anastomotic failure or flap loss occurred postoperatively. CONCLUSION: Free flap transfer is feasible and safe even after AVM resection. The feeding artery can be used as the recipient artery in the absence of a normal artery especially for AVMs in the extremity although the safety of the drainage vein as the recipient vein remains unclear. ABBREVIATIONS: AVM: arteriovenous malformation; MRI: magnetic resonance imaging; 3DCT: threedimensional computed tomography; HN: head and neck; NR: not reported.