Ischemic Foot Research Articles

ICAM1 expression by the microvasculature impairs capillary perfusion which compromises hind limb ischemia recovery in diabetic mice

Chronic limb threatening ischemia (CLTI), which is one of the major complications of diabetes, is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. However, the pathophysiology of this disease is poorly understood and therapeutic targets are missing. Our objective is to explore the contribution of endothelial dysfunction in the development of CLTI in diabetic mice. Hind limb ischemia (HLI) was induced by ligation and resection of the femoral artery in C57BL6/J male mice, in which insulin resistance was induced by a high fat diet, and hyperglycaemia was induced one month later by low dose streptozotocin administrations. According to our previous investigations, ischemic foot re-perfusion, assessed via laser doppler perfusion imaging, was significantly reduced in diabetic animal 28 days after HLI surgery was performed (ratio blood flow in the ischemic leg vs non ischemic leg = 0.27 ± 0.09 vs 0.44 ± 0.21 in control mice; P = 0.03), even though angiogenesis was identical in both groups. On the contrary, we found that impaired ischemic foot re-perfusion was associated with an increased endothelial cell activation attested by an increased ICAM1 expression (P < 0.0001). We then hypothesized that ICAM1, by interacting with white blood cells (WBC), may compromise the perfusion of capillaries with a diameter smaller than a WBC. Accordingly, we found that WBC circulation velocity in the microvasculature was significantly diminished in diabetic mice (533 ± 169 μm/s vs 960 ± 188 in control mice; P = 0.004) and associated with a decreased percentage of capillaries perfusion by BS-1 lectin (78.5 ± 10.5% vs 96.1 ± 5.7 in control mice; P = 0.03). With the aim to test whether ICAM1 overexpression may be responsible for impaired ischemic foot re-perfusion, diabetic mice were administered with anti-ICAM1 antibodies or isotype control for 14 days, starting 14 days after HLI surgery was performed. We found that anti-ICAM1 therapy significantly increased WBC circulation velocity within the microvasculature (779 ± 113 μm/s vs 447 ± 107 in mice treated with isotype control; P < 0.0001) and the percentage of perfused capillary (P = 0.009). Altogether, our results demonstrate that ICAM1 overexpression may compromise hind limb ischemia recovery in diabetic mice by decreasing WBC circulation velocity and impairing capillary perfusion.

Foot Dorsal and Plantar Flexion to Enhance Crossing of Tortuous Highly-Calcific Ankle Vessels During Lower Limb Revascularization Procedures: A Technical Note.

To describe a crossing technique of stenotic/occluded and tortuous highly calcific ankle vessels during complex percutaneous limb salvage intervention in diabetic patients with ischaemic foot ulcers (Rutherford 5 and 6). We propose a simple technique to achieve "straightening" of the tortuous vessel and allow safe devices passage into the foot arteries, Patients were asked to hold their foot in plantar or dorsal flexion, accordingly to the treated artery. If unable to do so, an equipe member executed the manoeuvre on their behalf. The technique was applied in 148 cases, with a success rate of 81% (120/148). No complications related to the manoeuvre were observed. Crossing of tortuous distal crural vessels can be challenging in diabetic patients; in our experience, this technique can be auseful tool to obtain a successful recanalization in complex procedures with high risk of failure.

Clinical Pharmacology of Gentamicin

Gentamicin is an important agent for the treatment of many serious gram-negative bacillary infections. Gentamicin is the aminoglycoside of first-choice because the reliable activity against all but the most resistant gram-negative aerobes. Gentamicin preparations are available for parenteral, ophthalmic, and topical administration. The recommended intramuscular or intravenous dose of gentamicin sulphate for treatment of gram-negative organisms in adults with normal renal function is 5 to 7 mg/kg daily. For patients with renal dysfunction the interval between may be extended. The efficacy and safety of gentamicin have been reported but gentamicin may induce nephrotoxicity and/or ototoxicity in some patients. Gentamicin penetrates in significant amounts into bone, skeletal muscle, wound tissue, ischemic foot ulcers, and in subcutaneous tissue. The pharmacokinetics of gentamicin have been studied in febrile neutropenic adult patients and in healthy adult subjects and gentamicin elimination half-life is about 3 hours. The pharmacokinetics of gentamicin have been investigated in tetraplegic and in paraplegic adult patients and in healthy adult subjects and the elimination half-life of gentamicin is about 2 hours. The prophylaxis, treatment, and trials with gentamicin have been extensively reported. Gentamicin penetrates into the cerebrospinal fluid in significant amounts and treats bacterial meningitis in infants. Gentamicin is poorly transferred across the human placenta and poorly migrates into the breast-milk. The aim of this study is to review gentamicin efficacy and safety, toxicity, diffusion into body-tissues, pharmacokinetics, prophylaxis, treatment, trials, penetration into the cerebrospinal fluid, treatment of bacterial meningitis, transfer across the human placenta, and migration into the breast-milk.

Timing of Revascularization and Parenteral Antibiotic Treatment Associated with Therapeutic Failures in Ischemic Diabetic Foot Infections.

For ischemic diabetic foot infections (DFIs), revascularization ideally occurs before surgery, while a parenteral antibiotic treatment could be more efficacious than oral agents. In our tertiary center, we investigated the effects of the sequence between revascularization and surgery (emphasizing the perioperative period of 2 weeks before and after surgery), and the influence of administering parenteral antibiotic therapy on the outcomes of DFIs. Among 838 ischemic DFIs with moderate-to-severe symptomatic peripheral arterial disease, we revascularized 608 (72%; 562 angioplasties, 62 vascular surgeries) and surgically debrided all. The median length of postsurgical antibiotic therapy was 21 days (given parenterally for the initial 7 days). The median time delay between revascularization and debridement surgery was 7 days. During the long-term follow-up, treatment failed and required reoperation in 182 DFI episodes (30%). By multivariate Cox regression analyses, neither a delay between surgery and angioplasty (hazard ratio 1.0, 95% confidence interval 1.0-1.0), nor the postsurgical sequence of angioplasty (HR 0.9, 95% CI 0.5-1.8), nor long-duration parenteral antibiotic therapy (HR 1.0, 95% CI 0.9-1.1) prevented failures. Our results might indicate the feasibility of a more practical approach to ischemic DFIs in terms of timing of vascularization and more oral antibiotic use.

Transcatheter Arterialization of Deep Veins in Chronic Limb-Threatening Ischemia

BackgroundApproximately 20% of patients with chronic limb-threatening ischemia have no revascularization options, leading to above-ankle amputation. Transcatheter arterialization of the deep veins is a percutaneous approach that creates an artery-to-vein connection for delivery of oxygenated blood by means of the venous system to the ischemic foot to prevent amputation.MethodsWe conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure.ResultsWe enrolled 105 patients who had chronic limb-threatening ischemia and were of a median age of 70 years (interquartile range, 38 to 89). Of the patients enrolled, 33 (31.4%) were women and 45 (42.8%) were Black, Hispanic, or Latino. Transcatheter arterialization of the deep veins was performed successfully in 104 patients (99.0%). At 6 months, 66.1% of the patients had amputation-free survival. According to Bayesian analysis, the posterior probability that amputation-free survival at 6 months exceeded a performance goal of 54% was 0.993, which exceeded the prespecified threshold of 0.977. Limb salvage (avoidance of above-ankle amputation) was attained in 67 patients (76.0% by Kaplan–Meier analysis). Wounds were completely healed in 16 of 63 patients (25%) and were in the process of healing in 32 of 63 patients (51%). No unanticipated device-related adverse events were reported.ConclusionsWe found that transcatheter arterialization of the deep veins was safe and could be performed successfully in patients with chronic limb-threatening ischemia and no conventional surgical or endovascular revascularization treatment options. (Funded by LimFlow; PROMISE II study ClinicalTrials.gov number, NCT03970538.)

The Effectiveness of a Medical Cocktail Therapy for Nonhealing Refractory Ischemic Diabetic Foot Ulcers

Abstract Diabetic foot ulcers are a serious complication of diabetes mellitus. Healing of ischemic or neuroischemic foot ulcers is most challenging as conventional therapies often fail to achieve adequate vascularity. Heel ulcers can be very severe and strenuous to treat and can eventually lead to amputation of the limb due to poor vascularity. Optimizing therapies to improve vascularity should, therefore, be a major goal in treating such cases. Here, we report two cases of chronic nonhealing ischemic ulcers of the heel. Patients approached us after conventional medical treatments failed to achieve healing. We treated them with a cocktail (Diabcare protocol) that we formulated using existing medications along with appropriate wound care and antibiotics. Diabcare protocol comprises rosuvastatin, aspirin, rivaroxaban, cilostazol, tadalafil, and zinc sulfate. Serial measurements of ulcers revealed progressive healing and wound contraction. Vascularity improved significantly, and fresh granulation appeared within days to weeks of initiation of therapy. Ulcers healed completely, with spontaneous epithelialization in the first case and after a split skin graft (SSG) in the second case, within a mean period of 3 months.

Single crural artery angioplasty in healing of ischemic diabetic foot ulcers: a cohort study

Single crural artery angioplasty in healing of ischemic diabetic foot ulcers: a cohort study

Characteristics of Neuropathic, Ischaemic and Neuroischaemic Diabetic Foot Ulcers- A Prospective Cohort Study

Introduction: Diabetic Foot Ulcers (DFU) can be divided into neuropathic, ischaemic and neuroischaemic types. Since the pathophysiology is different, it is important to ascertain the outcome data on the three subgroups of DFU. Aim: To compare and assess the differences in the characteristics and healing process of the three types (Neuropathic, Ischaemic, and Neuroischaemic) of DFU. Materials and Methods: A prospective cohort study was conducted from April 2019 to July 2021 in the Department of Surgery, Regional Institute of Medical Sciences (RIMS) Hospital, Imphal, Manipur, India. Age, gender, duration of diabetes mellitus, smoking, hypertension, glycosylated haemoglobin, aetiology of DFU, osteomyelitis, gangrene, estimated Glomerular Filtration Rate (eGFR), and presence of multiple ulcer were recorded. Healing time and outcome (healed, non healed and amputation) of ulcer were the dependent variable. Data collected were analysed using SPSS-version-21. Fisher’s-exact test was used for proportions. Analysis of the time needed for healing was performed using the Kaplan-Meier method. A p-value of &lt;0.05 was taken as significant. Results: A total of 42 patients were recruited for the study and 29 (69%) were males. Patients in neuropathic, ischaemic and neuroischaemic DFUs were 18,14 and 10, respectively. Hypertension (100%) and smoking history (100%) were present in the ischaemic group. Maximum healing (88.9%) was seen in patient with neuropathic ulcers and maximum non healing (28.6%) and amputation (21.4%) occurred in ischaemic group. Mean (SD) heal time in days were 165.5 (4.62), 141.1 (9.17) and 86.4 (8.02) for ischaemic, neuroischaemic and neuropathic respectively (p&lt;0.001). The average time in which 50% of patients (median) had healed wounds was 75, 136, and 171 days for neuropathic, ischaemic, and neuroischaemic ulcers, respectively. Conclusion: Neuropathic DFU has better healing than the other DFUs. Ischaemic DFU have maximum non heal ulcers and amputation.

The use of innovative targeted angiogenic therapies for ischemic diabetic foot ulcer repair: From nanomedicine and microRNAs toward hyperbaric oxygen therapy.

Diabetes mellitus is a metabolic disease that has a high prevalence worldwide and is characterized by chronic hyperglycemia leading to the development of vascular or nonvascular complications. It is these complications that result in huge mortality rates in patients with diabetes, especially vascular ones. This work focuses on diabetic foot ulcers (DFUs), which are one of the most common complications of type 2 diabetes mellitus (T2DM) and cause significant morbidity, mortality, and healthcare costs. The healing of DFUs is hindered by deregulation of nearly all phases of this process because of the hyperglycemic environment. Although therapies currently exist to treat a patient with DFU, they are proving inadequate. In the present work, angiogenesis is highlighted as part of the proliferative phase, which, when diminished, plays an important role in the impaired healing of DFU and other chronic wounds. Therefore, the search for new therapeutic strategies targeting angiogenesis is of great interest. In this study, we provide an overview of molecular targets with therapeutic potential and therapies that act on angiogenesis. To this end, a search of articles in PubMed and Scopus databases from 2018 to 2021 was performed to review angiogenesis as a therapeutic target for DFU. Growth factors, microRNAs, and signaling pathways were investigated as molecular targets, and negative pressure, hyperbaric oxygen therapy, and the use of nanomedicine were explored as therapies.

Effect of Percutaneous Endovascular Angioplasty Combined with Negative Pressure Drainage on the “One-Stop” Treatment of Ischemic Diabetic Foot Ulcer

To explore the therapeutic effect, safety, and economic benefit of a "one-stop" diagnosis and treatment mode of vascular surgery for ischemic diabetic foot (DF) ulcer and to analyze the associated and independent factors that affect ulcer healing. In a prospective, single-center study, patients with ischemic DF ulcers from January 2017 to July 2021 were treated with either percutaneous endovascular angioplasty combined with negative pressure closed drainage (PTA-VSD) or percutaneous endovascular angioplasty combined with depuration (PTA-UD). The effectiveness and economic benefits of the 2 measures were compared, and independent factors affecting ulcer healing were explored via univariate and logistic regression analyses. Fifty patients with ischemic DF ulcer (25 patients in the PTA-VSD group and 25 patients in the PTA-UD group; 40 males and 10 females) were included, with an average age of 67.74±10.71years. No difference was observed in the demographic data. The findings showed that the ulcer healing time in the PTA-VSD group was significantly shorter than that in the PTA-UD group (154.79 vs. 238.31days), and the ulcer healing rate at 180days post surgery was significantly greater in the PTA-VSD group (52% vs. 12%) (P=0.002, < 0.05). The ulcer score in the PTA-VSD group decreased significantly at 3, 6, and 12months post surgery. The duration of hospitalization in the PTA-VSD group was greater (P=0.002, <0.05), but no significant difference in hospitalization frequency and cost was observed between the 2 groups. During follow-up, there was 1 death and 1 amputation in the PTA-UD group, but no death or amputation in the PTA-VSD group. Arterial occlusion was primarily located in the femoral-popliteal artery and the inferior knee artery in the 2 groups, and PTA intervention effectively opened the outflow tract of the affected limb. Two to three outflow tracts were opened in 41 patients. The ankle-brachial index (ABI) after surgery was significantly higher in both groups than before. Univariate and multivariate logistic regression analyses revealed that the Wagner grade and number of outflow channels and therapies (PTA-VSD) could be independent factors affecting ulcer healing. The severity of DF ulcers is an important factor affecting the quality of life of patients. A multidisciplinary "one-stop" treatment strategy based on percutaneous endovascular angioplasty combined with negative pressure-sealing drainage can rapidly and effectively restore the blood flow to the affected limb and promote ulcer healing without increasing medical costs.

Maybe we are overdoing revascularization.

The goal of value-based health care conflicts with current volume-based reimbursement models. Value-based care hinges upon the ability to define appropriate use for a given procedure/intervention. Understanding appropriateness of revascularization requires comparisons of outcomes with best medical therapy. With respect to chronic limb-threatening ischemia (CLTI), this also includes optimal wound care, offloading, and infection control. Among the subset of patients with mild ischemia (Wound Ischemia foot Infection [WIfI] grade 1 and 2 ischemia), recent recommendations1 from the Society of Vascular Surgery state that revascularization may be of little benefit and recommend optimizing wound care, offloading, and infection control before considerations of revascularization.

Praliciguat Promotes Ischemic Leg Reperfusion in Leptin Receptor-Deficient Mice.

Lower-limb peripheral artery disease is one of the major complications of diabetes. Peripheral artery disease is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. Despite major medical advances in the treatment of diabetes, a substantial therapeutic gap remains in the peripheral artery disease population. Praliciguat is an orally available sGC (soluble guanylate cyclase) stimulator that has been reported both preclinically and in early stage clinical trials to have favorable effects in metabolic and hemodynamic outcomes, suggesting that it may have a potential beneficial effect in peripheral artery disease. We evaluated the effect of praliciguat on hind limb ischemia recovery in a mouse model of type 2 diabetes. Hind limb ischemia was induced in leptin receptor-deficient (Leprdb/db) mice by ligation and excision of the left femoral artery. Praliciguat (10 mg/kg/day) was administered in the diet starting 3 days before surgery. Twenty-eight days after surgery, ischemic foot perfusion and function parameters were better in praliciguat-treated mice than in vehicle controls. Improved ischemic foot perfusion was not associated with either improved traditional cardiovascular risk factors (ie, weight, glycemia) or increased angiogenesis. However, treatment with praliciguat significantly increased arteriole diameter, decreased ICAM1 (intercellular adhesion molecule 1) expression, and prevented the accumulation of oxidative proangiogenic and proinflammatory muscle fibers. While investigating the mechanism underlying the beneficial effects of praliciguat therapy, we found that praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression in cultured myoblasts and that conditioned medium form praliciguat-treated myoblast decreased ICAM1 mRNA expression in endothelial cells. These results suggest that praliciguat therapy may decrease ICAM1 expression in endothelial cells by downregulating Cxcl12 in myocytes. Our results demonstrated that praliciguat promotes blood flow recovery in the ischemic muscle of mice with type 2 diabetes, at least in part by increasing arteriole diameter and by downregulating ICAM1 expression.

Use of Recanalized Vessels for Diabetic Foot Reconstruction: Pushing the Boundaries of Reconstruction in a Vasculopathic Lower Extremity.

Free flap after lower extremity revascularization may enable limb salvage in defects after critical limb ischemia. This study examined the outcomes of reconstruction of ischemic diabetic foot according to the severity of the vessel occlusion and assessed whether recanalized vessels may serve as a reliable recipient vessel. A total of 62 patients who underwent diabetic foot reconstruction with free flaps after successful percutaneous transluminal angioplasty (PTA) from February of 2010 to February of 2016 were identified and divided into three groups: group 1, nonoccluded vessels as recipient ( n = 11); group 2, recanalized artery after PTA for partially occluded artery ( n = 30); and group 3, recanalized artery after PTA for completely occluded artery ( n = 21). Flap survival was statistically higher in group 2 (90%) compared with group 3 (67%) ( P < 0.05). Subsequent major amputation was significantly lower in groups 1 and 2 [0/7 and 1/30 (3.3%)] compared with group 3 [5/21 (23.8%)] ( P < 0.05). The patient survival and limb salvage rate was 90.9% at 1 and 3 years in group 1, 89.8% at 1 year and 86.3% at 3 and 5 years in group 2, and 76.2% at 1, 3, and 5 years in group 3. This difference was not statistically significant ( P = 0.485). The use of recanalized vessels after PTA can be safe for partially occluded arteries but requires caution for completely occluded arteries. Using completely occluded vessels after PTA can be attempted when other options are not available and achieves a 76% chance of limb salvage. Therapeutic, III.

Minimally Invasive Procedure Vs Standard Open Approach For Lumbar Sympathectomy

Aim: Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis. Thepresent study was conducted for comparing the efficacy of minimally invasive procedure vs standard open approach for lumbarsympathectomy.Materials &amp; methods: 100 patients were enrolled in the present study (who were scheduled to undergo lumbar sympathectomy) andwere divided broadly and randomly into two study groups: Group 1: Patients undergoing lumbar sympathectomy by minimal invasiveprocedure, and Group 2: Patients undergoing lumbar sympathectomy through standard open approach. Only those patients wereincluded who had Ischemic rest pain that requires continuous analgesia for more than 3 weeks and Ischemic foot ulcers that failed toheal for more than 6 weeks. All the patients underwent surgical procedures according to their respective study groups. All the resultswere recorded in Microsoft excel sheet and were analysed using SPSS software.Results: Mean duration of analgesic consumption for controlling pain postoperatively was 3.9 weeks in group 1 while it was 3.7weeks in group 2. Mean operative time among the patients of group 1 and group 2 was 51 minutes and 83 minutes respectively (pvalue &lt; 0.05). Incidence of complications was significantly higher among the patients of group 2 in comparison to the patients ofgroup 1. Mean recovery time among the patients of group 1 and group 2 was 5.2 days and 7.3 days respectively (p- value &lt; 0.05).Conclusion: Among patients undergoing lumbar sympathectomy, minimally invasive procedure is better in comparison to standardopen procedure.

Effect of new oral anticoagulants on microcirculation in ischemic diabetic foot ulcer

Background and aim Diabetic patients with foot ulcer and peripheral ischemia were shown to be associated with hypercoagulation and dysfunction in the fibrinolytic system that in turn would affect the healing of the ulcer. The authors aimed to investigate the role of rivaroxaban in improving the microcirculation of the skin and peripheral tissues and how it can improve ischemic diabetic foot ulcers. Patient and methods The authors conducted an observational retrospective case–control study at Al-Azhar University Hospital, New Damietta, from January 2015 till December 2020. Diabetic patients with foot ulcer and peripheral limb ischemia who received rivaroxaban till ulcer healing were considered as the case group, whereas patients who did not receive rivaroxaban were considered as the control group. Clinical assessment and pulse oximeter were used for the assessment of transcutaneous microcirculation. Results Throughout the 5 years of the study, 172 patients were included; the case group included 87 patients and the control group included 85 patients. There was a significant difference between the two groups regarding the improvement of limb ischemia, tissue plasminogen activator antigen, and transcutaneous microcirculation (P&lt;0.05). Before the treatment, there was a significant correlation between both permeability coefficient and plasma fibrinogen and transcutaneous microcirculation. Conclusion The oxygenation of the ulcer and the microcirculation were found to be improved in the case group and accelerate wound healing in the ischemic diabetic foot.

Analyzing Risk Factor for Wound Healing after Delayed Primary Closure of Diabetic Foot

Category: Diabetes; Other Introduction/Purpose: Part of hospitalized diabetic foot disease patients with infectious necrosis develop wound dehiscence after delayed primary closure for improved wound status without erythema and induration following appropriate wound management, amputation, and vascular intervention. Dehisced wound could be the source of reinfection, further admission, financial burden. We aimed to analyze predictors for failure of wound management. Methods: We retrospectively reviewed medical records and find 105 patients with delayed primary closure among 403 ischemic and/or infectious diabetic foot admitted cases from 2013 to 2021. Vascular intervention was performed for patient with ankle brachial index (ABI) less than 0.8. Total stitches were removed two to three weeks after delayed primary closure. Wound dehiscence was decided when it was developed within two weeks. Eighty-two cases (78.1%) with wound healing were designated as group I, and twenty-three cases (21.9%) with dehiscence were designated as group II. Two groups were compared for various demographic, laboratory and physical state. Then, multivariate logistic regression analysis was done to find predictors for failure of wound management. Results: In univariate analysis between two groups, smoking, wound site, initial C-reactive protein (CRP), White blood cell count (WBC), albumin (initial and adjacent to closure) and sequential negative culture result between two groups among 22 potential risk factors. In multivariate logistic regression analysis performed with variables showing p &lt;0.05 during univariate comparison, there was no significant predictor. Conclusion: The wound healing ratio for delayed primary closure reached to 78.1% in patients with improved wound status and ABI more than 0.8 in ischemic and/or infectious diabetic foot disease irrelevant to specific factors.

Free Flap Salvage in the Ischemic Foot: A Case Report.

We performed distal bypass and free flap transfer in a single-stage operation to repair an extensive soft tissue defect in an ischemic foot of an 84-year-old woman. The nutrient artery of the free flap was anastomosed to the bypass graft in an end-to-side manner. Subsequently, the bypass graft became occluded on several occasions. Although intravascular and surgical interventions were performed each time, the bypass graft eventually became completely occluded. However, despite late occlusion of the nutrient artery, the free flap has remained viable and the patient is ambulatory. The time required for a transplanted free flap to become completely viable without a nutrient artery is likely longer for an ischemic foot compared with a healthy foot. However, the exact period of time required is not known. A period of month was required in our patient. We report this case to help clarify the process by which a free flap becomes viable when applied to an ischemic foot.

A Comparative Study of Xi's Tendon Gangrene (Nonischemic Type of Diabetic Foot) and Gangrene (Diabetic Foot Ischemic Type).

Background Diabetic foot gangrene refers to a lesion in which the tissue of the foot or lower extremities of diabetic patients is damaged, and the cause is the infection of peripheral blood vessels and neuropathy caused by diabetes. Objective To compare the related indexes of blood glucose, inflammation, blood viscosity, and peripheral neuropathy between the nonischemic diabetic foot and ischemic diabetic foot, the same and different characteristics of the two different types of diabetic foot in pathogenesis were discussed and studied. Methods A total of 122 patients with diabetic foot were selected from the Department of Vascular Medicine, Shanghai Hospital of Integrated Traditional Chinese and Western Medicine, including 61 cases of ischemic type and 61 cases of nonischemic type. The differences in blood glucose, inflammation, blood supply, and peripheral neuropathy between the nonischemic diabetic foot and ischemic diabetic foot were compared to explore their different characteristics. Results The blood glucose index, inflammatory index, and plasma fibrinogen in patients with nonischemic diabetic foot were significantly higher than those in patients with ischemic diabetic foot (P < 0.05). The patients with ischemic diabetic foot were higher in age and blood lipid index than those with the nonischemic diabetic foot (P < 0.05), while having no significant difference in platelet count, plasma viscosity, hematocrit, and end products of glycation (AGEs). Conclusion The nonischemic diabetic foot is mainly infective necrosis, and the ischemic type is ischemic necrosis. The former occurs in the middle-aged and elderly with good blood supply between 40 and 60 years old, while the latter occurs in the elderly with the severe vascular disease over 60 years old. The blood glucose level of nonischemic patients is significantly higher than that of ischemic patients, but it has little to do with the course of diabetes.

Evaluation of Infrapopliteal Revascularization for Ischemic Diabetic Foot in Hemodialysis Patients

Objective: To evaluate the outcomes of infrapopliteal revascularization for diabetic hemodialysis patients with ischemic diabetic foot. Methods: From 2017 to 2021, 250 patients with diabetic foot identified as stage C (ischemia) or D (ischemia and infection) of Texas Wound Classification underwent successful infrapopliteal surgical and endovascular revascularization at the vascular surgery department of Moulay Ismail Military Hospital in Meknes. The outcomes were retrospectively compared in hemodialyzed patients (HD group: 48 patients), and not hemodialyzed patients (not HD group: 202 patients) during the same period. Results: Outcomes were expressed as healing, major amputation, revascularization patency and mortality rate. Hemodialysis was a negative predictor of healing and a positive predictor of major amputation. Outcomes for HD and not HD groups were respectively: healing (62.5 vs 82 %), major amputation (37.5 vs 18 %). There was no significant difference in revascularization primary patency between the two groups (70 vs 73.6%). The mortality rate was higher in the HD group than in the not HD group (21 vs 10%). Conclusions: Our study shows that ischemic diabetic foot associated with hemodialysis have a bad prognosis with a higher risk of major amputation and death. Infrapopliteal revascularization with infection control should be performed to enhance the rate of limb salvage in this risk group.

Soluble guanylate cyclase stimulator praliciguat promotes ischemic leg reperfusion in db/db mice

Lower-limb peripheral artery disease (PAD) is a prevalent and challenging complication of diabetes, requiring innovating therapies. Praliciguat is an orally available stimulator of soluble guanylate cyclase (sGC) reported to have favorable effects on metabolic and hemodynamic endpoints in preclinical and clinical studies, suggesting the potential for benefit in PAD. We evaluated the effect of praliciguat on hindlimb ischemia recovery in a mouse model of diabetes and investigated the molecular mechanism of sGC stimulation. Hindlimb ischemia was induced in db/db mice by ligation and excision of the left femoral artery. Praliciguat 10 mg/kg/day ( n = 10 mice) or vehicle ( n = 10) were administered in the diet for 31 days starting 3 days before surgery. Foot perfusion was assessed with a Laser Doppler Imager and reported as a ratio in the ischemic versus non-ischemic limb. Ischemic leg function was assessed with a 4-point scale: 0, plantar/toe flexion in response to tail traction; 1, plantar but not toe flexion; 2, no flexion; 3, foot dragging. Ischemic foot perfusion and function were better 28 days after surgery in praliciguat than in vehicle treated mice (mean ± SD: perfusion 1.05 ± 0.23 vs. 0.38 ± 0.16; P < 0.0001; function 1.14 ± 0.36 vs. 1.73 ± 0.80; P = 0.03). Praliciguat did not impact angiogenesis. Arteriolar diameter was higher (9.88 ± 0.96 vs. 8.57 ± 0.64 μm; P = 0.004) and ICAM-1 expression lower (186 ± 41 vs. 403 ± 177% of healthy muscle; P = 0.005) in the ischemic limb of mice treated with praliciguat than with vehicle. Praliciguat attenuated accumulation of oxidative pro-angiogenic and pro-inflammatory muscle fibers. In cultured myoblasts praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression. Conditioned medium from praliciguat-treated myoblast decreased ICAM-1 mRNA expression in HUVECs. These results suggest that praliciguat restored perfusion and function in the ischemic muscle of db/db mice by increasing arteriolar diameter and decreasing ICAM-1 expression in endothelial cells via downregulation of Cxcl12 in myocytes.