One-stage cartilage repair using the autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells technique: clinical results and magnetic resonance imaging evaluation at five-year follow-up.

PURPOSE: To evaluate medium-term outcomes of knee cartilage defects repair by autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells, defined as LIPO-AMIC technique. METHODS: The LIPO-AMIC technique has been used in ICRS degree III-IV knee defects. Eighteen patients have been prospectively evaluated during two and five years both clinically and by MRI. RESULTS: Patients showed progressive significant improvement of all scores starting early at six months, and further increased values were noted till the last follow-up at 60 months. Mean subjective pre-operative IKDC score of 36.1 significantly increased to 86.4 at 24 months and to 87.2 at 60 months. Mean pre-operative Lysholm score of 44.4 reached 93.5 at two years and 93.5 at five years. MRI examination showed early subchondral lamina regrowth and progressive maturation of repair tissue and filling of defects. The mean total MOCART score showed that a significative improvement from two year follow-up (69.1 points) to last follow-up was 81.9 points (range, 30-100 points, SD 24). Complete filling of the defect at the level of the surrounding cartilage was found in 77.8%. CONCLUSIONS: Adipose tissue can represent ideal source of MSCs since easiness of withdrawal and definite chondrogenic capacity. This study clearly demonstrated the LIPO-AMIC technique to be feasible for treatment of knee cartilage defects and to result in statistically significant progressive clinical, functional and pain improvement in all treated patients better than what reported for the AMIC standard technique, starting very early from the 6-month follow-up and maintaining the good clinical results more durably with stable results at mid-term follow-up.

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis.

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 +/- 6 days after the event. IRA was patent in 61 patients and occluded in 40. Overall MTHFR 677TT frequency was 22%. Patients with MTHFR 677TT homozygosis had higher prevalence of occluded IRA (73%) versus those with MTHFR 677CT/CC genotype (30%, P < 0.001); MTHFR 677TT genotype predicted independently the risk of IRA occlusion with a specificity of 90% (odds ratio 3.8, 95% confidence interval 1.1-9.1; P = 0.03). Moreover, patients with occluded IRA and MTHFR 677TT genotype had the highest homocysteine levels (21 +/- 7.6 micromol/l vs. < or =14.9 +/- 3.8 micromol/l; P = 0.011). In patients with AMI, MTHFR 677TT homozygosis is independently associated with a persistently occluded IRA after thrombolysis. This finding may have pathophysiological and therapeutic implications for recanalization strategies in patients with AMI.

Treatment of 72 newly diagnosed Waldenstrom macroglobulinemia cases with oral melphalan, cyclophosphamide, and prednisone: results and cost analysis.

BACKGROUND: Current treatment regimens for Waldenstrom macroglobulinemia (WM) are based on the use of oral alkylating agents. Recently, however, other more costly agents have been proposed for the treatment of WM. In the current study, the authors report on results obtained using oral melphalan, cyclophosphamide, and prednisone (MCP) to treat 72 patients with WM, and they compare these results (and the associated costs) with those observed using more aggressive protocols. METHODS: Between July 1973 and April 2002, the authors documented overexpression of the immunoglobulin M paraprotein in 317 consecutive patients. Of these, 100 had newly diagnosed WM, and the 72 who were symptomatic were treated using the MCP protocol. Response rate, overall survival (OS), response duration, freedom from progression (FFP), event-free survival (EFS) duration, toxicity, and cost per course in Euro and U.S. dollars were evaluated for patients receiving this regimen. RESULTS: Seventy-one of 72 patients (99%) were evaluable. Of these patients, 55 (77%) achieved a response; 7 others (10%) experienced disease stabilization, and the remaining 9 (13%) experienced disease progression. After a median follow-up of 72 months (range, 3-195 months), the median durations of EFS, FFP, response, and OS were 47, 55, 64, and 66 months, respectively. No World Health Organization Grade III or IV toxicities were observed, and side effects were limited to transient nausea, emesis, and mild neutropenia. The cost per course of the MCP regimen was $16, similar to that of standard protocols involving chlorambucil and much less than that of more aggressive protocols (price range, $91-11091) proposed for the treatment of WM. CONCLUSIONS: Like chlorambucil-based protocols, the MCP regimen is a cost-effective and safe option for the treatment of patients with WM. Furthermore, the results obtained do not appear to be inferior to those yielded by more expensive, aggressive, and toxic intravenous protocols.