Peripheral blood-derived autologous stem cell therapy for the treatment of patients with late-stage peripheral artery disease-results of the short- and long-term follow-up.

BACKGROUND AIMS: Regeneration of the occluded peripheral arteries by autologous stem cell therapy is an emerging treatment modality for no-option patients with peripheral artery disease (PAD). The purpose of this study was to assess safety and efficacy of in vitro-expanded, peripheral blood-derived, autologous stem cells (VesCell) in no-option patients with PAD. METHODS: A phase II, open-label, randomized clinical study was performed on 20 patients to investigate the safety and efficacy of VesCell therapy at 1 and 3 months of follow-up. The long-term (2 years) efficacy of the therapy was also evaluated. RESULTS: No side effects of VesCell therapy were found. During the 3 month follow-up in the control group, one death occurred and six major amputations were performed; in the treated group, there were no deaths or major amputations. The difference of limb loss is significant between the two groups. At 2-year follow-up in the control group, two deaths and six major amputations occurred; in the treated group, there were three major amputations. At 3-month follow-up, the change in hemodynamic parameters showed a significant increase in the treated group over the control group; in the treated group, further improvement was detected at 2 years. As the result of the VesCell treatment, change in pain score, wound healing and walking ability test showed an improvement compared with the control group; at 2 years, incremental improvement was observed. CONCLUSIONS: Peripheral blood-derived, in vitro-expanded autologous angiogenic precursor therapy appears to be a safe, promising and effective adjuvant therapy for PAD patients.

Wound stimulation by growth-arrested human keratinocytes and fibroblasts: HP802-247, a new-generation allogeneic tissue engineering product.

BACKGROUND: HP802-247 is a new-generation, allogeneic tissue engineering product consisting of growth-arrested, human keratinocytes (K) and fibroblasts (F) delivered in a fibrin matrix by a spray device. OBJECTIVE: To identify the preferred dose of HP802-247 based on cell concentration and K/F ratio. METHODS: A multicenter, randomized, double-blind, placebo-controlled, explorative phase II study of 6 different doses of HP802-247 administered once per week for 12 consecutive weeks in chronic venous leg ulcers. RESULTS: HP802-247 was safe and well tolerated and showed increasing efficacy dependent on cell concentration and K/F ratio, in line with in vitro growth factor release data. The mean complete closure rate at week 12 for all patients treated with HP802-247 was 40%, and for placebo it was 33%. In contrast to placebo, all HP802-247 dose groups improved from week 12 to 24. CONCLUSION: As an integral part of a rational tissue engineering product development, this explorative trial identified the preferred dose of HP802-247 for further clinical studies.

[Lipedema, a barely known disease: diagnosis, associated diseases and therapy]. / A lipoedema, egy alig ismert kórkép: diagnózis, társbetegségek, kezelés.

Lipedema is a common but rarely diagnosed disease or frequently confused with obesity. Patients are almost exclusively women. It is characterised by symmetrical, circumscribed, in advanced form deforming fat tissue accumulation on the legs that is associated with lymphedema. Spontaneous pain, pain to pressure and tendency to hematoma are characteristic. One of the possible causes of a fat leg, that is a very common complaint, is lipedema. Main differential diagnoses are obesity, lipohypertrophy and primary and secondary lymphedema. It is often associated with chronic venous and lymphatic insufficiency, early degenerative articular disease and obesity. The disease is rarely recognized and the treatment modalities are not widely known. Therefore patients feel very frustrated that leads to psychologic disorders. Until recently only conservative treatment was possible (combination of manual or intermittent pneumatic drainage, compression bandages and garments and physiotherapy). More recently surgical intervention (liposuction) is also included in the treatment options. The significance of lipedema is due not only to the disease itself, but also to the combination of lipedema and the group of associated and secondary diseases (articular and venous diseases, lymphedema, obesity, psychologic disorders). The more diseases coexist, the worse is the prognosis of lipedema itself. To prevent and delay this disease, it is indispensable to recognise it as early as possible and to treat it expertly and follow up patients suffering from lipedema.

Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy.

BACKGROUND: The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema. OBJECTIVES: To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers. PATIENTS AND METHODS: 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection. RESULTS: Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%). CONCLUSION: Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).

[Microcirculatory changes in patients with chronic venous and lymphatic insufficiency and heavy leg symptoms before and after therapy with procyanidol oligomers (laser-Doppler study)]. / Krónikus vénás-lymphás elégtelenség következtében kialakult "nehéz láb" tünetegyüttesben szenvedo betegek mikrocirkulációjának változása flavonoid-származékkal (procyanidol oligomerek) végzett kezelés hatására (lézer-Doppler módszer alkalmazása).

INTRODUCTION: To study the efficacy of venotonica and medicaments having anti-edema effect is very actual. AIMS: Patients suffering from venous-lymphatic insufficiency were treated with procyanidol oligomers in an open, prospective study. The effective substance of this medication protects the fibrous connective tissue protein, thus improving the function of the venous and lymphatic capillaries. METHODS: For three months, the daily dose was 2 x 150 mg 30 patients were included into the study. The efficacy of the treatment was evaluated by statistical methods analysing the changes of the clinical symptoms and the satisfaction of the patients. For the first time, laser-Doppler method was used to determine the pathological condition of the dermal microcirculation before and after 3 months of treatment. The laser-Doppler tests used as indicators of the functional changing of the microcirculations were as follows: venoarterial response, reactive hyperemic response, and thermal stimulation response. The authors established the standard values and compared the measurement scores to those. According to the resulting scores, the status before and after the treatment can be compared by statistic analysis. Subjective complaints of the patients such as pain, heaviness of the leg, nightly muscle cramps were estimated by a visual analog scale. RESULTS: The treatment (procyanidol oligomers) significantly reduced lymphedema (p < 0.001) in the "heavy leg" syndrome. Symptoms as pain, heaviness of the leg, muscle cramps, improved significantly (p < 0.001) after treatment. The microcirculatory status was pathologic before treatment. After treatment, there was no significant improvement in the laser-Doppler results. CONCLUSIONS: The study revealed that in venous-lymphatic insufficiency, the arterial-capillary system is also damaged. The authors bring to attention that the disorder of the dermal arteries playing a role in the pathogenesis of venous-lymphatic insufficiency first detected in this study needs to be further investigated.