Poor short-term outcomes for prognostic high-risk patients with chronic limb-threatening ischemia undergoing endovascular therapy.

BACKGROUND: The prognosis of chronic limb-threatening ischemia (CLTI) is poor, with an expected life expectancy of 2 or more years, which significantly influences treatment decisions. However, death may occur at the early stages of treatment for wound healing, and aggressive treatment may limit the quality of life of such patients. In patients with CLTI undergoing endovascular therapy (EVT), the Wound, Ischemia, and foot Infection (WIfI) clinical stage, male sex, older age, non-ambulatory status, low body mass index, and dialysis have been reported as predictors of mortality risk. However, most studies have not fully investigated the WIFI clinical stage as a prognostic predictor of CLTI. This study aimed to evaluate short-term prognosis and wound healing rates using the prognostic predictors (PPs) indicated above in risk-stratified patients with CLTI who underwent EVT. METHODS: This retrospective single-center observational study included 61 CLTI patients undergoing EVT from April 2020 to October 2022. The patients were divided into a high-risk group (PPs ≥ 4, n = 20) and low-risk group (PPs ≤ 3, n = 41) according to the number of PPs. Survival and wound healing rates within one year were compared between these two groups. RESULTS: The mean age of the patients was 74.7 ± 1.6 years, and 42 (68.9%) were male. Among these patients, the high-risk group compared with the low-risk group had a significantly worse survival rate within one year (46.4% vs. 84.7%, log-rank p < 0.001). Fifteen patients died within one year. Of these, seven deaths were cardiovascular deaths and six were deaths from infectious diseases. Cox proportional hazards analysis showed that WIfI clinical stage 4 (p = 0.043, hazard ratio [HR] = 4.85) and the male sex (p = 0.037, HR = 6.34) influenced the prognosis of this population. The high-risk group tended to have a worse wound healing rate within one year than that had by the low-risk group (55.4% vs. 83.0%, log-rank p = 0.086). CONCLUSIONS: The assessment of short-term prognosis and wound healing rates using PPs may be useful. Discussing the results of short-term clinical outcome assessments with patients should be considered when determining their individualized treatment plans.

Primary results of the SAVAL randomized trial of a paclitaxel-eluting nitinol stent versus percutaneous transluminal angioplasty in infrapopliteal arteries.

BACKGROUND: Effective and durable options for infrapopliteal artery revascularization for patients with chronic limb-threatening ischemia (CLTI) are limited. METHODS: The SAVAL trial is a prospective, multicenter, randomized trial of patients with CLTI and infrapopliteal artery lesions with total lesion length ⩽ 140 mm, stenosis ⩾ 70%, and Rutherford category 4-5 assigned 2:1 to treatment with the SAVAL self-expandable paclitaxel drug-eluting stent (DES) or percutaneous transluminal angioplasty (PTA) with an uncoated balloon. The primary effectiveness endpoint was primary vessel patency (i.e., core lab-adjudicated duplex ultrasound-based flow at 12 months in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion). The primary safety endpoint was the 12-month major adverse event (MAE)-free rate; MAEs were defined as a composite of above-ankle index limb amputation, major reintervention, and 30-day mortality. The endpoints were prespecified for superiority (effectiveness) and noninferiority (safety) at a one-sided significance level of 2.5%. RESULTS: A total of 201 patients were enrolled and randomly assigned to treatment (N = 130 DES, N = 71 PTA). Target lesion length was 68.1 ± 35.2 mm for the DES group and 68.7 ± 49.2 mm for the PTA group, and 31.0% and 27.6% of patients, respectively, had occlusions. The 12-month primary patency rates were 68.0% for the DES group and 76.0% for the PTA group (Psuperiority = 0.8552). The MAE-free rates were 91.6% and 95.3%, respectively (Pnoninferiority = 0.0433). CONCLUSION: The SAVAL trial did not show benefit related to effectiveness and safety with the nitinol DES compared with PTA in infrapopliteal artery lesions up to 140 mm in length. Continued innovation to provide optimal treatments for CLTI is needed. (ClinicalTrials.gov Identifier: NCT03551496).

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

AIMS: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). RESULTS: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. CONCLUSIONS: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Percutaneous deep venous arterialization with balloon angioplasty salvaged a life-threatening critical limb in a hemodialysis patient after repeated pedal angioplasty failed: A case report.

Chronic limb-threatening ischemia (CLTI) with severe below-the-ankle (BTA) lesions is often difficult to revascularize with endovascular treatment (EVT) and surgical treatment. We present a case of successful limb salvage using percutaneous deep venous arterialization (pDVA) in a patient with CLTI whose BTA lesion reconstruction failed. A 57-year-old man with diabetes mellitus and end-stage renal failure on maintenance hemodialysis was referred to our hospital because of gangrene in the second and third toes of his left foot. EVT was repeated for the anterior tibial artery, posterior tibial artery (PTA), dorsal foot artery, and plantar artery lesions; however, revascularization below the ankle was unsuccessful. As the infection had spread to the sole of the foot, below-the-knee amputation was indicated, but the patient refused. Therefore, we performed pDVA on the left PTA simultaneously with a Lisfranc amputation. An arteriovenous fistula was created at the ankle joint using a Venous Arterialization Simplified Technique and a guidewire was inserted into the plantar vein. Balloon dilatation from PTA to the plantar vein was performed to complete the pDVA. Although repeated EVT was required to maintain blood flow in the pDVA, skin grafting was performed 3 months after the pDVA, the wound completely healed, and he was discharged 6 months after the DVA. The pDVA can be an option for limb salvage in patients with no-option CLTI who are confronted by imminent amputation.

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.

Social isolation in patients with chronic limb-threatening ischemia: a cross-sectional study.

Assistance by family members or friends plays important roles in the course of treating patients with chronic limb-threatening ischemia (CLTI), both during hospitalization and after discharge. The aim of this study was to reveal the prevalence of social isolation and to explore relevant clinical backgrounds in patients with CLTI presenting with tissue loss and requiring revascularization. We analyzed 413 patients registered in a multicenter study in whom revascularization were scheduled for CLTI with tissue loss. Social isolation was analyzed by assessing the residence status of the patients and the involvement of a trusted family member or friend in their daily lives and during hospitalization. Patients living alone accounted for 24.5% (95% confidence interval [CI] 20.1-28.8%) of the study population. Patients receiving welfare were more likely to live alone (P < 0.001). For patients living alone, 21.8% (95% CI 12.8-30.8%) met a trusted family member or friend in their daily lives less than once per year. Younger age and receiving welfare were independently associated with lower frequency of meeting the trusted person in their daily lives (both P < 0.05). The adjusted odds ratio of age and receiving welfare was 0.44 (95% CI 0.29-0.67) per 10-year increase and 3.47 (95% CI 1.43-8.44), respectively. During hospitalization, 9.9% (95% CI 6.8-13.0%) of the patients had no hospital visits by a trusted family member or friend on three key occasions: the patient's first hospital visit, the preoperative explanation regarding the planned operation, and the day of the operation. Younger age and receiving welfare were independently associated with lower frequency of hospital visits by a family member or friend (both P < 0.05). The adjusted odds ratio of age and receiving welfare for no visit versus ≥ 1 visit was 0.51 (0.36-0.74) per 10-year increase and 5.29 (2.46-11.4), respectively. In conclusion, social isolation is common among patients with CLTI, especially younger patients and those on welfare. Practical countermeasures against social isolation are warranted in the management of CLTI.

Two stages of salvaging an extensively necrotic foot with chronic limb-threatening ischemia by arterialization of great saphenous vein and free latissimus dorsi musculocutaneous flap transfer for wound coverage with the arterialized vein as the recipient vessel: A case report.

Patients with chronic limb-threatening ischemia (CLTI) without other options for adequate arterial revascularization could undergo deep (or distal) venous arterialization for limb salvage. Additionally, patients with extensive foot wound with CLTI sometimes require free flap transfer for limb salvage. We herein report a case of successful reconstructive limb-salvage surgery for an extensively necrotic foot with CLTI, using a two-stage operation involving venous arterialization using foot-perforating veins and subsequent free flap transfer (with preservation of the arterialized vein). The patient was a 59-year-old man with CLTI. The patient's right foot had dry necrotic tissue after Lisfranc joint amputation. Only one straight-line to the posterior tibial artery was achieved after endovascular therapies (four times). At the first stage of surgery, an arterial-venous shunt bypass from the superficial femoral artery to the distal great saphenous vein (GSV) (near the foot-perforating vein) was created. Arterial blood supply reached the necrotic area via the foot venous circulation system. At the second stage of surgery, free latissimus dorsi musculocutaneous flap (8 × 27 cm) transfer with preservation of the arterialized vein was performed. The pedicle artery was anastomosed to the bypass graft (end-to-side). The pedicle vein was anastomosed to the proximal stump of the GSV (end-to-end). The flap and residual foot survived completely, at a one-year follow-up postoperatively. An indocyanine green bypass-through angiography revealed the angiosome through the venous arterialization bypass graft, which included the flap; entire forefoot; and partial regions of the midfoot and heel. This two-stage operation might be considered a useful option for limb-salvage and complete wound-healing in patients with severe non-healing wound with CLTI. The two methods could compensate and overcome the problems of either method: incomplete wound-healing after venous arterialization, and the absence of a recipient artery for free flap transfer.

Injury Precipitating Tissue Loss and Time to Referral to a Vascular Center in Patients with Chronic Limb-Threatening Ischemia.

AIM: This study aimed to report injury precipitating tissue loss and to provide updated information on the time from tissue loss occurrence to referral to a vascular center for patients who developed chronic limb-threatening ischemia (CLTI) in Japan. METHODS: We examined 450 patients who developed CLTI with tissue loss and were registered in a multicenter prospective study between October 2017 and June 2020. They were referred to the participating vascular centers for revascularization. Information on the injury precipitating tissue loss and time to referral was collected at registration. The severity of tissue loss was evaluated using the Wound, Ischemia, and foot Infection classification. RESULTS: Injury precipitating tissue loss was absent in 52.0% (95% confidence interval, 47.3%-56.6%) of the patients. The absence was associated with lower albumin levels and preserved pressure sensation. Although the time to referral was significantly shorter in cases without a history of prereferral revascularization, 16.8% (12.8%-20.7%) of the patients were referred to the vascular centers more than 3 months after tissue loss occurrence. Time to referral, but not the lack of a clear precipitant for tissue loss, was significantly associated with the severity of tissue loss. CONCLUSION: A clear precipitant for tissue loss was often lacking, particularly in patients with low albumin levels and preserved pressure sensation. Delayed referral to a vascular center is still common.

Evidence of nutritional vascular formation from the "nutrient flap" in a patient with no-option chronic limb-threatening ischemia: An indocyanine green fluorescence imaging study.

The concept of a "nutrient flap," in which ischemic tissue is nourished by a transferred well-perfused flap, has been advocated for use since the early days of free flap procedures. Several studies have reported cases of no-option chronic limb-threatening ischemia salvaged by nutrient free flap transfer. However, it has been difficult to prove the actual dynamic flow and nutritional vascular formation. Thus, the existence of a nutrient flap has remained unproved. In the present report, we have described the case of free flap transfer for a patient with no-option chronic limb-threatening ischemia in whom we detected evidence of a nutrient flap using indocyanine green fluorescence imaging.

Effectiveness of negative pressure wound therapy for the wound of ileostomy closure: a multicenter, phase II randomized controlled trial.

BACKGROUND: The American Society of Surgery and American Society for Surgical Infections issued guidelines for surgical site infections (SSIs) in December 2016. These guidelines recommend a purse-string suture (PSS) for stoma closure as it facilitates granulation and enables open wound drainage. This study investigated the effect of using negative pressure wound therapy (NPWT) along with standard PSS and aimed to determine the optimal period of NPWT use. METHODS: The patients were divided into three groups as follows: Group A, postoperative wound management alone with gauze exchange as the representative of conventional PSS; Group B, the performed management was similar to that of Group A plus NPWT for 1 week; and Group C, the performed management was similar to that of Group A plus NPWT for 2 weeks. Regarding objective measures, the wound reduction rate was the primary outcome, and the incidence of SSIs, length of hospital stay, and wound healing duration were the secondary outcomes. RESULTS: In total, 30 patients (male: 18, female: 12) were enrolled. The average age was 63 (range: 43-84) years. The wound reduction rate was significantly higher in Group B than in Group A on postoperative days (PODs) 7 (66.1 vs. 48.4%, p = 0.049) and 10 (78.6 vs. 58.2%, p = 0.011), whereas no significant difference was observed on POD 14. Compared with Group A, Group C (POD 7: 65.9%, POD 10: 69.2%) showed an increase in the wound reduction rate on POD 7, although the difference was not significant (p = 0.075). SSIs were observed in Groups B (n = 2) and C (n = 2) (20%) but not in Group A (0%). CONCLUSIONS: The most effective duration of NPWT use for ileostomy closure with PSS in terms of the maximum wound reduction rate was from PODs 3 to 10. However, NPWT did not shorten the wound healing duration. NPWT may reduce the wound size but should be used with precautions for SSIs. The small sample size (30 cases), the use of only one type of NPWT system, and the fact that wound assessment was subjective and not blinded were the limitations of this study. Further studies are needed to confirm our findings. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000032174 (10/04/2018).

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.

Challenges and Management in Wound Care.

SUMMARY: Wounds have been one of the most prominent pathologies since the beginning of humanity. For the last 5 decades, a drastic improvement of healing has been observed, thanks to new medical devices based on fluid aspiration capacities and the development of negative pressure wound therapy. Negative-pressure wound therapy was initially designed for a double action, fluid aspiration and mechanical stimulation of wound edges by a foam. Successive technical evolutions of negative pressure wound therapy were declined since 1997 when Argenta and Morykwas first presented their solution. The adjunct of instillation in 2009 was considered as the first interactive dressing, allowing topical wound solutions to sequentially reach the wound, in alternance with negative pressure. Other devices based on the same principle were designed to prevent postoperative infections when placed over a suture after surgery. This long evolution could enhance the armamentarium of possible solutions, considerably reducing the wound healing time.

An international consensus on device-related pressure ulcers: SECURE prevention.

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com.

High body mass index is a strong predictor of intraoperative acquired pressure injury in spinal surgery patients when prophylactic film dressings are applied: A retrospective analysis prior to the BOSS Trial.

We reported the efficacy of soft silicone multilayered foam dressings in preventing intraoperatively acquired pressure injuries (IAPIs) in the prone position using a Relton-Hall frame (BOSS trial). The aim of this study was to clarify the incidence and extract the risk factors for IAPIs in cases in which polyurethane film dressing was used against IAPIs before the BOSS trial period. This study conducted as a retrospective dual-center cohort study between August 2014 and Jun 2015 using the medical records in the operating room. The incidence of IAPIs that developed within 24 hours after surgery was 7.1% (7/99). The multivariate logistic regression analysis revealed that body mass index (BMI) (P = .0016, odds ratio [OR]: 1.22, 95% confidence interval (CI) 1.08-1.4) and length of surgery (P < .0001, OR 2.47, 95% CI 1.86-3.51) were independently associated with the development of IAPIs. Since high BMI was not extracted in BOSS trial, we conclude that the application of soft silicone multilayer foam dressings is important for preventing the development of IAPIs in patients with high BMI values.

Negative pressure wound therapy with instillation: International consensus guidelines update.

The use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) has gained wider adoption and interest due in part to the increasing complexity of wounds and patient conditions. Best practices for the use of NPWTi-d have shifted in recent years based on a growing body of evidence and expanded worldwide experience with the technology. To better guide the use of NPWTi-d with all dressing and setting configurations, as well as solutions, there is a need to publish updated international consensus guidelines, which were last produced over 6 years ago. An international, multidisciplinary expert panel of clinicians was convened on 22 to 23 February 2019, to assist in developing current recommendations for best practices of the use of NPWTi-d. Principal aims of the meeting were to update recommendations based on panel members' experience and published results regarding topics such as appropriate application settings, topical wound solution selection, and wound and patient characteristics for the use of NPWTi-d with various dressing types. The final consensus recommendations were derived based on greater than 80% agreement among the panellists. The guidelines in this publication represent further refinement of the recommended parameters originally established for the use of NPWTi-d. The authors thank Karen Beach and Ricardo Martinez for their assistance with manuscript preparation.

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.

Branched xenopericardial roll graft replacement of an infected aortic arch graft.

Which graft material is the optimal graft material for the treatment of aortic graft infections is still a matter of controversy. We used a branched xenopericardial roll graft to replace an infected aortic arch graft as a "rescue" operation. The patient is alive and well 37 months postoperatively without recurrence of the infection and any surgical complication. This procedure may have the possibility to serve as an option for the treatment of aortic arch graft infection.

Design Strategies for Global Clinical Trials of Endovascular Devices for Critical Limb Ischemia (CLI)　- A Joint USA-Japanese Perspective.

For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort by members from academia, industry and regulators from the United States of America (USA) and Japan, has been working to increase timely regulatory approval for cardiovascular devices through the development of practical global clinical trial paradigms. Consistent with this mission and in recognition of the increasing global public health effects of critical limb ischemia (CLI), academic and government experts from the USA and Japan have developed a basic framework of global clinical trials for endovascular devices for CLI. Despite differences in medical and regulatory environments and complex patient populations in both countries, we developed a pathway for the effective design and conduct of global CLI device studies by utilizing common study design elements such as patients' characteristics and study endpoints, and minimizing the effect of important clinical differences. Some of the key recommendations for conducting global CLI device studies are: including patients on dialysis; using a composite primary endpoint for effectiveness that includes 6-month post-procedure therapeutic success and target vessel patency; and using a 30-day primary safety endpoint of perioperative death and major adverse limb events. The proposed approach will be uniquely beneficial in facilitating both the initiation and interpretation of CLI studies and accelerating worldwide CLI device development and innovation.