SIM: The Surgery Imagery Mindset and Preparing for Surgery.

Discussed under various terms such as mental skills, mental rehearsal, cognitive training, and non-technical skills, psychological performance skills are gaining greater acceptance for their contributions to excellence in surgical performance. Mental imagery, specifically performance-enhancing mental imagery for surgeons, has received the greatest attention in the surgical literature. As part of the surgeon's imagery mindset (SIM), this form of mental rehearsal contributes to optimal surgical performance for both developing and practicing surgeons. We discuss the nature of SIM and describe 5 basic guidelines for maximizing the application of performance-enhancing mental imagery in surgical contexts.

Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients.

BACKGROUND: In a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported. METHODS: Evaluations included patient and graft survival, study drug discontinuations, laboratory values including renal function and development of new-onset diabetes after transplantation, concomitant medications, and adverse events. RESULTS: At study termination, 129 Astagraf XL, 113 Prograf, and 79 CsA patients had continued follow-up. Demographic and baseline characteristics were similar in all arms. Four-year Kaplan-Meier estimates of patient survival in the Astagraf XL, Prograf, and CsA groups were 93.2, 91.2, and 91.7%, respectively, while graft survival was 84.7, 82.7, and 83.9%, respectively. At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA). Renal function was not significantly different between Astagraf XL and Prograf. HgbA1c levels were collected every 6 months; the 4-year Kaplan-Meier estimate for incidence of HgbA1c levels ≥ 6.5% was significantly higher for both tacrolimus formulations compared to CsA; 41.1% (Astagraf XL), 33.6% (Prograf), and 21.3% (CsA). CONCLUSIONS: In this 4-year follow-up report, patients receiving Astagraf XL and Prograf showed comparable efficacy and safety profiles, with a higher incidence of new-onset diabetes after transplantation but superior renal function compared to patients receiving CsA.

A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year.

BACKGROUND: This is the 1-year report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. METHODS: Prior to transplantation, recipients were randomized to receive tacrolimus plus corticosteroids with either sirolimus (n=185) or MMF (n=176). The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study. Patient and graft survival, renal function, study drug dosing and discontinuations were evaluated at 1 year. RESULTS: At 1 year, there was no difference in patient survival (95.7% sirolimus vs. 97.2% MMF; P=0.45) or graft survival (90.8% sirolimus vs. 94.3% MMF; P=0.22). Patients without delayed graft function (DGF) receiving MMF had significantly better graft survival (99% vs. 93%; P=0.01). Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus (98% vs. 91%; P=0.07). Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation (26.5% vs. 14.8% MMF; P=0.006). Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels (1.3 mg/dL vs. 1.5 mg/dL; P=0.03) and a trend towards higher calculated creatinine clearance (CrCl), (58.4 ml/min vs. 54.3 ml/min; P=0.06). More patients in the sirolimus group had a serum creatinine >2.0 mg/dL, (20.4% vs. 11.0%; P=0.02). CONCLUSIONS: Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF. Patient and graft survival were excellent in both arms. Renal function is superior for patients treated with tacrolimus + MMF combination.

Tailoring tacrolimus-based immunotherapy in renal transplantation.

Tacrolimus is a cornerstone immunosuppressive agent in renal transplantation and compared with cyclosporin, its use is associated with a reduced incidence of acute rejection. Optimizing immunosuppressive management in the early post-transplant period is important for achieving long-term graft function and survival. In attempts to improve the long-term outcomes of renal transplantation further, tacrolimus has been combined with two novel immunosuppressive agents, mycophenolate mofetil (MMF) and sirolimus, with encouraging results in terms of patient and graft survival, acute rejection rates and renal graft function. Tacrolimus in combination with MMF adjunctive therapy showed significantly better graft survival in patients with delayed graft function, fewer episodes of corticosteroid-resistant rejection and better renal function at the 3-year follow-up compared with cyclosporin microemulsion plus MMF immunosuppression. A tacrolimus plus MMF regimen was also effective for renal transplant recipients at our centre in Pennsylvania, resulting in excellent survival and rejection rates at 1 year post-transplantation. The 3-month results of a US multicentre study comparing tacrolimus in combination with either MMF or sirolimus showed these two treatment regimens to be equivalent in terms of patient and graft survival, delayed graft function, the incidence of biopsy-confirmed acute rejection and renal graft function, although differences were apparent in terms of acute tubular necrosis and hyperlipidaemia. In conclusion, the development of a new immunosuppressive regimen in renal transplantation should take account of factors that influence graft function, both in the short and long term, as a way of optimizing individual maintenance therapy.

Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months.

BACKGROUND: This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented. METHODS: Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176). The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection. Patient and graft survival, renal function, and composite endpoints also were evaluated. Safety was assessed by monitoring laboratory parameters and adverse events. RESULTS: By 6 months of follow-up, the incidence of biopsy-confirmed acute rejection was similar in both treatment groups (13.0% tacrolimus+sirolimus vs. 11.4% tacrolimus+MMF; P=0.64 log-rank). Patient survival (97.3% tacrolimus+sirolimus vs. 97.7% tacrolimus+MMF) and graft survival (93.0% tacrolimus+sirolimus vs. 95.5% tacrolimus+MMF) were equivalent (P=0.53, overall survival log-rank). There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus (21.1% vs. 10.8%; P=0.008). Renal function was significantly better in the MMF-treatment group (serum creatinine 1.44+/-0.45 mg/dL vs. 1.77+/-1.42 mg/dL; P=0.018). Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group. Diastolic blood pressure was significantly higher in sirolimus-treated patients. There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group. The incidence of posttransplant diabetes mellitus was 7.6% in the sirolimus group and 7.7% in the MMF group. CONCLUSION: Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF. The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension.

Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation.

This study prospectively compared immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a prednisone-based immunosuppression regimen. One hundred recipients of first-kidney transplant were enrolled into the study to receive either anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited anti-IL-2R) or no induction (control). Each patient also received oral tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and prednisone. The primary efficacy end-point was the incidence of biopsy proven acute rejection during the first 6 months post-transplant. The patients were also followed for 12-month graft function, and graft and patient survival rates. Other than the donor's age being significantly lower in the control group, both groups were comparable with respect to age, weight, gender, race, human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and duration and modes of renal replacement therapy (RRT). During the first 6 months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05). Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not statistically different. The group receiving limited anti-IL-2R did not have any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when combined with tacrolimus/MMF/steroid allows significant reduction in early renal allograft rejection to the single digit level. The therapy with anti-IL-2R antibody is simple and is well tolerated.