A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.     

The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study.

BACKGROUND CONTEXT: Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stem cells. Osteogenic protein-1 (OP-1) Putty is a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up. PURPOSE: The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft. STUDY DESIGN/SETTING: A prospective, randomized, controlled, multicenter clinical pilot study. PATIENT SAMPLE: Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients). OUTCOME MEASURES: Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups. METHODS: Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes. RESULTS: At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty. CONCLUSION: Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications.     

The efficacy of rhBMP-2 versus autograft for posterolateral lumbar spine fusion in elderly patients

Few studies have specifically examined the outcomes following rhBMP-2 usage in patients 65 years and older. The purpose of this retrospective study is to evaluate the efficacy of rhBMP-2 with allograft versus autograft for posterolateral lumbar fusion in patients 65 years and older. One hundred twenty-seven patients were divided into three groups based on fusion material and age. Subjects in group A (n = 34) consisted of patients 65 years and older who received rhBMP-2 and allograft. Group B (n = 52) was composed of patients under 65 years of age with rhBMP-2 and allograft. Subjects in group C (n = 41) were 65 years and older with autograft use. A comparison was made of fusion rate, fusion time (noticed, solid), clinical outcome, VAS, perioperative complications and revision rate between each group. The fusion rate and fusion time were similar in groups A and C; however, these were lower than that observed in group B. Clinical outcomes were similar amongst the groups. There were no significant differences in VAS and perioperative complication rate between groups A and C. In patients 65 years and older, rhBMP-2 with allograft may lead to acceptable fusion rates and fusion times, good clinical outcomes and reduced perioperative complications. The combination of rhBMP-2 with allograft yields equivalent outcomes as autograft in elderly patients undergoing instrumented posterolateral lumbar fusion. Additionally, when compared to patients under 65 years of age undergoing posterolateral lumbar fusion, the use of rhBMP-2 was not sufficient to overcome all aspects of the age-related weakened osteoinductive capacity encountered in elderly patients.     

成骨蛋白-1在腰椎融合术中应用的实验研究

目的:探讨成骨蛋白-1(OP-1)在脊柱融合术中的作用。方法:选用12只成年猕猴接受腰椎融合术,实验组、对照组分别采用OP-1加自体骨、单纯自体骨植骨。术后当日和术后4、8、12、16、20周分别拍腰椎正位片,观察植骨生长的情况。术后12周和20周分批处死动物,取脊柱标本进行生物力学和组织学研究。结果:术后第12周X线检查发现,OP-1组中,3只猕猴获双侧牢固融合,2只单侧牢固融合,1只部分融合;对照组只有1只获单侧牢固融合。实验组的植骨融合效果明显优于对照组,而且融合时间也明显提前,但两组的扭转刚度无显著性差异(P>0.05)。组织形态学评估发现,实验组的总平均成骨值为0.87±0.10,对照组为0.45±0.20,两组的成骨值有显著性差异(P<0.01),实验组的成骨活性明显高于对照组。结论:在无脊柱内固定的条件下,OP-1对脊柱后外侧融合具有显著的促进作用,可提高融合效率,缩短融合时间。     

Safety and efficacy of ultrasonography as an adjunct to fluoroscopy for renal access in percutaneous nephrolithotomy (PCNL)

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

? To evaluate the safety and efficacy of ultrasonography (US)‐guided renal access in percutaneous nephrolithotomy (PCNL), as compared with conventional fluoroscopy‐guided renal access in a prospective randomized trial.

PATIENTS AND METHODS

? From January 2008 to October 2009, 224 patients with renal calculi undergoing PCNL were randomized into two groups. ? Group 1 (112 patients) underwent PCNL using only fluoroscopy‐guided renal access; while in group 2 (112 patients), US guidance for puncture was used in addition to fluoroscopy. ? The inclusion criteria were: normal renal functions, American Society of Anesthesiology scores 1 or 2, absence of congenital abnormalities, aged 15–70 years, and anticipated single‐tract procedure. The patients in both groups were matched for age, sex, and stone characteristics. ? The Student t‐test was used for statistical analysis with an allowable error of 5%.

RESULTS

? The mean time to successful puncture was 3.2 min and 1.8 min in group 1 and group 2, respectively (P < 0.01). ? The mean duration of radiation exposure to successful puncture was 28.6 s in group 1 and 14.4 s in group 2 (P < 0.01). ? The mean numbers of attempts for successful puncture in the desired calyx was 3.3 in group 1 as compared with 1.5 in group 2 (P < 0.01). ? The meantime taken for tract formation in group 1 was 7.4 min with radiation exposure of 82 s, while in group 2 it took 4.8 min with radiation exposure of 58 s (P < 0.01). ? Successful access was achieved in all patients. All patients were stone‐free at the end of the operation. The hospital stay (2–3 days) was same in both groups. There was no incidence of significant bleeding requiring transfusion during or after surgery. All the patients were followed‐up for a ≥6 months.

CONCLUSION

? US‐guided puncture in PCNL helps in increasing accuracy of puncture and decreasing radiation exposure for the surgical team and the patients.     

Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model

Background Context

Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model.

A prospective cohort pilot study to assess the safety and efficacy of combining autologous platelet-rich plasma (PRP) with autologous dermal fibroblast for skin augmentation

Background

There is a renewed interest in autologous fillers for facial rejuvenation. We used PRP combined with cultured fibroblasts as an attractive alternative to synthetic fillers.

Methods

Twenty adults (17 women and 3 men: mean age 45 years: range 36–65 years) participated in a clinical trial to improve the fold in the skin of the nasolabial folds by having 1 ml of platelet-rich plasma (PRP) combined with cultured fibroblasts injected into each side.

Results

Sixteen patients had an 80 % increase in thickness of the skin adjacent to the nasolabial fold at the 9-month follow-up. Fifteen patients also showed an increase in dermal density, and in 7, there was an increase in the hydration of the facial skin. In 16 patients, the sebum quality of the skin either improved on one side or both sides of the cheek (adjacent to the nasolabial fold). Wrinkle depth on either one or both sides of the nasolabial fold was reduced in 15 patients. Seventeen patients (85 %) were satisfied with the result and would undergo the procedure again. In standardised photography, the contour of the nasolabial fold was improved in 15 patients.

Conclusions

This technique softens the nasolabial folds as well as improves the condition of the adjacent skin. This improvement was present after 9 months and did not appear to diminish with time. PRP when combined with cultured fibroblasts can act as an effective autologous filler.Level of Evidence: Level IV, therapeutic study

     

Autologous platelet‐derived growth factors (platelet‐rich plasma) as an adjunct to mucosal advancement flap in high cryptoglandular perianal fistulae: a pilot study

Aim The aim of this study was to explore autologous platelet‐rich plasma as an adjunct to the staged mucosal advancement flap in the treatment of perianal fistulae. Method Between February 2006 and May 2007, 10 patients with fistula tracts transversing from the middle‐third or upper part of the anal sphincter were treated for at least 3 months with noncutting setons prior to definitive closure by autologous platelet‐rich plasma as an adjunct to a mucosal advancement flap. Five patients smoked tobacco. Results The study group consisted of six women and four men with a median age of 44 (range 30–75) years and a median follow up of 26 (range 17–32) months. One (10%) patient had a recurrent fistula. No new continence disorders developed after definitive treatment in both groups. Conclusion Platelet‐rich plasma as an adjunct to a staged mucosal advancement flap for the treatment of perianal cryptoglandular fistulae is a promising treatment modality and seems to establish a high healing rate.     

A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis)

OBJECTIVE: To determine if finasteride can reduce symptoms in men with a clinical diagnosis of chronic nonbacterial prostatitis (National Institutes of Health, NIH, category IIIA chronic pelvic pain syndrome, CPPS) compared with placebo. PATIENTS AND METHODS: Men (76) with category IIIA CPPS enrolled in four North American prostatitis research centres were randomized after a 2-week placebo run-in to finasteride or placebo for 6 months. The primary efficacy variable was a subjective overall assessment (SOA); the secondary efficacy variables included the NIH chronic prostatitis symptom index (NIH-CPSI) and safety data. Patients were assessed at screening, baseline (after the 2-week placebo run-in), 3 and 6 months. RESULTS: Sixty-four patients had at least one assessment on medication (31 placebo, 33 finasteride); 75% of the finasteride and 54% of the placebo group had at least a mild improvement (defined as > 25% improvement in SOA), and 44% and 27%, respectively, a moderate or marked improvement (>50% improvement in SOA). The trend was similar in the NIH-CPSI scores. Five patients in the finasteride and seven in the placebo group reported medication-related adverse events. CONCLUSION: This randomized placebo-controlled pilot study suggests that finasteride was of benefit for some men with category IIIA CPPS, but the results do not justify recommending finasteride as monotherapy, except for men who also have benign prostatic hyperplasia. A larger, properly powered study, possibly evaluating combination with other therapies or specifically in men with prostatitis and benign prostatic hyperplasia, is required to confirm any clinical benefit.     

A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge.