Search

David C Klonoff,1 Brian L Levy,2 Michael J Jaasma,3 Manish Bharara,3 Deborah R Edgar,4 Christian Nasr,5 David L Caraway,3 Erika A Petersen,6 David G Armstrong7 1Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA; 2New York University Grossman School of Medicine, New York, NY, USA; 3Nevro Corp, Redwood City, CA, USA; 4Commexus Ltd, Dunblane, Scotland, UK; 5Division of Endocrinology, Department of Internal Medicine, The University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; 6Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 7Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, USACorrespondence: David C Klonoff, Diabetes Research Institute, Mills-Peninsula Medical Center, 100 South San Mateo Drive, Room 1165, San Mateo, CA, 94401, USA, Tel +1650-218-1142, Email dklonoff@diabetestechnology.orgPurpose: The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D).Patients and Methods: This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (> 7% and > 8%) and body mass index (BMI; ≥ 30 and ≥ 35 kg/m2).Results: At 24 months, participants with preimplantation HbA1c > 7% and > 8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥ 30 and ≥ 35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts.Conclusion: This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief.Trial Registration: ClincalTrials.gov Identifier, NCT03228420.Keywords: diabetic peripheral neuropathy, painful diabetic neuropathy, spinal cord stimulation, neuromodulation, neuropathic pain

Xiaoyan Jiang,1,&ast; Fang Deng,1,2,&ast; Shunli Rui,1 Yu Ma,1 Min Wang,1 Bo Deng,1 Hongyan Wang,1 Chenzhen Du,1 Bing Chen,2 Xiuhua Yang,3 Johnson Boey,4 David G Armstrong,5 Wuquan Deng,1 Xiaodong Duan6 1Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, Chongqing, 400014, People’s Republic of China; 2Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, 400038, People’s Republic of China; 3Department of Lower Extremity Surgery, NO.1 Orthopedics Hospital of Chengdu, Chengdu City, 610000, Sichuan, People’s Republic of China; 4Department of Podiatry, National University Hospital, 169608, Singapore; 5Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA; 6Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng, Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, No. 1 Jiankang Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +86 23 63692185, Email wuquandeng@cqu.edu.cn Xiaodong Duan, Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email duanxiaodong2032@sina.comObjective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p< 0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p< 0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p< 0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p< 0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p< 0.05).Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.Keywords: gait, balance, diabetic peripheral neuropathy, risk assessment, wearable biomechanical system

Xi Zhang,1,&ast; Hongyan Wang,1,&ast; Chenzhen Du,1 Xiaoyun Fan,2 Long Cui,3 Heming Chen,4 Fang Deng,5 Qiang Tong,6 Min He,7 Mei Yang,8 Xingrong Tan,9 Lin Li,10 Zerong Liang,11 Yaqin Chen,12 Deqing Chen,13 David G Armstrong,14 Wuquan Deng1 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing University, Chongqing, People’s Republic of China; 2Department of Endocrinology, Hospital for Occupational Diseases of Chongqing, Chongqing, People’s Republic of China; 3Department of Endocrinology, Armed Police Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Endocrinology, Ankang Central Hospital, Ankang, Shaanxi, People’s Republic of China; 5Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, People’s Republic of China; 6Department of Endocrinology, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 7Department of Endocrinology, The People’s Hospital of Shapingba District, Chongqing, People’s Republic of China; 8Department of Endocrinology, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China; 9Department of Endocrinology, The 9th People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 10Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 11Department of Endocrinology, Chongqing Red Cross Hospital, People’s Hospital of Jiangbei District, Chongqing, 400020, People’s Republic of China; 12Department of Endocrinology, The People’s Hospital of Shizhu, Chongqing, People’s Republic of China; 13Department of Endocrinology, The People’s Hospital of Rongchang, Chongqing, People’s Republic of China; 14Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng Email wuquandeng@cqu.edu.cnBackground: Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy’s clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions.Methods: A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy.Results: Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up.Conclusion: Patients’ adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.Keywords: custom-molded offloading footwear, high-risk diabetic foot, patient adherence

Xiaoyan Jiang,1,* Ning Li,1,* Yi Yuan,1 Cheng Yang,1 Yan Chen,1 Yu Ma,1 Jianbai Wang,2 Dingyuan Du,2 Johnson Boey,3 David G Armstrong,4 Wuquan Deng1 1Department of Endocrinology and Nephrology, Diabetic Foot Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 2Department of Traumatology, Diabetic Foot Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 3Department of Podiatry, National University Hospital, Singapore; 4Keck School of Medicine of University of Southern California, Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Wuquan DengDepartment of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No. 1 Jiankang Road, Chongqing 400014, People’s Republic of ChinaTel +86 23 63692186Email wuquandeng@gmail.comAbstract: Biomechanical changes caused by structural foot deformities predispose patients to plantar ulceration. Plantar ulcer recurrence often leads to osteomyelitis, which is more commonly observed in patients with diabetes. Once the infection of diabetic foot ulcer (DFU) spreads and is complicated by osteomyelitis, treatment becomes more complicated and difficult. Osteomyelitis treatment remains challenging because of low drug concentration within the tissue caused by poor circulation and inadequate localized nutrition. Moreover, tissues around plantar ulcers are fewer and are thin, making the formation of granulation tissues difficult due to elevated plantar pressure. Furthermore, the skin around the wound is excessively keratinized, and the epidermis is hard to regenerate. Meanwhile, skin grafting at that site is often not successful due to poor blood circulation. Therefore, it is technically challenging to manage diabetic pressure plantar ulcer with osteomyelitis and prevent its recurrence. Here, we present a case of chronic DFU complicated by osteomyelitis due to foot deformity. The ulcer was successfully healed using advanced wound repair technology comprising of surgical bone resection, vancomycin-loaded bone cement implant, negative-pressure wound therapy, and autologous platelet-rich gel. Subsequently, preventive foot care with custom-made offloading footwear was prescribed. The plantar ulcer did not recur and improvement in biomechanical parameters was observed after the intervention. This case represents an effective and comprehensive management strategy for limb salvage and prevention in patients with complicated foot conditions.Keywords: diabetic foot ulcer, osteomyelitis, antibiotic-loaded bone cement, autologous platelet-rich gel, negative-pressure wound therapy, offloading footwear

Tao Li,1 Yu Ma,2 Min Wang,1 Tao Wang,3 Jing Wei,4 Rui Ren,1 Min He,1 Guixue Wang,2 Johnson Boey,5 David G Armstrong,6 Wuquan Deng,2 Bing Chen1 1Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Endocrinology and Nephrology, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Affiliated Central Hospital of Chongqing University, Chongqing, People’s Republic of China; 3Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, People’s Republic of China; 4Department of Endocrinology, General Hospital of Xinjiang Military Region, The Chinese People’s Liberation Army, Urumqi, People’s Republic of China; 5Department of Podiatry, Singapore General Hospital, Singapore; 6Southwestern Academic Limb Salvage Alliance (SALSA), Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Aim: This study was designed to examine the potential mechanism underlying these roles of platelet-rich plasma in treating diabetic foot ulcers (DFUs). Methods: Staphylococcus aureus and HaCaT were co-cultured under high glucose conditions to serve as an in vitro model for infected cells in DFUs. Platelet-rich gel (PRG) or extract liquid of platelet-rich gel (EPG) were used to interfere with the model to observe the growth of HaCaT cells and S. aureus, and the effect of miR-21 changes in HaCaT cells on PDCD4, NF-κB activity and related inflammatory factors. Results: Incubation of HaCaT cells with S. aureus promoted the decline of cell proliferation. Under this condition, the level of PDCD4 and the activity of NF-κB were increased in HaCaT cells with concomitant increased of IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant. Both of PRG and EPG exhibited specific anti-S. aureus activity where they protect HaCaT cells from bacterial damage and promote cell proliferation. Meanwhile, EPG was observed to increase intracellular miRNA-21 while reduce PDCD4 expression and inhibit NF-κB activity to suppress the inflammation in HaCaT cells. Conclusion: This in vitro model provides a valuable tool for study of wound healing in the treatment of DFUs. Our results suggest that miRNA-21 may regulate the expression of NF-κB through PDCD4 where it plays an anti-inflammatory role and promote proliferation in infected DFUs treated by PRP. These findings could provide novel therapeutic targets for refractory wounds. Keywords: platelet-rich plasma, antibacterial, anti-inflammatory, cell proliferation-promoting, diabetic infected wound

Jano A Boghossian,1 John D Miller,2 David G Armstrong1 1Department of Surgery, Southern Arizona Limb Salvage Alliance, University of Arizona, Tucson, AZ, 2Department of Podiatric Surgery and Medicine, DVA Maryland Healthcare System, Baltimore, MD, USA Abstract: Management of the diabetic foot is multifaceted and requires constant monitoring from patients and health care providers. The alarmingly high rate of recurrence of ulcerations in diabetic foot requires a change in our approach to care and to the vernacular in the medical literature. With its high rates of morbidity and recurrence, care of the complex diabetic foot may be aptly comparable to many forms of cancer. Therefore, our efforts should be not only in rapid healing of open wounds but also in maximizing ulcer-free days for the patient in diabetic foot remission. One facet of the multidisciplinary approach in managing wounds is achieved by reducing peak plantar pressures by offloading the foot with various conservative and surgical techniques aimed at reducing areas of stress caused by ambulation and improper shoe gear. Evidence supports the use of total contact casts as the gold standard for offloading open wounds; however, other methods have gained popularity as well. Novel approaches in surgical techniques and advances in wearable technology appear to show promise in measuring and modulating dangerous pressure and inflammation to extend remission and improve quality of life for these most complex patients. Keywords: diabetic foot, ulcer, remission, amputation, offloading, wearables

Objective: There is a dearth of long-term data regarding patient and limb survival in patients with diabetic foot ulcers (DFUs). The purpose of our study was therefore to prospectively investigate the limb and person survival of DFU patients during a follow-up period of more than 10 years.Research Design and Methods: Two hundred forty-seven patients with DFUs and without previous major amputation consecutively presenting to a single diabetes center between June 1998 and December 1999 were included in this study and followed up until May 2011. Mean patient age was 68.8 ± 10.9 years, 58.7% were male, and 55.5% had peripheral arterial disease (PAD). Times to first major amputation and to death were analyzed with Kaplan-Meier curves and Cox multiple regression.Results: A first major amputation occurred in 38 patients (15.4%) during follow-up. All but one of these patients had evidence of PAD at inclusion in the study, and 51.4% had severe PAD [ankle-brachial pressure index ≤0.4]). Age (hazard ratio [HR] per year, 1.05 [95% CI, 1.01-1.10]), being on dialysis (3.51 [1.02-12.07]), and PAD (35.34 [4.81-259.79]) were significant predictors for first major amputation. Cumulative mortalities at years 1, 3, 5, and 10 were 15.4, 33.1, 45.8, and 70.4%, respectively. Significant predictors for death were age (HR per year, 1.08 [95% CI, 1.06-1.10]), male sex ([1.18-2.32]), chronic renal insufficiency (1.83 [1.25-2.66]), dialysis (6.43 [3.14-13.16]), and PAD (1.44 [1.05-1.98]).Conclusions: Although long-term limb salvage in this modern series of diabetic foot patients is favorable, long-term survival remains poor, especially among patients with PAD or renal insufficiency. [ABSTRACT FROM AUTHOR]

Abstract Patients with diabetes are prone to ulcerations of the lower extremities, frequently complicated by infection, and are then reliant upon their caregivers for preservation of their limbs without the dreaded outcome of amputation. The enormous tolls of foot infections in diabetes, in terms of both health-related quality of life issues and associated economic burdens, have only been fully realized within the last few decades, and it is anticipated that these burdens will only increase over time. Early and appropriate antibiotic treatment targeting the most likely etiologic pathogens is a cornerstone of management of foot infections in diabetes, but these decisions are now complicated by the emergence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative species. This review will examine the impact of foot infections in diabetes and the overall care and management of the diabetes patient with foot infection, including the potential value of emerging antibiotic therapies within the milieu of antibiotic resistance. [ABSTRACT FROM AUTHOR]

This investigation was conducted to determine if a correlation exists between wound healing outcomes and serial debridement in chronic venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). We retrospectively analyzed the results from two controlled, prospective, randomized pivotal trials of topical wound treatments on 366 VLUs and 310 DFUs over 12 weeks. Weekly wound surface area changes following debridement and 12-week wound closure rates between centers and patients were evaluated. VLUs had a significantly higher median wound surface area reduction following clinical visits with surgical debridement as compared with clinical visits with no surgical debridement (34%, p=0.019). Centers where patients were debrided more frequently were associated with higher rates of wound closure in both clinical studies ( p=0.007 VLU, p=0.015 DFU). Debridement frequency per patient was not statistically correlated to higher rates of wound closure; however, there was some minor evidence of a positive benefit of serial debridement in DFUs (odds ratio-2.35, p=0.069). Our results suggest that frequent debridement of DFUs and VLUs may increase wound healing rates and rates of closure, though there is not enough evidence to definitively conclude a significant effect. Future clinical research in wound care should focus on the relationship between serial surgical wound debridement and improved wound healing outcomes as demonstrated in this study. [ABSTRACT FROM AUTHOR]