Revascularisation Options for Chronic Limb Threatening Ischaemia in Diabetes: Implications From Two Recent Trials.

Chronic limb-threatening ischaemia (CLTI) is a severe form of peripheral arterial disease (PAD) and is associated with an increased risk of amputation, mortality, and significantly impaired quality of life. International guidelines recommend considering timely revascularisation and optimal medical therapy to improve limb perfusion in individuals with CLTI. The 2 primary revascularization approaches for CLTI are open bypass surgery (BS) and endovascular therapy (EV), however, there is currently no consensus on the best initial treatment strategy for CLTI, leading to uncertainty among clinicians. To shed light on this issue, 2 recent trials, namely best endovascular versus best surgical therapy in patients with CLI (BEST-CLI) and bypass versus angioplasty for severe ischaemia of the leg (BASIL-2), have tried to provide valuable insights. While a definitive conclusion on the optimal revascularisation approach is still pending, these trials offer immediate and clinically relevant information to the diabetic foot multidisciplinary team. The trials encompassed a distinct range of patient cohorts and included participants with varying degrees of medical and physical frailty. Taken together, their findings, highlight the need for an individualised revascularisation strategy which accounts for underlying comorbidities, risk factors, disease severity, availability of suitable bypass conduits, surgical risks, and timely access to procedures. Regardless of the chosen strategy, early referral of patients with diabetes and CLTI to a specialist team within a multidisciplinary environment is crucial. Comprehensive care should encompass essential elements such as adequate debridement, infection control, offloading, glycaemic control, smoking cessation, and patient education. By addressing these aspects, healthcare providers can optimise the management and outcomes for individuals with CLTI and diabetes.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy. However, additional testing showed reduced sweat gland function most likely related to degeneration of c-fibres (small fibre neuropathy). This case raises the awareness that in addition to the "textbook" description, in diabetes, Charcot foot can develop in individuals with "minimal" or "no signs" of clinical neuropathy. The onset of active Charcot foot should be suspected in every person with diabetes and history of trauma even when foot and ankle x-rays are normal. Offloading should be initiated until the diagnosis is proven otherwise.

Outcomes after Emergency Admission with a Diabetic Foot Attack Indicate a High Rate of Healing and Limb Salvage But Increased Mortality: 18-Month Follow-up Study.

AIM: The diabetic foot attack (DFA) is perhaps the most devastating form of diabetic foot infection, presenting with rapidly progressive skin and tissue necrosis, threatening both limb and life. However, clinical outcome data in this specific group of patients are not available. METHODS: Analysis of 106 consecutive patients who underwent emergency hospitalisation for DFA (TEXAS Grade 3B or 3D and Infectious Diseases Society of America (IDSA) Class 4 criteria). Outcomes evaluated were: 1) Healing 2) major amputation 3) death 4) not healed. The first outcome reached in one of these four categories over the follow-up period (18.4±3.6 months) was considered. We also estimated amputation free survival. RESULTS: Overall, 57.5% (n=61) healed, 5.6% (n=6) underwent major amputation, 23.5% (n=25) died without healing and 13.2% (n=14) were alive without healing. Predictive factors associated with outcomes were: Healing (age<60, p=0.0017; no Peripheral arterial disease (PAD) p= 0.002; not on dialysis p=0.006); major amputation (CRP>100 mg/L, p=0.001; gram+ve organisms, p=0.0013; dialysis, p= 0.001), and for death (age>60, p= 0.0001; gram+ve organisms p=0.004; presence of PAD, p=0.0032; CRP, p=0.034). The major amputation free survival was 71% during the first 12 months from admission, however it had reduced to 55.4% by the end of the follow-up period. CONCLUSIONS: In a unique population of hospitalised individuals with DFA, we report excellent healing and limb salvage rates using a dedicated protocol in a multidisciplinary setting. An additional novel finding was the concerning observation that such an admission was associated with high 18-month mortality, almost all of which was after discharge from hospital.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.

People living with diabetes are unaware of their foot risk status or why they are referred to a multidisciplinary foot team.

AIM: People with active diabetic foot disease should be rapidly referred by health professionals along a pathway of care to a multidisciplinary foot team. The aim was to investigate patients' self-reported understanding of their foot risk status and reasons for their referral to a multidisciplinary foot team. METHOD: This seven-month service evaluation included consecutive newly referred patients. Participants completed a questionnaire which asked firstly about their understanding of their foot risk status, secondly about their pathway of care before presentation to the multidisciplinary foot team, and thirdly about their interest in diabetes-related foot education and preferred learning style. RESULTS: There were 202 participants; 65% were male, mean age was 64±15 years (mean±standard deviation (SD)), 86% had type 2 diabetes, and mean HbA1c was 65±23mmol/mol (8.3±3.7%). Only 4% of participants knew their current foot risk status and 52% did not know why their care had been escalated to a multidisciplinary foot clinic. Participants with type 2 diabetes more readily expressed an interest in further foot education compared with participants with type 1 diabetes, (70% versus 29%, p=0.001). CONCLUSIONS: These findings show that people with diabetes and foot disease are less aware of their foot risk status or why they are referred to a multidisciplinary team. Participants indicated a variable interest in further learning about foot complications. These findings indicate possible communication and educational barriers between patients and health professionals which may contribute to delayed presentation or suboptimal engagement.

Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

Diabetic Peripheral Neuropathy and Depression: Dancing with Wolves? - Mini-Review and Commentary on Alghafri et al. "Screening for depressive symptoms amongst patients with diabetic peripheral neuropathy".

The co-existence of diabetic peripheral neuropathy (DPN) and depression in subjects with diabetes is being increasingly recognized. The interaction of these two serious comorbidities may increase morbidity and mortality. An emerging thought is that persisting depression, along with stroke and cognitive dysfunction, may represent a cluster of potential microvascular injuries affecting the brain, which shares a common risk factor with DPN. Current evidence highlights metabolic and clinical covariates, which may interact in subjects with DPN and depression. However, there is a lack of rigorous enquiry into the confounding effect of cognitive dysfunction and vascular brain disease. Furthermore, high-quality longitudinal studies exploring the direct impact of these comorbidities on diabetes course and on the progression of the comorbidities themselves are lacking. Improved insights into comorbid DPN and depression may help to improve screening for and treatment of both these conditions.

Admission Time Deep Swab Specimens Compared With Surgical Bone Sampling in Hospitalized Individuals With Diabetic Foot Osteomyelitis and Soft Tissue Infection.

Whether deep swab cultures taken at admission reliably identify pathogens compared to surgical bone specimens in hospitalized individuals with diabetic foot osteomyelitis and soft tissue infection is unclear. Comparison of microbiological isolates between a deep wound swab (DWS) taken at the time of admission through the actively infected, discharging ulcer probing to the bone and the subsequent surgical bone sample (SBS) taken during surgical debridement was made. A total of 63 subjects (age 60.8 ± 13.5 years, 75% male, 80% Type 2 diabetes, HbA1C 8.9%±2.2%) were included. The proportion of Gram-positive (DWS 49% v SBS 52%) and Gram-negative (DWS 60% v SBS 60%) isolates was similar between the techniques. However, the overall concordance of isolates between the two techniques was only fair (κ=0.302). The best concordance was observed for Staphylococcus aureus (κ=0.571) and MRSA (κ=0.644). There was a correlation between number of isolates in SBS with prior antibiotic therapy of any duration (r= -0.358, p=0.005) and with the duration of ulceration (r=0.296, p=0.045); no clinical correlations were found for DWS. Prior antibiotic therapy (p=0.03) and duration of ulceration <8 weeks (p=0.025) were predictive of negative growth on SBS. In conclusion, we found only a fair concordance between deep wound swabs acquired at admission and surgical bone specimens in those presenting with a severe diabetic foot infection and features of osteomyelitis. Ensuring early surgical debridement of all infected tissue and obtaining bone specimens should be considered a clinical priority, which may also reduce the likelihood of negative growth on SBS.

Pharmacological Treatments for Diabetic Foot Disease: Current State and Future Perspectives.

The care of the individual with diabetic foot disease (DFD) represents a significant challenge. In addition to the primary foot pathology, individuals with DFD are frequently compromised by multiple co-existent medical complications. Successful management of DFD, therefore requires simultaneous addressal of these issues alongside high-quality foot care. We explore the pharmacological treatments in DFD with an emphasis on the emerging putative technologies centred on addressing the pathobiology of wound healing but also discuss developments in infection control, Charcot neuroarthropathy, cardiovascular and diabetes care. Many of these will have a significant impact on future treatment paradigms and how we amalgamate these novel technologies may help shape the standard of care in DFD hereafter. However, there is a need for better quality of evidence and cost-effectiveness data prior to widespread adoption into routine care is considered.

Ultrasound Devices to Treat Chronic Wounds: The Current Level of Evidence.

Chronic wounds cause considerable morbidity and utilize significant health care resources. In addition to addressing wound etiology and treating infection, regular debridement is a key component of wound care with a proven ability to accelerate healing. In this regard, a significant innovation in wound care has been the development of ultrasound debridement technology. The purpose of this review is to evaluate the current evidence behind the technology with an emphasis on noncontact low-frequency (NCLF) ultrasound. A number of studies, especially those evaluating NCLF technology, have demonstrated the potential of ultrasound debridement to effectively remove devitalized tissue, control bioburden, alleviate pain, and expedite healing. However, most of the studies are underpowered, involve heterogeneous ulcer types, and demonstrate significant methodological limitations making comparison between studies difficult; there is a paucity of data on cost-effectiveness. Future clinical trials on ultrasound debridement technology must address the design issues prevalent in current studies, and report on clinically relevant endpoints before adoption into best-practice algorithms can be recommended.

Charcot foot reconstruction outcomes: A systematic review.

BACKGROUND: Charcot neuroarthropathy is a complex condition characterised by progressive deformity, limited treatment options and a high amputation rate. Surgical reconstruction of Charcot foot has been proposed as a method to preserve the foot. However, limited information exists on the different methods of reconstruction available, their outcomes and complications. METHODS: We systematically analysed published data from Jan 1993 to Dec 2018 to assess methods of fixation and associated outcomes for the surgical reconstruction in Charcot neuroarthropathy. Statistical analyses were undertaken to determine the amputation rates, return to ambulation and complications associated with these techniques. RESULTS: A total of 1116 feet (1089 patients) were reported to have undergone reconstruction with significant heterogeneity in patient selection. Of these, 726 (65%) were reported to undergo internal fixation, 346 feet (31%) external fixation and 44 (4%) undergoing simultaneous internal and external fixation. No single technique demonstrated a significant benefit over the other. Overall, the bone fusion rate was 86.1%. Complications directly attributable to the technique employed were noted in 36% of individuals. The reported post-reconstruction amputation rate was only 5.5% with 91% apparently returning to ambulation. CONCLUSIONS: Although no preferential method of fixation was identified, we find that the current options for surgical reconstruction could offer limb salvage with a low amputation risk in a highly selected population. However, the lack of controlled studies, inconsistent reporting of outcomes and heterogeneity of patient selection mean that the quality of evidence is low.

Depression and Diabetic Peripheral Neuropathy: Birds of a Feather, But When do They Flock Together?

The association between diabetes and depression is well recognised. Similarly, diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes. Given the high prevalence of these conditions individually, it is hardly surprising they frequently interact, conferring additional morbidity and a higher mortality risk. Despite this, the specific clinical characteristics that underpin co-morbid depression and DPN remain unclear. Additionally, there is insufficient insight into causal pathways and temporal trends. High-quality epidemiological data is limited, but they suggest that these conditions may share certain common risk factors, although there are also distinct differences such as gender. Improved insights into the risk factors for the co-existence of DPN and depression may help towards improved screening for and treatment of these conditions.

Editorial and Mini-Review: Topical Oxygen Therapy for Diabetic Foot Ulcerations - Avenue Towards New Hope?

Diabetic foot complications now represent the 10th leading cause of disease burden and disability. Wound healing is impaired, leading to chronic ulceration. Local high oxygen concentration is required by the metabolically active cells in the wound, which may render the region hypoxic, even in the absence of peripheral arterial disease. Therefore, the contribution of hyperbaric oxygen to improved healing rates has been extensively investigated. More recent developments include products delivering topical oxygen therapy (TOT) directly at the wound site, either by continuous delivery or by pressurized systems. A very recent systematic review has found that TOT increases wound healing rates in chronic, less severe diabetic foot ulcers (DFUs), and it promotes high rates of healing in more severe ulcers. Thus, TOT appears to be very promising to improve healing in DFUs. We now need more experience regarding its therapeutic place in the algorithm of DFU management and in relation to optimal patient selection.

The influence of age, anthropometric and metabolic variables on LDIFLARE and corneal confocal microscopy in healthy individuals.

INTRODUCTION: The laser Doppler imaging (LDI) FLARE and corneal confocal microscopy (CCM) are reliable markers of small fibre function (SFF) and structure (SFS), respectively, but the impact of potential confounding variables needs to be defined. The objective of this study was to determine the influence of age, anthropometric and biochemical variables on LDI and CCM. METHODS: 80 healthy volunteers (43 males) (age: 39.7±15.2 yrs.) underwent LDIFLARE and CCM assessment and the effect of age, anthropometric and biochemical variables was determined using multivariate analysis. RESULTS: There was an age-related decline in LDIFLARE (0.07cm2/yr; R2 = 0.669; p = <0.0001) and CCM parameters (CNFD: 0.05 fibres/mm2 /yr; R2 = 0.590; p = <0.0001, CNBD: 0.06 branches/mm2/yr; R2 = 0.549; p = 0.001and CNFL 0.07 mm/mm2/yr; R2 = 0.369; p = 0.009). BMI did not influence SFF (p = 0.08) but had a significant independent association with CNFD (p = 0.01). Fasting triglycerides (TG) independently influenced the LDIFLARE (ßc:-0.204; p = 0.008) and all CCM indices (ßc:-0.191 to -0.243; p = <0.05). HbA1c was significantly associated with CNFD only (p = 0.001) but not with LDIFLARE, CNBD or CNFL (p = ≥0.05). Blood pressure and total cholesterol were not associated with LDIFLARE or any CCM parameters. There was a significant correlation between LDIFLARE and all CCM parameters (p = ≤0.01). CONCLUSIONS: This study shows that in healthy controls, both SFF measured by LDIFLARE and SFS assessed by CCM showed a significant inverse correlation with age and triglycerides, perhaps suggesting the use of age-specific normative values when interpreting these outcomes. Furthermore, this study shows that in healthy controls, despite measuring different neural parameters, both methods correlated significantly with each other.

The Diabetic Foot Attack: "'Tis Too Late to Retreat!"

The "diabetic foot attack" is one of the most devastating presentations of diabetic foot disease, typically presenting as an acutely inflamed foot with rapidly progressive skin and tissue necrosis, at times associated with significant systemic symptoms. Without intervention, it may escalate over hours to limb-threatening proportions and poses a high amputation risk. There are only best practice approaches but no international protocols to guide management. Immediate recognition of a typical infected diabetic foot attack, predominated by severe infection, with prompt surgical intervention to debride all infected tissue alongside broad-spectrum antibiotic therapy is vital to ensure both limb and patient survival. Postoperative access to multidisciplinary and advanced wound care therapies is also necessary. More subtle forms exist: these include the ischemic diabetic foot attack and, possibly, in a contemporary categorization, acute Charcot neuroarthropathy. To emphasize the importance of timely action especially in the infected and ischemic diabetic foot attack, we revisit the concept of "time is tissue" and draw parallels with advances in acute myocardial infarction and stroke care. At the moment, international protocols to guide management of severe diabetic foot presentations do not specifically use the term. However, we believe that it may help increase awareness of the urgent actions required in some situations.