Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization were randomized to treatment with 40 ml BMCs using local IM (n = 21) or selective IA infusion (n = 20). Primary endpoints were limb salvage and wound healing. Secondary endpoints were changes in transcutaneous oxygen pressure (tcpO 2 ), quality-of-life questionnaire (EQ5D), ankle-brachial index (ABI), and pain scale (0-10). Patients with limb salvage and wound healing were considered to be responders to BMC therapy. At 6-month follow-up, overall limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four patients died unrelated to stem cell therapy. There was significant improvement in tcpO 2 (15 ± 10 to 29 ± 13 mmHg, p < 0.001), pain scale (4.4 ± 2.6 to 0.9 ± 1.4, p < 0.001), and EQ5D (51 ± 15 to 70 ± 13, p < 0.001) and a significant decrease in the Rutherford category of CLI (5.0 ± 0.2 to 4.3 ± 1.6, p < 0.01). There were no differences among functional parameters in patients undergoing IM versus IA delivery. Responders (n = 27) were characterized by higher CD34 + cell counts in the bone marrow concentrate (CD34 + 29 ± 15×10 6 vs. 17 ± 12×10
BackgroundThe present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with “no-option” critical limb ischemia (CLI).Methods and resultsSixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular (n = 32) or intra-arterial (n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34+ cell count (p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) (p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger (p = 0.028), had lower C-reactive protein levels (p = 0.038), and had higher transcutaneous oxygen pressure (tcpO2) (p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34+ cells (p = 0.046) and baseline tcpO2 (p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage (p = 0.0008).ConclusionPatients who benefited from autologous BMC therapy for “no-option” CLI were treated with high doses of CD34+ cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy.Trial registrationThe study was approved and registered by the ISRCTN registry. Trial registration: ISRCTN16096154. Registered: 26 July 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0379-z) contains supplementary material, which is available to authorized users.
Cardiac myxomas make up approximately 50% of all benign cardiac tumors and represented 86% of all surgically treated cardiac tumors. Most of them originated from the left atrium, in some cases from both of atria. We report a case of male patient with biatrial myxomas and other extra-cardiac involvement: hypophyseal adenoma, enlargement of thyroid gland, tubular adenoma polyp of colon and bilateral large cell calcifying Sertoli cell tumor (LCCSCT) of testis. These findings led to the diagnosis of Carney's complex, which is a syndrome with multiple neoplasias, cardiac myxomas, lentigines, and endocrine abnormalities. A genetic test confirm this diagnosis. was revealed and resected the left atrial myxoma. This tumor was of identic consistence, 6 × 5 × 3 cm, attached to the free wall of the atrium by a small stalk 3 × 1 cm. The diagnosis of bilateral atrial myxomas was confirmed by histologic studies (Fig. 2). We assumed association between the endocrine abnormalities-hypophyseal adenoma, struma nodosa and benign tumors (bilateral LCCSCT of testis and biatrial tumor), and therefore we signed this patient with Carney complex. Carney complex is an autosomal dominant condition most commonly caused by mutations in the PRKAR1A gene on chromosome 17q23-q24. In our patient mutation c.491-492delTG/p.V164Dfs*5 in exon 4 of PRKAR1A gene was identified and the diagnosis of Carney complex was confirmed (Fig. 3). The patient was discharged in good condition. Keywords DiscussionAlthough primary tumors of the heart are rare, the myxoma is the most frequent benign primary heart tumor as it accounts for 0.3% of open-heart surgery. 4) Cardiac myxomas usually appear as a sporadic isolated condition in the left atrium of middle-aged women with no other coincidental pathology. A small percentage of primary cardiac tumors have familial penetrance. Recurrence is more frequent in patients with the family history of myxoma, and familial myxomas frequently appear et early ages, with atypical and multicentric location. 5) In 1985, Carney and others described in young people a special complex group of cardiac myxomas associated to a distinctive complex pathology, giving identity to the There is a marked familial trend (52%), a high incidence of recurrence (20%). 6) The most frequent extra-cardiac involvements are pigmented skin lesions, cutaneous myxomas, adrenal cortical disease, myxoid mammary fibroadenoma, pituitary adenoma, melanotic schwannomas, thyroid disease and male patients with testes tumors. The diagnosis is made when two or more of these criteria are present. The myxom in CNC is usually in left atrium, biatrial myxomas are rare. The four chambers of the heart should be examined at surgery for typical myxoma locations, right atriotomy and combined superior-transseptal approach improve exposure of the cavities. In our patient, the tumor size and attachment were identified by echocardiogram, and a safe and efficient transseptal incision was achieved. Myxoma is known to recur in 30%-70% of patients with familial myxomas. Close follo...
Heart transplantation ranks among those surgical interventions associated with ischemia-reperfusion injury to the donor heart as well as to the recipient. These events are connected with increased production of reactive oxygen species which evoke metabolic, structural and functional disturbances. Twenty-four transplant patients were investigated for oxidative stress (plasma levels of thiobarbituric acid reactive substances, TBARS) and antioxidant capacity (plasma total antioxidant status, TAS), and for activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) during the first year after heart transplantation. The post-transplant period was characterized by progressive decrease of plasma TAS, indicating a significant long-term drop of antioxidant reserves in patients after successful heart transplantation. The decrease in plasma TAS is accompanied by long-lasting increase of TBARS levels, which may represent oxidative stress of the organism. We conclude that additional therapy with antioxidant substances should be an important component of the complex therapeutic programme of patients after heart transplantation.
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