A novel low-density lipoprotein/fibrinogen apheresis method for chronic limb-threatening ischemia in patients with poor options for revascularization: A multicenter, single-arm clinical trial.

INTRODUCTION: Low-density lipoprotein (LDL) apheresis is a treatment option for patients with unhealed chronic limb-threatening ischemia (CLTI) after revascularization. The newly developed AS-25 is a direct hemoperfusion-type apheresis device that differs from conventional LDL apheresis therapy and is designed to specifically adsorb both LDL-C and fibrinogen. We evaluate the efficacy and safety of AS-25. METHODS: This study included 61 patients whose ulcers failed to heal after revascularization or were ineligible for revascularization. Of these, 50 were undergoing hemodialysis. The primary endpoint was the healing rate of a target lesion of interest (ulcer), using historical data as control. RESULTS: The ulcer healing rate of 45.9% was significantly higher than the historical data. No significant safety concerns were observed. CONCLUSIONS: AS-25 was effective in healing ulcers and preventing major amputation even in CLTI refractory patients on hemodialysis, thus showing potential clinical applicability and high significance. CLINICAL TRIAL REGISTRATION: UMIN study ID UMIN000020336.

Ultrasonic Debridement of Fournier Gangrene.

Ultrasonic debridement devices are minimally invasive and effective for biofilm removal, allowing for debridement of necrotic tissue while minimizing damage to normal tissues, such as the blood vessels and nerves. The use of ultrasonic debridement has been reported for foot ulcers and pressure ulcers but not Fournier gangrene. The perineal area, which is difficult to surgically debride using electrocautery, is a suitable site for the use of an ultrasonic debridement device because of its proximity to vital organs. We report here a case of Fournier gangrene that healed with testicular sparing using an ultrasonic debridement device.

Salvage Case of Corpus Cavernosum Necrosis and Urethral Perforation associated with Infection after Penile Prosthesis Insertion.

Penile prosthesis implantation can be considered in patients with unsuccessful treatment with phosphodiesterase type 5 inhibitors for erectile dysfunction. Its associated postoperative complications include infection and urethral injury. Nevertheless, only a few studies have reported the successful management of severe cases. Herein, we report a case of corpus cavernosum necrosis and distal urethral perforation caused by infection after penile prosthesis insertion, which had favorable outcomes. A 60-year-old man with multiple atherosclerotic risks underwent penile prosthesis implantation for erectile dysfunction at another hospital. Postoperatively, he developed infectious necrosis and underwent prosthesis removal. However, he presented at our department because of technical difficulties in the treatment at other hospitals. The initial examination revealed extensive necrosis of the corpus cavernosum and perforation of the peripheral urethra. A thin urethral catheter was inserted, and the necrotic corpus cavernosum was debrided to preserve the artery and urethra. Then, the perforated urethra was sutured. Subsequent negative pressure wound therapy resulted in sufficient granulation and closure of the perforated urethra. One month after the surgery, the scar was resected and sutured following the circumcision line. Despite experiencing this severe postoperative complication, good functional and cosmetic outcomes were achieved after minimal surgery with a blood-flow-conserving method.

Reconstruction of necrotizing soft tissue infection in the auricle and temporal region: a case report.

A 43-year-old female patient had a necrotizing soft tissue infection in the temporal region. Because of the necrotic temporoparietal fascia, auricular reconstruction was attempted using the temporalis muscle flap; the flap was successfully placed. The use of the temporalis muscle flap was considered a treatment option for salvaging the auricle.

Endovascular therapy and free flap transfer in chronic limb-threatening ischemia.

Although revascularization has evolved, treating foot gangrene with chronic limb-threatening ischemia remains challenging. There have been many reports on bypass surgery and free flap transfer. Meanwhile, few studies have reported on endovascular therapy and free flap transfer, with high flap survival rates and high wound complication rates. Wound complications are a serious problem that can lead to limb amputation, but previous studies have failed to identify risk factors for wound complications. In this study, we evaluated the results of endovascular therapy and free flap transfer for chronic limb-threatening ischemia and analyzed risk factors for wound complications. A total of 31 legs from 28 patients who underwent endovascular therapy and free flap transfer for lower limb salvage between August 2016 and April 2020 were retrospectively reviewed. The primary endpoints were flap survival and limb salvage rates and wound complication rates. In addition, we performed a statistical analysis of risk factors for wound complications. The flap survival rate was 100%, with partial necrosis in 6% of the patients. The limb salvage rate was 100%. The wound complication rate was 45%. The multivariate analysis showed end-stage renal failure on dialysis as a significant risk factor for wound complications (odds ratio = 133, 95% confidence interval = 2.74-6430, p = 0.014). Endovascular therapy and free flap transfer in chronic limb-threatening ischemia achieved high flap survival rate and limb salvage, but had a high incidence of wound complications. We identified end-stage renal failure on dialysis was a significant risk factor for wound complications.

Multiple free dorsal flaps for symmetrical peripheral gangrene of the extremities: A case report.

We present a case of symmetrical peripheral gangrene of the extremities due to acute infectious purpura fulminans that was reconstructed with four free flaps harvested from the bilateral backs. We reconstructed the right and left, upper and lower limbs using the parascapular flap and latissimus dorsi muscle flap from one side and the scapular flap and thoracodorsal artery perforator flap from the other side, in multiple stages. All four flaps survived, preserving the right and left heels and function of the bilateral wrist joints. Although there have been several reports of single-stage elevation of the combined scapular and latissimus dorsi flaps, there has been no report of multi-stage elevations of these flaps. When multiple flaps are required in multi-stage, raising the flaps based on the thoracodorsal artery and scapular circumflex artery from the ipsilateral back is a useful method because it does not require additional donor sites.

Sacral Pressure Ulcer in Leriche Syndrome: A Case Report.

We experienced a case of a sacral pressure ulcer complicated with Leriche syndrome, an aortoiliac artery occlusion that has not been previously reported. In this case, the abdominal aorta below the bifurcation of the renal arteries into the bilateral common iliac arteries was occluded, and wound healing was delayed. Therefore, endovascular treatment was used for managing this condition, and wound healing was accelerated. Then, reconstructive surgery with a local flap was performed, and wound healing was achieved. In the case of delayed healing of buttock pressure ulcers, it is important to evaluate the blood flow in the iliac artery as well as the infection and nutritional status of the wound. In addition, after endovascular treatment, blood flow in the local flap is a matter of concern. If the wound healing is good, and imaging confirms that there is no restenosis at the endovascular treatment site and the perforator of the flap, reconstructive surgery can be performed safely.

Hard-to-heal wound treatment medical devices: clinical trial protocol in Japan.

In consultation with academia and the Pharmaceuticals and Medical Devices Agency (PMDA), we have developed guidance for drafting protocols for clinical trials concerning medical devices for the healing of hard-to-heal wounds without ischaemia. The guidance summarises the validity of single-arm trials for hard-to-heal wounds, the definition of hard-to-heal wounds without ischaemia, methods of patient enrolment and clinical endpoints. This review focuses on the logical thinking process that was used when establishing the guidance for improving the efficiency of clinical trials concerning medical devices for hard-to-heal wounds. We particularly focused on the feasibility of conducting single-arm trials and also tried to clarify the definition of hard-to-heal wounds. If the feasibility of randomised control trials is low, conducting single-arm trials should be considered for the benefit of patients. In addition, hard-to-heal wounds were defined as meeting the following two conditions: wounds with a wound area reduction <50% at four weeks despite appropriate standards of care; and wounds which cannot be closed by a relatively simple procedure (for example, suture, skin graft and small flaps). Medical devices for hard-to-heal wound healing are classified into two types: (1) devices for promoting re-epithelialisation; and (2) devices for improving the wound bed. For medical devices for promoting re-epithelialisation, we suggest setting complete wound closure, percent wound area reduction or distance moved by the wound edge as the primary endpoint in single-arm trials for hard-to-heal wounds. For medical devices for improving the wound bed, we suggest setting the period in which wounds can be closed by secondary intention or a simple procedure, such as the primary endpoint.

Hydrosurgical debridement as an approach to wound healing: an animal thermal burn model.

OBJECTIVE: This study investigates the advantages of hydrosurgical debridement compared with surgical debridement. METHOD: Thermal skin burns were created on the backs of male Wistar rats. Surgical debridement was used to treat one wound and hydrosurgical debridement (Versajet Hydrosurgery System, Smith&Nephew, UK) used to treat the second wound. Debridement time, blood loss volume, time-to-heal and histologic changes in the wound areas were compared. RESULTS: A total of 23 rats were used in the study. Debridement time and time-to-heal were significantly shorter with hydrosurgical debridement than with surgical debridement (p<0.01 and p<0.05, respectively). Blood loss volume was significantly less with hydrosurgical debridement (p<0.01), and the wound surface area was significantly smaller on days two (p<0.01), four (p<0.05) and seven (p<0.05). Dense inflammatory cell infiltration into dermal muscle was deeper after surgical debridement (p=0.017). Reactive fibrotic tissue at the wound surface was significantly thinner (p<0.001) and the vascular endothelial cell count was significantly higher (p<0.001) after hydrosurgical debridement. CONCLUSION: The hydrosurgical system used appears to provide for minimally invasive debridement that can be performed in a relatively short period of time. Use of the device appears to minimise injury to healthy tissue and ameliorate inflammation, which in turn promotes early wound healing and reduces scar contracture. Hydrosurgical debridement appears to cause less damage to normal tissues. Furthermore, it is easier and requires less time.

Reconstruction for labial adhesion in postmenopausal woman using vulvoperineal flap.

We report the case of an 86-year-old postmenopausal woman with severe labial adhesion. The adhesion overlying the vestibule was manually separated and the skin defect was covered with bilateral vulvoperineal flaps. Reconstruction using the vulvoperineal flap enabled to prevent recurrence by covering with normal skin tissue.

Gluteal fold flap for pelvic and perineal reconstruction following total pelvic exenteration.

BACKGROUND: The rectus abdominis myocutaneous flap has been used as the first choice for pelvic and perineal reconstruction. However, due to previous abdominal surgery and multiple stoma placements in our patients, the rectus abdominis myocutaneous flap could not be used for such reconstruction. Here, we describe the use of bilateral gluteal fold flaps for pelvic and perineal reconstruction following total pelvic exenteration to treat recurrent cervical cancer. METHODS: We performed three bilateral gluteal fold flap operations for perineal reconstruction in three patients between 2008 and 2011. The cause of the perineal defect was total pelvic exenteration, which was performed to treat recurrent cervical cancer in all patients. RESULTS: All flaps completely survived and there were no severe postoperative complication. Good cosmetic results were achieved in all patients. CONCLUSIONS: The gluteal fold flap is a useful option for reconstructing extensive pelvic and perial defect after total pelvic exenteration because of sufficient soft tissue volume, reliable blood supply, cosmetic results and minimal donor-site morbidity.

Hyperbaric oxygen therapy for digital ulcers due to Raynaud's disease.

We present a case of Raynaud's disease with digital ulcers that was successfully treated with hyperbaric oxygen therapy. Hyperbaric oxygen therapy can be considered as a safe and useful adjunct treatment for intractable digital ulcers in patients with Raynaud's disease.

Factors impairing cell proliferation in the granulation tissue of pressure ulcers: Impact of bacterial burden.

The authors aimed to assess the factors that impair cell proliferation in the granulation tissue of pressure ulcers using immunohistochemistry for the cell proliferation marker Ki-67. This was a single center, cross-sectional study. The study included 86 patients with stage III or IV pressure ulcers. Two granulation tissue biopsy specimens were obtained from 86 patients. The specimens were used for histological examination, Ki-67 immunohistochemistry, and bacterial count assessment. The % of Ki-67-stained cells was considered as the Ki-67 index. Pearson's product-moment correlation coefficient (r) was used to assess the relationship between the Ki-67 index and other quantitative variables, including age, body mass index, bacterial count (Log10 CFU/g), serum albumin level, hemoglobin level, white blood cell count, and C-reactive protein level. The Mann-Whitney U test was used to compare the mean Ki-67 index according to gender, diabetes, smoking status, and wound culture. Univariate and multivariate linear regression analyses were used to assess the association between the Ki-67 index and other parameters. The Mann-Whitney U test revealed that the bacteria-positive group had a lower Ki-67 index (p = 0.045). Bacterial count demonstrated a significant negative correlation with the Ki-67 index (r = -0.325, p = 0.002). Multivariate linear regression analysis showed that bacterial count was a significant predictor of the Ki-67 index. The adjusted ß-coefficient was -1.34 (95% confidence interval, -2.01 to -0.66, p < 0.001). Among the isolated bacteria, Corynebacterium spp. and Staphylococcus aureus were significantly associated with a low Ki-67 index, but Pseudomonas aeruginosa was not. These results suggest a negative relationship between bacterial count and cell proliferation in pressure ulcer granulation tissue, as indicated by the Ki-67 index. Granulation tissue formation in pressure ulcers may be accelerated if high bacterial load is treated appropriately.

Microsurgical replantation of an amputated ear.

We report a case of successful microsurgical reattachment of an amputated ear. Microsurgical reattachment should be considered whenever possible.

Free flap reconstruction for diabetic foot limb salvage.

BACKGROUND: Although free flap is gaining popularity for the reconstruction of diabetic foot ulcers, it is unclear whether free flap reconstruction increases the chances of postoperative independent ambulation. The aim of this study is to evaluate the relationship between free flap success and postoperative ambulation. METHODS: This study reviewed 23 cases of free flap reconstruction for diabetic foot ulcers between January 2007 and March 2014. Free rectus abdominis, latissimus dorsi, and anterolateral thigh flaps were used in ten, eight, and five patients, respectively. A comparison was made between free flap success and postoperative independent ambulation using Fisher's exact test. RESULTS: Two patients developed congestive heart failure with fatal consequences within 14 days postoperatively, resulting in an in-hospital mortality rate of 8.7%. Five patients lost their flaps (21.7%). Of the 16 patients who had flap success, 12 achieved independent ambulation. Five patients with flap loss did not achieve independent ambulation, except one patient who underwent secondary flap reconstruction using a distally based sural flap. Fisher's exact test revealed that independent ambulation was associated with free flap success (p = 0.047). CONCLUSION: The present study indicates that free flap reconstruction may increase the possibility of independent ambulation for patients with extensive tissue defects due to diabetic ulcers. Intermediate limb salvage rates and independent ambulation rates were favourable in patients with successful reconstruction. The use of foot orthoses and a team approach with pedorthists were effective to prevent recurrence.

A Novel Index Using Ankle Hemodynamic Parameters to Assess the Severity of Peripheral Arterial Disease: A Pilot Study.

In peripheral arterial disease (PAD) of the lower extremities, the presence of flow-limiting stenoses can be objectively detected by the ankle-brachial index (ABI). However, the severity of ischemic symptoms is not necessarily associated with the ABI value. Atherosclerotic plaque in lower extremity PAD induces ankle arterial stiffness and reduces ankle vascular resistance, which may decrease ankle blood flow and cause ischemic symptoms. We hypothesized that the ankle hemodynamic index (AHI), defined as the ratio of ankle arterial stiffness to ankle vascular resistance, could be used to assess the blood supply deficiency in a diseased lower limb in patients with PAD. The 85 consecutive patients with PAD who were retrospectively analyzed in this study had Rutherford grade 1 to grade 6 ischemia diagnosed as PAD and significant stenotic lesions (>50% diameter stenosis) of the lower extremity on contrast angiography. The AHI was calculated as the product of the ankle pulse pressure and the ratio of heart rate to ankle mean arterial pressure (ankle pulse pressure × heart rate/ankle mean arterial pressure). The Rutherford grade was significantly correlated with the AHI (r = 0.50, P < 0.001), but not with the ABI (r = 0.07, P = 0.52). Multiple ordinal regression analysis showed that anemia (odds ratio 0.66, P = 0.002) and AHI (odds ratio 1.04, P = 0.02) were independently associated with Rutherford grade. Our study shows that AHI, a novel parameter based on the ABI measurement, is well correlated with ischemic symptoms, and may be a useful means to assess the arterial blood supply of the lower extremities of patients with PAD.

Acute Limb-Threatening Ischemia Associated With Antiphospholipid Syndrome: A Report of Two Cases.

Acute limb ischemia results from sudden deterioration in the arterial supply to the limb, occasionally leading to limb loss or fatality. Antiphospholipid syndrome (APS) is known to induce acute limb ischemia among the various etiologies responsible for arterial obstruction. APS is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis and limb loss. It is often accompanied by a mild-to-moderate thrombocytopenia and elevated titers of antiphospholipid antibodies, including the lupus anticoagulant and the anticardiolipin antibodies. In the present report, we present 2 cases of acute limb ischemia due to APS associated with systemic lupus erythematosus. Angiography revealed arterial obstruction distal to the popliteal artery in both patients, and each patient eventually underwent below-the-knee amputation. Surgeons treating acute limb ischemia should remember APS, although this disease might not be common in daily clinical practice.

Ostectomy and Medial Plantar Artery Flap Reconstruction for Charcot Foot Ulceration Involving the Midfoot.

Charcot foot is a serious complication of diabetes, characterized by deformity and overlying ulceration. The condition most commonly affects the midfoot. However, little information is available on the use of a medial plantar artery flap to treat diabetic midfoot ulceration. The purpose of the present study was to evaluate the versatility of ostectomy and medial plantar flap reconstruction for midfoot plantar ulceration associated with rocker-bottom deformity secondary to Charcot foot. Four patients underwent ostectomy and medial plantar flap reconstruction. Before flap reconstruction, the devitalized soft tissues and bone were radically resected. After the infection had been controlled, the ulcerated portion was minimally excised, and the bony prominence underlying the ulcer was removed. A medial plantar artery flap was applied to the ulcer. The donor site was covered with a split-thickness skin graft or artificial dermis. In all patients, the ulcers healed and independent ambulation was achieved. However, 1 patient experienced ulcer recurrence, and subsequent infection necessitated a major amputation. Limb salvage is challenging in the setting of deformity and intractable plantar ulceration. The advantages of medial plantar artery flap reconstruction are that tissues with a rich blood supply are used to cover the exposed bone, and the flap can withstand the pressure and shear stress of the patient's body weight. However, a dominant artery in the foot is sacrificed. Therefore, the patency of the dorsalis pedis artery must be confirmed in every patient. The results of the present study have demonstrated that a medial plantar artery can be an effective alternative for diabetic patients with a plantar ulcer secondary to Charcot foot.

Efficacy of Ultrasonography at the Ankle Level for Estimation of Pedal Microcirculation.

Chronic wounds due to diabetes mellitus (DM) and/or peripheral arterial disease (PAD) often occur in the pedal region peripheral to the ankle. To predict wound healing potential of limb ulcers, skin perfusion pressure (SPP) and transcutaneous oxygen tension (TcPO2) have recently become popular as the parameters that reflect skin microcirculation. On the other hand, ultrasonography for the macrocirculatory vessels has already prevailed widely as the standard vascular investigation. The skin microcirculation peripheral to the ankle probably depends on the macrocirculatory blood flow at the ankle level. Thus, this study aims to estimate whether the blood flow of the anterior tibial artery (ATA) and the posterior tibial artery, at the ankle level, reflect the values of SPP and TcPO2 on the foot. The protocol enrolled 88 patients (122 limbs) with foot ulcers due to DM and/or PAD. The statistical analysis revealed that the sum of blood flow of the ATA and the PTA (posterior tibial artery), at the ankle level, significantly correlated with SPP on the foot. The findings support the availability of conventional ultrasonographic investigation to estimate microcirculation of the foot crucial for wound healing. (This article is a translation of J Jpn Coll Angiol 2014; 54: 45-50.).

Which cleansing care is better, foot bath or shower? Analysis of 236 limb ulcers.

Foot baths and showering are two widely used methods to cleanse limb ulcers. However, some clinicians warn that foot baths may contribute to the spread of infection at the ulcer site. This study aimed to retrospectively investigate the relationship between cleansing methods and the limb prognoses of 236 patients with chronic limb ulcers. These patients were divided into two groups according to the method used to cleanse their ulcers, foot bath and showering. Limb prognosis, including loss of all toes and major amputation, was retrospectively analysed. The rates of loss of all toes and major amputation were 53·0% and 30% in the foot bath group, and 35·3% and 18·4% in the showering group, respectively. The rates of loss of all toes (adjusted odds ratios = 2·07; P = 0·0066; 95% confidence intervals, 1·22-3·50) and major amputation (adjusted odds ratio = 1·90; P = 0·037; 95% confidence intervals, 1·03-3·50) were significantly higher in the foot bath group than those in the showering group. Our results demonstrate that showering is preferable to foot baths for the cleansing of chronic limb ulcers. Clinicians should be cautious that inappropriate cleansing may cause ulcer infections to spread.