Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and ...risk factors for DFU recurrence after healing during a 3‐year follow‐up period. At our site, 93 Eurodiale‐enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes‐related factors duration, and glycated haemoglobin (HbA1c) levels; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU‐related factors peripheral arterial disease, ulcer infection, C‐reactive protein (CRP) and; foot deformities. During the 3‐year follow‐up period, a DFU had recurred in 42 patients (57·5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location odds ratio (OR) 8·62, 95% confidence interval (CI) 2·2–33·2; presence of osteomyelitis (OR 5·17, 95% CI 1·4–18·7); HbA1c > 7·5% (DCCT, OR 4·07, 95% CI 1·1–15·6) and CRP > 5 mg/l (OR 4·27, 95% CI 1·2–15·7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3‐year follow‐up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.
Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent ...predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation.
We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries.
Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively).
For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.
Background
Autologous cell therapy (ACT) is a new treatment method for patients with diabetes and no-option chronic limb-threatening ischemia (NO-CLTI). We aimed to assess the impact of ACT on ...NO-CLTI in comparison with standard treatment (ST) in a randomized controlled trial.
Methods
Diabetic patients with NO-CLTI were randomized to receive either ACT (n=21) or ST (n=19). After 12 weeks, those in the ST group, who did not improve were treated with ACT. The effect of ACT on ischemia and wound healing was assessed by changes in transcutaneous oxygen pressure (TcPO
2
) and the number of healed patients at 12 weeks. Pain was evaluated by Visual Analogue Scale (VAS). Amputation rates and amputation-free survival (AFS) were assessed in both groups.
Results
During the first 12 weeks, TcPO
2
increased in the ACT group from 20.8 ± 9.6 to 41.9 ± 18.3 mm Hg (p=0.005) whereas there was no change in the ST group (from 21.2 ± 11.4 to 23.9 ± 13.5 mm Hg). Difference in TcPO
2
in the ACT group compared to ST group was 21.1 mm Hg (p=0.034) after 12 weeks. In the period from week 12 to week 24, when ST group received ACT, the TcPO
2
in this group increased from 20.1 ± 13.9 to 41.9 ± 14.8 (p=0.005) while it did not change significantly in the ACT in this period. At 24 weeks, there was no significant difference in mean TcPO
2
between the two groups. Wound healing was greater at 12 weeks in the ACT group compared to the ST group (5/16 vs. 0/13, p=0.048). Pain measured using VAS was reduced in the ACT group after 12 weeks compared to the baseline, and the difference in scores was again significant (p<0.001), but not in the ST group. There was no difference in rates of major amputation and AFS between ACT and ST groups at 12 weeks.
Conclusions
This study has showed that ACT treatment in patients with no-option CLTI and diabetic foot significantly improved limb ischemia and wound healing after 12 weeks compared to conservative standard therapy. Larger randomized controlled trials are needed to study the benefits of ACT in patients with NO-CLTI and diabetic foot disease.
Trial registration
The trial was registered in the National Board of Health (EudraCT 2016-001397-15).
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.
Background: Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting ...in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO. Aim: The aim of this study is to review European national diabetes CPGs for the diagnosis and management of active CNO and to assess their methodological rigor and transparency. Methods: A systematic search was performed to identify diabetes national CPGs across Europe. Guidelines in any language were reviewed to explore whether they provided a definition for active CNO and recommendations for diagnosis, monitoring, and management. Methodological rigor and transparency were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool, which comprises 23 key items organized within six domains with an overall guideline assessment score of ≥60% considered to be of adequate quality to recommend use. Each guideline was assessed by two reviewers, and inter-rater agreement (Kendall's W) was calculated for AGREE-II scores. Results: Seventeen CPGs met the inclusion criteria. Breadth of CNO content varied across guidelines (median (IQR) word count: 327; Q1=151; Q3=790), and 53% provided a definition for active CNO. Recommendations for diagnosis and monitoring were provided by 82% and 53%, respectively, with offloading being the most common management recommendation (88%). Four guidelines (24%) reached threshold for recommendation for use in clinical practice (≥60%) with the scope and purpose domain scoring highest (mean (SD): 67%, ±23%). The remaining domains had average scores ranging between 19% and 53%. Inter-rater agreement was strong (W=0.882; p<0.001). Conclusions: European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.
Objectives
Diabetic foot syndrome (DFS) is a serious late diabetic complication characterised by limited joint mobility and other biomechanical and muscle abnormalities.
Aim
To evaluate the effect of ...an interventional exercise programme on anthropometric parameters, muscle strength, mobility and fitness in patients with diabetic foot in remission.
Data Sources and Study Selection
Thirty-eight patients with type 2 diabetes and DFS without active lesions (mean age 65 ± 6.9 years, BMI 32 ± 4.7 kg.m
-2
, waist-hip ratio (WHR)1.02 ± 0.06) were enrolled in our randomised controlled trial. All subjects were randomised into two groups: an intervention group (I; n=19) and a control group (C; n=19). The 12-week exercise intervention focused on ankle and small-joint mobility in the foot, strengthening and stretching of the lower extremity muscles, and improvements
in
fitness. Changes (Δ=final minus initial results) in physical activity were assessed using the International Physical Activity Questionnaire (IPAQ), with joint mobility detected by goniometry, muscle strength by dynamometry, and fitness using the Senior
Fitness
Test (SFT).
Data extraction
Due to reulceration, 15.8% of patients from group I (3/19) and 15.8% of patients from group C were excluded. Based on the IPAQ, group I was more active when it came to heavy (p=0.03) and moderate physical activity (p=0.06) after intervention compared to group C. Group I improved significantly in larger-joint flexibility (p=0.012) compared to controls. In group I, dynamometric parameters increased significantly in both lower limbs (left leg; p=0.013, right leg; p=0.043) compared to group C. We observed a positive trend in the improvement of fitness in group I compared to group C. We also confirmed positive correlations between heavy physical activity and selected parameters of flexibility (r=0.47; p=0.007), SFT (r=0.453; p=0.011) and dynamometry (r=0.58; p<0.0025). Anthropometric parameters, such as BMI and WHR, were not significantly influenced by the intervention programme.
Conclusion
Our 12-week interventional exercise programme proved relatively safe, resulting in improved body flexibility and increased muscle strength in DF patients in remission.
Highlights • Cell therapy of critical limb ischemia (CLI) is new therapeutic technique for patients not eligible for standard revascularization. • Presence of CLI in patients with diabetic foot ...disease is associated with worse clinical outcomes such as lack of healing of foot ulcers, major amputations and premature mortality. • Main criteria for cell therapy may vary in diabetic patients and non-diabetic persons and results of this treatment method should always be assessed in the context of ensuring comprehensive therapy. • Analysis of the studies in terms of diabetes is difficult, because in most of them sub-analysis for diabetic patients is not performed separately. • Cell therapy in diabetic patients with no-option CLI significantly improves ischemia parameters in majority of the studies. • The discrepancy in amputation rates after cell therapy in several studies can be explained by different factors influencing the major amputation in diabetic patients.
Endothelial progenitors are a population of cells with the inherent capacity to differentiate into mature endothelial cells and proangiogenic paracrine action. These characteristics have led to ...extensive studies being performed and tested in the treatment of tissue ischemia. The natural course of diabetes mellitus (DM) results in multiple areas of vascular damage. Thus endothelial progenitor cells‘(EPCs) beneficial potential is particularly desirable in diabetic patients. In this review, we summarize contemporary knowledge of EPC biology in DM. It has been shown that EPC functions are considerably impaired by DM. The presence of peripheral arterial disease (PAD) seems to further exacerbate the deficiencies of EPCs. However, studies examining EPC counts in PAD and DM observed disparate results, which can be due to a lack of consensus on precise EPC immunotype used in the different studies. Nevertheless, the results of EPC-based autologous cell therapy (ACT) are promising. In addition, EPCs have been shown to bean independent predictor of cardiovascular risk and diabetic foot ulcer healing.
The aim of our case-control study was to compare selected psychological and social characteristics between diabetic patients with and without the DF (controls). Methods. 104 patients with and 48 ...without DF were included into our study. Both study groups were compared in terms of selected psychosocial characteristics. Results. Compared to controls, patients with DF had a significantly worse quality of life in the area of health and standard of living as shown by lower physical health domain ( 12.7 ± 2.8 versus 14.7 ± 2.5 ; P < 0.001 ) and environment domain ( 14.1 ± 2.2 versus 15 ± 1.8 ; P < 0.01 ) that negatively correlated with diabetes duration ( r = - 0.061 ; P = 0.003 ). Patients with DF subjectively felt more depressed in contrast to controls (24.5 versus 7.3%; P < 0.05 ); however, the depressive tuning was objectively proven in higher percentage in both study groups (83.2 versus 89.6; NS). We observed a significantly lower level of achieved education ( P < 0 . 01 ), more patients with disability pensions ( P < 0 . 01 ), and low self-support ( P < 0 . 001 ) in patients with the DF compared to controls. In the subgroup of patients with a previous major amputation and DF ( n = 6 ), there were significantly worse outcomes as in the environment domain ( P < 0.01 ), employment status, and stress readaptation ( P < 0.01 ) in contrast to the main study groups. Conclusions. Patients with DF had a predominantly worse standard of living. In contrast to our expectations, patients with DF appeared to have good stress tolerability and mental health (with the exception of patients with previous major amputation) and did not reveal severe forms of depression or any associated consequences.
Autologous cell therapy (ACT) is a new treatment for patients with no-option critical limb ischemia (NO-CLI). We evaluated the factors involved in the nonresponse to ACT in patients with CLI and ...diabetic foot. Diabetic patients (n = 72) with NO-CLI treated using ACT in our foot clinic over a period of 8 years were divided into responders (n = 57) and nonresponders (n = 15). Nonresponder was defined as an insufficient increase in transcutaneous oxygen pressure by <5 mm Hg, 3 months after ACT. Patient demographics, diabetes duration and treatment, and comorbidities as well as a cellular response to ACT, limb-related factors, and the presence of inherited thrombotic disorders were compared between the 2 groups. The main independent predictors for an impaired response to ACT were heterozygote Leiden mutation (OR 10.5; 95% CI, 1.72-4) and homozygote methylenetetrahydrofolate reductase (MTHFR 677) mutation (OR 3.36; 95% CI, 1.0-14.3) in stepwise logistic regression. Univariate analysis showed that lower mean protein C levels (P = .041) were present in nonresponders compared with responders. In conclusion, the significant predictors of an impaired response to ACT in diabetic patients with NO-CLI were inherited thrombotic disorders.
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