In this review we report on the state of cell therapy of critical limb ischemia (CLI) with respect to differences between diabetic and non-diabetic patients mainly from the clinical point of view. CLI is the most severe form of peripheral arterial disease and its diagnosis and treatment in diabetic patients is very difficult. The therapeutic effect of standard methods of CLI treatment is only partial - more than one third of diabetic patients are not eligible for standard revascularization; therefore, new therapeutic techniques such as cell therapy have been studied in clinical trials. 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. A revascularization procedure cannot be successful as the only method in contrast to patients without diabetes, but it must always be part of a complex therapy focused not only on ischemia, but also on treatment of infection, off-loading, metabolic control of diabetes and nutrition, local therapy, etc. Therefore, the 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. This review carries out an analysis of the source of precursor cells, route of administration and brings a brief report of published data with respect to diabetic and non-diabetic patients and our experience with autologous cell therapy of diabetic patients with CLI. Analysis of the studies in terms of diabetes is difficult, because in most of them sub-analysis for diabetic patients is not performed separately. The other problem is that it is not clear if diabetic patients received adequate complex treatment for their foot ulcers which can strongly affect the rate of major amputation as an outcome of CLI treatment.

• Klíčová slova
• Cell therapy, Critical limb ischemia, Diabetes mellitus,
• MeSH
• amputace škodlivé účinky   MeSH
• buněčná a tkáňová terapie * metody   trendy   MeSH
• diabetická noha terapie   MeSH
• diabetické angiopatie terapie   MeSH
• hojení ran MeSH
• ischemie etiologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• onemocnění periferních arterií komplikace   terapie   MeSH
• vředy na noze (od hlezna dolů) etiologie   terapie   MeSH
• záchrana končetiny metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Limb ischemia is an extremely rare event occuring in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). The authors describe a case of TTTS and TAPS treated successfully using amnioreduction and laser ablation. However, severe ischemia of both lower extremities in the recipient twin developed after the fetal treatment. This serious complication was diagnosed on MRI in utero and confirmed postnatally. Elective amputation of the affected limbs was performed. The etiology of the disease remains unclear despite profound clinical and histopathological examinations; although the role of thromboembolism in monochorionic pregnancy seems to be most likely, this unique case of multiple limb ischemia with distinct macroscopic findings has not yet been described.

• Klíčová slova
• Monochorionic pregnancy, Multiple limb ischemia, Twin-to-twin transfusion syndrome,
• MeSH
• amputace metody   MeSH
• anemie komplikace   diagnostické zobrazování   chirurgie   MeSH
• dolní končetina krevní zásobení   diagnostické zobrazování   chirurgie   MeSH
• dvojčata monozygotní * MeSH
• fetofetální transfuze komplikace   diagnostické zobrazování   chirurgie   MeSH
• ischemie komplikace   diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• novorozenec s velmi nízkou porodní hmotností * MeSH
• polycytemie komplikace   diagnostické zobrazování   chirurgie   MeSH
• těhotenství MeSH
• vrozené deformity dolní končetiny komplikace   diagnostické zobrazování   chirurgie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

INTRODUCTION: Pedal bypass is a therapeutic option for limb salvage in critical limb ischemia. METHOD: Retrospective analysis of 20 patients who underwent either simple (14 patients) or branched (6 patients) pedal bypass in a single center and had at least one postoperative follow-up. In patients with branched pedal bypass, the main trunk was connected to the pedal artery of better quality and the side branch to an artery on the opposite side of the foot. The main trunk was constructed as a reverse saphenous bypass in all patients with branched bypass. From patients with simple bypass, nine had reverse saphenous graft, three had an allograft, one patient had in situ saphenous graft, and one PTFE prosthesis. RESULTS: The difference in the operation time was not significant. One patient with simple bypass required reoperation for wound bleeding and there was one case of perioperative mortality in the same group. The difference between the groups in the primary or secondary patency rates, limb salvage and overall survival was not significant. CONCLUSIONS: We did not find any significant difference in patency rates, limb salvage, or perioperative complications between patients with simple and branched pedal bypass in our cohort. We believe that the anticipated benefits of constructing an additional branch are masked by the disadvantageous presence of an additional anastomosis. Adoption of a branched pedal bypass may therefore require further improvements - perhaps the utilization of a branched saphenous graft. Key words: critical limb ischemia - peripheral arterial disease - bypass - revascularization - amputation.

• Klíčová slova
• critical limb ischemia - peripheral arterial disease - bypass - revascularization - amputation,
• MeSH
• ischemie * chirurgie   MeSH
• lidé MeSH
• průchodnost cév MeSH
• reoperace MeSH
• retrospektivní studie MeSH
• vena saphena MeSH
• výsledek terapie MeSH
• záchrana končetiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

(1) Background: The treatment of peripheral arterial disease (PAD) is focused on improving perfusion and oxygenation in the affected limb. Standard revascularization methods include bypass surgery, endovascular interventional procedures, or hybrid revascularization. Cell-based therapy can be an alternative strategy for patients with no-option critical limb ischemia who are not eligible for endovascular or surgical procedures. (2) Aims: The aim of this narrative review was to provide an up-to-date critical overview of the knowledge and evidence-based medicine data on the position of cell therapy in the treatment of PAD. The current evidence on the cell-based therapy is summarized and future perspectives outlined, emphasizing the potential of exosomal cell-free approaches in patients with critical limb ischemia. (3) Methods: Cochrane and PubMed databases were searched for keywords "critical limb ischemia and cell therapy". In total, 589 papers were identified, 11 of which were reviews and 11 were meta-analyses. These were used as the primary source of information, using cross-referencing for identification of additional papers. (4) Results: Meta-analyses focusing on cell therapy in PAD treatment confirm significantly greater odds of limb salvage in the first year after the cell therapy administration. Reported odds ratio estimates of preventing amputation being mostly in the region 1.6-3, although with a prolonged observation period, it seems that the odds ratio can grow even further. The odds of wound healing were at least two times higher when compared with the standard conservative therapy. Secondary endpoints of the available meta-analyses are also included in this review. Improvement of perfusion and oxygenation parameters in the affected limb, pain regression, and claudication interval prolongation are discussed. (5) Conclusions: The available evidence-based medicine data show that this technique is safe, associated with minimum complications or adverse events, and effective.

• Klíčová slova
• adipose tissue, bone marrow, cell therapy, critical limb ischemia, exosome, mesenchymal stem cells, peripheral arterial disease,
• MeSH
• buněčná a tkáňová terapie * MeSH
• ischemie terapie   MeSH
• končetiny krevní zásobení   MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• stanovení cílového parametru MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We present a case report of a patient with acute upper and lower limb ischemia due to paradoxical embolism. A 67-year old woman without history of venous thromboembolism suffered dislocated patellar fracture requiring surgery in November 2017. Two months after surgery she presented to the emergency room with bilateral pulmonary embolism, occlusion of the left subclavian artery, left common femoral artery and superior mesenteric artery. Transesophageal echocardiography detected patent foramen ovale. Vascular surgeon decided against embolectomy, interventional radiologist against pharmacomechanical thrombolysis due to the extent of the occlusions. Systemic thrombolysis (alteplase) was administered successfully with resolution of the emboli in the left subclavian artery, left common femoral artery and superior mesenteric artery.

• Klíčová slova
• acute limb ischemia, orthopedic surgery, paradoxical embolism, patent foramen ovale, systemic thrombolysis, venous thromboembolism,
• MeSH
• embolektomie MeSH
• foramen ovale apertum * komplikace   diagnostické zobrazování   farmakoterapie   MeSH
• ischemie farmakoterapie   MeSH
• lidé MeSH
• paradoxní embolie * farmakoterapie   chirurgie   MeSH
• plicní embolie * chirurgie   MeSH
• senioři MeSH
• trombolytická terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The aim of this retrospective study was to assess the success rates of limb salvage, and the primary and secondary patency rates of reconstructions of critical limb ischemia (CLI) patients undergoing combined infrainguinal reconstruction and intraluminal angioplasty of crural arteries. In 2000-2005, infrainguinal reconstruction with concomitant intraluminal angioplasty of crural arteries was performed in 30 patients with CLI, mean age was 63 years (S.D.=10); according to the Fontaine classification, 28 (93%) patients had stage IV and 2 (7%) stage III ischemia. During mean follow-up of 12.9 (S.D.=16.9) months, primary 1-year patency of vascular reconstruction was seen in 16 (52.6%) patients of our group. Secondary 1-year patency over the same follow-up period was documented in 17 (56.2%) patients and 1-year limb salvage was obtained in 25 (82.6%) patients. Based on this finding, we consider a combined surgical and endovascular procedure to be the method of choice in limb salvage in patients with CLI not allowing for an isolated endovascular procedure.

• MeSH
• arteriální okluzní nemoci komplikace   patofyziologie   chirurgie   terapie   MeSH
• balónková angioplastika * škodlivé účinky   přístrojové vybavení   MeSH
• časové faktory MeSH
• dolní končetina krevní zásobení   MeSH
• ischemie etiologie   patofyziologie   chirurgie   terapie   MeSH
• kombinovaná terapie MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• průchodnost cév MeSH
• reoperace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stenóza MeSH
• stenty MeSH
• stupeň závažnosti nemoci MeSH
• výkony cévní chirurgie * škodlivé účinky   MeSH
• výsledek terapie MeSH
• záchrana končetiny * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

In the course of the study of the syndrome of severe limb ischemia (SLI) in a representative clinical material of 300 patients and a number of experimental studies, we arrived to the proposal of this optimal methodical procedure for acute vascular closures of traumatic and non-traumatic origin in the limbs: a) In every injury and sudden pain with a change of the function of the limb, it is necessary to think of the SLI syndrome and to search targetedly for it. b) In injuries connected with bleeding our first-rate task is the control of this bleeding. For a temporary arrest of the bleeding it is necessary to prefer more physiological methods sparing collateral circulation to the still most used tourniquet. For this purpose a new device for temporary hemostasis called Hemostop has proved itself, designed by the author and attested both experimentally and clinically, protected as a Czechoslovak patent. From surgical measures have acquitted themselves from this viewpoint the insertion of vascular clamp, ligature of the vessel or its temporary cannulation. c) To set the diagnosis of SLI, it usually suffices a careful anamnesis and clinical examination, advantageous is the investigation by ultrasound. The angiography because of time consumption should be used only in indicated cases. d) The time factor--"race against the time"--has to be always borne on our mind. It is necessary to achieve the recovery of blood circulation in the limb up to 6 or at the latest up to 10 hours from the onset of injury or closure. e) For shortening of the period of tissue hypoxia it is of advantage to use the temporary cannulation of injured vessels. This should be used always, whenever because of any reasons, it is not possible to execute the final reconstructive operation up to 10 hours since the injury, e. g. in polytraumatism, transport difficulties and the like. f) In isolated vascular injuries without bleeding (about 45%) and in all non-traumatic SLI the patients must be efficiently heparinized (i. v. administration, at best by infusion) to prevent the growth of the distal thrombus. g) Final vascular reconstruction should be performed only by erudited surgeons, always with thromboctomy and in protected coagulum. Optimal reconstructive performance should be chosen: for embolism the thromboembolectomy, for acute thrombosis usually the bypassing the afflicted vascular portion by the graft, in injuries appears as the optimal reconstructive measure the anastomosis end to end. At the simultaneous or isolated lesion of the stem vein, we must always try to reconstruct it.(ABSTRACT TRUNCATED AT 400 WORDS)

• MeSH
• ischemie * diagnóza   etiologie   terapie   MeSH
• končetiny krevní zásobení   MeSH
• lidé středního věku MeSH
• lidé MeSH
• psi MeSH
• senioři MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• psi MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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 (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. RESULTS: During 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. 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).

• Klíčová slova
• autologous cell therapy, chronic limb-threatening ischemia, diabetic foot, major amputation of lower extremity, revascularization,
• MeSH
• bolest MeSH
• buněčná a tkáňová terapie MeSH
• chronická kritická ischemie končetin MeSH
• diabetes mellitus * MeSH
• diabetická noha * terapie   MeSH
• ischemie terapie   MeSH
• kyslík MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyslík MeSH

Autologous stem cell therapy is the most promising alternative treatment in patients with chronic ischemic diseases, including ischemic heart disease and critical limb ischemia, which are characterized by poor prognosis related to serious impair of quality of life, high risk of cardiovascular events and mortality rates. However, one of the most serious shortcomings of stem cell transplantation are low survival after transplantation to the site of injury, as large number of stem cells are lost within 24 hours after delivery. Multiple studies suggest that combination of lipid-lowering drugs, statins, and stem cell transplantation might improve therapeutic efficacy in regenerative medicine. Statins are inhibitors of HMG-CoA reductase and belong to recommended therapy in all patients suffering from critical limb ischemia. Statins possess non-lipid effects which involve improvement of endothelial function, decrease of vascular inflammation and oxidative stress, anti-cancer and stem cell modulation capacities. These non-lipid effects are explained by inhibition of mevalonate synthesis via blocking isoprenoid intermediates synthesis, such as farnesylpyrophospate and geranylgeranylpyrophospate and result in modulation of the PI3K/Akt pathway. Moreover, statin-mediated microRNA regulation may contribute to the pleiotropic functions. MicroRNA interplay in gene regulatory network of IGF/Akt pathway may be of special significance for the treatment of critical limb ischemia. We assume further studies are needed for detailed analysis of statin interactions with microRNA at the molecular level and their link to PI3K/Akt and IGF/Akt pathway in stem cells, which are currently the most promising treatment strategy used in chronic ischemic diseases.

• MeSH
• atorvastatin * farmakologie   terapeutické užití   MeSH
• chronická kritická ischemie končetin * farmakoterapie   terapie   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• ischemie * farmakoterapie   terapie   MeSH
• končetiny * krevní zásobení   MeSH
• kvalita života MeSH
• lidé MeSH
• statiny * farmakologie   terapeutické užití   MeSH
• transplantace kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• atorvastatin * MeSH
• statiny * MeSH

• MeSH
• aorta abdominalis MeSH
• arteria iliaca * diagnostické zobrazování   MeSH
• chronická kritická ischemie končetin MeSH
• disekce aorty * komplikace   diagnóza   chirurgie   MeSH
• ischemie etiologie   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH