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BACKGROUND This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared to patients without TWO2. METHODS We conducted a retrospective review of deidentified patient medical records at 2 US Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. FINDINGS Among unmatched cohorts of 202 patients with DFU (91 TWO2, 111 NO TWO2), 66% and 121% of TWO2 patients had hospitalizations and amputations, respectively, compared to 541% and 414% of NO TWO2 patients within 360 days (P < 00001, P < 00001), representing 88% and 71% reductions. Among propensity score matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared to NO TWO2, 82% fewer TWO2 patients were hospitalized (71% vs 400%, P < 00001) and 73% fewer TWO2 patients had amputations (86% vs. 314%, P = 00007). Logistic regression among matched cohorts demonstrated nearly 9-fold and 5-fold higher risk of hospitalization and amputation, respectively, for NO TWO2 vs. TWO2. INTERPRETATION This retrospective cohort study demonstrates that treating patients with DFU with TWO2 is associated with significant reductions in hospitalizations and amputations in the real-world setting.

Prevention of amputation has become a key objective of clinicians providing care to patients with high-risk diabetic foot problems. In this regard, the multidisciplinary diabetic foot team (MDFT) has been embraced as the most effective way to manage patients with foot ulcers, infections, and Charcot feet. Importantly, such specialized teams have also integrated various surgical specialties to enable more expedient management of these often complex conditions. Experienced diabetic foot surgeons over the last three or four decades have contributed much to this discipline, whereby foot-sparing reconstructive procedures or minor amputations have become fundamental strategies for limb preservation teams. Central to limb salvage, of course, is the recognition of underlying vascular insufficiency and the importance of prompt (endo)vascular intervention. Restoration of adequate perfusion is essential to allow the podiatric, orthopaedic, or plastic surgeon to perform indicated functional reconstructive or minor amputation procedures. This evidence-based overview discusses the various indications and surgical principles inherent in modern concepts aimed at preventing amputation in the high-risk diabetic foot.

In the last 15 years an abundance of literature has demonstrated that angiosome-targeted revascularization, either endovascular or open, can lead to better clinical results in patients with chronic limb-threatening ischemia. According to this literature, the angiosome concept should guide our treatment strategy in every chronic limb-threatening ischemia patient. However, in our daily practice, its application is often difficult or impossible. Most foot wounds spread over multiple angiosomes and, moreover, the value of an angiosome-guided revascularization approach can vary according to vascular anatomy, collateral vessel network, type of revascularization, and wound. The aim of this article is to explore values and limits of the angiosome concept, and to propose some “instructions for use” regarding its application in our daily practice.

Background: This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared to patients without TWO2. Methods: We conducted a retrospective review of deidentified patient medical records at 2 US Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. Findings: Among unmatched cohorts of 202 DFU patients (91 TWO2, 111 NO TWO2), 6·6% and 12·1% of TWO2 patients had hospitalizations and amputations, respectively, compared to 54·1% and 41·4% of NO TWO2 patients within 360 days (P < 0·0001, P < 0·0001), representing 88% and 71% reductions. Among propensity score matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared to NO TWO2, 82% fewer TWO2 patients were hospitalized (7·1% vs 40·0%, P < 0·0001) and 73% fewer TWO2 patients had amputations (8·6% vs. 31·4%, P = 0·0007). Logistic regression among matched cohorts demonstrated nearly 9-fold and 5-fold higher risk of hospitalization and amputation, respectively, for NO TWO2 vs. TWO2. Interpretation: This retrospective cohort study demonstrates that treating DFU patients with TWO2 leads to significant reductions in hospitalizations and amputations in the real-world setting. Funding: AOTI Ltd. Declaration of Interest: This study was sponsored by AOTI Ltd. (Galway, Ireland). Health Advances received consultative reimbursement from AOTI, and T.N. received consultative reimbursement from Health Advances for his independent performance of the statistical analysis. R.G.F. has received research funding from and is a consultant for AOTI. M.G.G. has received research funding and is a consultant for AOTI. A.M.L. has received research funding from AOTI. No other potential conflicts of interest relevant to this article were reported. Ethical Approval: The protocol 18 was approved by the Institutional Review Board at each facility.

OBJECTIVE We conducted a multicenter evaluation of a novel remote foot-temperature monitoring system to characterize its accuracy for predicting impending diabetic foot ulcers (DFU) in a cohort of patients with diabetes with previously healed DFU. RESEARCH DESIGN AND METHODS We enrolled 132 participants with diabetes and prior DFU in this 34-week cohort study to evaluate a remote foot-temperature monitoring system (ClinicalTrials.gov Identifier NCT02647346). The study device was a wireless daily-use thermometric foot mat to assess plantar temperature asymmetries. The primary outcome of interest was development of nonacute plantar DFU, and the primary efficacy analysis was the accuracy of the study device for predicting the occurrence of DFU over several temperature asymmetry thresholds. RESULTS Of the 129 participants who contributed evaluable data to the study, a total of 37 (28.7%) presented with 53 DFU (0.62 DFU/participant/year). At an asymmetry of 2.22°C, the standard threshold used in previous studies, the system correctly identified 97% of observed DFU, with an average lead time of 37 days and a false-positive rate of 57%. Increasing the temperature threshold to 3.20°C decreased sensitivity to 70% but similarly reduced the false-positive rate to 32% with approximately the same lead time of 35 days. Approximately 86% of the cohort used the system at least 3 days a week on average over the study. CONCLUSIONS Given the encouraging study results and the significant burden of DFU, use of this mat may result in significant reductions in morbidity, mortality, and resource utilization.

We appreciate the thoughtful commentary by Londahl (1) on our recent article (2) describing the positive results of our double-blinded, randomized, placebo-controlled trial of the effect of cyclical, pressurized Topical Wound Oxygen (TWO2) therapy for healing chronic diabetic foot ulcers (DFUs). Recognizing that no study can be considered perfect in design, execution, or outcomes, we welcome this opportunity to address the concerns raised by Dr. Londahl pertaining to the aforementioned randomized controlled trial (RCT) (2). First, we do agree that the results of recent hyperbaric oxygen therapy (HBOT) trials are inconsistent and generally fail to provide robust evidence to support the adjunctive use of HBOT for DFUs (3–5). Much of the failure to provide consistent results is due to study design deficiencies; heterogeneity in study populations, inclusion criteria, and outcome measures (DFU healing vs. amputation); lack of sham controls; and loss of subjects because of adverse events and early terminations (6,7). Furthermore, intention-to-treat (ITT) analyses of all enrolled study populations has not been uniformly reported (3). Another difficulty in this regard …

Surgery for acute and chronic diabetic foot problems has long been an integral component of care. While partial foot amputations remain as important diabetic limb-salvaging operations, foot-sparing reconstructive procedures have become equally important strategies to preserve the functional anatomy of the foot while addressing infection, chronic deformities, and ulcerations. A classification of types of diabetic foot surgery is discussed in accordance with the soft tissue status and acuity of the presenting foot problem. This brief overview from the Association for Diabetic Foot Surgeons describes common conditions best treated by surgical interventions, as well as specific indications. While techniques and indications continue to evolve, effective surgical management of the diabetic foot remains an integral component of care as well as for the prevention of recurrent ulceration.

OBJECTIVE Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone. RESEARCH DESIGN AND METHODS Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy—both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase. RESULTS At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013). CONCLUSIONS This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.

Early diagnosis and a multidisciplinary team approach to managing comorbidities are essential in treating foot ulcerations.

The objective of this study was to examine the safety of cenplacel (PDA-002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal-like cell population derived from full-term human placenta. This phase 1, dose-escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle-brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 106 , 10 × 106 , 30 × 106 and 100 × 106 cells; administered intramuscularly on study days 1 and 8 in combination with standard of care). Overall, cenplacel was well tolerated in all 15 patients in the study. Before enrollment, nine patients had an ulcer for ≥6 months and 11 had an ABI of 0·7-0·85. No patient met dose-limiting toxicity criteria and no treatment-related serious adverse events were reported. There was preliminary evidence of ulcer healing in seven patients (five complete; two partial) within 3 months of cenplacel treatment, and circulating endothelial cell levels (a biomarker of vascular injury in PAD) were decreased within 1 month. Cenplacel was generally safe and well tolerated in patients with chronic DFUs and PAD. Outcomes from this study informed the doses, endpoints, biomarkers and patient population for an ongoing phase 2 trial.

Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a challenge. They are more susceptible to complications such as infection and amputation and require treatments that promote rapid development of granulation tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable cryopreserved human placental membrane (vCHPM) for DFUs has been established in a level 1 trial. However, complex wounds with exposed deeper structures are typically excluded from randomised controlled clinical trials despite being common in clinical practice. We report the results of a prospective, multicentre, open‐label, single‐arm clinical trial to establish clinical outcomes when vCHPM is applied weekly to complex DFUs with exposed deep structures. Patients with type 1 or type 2 diabetes and a complex DFU extending through the dermis with evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The mean wound area was 14·6 cm2, and mean duration was 7·5 months. For patients completing the protocol, the primary endpoint, 100% wound granulation by week 16, was met by 96·3% of patients in a mean of 6·8 weeks. Complete wound closure occurred in 59·3% (mean 9·1 weeks). The 4‐week percent area reduction was 54·3%. There were no product‐related adverse events. Four patients (13%) withdrew, two (6·5%) for non‐compliance and two (6·5%) for surgical intervention.

BACKGROUND: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. METHODS: The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. RESULTS: Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various débridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. CONCLUSIONS: Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly.

Background: Foot complications such as ulceration and neuropathy are common complications of diabetes mellitus (DM). Previous reports have demonstrated a possible increased risk of these complications in diabetic patients with low levels of serum vitamin D.Objectctive: The purpose of this study is to compare serum vitamin D levels in diabetic patients with and without Charcot neuroarthropathy (CN), peripheral arterial disease (PAD), infection (DFI), ulceration (DFU), and peripheral neuropathy (DPN). Design: A retrospective chart review of all patients undergoing foot and ankle surgery with a history of DM over a 13 month period was performed. From this cohort, fifty subjects with CN were matched with 50 without CN and preoperative lab values were compared. A secondary evaluation was performed on the subjects’ other comorbidities including PAD, DFI, DFU, and DPN. Results: Seventy-eight percent of our patients had vitamin D deficiency or insufficiency. Preoperative serum vitamin D levels were not significantly different between diabetic patients with and without CN (p = 0.55). Diabetic patients with PAD (p = 0.03), DFI (p = 0.0006), and DFU (p = 0.04) were all found to have significantly lower serum vitamin D levels than diabetic patients without these complications. Lower levels of serum albumin and higher serum creatinine were also noted with subjects with PAD, DFI, DPN, and DFU. While seasonal serum vitamin D level fluctuation was noted, this difference did not reach statistical significance with the numbers available. Conclusion: We found various lower extremity complications to be associated with low serum vitamin D including PAD, DFI, and DFU. While other studies have questioned the role of vitamin D and CN, we were unable to identify any significant difference between diabetic patients with and without Charcot neuroarthropathy. Level of evidence: Level 2

Non-healing DFUs lead to increased mortality, morbidity and health economic burden. Our RCT (NCT02326337) was undertaken to explore the efficacy of Topical Wound Oxygen (TWO2) homecare therapy in healing DFUs that had failed to heal with Standard of Care (SOC) alone. A Group Sequential Design was utilized with 2 interim analyses, requiring a significance of p Disclosure R. Frykberg: Research Support; Self; AOTI, Podometrics. P.J. Franks: Consultant; Self; AOTI. M.E. Edmonds: Advisory Panel; Self; Urgo Medical, Edixomed. J.N. Brantley: None. L. Téot: Advisory Panel; Self; Acelity, Integra LifeSciences. T. Wild: None. M.G. Garoufalis: None. A.M. Lee: None. J. Thompson: None. G. Reach: Other Relationship; Self; Abbott, AbbVie Inc., Janssen Pharmaceuticals, Inc., LifeScan, Inc., Eli Lilly and Company, Novo Nordisk Inc., Sanofi-Aventis, Servier, Becton, Dickinson and Company, AstraZeneca. C.R. Dove: None. K. Lachgar: None. D. Grotemeyer: Other Relationship; Self; AOTI Ltd.. Research Support; Self; Gore, Endologix.

Linezolid, a mild monoamine oxidase inhibitor, is a commonly used antibiotic drug for the treatment of complicated skin and skin structure infections, including diabetic foot infections. Use of linezolid has been associated with serotonin syndrome, a potentially life-threatening condition typically caused by the combination of two or more medications with serotonergic properties, due to increased serotonin release. The goals of this article are to highlight the risk factors associated with the development of serotonin syndrome related to the use of linezolid and to aid in its prevention and early diagnosis. In this case series we report on two hospitalized patients who, while being treated with linezolid for pedal infections, developed serotonin syndrome. Both individuals were also undergoing treatment with at least one serotonergic agent for depression and had received this medication within 2 weeks of starting the antibiotic drug therapy. In these individuals, we noted agitation, confusion, tremors, and tachycardia within a few days of initiation of linezolid therapy. Owing to the risk of serotonin toxicity, care should be taken when prescribing linezolid in conjunction with any other serotonergic agent. Although serotonin syndrome is an infrequent complication, it can be potentially life threatening. Therefore, risks and benefits of therapy should be weighed before use.

The diabetic Charcot foot is a potentially limb-threatening deformity associated with peripheral neuropathy and concomitant injury. Often the precipitating injury is fairly minor, but unrecognized due to the underlying peripheral sensory neuropathy. With existing loss of protective sensation the neuropathic individual continues to walk on the injured extremity causing progressive inflammation with varying degrees of bone and joint pathology. Severe deformity can ensue that predisposes to ulceration, infection, and potential amputation. It is therefore critical to diagnose this condition early in its natural history to prevent progressive foot or ankle deformity and instability.

Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

Objective Diabetic foot ulcers (DFUs) are frequently recalcitrant and at risk for infection, which may lead to lower-extremity amputation or bone resection. Reporting the incidence of amputations/bone resections may shed light on the relationship of ulcer healing to serious complications. This study aimed to evaluate the incidence of amputations/bone resections in a randomized controlled trial comparing human fibroblast-derived dermal substitute plus conventional care with conventional care alone for the treatment of DFUs. Design Ulcer-related amputation/bone resection data were extracted from data on all adverse events reported for the intent-to-treat population (N = 314), and amputations were categorized by type: below the knee, Syme, Chopart, transmetatarsal, ray, toe, or partial toe. Data were analyzed retrospectively for the incidence of amputation/bone resection by treatment. Setting Randomized controlled trial. Patients Patients with full-thickness DFUs greater than 6 weeks' duration. Interventions Standard wound care plus human fibroblast-derived dermal substitute versus standard wound care alone. Main results The incidence of amputation/bone resection in the study was 8.9% (28/314) overall, 5.5% (9/163) for patients receiving human fibroblast-derived dermal substitute, and 12.6% (19/151) for patients receiving conventional care (P = .031). Of the 28 cases of amputation/bone resection, 27 were preceded by ulcer-related infection. Conclusion There were significantly fewer amputations/bone resections in patients who received human fibroblast-derived dermal substitute versus conventional care, likely related to the lower incidence of infection adverse events observed in the human fibroblast-derived dermal substitute treatment group.

Objective: The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs). Method: A randomised, multicentre study was conducted at thirteen centers throughout the US. It was designed to evaluate the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence. Those subjects whose DFUs decreased in size by ≤30% or increased by ≤50% during the standard of care (SOC) phase were randomised into the treatment phase of the study. The study evaluated complete wound closure by eight weeks with weekly device application. A two-week post treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks, and wound closure was also evaluated at the end of that period. Ulcer recurrence at 6 months post-treatment was evaluated in the subjects that showed wound healing by the end of the post-treatment SOC phase. Standard adjunctive therapy, including debridement, saline irrigation and foot off-loading, was provided to both arms during the four-week screening period, after which eligible subjects were randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This study was developed to evaluate the hypothesis that the wound outcomes observed after wound management with MS were non-inferior to those of DG after eight weeks. The authors present the planned interim results of this study after one half of the projected enrolment was completed. Results: There were 95 subjects consented and entered into the SOC four-week screening phase of the trial and 56 were randomised into the treatment phase. At the planned interim analysis, there was a significantly lower cost per subject and significant improvement in patient quality of life for the subjects treated with MS compared with those managed with DG. However, there was not a statistically significant difference found during the analysis of the interim data between the two study groups for rate of wound healing or number of subjects with complete wound closure. Conclusion: The data from this interim analysis show that MSMM and MSWM provide results for healing DFUs that are similar to the results obtained for DG at a significant quality of life and economic advantage. Declaration of interest: The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs or the United States Government. T.W. Gilbert is employed as the Chief Science Officer and is a stockholder in ACell, Inc., which commercializes MatriStem Wound Matrix and MicroMatrix. None of the other authors have a conflict of interest to declare.

BackgroundWe sought to develop a consensus statement for the use of off-loading in the management of diabetic foot ulcers (DFUs).MethodsA literature search of PubMed for evidence regarding off-loading of DFUs was initially conducted, followed by a meeting of authors on March 15, 2013, in Philadelphia, Pennsylvania, to draft consensus statements and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to assess quality of evidence and develop strength of recommendations for each consensus statement.ResultsEvidence is clear that adequate off-loading increases the likelihood of DFU healing and that increased clinician use of effective off-loading is necessary. Recommendations are included to guide clinicians on the optimal use of off-loading based on an initial comprehensive patient/wound assessment and the necessity to improve patient adherence with off-loading devices.ConclusionsThe likelihood of DFU healing is increased with off-loading adherence, and, current evidence favors the use of nonremovable casts or fixed ankle walking braces as optimum off-loading modalities. There currently exists a gap between what the evidence supports regarding the efficacy of DFU off-loading and what is performed in clinical practice despite expert consensus on the standard of care.

The implementation of an inpatient diabetic foot service should be the goal of all institutions that care for patients with diabetes. The objectives of this team are to prevent problems in patients while hospitalized, provide curative measures for patients admitted with diabetic foot disorders, and optimize the transition from inpatient to outpatient care. Essential skills that are required for an inpatient team include the ability to stage a foot wound, assess for peripheral vascular disease, neuropathy, wound infection, and the need for debridement; appropriately culture a wound and select antibiotic therapy; provide, directly or indirectly, for optimal metabolic control; and implement effective discharge planning to prevent a recurrence. Diabetic foot ulcers may be present in patients who are admitted for nonfoot problems, and these ulcers should be evaluated by the diabetic foot team during the hospitalization. Pathways should be in place for urgent or emergent treatment of diabetic foot infections and neuropathic fractures/dislocations. Surgeons involved with these patients should have knowledge and interest in limb preservation techniques. Prevention of iatrogenic foot complications, such as pressure sores of the heel, should be a priority in patients with diabetes who are admitted for any reason: all hospitalized diabetic patients require a clinical foot exam on admission to identify risk factors such as loss of sensation or ischemia. Appropriate posthospitalization monitoring to reduce the risk of reulceration and infection should be available, which should include optimal glycemic control and correction of any fluid and electrolyte disturbances.

Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved.

Among other things wound healing requires restoration of macro-And microcirculation as essential conditions for healing.1,2 One of the most 'immediate' requirements is oxygen, which is critically important for reconstruction of new vessels and connective tissue and to enable competent resistance to infection.

Heparin is an anticoagulant commonly used to treat and prevent deep venous thrombosis. Heparin-induced thrombocytopenia and possible thrombosis are serious complications associated with its use. This can occasionally complicate treatment of patients undergoing podiatric surgery. Heparin-induced thrombocytopenia is often not immediately recognized and is underreported in podiatric medicine literature. The goal of this case report is to highlight the multiple risk factors associated with the development of heparin-induced thrombocytopenia and to aid with early recognition, understanding of pathogenesis, and treatment options. (J Am Podiatr Med Assoc 103(1): 67–72, 2013)

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity. (J Am Podiatr Med Assoc 101(5): 437–446, 2011)

The following case is an interesting presentation of gout and its long-term affects in a diabetic individual. The patient initially presented with ankle pain and, after radiographic examination, a suspicious lytic lesion in the talus and a fracture of the medial malleolus were identified. A full workup with bone biopsy was undertaken and, although the patient did not present in the typical fashion, gout was ultimately diagnosed. Based on our experience with this patient, we recommend that gout be included in the list of differential diagnoses in diabetic patients with ankle pain and radiographic evidence of articular and bone destruction. The diagnosis and treatment of gout are addressed in this paper as well. Level of Clinical Evidence: 4

The following article1 is the report of an American Diabetes Association task force that summarizes the recent literature on tests and measures to identify people at risk for foot ulceration and to recommend what should be included in the comprehensive foot exam for adult patients with diabetes. Although this information would be timely and pertinent for physical therapists at any time, its content is particularly complementary to the content of PTJ's Special Issue on Diabetes. This article has been reprinted with permission of the American Diabetes Association from Boulton AJM, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care . 2008;31:1679-1685. DOI: 10.2337/dc08-9021. Available online at: http://care.diabetesjournals.org. Copyright ©2008 American Diabetes Association. From Diabetes Care ®, Vol 31, 2008; 1679-1685. Reprinted with permission from The American Diabetes Association . Reference 1 Boulton AJM, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. 2008;31:1679–1685. [OpenUrl][1][FREE Full Text][2] [1]: {openurl}?query=rft.jtitle%253DDiabetes%2BCare%26rft.stitle%253DDiabetes%2BCare%26rft.issn%253D0149-5992%26rft.aulast%253DBoulton%26rft.auinit1%253DA.%2BJ.M.%26rft.volume%253D31%26rft.issue%253D8%26rft.spage%253D1679%26rft.epage%253D1685%26rft.atitle%253DComprehensive%2BFoot%2BExamination%2Band%2BRisk%2BAssessment%253A%2BA%2Breport%2Bof%2Bthe%2BTask%2BForce%2Bof%2Bthe%2BFoot%2BCare%2BInterest%2BGroup%2Bof%2Bthe%2BAmerican%2BDiabetes%2BAssociation%252C%2Bwith%2Bendorsement%2Bby%2Bthe%2BAmerican%2BAssociation%2Bof%2BClinical%2BEndocrinologists%26rft_id%253Dinfo%253Adoi%252F10.2337%252Fdc08-9021%26rft_id%253Dinfo%253Apmid%252F18663232%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=diacare&resid=31/8/1679&atom=%2Fptjournal%2F88%2F11%2F1436.atom

Background: The purpose of this study was to identify and report the complications associated with the use of circular ring fixation in diabetic patients, and to compare the frequency of complications in patients without diabetes. We hypothesized that complications with circular ring fixation occurred more frequently in patients with diabetes than patients without diabetes. Materials and Methods: Institutional Review Board approval was obtained and patient charts were retrospectively reviewed from June 2004 and February 2007. Fifty six consecutive patients undergoing midfoot, hindfoot and/or ankle surgery were treated with circular ring fixation which included 33 diabetic patients in the study group and 23 non-diabetic patients in the control group. Patient demographics, the duration of treatment with the external fixator, and complications were recorded. Results: Males had a greater number of complications compared to females ( p = 0.0014). The total number of complications was statistically greater in diabetic patients (study group) versus non-diabetic patients (control group) ( p = 0.003). In multivariate logistic regression, diabetes and male sex were the only significant variables associated with wire complications (OR 7.35, 95% CI 1.93-28.04 and OR 0.22, 95% CI 0.05-8584111, respectively). Conclusion: Women are protected from wire complications with a risk reduction of 78% compared to males. Diabetics have a 7-fold risk for any wire complication compared to patients without diabetes. We found no adverse effects of BMI, obesity, age, smoking, neuropathy, or Charcot neuroarthropathy on a satisfactory recovery.Level of Evidence: IV, Retrospective Case Study

Background: This study was undertaken to assess the benefits of negative-pressure wound therapy (NPWT) versus traditional wound therapies in reducing the incidence of lower-extremity amputations in patients with diabetic foot ulcers. Methods: Administrative claims data for patients with diabetic foot ulcers from commercial payers (n = 3,524) and Medicare (n = 12,795) were retrospectively analyzed. Patients were divided into NPWT and control/traditional therapy groups on the basis of administrative codes. Risk-adjustment procedures were then performed to match patient risk categories (through total treatment costs) and wound severities (through debridement depth). Results: The incidence of amputations in the NPWT groups was lower than that in the control groups. For the cost-based risk-adjustment analysis, amputation incidences with NPWT versus traditional therapy were 35% lower in the Medicare sample (10.8% versus 16.6%; P = .0077) and 34% lower in the commercial payer sample (14.1% versus 21.4%; P = .0951). Whereas overall amputation rates increased progressively with increasing wound debridement depth in both control groups, the same increasing trend did not occur in the NPWT groups. Conclusions: Patients with diabetic foot ulcers in the Medicare sample treated with NPWT had a lower incidence of amputations than those undergoing traditional wound therapy; this finding was evident in wounds of varying depth in both populations studied. (J Am Podiatr Med Assoc 97(5): 351–359, 2007)

Our objective was to determine factors associated with complications of Ilizarov external ring fixator surgery for foot and ankle disorders in persons with diabetes mellitus. We reviewed the records of patients who underwent Charcot foot reconstruction or soft tissue offloading surgery over 1 year at a single institution. We compared the association of serious pin tract infection, pin fracture, and surgical wound dehiscence with the patient age, weight, duration device was used, preoperative glucose, preoperative hemoglobin, tourniquet time, and total operating time. Fifteen patients (16 limbs) underwent reconstructive surgery. Younger age, elevated preoperative glucose, and lengthy tourniquet times were associated with complications (P = .03). These data demonstrate that 2 modifiable factors (preoperative hyperglycemia and tourniquet time) predict complications and should be mitigated to lower risk.

The Syme amputation is often overlooked as an alternative to below-knee amputation or above-knee amputation in cases of limb-threatening foot infections and gangrene. Even though the advantages of the Syme amputation over major amputation are well cited in the literature, many surgeons do not view this amputation as a viable option for limb salvage. We herein present our initial experience with this operation in a series of patients at imminent risk for major lower extremity amputation. This study included our initial 26 patients at high risk (92% had diabetes) with infection and/or significant peripheral arterial disease who underwent ankle disarticulation for limb salvage. Medical records were abstracted for pertinent demographic and clinical data. Variables of interest included diabetes status and duration, presence of peripheral arterial disease, infection, osteomyelitis, and gangrene. Our primary outcome variable was a healed amputation, whereas secondary outcomes included time to healing, subsequent major amputations, and complications. Despite prior recommendation for below-knee amputation or above-knee amputation in each of these patients, 50% remained healed at an average of 49.3 weeks of follow-up. Although 17 patients (65.4%) ambulated in a Syme prosthesis after healing of the original Syme operation, several patients went on to major amputation for progressive sepsis or recurrent ulcers, and 1 patient subsequently died. Because of the relatively small number of study subjects, we could find no significant predictors of success or failure of this procedure. However, all 10 patients eventually succumbing to major amputation and all 3 patients who died during follow-up had diabetes mellitus. At the end of follow-up, 46.2% (12/26) patients were functioning well in a Syme prosthesis. In this high-risk cohort of patients in whom major amputation had been recommended, we achieved a healing rate of 50% at an approximate 1-year follow-up. With the majority of patients having diabetes and peripheral vascular disease, we could not find any clear predictive factors for failure or successful outcome in this small population. Nonetheless, the Syme amputation deserves further study and consideration as a viable limb salvage option in patients threatened with major lower extremity amputation.

Linezolid, a mild monoamine oxidase inhibitor, is a commonly used antibiotic drug for the treatment of complicated skin and skin structure infections, including diabetic foot infections. Use of linezolid has been associated with serotonin syndrome, a potentially life-threatening condition typically caused by the combination of two or more medications with serotonergic properties, due to increased serotonin release. The goals of this article are to highlight the risk factors associated with the development of serotonin syndrome related to the use of linezolid and to aid in its prevention and early diagnosis. In this case series we report on two hospitalized patients who, while being treated with linezolid for pedal infections, developed serotonin syndrome. Both individuals were also undergoing treatment with at least one serotonergic agent for depression and had received this medication within 2 weeks of starting the antibiotic drug therapy. In these individuals, we noted agitation, confusion, tremors, and tachycardia within a few days of initiation of linezolid therapy. Owing to the risk of serotonin toxicity, care should be taken when prescribing linezolid in conjunction with any other serotonergic agent. Although serotonin syndrome is an infrequent complication, it can be potentially life threatening. Therefore, risks and benefits of therapy should be weighed before use.

The infected or ulcerated diabetic foot is a suitable environment for Clostridium tetani. Tetanus intoxication as a result of foot ulcer has been described in the literature. Immunopathy, vasculopathy, and ulceration place the diabetic patient at risk for developing tetanus. Of diabetic patients who contract generalized tetanus in the United States, foot ulcer or gangrene are responsible for 25% of cases. Patients who have diabetic wounds should receive tetanus prophylaxis. The prophylaxis should follow the "tetanus-prone" wound recommendations as set by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices.

The prevalence of diabetes mellitus is growing at epidemic proportions in the United States and worldwide. Most alarming is the steady increase in type 2 diabetes, especially among young and obese people. An estimated 7% of the US population has diabetes, and because of the increased longevity of this population, diabetes-associated complications are expected to rise in prevalence. Foot ulcerations, infections, Charcot neuroarthropathy, and peripheral arterial disease frequently result in gangrene and lower limb amputation. Consequently, foot disorders are leading causes of hospitalization for persons with diabetes and account for billion-dollar expenditures annually in the US. Although not all foot complications can be prevented, dramatic reductions in frequency have been achieved by taking a multidisciplinary approach to patient management. Using this concept, the authors present a clinical practice guideline for diabetic foot disorders based on currently available evidence, committee consensus, and current clinical practice. The pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are reviewed. While these guidelines cannot and should not dictate the care of all affected patients, they provide evidence-based guidance for general patterns of practice. If these concepts are embraced and incorporated into patient management protocols, a major reduction in diabetic limb amputations is certainly an attainable goal.

PURPOSETo familiarize the physician and registered professional nurse with an overview of updated guidelines for the prevention and/or management of pressure ulcers, diabetic foot ulcers, and surgical site infections.TARGET AUDIENCEThis continuing education activity is intended for physicians and nu

Foot infections are a major complication of diabetes mellitus and contribute to the development of gangrene and lower extremity amputation. Recent evidence indicates that persons with diabetes are at greater risk for infection because of underlying neuropathy, peripheral vascular disease, and impaired responses to infecting organisms. This article reviews the underlying pathophysiology, causes, microbiology, and current management concepts for this potentially limb-threatening complication. Multidisciplinary management consisting of teams of specialists with a focus on limb preservation can make significant improvements in outcomes, including a reduction in rates of lower extremity amputation.

Foot ulcerations, infections, gangrene, and lower extremity amputation are major causes of disability to the patient who has diabetes mellitus, often resulting in significant morbidity, extensive periods of hospitalization, and mortality. Although not all such lesions can be prevented, it is possible to dramatically reduce their incidence through appropriate management and prevention protocols incorporating a multidisciplinary team approach.

This review discusses some of the significant studies and events from the 61st American Diabetes Association’s Scientific Symposium. Many of the issues raised at the meeting will form building blocks for future research into offloading, footwear, wound classification, wound healing, tissue engineering, and psychological aspects of therapy and prevention. (J Am Podiatr Med Assoc 92(1): 2-6, 2002)

Multiple offloading modalities are currently used in the management of diabetic plantar foot ulcerations. A relatively new device, the Rocker Insole, was tested for its ability to relieve plantar forefoot pressures when inserted into a surgical boot as compared to a patient’s customary footwear and the surgical boot alone. The Rocker Insole significantly reduced forefoot pressures by 48% when worn inside the surgical boot. Mean peak pressures unexpectedly increased 12% when the surgical boot was worn alone. This preliminary investigation suggests that when worn in conjunction with a surgical boot, the Rocker Insole can effectively offload plantar forefoot pressures and may be useful in the management of plantar metatarsal ulcerations. (J Am Podiatr Med Assoc 92(1): 48-53, 2002)

OBJECTIVE This prospective study was designed to evaluate the rate of surgical site infection (SSI) after foot and ankle surgery in patients with and without diabetes. RESEARCH DESIGN AND METHODS The study prospectively evaluated 1,465 consecutive foot and ankle surgical cases performed by a single surgeon. RESULTS The overall SSI rate in this study was 3.5%, with significantly more infections occurring in individuals with diabetes than in those without (9.5 vs. 2.4%, P < 0.001). Peripheral neuropathy, Charcot neuroarthropathy, current or past smoking, and increasing length of surgery were significantly associated with SSI on multivariate analysis. CONCLUSIONS This study demonstrates significant associations between the development of SSI and chronic complications of diabetes. We confirm previous findings that it is peripheral neuropathy and not diabetes itself that most strongly determines the development of postoperative infections in these surgical patients.

We sought to develop a consensus statement for the use of off-loading in the management of diabetic foot ulcers (DFUs).A literature search of PubMed for evidence regarding off-loading of DFUs was initially conducted, followed by a meeting of authors on March 15, 2013, in Philadelphia, Pennsylvania, to draft consensus statements and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to assess quality of evidence and develop strength of recommendations for each consensus statement.Evidence is clear that adequate off-loading increases the likelihood of DFU healing and that increased clinician use of effective off-loading is necessary. Recommendations are included to guide clinicians on the optimal use of off-loading based on an initial comprehensive patient/wound assessment and the necessity to improve patient adherence with off-loading devices.The likelihood of DFU healing is increased with off-loading adherence, and, current evidence favors the use of nonremovable casts or fixed ankle walking braces as optimum off-loading modalities. There currently exists a gap between what the evidence supports regarding the efficacy of DFU off-loading and what is performed in clinical practice despite expert consensus on the standard of care.

Background: This prospective study was designed to evaluate the frequency of surgical site infection in patients treated with foot and ankle surgery. Our hypothesis was that patients with complications of diabetes are at increased risk for surgical site infection compared with patients without diabetes and patients with diabetes who do not have diabetic complications. Another goal was to compare the association of neuropathy with surgical site infection in both nondiabetic and diabetic patients. Methods: Two thousand and sixty consecutive surgical cases were evaluated. Group 1 included nondiabetic patients without neuropathy, Group 2 included nondiabetic patients with neuropathy, Group 3 included patients with diabetes but no diabetic complications, and Group 4 included patients with diabetes who had at least one complication of diabetes. Results: The surgical site infection rate in this study was 3.1%. Patients with complicated diabetes had a 7.25-fold increased risk of surgical site infection compared with nondiabetic patients without neuropathy and a 3.72-fold increased risk compared with patients with uncomplicated diabetes. Patients with complicated diabetes had a nonsignificant 1.54-fold higher rate of surgical site infection compared with nondiabetic patients with neuropathy. Nondiabetic patients with neuropathy had a significant 4.72-fold increased risk of surgical site infection compared with nondiabetic patients without neuropathy. Despite this, nondiabetic patients with neuropathy did not have a significantly higher rate of surgical site infection than patients with uncomplicated diabetes, and the frequency of surgical site infection in the group with uncomplicated diabetes was not significantly different from that in the nondiabetic patients without neuropathy. Multivariable logistic regression analysis demonstrated that peripheral neuropathy and a hemoglobin A1c of ≥8% were independently associated with surgical site infection. Conclusions: Complicated diabetes increases the risk of surgical site infection after foot and ankle surgery. Patients who had diabetes without complications did not have a greater risk of surgical site infection compared with nondiabetic patients without neuropathy. The presence of neuropathy increases the risk of surgical site infection even in patients without diabetes. Poor long-term glycemic control is also associated with an increased risk of surgical site infection. Level of Evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.