Defensins are the most widespread antimicrobial peptides characterised in insects. These cyclic peptides, 4-6 kDa in size, are folded into α-helical/β-sheet mixed structures and have a common ...conserved motif of three intramolecular disulfide bridges with a Cys1-Cys4, Cys2-Cys5 and Cys3-Cys6 connectivity. They have the ability to kill especially Gram-positive bacteria and some fungi, but Gram-negative bacteria are more resistant against them. Among them are the medicinally important compounds lucifensin and lucifensin II, which have recently been identified in the medicinal larvae of the blowflies Lucilia sericata and Lucilia cuprina, respectively. These defensins contribute to wound healing during a procedure known as maggot debridement therapy (MDT) which is routinely used at hospitals worldwide. Here we discuss the decades-long story of the effort to isolate and characterise these two defensins from the bodies of medicinal larvae or from their secretions/excretions. Furthermore, our previous studies showed that the free-range larvae of L. sericata acutely eliminated most of the Gram-positive strains of bacteria and some Gram-negative strains in patients with infected diabetic foot ulcers, but MDT was ineffective during the healing of wounds infected with Pseudomonas sp. and Acinetobacter sp. The bactericidal role of lucifensins secreted into the infected wound by larvae during MDT and its ability to enhance host immunity by functioning as immunomodulator is also discussed.
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.
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.
A novel homologue of insect defensin designated lucifensin (Lucilia defensin) was purified from the extracts of various tissues (gut, salivary glands, fat body, haemolymph) of green bottle fly ...(Lucilia sericata) larvae and from their excretions/secretions. The primary sequence of this peptide of 40 residues and three intramolecular disulfide bridges was determined by ESI-QTOF mass spectrometry and Edman degradation and is very similar to that of sapecin and other dipteran defensins. We assume that lucifensin is the key antimicrobial component that protects the maggots when they are exposed to the highly infectious environment of a wound during the medicinal process known as maggot therapy. We also believe that lucifensin is that long-sought larger molecular weight antimicrobial factor of the Lucilia sericata excretions/secretions believed to be effective against pathogenic elements of the wound microbial flora.
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.
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).
Chronic venous disease (CVD) is a vascular disorder in which blood return is severely compromised and CVD is usually characterized by venous hypertension. Along with obesity and diabetes mellitus, ...CVD is one of the most common civilization diseases. In general, the estimated prevalence of CVD ranges from 60-80 %. Early diagnosis and adequate treatment are important for preventing progression to more severe stages of the disease like venous leg ulcers. Clinical manifestations of CVD in initial stages of the disease are often asymptomatic. However, as CVD progresses, symptoms begin to develop. Treatment of CVD could be divided into conservative and surgical. Conservative therapy consists of compression, pharmacological treatment and lifestyle change. In cases where conservative therapy is ineffective, surgical or endovascular treatment may be required. The intersections between diabetes mellitus (DM) and CVD are not to be underestimated. CVD and DM have often the same risk factors. Symptoms of CVD can be modified by late complications of DM, but the incidence of different CVD degrees seems to be the same as in diabetics as in non-diabetics population. We are particularly concerned in diabetics about worse compliance with treatment due to their often-poorer adherence to treatment of DM and lifestyle changes. Moreover, there exist a higher risk of CVD and peripheral arterial disease in diabetics patients. Patients with CVD should always be inspected for the presence of DM, considering its presence can have a bearing on CVD symptoms, diagnostic procedures, and therapeutic strategies.
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.
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.
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