Data about long-term clinical outcomes of revascularization procedures, especially for autologous cell therapy (ACT), in diabetic patients with chronic limb-threatening ischaemia (CLTI) are lacking. The aim of our study was to compare the mortality and amputation rates in patients with diabetic foot ulcers (DFU) and CLTI treated by ACT with patients treated by repeated percutaneous transluminal angioplasty (re-PTA) and those treated conservatively.

One-hundred and thirty patients with DFU and CLTI (defined as transcutaneous oxygen pressure-TcPO2 <30 mmHg after unsuccessful standard revascularization) treated in our foot clinic over 9 years were enrolled in the study. Forty-five patients were treated by ACT, 43 patients underwent re-PTA, and 42 patients were treated conservatively and formed the control group. Overall survival, amputation-free survival (AFS) and major amputation rate were assessed over a 7-year follow-up period.

Baseline demographic characteristics and comorbidities were similar between groups. However, patients in ACT and control groups had significantly worse baseline angiograms in accordance with Graziani and GLASS (infrapopliteal region) classifications than the re-PTA group (both p < 0.001), but there were no differences in baseline values of TcPO2 between groups. AFS in the ACT and re-PTA groups were significantly longer compared to control (both p < 0.001). The rate of major amputation was significantly lower in both active groups (both p < 0.001). The re-PTA group showed significantly longer overall survival compared to the control group (p < 0.001), but there was no significant difference between ACT and control groups (p = 0.063) and ACT and re-PTA groups (p = 0.081) in this parameter.

Our study showed significantly longer AFS and lower major amputation rates in patients treated by ACT and re-PTA in contrast to patients treated conservatively. Overall survival was significantly longer only in the re-PTA group. ACT was shown to be effective in long-term limb salvage in people with no-option CLTI.

Osteomyelitis (OM) associated with diabetic foot ulceration (DFU) is a growing public health challenge worldwide. Since 2012 the number of patients presenting with DFU per year to our centre has doubled.

This study aims to evaluate outcomes from outpatient antibiotic therapy (OPAT) in the management of OM in DFU patients.

A retrospective analysis was performed of medical notes, radiology, and vascular laboratory reports for all DFU patients with OM treated from April 2016 to April 2020. Variables analyzed included age, gender, site of OM, WIfI Score (Wound Ischaemia and foot Infection Score), probe-to-bone test (PTB), imaging (X-ray/magnetic resonance imaging (MRI), co-morbidities (peripheral arterial disease (PAD), chronic kidney disease (CKD), hypertension (HTN), smoking, ischemic heart disease (IHD), and dyslipidaemia. Outcomes evaluated were healing, recurrent DFU, and freedom from amputation at 12 months.

185 patients were admitted with 264 infected digits (Male 223; Female 41). The mean age was 66 years. Only 168 (63.6%) were fully healed at 12 months. Of the 96 patients who failed to heal, 43 underwent a repeat course of prolonged antibiotics without improvement. Factors associated with treatment failure were PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene.

Extended outpatient antibiotic therapy (with an inpatient multidisciplinary approach) is an effective treatment for digital OM in DFU with a success rate of 63%. In recurrence, repeating prolonged antibiotics is unlikely to achieve healing. PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene are predictors of treatment failure.

Chronic limb-threatening ischemia (CLTI) is associated with significant mortality and limb loss. The interventional lumbar sympathectomy (LS) is one of the supportive treatment options for CLTI patients, reducing pain intensity and peripheral arterial resistance. The use of LS has gradually declined despite its positive effects. The contradictory results of studies dealing with evidence of tissue perfusion improvement after LS are one of the possible explanations. We describe a new approach for the evaluation of LS efficacy in 2 CLTI patients and below-the-knee arteries pathology in our observational cohort experimental trial. We utilized the angiosome concept of foot. Angiography identified angiosomes with occluded source artery. The relationship between angiosomes and corresponding surface areas of angiosomes-dermatomes was identified. The infrared thermography was used for the measurement of thermal changes in dermatomes before and after LS. Based on the thermal changes in dermatomes and the relationship between angiosomes and their dermatomes, we estimated perfusion in angiosomes after the LS procedure. We found that the clinically relevant increase in temperature (>1°C) was presented only in dermatomes corresponding to angiosomes with occluded source artery. We hypothesize that LS opens up anastomoses between angiosomes, resulting in redistribution of blood flow between angiosomes that is associated with an increase in temperature in angiosomes with occluded source artery.

Objective: The objective of this open-label, interventional, prospective clinical study was to evaluate the effectiveness of a multimodal wound matrix (MWM) in moving chronic, nonhealing wounds that had failed prior therapies onto a healing trajectory. The overall response rate was the proportion of subjects who had greater than 40% reduction in size after 4 weeks of treatment. Secondary objectives included the percentage area reduction (PAR) after 4 and 12 weeks, incidence of ulcer closing, and changes in quality of life. Approach: An open-label, interventional, prospective cohort, real-world evidence study was conducted following the STROBE criteria. Criteria included chronic nonhealing wounds of multiple etiologies in subjects with extensive comorbidities. Results were compared with data from the U.S. Wound Registry. Results: A total of 111 subjects entered the screening phase and 64 were treated. Fifty-three wounds were eligible for the dataset that included 18 diabetic foot ulcers, 19 venous leg ulcers, 2 pressure injuries, 1 surgical, 1 lower extremity wound, and 12 unclassified etiologies. The objective response rate was 42%. The 4-week PAR was 34%. The 12-week PAR was 66%. Eighteen wounds closed by week 12. Innovation: MWM is a formulation technology developed to address the major obstacles that prevent healing. Results were evaluated in a patient population with extensive comorbidities that had failed prior treatments and would be generally excluded from controlled trials. Conclusion: The results from this study support the contention that MWM achieves substantial clinical improvement in a complex patient population not enrolled in clinical trials and demonstrates an advancement in wound management.

The timely provision of load-bearing prostheses significantly reduces healthcare costs and lowers post-amputation mortality risk. However, current methods for assessing residuum health remain subjective, underscoring the need for standardized, evidence-based approaches incorporating physical biomarkers to evaluate residual limb healing and determine readiness for prosthetic rehabilitation.

This review aimed to identify predictive, diagnostic, and indicative physical biomarkers of healing of the tissues and structures found in the residual limbs of adults with amputation.

A scoping review was conducted following Joanna Briggs Institute (JBI) and PRISMA-ScR guidance. Searches using "biomarkers", "wound healing", and "amputation" were performed on May 6, 2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Inclusion criteria were: 1) References to physical biomarkers and healing; 2) Residuum tissue healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system), and categorized by study, wound, and model type. Physical biomarkers that were repeated not just within categories, but across more than one of the study categories were reported on.

The search strategy identified 3,306 sources, 157 of which met the inclusion criteria. Histology was the most frequently repeated physical biomarker used in 64 sources, offering crucial diagnostic insights into cellular healing processes. Additional repeated indicative and predictive physical biomarkers, including ankle-brachial index, oxygenation measures, perfusion, and blood pulse and pressure measurements, were reported in 25, 19, 13, and 12 sources, respectively, providing valuable data on tissue oxygenation and vascular health.

Ultimately, adopting a multifaceted approach that integrates a diverse array of physical biomarkers (accounting for physiological factors and comorbidities known to influence healing) may substantially enhance our understanding of the healing process and inform the development of effective rehabilitation strategies for individuals undergoing amputation.

To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM).

This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points.

Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA.

Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

Decision-making regarding level of lower extremity amputation is sometimes challenging. Selecting an appropriate anatomic level for major amputation requires consideration of tradeoffs between postoperative function and risk of wound complications that may require additional operations, including debridement and/or conversion to above-knee amputation (AKA). We evaluated the utility of common, non-invasive diagnostic tests used in clinical practice to predict the need for reoperations among patients undergoing primary, elective, below knee-amputations (BKAs) by vascular surgeons.

Patients undergoing elective BKA over a 5-year period were identified using Current Procedural Terminology codes. Medical records were reviewed to characterize demographics, pre-amputation testing transcutaneous oxygen tension (TcPO2), and ankle-brachial index (ABI). The need for ipsilateral post-BKA reoperation (including BKA revision and/or conversion to AKA) regardless of indication was the primary outcome. Associations were evaluated using univariable and multivariable logistic regression models. Cutpoints for TcPO2 values associated with amputation reoperation were evaluated using receiver operating characteristic curves.

We identified 175 BKAs, of which 46 (26.3%) required ipsilateral reoperation (18.9% BKA revisions and 14.3% conversions to AKA). The mean age was 63.3 ± 14.8 years. Most patients were male (65.1%) and White (72.0%). Mean pre-amputation calf TcPO2 was 40.0 ± 20.5 mmHg, and mean ABI was 0.64 ± 0.45. In univariable models, post-BKA reoperation was associated with calf TcPO2 (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = .013) but not ABI (OR, 0.53; 95% CI, 0.19-1.46; P = .217). Univariable associations with reoperation were also identified for age (OR, 0.97; 95% CI, 0.94-0.990; P = .003) and diabetes (OR, 0.43; 95% CI, 0.21-0.87; P = .019). No associations with amputation revision were identified for gender, race, end-stage renal disease, or preoperative antibiotics. Calf TcPO2 remained associated with post-BKA reoperation in a multivariable model (OR, 0.97; 95% CI, 0.94-0.99; P = .022) adjusted for age (OR, 0.98; 95% CI, 0.94-1.01; P = .222) and diabetes (OR, 0.98; 95% CI, 0.94-1.01; P = .559). Receiver operating characteristic analysis suggested a TcPO2 ≥38 mmHg as an appropriate cut-point for assessing risk for BKA revision (area under the curve = 0.682; negative predictive value, 0.91).

Reoperation after BKA is common, and reoperation risk was associated with pre-amputation TcPO2. For patients undergoing elective BKA, higher risk of reoperation should be discussed with patients with an ipsilateral TcPO2 <38 mmHg.

Patients with type-2 diabetes (T2DM) are at increased risk of developing diabetic foot ulcers (DFU) and experiencing impaired wound healing related to underlying microvascular disease.

To evaluate the sensitivity of intra-voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI to microvascular changes in patients with DFUs.

Case-control.

20 volunteers who were age and body mass index matched, including T2DM patients with DFUs (N = 10, mean age = 57.5 years), T2DM patients with controlled glycemia and without DFUs (DC, N = 5, mean age = 57.4 years) and healthy controls (HC, N = 5, mean age = 52.8 years).

3T/multi-b-value IVIM and dynamic BOLD.

Resting IVIM parameters were obtained using a multi-b-value diffusion-weighted imaging sequence and two IVIM models were fit to obtain diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and microvascular volume fraction (MVF) parameters. Microvascular reactivity was evaluated by inducing an ischemic state in the foot with a blood pressure cuff during dynamic BOLD imaging. Perfusion indices were assessed in two regions of the foot: the medial plantar (MP) and lateral plantar (LP) regions.

Effect sizes of group mean differences were assessed using Hedge's g adjusted for small sample sizes.

DFU participants exhibited elevated D*, f, and MVF values in both regions (g ≥ 1.10) and increased D (g = 1.07) in the MP region compared to DC participants. DC participants showed reduced f and MVF compared to HC participants in the MP region (g ≥ 1.06). Finally, the DFU group showed reduced tolerance for ischemia in the LP region (g = -1.51) and blunted reperfusion response in both regions (g < -2.32) compared to the DC group during the cuff-occlusion challenge.

The combined use of IVIM and BOLD MRI shows promise in differentiating perfusion abnormalities in the feet of diabetic patients and suggests hyperperfusion in DFU patients.

1 TECHNICAL EFFICACY: Stage 1.

Background and Objectives: Medical registries evolved from a basic epidemiological data set to further applications allowing deriving decision making. Revision rates after non-traumatic amputation are high and dramatically impact the following rehabilitation of the amputee. Risk scores for revision surgery after non-traumatic lower limb amputation are still missing. The main objective was to create an amputation registry allowing us to determine risk factors for revision surgery after non-traumatic lower-limb amputation and to develop a score for an early detection and decision-making tool for the therapeutic course of patients at risk for non-traumatic lower limb amputation and/or revision surgery. Materials and Methods: Retrospective data analysis was of patients with major amputations lower limbs in a four-year interval at a University Hospital of maximum care. Medical records of 164 patients analysed demographics, comorbidities, and amputation-related factors. Descriptive statistics analysed demographics, prevalence of amputation level and comorbidities of non-traumatic lower limb amputees with and without revision surgery. Correlation analysis identified parameters determining revision surgery. Results: In 4 years, 199 major amputations were performed; 88% were amputated for non-traumatic reasons. A total of 27% of the non-traumatic cohort needed revision surgery. Peripheral vascular disease (PVD) (72%), atherosclerosis (69%), diabetes (42%), arterial hypertension (38%), overweight (BMI > 25), initial gangrene (47%), sepsis (19%), age > 68.2 years and nicotine abuse (17%) were set as relevant within this study and given a non-traumatic amputation score. Correlation analysis revealed delayed wound healing (confidence interval: 64.1% (47.18%; 78.8%)), a hospital length of stay before amputation of longer than 32 days (confidence interval: 32.3 (23.2; 41.3)), and a BKA amputation level (confidence interval: 74.4% (58%; 87%)) as risk factors for revision surgery after non-traumatic amputation. A combined score including all parameters was drafted to identify non-traumatic amputees at risk for revision surgery. Conclusions: Our results describe novel scoring systems for risk assessment for non-traumatic amputations and for revision surgery at non-traumatic amputations. It may be used after further prospective evaluation as an early-warning system for amputated limbs at risk of revision.

Diabetes-related foot disease is a major source of patient burden and societal costs. Investing in evidence-based international guidelines on diabetes-related foot disease is important to reduce this burden and costs, provided the guidelines are focused on outcomes important to key stakeholders and are evidence-based and properly implemented.

The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2023 updates were made using the Grading of Recommendations Assessment Development and Evaluation evidence-to-decision framework. This concerns formulating relevant clinical questions and important outcomes, conducting systematic reviews of the literature and meta-analyses where appropriate, completing summary of judgement tables, and writing recommendations that are specific, unambiguous and actionable, along with their transparent rationale.

We herein describe the development of the 2023 IWGDF Guidelines on the prevention and management of diabetes-related foot disease, which consists of seven chapters, each prepared by a separate working group of international experts. These chapters provide guidelines related to diabetes-related foot disease on prevention; classification of diabetes-related foot ulcer, offloading, peripheral artery disease, infection, wound healing interventions, and active Charcot neuro-osteoarthropathy. Based on these seven guidelines, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field.

We believe that the adoption and implementation of the 2023 IWGDF guidelines by healthcare providers, public health agencies, and policymakers will improve the prevention and management of diabetes-related foot disease, and subsequently reduce the worldwide patient and societal burden caused by this disease.

As a progressive disease process, early diagnosis and ongoing monitoring and treatment of lower limb peripheral artery disease (PAD) is critical to reduce the risk of diabetes-related foot ulcer (DFU) development, non-healing of wounds, infection and amputation, in addition to cardiovascular complications. There are a variety of non-invasive tests available to diagnose PAD at the bedside, but there is no consensus as to the most diagnostically accurate of these bedside investigations or their reliability for use as a method of ongoing monitoring. Therefore, the aim of this systematic review was to first determine the diagnostic accuracy of non-invasive bedside tests for identifying PAD compared to an imaging reference test and second to determine the intra- and inter-rater reliability of non-invasive bedside tests in adults with diabetes. A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective and retrospective investigations of the diagnostic accuracy of bedside testing in people with diabetes using an imaging reference standard and reliability studies of bedside testing techniques conducted in people with diabetes were eligible. Included studies of diagnostic accuracy were required to report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) which were the primary endpoints. The quality appraisal was conducted using the Quality Assessment of Diagnostic Accuracy Studies and Quality Appraisal of Reliability quality appraisal tools. From a total of 8517 abstracts retrieved, 40 studies met the inclusion criteria for the diagnostic accuracy component of the review and seven studies met the inclusion criteria for the reliability component of the review. Most studies investigated the diagnostic accuracy of ankle -brachial index (ABI) (N = 38). In people with and without DFU, PLRs ranged from 1.69 to 19.9 and NLRs from 0.29 to 0.84 indicating an ABI <0.9 increases the likelihood of disease (but the extent of the increase ranges from a small to large amount) and an ABI within the normal range (≥0.90 and <1.3) does not exclude PAD. For toe-brachial index (TBI), a threshold of <0.70 has a moderate ability to rule PAD in and out; however, this is based on limited evidence. Similarly, a small number of studies indicate that one or more monophasic Doppler waveforms in the pedal arteries is associated with the presence of PAD, whereas tri- or biphasic waveform suggests that PAD is less likely. Several forms of bedside testing may also be useful as adjunct tests and 7 studies were identified that investigated the reliability of bedside tests including ABI, toe pressure, TBI, transcutaneous oxygen pressure (TcPO2 ) and pulse palpation. Inter-rater reliability was poor for pulse palpation and moderate for TcPO2. The ABI, toe pressure and TBI may have good inter- and intra-rater reliability, but margins of error are wide, requiring a large change in the measurement for it to be considered a true change rather than error. There is currently no single bedside test or a combination of bedside tests that has been shown to have superior diagnostic accuracy for PAD in people with diabetes with or without DFU. However, an ABI <0.9 or >1.3, TBI of <0.70, and absent or monophasic pedal Doppler waveforms are useful to identify the presence of disease. The ability of the tests to exclude disease is variable and although reliability may be acceptable, evidence of error in the measurements means test results that are within normal limits should be considered with caution and in the context of other vascular assessment findings (e.g., pedal pulse palpation and clinical signs) and progress of DFU healing.

The triad of ischaemia, neuropathy, and infection are among the principal causes of lower extremity wounds that are commonly prevalent in patients with diabetic foot (DF) a condition in which peripheral arterial disease commonly co-exists. The prevalence of this condition is increasing globally and with it, the mounting costs of its management. One aspect of management is saving limbs and or digits, a crucial part of this process is assessing tissue viability of skin which is a focus of this review: there are other aspects which are well described in the literature. Amputations are offered to limit the damage resulting from acute/chronic ischaemia. Holstein measured skin perfusion pressure using a radioisotope clearance technique to describe critically ischaemic skin; he found 30 mm Hg as the threshold above which healing may reliably be expected. Recent advances in vascular surgery and related technology have informed evidence-based advice to revascularize and save limbs; in practice, this may leave a wound in the distal skin unhealed; managing these raises questions of tissue viability. Much effort has been made to manage, prevent and to better understand these lower extremity wounds using measurements of tissue oxygen, oxygen saturation and skin imaging. The measurement techniques and their relevant merits are examined in this article. Advances in wound management systems and protocols can also facilitate the repair processes, and those which can have a particular impact on restoring or maintaining tissue perfusion are also discussed in the article.

At least 7000 major lower limb amputations (MLLAs) are performed in the UK each year, 80% of which are due to peripheral arterial disease (PAD). Intraoperative blood loss can have a deleterious effect on patient outcomes, and its replacement with transfused blood is not without risk. Tourniquets can be used in lower limb surgical procedures to provide a bloodless surgical field, minimise intraoperative blood loss, and reduce perioperative blood transfusion requirements. Although their safety has been demonstrated in certain orthopaedic operations, their use among people with PAD undergoing MLLA remains controversial. Many clinicians are concerned about tourniquets potentially compromising perfusion of the stump and thereby impacting wound healing through direct tissue injury, damage to the arterial supply of the wound, or both.

To assess the safety and effectiveness of tourniquet use in people undergoing MLLA for complications of PAD, specifically with regard to intraoperative blood loss, change in haemoglobin levels, transfusion rates, wound healing, need for revision surgery, and postoperative complications including mortality.

We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers from inception to 17 May 2022.

We included randomised controlled trials (RCTs) comparing tourniquet use to no tourniquet use among people with PAD undergoing MLLA.

We used standard Cochrane methods. Primary outcomes were intraoperative blood loss, fall in haemoglobin levels, and perioperative blood transfusion requirement. Secondary outcomes were primary wound-healing rates, stump revision rates, other postoperative complications defined as per Clavien-Dindo classification, and postoperative mortality at 30 days and at maximal follow-up. We used GRADE to assess the certainty of evidence for each outcome.

One RCT met our inclusion criteria, which was a prospective randomised blinded controlled trial conducted in Sheffield, UK in 2006. In total 64 participants undergoing transtibial amputation for non-reconstructable PAD were randomised to either tourniquet or no tourniquet to assess for intraoperative blood loss, fall in haemoglobin, transfusion requirement, wound healing, stump breakdown and revision. Ten participants were excluded postrandomisation (five from the tourniquet group and five from the no tourniquet group). The reported median volume of intraoperative blood loss was significantly less in the tourniquet group (255 mL (interquartile range (IQR) 150 to 572.5 mL))) compared to the control group (550 mL (IQR 255 to 1050 mL)) (P = 0.014). There was a significantly lower median drop in haemoglobin concentration in the tourniquet group (1.0 g/dL (IQR 0.6 to 2.4 g/dL)) compared to the control group (1.8 g/dL (IRQ 0 to 1.2 g/dL)) (P = 0.035). There was a significantly lower perioperative blood transfusion requirement in the tourniquet group (8 participants, 32%) compared to the control group (14 participants, 48%) (P = 0.047). There were no clear differences in wound breakdown, stump revision, primary wound healing at six weeks, postoperative complications (myocardial infarction, cardiac arrhythmias, pulmonary oedema), and death between groups. We assessed the one included study as at low risk of bias for sequence generation and blinding of outcome assessors; high risk of bias for incomplete outcome data and selective outcome reporting; and unclear risk of bias for allocation concealment, blinding of participants and personnel, and other sources of bias. We assessed the certainty of the evidence as low or very low due to risk of bias, small sample size, and the study being insufficiently powered for most outcomes.

This review identified only one small historical RCT evaluating tourniquet use in MLLA. Tourniquets appeared to reduce intraoperative blood loss, drop in haemoglobin, and blood transfusion requirements following transtibial amputations for people with PAD. However, it is unclear whether tourniquets affect wound healing, stump revision rates, postoperative complications, or mortality. High-certainty evidence is required to inform clinical decision-making for the use of tourniquets in these patients.

Approximately 18.6 million people worldwide are affected by a diabetic foot ulcer each year, including 1.6 million people in the United States. These ulcers precede 80% of lower extremity amputations among people diagnosed with diabetes and are associated with an increased risk of death.

Neurological, vascular, and biomechanical factors contribute to diabetic foot ulceration. Approximately 50% to 60% of ulcers become infected, and about 20% of moderate to severe infections lead to lower extremity amputations. The 5-year mortality rate for individuals with a diabetic foot ulcer is approximately 30%, exceeding 70% for those with a major amputation. The mortality rate for people with diabetic foot ulcers is 231 deaths per 1000 person-years, compared with 182 deaths per 1000 person-years in people with diabetes without foot ulcers. People who are Black, Hispanic, or Native American and people with low socioeconomic status have higher rates of diabetic foot ulcer and subsequent amputation compared with White people. Classifying ulcers based on the degree of tissue loss, ischemia, and infection can help identify risk of limb-threatening disease. Several interventions reduce risk of ulcers compared with usual care, such as pressure-relieving footwear (13.3% vs 25.4%; relative risk, 0.49; 95% CI, 0.28-0.84), foot skin measurements with off-loading when hot spots (ie, greater than 2 °C difference between the affected foot and the unaffected foot) are found (18.7% vs 30.8%; relative risk, 0.51; 95% CI, 0.31-0.84), and treatment of preulcer signs. Surgical debridement, reducing pressure from weight bearing on the ulcer, and treating lower extremity ischemia and foot infection are first-line therapies for diabetic foot ulcers. Randomized clinical trials support treatments to accelerate wound healing and culture-directed oral antibiotics for localized osteomyelitis. Multidisciplinary care, typically consisting of podiatrists, infectious disease specialists, and vascular surgeons, in close collaboration with primary care clinicians, is associated with lower major amputation rates relative to usual care (3.2% vs 4.4%; odds ratio, 0.40; 95% CI, 0.32-0.51). Approximately 30% to 40% of diabetic foot ulcers heal at 12 weeks, and recurrence after healing is estimated to be 42% at 1 year and 65% at 5 years.

Diabetic foot ulcers affect approximately 18.6 million people worldwide each year and are associated with increased rates of amputation and death. Surgical debridement, reducing pressure from weight bearing, treating lower extremity ischemia and foot infection, and early referral for multidisciplinary care are first-line therapies for diabetic foot ulcers.

The aim of this study was to evaluate the prevalence and extent of lower extremity Mönckeberg's Medial Calcific Sclerosis (MMCS) in patients with and without diabetes in patients admitted to the hospital for foot infections. This study retrospectively reviewed 446 patients admitted to the hospital with a moderate or severe foot infection. We defined diabetes based on ADA criteria and reviewed electronic medical records for demographics, medical history and physical examination data. Anterior-posterior and lateral foot radiographs were examined to identify the presence and extent of vascular calcification. We categorised MMCS based on anatomical location: ankle joint to the navicular-cuneiform joint, Lis Franc joint to metatarsophalangeal joints and distal to the metatarsophalangeal joints. The prevalence of MMCS was 40.6%. The anatomic extent of MMCS was 19.3% in the toes, 34.3% in the metatarsals and 40.6% in the hindfoot/ankle. Calcification was not common solely in the dorsalis pedis artery (DP) (3.8%) or solely in the posterior tibial artery (PT) (7.0%). Usually, both DP and PT arteries were affected by MMCS (29.8%). The prevalence of MMCS was higher in people with diabetes (in hindfoot and ankle [50.1% vs. 9.9%, p ≤ 0.01]; metatarsals [42.6% vs. 5.9%, p ≤ 0.01]; and toes [23.8% vs. 4.0%, p ≤ 0.01]). People with diabetes were 8.9 (CI: 4.5-17.8) times more likely to have MMCS than those without diabetes. This is a group that often has poor perfusion and needs vascular assessment. The high prevalence of MMCS raises questions about the reliability of the conventional segmental arterial Doppler studies to diagnose PAD.

Previous studies demonstrate geographic and racial/ethnic variation in diagnosis and complications of diabetes and peripheral artery disease (PAD). However, recent trends for patients diagnosed with both PAD and diabetes are lacking. We assessed the period prevalence of concurrent diabetes and PAD across the United States from 2007 to 2019 and regional and racial/ethnic variation in amputations among Medicare patients.

Using Medicare claims from 2007 to 2019, we identified patients with both diabetes and PAD. We calculated period prevalence of concomitant diabetes and PAD and incident cases of diabetes and PAD for every year. Patients were followed to identify amputations, and results were stratified by race/ethnicity and hospital referral region.

9 410 785 patients with diabetes and PAD were identified (mean age, 72.8 [SD, 10.94] years; 58.6% women, 74.7% White, 13.2% Black, 7.3% Hispanic, 2.8% Asian/API, and 0.6% Native American). Period prevalence of diabetes and PAD was 23 per 1000 beneficiaries. We observed a 33% relative decrease in annual new diagnoses throughout the study. All racial/ethnic groups experienced a similar decline in new diagnoses. Black and Hispanic patients had on average a 50% greater rate of disease compared with White patients. One- and 5-year amputation rates remained stable at ≈1.5% and 3%, respectively. Native American, Black, and Hispanic patients were at greater risk of amputation compared with White patients at 1- and 5-year time points (5-year rate ratio range, 1.22-3.17). Across US regions, we observed differential amputation rates, with an inverse relationship between the prevalence of concomitant diabetes and PAD and overall amputation rates.

Significant regional and racial/ethnic variation exists in the incidence of concomitant diabetes and PAD among Medicare patients. Black patients in areas with the lowest rates of PAD and diabetes are at disproportionally higher risk for amputation. Furthermore, areas with higher prevalence of PAD and diabetes have the lowest rates of amputation.

The purpose of this study was to leverage a magnetic resonance imaging (MRI) approach to characterize foot perfusion distribution in patients with diabetes, with or without foot ulcers, and determine the ability of the regional perfusion measurements to identify ulcer-healing status.

Three groups of participants (n = 15 / group) were recruited: controls (without diabetes), type II diabetes, and type II diabetes with foot ulcers. All participants underwent MRI evaluating foot perfusion in three muscle layers (from plantar to dorsal) at rest and during a standardized toe-flexion exercise. The exercise perfusion and perfusion reserve values were analyzed around and away from ulcers. Participants with foot ulcers were followed up 3 months after the MRI exams to determine the foot healing status.

Foot plantar muscle perfusion reserves were progressively lower from controls to diabetes, and to diabetes with foot ulcers (e.g., 2.58 ± 0.67, 1.48 ± 0.71, 1.12 ± 0.35, p < 0.001). In controls, the plantar layer had significantly higher perfusion reserve than the dorsal layer, whereas in either diabetes group, there was no significant difference in perfusion reserve among muscle layers. Using the ratio of total exercise perfusion around ulcers to that away from ulcers, the sensitivity and specificity to differentiate healing from non-healed ulcers were 100% and 86%, respectively.

Our study reveals significantly different foot perfusion distribution among controls, diabetes, and diabetes with foot ulcers. The prognostic value of MRI regional perfusion assessments has the potential to monitor interventions to improve ulcer healing outcomes.

• Contrast-free MRI permits quantitative assessment of regional foot muscle perfusion at rest and during isometric exercise. • Patients with diabetes and foot ulcers, without clinical evidence of peripheral arterial disease, had significantly impaired foot muscle perfusion and perfusion reserve. • Regional foot perfusion distribution may be used to predict the short-term healing status of foot ulcers in diabetes.

Although diabetic and atherosclerotic vascular diseases have different pathophysiological mechanisms, the screening methods currently used for diabetic lower-extremity vascular diseases are mainly based on the evaluation methods used for atherosclerotic vascular diseases. Thus, assessment of microvascular perfusion is of great importance in early detection of lower-extremity ischemia in diabetes.

This cross-sectional study aimed to develop a quantitative model for evaluating lower-extremity perfusion.

We recruited 57 participants (14 healthy participants and 43 diabetes patients, of which 16 had lower-extremity arterial disease [LEAD]). All participants underwent technetium-99 m sestamibi (99mTc-MIBI) scintigraphy and ankle-brachial index (ABI) examination. We derived two key perfusion kinetics indices named activity perfusion index (API) and basal perfusion index (BPI). This study was registered in ClinicalTrials.gov (URL: https://www.

gov, NCT02752100).

The estimated limb perfusion values in our lower-extremity perfusion assessment (LEPA) model showed excellent consistency with the actual measured data. Diabetes patients showed reduced lower-extremity perfusion in comparison with the control group (BPI: 106.21 ± 11.99 vs. 141.56 ± 17.38, p < 0.05; API: 12.34 ± 3.27 vs. 14.56 ± 3.12, p < 0.05). Using our model, the reductions in lower-extremity perfusion could be detected early in approximately 96.30% of diabetes patients. Patients with LEAD showed more severe reductions in lower-extremity perfusion than diabetes patients without LEAD (BPI: 47.85 ± 20.30 vs. 106.21 ± 11.99, p < 0.05; API: 7.06 ± 1.70 vs. 12.34 ± 3.27, p < 0.05). Discriminant analysis using API and BPI could successfully screen all diabetes patients with LEAD with a sensitivity of 100% and specificity of 80.77%.

We established a LEPA model that could successfully assess lower-extremity microvascular perfusion in diabetes patients. This model has important application value for the recognition of early-stage LEAD in patients with diabetes.

This cohort study investigates the extent to which variation in ulcer healing between services can be explained by demographic and clinical characteristics.

The National Diabetes Foot Care Audit collated data on people with diabetic foot ulcers presenting to specialist services in England and Wales between July 2014 and March 2018. Logistic regression models were created to describe associations between risk factors and a person being alive and ulcer-free 12 weeks from presentation, and to investigate whether variation between 120 participating services persisted after risk factor adjustment.

Of 27,030 people with valid outcome data, 12,925 (47.8%) were alive and ulcer-free at 12 weeks, 13,745 (50.9%) had an unhealed ulcer and 360 had died (1.3%). Factors associated with worse outcome were male sex, more severe ulcers, history of cardiac or renal disease and a longer time between first presentation to a non-specialist healthcare professional and first expert assessment. After adjustment for these factors, four services (3.3%) were more than 3SD above and seven services (5.8%) were more than 3SD below the national mean for proportions that were alive and ulcer-free at follow-up.

Variation in the healing of diabetic foot ulcers between specialist services in England and Wales persisted after adjusting for demographic characteristics, ulcer severity, smoking, body mass index and co-morbidities. We conclude that other factors contribute to variation in healing of diabetic foot ulcers and include the time to specialist assessment.

Diabetic foot disease is a serious complication of diabetes mellitus. Patients with diabetes mellitus have a 25% lifetime risk for developing a foot ulcer, and between 14% and 24% of patients require a major or minor lower limb amputation due to severe gangrene. However, decisions concerning whether to amputate or whether to perform a major or minor lower limb amputation, and how best to determine the amputation plane remain unclear.

To consolidate the current literature with expert opinion to make recommendations that will guide surgical amputation for patients with diabetic foot ulcers. A total of 23 experts experienced in surgical treatment of patients with diabetic foot ulcers formed an expert consensus panel, and presented the relevant evidence, discussed clinical experiences, and derived consensus statements on surgical amputation for patients with diabetic foot ulcers. Each statement was discussed and revised until a unanimous consensus was achieved.

A total of 16 recommendations for surgical amputation for patients with diabetic foot ulcers were formulated. The experts believe that determination of the amputation plane should be comprehensively evaluated according to a patient's general health status, the degree of injury, and the severity of lower limb vasculopathy. The Wagner grading system and the severity of diabetic lower extremity artery disease are important criteria when determining the degree of amputation. The severity of both diabetic foot infection and systemic underlying diseases are important factors when considering appropriate treatment. Moreover, consideration should also be given to a patient's socioeconomic status. Given the complexities of treating the diabetic foot, relevant issues in which consensus could not be reached will be discussed and revised in future.

This expert consensus could be used to guide doctors in clinical practice, and help patients with diabetic foot ulcers gain access to appropriate amputation treatment.

This study was performed to analyze the clinical characteristics, related factors, and prognosis of repeated lesions after diabetic forefoot amputation.

The medical records of 998 patients who underwent forefoot amputation because of their diabetic feet from March 2002 to February 2021 were retrospectively analyzed. Of the 508 selected patients with a follow-up period of at least 6 months, 288 had repeated lesions in the forefoot, and 220 did not have repeated lesions. The related factors of repeated lesions were compared and analyzed. Of the patients with repeated lesions, 142 and 104 on the ipsilateral and contralateral sides, respectively were also compared and examined.

Repeated lesions were statistically significant in diabetic polyneuropathy, vascular calcification, and dialysis. However, the anatomical positions of diabetic foot lesions, causes of lesions, anatomical amputation levels, number of surgeries, and management duration had no significant differences. Contralateral lesions occurred 8 months later than ipsilateral lesions, but reamputation above the Lisfranc joint was more frequent and prognosis was poorer.

Repeated lesions were affected by general conditions, and the contralateral side must be carefully examined after diabetic forefoot amputation.

Foot ulcers are a leading cause of morbidity in diabetics. One of the known complications of diabetic foot ulcers is lower limb amputation which makes it a major socioeconomic problem. Currently, there's a lack of knowledge on the predictors of amputations in diabetics with foot ulcers. We performed a systematic review of studies that identified risk factors of amputation in patients with diabetic foot ulcers. This systematic review aims to identify the predictors of amputation in order to optimize the management strategy and care plan. Medline database was searched and inclusion criteria were implemented for the selection of studies. The risk factors extracted were part of four categories: (i) history and physical examination, (ii) ulcer characteristics, (iii) lab results, and (iv) co-morbidities. The data extracted were in the form of odds ratios, 95% confidence intervals, and predictive values. The mean values with standard deviations of the included risk factors were recorded, and the incidence of risk factors among the amputation groups was identified or calculated when the data were sufficient. Seven articles were selected reporting on 3481 patients. This review identified peripheral arterial disease, neuropathy, high Wagner's grade, osteomyelitis, postprandial glucose level, white cell count, c-reactive protein, erythrocyte sedimentation rate, low hemoglobin, and albumin as the most significant predictors of amputation.

The objective of this study was to evaluate a measure of the responsiveness and reliability of the pulse volume recording upstroke ratio (PVRr). A database of 389 subjects undergoing lower extremity revascularization was analyzed. Subjects were included in the analysis if they had undergone pedal radiographs, had PVRs performed pre- and postlower extremity revascularization, and had regular pulsatile digital waveforms with a pressure recording on both PVRs. The responsiveness of the PVRr was assessed by means of the postoperative percent change in comparison to the digital pressures. A statistically significant negative correlation was observed (Pearson -0.421; p = .007) indicating that as digital pressures increased, the PVRr decreased. Further, measurement of the reliability of the PVRr was performed on a selection of 10 recordings by 2 residents and 3 board-certified surgeons. The observed intraclass correlation coefficient of measurements was 0.960. Results of this investigation provide evidence in support of the responsiveness and inter-rater reliability in the calculation of the pulse volume recording upstroke ratio.

Diabetic foot ulcers (DFUs) are the main cause of hospitalizations and amputations in diabetic patients. Failure of standard foot care is the most important cause of impaired DFU healing. Dakin's solution (DS) is a promising broad-spectrum bactericidal antiseptic for management of DFUs. Studies investigating the efficacy of using DS on the healing process of DFUs are scarce. Accordingly, this is the first evidence-based, randomized, controlled trial conducted to evaluate the effect of using diluted DS compared with the standard care in the management of infected DFUs.

A randomized controlled trial was conducted to assess the efficacy of DS in the management of infected DFUs. Patients were distributed randomly to the control group (DFUs irrigated with normal saline) or the intervention group (DFUs irrigated with 0.1% DS). Patients were followed for at least 24 weeks for healing, reinfection, or amputations. In vitro antimicrobial testing on DS was performed, including determination of its minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and suspension test.

Replacing normal saline irrigation in DFU standard care with 0.1% DS followed by soaking the ulcer with commercial sodium hypochlorite (0.08%) after patient discharge significantly improved ulcer healing (P < .001) and decreased the number of amputations and hospitalizations (P < .001). The endpoint of death from any cause (risk ratio, 0.13; P = .029) and the amputation rate (risk ratio, 0.27; P < .001) were also significantly reduced. The effect on ulcer closure (OR, 11.9; P < .001) was significantly enhanced in comparison with the control group. Moreover, DS irrigation for inpatients significantly decreased bacterial load (P < .001). The highest values for the in-vitro analysis of DS were as follows: minimum inhibitory concentration (MIC), 1.44%; minimum bactericidal concentration (MBC), 1.44%; minimum biofilm inhibitory concentration (MBIC), 2.16%; and minimum biofilm eradication concentration (MBEC), 2.87%.

Compared with standard care, diluted DS (0.1%) was more effective in the management of infected DFUs. Dakin's solution (0.1%) irrigation with debridement followed by standard care is a promising method in the management of infected DFUs.

The presence of medial arterial calcific sclerosis is known to cause inaccuracy in the interpretation of noninvasive vascular testing. This substantially limits the utility of an important baseline diagnostic test for peripheral arterial disease. Therefore, the objective of this investigation was to derive a method to effectively factor out calcification in the interpretation of the ankle and digital brachial indices. The noninvasive vascular testing results of 160 subjects were stratified into the absence of calcification, mild calcification, moderate calcification, and severe calcification based on plain film radiographic findings of the infrageniculate vessels. Measurements were then performed of the pulse volume recording (PVR) waveforms at brachial, ankle and digital anatomic levels to include PVR wavelength and PVR upstroke length, with a calculation of the ratio of PVR upstroke length to PVR wavelength. These measurements were compared between groups and then correlated to the ankle and digital brachial indices. A significant difference was observed in the PVR upstroke ratio between the 3 anatomic levels (0.1818 vs 0.2622 vs 0.3191; p < .001), but not between the 4 calcification groups (0.2457 vs 0.2363 vs 0.2694 vs 0.2631; p = .242). A significant negative correlation was observed between the PVR upstroke ratio and the ankle brachial index (ABI) (Pearson -0.454; p = .002) with linear regression indicating the relationship is defined by the formula: Effective ankle brachial index = 1.17 - (1.33 × PVR upstroke ratio at ankle level). A significant negative correlation was also observed between the PVR upstroke ratio and the digital brachial index (Pearson -0.553; p < .001) with linear regression indicating the relationship is defined by the formula: Effective toe brachial index = 1.04 - (1.61 × PVR upstroke ratio at digital level). The results of this investigation demonstrate the feasibility of, and provide equations to approximate, the effective ankle brachial and toe brachial indices in the setting of medial arterial calcification.

This study aimed to investigate incidence and predictors of wound healing, relapse, major amputation, and/or death among patients with chronic leg wounds who were referred to specialist treatment at hospital for their condition. A nationwide register-based cohort study design was applied with 5 years of follow-up. All patients with diagnoses of chronic leg wounds in Denmark between 2007 and 2012 were included (n = 8394). Clinical, social, and demographic individual-level linked data from several Danish national registries were retrieved. Incidence rate per 1000 person-years (PY) was calculated. Predictors were investigated using Cox proportional hazards regression analysis. Incidence rates of having a healed wound was 236 per 1000 PY. For relapse, the incidence rate was 75 per 1000 PY, for amputation 16 per 1000 PY, and for death 100 per 1000 PY. Diabetes, peripheral arteria disease, or other comorbidities were associated with decreased chance of wound healing and increased risk of relapse, major amputation, and death. Regional differences in all four outcomes were detected. Basic or vocational education independently predicted risk of amputation and death. This study provides epidemiological data that may help identify patients at particular risk of poor outcomes. It also elucidates social inequality in outcomes.

Diabetic Foot Infection (DFI), in its severest form the acute infected 'diabetic foot attack', is a limb and life threatening condition if untreated. Acute infection may lead to tissue necrosis and rapid spread through tissue planes, in the patient with poorly controlled diabetes facilitated by the host status. A combination of soft tissue infection and osteomyelitis may co-exist, in particular if chronic osteomyelitis serves as a persistent source for recurrence of soft tissue infection. This "diabetic foot attack" is characterised by acutely spreading infection and substantial soft tissue necrosis. In the presence of ulceration, the condition is classified by the Infectious Diseases Society of America/International Working Group on the Diabetic Foot (IDSA/IWGDF Class 3 or 4) presentation requiring an urgent surgical intervention by radical debridement of the infection. Thus, 'time is tissue', referring to tissue salvage and maximal limb preservation. Emergent treatment is important for limb salvage and may be life-saving. We provide a narrative current treatment practices in managing severe DFI with severe soft tissue and osseous infection. We address the role of surgery and its adjuvants, the long term outcomes, potential complications and possible future treatment strategies.

The aim of this study was to isolate and characterize staphylococcal isolates from diabetic foot ulcers (DFU) in Jordanian patients.

Selected aerobic pathogens recovered from DFU specimens and patients' nares with a focus on staphylococci were investigated. Antimicrobial susceptibilities and the prevalence of methicillin-resistant staphylococci (MRS) were determined. SCCmec types and toxigenic characteristics were analysed and spa typing was performed for methicillin-resistant Staphylococcus aureus (MRSA) isolates. The relationship between toxigenic characteristics of MRSA and the Wagner ulcer grading system was statistically analysed. A total number of 87 DFU patients were recruited for the study. The DFU cultures were polymicrobial. Members of the genus Staphylococcus were the most common among DFU-associated isolates found in 48·3% (n = 42) of all patients enrolled. Coagulase-negative staphylococci (CoNS) comprised 63·3% of staphylococci isolated from DFUs predominated by Staphylococcus epidermidis in both DFU (7·6%) and nares (39·2%). Staphylococcus aureus was isolated from DFUs and nares in 14·2 and 9·8%, respectively, while 93 and 70% of these isolates were MRSA. Most of MRSA carried SCCmec type IV (76·2%) while SCCmec elements were non-typeable in most methicillin resistant coagulase negative staphylococci (MR-CoNS) (61·9%). The most frequent MRSA spa type was t386 (23·8%). Most MRSA and MR-CoNS exhibited resistance towards aminoglycosides, fluoroquinolones and macrolides and susceptibility towards vancomycin, mupirocin and linezolid. No association was found between the possession of pvl, tst, sea and hlg toxins and Wagner ulcer grading system (P value >0·05).

This analysis of Jordanian DFU culture demonstrated its polymicrobial nature with predominance of Staphylococcus sp.

This study is the first of its type to assess the microbiology of DFU among Jordanian patients. The results will help in the appropriate application of antimicrobial chemotherapy in the management of DFU.

Internal partial forefoot amputation (IPFA) is a treatment option for osteomyelitis and refractory and recurrent chronic ulcers of the forefoot. The aim of our study was to assess the healing rate of chronic ulcers, risk of ulcer recurrence at the same area or re-ulceration at a different area and revision rate in patients treated with IPFA.

All patients who underwent IPFA of a phalanx and/or metatarsal head and/or sesamoids at our institution because of chronic ulceration of the forefoot and/or osteomyelitis from 2004 to 2014 were included. Information about patient characteristics, ulcer healing, new ulcer occurrence, and revision surgery were collected. Kaplan-Meier survival curves were plotted for new ulcer occurrence and revision surgery.

A total of 102 patients were included (108 operated feet). 55.6% of our patients had diabetes. In 44 cases, an IPFA of a phalanx was performed, in 60 cases a metatarsal head resection and in 4 cases an isolated resection of sesamoids. The mean follow-up was 40.9 months. 91.2% of ulcers healed after a mean period of 1.3 months. In 56 feet (51.9%), a new ulcer occurred: 11 feet (10.2%) had an ulcer in the same area as initially (= ulcer recurrence), in 45 feet (41.7%) the ulcer was localized elsewhere (= re-ulceration). Revision surgery was necessary in 39 feet (36.1%). Only one major amputation and five complete transmetatarsal forefoot amputations were necessary during the follow-up period. Thus, the major amputation rate was 0.9%, and the minor amputation rate on the same ray was 13.9%.

IPFA is a valuable treatment of chronic ulcers of the forefoot. However, new ulceration is a frequent event following this type of surgery. Our results are consistent with the reported re-ulceration rate after conservative treatment of diabetic foot ulcers. The number of major amputations is low after IPFA.

Retrospective Case Series Study (Level IV).

Conventional bacterial cultures frequently fail to identify the dominant pathogen in polymicrobial foot infections, in which Staphylococcus aureus is the most common infecting pathogen. Previous work has shown that species-specific immunoassays may be able to identify the main pathogen in musculoskeletal infections. We sought to investigate the clinical applicability of a S. aureus immunoassay to accurately identify the infecting pathogen and monitor its infectivity longitudinally in foot infection. We hypothesized that this species-specific immunoassay could aid in the diagnosis of S. aureus and track the therapeutic response in foot infections.

From July 2015 to July 2019, 83 infected foot ulcer patients undergoing surgical intervention (debridement or amputation) were recruited and blood was drawn at 0, 4, 8, and 12 weeks. Whole blood was analyzed for S. aureus-specific serum antibodies (mix of historic and new antibodies) and plasmablasts were isolated and cultured to quantify titers of newly synthesized antibodies (NSAs). Anti-S. aureus antibody titers were compared with culture results to assess their concordance in identifying S. aureus as the pathogen. The NSA titer changes at follow-ups were compared with wound healing status to evaluate concordance between evolving host immune response and clinically resolving or relapsing infection.

Analysis of serum for anti-S. aureus antibodies showed significantly increased titers of 3 different anti-S. aureus antibodies, IsdH (P = .037), ClfB (P = .025), and SCIN (P = .005), in S. aureus culture-positive patients compared with culture-negative patients. Comparative analysis of combining antigens for S. aureus infection diagnosis increased the concordance further. During follow-up, changes of NSA titers against a single or combination of S. aureus antigens significantly correlated with clinically resolving or recurring infection represented by wound healing status.

In the management of foot infection, the use of S. aureus-specific immunoassay may aid in diagnosis of the dominant pathogen and monitoring of the host immune response against a specific pathogen in response to treatment. Importantly, this immunoassay could detect recurrent foot infection, which may guide a surgeon's decision to intervene.

Level II, prospective comparative study.

All diagnostic procedures of peripheral arterial disease (PAD) in diabetic foot (DF) are complicated due to diabetes mellitus and its late complications.The aim of our study is to enhance diagnosis of PAD using a novel transcutaneous oximetry (TcPO2) stimulation test.

The study comprised patients with mild-to-moderate PAD(WIfI-I 1 or 2) and baseline TcPO2 values of 30-50 mmHg.TcPO2 was measured across 107 different angiosomes. Stimulation examination involved a modification of the Ratschow test. All patients underwent PAD assessment (systolic blood pressures (SBP), toe pressures (TP), the ankle-brachial indexes (ABI) and toe-brachial indexes (TBI), duplex ultrasound of circulation). Angiosomes were divided into two groups based on ultrasound findings: group M(n=60) with monophasic flow; group T(n=47) with triphasic flow. Large vessel parameters and TcPO2 at rest and after exercise (minimal TcPO2, changes in TcPO2 from baseline (Δ,%), TcPO2 recovery time) measured during the stimulation test were compared between study groups.

During the TcPO2 stimulation exercise test, group M exhibited significantly lower minimal TcPO2 (26.2 ± 11.1 vs. 31.4 ± 9.4 mmHg; p<0.01), greater Δ and percentage decreases from resting TcPO2 (p=0.014 and p=0.007, respectively) and longer TcPO2 recovery times (446 ± 134 vs. 370 ± 81ms;p=0.0005) compared to group T. SBPs, TPs and indexes were significantly lower in group M compared to group T. Sensitivity and specificity of TcPO2 stimulation parameters during PAD detection increased significantly to the level of SBP, ABI, TP and TBI.

Compared to resting TcPO2, TcPO2 measured during stimulation improves detection of latent forms of PAD and restenosis/obliterations of previously treated arteries in diabetic foot patients.

ClinicalTrials.gov [https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009V7W&selectaction=Edit&uid=U0005381&ts=2&cx=3j24u2], identifier NCT04404699.

The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM).

We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied.

There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history.

Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.

Diabetes mellitus is an established risk factor of colorectal anastomosis failure. The purpose of the present study was to evaluate the effect of TISSEEL® in anastomotic healing.

Forty male, Sprague-Dawley rats were used. Diabetes was induced in half of them by intraperitoneal injection of Streptozotocin, 60 mg/kg. One week after the injection, animals were operated and a 1 cm segment was removed and an end-to-end hand sewn anastomosis was performed. TISSEEL® was applied in each group (diabetic, non-diabetic) following randomization.

The pathology analysis revealed improved tissue remodeling in the TISSEEL® group, both for the normoglycemic and the diabetic group. Specifically, the extent of inflammation was decreased (p<0.001), whereas fibroblast and collagen formation were improved (p=0.040 and p=0.008). Neovascularization was also improved (p=0.047).

Application of TISSEEL® on colorectal anastomoses improves healing in rats that suffer from severe hyperglycemia.

The aim of this study was to explore the different meanings of the experience of lower-limb amputation due to vascular causes in the time period from the fifth to twelfth week post-amputation. A phenomenological study involving semi-structured interviews was carried out. Data collection took place in a Public Hospital in Spain and included a convenience sample of 20 patients who had undergone amputation. The study highlighted patients' fears related to mobility, pain, dependence, and autonomy. Moreover, patients experience of the rehabilitation process and resources for adaptation were described as well as all the changes related to the social environment. The figure of a nurse was considered essential after amputation by the patients. This study provides a deep understanding of their experiences at the immediate time after amputation considering patients demographical associations and the etiology of the vascular pathology. This could be the starting point to understand patients' immediate needs upon discharge.