Michal Dubsky
@ikem.cz
Diabetes Centre
Institute for Clinical and Experimental Medicine
Scopus Publications
Scopus Publications
Veronika Lovasova, Robert Bem, Jaroslav Chlupac, Michal Dubsky, Jitka Husakova, Andrea Nemcova, and Jiri Fronek
Elsevier BV
Michal Dubský, Jitka Husáková, Dominika Sojáková, Vladimíra Fejfarová, and Edward B. Jude
Springer Science and Business Media LLC
Jitka Husakova, Barbora Echalar, Jan Kossl, Katerina Palacka, Vladimira Fejfarova, and Michal Dubsky
MDPI AG
Background: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs on the characteristics of bone marrow-derived stem cells (BM-MSCs). Methods: The cells were isolated from the bone marrow of DPs, cultivated for 14–18 days, and phenotypically characterized using flow cytometry. These precursor cells were cultured in the presence of various IS drugs. The impact of IS drugs on metabolic activity was measured using a WST-1 assay, and the expression of genes for immunoregulatory molecules was detected through RT-PCR. Cell death was analyzed through the use of flow cytometry, and the production of cytokines was determined by ELISA. Results: The mononuclear fraction of cultured cells contained mesenchymal stem cells (CD45−CD73+CD90+CD105+), myeloid angiogenic cells (CD45+CD146−), and endothelial colony-forming cells (CD45−CD146+). IS drugs inhibited metabolic activity, the expression of genes for immunoregulatory molecules, the production of cytokines, and the viability of the cells. Conclusions: The results indicate that IS drugs in a dose-dependent manner had a negative impact on the properties of BM-MSCs used to treat ischemic diabetic foot ulcers, and that these drugs could affect the therapeutic potential of BM-MSCs.
Michal Dubsky, Jiri Veleba, Dominika Sojakova, Natalia Marhefkova, Vladimira Fejfarova, and Edward B. Jude
MDPI AG
Endothelial dysfunction (ED) is an important marker of future atherosclerosis and cardiovascular disease, especially in people with diabetes. This article summarizes the evidence on endothelial dysfunction in people with diabetes and adds different perspectives that can affect the presence and severity of ED and its consequences. We highlight that data on ED in type 1 diabetes are lacking and discuss the relationship between ED and arterial stiffness. Several interesting studies have been published showing that ED modulates microRNA, microvesicles, lipid levels, and the endoplasmatic reticulum. A better understanding of ED could provide important insights into the microvascular complications of diabetes, their treatment, and even their prevention.
Jiri Kanta, Anna Zavadakova, Eva Sticova, and Michal Dubsky
Wiley
Dominika Sojáková, Jitka Husáková, Vladimíra Fejfarová, Veronika Wosková, Andrea Němcová, Radka Jarošíková, and Michal Dubský
Solen s.r.o.
R Jarošíková, K Roztočil, J Husáková, M Dubský, R Bém, V Wosková, and V Fejfarová
Institute of Physiology of the Czech Academy of Sciences
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.
Vladimíra Fejfarová, Radka Jarošíková, Jan Polák, Blanka Sommerová, Jitka Husáková, Veronika Wosková, Michal Dubský, and Petr Tůma
Frontiers Media SA
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.
Michal Dubský, Jitka Husáková, Robert Bem, Alexandra Jirkovská, Andrea Němcová, Vladimíra Fejfarová, Karol Sutoris, Michal Kahle, and Edward B. Jude
Frontiers Media SA
BackgroundAutologous 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.MethodsDiabetic 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 (TcPO2) 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.ResultsDuring the first 12 weeks, TcPO2 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 TcPO2 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 TcPO2 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 TcPO2 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.ConclusionsThis 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 registrationThe trial was registered in the National Board of Health (EudraCT 2016-001397-15).
Michal Dubský, Vladimira Fejfarova, Robert Bem, and Edward B. Jude
Springer Science and Business Media LLC
Eliška Vrátná, Jitka Husáková, Radka Jarošíková, Michal Dubský, Veronika Wosková, Robert Bém, Alexandra Jirkovská, Kateřina Králová, Bára Pyšková, Věra Lánská,et al.
Frontiers Media SA
ObjectivesDiabetic foot syndrome (DFS) is a serious late diabetic complication characterised by limited joint mobility and other biomechanical and muscle abnormalities.AimTo 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 SelectionThirty-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 extractionDue 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.ConclusionOur 12-week interventional exercise programme proved relatively safe, resulting in improved body flexibility and increased muscle strength in DF patients in remission.
Veronika Lovasova, Robert Bem, Jaroslav Chlupac, Michal Dubsky, Jitka Husakova, Andrea Nemcova, and Jiri Fronek
Wiley
Critical limb ischemia is a serious form of peripheral arterial disease (PAD). The consequences of lower limb ischemia are pain, claudication and chronic non-healing wounds. Patients with diabetes are especially at a high risk for developing non-healing ulcers. The most serious complication is major amputation. For this reason, there is a significant medical requirement to develop new therapies in order to prevent the progression of PAD. For research purposes, it is crucial to find an appropriate model of chronic ischemia to explore the processes of wound healing. According to recently acquired information, rodents are currently the most commonly used animals in these types of studies. The main advantage of using small animals is the low financial cost due to the relatively small demand for food, water and living space. The disadvantage is their anatomy, which is different from that of humans. Larger animals have a more human-like anatomy and physiology, but they require more expense and space for housing. A bipedicle skin flap and its modifications are popular models for ischemic wounds. In order to secure healing through re-epithelisation, as opposed to contraction in rodents, there is a need to remove the panniculus carnosus muscle. Wounds in other experimental animals heal primarily through re-epithelisation. The application of a silicone mesh underneath the flap prevents vascular regrowth in ischemic tissue. There is an ongoing effort to create in vivo diabetic models for chronic ulcer research. This work presents an overview of existing animal models of ischemic wounds.
Jitka Husáková, Klára Sochorová, Vladimíra Fejfarová, and Michal Dubský
Solen s.r.o.
Diabetes mellitus představuje onemocnění, které je často spojeno s mnohočetnými komplikacemi, a to zejména vlivem dlouhodobě neuspokojivé kompenzace. Ve spojitosti s diabetem je však málokdy zmiňováno riziko rozvoje sexuálních dysfunkcí, které postihují muže i ženy (1). Sexuální komplikace nenarušují pouze sociální a pohlavní život pacientů, ale jsou mnohdy prvním příznakem dalších zdravotních obtíží. Z těchto důvodů by u lidí s diabetem měl být včasný záchyt a správná léčba sexuálních dysfunkcí předmětem zájmu lékařů pečujících o diabetiky. Klíčová slova: diabetes mellitus, sexuální dysfunkce, erektilní dysfunkce, ejakulace, hypogonadismus, libido, dyspareunie.
Jitka Husakova, Robert Bem, Alexandra Jirkovska, Andrea Nemcova, Vladimira Fejfarova, Karol Sutoris, Michal Kahle, Edward B. Jude, and Michal Dubsky
SAGE Publications
Autologous cell therapy (ACT) is a new therapeutic approach for diabetic patients with no-option chronic limb-threatening ischemia (NO-CLTI). The aim of our study was to quantify cell populations of cell therapy products (CTPs) obtained by three different isolation methods and to correlate their numbers with changes in transcutaneous oxygen pressure (TcPO2). CTPs were separated either from stimulated peripheral blood (PB) (n = 11) or harvested from bone marrow (BM) processed either by Harvest SmartPReP2 (n = 50) or sedimented with succinate gelatin (n = 29). The clinical effect was evaluated by the change in TcPO2 after 1, 3 and 6 months. TcPO2 increased significantly in all three methods at each time point in comparison with baseline values ( p < .01) with no significant difference among them. There was no correlation between the change in TcPO2 and the size of injected cell populations. We only observed a weak correlation between the number of injected white blood cells (WBC) and an increase in TcPO2 at 1 and 3 months. Our study showed that all three isolation methods of ACT were similarly relatively efficient in the treatment of NO-CLTI. We observed no correlation of TcPO2 increase with the number of injected monocytes, lymphocytes or CD34+. We observed a weak correlation between TcPO2 increase and the number of injected WBCs.
J. Husakova, R. Bem, V. Fejfarova, A. Jirkovska, V. Woskova, R. Jarosikova, V. Lovasova, E. B. Jude, and M. Dubsky
Hindawi Limited
Introduction. Autologous cell therapy (ACT) is one of the last options for limb salvage in patients with chronic limb-threatening ischemia (CLTI) and diabetic foot ulcers (DFU). However, some patients may still undergo a major amputation even after ACT, but the risk factors for this are not known. Therefore, the aim of our study was to assess the risk factors for major amputation in patients with CLTI and DFU during a 2-year follow-up after ACT. Methods. One hundred and thirteen patients after ACT were included in our study and divided into two groups: Group 1 with major amputation (AMP; n = 37 ) and Group 2 without amputation (nAMP, n = 76 ). The risk factors for major amputation were evaluated before ACT and included factors relating to the patient, the DFU, and the cell product. Results. The AMP group had significantly higher C-reactive protein (CRP) levels compared to the nAMP group (22.7 vs. 10.7 mg/L, p = 0.024 ). In stepwise logistic regression, independent predictors for major amputation were mutation of the gene for methylenetetrahydrofolate reductase (MTHFR) with heterozygote and homozygote polymorphism 1298 (OR 4.33 [95% CI 1.05-17.6]), smoking (OR 3.83 [95% CI 1.18-12.5]), and CRP > 10 mg / L (OR 2.76 [95% CI 0.93-8.21]). Lower transcutaneous oxygen pressure (TcPO2) values were observed in AMP patients compared to the nAMP group at one month (24.5 vs. 33.2, p = 0.012 ) and at 3 months (31.1 vs. 40.9, p = 0.009 ) after ACT. Conclusion. Our study showed that the risk for major amputation after ACT in patients with CLTI and DFU is increased by the presence of MTHFR heterozygote and homozygote gene mutations, smoking, and higher CRP at baseline. Lower TcPO2 at one and 3 months after ACT may also have a predictive value. Therefore, it is necessary to stop smoking before ACT, treat any infection, and, above all, consider antiaggregation or anticoagulant treatment after the procedure.
Vladimíra Fejfarová, Jiří Matuška, Edward Jude, Pavlína Piťhová, Milan Flekač, Karel Roztočil, Veronika Wosková, Michal Dubský, Alexandra Jirkovská, Robert Bém,et al.
Frontiers Media SA
BackgroundAll 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.MethodsThe 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.ResultsDuring the TcPO2 stimulation exercise test, group M exhibited significantly lower minimal TcPO2 (26.2 ± 11.1 vs. 31.4 ± 9.4 mmHg; p&lt;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.ConclusionCompared 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.Clinical Trial RegistrationClinicalTrials.gov [https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009V7W&amp;selectaction=Edit&amp;uid=U0005381&amp;ts=2&amp;cx=3j24u2], identifier NCT04404699
Michal Dubský, Vladimíra Fejfarová, Robert Bem, Alexandra Jirkovská, Andrea Nemcová, Karol Sutoris, Jitka Husáková, Jelena Skibová, and Edward B. Jude
SAGE Publications
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.
Katherine Ogurtsova, Stephan Morbach, Burkhard Haastert, Michal Dubský, Gerhard Rümenapf, Dan Ziegler, Alexandra Jirkovska, and Andrea Icks
Elsevier BV
AIMS
Our aim was to comprehensively estimate the incidence of diabetic foot ulcer (DFU) recurrence and corresponding risk factors in two cohorts.
METHODS
Prospective data from patients with active DFU from two diabetes centres in Germany (GER, n=222) and the Czech Republic (CZ, n=99) were analysed. Crude cumulative incidences were obtained. Additionally, time to recurrence and risk factors were investigated using multivariate Cox models.
RESULTS
69%(154) of patients in GER and 70%(69) in CZ experienced at least one DFU recurrence; 25%(56) in DEU and 15%(15) in CZ died; 5%(11) and 9%(9) were lost to follow-up. The crude cumulative incidence in the first year was 28% in GER and 25% in CZ; 68% / 70% within ten years, and 69%/70% in 15 years. In GER, renal replacement therapy was associated with shorter time to recurrence (HR=3.71, 95%CI:1.26-10.87); no history of DFU before the index lesion with longer time to recurrence (HR=0.62,0.42-0.92). In CZ, type 2 diabetes (HR=2.57,1.18-5.62) and index ulcer treatment by minor amputation (HR=2.11,1.03-4.33) were associated with shorter time to recurrence.
CONCLUSIONS
Cumulative DFU recurrence was approximately 70% in 15 years in both cohorts. We found a significantly higher risk of future recurrence in patients having a consecutive ulcer compared with the first ever ulcer.
Alexandra Jirkovská, Vladimíra Fejfarová, Michal Dubský, Veronika Wosková, Jiří Jarkovský, Klára Benešová, and Tomáš Pavlík
Solen s.r.o.
Péče o pacienty se syndromem diabetické nohy (SDN) vyžaduje mezioborovou spolupráci, a proto jsou na místě i mezioborová doporučení zaměřená na diagnostiku i léčbu a prevenci SDN. Tato doporučení potřebujeme také proto, že SDN má svá specifika, která ovlivňují jeho diagnostiku, terapii, ale i prognózu pacientů. Patří mezi ně např. odlišný průběh infekce a ICHDK u pacientů s diabetem, diagnostika neuropatické Charcotovy osteoartropatie i častá asociace s pokročilým onemocněním ledvin, které zhoršuje průběh SDN a zvyšuje jeho riziko. V neposlední řadě patří mezi specifika SDN problematika amputací s výrazně horší prognózou než u osob bez diabetu. Vytvoření interdisciplinárního týmu v podiatrických ambulancích, zajišťujícího komplexní péči o pacienty se SDN podle zásad uvedených v doporučeném postupu, je spojeno se zlepšením prognózy pacientů se SDN, zejména snížením amputací. Klíčová slova: syndrom diabetické nohy, ICHDK, infekce, amputace, Charcotova osteoartropatie.
E. Vrátná, J. Husáková, K. Králová, S. Kratochvílová, P. Girman, F. Saudek, M. Dubský, R. Bém, V. Wosková, A. Jirkovská,et al.
SAGE Publications
Diabetic foot (DF) can develop in diabetic patients after organ transplantation (Tx) due to several factors including peripheral arterial disease (PAD), diabetic neuropathy and inappropriate DF prevention. Aim: To assess the occurrence of DF and associated risk factors in transplant patients. Methods: Fifty-seven diabetic patients were enrolled as part of this prospective study. All patients underwent organ Tx (01/2013-12/2015) and were followed up for minimum of 12 months up to a maximum of 50 months. Over the study period we evaluated DF incidence and identified a number of factors likely to influence DF development, including organ function, presence of late complications, PAD, history of DF, levels of physical activity before and after Tx, patient education and standards of DF prevention. Results: Active DF developed in 31.6% (18/57) of patients after organ Tx within 11 months on average (10.7 ± 8 months). The following factors significantly correlated with DF development: diabetes control (p = .0065), PAD (p<0.0001), transcutaneous oxygen pressure (TcPO2;p = .01), history of DF (p = .0031), deformities (p = .0021) and increased leisure-time physical activity (LTPA) before Tx (p = .037). However, based on logistic stepwise regression analysis, the only factors significantly associated with DF during the post-transplant period were: PAD, deformities and increased LTPA. Education was provided to patients periodically (2.6 ± 2.5 times) during the observation period. Although 94.7% of patients regularly inspected their feet (4.5 ± 2.9 times/week), only 26.3% of transplant patients used appropriate footwear. Conclusions: Incidence of DF was relatively high, affecting almost 1/3 of pancreas and kidney/pancreas recipients. The predominant risk factors were: presence of PAD, foot deformities and higher LTPA before Tx. Therefore, we recommend a programme involving more detailed vascular and physical examinations and more intensive education focusing on physical activity and DF prevention in at-risk patients before transplantation.
Petr Sedivy, Monika Dezortova, Miloslav Drobny, Michal Dubsky, Tereza Dusilova, Jan Kovar, and Milan Hajek
Wiley
An unknown intense signal (Pun) with a mean chemical shift of 5.3 ppm was observed in 31P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m2) and 12 age‐matched healthy controls were examined by (dynamic) 31P MRS (3 T system, 31P/1H coil). Phantoms (glucose‐1‐phosphate, Pi and PCr) were measured at pH values of 7.05 and 7.51. At rest, Pun signals with intensities higher than 50% of the Pi intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the Pun signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra‐ and intracellular alkaline phosphate pools. 2,3‐diphosphoglycerate and glucose‐1‐phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3‐diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose‐1‐phosphate because its chemical shifts are about 0.2 ppm downfield from the Pi signal (4.9 ppm). If the Pun signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of Pi in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the Pun signal probably originates from interstitia. Our data suggest that the increased Pun signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.
Vladimíra Fejfarová, Hana Tibenská, Jitka Niklová, Robert Bém, Michal Dubský, Veronika Wosková, Andrea Němcová, Alexandra Jirkovská, Edward Jude, and Věra Lánská
SAGE Publications
Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents—particularly acidifying solutions—on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by Pseudomonas species. Patients were divided into 2 groups according to the local therapy provided: group 1 (n = 15)—modern local treatment; group 2 (n = 17)—acidifying antiseptic solutions. The study groups differed only with regard to ATB usage prior to enrolment in the study ( P = .004), but did not differ with regard to age, diabetes control, peripheral arterial disease, or microcirculation status. During the follow-up period, DFUs healed in 20% of cases in group 1, but there were no cases of healing in group 2 (NS). The length of ATB therapy, the number of new osteomyelitis, lower limb amputations, and the changes of DFUs status/proportions did not differ significantly between study groups. Pseudomonas was eradicated in 67% of cases in group 1 and in 65% of cases in group 2. The local treatment given to group 2 patients was associated with lower costs ( P < .0001). Conclusion. Acidifying agents had the same effect as modern healing agents on wound healing, the number of amputations, and the eradication of Pseudomonas. Moreover, therapy performed using acidifying solutions proved in our pilot study markedly cheaper.