Can the introduction of a 12-lead ECG help reduce mortality in those presenting with foot ulceration to multidisciplinary diabetic foot clinics? An observational evaluation of a real-world implementation pilot in England.

AIMS/HYPOTHESIS: The risk of dying within 2 years of presentation with diabetic foot ulceration is over six times the risk of amputation, with CVD the major contributor. Using an observational evaluation of a real-world implementation pilot, we aimed to assess whether for those presenting with diabetic foot ulceration in England, introducing a 12-lead ECG into routine care followed by appropriate clinical action was associated with reduced mortality. METHODS: Between July 2014 and December 2017, ten multidisciplinary diabetic foot services in England participated in a pilot project introducing 12-lead ECGs for new attendees with foot ulceration. Inception coincided with launch of the National Diabetes Footcare Audit (NDFA), whereby all diabetic footcare services in England were invited to enter data on new attendees with foot ulceration. Poisson regression models assessed the mortality RR at 2 and 5 years following first assessment of those receiving care in a participating pilot unit vs those receiving care in any other unit in England, adjusting for age, sex, ethnicity, deprivation, type and duration of diabetes, ulcer severity, and morbidity in the year prior to first assessment. RESULTS: Of the 3110 people recorded in the NDFA at a participating unit during the pilot, 33% (1015) were recorded as having received an ECG. A further 25,195 people recorded in the NDFA had attended another English footcare service. Unadjusted mortality in the pilot units was 16.3% (165) at 2 years and 37.4% (380) at 5 years for those who received an ECG, and 20.5% (430) and 45.2% (950), respectively, for those who did not receive an ECG. For people included in the NDFA at other units, unadjusted mortality was 20.1% (5075) and 42.6% (10,745), respectively. In the fully adjusted model, mortality was not significantly lower for those attending participating units at 2 (RR 0.93 [95% CI 0.85, 1.01]) or 5 years (RR 0.95 [95% CI 0.90, 1.01]). At participating units, mortality in those who received an ECG vs those who did not was lower at 5 years (RR 0.86 [95% CI 0.76, 0.97]), but not at 2 years (RR 0.87 [95% CI 0.72, 1.04]). Comparing just those that received an ECG with attendees at all other centres in England, mortality was lower at 5 years (RR 0.87 [95% CI 0.78, 0.96]), but not at 2 years (RR 0.86 [95% CI 0.74, 1.01]). CONCLUSIONS/INTERPRETATION: The evaluation confirms the high mortality seen in those presenting with diabetic foot ulceration. Overall mortality at the participating units was not significantly reduced at 2 or 5 years, with confidence intervals just crossing parity. Implementation of the 12-lead ECG into the routine care pathway proved challenging for clinical teams-overall a third of attendees had one, although some units delivered the intervention to over 60% of attendees-and the evaluation was therefore underpowered. Nonetheless, the signals of potential mortality benefit among those who had an ECG suggest that units in a position to operationalise implementation may wish to consider this. DATA AVAILABILITY: Data from the National Diabetes Audit can be requested through the National Health Service Digital Data Access Request Service process at: https://digital.nhs.uk/services/data-access-request-service-dars/dars-products-and-services/data-set-catalogue/national-diabetes-audit-nda.

Diabetes foot complications and standardized mortality rate in type 2 diabetes.

AIM: To quantify the impact of foot complications on mortality outcomes in people with type 2 diabetes (T2D), and how routinely measured factors might modulate that risk. MATERIALS AND METHODS: Data for individuals with T2D for 2010-2020, from the Salford Integrated Care Record (Salford, UK), were extracted for laboratory and clinical data, and deaths. Annual expected deaths were taken from Office of National Statistics mortality data. An index of multiple deprivation (IMD) adjusted the standardized mortality ratio (SMR_IMD). Life years lost per death (LYLD) was estimated from the difference between expected and actual deaths. RESULTS: A total of 11 806 T2D patients were included, with 5583 new diagnoses and 3921 deaths during 2010-2020. The number of expected deaths was 2135; after IMD adjustment, there were 2595 expected deaths. Therefore, excess deaths numbered 1326 (SMR_IMD 1.51). No foot complications were evident in n = 9857. This group had an SMR_IMD of 1.13 and 2.74 LYLD. In total, 2979 patients had any foot complication recorded. In this group, the SMD_IMR was 2.29; of these, 2555 (75%) had only one foot complication. Patients with a foot complication showed little difference in percentage HbA1c more than 58 mmol/mol. In multivariate analysis, for those with a foot complication and an albumin-to-creatinine ratio of more than 3 mg/mmol, the odds ratio (OR) for death was 1.93, and for an estimated glomerular filtration rate of less than 60 mL/min/1.73m2 , the OR for death was 1.92. CONCLUSIONS: Patients with T2D but without a foot complication have an SMR_IMD that is only slightly higher than that of the general population. Those diagnosed with a foot complication have a mortality risk that is double that of those without T2D.

The importance of socio-economic determinants of health in the care of patients with peripheral artery disease: A narrative review from VAS.

Socio-economic determinants of health (SDoH) include various nonmedical factors in the socio-economic sphere with a potentially significant impact on health outcomes. Their effects manifest through several mediators/moderators (behavioral characteristics, physical environment, psychosocial circumstances, access to care, and biological factors). Various critical covariates (age, gender/sex, race/ethnicity, culture/acculturation, and disability status) also interact. Analyzing the effects of these factors is challenging due to their enormous complexity. Although the significance of SDoH for cardiovascular diseases is well documented, research regarding their impact on peripheral artery disease (PAD) occurrence and care is less well documented. This narrative review explores to what extent SDoH are multifaceted in PAD and how they are associated with its occurrence and care. Additionally, methodological issues that may hamper this effort are addressed. Finally, the most important question, whether this association may contribute to reasonable interventions aimed at SDoH, is analyzed. This endeavor requires attention to the social context, a whole systems approach, multilevel-thinking, and a broader alliance that reaches out to more stakeholders outside the medical sphere. More research is needed to justify the power in this concept to improve PAD-related outcomes like lower extremity amputations. At the present time, some evidence, reasonable consideration, and intuitive reasoning support the implementation of various interventions in SDoH in this field.

Point-of-care fluorescence imaging reveals extent of bacterial load in diabetic foot ulcers.

Elevated levels of bacteria, including biofilm, increase the risk of chronic wound infection and inhibit healing. Addressing asymptomatic high bacterial loads is challenged by a lack of clinical terminology and diagnostic tools. This post-hoc multicenter clinical trial analysis of 138 diabetic foot ulcers investigates fluorescence (FL)-imaging role in detecting biofilm-encased and planktonic bacteria in wounds at high loads. The sensitivity and specificity of clinical assessment and FL-imaging were compared across bacterial loads of concern (104 -109 CFU/g). Quantitative tissue culture confirmed the total loads. Bacterial presence was confirmed in 131/138 ulcers. Of these, 93.9% had loads >104 CFU/g. In those wounds, symptoms of infection were largely absent and did not correlate with, or increase proportionately with, bacterial loads at any threshold. FL-imaging increased sensitivity for the detection of bacteria across loads 104 -109 (P < .0001), peaking at 92.6% for >108 CFU/g. Imaging further showed that 84.2% of ulcers contained high loads in the periwound region. New terminology, chronic inhibitory bacterial load (CIBL), describes frequently asymptomatic, high bacterial loads in diabetic ulcers and periwound tissues, which require clinical intervention to prevent sequelae of infection. We anticipate this will spark a paradigm shift in assessment and management, enabling earlier intervention along the bacterial-infection continuum and supporting improved wound outcomes.

Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS.

BACKGROUND: High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol. METHODS: We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals. RESULTS: Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%]; P=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%]; P=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95-1.83]; P=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05-2.46]; P=0.030). CONCLUSIONS: Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.

Resource use within a multidisciplinary foot team clinic.

OBJECTIVE: The establishment of multidisciplinary foot team clinics reduces the risk of amputation, but little is known about its resource requirement. This study evaluates the service's resource use for first visit attendees to an established multidisciplinary foot team clinic. METHOD: A retrospective evaluation was performed for new referrals to the clinic over six months, including demographics, resource use and clinical outcome. Data were extracted electronically with retrospective review of electronic clinical notes. RESULTS: A total of 240 first visit attendees were analysed. Mean age was 64±15years, 63% were male, 72% had type 2 diabetes, 16% had type 1 diabetes, 15% had a previous amputation, and 40% had a previous ulceration. Common presentations were ulcers (62%), osteomyelitis (11%), Charcot foot (19%), foot ischaemia (17%), post-surgical wounds (13%), and osteomyelitis (11%). At first attendance, 79% of patients required specialist services including diabetologist (45%), joint vascular review (23%), joint orthopaedics services (8%), dermatologist (2%), and orthotics services (1%). A total of 4% of patients had complex debridement, 0.4% total nail excision, 0.8% pus drainage, 3% cast-related procedures, and 1% vacuum-assisted dressing. Of the patients, 4% were admitted to hospital, 38% had vascular duplex investigations, 7% had a deep vein thrombosis scan, 16% had magnetic resonance imagine (MRI), and 5% had a bone scan. CONCLUSION: A functional multidisciplinary foot team clinic requires significant resources-both clinical and administrative-for prompt investigations and revascularisation to sustain low amputation rates. Regular appraisal of resource use helps with clinic and pathway planning.

Mortality in 98 type 1 diabetes mellitus and type 2 diabetes mellitus: Foot ulcer location is an independent risk determinant.

INTRODUCTION: We previously demonstrated in both a longitudinal study and in meta-analysis (pooled relative-risk RR, 2.45) that all-cause mortality is significantly higher in people with diabetes foot ulceration (DFU) than with those without a foot ulcer. In this prospective study, we looked at the factors linked to mortality after presentation to podiatry with DFU. METHODS: Ninety-eight individuals recruited consecutively from the Salford Royal Hospital Multidisciplinary Foot Clinic in Spring 2016 were followed up for up to 48 months. Data concerning health outcomes were extracted from the electronic patient record (EPR). RESULTS: Seventeen people (17) had type 1 diabetes mellitus, and 81 had type 2 diabetes mellitus. Thirty-one were women. The mean age (range) was 63.6 (28-90) years with maximum diabetes duration 45 years. Mean HbA1c was 72 (95% CI: 67-77) mmol/mol; 97% had neuropathy (International Working Group on the Diabetic Foot (IWGDF) monofilament); 62% had vascular insufficiency (Doppler studies); 69% of ulcers were forefoot, and 23% of ulcers were hind foot in location. Forty of 98 (40%) patients died in follow-up with 27% of death certificates including sepsis (not foot-related) and 35% renal failure as cause of death. Multivariate regression analysis indicated a 6.3 (95% CI: 3.9-8.1) fold increased risk of death with hind foot ulcer, independent of age/BMI/gender/HbA1c/eGFR/total cholesterol level. CONCLUSION: This prospective study has indicated a very high long-term mortality rate in individuals with DFU, greater for those with a hind foot ulcer and shown a close relation between risk of sepsis/renal failure and DFU mortality, highlighting again the importance of addressing all risk factors as soon as people present with a foot ulcer.

Isolated low toe-brachial index is associated with increased mortality and morbidity: a retrospective cohort study.

OBJECTIVE: The aim was to assess the prognostic impact of perfusion assessments including ankle-brachial Index (ABI) and toe-brachial Index (TBI) on survival of patients who present with diabetic foot ulceration and to analyse clinical outcomes when patients are categorised into three levels of limb ischaemia. METHOD: This was a retrospective cohort analysis of consecutive patients presenting with foot ulceration. Patients continued with their standard of care, after having baseline assessments of limb perfusion. Patients were retrospectively categorised into three groups according to baseline ABI and TBI: Group 1 (n=31) non-ischaemic (TBI≥0.75, ABI≥0.9), Group 2 (n=67) isolated low TBI with foot ischaemia (TBI<0.75, ABI≥0.90) and Group 3 (n=30) foot-leg ischaemia (TBI<0.75, ABI<0.90). RESULTS: A total of 128 patients took part in the study. Low TBI was associated with a significant decrease in patient survival (42±20 versus 51±16 months, p=0.011). There was a progressive and significant decline in mean patient survival time (51±16 versus 44±20 versus 39±22 months, respectively, for ANOVA across the three groups, p=0.04). Patients with isolated low TBI had angioplasty and bypass at a rate similar to that of patients in Group 3 (low ABI and low TBI). The proportion of angioplasties was significantly higher in the isolated low TBI (19.4% (13/67) versus the non-ischaemic 3.2% (1/31), p=0.033). Such revascularisation resulted in ulcer healing within the foot ischaemic group that was similar to the non-ischaemic group (68% versus 60% over 12 months, p=0.454). CONCLUSION: Regardless of ABI level, measurement of TBI identifies patients with isolated low TBI who require specialised care pathways and revascularisation to achieve ulcer healing that is similar to non-ischaemic patients.

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

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

A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With High-Sensitivity Troponin T Study (RAPID-TnT).

BACKGROUND: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED). METHODS: Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression. RESULTS: In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49-70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P<0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4-6.4] hours versus standard arm: 5.6 (interquartile range, 4.0-7.1) hours, P<0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P<0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 17/1646 [1.0%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53-2.11], noninferiority P value=0.006, superiority P value=0.867), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0-99.9%) for 30-day death or myocardial infarction. CONCLUSIONS: This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au. Unique identifier: ACTRN12615001379505.

Optimal wound closure of diabetic foot ulcers with early initiation of TLC-NOSF treatment: post-hoc analysis of Explorer.

OBJECTIVE: In March 2018, the Explorer study, an international, double-blind, randomised controlled trial (RCT), established that adding a TLC-NOSF (UrgoStart Contact, Laboratoires Urgo, France) dressing to good local standard of care (SoC) significantly and substantially increases wound closure and reduces the healing time of neuroischaemic diabetic foot ulcers (DFU). Besides the TLC-NOSF treatment, the wound duration was the only other covariate that had an influence on the wound closure rate in the regression model used in the original study. The purpose of this work was to further document the impact of wound duration on the healing outcomes of the DFUs included in the Explorer study and to discuss complementary pragmatic observations on the TLC-NOSF effect. METHOD: In this post-hoc analysis of the Explorer data, the wound closure rates by week 20 are reported for the global cohort (n=240, Intention-to-treat population) and for the treated (n=126) and control groups (n=114) according to DFU duration and location. RESULTS: For the combined group, wound closure rates decreased with the increase of wound duration at baseline (from 57% in wounds ≤2 months to 19% in wounds >11 months). Whatever the wound duration subgroups analysed, higher closure rates were reported in the TLC-NOSF group than in the control group. However, the maximal difference between the two treatments was reported in wounds with a duration of ≤2 months (71% versus 41%, 30 percentage points difference, Relative Risk 1.7, 95% Confidence Interval 1.1 to 2.8). Regarding wound location subgroup analyses, the outcomes were always in favour of the TLC-NOSF treatment, with closure rates ranging between 43% and 61% within the TLC-NOSF group, and between 25% and 40% within the control group. CONCLUSION: This clinical evidence supports that treating DFUs with TLC-NOSF dressing and good SoC results in higher wound closure rates than with a neutral dressing and the same good standard of care, whatever the duration and the location of the treated wounds. However, the earlier the TLC-NOSF dressing is initiated in DFU treatment, the greater the benefits.

Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes-ProNOx1 study.

The aim of this multicenter, prospective, observer-blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting "real world" clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25-2,500 mm2 and either a palpable pedal pulse or ankle brachial pressure index > 0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12-week follow-up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110-75; Control-73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks in the intention-to-treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice.

A randomized trial of a 1-hour troponin T protocol in suspected acute coronary syndromes: Design of the Rapid Assessment of Possible ACS In the emergency Department with high sensitivity Troponin T (RAPID-TnT) study.

BACKGROUND: Protocols incorporating high-sensitivity troponin to guide decision making in the disposition of patients with suspected acute coronary syndromes (ACS) in the emergency department have received a lot of attention. Traditionally, patients with chest pain have required long periods of observation in emergency department before being deemed safe for discharge. In an era of limited health service resources, a protocol that could discharge patients safely within an hour of presentation is extremely attractive. Unfortunately, despite incorporation into some guidelines, these protocols have not been subjected to randomized comparisons evaluating safety, effectiveness, and cost-effectiveness. OBJECTIVE: This study is designed to provide the evidence required to allow key decision makers to implement these protocols: specifically, to provide evidence that a decision rule based on 0- and 1-hour high-sensitivity troponin T (hs-TnT) is safe, provides noninferior outcomes in all patients with suspected ACS, and that implementation of a rapid troponin protocol leads to efficient care. DESIGN: This prospective pragmatic trial (n=5,400, 5 hospitals) randomly allocates patients with suspected ACS to either a 0/1-hour hs-TnT protocol as advocated in clinical guidelines, versus usual care of standard troponin reporting evaluated at 3 and 6hours. The primary effectiveness composite end points of this study are all-cause death and new/recurrent ACS within 30days. To evaluate cost-effectiveness, follow-up will determine clinical events, quality of life, and resource utilization within 12 months. SUMMARY: Demonstrating that a 0/1-hour hs-TnT protocol improves the effectiveness and efficiency of care within a robust comparative study will fill an evidence gap that currently limits the translation of more precise hs-TnT testing into better patient and health service outcomes.

Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κß ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (µm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 µm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) µm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) µm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone.

Infrared Thermography Shows That a Temperature Difference of 2.2°C (4°F) or Greater Between Corresponding Sites of Neuropathic Feet Does Not Always Lead to a Diabetic Foot Ulcer.

BACKGROUND: There is emerging interest in the application of foot temperature monitoring as means of diabetic foot ulcer (DFU) prevention. However, the variability in temperature readings of neuropathic feet remains unknown. The aim of this study was to analyze the long-term consistency of foot thermograms of diabetic feet at the risk of DFU. METHODS: A post-hoc analysis of thermal images of 15 participants who remained ulcer-free during a 12-month follow-up were unblinded at the end of the trial. Skin foot temperatures of 12 plantar, 15 dorsal, 3 lateral, and 3 medial regions of interests (ROIs) were derived on monthly thermograms. The temperature differences (∆Ts) of corresponding ROIs of both feet were calculated. RESULTS: Over the 12-month study period, out of the total 2026 plantar data points, 20.3% ROIs were rated as abnormal (absolute ∆T ≥ 2.2°C). There was a significant between-visit variability in the proportion of plantar ROIs with ∆T ≥ 2.2°C (range 7.6%-30.8%, chi-square test, P = .001). The proportion of patients presenting with hotspots (ROIs with ∆T ≥ 2.2°C), abnormal plantar foot temperature (mean ∆T of 12 plantar ROIs ≥ 2.2°C), and abnormal whole foot temperature (mean ∆T of 33 ROIs ≥ 2.2°C) varied between visits and showed no pattern (P > .05 for all comparisons). This variability was not related to the season of assessment. CONCLUSIONS: Despite the high rate of hotspots on monthly thermograms, all feet remained intact. This study underscores a significant between-visit inconsistency in thermal images of neuropathic feet which should be considered when planning DFU-prevention programs for self-testing and behavior modification.

A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Who was first to diagnose and report neuropathic arthropathy of the foot and ankle: Jean-Martin Charcot or Herbert William Page?

In November 1883, Jean-Martin Charcot and Charles Féré reported on bone and joint disease of the foot in cases of tabes dorsalis, and referred to the condition as 'pied tabétique'--a disabling neuropathic osteoarthropathy that we usually now refer to as the Charcot foot. Charcot had originally described neuropathic osteoarthropathy in more proximal joints in 1868, and in his 1883 paper with Féré stated that involvement of the short bones and small joints of the foot had not yet been described. They emphasised in the paper that one of their cases was the first ever observed, two years earlier, in 1881. It is relevant, however, that it was in this same year that involvement of the foot by tabetic arthropathy was presented to the International Medical Congress in London by an English surgeon, Herbert William Page. We believe that Page was the first to diagnose and to report a case of tabetic neuropathic osteoarthropathy in which the bones of the foot and ankle were involved. He was also the first to propose a link between the tabetic foot and disease of the peripheral nerves, as opposed to the central nervous system.

The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.

OBJECTIVE: This study evaluated the effect of pedal arch quality on the amputation-free survival and patency rates of distal bypass grafts and its direct impact on the rate of healing and time to healing of tissue loss after direct angiosome revascularization in patients with critical limb ischemia (CLI). METHODS: Between 2004 and 2011, patients undergoing distal bypass for CLI (Rutherford 4-6) were divided in groups taking into consideration the state of the pedal arch and direct angiosome revascularization (DAR) and non-DAR. Angiography was used to divide the pedal arch into three groups: complete pedal arch (CPA), incomplete pedal arch (IPA), and no pedal arch (NPA). The primary end points were patency rates at 12 months, amputation-free survival at 48 months, and the rate of healing and time to healing of foot tissue loss. RESULTS: A total of 154 patients (75% men) with CLI underwent 167 infrapopliteal bypasses. Patients were a median age of 75 years (range, 46-96 years). Diabetic mellitus was present in 76%, chronic renal failure in 28%, and ischemic heart disease in 44%. The primary patency rates at 1 year in the CPA, IPA, and NPA groups were 58.4%, 54.6%, and 63.8%, respectively (P = .5168), the secondary patency rates were 86.0%, 84.7%, and 88.8%, respectively (P = .8940), and the amputation-free survival at 48 months was 67.2%, 69.7%, and 45.9%, respectively (P = .3883). Tissue loss was present in 141 of the 167 bypasses. In the CPA group, 83% of tissue loss with DAR healed compared with 92% in the non-DAR (median time to healing, 66 vs 74 days). Similarly in the IPA group, 90% with DAR healed compared with 81% in the non-DAR (median time to healing, 96 vs 86 days). In the NPA group, only 75% with DAR healed compared with 73% in the non-DAR (median time to healing, 90 vs 135 days). There was a significant difference in healing and time to healing between the CPA/IPA and NPA groups (P = .0264). CONCLUSIONS: The quality of the pedal arch did not influence the patency or the amputation-free survival rates. However, the rates for healing and time to healing were directly influenced by the quality of the pedal arch rather than the angiosome revascularized.