Diabetic Limb Research Articles

The Value of Using a Dedicated Vascular Lab in Managing and Treating Diabetic Critical Limb Ischemia Patients Test 0.5 CME

The Value of Using a Dedicated Vascular Lab in Managing and Treating Diabetic Critical Limb Ischemia Patients Test 0.5 CME

602-P: The Use of Thermography for Studying Diabetic Foot Complication through the Alteration of Thermoregulation Mechanism

The aim of the present study was to characterize thermoregulatory mechanism in the feet depending on the lower limb diabetes complication (i.e., diabetic foot neuropathy, peripheral arterial disease or both) using a thermal camera. A transversal study was conducted to analyse the effect of diabetes complication on thermoregulation mechanism. This study was approved by the Hospital of Lapeyronie (Montpellier, France, clinical trials NCT03872089). 51 participants were enrolled, among these participants 8 were subjects without diabetes and 43 were subjects with diabetes mellitus. Among them, 10 were diagnosed with a peripheral neuropathy (PN), 4 with a peripheral arterial disease (PAD), 8 with both complication (PN-PAD) and 23 without these specific complication (DM). Enrolled participants were placed barefoot in a semi-Fowler’s position in a room at 25°C controlled temperature during 5 min, enabling thermal acclimation. A first 10 min thermal recording of both plantar foot sole was done, acting as baseline, then they were asked to perform the 6-min walking test. It was assumed that thermoregulation activation would occur during exercise or during the hyperaemia phase (post-exercise). Finally, subjects were then recorded for a further 10 min, just after the exercise period. In each case, foot skin temperature oscillations were under interest. Evaluation of results before the 6-minute walk exercise revealed poorer difference, it seems crucial to activate thermoregulation mechanism before any interpretation. Finally, we found that it was possible to distinguish the presence of PN, or PAD, among diabetic subjects. It seems also possible to scale the severity of the complication. In conclusion, alteration of thermoregulatory mechanism amplitude is associated with presence of PN or PAD. Thermal camera may give valuable information to the practitioner, allowing the latter one of having accurate information about the complication, linked to the DF, for each patient. Disclosure V. Serantoni: None. F. Jourdan: None. H. Louche: None. A. Sultan: None. Funding LabEx NUMEV (2011-LABX-076)

All Feet on Deck: The Role of Podiatry During the COVID-19 Pandemic: Preventing Hospitalizations in an Overburdened Health-Care System, Reducing Amputation and Death in People with Diabetes.

The coronavirus disease of 2019 pandemic is driving significant change in the health-care system and disrupting the best practices for diabetic limb preservation, leaving large numbers of patients without care. Patients with diabetes and foot ulcers are at increased risk for infections, hospitalization, amputations, and death. Podiatric care is associated with fewer diabetes-related amputations, emergency room visits, hospitalizations, length-of-stay, and costs. However, podiatrists must mobilize and adopt the new paradigm of shifts away from hospital care to community-based care. Implementing the proposed Pandemic Diabetic Foot Triage System, in-home visits, higher acuity office visits, telemedicine, and remote patient monitoring can help podiatrists manage patients while reducing the coronavirus disease of 2019 risk. The goal of podiatrists during the pandemic is to reduce the burden on the health-care system by keeping diabetic foot and wound patients safe, functional, and at home.

Role of Cilostazol in Rats with Diabetic Lower Limb Ischemia and Its Influences on Changes in Matrix Metallopeptidase-9 and Matrix Metalloproteinase-8

Objective: To assess cilostazol’s effect on rats with diabetic lower limb ischemia. Methods: 36 Sprague-Dawley rats were randomly separated into normal group (n = 12), model group (n = 12) and cilostazol group (n = 12). The model of diabetic lower limb ischemia was prepared and normal saline was intraperitoneally injected postoperatively into model group. Besides, cilostazol was administrated through intraperitoneal injection after establishment of model in cilostazol group. After intervention for 6 weeks, doppler blood flow imager was employed to detect blood flow, and the expressions of MMP-8 and MMP-9 were assessed via immunohistochemistry, western blotting or quantitative polymerase chain reaction (qPCR). TUNEL assay was performed to evaluate cell apop-tosis. Results: Doppler blood flow imager showed that compared with normal group, perfusion unit (PU) index was significantly reduced in the other two groups (P < 0.05) with higher value in cilosta-zol group (P < 0.05). The immunohistochemistry results revealed that in comparison with those in normal group, MMP-8 and MMP-9 positive staining was significantly elevated in the other two groups (P < 0.05) with higher level in cilostazol group than model group. In addition, MMP-8 and MMP-9 expressions were significantly elevated in other two groups (P < 0.05), with higher level in cilostazol group (P < 0.05). Moreover, the vascular wall smooth muscle cells in the other two groups had a significantly elevated apoptosis rate (P < 0.05) with higher apoptosis in cilostazol group (P < 0.05). Conclusion: Cilostazol up-regulates MMP-8 and MMP-9 to increase the apoptosis of vascular wall smooth muscle cells, thereby improving the blood flow in rats with diabetic lower limb ischemia.

Use of home negative pressure wound therapy in peripheral artery disease and diabetic limb salvage.

Use of negative pressure wound therapy (NPWT) in peripheral artery disease (PAD) and diabetic limb salvage (DLS) improves wound healing by providing moist wound conditions, reducing exudate, controlling wound-bed infection, and stimulating granulation. NPWT duration may take several weeks, and home-based NPWT allows patient to recover in the community while minimising risks of prolonged hospitalisation. The aim of this study is to review the use and outcomes of home NPWT in PAD and DLS. The methodology is the retrospective review of patients who were discharged with home NPWT after in-patient PAD revascularisation and DLS debridement or minor amputations. The results included a total of 118 patients who received home NPWT between January 2017 and December 2017. The mean age was 62.8 years with 66% male and 34% female patients. The study population comprised 25% smokers, 98% patients with diabetics, 35% with ischemic heart disease, and 21% with end-stage renal failure (ESRF). Of which, 56% of patients required revascularisation while 31% of patients underwent foot debridement, 48% underwent toe amputations, and 20% underwent forefoot amputations. All patients received in-patient NPWT for a week before being discharged on home NPWT for 4 weeks. Then, 62% received targeted antibiotics regime while 36% received empirical antibiotics on discharge; 60% of patients achieved wound healing on home NPWT, with 9% requiring split-thickness skin graft; 4% required further surgical debridement, 16% required further minor amputation while 20% required major amputation. 9% required further home NPWT extension, with a mean length of 7.1 ± 4.7 weeks' extension. Overall survival of 1 year was 89%. Risk factors that predict the failure of home NPWT includes subjects with a background of ESRF and wet gangrene on presentation. Home NPWT is a useful adjunct in the management of PAD and DLS foot wounds.

Limb Preservation Using Edetate Disodium-based Chelation in Patients with Diabetes and Critical Limb Ischemia: An Open-label Pilot Study.

BackgroundIn 2015, there were 30.3 million patients with diabetes in the US, including 25.2% of people ages 65 or older and 108,000 hospitalizations for non-traumatic amputations. Severe diabetic limb disease includes critical limb ischemia (CLI ) due to an infrapopliteal disease with foot pain and ischemic ulcerations including gangrene. Environmentally acquired toxic metals, such as lead and cadmium, have been associated with cardiovascular disease. Thus, we designed the present unblinded pilot study to determine whether there was a signal of benefit for edetate disodium-based infusions in patients with critical limb ischemia.MethodsThis was an open-label pilot study in 10 patients with diabetes and critical limb ischemia. Each patient received up to 50 edetate disodium-based infusions and was assessed for safety, clinical efficacy, metal excretion, and quality of life. The primary endpoint was to assess the effect of edetate disodium-based therapy plus vitamins in patients with diabetes and infra-popliteal peripheral artery disease presenting with severe CLI and determine if there were improvements in vascular flow parameters.ResultsWe enrolled 10 (60% male) predominantly Caucasian (90%) subjects. The mean age was 75.3 (8.0) years. Smoking was reported by 30%. There were 70% with coronary artery disease (30% had prior coronary artery bypass grafting) and 50% had a prior lower-extremity amputation, three having previous minor amputations and two major amputations. There were no major adverse cardiovascular events during the infusion phase through the one-year follow-up. Patients completing 40 infusions demonstrated complete wound healing and improvement in the quality of life.ConclusionPatients with diabetes and CLI treated with a regimen of edetate disodium-based infusions demonstrated a potential signal of benefit and preliminary evidence of safety. The Trial to Assess Chelation Therapy in Critical Limb Ischemia (TACT3a), a randomized double-blind, placebo-controlled clinical trial now in progress, will further test these findings.

Treatment of lower limb ischaemia in patients with diabetes.

Diabetic chronic limb-threatening ischaemia is a challenging clinical problem with patients at high risk of diabetic foot ulceration (DFU) and limb loss. Patients often remain asymptomatic even in the presence of severe pedal ischaemia until first presenting with tissue loss such as DFU or frank gangrene. Limb salvage units should have the facilities and expertise to provide multidisciplinary team-based holistic care through best medical therapy, rapid diagnosis, prompt revascularisation with endovascular or open surgical techniques and expert wound management. Endovascular revascularisation has become the first line strategy in contemporary clinical practice because of similar outcomes in wound healing and amputation rates in most patients when compared with open surgery. The primary goal is restoration of pulsatile in-line blood flow to the ankle or foot, with an angiosome-directed approach possibly achieving superior outcomes especially in diabetics with poor collaterals. A comprehensive overview of conventional endovascular techniques (such as antegrade true lumen and subintimal approaches), advanced techniques for complex disease (such as retrograde subintimal and pedal-plantar loop approaches or even deep venous arterialisation) and the various treatment options are described. Diabetic limb salvage rates can be excellent with suitable multidisciplinary expertise and care.

Incidence and Risk Factors Associated With Ulcer Recurrence Among Patients With Diabetic Foot Ulcers Treated in a Multidisciplinary Setting

BackgroundRecent studies demonstrate favorable diabetic foot ulcer (DFU) healing outcomes with the implementation of a multidisciplinary team. We aimed to describe the incidence of and risk factors associated with ulcer recurrence after initial complete healing among a cohort of patients with DFU treated in a multidisciplinary setting. MethodsAll patients presenting to our multidisciplinary diabetic limb preservation service from 6/2012-04/2018 were enrolled in a prospective database. The incidence of ulcer recurrence after complete wound healing was assessed per limb using the Kaplan-Meier method, and a stepwise multivariable Cox proportional hazards model was created to identify independent predictors of ulcer recurrence. ResultsA total of 244 patients with 304 affected limbs were included. Ulcer recurrence rates at one and 3 y after healing were 30.6 ± 3.0% and 64.4 ± 5.2%, respectively. Recurrent ulcers were smaller (4.4 ± 1.1 cm2versus 8.2 ± 1.2 cm2; P = 0.04) and had a lower Wound, Ischemia, and foot Infection stage (stage 4: 7.7% versus 22.4%; P < 0.001) than initial ulcers, and wound healing time was significantly reduced (95.0 ± 9.8 versus 131.8 ± 7.0 d; P = 0.004). Independent predictors of ulcer recurrence included abnormal proprioception (HR, 1.57 [95% CI 1.02-4.43]) and younger age (HR 1.02 per year [95% CI 1.01-1.04]). ConclusionsIn this prospective cohort of patients with DFU, time to diagnosis and healing was significantly lower for recurrent ulcers, and downstaging was common. These data suggest that engaging patients with DFU in a multidisciplinary care model with frequent follow-up and focused patient education may serve to decrease DFU morbidity.

Abstract 149: Endothelial-specific Overexpression of Metallothionein Prevents Diabetes Mellitus-induced Impairment in Ischemia Angiogenesis via Preservation of Hif-1á/sdf-1 in Endothelial Progenitor Cells

Diabetes mellitus associated dysfunction of endothelial progenitor cells (EPCs) may contribute to dysregulation of endothelial regeneration. Whether oxidative protection of EPCs by an antioxidant, such as the protein metallothionein (MT) can have positive angiogenic effects and by what mechanisms remain unclear. Endothelial-specific MT overexpression (JTMT) mice were made diabetic by high fat diet followed by streptozocin administration (HFD/STZ). Diabetic hind limb ischemia (HLI) was established by femoral artery ligation. Bone marrow mononuclear cells (MNCs) collected from JTMT mice were transplanted into db/db mice with HLI. Blood reperfusion was monitored. High glucose and hypoxia conditions in culture were adopted to mimic diabetic ischemia. Compared with wild-type (WT) littermates, JTMT mice were resistant to diabetes-induced impairment in ischemia angiogenesis and blood reperfusion in HFD/STZ diabetes. Similarly, transplantation of MT overexpressing MNCs showed better therapeutic effect on db/db mice with HLI than transplantation of WT MNCs. These changes were accompanied by increased mobilization and infiltration of EPCs in JTMT mice, and enhanced incorporation of EPCs into capillaries in JTMT MNCs transplanted db/db mice. Furthermore, EPCs from JTMT mice exhibited augmented cell survival, tube formation, and migration capacities under diabetic ischemia-like conditions. Mechanistically, the expression of hypoxia-inducible factor 1α (HIF-1α) and the secretion of stromal cell-derived factor (SDF-1) in blood and expression in ischemic tissues were upregulated in JTMT and JTMT-MNC transplanted db/db mice, and in cultured JTMT EPCs, which were accompanied by marked amelioration of oxidative stress. However, MT-mediated elevation of SDF-1 and improvements of function in EPCs were all abrogated by siRNA knockdown of HIF-1α expression without effect on the anti-oxidative capacity of MT. Endothelial-specific MT elevation is sufficient to protect against diabetes mellitus-induced impairment of ischemia angiogenesis by promoting EPC function. The benefits of MT are predominantly mediated by upregulation of the HIF-1α/SDF-1 pathway.

Fighting Type-2 Diabetes: Present and Future Perspectives.

Type-2 diabetes mellitus accounts for 80-90% of diabetic patients. So far, the treatment of diabetes mainly aims at elevating insulin level and lowering glucose level in the peripheral blood and mitigating insulin resistance. Physiologically, insulin secretion from pancreatic β cells is delicately regulated. Thus, how insulin-related therapies could titrate blood glucose appropriately and avoid the occurrence of hypoglycemia remains an important issue for decades. Similar question is addressed on how to attenuate vascular complication in diabetic subjects. We overviewed the evolution of each class of anti-diabetic drugs that have been used in clinical practice, focusing on their mechanisms, clinical results and cautions. Glucagon-like peptide-1 receptor agonists stimulate β cells for insulin secretion in response to diet but not in fasting stage, which make them superior than conventional insulinsecretion stimulators. DPP-4 inhibitors suppress glucagon-like peptide-1 degradation. Sodium/ glucose co-transporter 2 inhibitors enhance glucose clearance through urine excretion. The appearance of these new drugs provides new information about glycemic control. We update the clinical findings of Glucagon-like peptide-1 receptor agonists, DPP-4 inhibitors and Sodium/glucose cotransporter 2 inhibitors in glycemic control and the risk or progression of cardiovascular disease in diabetic patients. Stem cell therapy might be an alternative tool for diabetic patients to improve β cell regeneration and peripheral ischemia. We summarize the clinical results of mesenchymal stem cells transplanted into patients with diabetic limb and foot. A stepwise intensification of dual and triple therapy for individual diabetic patient is required to achieve therapeutic target.

Fungal isolates from diabetic amputations: Histopathologic spectrum and correlation with culture

Fungal isolates from diabetic amputations: Histopathologic spectrum and correlation with culture - IJMR- Print ISSN No: - 2394-546X Online ISSN No:- 2394-5478 Article DOI No:- 10.18231/j.ijmr.2019.028, Indian Journal of Microbiology Research-Indian J Microbiol Res

625-P: Metallothionein Improves Angiogenic Function of Endothelial Progenitor Cells via HIF-1α/SDF-1/Akt Pathway in Diabetic Limb Ischemia

Diabetes mellitus associated dysfunction of endothelial progenitor cells (EPCs) may contribute to dysregulation of endothelial regeneration. Metallothionein (MT) acts as an antioxidant in various pathophysiological processes. Whether MT in EPCs has positive angiogenic effects and the mechanisms involved remain unclear. Endothelial MT overexpression (JTMT) mice were made diabetic by high fat diet followed by STZ administration (HFD/STZ). Diabetic hind limb ischemia model was established by femoral artery ligation. Bone marrow derived mononuclear leucocytes (MNCs) collected from JTMT mice were transplanted into db/db mice with hind limb ischemia. Blood reperfusion was monitored and oxidative stress was measured. High glucose and hypoxia conditions in culture were adopted to mimic diabetic ischemia in vitro. MT improved blood perfusion of ischemic hind limb and promoted angiogenesis in HFD/STZ diabetes. Oxidative stress of ischemic muscles was aggravated under diabetic condition, which was reduced in JTMT mice. Compared with WT mice, the expression of HIF-1α, SDF-1, VEGF and p-Akt were all increased in JTMT mice, along with elevation of plasma SDF-1α and VEGF. Moreover, transplantation of MT overexpressed MNCs showed better therapeutic effect on db/db diabetic mice with hind limb ischemia than control or transplantation of normal MNCs. Transplantation was accompanied by elevated HIF-1α, SDF-1 and Akt signaling. Vitro studies demonstrated that MT overexpression reduced high glucose and hypoxia induced EPC dysfunction and preserved high glucose and hypoxia impaired HIF-1α, SDF-1, VEGF and Akt signaling, all of which were abolished by siRNA knockdown of HIF-1α. In conclusion, elevated MT enhances angiogenic function and therapeutic efficacy of EPCs in diabetic limb ischemia. The benefits of MT are predominantly mediated by a HIF-1α/SDF-1/Akt pathway under diabetic ischemia conditions. Disclosure K. Wang: None. X. Dai: None. J. He: None. C. Yang: None. J. Chen: None. K.A. Wintergerst: None. P.N. Epstein: None. L. Cai: None. Y. Tan: None. Funding American Diabetes Association (1-15-BS-018, 1-18-IBS-082 to L.C.); 1-13-JF-53 (to Y.T.)

2256-PUB: Fixed-Ratio Insulin Degludec/Liraglutide (IDegLira) vs. Basal-Bolus Treatment in Type 2 Diabetic (T2DM) Patients with Diabetic Foot Ulcers (DFU) and Critical Limb Ischemia (CLI)

We report results from the clinical use of IDegLira compared to basal-bolus (BB) insulin regimen in T2DM patients admitted to our department because of DFU and CLI. We retrospectively identified 44 consecutive T2DM patients admitted to our diabetes ward because of DFU (M/F: 24/20; age: 67.3±9.5 years; BMI: 30.6±5.2 Kg/m2; diabetes duration (DD): 23.5±9.9 years; HbA1c 71.7±24.5 mmol/mol). During hospitalization, 28 patients (Group A: M/F: 15/13; age: 65.7±8.9 years; BMI: 32.6±4.8 Kg/m2; DD: 21.1±9.9 years; HbA1c 76.1±25.2 mmol/mol) previously on BB (63.7±33.9 U/day), were started on IDegLira (IDeg 22.8±7.8 U/day, liraglutide 0.82±0.3 mg/day) while the remaining 16 (Group B; M/F: 9/7; age: 70.4±10.1 years; BMI: 30.3±2.2 Kg/m2; DD: 27±9.2 years; HbA1c 63.9±22.0 mmol/mol; all p=NS vs. Group A) continued BB (43±18 U/day), allowing comparison over a mean follow-up period of 3 months. Patients were comparable with respect to distal lesions, pain-relieving, antibiotic therapies, revascularization procedures and surgical treatments performed. In Group A, BMI, HbA1c and LDL-C improved significantly (26.4±10.1 Kg/m2; 54±11 mmol/mol; 61.5±32 mg/dl; p&amp;lt;0.05 vs. baseline) during the follow-up period. No change occurred in Group B whereas Group A also had significant improvement of inflammatory markers (Fibrinogen: 635±178 vs. 437±121 mg/dl; ESR: 74±34 vs. 48±13 mm/h; CRP: 5.2±1.7 vs. 0.8±1.0 mg/dl; all p&amp;lt;0.05 vs. baseline). Ulcer healing was achieved in 17 patients in Group A (61%), and in 3 patients (19%) in Group B (p&amp;lt;0.05). These data suggest that treatment with IDegLira can have positive effects on metabolic and inflammatory parameters of complicated T2DM patients with DFU and CLI, probably contributing to greater ulcer healing observed in this category of patients. Disclosure P. Falcetta: None. F.S. Indovina: None. R. Giannarelli: None. A. Piaggesi: None. G. Penno: None. R. Miccoli: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. A. Coppelli: None.

986-P: Efficacy of Semaglutide by Background Sodium-Glucose Cotransporter 2 Inhibitor: A Post Hoc Analysis of SUSTAIN 9

The SUSTAIN clinical trials demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide, a glucagon-like peptide 1 analog for the treatment of type 2 diabetes (T2D). SUSTAIN 9 investigated semaglutide 1.0 mg vs. placebo as add-on to a stable dose of sodium-glucose co transporter-2 inhibitor (SGLT2i) therapy, with or without metformin or a sulfonylurea. The primary and secondary endpoints were, respectively, change from baseline in HbA1c and body weight at week 30. In this post hoc analysis, SUSTAIN 9 data were analyzed by background SGLT2i (empagliflozin, canagliflozin, dapagliflozin or other [ipragliflozin, luseogliflozin and tofogliflozin; drugs available only in Japan]). In total, 302 subjects were randomized to semaglutide or placebo. Reductions in HbA1c and body weight were greater with semaglutide vs. placebo. There was no significant interaction between background SGLT2i and treatment effect (interaction p-value &amp;gt;0.05 for both endpoints), with a smaller observed weight reduction in the ‘Other’ group (Table). No safety concerns were identified when adding semaglutide to SGLT2i therapy. No diabetic ketoacidosis or lower limb amputation events occurred. In conclusion, in subjects with T2D already receiving an SGLT2i, semaglutide generally resulted in superior HbA1c and body weight reductions vs. placebo, regardless of background SGLT2i therapy. Disclosure B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc. V. Bhosekar: None. R.S. Busch: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; Bayer AG. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US. Stock/Shareholder; Self; Amarin Corporation. I. Holst: Employee; Self; Novo Nordisk A/S. B. Ludvik: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Takeda Development Centre Europe Ltd. Research Support; Self; Akebia Therapeutics, Eli Lilly and Company, Novartis AG, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp. J. Thrasher: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Senseonics. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc. V.C. Woo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. A. Philis-Tsimikas: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Dexcom, Inc., Glooko, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Stock/Shareholder; Spouse/Partner; Ionis Pharmaceuticals, Inc., Novo Nordisk Inc. Funding Novo Nordisk A/S

627-P: Efficacy and Safety of Allogeneic Platelet Rich Plasma in Treatment of Diabetic Patients with Lower Limb Ulcers: A Pilot Study

Background and Objective: To observe the feasibility, efficacy and safety of al-PRP in the treatment of diabetic lower extremity ulcers. Furthermore, to explore the difference between au-PRP treatment, al-PRP treatment and only conventional treatment groups. Methods: A total of 75 inpatients with diabetic lower limbs ulcer (DLLU) were divided into au-PRP group (n=20), al-PRP group (n=25), conventional treatment group (n=30). All three groups were administered basic diabetic treatments. In addition, the above three different treatment methods were given. The feasibility, curative effect and safety of au-PRP in the treatment of DLLU were evaluated by observing wound healing time, the average daily healing area and adverse reactions. Results: No significant differences were observed in duration of diabetes, age, glycosylated hemoglobin, ankle brachial index, transcutaneous oxygen partial pressure, high-sensitivity C-reactive protein, IL-6, etc. among three groups (P&amp;gt;0.05). There was no significant difference in ulcer area and ulcer number between the three groups (8.43±6.93 cm2 vs. 5.64±3.91 cm2 vs. 9.73±9.72 cm2, P=0.19); The times and average of PRP treatment between two PRP groups have no significant difference (P&amp;gt;0.05). In the healing time, the al-PRP group and the au-PRP group were significantly shorter than the control group (56.9±29.22 days vs. 55.6±33.8 days vs. 88.0±43.4 days, P&amp;lt;0.01), while there was no significant difference between the al-PRP group and the au-PRP group (P&amp;gt;0.05). There was no significant difference in the average daily healing area (mm2) between the three groups (P&amp;gt;0.05). No significant adverse reactions (infection, itchy skin, redness, rash, etc.) were observed in two PRP groups. Conclusions: Al-PRP can effectively and safely promote the healing of diabetic lower extremity wounds. Al-PRP could be used as a beneficial cell therapy supplement when au-PRP is limited. Disclosure W. Deng: None. M. He: None. B. Chen: None. Y. Ma: None. D. Armstrong: None. J. Boey: None. Funding Natural Science Foundation of Chongqing (81500596)

Diabetic Limb Salvage With Endovascular Revascularisation and Free Tissue Transfer: Long-Term Follow up

Combining vascular bypass surgery with free flap coverage is one of the treatment methods for complex soft tissue defects in the ischaemic lower limb. Endovascular revascularisation has become the first line treatment for limb ischaemia in many centres. Surgeons now perform free tissue transfer after angioplasty. The early and long-term limb salvage rate in diabetic patients who had undergone infrapopliteal endovascular revascularisation and free flap reconstruction are assessed. This was retrospective study of all consecutive diabetic patients who had undergone endovascular revascularisation with free flap reconstruction for lower limb salvage between 2008 and 2014. They were followed up for at least 2 years or to death (mean follow up 39 ± 17 months). Cox regression analysis was used to analyse variables influencing outcome. There were 55 patients who had undergone 60 procedures. Five patients had undergone the procedure to the contralateral leg. All tissue lesions were Wagner–Meggit classification Grades 3 or 4. Thirty-six patients had TASC C lesions and 24 patients with TASC D lesions. Combined below knee triple vessel disease was seen in 30% of the cases, 28% involved both the anterior and posterior tibial artery, 7% and 2% involved the anterior tibial or the posterior tibial and the peroneal arteries. The free flap success rate was 95%. The peri-operative mortality was 1.7%. Twenty-one cases required surgical re-intervention. Mean length of hospital admission was 32 ± 9 days. One and five year amputation free survival rates were 94% and 68%, patient survival rates were 95% and 67%, limb salvage rates were 93% and 91% and respectively. The results show that excellent early and late limb salvage can be achieved with free tissue transfer based on endovascular revascularisation of infrapopliteal arteries. This can be a further treatment option in diabetic patients with complex soft tissue defects.

Contribution of 30-day readmissions to the increasing costs of care for the diabetic foot

ObjectiveThe inpatient cost of care for diabetic foot ulcers (DFUs) has been estimated to be $1.4 billion annually in the United States. We have previously demonstrated that the risk of 30-day unplanned readmission for patients with DFU is nearly 22%. Our aim was to quantify the cost of readmissions for patients admitted with DFU. MethodsAll patients presenting to our multidisciplinary diabetic limb preservation service from June 2012 to June 2016 were enrolled in a prospective database. Inpatient costs and net margins were calculated overall and for index admissions vs 30-day unplanned readmissions. ResultsA total of 249 admissions for 150 patients were included. Of these, 206 admissions were index admissions and 43 were 30-day readmissions. The most common reason for readmission was the foot wound (49%), followed by a bypass wound (14%), renal complications (9%), and other systemic complications. Surgical interventions during readmission were common (47%) and included both podiatric (37%) and vascular (23%). The wound healing outcomes were favorable, with 78% of all wounds achieving healing by 1 year. Limb salvage was 91% overall. The median hospital cost per admission was $20,111 (interquartile range, $12,589-$33,254) and did not differ between the index and readmissions ($22,165 vs $19,408; P = .46). However, the hospital net margins were lower after readmission ($3908 vs $1975; P = .02). The overall cost of care for patients requiring readmission was significantly greater than that for patients not readmitted ($79,315 vs $28,977; P < .001). During the study period, DFU care at our institution cost $7.9 million, of which $1.2 million (16%) was attributable to readmission costs. ConclusionsReadmissions for patients with DFU are common and associated with a substantial cost burden. The cost of readmission for patients with DFU was as high as the cost of the index admission but with lower hospital net margins. When extrapolated to national data, the 15% readmission cost burden we have reported would be equivalent to $210 million hospital costs annually. Focused efforts at preventing readmissions in this high-risk patient population are essential to reducing the overall costs of care associated with DFUs.

Quantifying the costs and profitability of care for diabetic foot ulcers treated in a multidisciplinary setting

ObjectiveIncreasing Wound, Ischemia, and foot Infection (WIfI) stage has previously been shown to be associated with prolonged wound healing time, higher number of surgical procedures, and increased cost of care in patients with diabetic foot ulcers (DFUs) treated in a multidisciplinary setting. However, the profitability of this care model is unknown. We aimed to quantify the hospital costs and net margins associated with multidisciplinary DFU care. MethodsAll patients presenting to our multidisciplinary diabetic limb preservation service (January 2012-June 2016) were enrolled in a prospective database. Inpatient and outpatient costs and net margin (U.S. dollars) were calculated for each wound episode (initial visit until complete wound healing) overall and per day of care according to WIfI classification. ResultsA total of 319 wound episodes in 248 patients were captured. Patients required an average of 2.6 ± 0.2 inpatient admissions and 0.9 ± 0.1 outpatient procedures to achieve complete healing. Limb salvage at 1 year was 95.0% ± 2.4%. The overall mean cost of care per wound episode was $24,226 ± $2176, including $41,420 ± $3318 for inpatient admissions and $11,265 ± $1038 for outpatient procedures. The mean net margin was $2412 ± $375 per wound episode, including $5128 ± $622 for inpatient admissions and a net loss ($−3730 ± $596) for outpatient procedures. Mean time to wound healing was 136.3 ± 7.9 days, ranging from 106.5 ± 13.1 days for WIfI stage 1 wounds to 229.5 ± 20.0 days for WIfI stage 4 wounds (P < .001). When adjusted for days of care, the net margin ranged from $2.6 ± $1.3 per day (WIfI stage 1) to $23.6 ± $18.8 (WIfI stage 4). ConclusionsThe costs associated with multidisciplinary DFU care are substantial, especially with advanced-stage wounds. Whereas hospitals can operate at a profit overall, the net margins associated with outpatient procedures performed in a hospital-based facility are prohibitive, and the overall net margins are relatively low, given the labor required to achieve good outcomes. Thus, reimbursement for the multidisciplinary care of DFUs should be re-examined.

LEA 10. Use of Home Negative Pressure Wound Therapy in Peripheral Artery Disease and Diabetic Limb Salvage

LEA 10. Use of Home Negative Pressure Wound Therapy in Peripheral Artery Disease and Diabetic Limb Salvage

A renaissance in diabetic foot care: new evidence-based treatments

Unhealed diabetic foot ulcers can result in up to 84% of lower extremity amputations. 1 Pecoraro R Reiber G Burgess E Pathways to diabetic limb amputation: basis for prevention. Diabetes Care. 1990; 13: 513-521 Crossref PubMed Scopus (1230) Google Scholar , 2 Larsson J Apelqvist J Agardh CD Stenström A Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?. Diabet Med. 1995; 12: 770-776 Crossref PubMed Scopus (315) Google Scholar It is thus important that ulcers are healed quickly. However, there has been a scarcity of evidence-based topical therapy to accelerate the healing of diabetic foot ulcers and this drought has led to a call for well-designed clinical trials. 3 Jeffcoate WJ Bus SA Game FL Hinchliffe RJ Price PE Schaper NC International Working Group on the Diabetic Foot and the European Wound Management AssociationReporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: required details and markers of good quality. Lancet Diabetes Endocrinol. 2016; 4: 781-788 Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar Over the past year, there has been a renaissance in diabetic foot care and three relatively robust trials on foot ulcers have been published. The first (the Explorer study 4 Edmonds M Lazaro-Martinez JL Alfayate-Garcia JM et al. Sucrose octasulfatedressing versus control dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre, double-blind, randomised, controlled trial. Lancet Diabetes Endocrinol. 2018; 6: 186-196 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar ) reported the benefit of sucrose octasulphate dressing and the second (the ProNOx1 study 5 Edmonds ME Bodansky HJ Boulton AJ et al. Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes – ProNOx1 study. Wound Repair Regen. 2018; (published online April 4.)DOI:10.1111/wrr.12630 Crossref Scopus (25) Google Scholar ) reported the positive outcome of a nitric oxide generating device. The third study (LeucoPatch 6 Game F Jeffcoate W Tarnow L et al. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-blinded, randomised controlled trial. Lancet Diabetes Endocrinol. 2018; (published online September 7.)http://dx.doi.org/10.1016/S2213-8587(18)30240-7 Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar ) reported the benefit of a multi-layered patch comprising autologous leucocytes, platelets, and fibrin, which releases cytokines and growth factors involved in tissue repair, 7 Game FL Apelqvist J Attinger C et al. Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review. Diabetes Metab Res Rev. 2016; 32: 154-168 Crossref PubMed Scopus (121) Google Scholar in a multinational, observer-blinded, randomised, controlled trial now published in The Lancet Diabetes & Endocrinology by Frances Game and colleagues. 6 Game F Jeffcoate W Tarnow L et al. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-blinded, randomised controlled trial. Lancet Diabetes Endocrinol. 2018; (published online September 7.)http://dx.doi.org/10.1016/S2213-8587(18)30240-7 Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar The trial recruited people with hard-to-heal ulcers, which were defined as ulcers that had less than a 50% reduction of area in response to standard care during a 4-week run-in period. 34% of these ulcers healed within 20 weeks in the intervention group (together with standard care) compared with 22% in patients undergoing standard care alone (odds ratio 1·58, 96% CI 1·04–2·40; p=0·0235). LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trialThe use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes. Full-Text PDF