***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Basic fibroblast growth factor ( bFGF ) has been shown to promote wound healing . The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer , a type of refractory skin ulcer , and the dose-response relationship . This was design ed as a r and omized , double-blind , dose-ranging , placebo-controlled trial . A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were r and omized into a placebo group ( n = 51 ) , a 0.001 % bFGF group ( n = 49 ) and a 0.01 % bFGF group ( n = 50 ) , and 148 of these patients received treatment for 8 weeks or less . The efficacy evaluation was carried out on 139 patients who met the protocol in this trial . The primary outcome was the percentage of patients showing 75 % or greater reductions in the area of ulcer . The area of ulcer decreased by 75 % or more in 57.5 % ( 27/47 ) , 72.3 % ( 34/47 ) , and 82.2 % ( 37/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively , and differences were significant between the 0.01 % bFGF and placebo groups ( p = 0.025 ) . The cure rate was 46.8 % ( 22/47 ) , 57.4 % ( 27/47 ) , and 66.7 % ( 30/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively . The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers Background —Bone-marrow mononuclear cell ( BM-MNC ) implantation improves ischemic symptoms in patients with critical limb ischemia ( CLI ) . The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI . Methods and Results —We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI , including 25 patients with peripheral arterial disease ( PAD ) and 26 patients with Buerger disease . Forty-six CLI patients who had no BM-MNC implantation served as control subjects . Median follow-up period was 4.8 years . The 4-year amputation-free rates after BM-MNC implantation were 48 % in PAD patients and 95 % in Buerger disease , and they were 0 % in control PAD patients and 6 % in control Buerger disease . The 4-year overall survival rates after BM-MNC implantation  were 76 % in PAD patients and 100 % in Buerger disease , and they were 67 % in control PAD patients and 100 % in control Buerger disease . Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation . In Buerger disease , ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up . However , in patients with PAD , ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels . Conclusions —These findings suggest that BM-MNC implantation is safe and effective in patients with CLI , especially in patients with Buerger disease . Clinical Trial Registration —URL : http://home.hiroshima-u.ac.jp/angio/. Unique identifier : 001769 OBJECTIVE  Chronic diabetic foot ulcers  are a source of major concern for both patients and health care systems . The aim of this study was to evaluate the effect of hyperbaric oxygen therapy ( HBOT ) in the management of  chronic diabetic foot ulcers .  RESEARCH DESIGN AND METHODS The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers ( HODFU ) study was a r and omized , single-center , double-blinded , placebo-controlled clinical trial . The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air . Treatments were given in a multi-place hyperbaric chamber for 85-min daily ( session duration 95 min ) , five days a week for eight weeks ( 40 treatment sessions ) . The study was performed in an ambulatory setting . RESULTS Ninety-four patients with Wagner grade 2 , 3 , or 4 ulcers , which had been present for > 3 months , were studied . In the intention-to-treat analysis , complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up : 25/48 ( 52 % ) in the HBOT group and 12/42 ( 29 % ) in the placebo group ( P = 0.03 ) . In a sub- analysis of those patients completing > 35 HBOT sessions , healing of the index ulcer occurred in 23/38 ( 61 % ) in the HBOT group and 10/37 ( 27 % ) in the placebo group ( P = 0.009 ) . The frequency of adverse events was low . CONCLUSIONS The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes OBJECTIVE To determine if partial wound closure surrogate markers proposed for neuropathic , small diabetic foot ulcers ( DFUs ) can be extended to advanced lesions and if the development of granulation tissue can be used to predict complete healing . RESEARCH DESIGN AND METHODS Data from two multicenter , double-blind , r and omized clinical trials ( one of them placebo controlled ) that used intralesional recombinant human epidermal growth factor ( rhEGF ) to promote granulation and healing were used . For confirmation in a larger sample from common clinical practice , the results of an active postmarketing surveillance of rhEGF treatment of DFUs in 60 healthcare units was included . The surrogates evaluated were percent area change , log healing rate , ratio of log areas , and percent of granulation tissue covering the wound area . The tests used were surrogate final end point correlation , receiver operating characteristic curves to discriminate healers from nonhealers , validation tests using logistic regression models , and the proportion-mediated estimation . RESULTS Two weeks > 50 % granulation , end of treatment > 75 % granulation , and 16.1 % area change showed significant predictive value ( > 70 % correct classification ) for final wound closure . The granulation-based variables fulfilled the criterion that the effect of rhEGF treatment on wound closure was mediated by the surrogate . CONCLUSIONS This work provides the first evidence for the use of granulation tissue development as a predictor of wound healing in advanced DFUs . These results can be useful for clinical trial design , particularly during the exploratory phase of new products OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) .  St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft — a 2-step HYAFF autograft — in the treatment of diabetic foot ulcers compared with st and ard care . In all , 180 patients with dorsal or plantar diabetic foot ulcers ( unhealed for ≥1 month ) were r and omized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks ( n = 90 ; treatment group ) or nonadherent paraffin gauze ( n = 90 ; control group ) . Efficacy and adverse events were assessed weekly for 12 weeks , at 20 weeks , and at 18 months . The primary efficacy outcome was complete ulcer healing at 12 weeks . Wound debridement , adequate pressure relief , and infection control were provided to both groups . At 12 weeks , complete ulcer healing was similar in both groups ( 24 % of treated vs 21 % controls ) . A 50 % reduction in ulcer area was achieved significantly faster in the treatment group ( mean 40 vs 50 days ; P = .018 ) . Weekly percentage ulcer reduction was consistently higher in the treatment group . At 20 weeks , ulcer healing was achieved in 50 % of the treated group as compared with 43 % of controls . Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment ( P = .047 ) . In a subgroup with hard-to-heal ulcers , there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers ( P = .035 ) . Adverse events were similar in both groups . The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers Despite advances in revascularization techniques , limb salvage and relief of pain can not be achieved in many diabetic patients with diffuse peripheral vascular disease . Our objective was to determine the effect of intramuscular administration of phVEGF165 ( vascular endothelial growth factor gene-carrying plasmid ) on critical limb ischemia ( CLI ) compared with placebo ( 0.9 % NaCl ) . A double-blind , placebo-controlled study was performed in 54 adult diabetic patients with CLI . The primary end point was the amputation rate at 100 days . Secondary end points were a 15 % increase in pressure indices ( ankle-to-brachial index and toe-to-brachial index ) , clinical improvement ( skin , pain , and Quality of Life score ) , and safety . In patients ( n=27 ) treated with placebo versus phVEGF165-treated patients ( n=27 ) the following results were found : 6 amputations versus 3 ( p = not significant [ NS ] ) ; hemodynamic improvement in 1 versus 7 ( p=0.05 ) ; improvement in skin ulcers , 0 versus 7 ( p=0.01 ) ; decrease in pain , 2 versus 5 ( p = NS ) ; and overall , 3 versus 14 responding patients ( p=0.003 ) . No grade 3 or 4 adverse effects were seen in these patients . We conclude that this small , r and omized gene therapy study failed to meet the primary objective of significant amputation reduction . However , significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid . There were no substantial adverse events OBJECTIVE To compare the efficacy and safety of topically applied recombinant human platelet-derived growth factor-BB ( rhPDGF-BB ) ( becaplermin ) with placebo gel in patients with chronic diabetic neuropathic ulcers of the lower extremities . RESEARCH DESIGN AND METHODS This multicenter double-blind placebo-controlled phase 111 trial included 382 patients with type 1 or type 2 diabetes and chronic ulcers of at least 8 weeks ' duration . After sharp debridement of the ulcer , patients were r and omized to receive becaplermin gel 30 μg/g , becaplermin gel 100 μg/g , or placebo gel , in conjunction with a st and ardized regimen of good wound care until complete wound closure was achieved or for a maximum of 20 weeks . Moist saline-soaked gauze dressings were changed twice daily with study medication applied by patients or caregivers at the evening dressing change . Safety was assessed by monitoring adverse events ( AEs ) and by clinical laboratory evaluations . RESULTS Compared with placebo gel , becaplermin gel 100 μg/g significantly increased 
    Output:
    
The available evidence suggests that while some biological therapies offer promise , more work is needed to substantiate their role in clinical practice .