The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation ...status.
For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB
efficacy was
the maximum serum and tissue ATB concentrations(C
and C
)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100%
and ≥50%/60%
fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO
).
Following bolus administration, the C
of AMC was 91.8 ± 52.5 μgmL
and the C
of AMC was 7.25 ± 4.5 μgmL
(
<0.001). The C
for CTZ was 186.8 ± 44.1 μgmL
and the C
of CTZ was 18.6 ± 7.4 μgmL
(
<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both C
and AUC
and arterial flow. Specifically, the correlation coefficient for the first phase was
0.42; (
=0.045), and for the second phase, it was
=0.55(
=0.01)and
=0.5(
=0.021).
Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus ...percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT (r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.
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.
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.
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.
Objective. Off-loading is one of the crucial components of diabetic foot (DF) therapy. However, there remains a paucity of studies on the most suitable off-loading for DF patients under postoperative ...care. The aim of our study was to evaluate the effect of different protective off-loading devices on healing and postoperative complications in DF patients following limb preservation surgery. Methods. This observational study comprised 127 DF patients. All enrolled patients had undergone foot surgery and were off-loaded empirically as follows: wheelchair+removable contact splint (RCS) (group R: 29.2%), wheelchair only (group W: 48%), and wheelchair+removable prefabricated device (group WP: 22.8%). We compared the primary (e.g., the number of healed patients, healing time, and duration of antibiotic (ATB) therapy) and secondary outcomes (e.g., number of reamputations and number and duration of rehospitalizations) with regard to the operation regions across all study groups. Results. The lowest number of postoperative complications (number of reamputations: p=0.028; rehospitalizations: p=0.0085; and major amputations: p=0.02) was in group R compared to groups W and WP. There was a strong trend toward a higher percentage of healed patients (78.4% vs. 55.7% and 65.5%; p=0.068) over a shorter duration (13.7 vs. 16.5 and 20.3 weeks; p=0.055) in the R group, as well. Furthermore, our subanalysis revealed better primary outcomes in patients operated in the midfoot and better secondary outcomes in patients after forefoot surgery—odds ratios favouring the R group included healing at 2.5 (95% CI, 1.04-6.15; p=0.037), reamputations at 0.32 (95% CI, 0.12-0.84; p=0.018), and rehospitalizations at 0.22 (95% CI, 0.08-0.58; p=0.0013). Conclusions. This observational study suggests that removable contact splint combined with a wheelchair is better than a wheelchair with or without removable off-loading device for accelerating wound healing after surgical procedures; it also minimises overall postoperative complications, reducing the number of reamputations by up to 77% and the number of rehospitalizations by up to 66%.
Determination of the broad‐spectrum antibiotics amoxicilline (AMX) and ceftazidime (CTZ) in blood serum and microdialysates of the subcutaneous tissue of the lower limbs is performed using CE ...with contactless conductivity detection (C4D). Baseline separation of AMX is achieved in 0.5 M acetic acid as the background electrolyte and separation of CTZ in 3.2 M acetic acid with addition of 13% v/v methanol. The CE‐C4D determination is performed in a 25 µm capillary with suppression of the EOF using INST‐coating on an effective length of 18 cm and the attained migration time is 4.2 min for AMX and 4.4 min for CTZ. The analysis was performed using 20 µl of serum and 15 µl of microdialysate, treated by the addition of acetonitrile in a ratio of 1/3 v/v and the sample is injected into the capillary using the large volume sample stacking technique. The LOQ attained in the microdialysate is 148 ng/ml for AMX and 339 ng/ml for CTZ, and in serum 143 ng/ml for AMX and 318 ng/ml for CTZ. The CE‐C4D method is employed for monitoring the passage of AMX and CTZ from the blood circulatory system into the subcutaneous tissue at the sites of diabetic ulceration in patients suffering from diabetic foot syndrome and also for measuring the pharmacokinetics following intravenous application of bolus antibiotic doses.
The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients ...treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n=50) and subgroup R by resistant pathogens (n=18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p<0.01) and total numbers of lymphocytes (p<0.001) involving B lymphocytes (p<0.01), CD4+ (p<0.01), and CD8+ T cells (p<0.01) and their naive and memory effector cells. Higher levels of IgG (p<0.05) including IgG1 (p<0.001) and IgG3 (p<0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p<0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p<0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls.
Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut ...microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.
Diabetic foot is a serious late complication frequently caused by infection and ischaemia. Both require prompt and aggressive treatment to avoid lower limb amputation. The effectiveness of peripheral ...arterial disease therapy can be easily verified using triplex ultrasound, ankle-brachial/toe-brachial index examination, or transcutaneous oxygen pressure. However, the success of infection treatment is difficult to establish in patients with diabetic foot. Intravenous systemic antibiotics are recommended for the treatment of infectious complications in patients with moderate or serious stages of infection. Antibiotic therapy should be initiated promptly and aggressively to achieve sufficient serum and peripheral antibiotic concentrations. Antibiotic serum levels are easily evaluated by pharmacokinetic assessment. However, antibiotic concentrations in peripheral tissues, especially in diabetic foot, are not routinely detectable. This review describes microdialysis techniques that have shown promise in determining antibiotic levels in the surroundings of diabetic foot lesions.
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