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.

Negative Pressure Wound Therapy with Instillation and Dwell Time Using Antiseptic Solution in Chronic Limb-threatening Ischemia.

Background: Chronic limb-threatening ischemia (CLTI) is a severe peripheral artery disease with rest pain and lower limb ulceration. After revascularization, limb ulceration treatment should be completed quickly before restenosis. We aimed to investigate the effect of negative pressure wound therapy with instillation and dwell (NPWTi-d) using an antiseptic solution (AS) versus a saline solution (SS) in CLTI. There is no research limited to CLTI on this topic. Methods: All patients underwent revascularization and surgical debridement. NPWTi-d was applied after surgical debridement. We evaluated wound tissue cultivation from pre- and post-NPWTi-d, length of NPWTi-d, and laboratory data pre- and post-NPWTi-d. All data are presented as the median, interquartile range. For univariate analysis, nonnormally distributed data were examined using the Wilcoxon rank sum test between the two groups of NPWTi-d (AS and SS group). A P value of less than 0.05 was considered statistically significant. Results: Forty-eight CLTI patients participated. The SS group included 24 patients (19 men, five women, average age 68.8 years) and the AS group included 24 patients (16 men, eight women, average age 67.4 years). The comorbidities included 23 and 19 patients with diabetes mellitus and hemodialysis in the SS group, and 22 and 16 patients in the AS group, respectively. There were no adverse events in either group. Both groups reduced the number of bacteria. The AS group required shorter NPWTi-d time (P = 0.02). Conclusion: The AS group was able to shorten the treatment duration in CLTI.

Compensatory gait mechanics in person with multiple toe amputation: A single case report.

This case highlights the biomechanical influence of toe amputation on contralateral limb force elevation, possibly through reduced ipsilateral plantar flexor torque production. These findings provide insight into toe amputation-related compensatory gait mechanics with greater inter-limb asymmetry, which may increase the risk of musculoskeletal comorbidities, including osteoarthritis in contralateral limb.

Pathological Analysis of Medial and Intimal Calcification in Lower Extremity Artery Disease: Impact of Hemodialysis.

Background: The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated. Objectives: The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification. Methods: Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification. Results: The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group (P < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; P = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque (P = 0.02). The prevalence of severe bone formation was more common in the HD patients (P = 0.01). Conclusions: Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.

Three years progress chronic limb-threatening ischemia case with simultaneous surgery.

INTRODUCTION AND IMPORTANCE: Chronic limb-threatening ischemia (CLTI) is a severe limb problem. The causes of foot ulcer are influenced by several factors, which lead to ischemia and foot deformity causing recurrence after wound healing. This report focuses on the long-term course. CASE PRESENTATION: An 80-year-old male with CLTI was treated. The patient had an ulcer in the second toe of his left foot and stenosis of above the knee vessels. He performed his daily activities independently and his left foot was hallux valgus. After improving blood flow, foot deformity was corrected with ulcer treatment. The patient's second toe was amputated after the endovascular treatment. Finally, the toe was closed and hallux abductive valgus was corrected at the same time. After three years, he had no recurrence of foot ulcer. The patient uses a foot orthosis and his life is independent with no recurrence. CLINICAL DISCUSSION: Surgical offloading is an effective method to prevent recurrence. Surgical offloading is sometimes performed in patients with CLTI, but there is few occasion to undergo. This is because, there are problems of re-ischemia and an advanced age. Therefore, simultaneous surgery, as in this case, could be useful and help reduce the ulcer recurrence rate. CONCLUSION: Simultaneous surgery for CLTI was useful in leading to a reduction in recurrence rate.

The Efficacy of the Transdermal Isosorbide Dinitrate Patch in Patients With Chronic Limb-Threatening Ischemia.

Recently, the number of patients with peripheral artery disease (PAD), including those with chronic limb-threatening ischemia (CLTI), has increased because of the increasing number of diabetic or dialysis patients worldwide. Revascularization is an important therapy for patients with CLTI. However, we sometimes experience refractory cases with insufficient peripheral circulation or microcirculation after revascularization. In this situation, additional therapy can be administered, such as low-density lipoprotein apheresis, high-pressure oxygen therapy, and spinal cord stimulation. However, they are not effective in some cases. Some reports have also indicated that transdermal isosorbide dinitrate patch (ISDN-P) is a useful therapy for PAD. As the efficacy of ISDN-P for patients with CLTI is not well-known, we examined it in this study. We assessed the skin perfusion pressure (SPP) after affixing an ISDN-P on the foot, because SPP measurement has proved useful in the assessment of PAD and is a good indicator of wound healing potential. The SPP (dorsal and plantar aspects) after ISDN-P application on the foot of healthy volunteers increased (n = 8; mean ± SD, 12.6 ± 7.9 [P = .12], and 21.2 ± 7.7 mm Hg [P < .05], respectively), as did SPP of patients with CLTI (n = 10; mean ± SD, 19.8 ± 2.5 [P < .01], and 14.1 ± 5.9 mm Hg [P < .05], respectively). All the patients who received an ISDN-P on the foot had no major complication, and no significant change in blood pressure. In conclusion, the ISDN-P is one of the effective and safe therapies for patients with CLTI.

Long-term efficient management of diabetic foot ulcer using simultaneous foot ulcer closure and surgical off-loading.

Foot deformity is one of the causes of foot ulcers. Foot ulcers often recur due to foot deformity. Foot ulcer healing alone does not reduce the risk factor of foot ulcer recurrence. The majority of foot ulcer patients, most of whom are elderly, have foot deformities. This limits the chances of undergoing surgical off-loading following surgery. We present a case of diabetic foot ulcer (DFU) in which surgical off-loading was performed simultaneously with foot ulcer closure that did not recur for a period of 2 years following surgery. A 70-year-old diabetic male with a DFU presented to our hospital. He underwent surgical debridement followed by reconstruction surgery (stump plasty) simultaneous with surgical off-loading (metatarsal head resection). The immediate postoperative period during which he used the off-loading device was uneventful. Following this, he used orthosis. After 2 years, the foot ulcer had not recurred, and he was able to independently perform his daily activities. Simultaneous surgery (reconstructive surgery and surgical off-loading) is less likely to limit daily activities and can reduce the ulcer recurrence rate.

Giant Hepatic Cyst: A Possible Cause of Inferior Vena Cava Syndrome.

An 80-year-old man was transferred to our institution with lower limb edema and worsening dyspnea following the administration of diuretic medication. Transthoracic echocardiography and computed tomography revealed a giant hepatic cyst (176×190 mm) compressing his right atrium and inferior vena cava (IVC). Laparoscopic cyst deroofing combined with omental packing and subsequent tube drainage immediately alleviated all his symptoms. The procedure was uneventful, and he was discharged without any complications on postoperative day 9; he had no recurrent symptoms or hepatic cysts at the postoperative 2-month follow-up. Therefore, a giant hepatic cyst can cause IVC syndrome, and laparoscopic deroofing is a beneficial approach for the treatment of accessible cysts.

Investigator-initiated clinical study of a functional peptide, SR-0379, for limb ulcers of patients with Werner syndrome as a pilot study.

AIM: An investigator-initiated clinical study was carried out to evaluate the therapeutic potency of SR-0379 for the treatment of leg ulcers in patients with Werner syndrome. METHODS: A multicenter, open-label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR-0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end-point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end-points, the DESIGN-R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR-0379 was evaluated during the study period. RESULTS: The reduction rate of ulcer size treated with 0.1% SR-0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN-R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events. CONCLUSION: Treatment with SR-0379 was safe, well-tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118-1123.

Convolutional neural networks for wound detection: the role of artificial intelligence in wound care.

OBJECTIVE: Telemedicine is an essential support system for clinical settings outside the hospital. Recently, the importance of the model for assessment of telemedicine (MAST) has been emphasised. The development of an eHealth-supported wound assessment system using artificial intelligence is awaited. This study explored whether or not wound segmentation of a diabetic foot ulcer (DFU) and a venous leg ulcer (VLU) by a convolutional neural network (CNN) was possible after being educated using sacral pressure ulcer (PU) data sets, and which CNN architecture was superior at segmentation. METHODS: CNNs with different algorithms and architectures were prepared. The four architectures were SegNet, LinkNet, U-Net and U-Net with the VGG16 Encoder Pre-Trained on ImageNet (Unet_VGG16). Each CNN learned the supervised data of sacral pressure ulcers (PUs). RESULTS: Among the four architectures, the best results were obtained with U-Net. U-Net demonstrated the second-highest accuracy in terms of the area under the curve (0.997) and a high specificity (0.943) and sensitivity (0.993), with the highest values obtained with Unet_VGG16. U-Net was also considered to be the most practical architecture and superior to the others in that the segmentation speed was faster than that of Unet_VGG16. CONCLUSION: The U-Net CNN constructed using appropriately supervised data was capable of segmentation with high accuracy. These findings suggest that eHealth wound assessment using CNNs will be of practical use in the future.

Physician-initiated clinical study of limb ulcers treated with a functional peptide, SR-0379: from discovery to a randomized, double-blind, placebo-controlled trial.

SR-0379 is a functional peptide that has wound healing effect with anti-microbial action, making it an ideal drug to prevent infection. To evaluate the safety, efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A multi-center, double-blind, randomized clinical study was conducted from October 2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes or critical limb ischemia and (2) wound size <6 cm in diameter. Twelve patients were randomized into four groups and administered 0.02%, 0.1%, or 0.5% SR-0379 or placebo treatment on skin ulcers once per day for 28 days. Efficiency was evaluated by determining the rate of wound size reduction as a primary endpoint at 4 weeks after the first treatment compared with the pre-treatment wound size. As a secondary endpoint, the DESIGN-R score index, time to wound closure, and the 50% wound size reduction ratio were also evaluated. The safety of SR-0379 was evaluated during the study period. In the evaluation of efficiency, the skin ulcer reduction rates at the last evaluation were 44.73% for the 0.02% SR-0379 group, 68.25% for the 0.1% group, and 71.61% for the 0.5% group, compared with 9.95% for the placebo group. Six adverse events were reported in four patients, of which one occurred in the placebo group, and causal relationships to study drugs were denied for all six events. Treatment with SR-0379 for chronic leg ulcers was safe, well tolerated, and effective.