The Limb Salvage Approach for the Surgical Management of Necrotizing Soft Tissue Infection.

Necrotizing soft tissue infection (NSTI) is a complex infection known for its rapid progression of necrosis within the subcutaneous tissue and fascia. Time is of essence for the management of NSTI. In this report, we present a case of NSTI after infection of poorly managed diabetic foot ulcer in the ankle. The limb salvage approach involves sequential staged procedures. Multiple surgical debridements and "washout" were performed for source control. At the same time, the patient also received a systemic antibiotic regimen. In the second stage, a perforator free flap taken from the anterolateral thigh was used to repair the extensive soft tissue defect and reconstruct a functional foot to achieve maximal limb salvage. The kickstand technique of external fixation was used to reduce soft tissue compression and enhance the surgical offloading of the skin flap. At the 2-year follow-up, the skin integrity of the flap was well-preserved, and the patient returned to his premorbid quality of life.

Associations between eating speed and food temperature and type 2 diabetes mellitus: a cross-sectional study.

Objective: This study aimed to evaluate the relationship between eating speed and food temperature and type 2 diabetes mellitus (T2DM) in the Chinese population. Methods: A cross-sectional survey was conducted between December 2020 to March 2022 from the department of Endocrinology at the Shandong Provincial Hospital. All recruited participants were asked to complete structured questionnaires on their eating behaviors at the time of recruitment. Clinical demographic data such as gender, age, height, weight, familial history of T2DM, prevalence of T2DM and various eating behaviors were collected. Univariate and multivariate logistic regression analyses were used to analyze the associations between eating behaviors and T2DM. Results: A total of 1,040 Chinese adults were included in the study, including 344 people with T2DM and 696 people without T2DM. Multivariate logistic regression analysis of the general population showed that gender (OR = 2.255, 95% CI: 1.559-3.260, p < 0.001), age (OR = 1.091, 95% CI: 1.075-1.107, p < 0.001), BMI (OR = 1.238, 95% CI: 1.034-1.483, p = 0.020), familial history of T2DM (OR = 5.709, 95% CI: 3.963-8.224, p < 0.001), consumption of hot food (OR = 4.132, 95% CI: 2.899-5.888, p < 0.001), consumption of snacks (OR = 1.745, 95% CI: 1.222-2.492, p = 0.002), and eating speed (OR = 1.292, 95% CI:1.048-1.591, p = 0.016) were risk factors for T2DM. Conclusion: In addition to traditional risk factors such as gender, age, BMI, familial history of T2DM, eating behaviors associated with Chinese culture, including consumption of hot food, consumption of snacks, and fast eating have shown to be probable risk factors for T2DM.

The role of allogeneic platelet-rich plasma in patients with diabetic foot ulcer: Current perspectives and future challenges.

The frequency of chronic cutaneous wounds are sharply increasing in aging populations. Patients with age-related diseases, such as diabetes, tumors, renal failure and stroke are prone to soft tissue and skin injury, compounded by slowed healing in aging. Imbalance of wound inflammation, loss of growth factor secretion, and impairment of tissue repair abilities are all possible reasons for failed healing. Therefore, it is vital to explore novel approaches to accelerate wound healing. Platelet-rich plasma (PRP) as a cell therapy has been widely applied for tissue repair and regeneration. PRP promotes wound healing by releasing antimicrobial peptides, growth factors and micro-RNAs. Medical evidence indicates that autologous platelet-rich plasma (au-PRP) can promote wound healing effectively, safely and rapidly. However, its clinical application is usually restricted to patients with chronic cutaneous wounds, generally because of other severe complications and poor clinical comorbidities. Allogeneic platelet-rich plasma (al-PRP), with abundant sources, has demonstrated its superiority in the field of chronic wound treatment. Al-PRP could overcome the limitations of au-PRP and has promising prospects in clinical applications. The aim of this review is to summarize the current status and future challenges of al-PRP in chronic cutaneous wound management. We also summarized clinical cases to further describe the application of al-PRP for chronic wounds in clinical practice.

The Evaluation of Gait and Balance for Patients with Early Diabetic Peripheral Neuropathy: A Cross-Sectional Study.

Objective: 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.

Time in range in relation to amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers.

AIMS: The aim of this study was to evaluate the association of time in range (TIR) with amputation and all-cause mortality in hospitalised patients with diabetic foot ulcers (DFUs). MATERIALS AND METHODS: A retrospective analysis was performed on 303 hospitalised patients with DFUs. During hospitalisation, TIR, mean blood glucose (MBG), coefficient of variation (CV), time above range (TAR) and time below range (TBR) of patients were determined from seven-point blood glucose profiles. Participants were grouped based on their clinical outcomes (i.e., amputation and death). Logistic regression was employed to analyse the association of TIR with amputation and all-cause mortality of inpatients with DFUs. RESULTS: Among the 303 enrolled patients, 50 (16.5%) had undergone amputation whereas seven (2.3%) were deceased. Blood glucose was determined in 41,012 samples obtained from all participants. Patients who underwent amputation had significantly lower TIR and higher MBG, CV, level 2 TAR and level 1 TBR whereas deceased patients had significantly lower TIR and higher MBG and level 2 TAR. Both amputation and all-cause mortality rate declined with an increase in TIR quartiles. Logistic regression showed association of TIR with amputation (p = 0.034) and all-cause mortality (p = 0.013) after controlling for 15 confounders. This association was similarly significant in all-cause mortality after further adjustment for CV (p = 0.022) and level 1 TBR (p = 0.021), respectively. CONCLUSIONS: TIR is inversely associated with amputation and all-cause mortality of hospitalised patients with DFUs. Further prospective studies are warranted to establish a causal relationship between TIR and clinical outcomes in patients with DFUs.

An explainable machine learning model for predicting in-hospital amputation rate of patients with diabetic foot ulcer.

Diabetic foot ulcer (DFU) is one of the most serious and alarming diabetic complications, which often leads to high amputation rates in diabetic patients. Machine learning is a part of the field of artificial intelligence, which can automatically learn models from data and better inform clinical decision-making. We aimed to develop an accurate and explainable prediction model to estimate the risk of in-hospital amputation in patients with DFU. A total of 618 hospitalised patients with DFU were included in this study. The patients were divided into non-amputation, minor amputation or major amputation group. Light Gradient Boosting Machine (LightGBM) and 5-fold cross-validation tools were used to construct a multi-class classification model to predict the three outcomes of interest. In addition, we used the SHapley Additive exPlanations (SHAP) algorithm to interpret the predictions of the model. Our area under the receiver-operating-characteristic curve (AUC) demonstrated a 0.90, 0.85 and 0.86 predictive ability for non-amputation, minor amputation and major amputation outcomes, respectively. Taken together, our data demonstrated that the developed explainable machine learning model provided accurate estimates of the amputation rate in patients with DFU during hospitalisation. Besides, the model could inform individualised analyses of the patients' risk factors.

A dual pressure indicator, two-layer compression system for treatment of venous leg ulcers: a review.

OBJECTIVE: Venous leg ulcers (VLUs) are considered the most frequent category of hard-to-heal limb ulcers. Although evidence-based care of VLUs suggests that compression therapy plays a pivotal role in the standard of care, patient adherence is considered low, with at least 33% non-compliance, either due to perceived problems from clinicians regarding their own competency in applying the bandages, or from the patient finding the wrapping bothersome. For many years, four-layer bandaging has been considered the 'gold standard', but application can be difficult and may also prove uncomfortable for patients. Accurate application may be facilitated by a stretch indicator which has been engineered to act as a surrogate for appropriate pressure application that can address the skill concern, while fewer layers can save clinicians' time and improve the quality of life of patients. Here, we review the literature supporting a two-layer system which combines elastic (long stretch) and inelastic (short stretch) components as well as both layers having graphic markers to define that the dressing has been applied at the proper tension. METHOD: An initial search was conducted on PubMed and then followed up by a manual search of Google Scholar to retrieve evidence of different levels, in order to evaluate the outcomes of use of the specific two-layer compression system with pressure indicators in the management of patients presenting with VLUs. RESULTS: A total of four papers discussing the specific compression system in question were identified from 32 publications retrieved from PubMed, while a further six were retrieved from Google Scholar. These 10 publications were considered relevant to the two-layer system and were analysed for the outcomes of care, including wound healing, appropriate application, time-saving and better patient acceptance and adherence. CONCLUSION: Previous authors have demonstrated that two-layer systems are equivalent to four-layer systems. However, the ability to reproducibly apply appropriate compression has remained a question. The papers reviewed demonstrate that evidence suggests that the two-layer compression bandage system with indicators provides continuous, consistent and comfortable treatment that may be easier to apply with accurate pressure levels due to their indicator systems, and therefore, is a procedure that may increase patient adherence and acceptability to the wound therapy.

Pain Management in People with Diabetes-Related Chronic Limb-Threatening Ischemia.

Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients' quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients' physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence.

The Feasibility and Effectiveness of Wearable Sensor Technology in the Management of Elderly Diabetics with Foot Ulcer Remission: A Proof-Of-Concept Pilot Study with Six Cases.

AIMS: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication. METHODS: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times. RESULTS: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased. CONCLUSIONS: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.

Limb Salvage and Prevention of Ulcer Recurrence in a Chronic Refractory Diabetic Foot Osteomyelitis.

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.

Platelet-rich plasma plays an antibacterial, anti-inflammatory and cell proliferation-promoting role in an in vitro model for diabetic infected wounds.

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-ß1 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.

Efficacy and long-term longitudinal follow-up of bone marrow mesenchymal cell transplantation therapy in a diabetic patient with recurrent lower limb bullosis diabeticorum.

Bullosis diabeticorum is a rare presentation of cutaneous manifestation most commonly affecting the lower limbs in patients with diabetes. The appearance, often as insidious as its resolution, is characterized by tense blisters on the skin surfaces of the lower limbs and the feet. The cause still remains unclear, but it may relate to microangiopathy and neuropathy. In this report, we present a case of a 64-year-old male with multiple episodes of blistering in the left lateral lower limb after a traumatic fall who was subsequently diagnosed with type 2 diabetes mellitus. The patient had a history of poorly controlled blood glucose and subsequently developed vasculopathy and peripheral neuropathy. Despite appropriate glycemic control and antibiotics therapy, the patient developed recurrent bullosis diabeticorum on five separate occasions during a 2-year span from 2005 to 2007. Building on our success with ischemic diabetic foot, we used bone marrow mesenchymal stem cell (BMMSC) transplantation therapy for bullosis diabeticorum. After a 9-month treatment, this patient developed another episode of cellulitis in the same lower limb which was successfully treated with antibacterial therapy. It is interesting that the patient reported no recurrence in the next 10-year follow-up span. This study demonstrates that bullosis diabeticorum could appear even before the onset of diabetes, and vascular insufficiency predisposes to the occurrence of bullosis diabeticorum. Our findings suggest that autologous BMMSC transplantation therapy may be an effective measure for recurrent bullosis diabeticorum; however, this will require further investigation to be conclusive. Early identification of diabetes and its complications and appropriate treatment may improve clinical outcomes and prevent lower limb amputation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00955669 . Registered on August 10, 2009.

Association between Serum Cystatin C and Diabetic Foot Ulceration in Patients with Type 2 Diabetes: A Cross-Sectional Study.

Serum cystatin C (CysC) has been identified as a possible potential biomarker in a variety of diabetic complications, including diabetic peripheral neuropathy and peripheral artery disease. We aimed to examine the association between CysC and diabetic foot ulceration (DFU) in patients with type 2 diabetes (T2D). 411 patients with T2D were enrolled in this cross-sectional study at a university hospital. Clinical manifestations and biochemical parameters were compared between DFU group and non-DFU group. The association between serum CysC and DFU was explored by binary logistic regression analysis. The cut point of CysC for DFU was also evaluated by receiver operating characteristic (ROC) curve. The prevalence of coronary artery disease, diabetic nephropathy (DN), and DFU dramatically increased with CysC (P < 0.01) in CysC quartiles. Multivariate logistic regression analysis indicated that the significant risk factors for DFU were serum CysC, coronary artery disease, hypertension, insulin use, the differences between supine and sitting TcPO2, and hypertension. ROC curve analysis revealed that the cut point of CysC for DFU was 0.735 mg/L. Serum CysC levels correlated with DFU and severity of tissue loss. Our study results indicated that serum CysC was associated with a high prevalence of DFU in Chinese T2D subjects.