Endothelialization of sirolimus-eluting stents with slow and extended drug release in the porcine overstretch model

BACKGROUND: Vascular healing of intracoronary stents has been shown to be delayed in drug-eluting stents (DES) due to the cytotoxic compounds on the stent surface that prevent stent ingrowth and endothelialization. The lack of endothelialization explains the occurrence of late and very late stent thrombosis in DES. MATERIALS AND METHODS: In 11 house swines (body weight 38-45 kg), 3 stents were implanted randomly into the 3 large epicardial coronary arteries, namely a bare-metal stent (BMS), a sirolimus-eluting stent with slow-release (SES) and a SES with extended-release (SESXR). Stent length was 18 mm, and stent diameter 3 mm. All stents were of identical design. Animals were followed for 3 (n = 3), 7 (n = 4) and 14 (n = 4) days, respectively. One animal died before implantation due to hyperthermia. On the day of explantation, the animals were euthanized and endothelialization was tested by scanning electron microscopy after drying and sputtering the samples. Endothelial coverage was determined semiquantitatively by 2 observers. RESULTS: Endothelialization was more rapid with BMS and SESXR than SES at 3 and 14 days. At 7 days there were no significant differences between the 2 SES. CONCLUSIONS: Endothelialization of intracoronary stents is faster with BMS and SESXR at 3 days than with SES. These differences persist at 14 days, suggesting delayed vascular healing with the slow-release SES.

Outcome after radical cystectomy with limited or extended pelvic lymph node dissection

PURPOSE: We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. MATERIALS AND METHODS: Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. RESULTS: The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. CONCLUSIONS: Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

Extended lymph node dissection for prostate cancer

Lymph node status is an important determinant for the management of patients with newly diagnosed prostate cancer. Given the significant limitations of cross-sectional and functional preoperative imaging in the detection of small metastases, pelvic lymph node dissection remains the only reliable staging method in clinically localized prostate cancer. Although lymph node dissection is a well-established form of staging in prostate cancer, controversy remains about indications and the surgical extent of the procedure. Reported practices vary from omitting pelvic lymph node dissection in low-risk disease to routine pelvic lymph node dissection in all radical prostatectomy patients. This review highlights the recent literature concerning pelvic lymphadenectomy in prostate cancer with respect to anatomical extent and oncologic outcome.

Maximum principle preserving high order schemes for convection-dominated diffusion equations

The maximum principle is an important property of solutions to PDE. Correspondingly, it's of great interest for people to design a high order numerical scheme solving PDE with this property maintained. In this thesis, our particular interest is solving convection-dominated diffusion equation. We first review a nonconventional maximum principle preserving(MPP) high order finite volume(FV) WENO scheme, and then propose a new parametrized MPP high order finite difference(FD) WENO framework, which is generalized from the one solving hyperbolic conservation laws. A formal analysis is presented to show that a third order finite difference scheme with this parametrized MPP flux limiters maintains the third order accuracy without extra CFL constraint when the low order monotone flux is chosen appropriately. Numerical tests in both one and two dimensional cases are performed on the simulation of the incompressible Navier-Stokes equations in vorticity stream-function formulation and several other problems to show the effectiveness of the proposed method.

Oral heroin in opioid-dependent patients: pharmacokinetic comparison of immediate and extended release tablets

In diacetylmorphine prescription programs for heavily dependent addicts, diacetylmorphine is usually administered intravenously, but this may not be possible due to venosclerosis or when heroin abuse had occurred via non-intravenous routes. Since up to 25% of patients administer diacetylmorphine orally, we characterised morphine absorption after single oral doses of immediate and extended release diacetylmorphine in 8 opioid addicts. Plasma concentrations were determined by liquid chromatography-mass spectrometry. Non-compartmental methods and deconvolution were applied for data analysis. Mean (+/-S.D.) immediate and extended release doses were 719+/-297 and 956+/-404 mg, with high absolute morphine bioavailabilities of 56-61%, respectively. Immediate release diacetylmorphine caused rapid morphine absorption, peaking at 10-15 min. Morphine absorption was considerably slower and more sustained for extended release diacetylmorphine, with only approximately 30% of maximal immediate release absorption being reached after 10 min and maintained for 3-4h, with no relevant food interaction. The relative extended to immediate release bioavailability was calculated to be 86% by non-compartmental analysis and 93% by deconvolution analysis. Thus, immediate and extended release diacetylmorphine produce the intended morphine exposures. Both are suitable for substitution treatments. Similar doses can be applied if used in combination or sequentially.

Production of Iron-Tin Compacts by Powder Metallurgy and a Synopsis of their Principle Properties

This thesis is concerned primarily with the production of metal powder compacts of iron and tin. In producing these compacts, the effects of process­ing variables on some of the essential properties of the pellets made were investigated.

Extracorporeal membrane oxygenation (ECMO): extended indications for artificial support of both heart and lungs

Extracorporeal membrane oxygenation (ECMO) was used to achieve temporary artificial support in cardiac and pulmonary function in 22 patients from 1987 to September 1990. Standard indications were postcardiotomy cardiogenic shock (n = 4), neonatal (n = 1) and adult respiratory distress syndrome (n = 4). ECMO was also used for extended indications, such as graft failure following heart (n = 11) or lung transplantation (n = 2). In six of these cases ECMO was instituted as a bridge device to subsequent retransplantation of either the heart (n = 4) or one lung (n = 2). One out of nine patients supported by ECMO for standard indications, and two out of 13 patients supported for extended indications are long-term survivors. This series illustrates the results with ECMO in emergency situations, in patients under immunosuppressive protocols, or in patients with advanced lung failure requiring almost complete artificial gas exchange. In such complex situations, ECMO does provide stabilization until additional therapeutic measures are in effect. ECMO cannot be recommended for postoperative cardiogenic shock but short-term ECMO support is an accepted method in most cases with graft failure or pulmonary failure or other origin.

Extended retinacular soft-tissue flap for intra-articular hip surgery: surgical technique, indications, and results of application

Osteotomies of the proximal femur for hip joint conditions are normally done at the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would be more direct and therefore allow a more powerful correction with no or very little undesired side correction. However, concerns about the risk of vascular damage and osteonecrosis of the femoral head have so far basically excluded this technique from practical use. Based on detailed knowledge of the vascular anatomy of the proximal femur, an approach to safely dislocate the femoral head has been described and successfully performed. Experience as well as further studies of femoral head perfusion allowed a substantial extension of this approach, with subperiosteal exposure of the circumference of the femoral neck with constant intraoperative control of the blood supply to the head. Using the extended retinacular soft-tissue flap, four surgical techniques (relative neck lengthening, subcapital realignment in slipped capital femoral epiphysis, true femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became safer with respect to perfusion of the femoral head. The extended retinacular soft-tissue flap offers the technical and biologic possibility for a new class of intra articular procedures. Although meticulous execution of the surgical steps is important, the procedures have a high level of safety for femoral head perfusion.

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL)

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

SWISSspine: a nationwide registry for health technology assessment of lumbar disc prostheses

SWISSspine is a so-called pragmatic trial for assessment of safety and efficiency of total disc arthroplasty (TDA). It follows the new health technology assessment (HTA) principle of "coverage with evidence development". It is the first mandatory HTA registry of its kind in the history of Swiss orthopaedic surgery. Its goal is the generation of evidence for a decision by the Swiss federal office of health about reimbursement of the concerned technologies and treatments by the basic health insurance of Switzerland. During the time between March 2005 and 2008, 427 interventions with implantation of 497 lumbar total disc arthroplasties have been documented. Data was collected in a prospective, observational multicenter mode. The preliminary timeframe for the registry was 3 years and has already been extended. Data collection happens pre- and perioperatively, at the 3 months and 1-year follow-up and annually thereafter. Surgery, implant and follow-up case report forms are administered by spinal surgeons. Comorbidity questionnaires, NASS and EQ-5D forms are completed by the patients. Significant and clinically relevant reduction of low back pain VAS (70.3-29.4 points preop to 1-year postop, p < 0.0001) leg pain VAS (55.5-19.1 points preop to 1-year postop, p < 0.001), improvement of quality of life (EQ-5D, 0.32-0.73 points preop to 1-year postop, p < 0.001) and reduction of pain killer consumption was revealed at the 1-year follow-up. There were 14 (3.9%) complications and 7 (2.0%) revisions within the same hospitalization reported for monosegmental TDA; there were 6 (8.6%) complications and 8 (11.4%) revisions for bisegmental surgery. There were 35 patients (9.8%) with complications during followup in monosegmental and 9 (12.9%) in bisegmental surgery and 11 (3.1%) revisions with 1 [corrected] new hospitalization in monosegmental and 1 (1.4%) in bisegmental surgery. Regression analysis suggested a preoperative VAS "threshold value" of about 44 points for increased likelihood of a minimum clinically relevant back pain improvement. In a short-term perspective, lumbar TDA appears as a relatively safe and efficient procedure concerning pain reduction and improvement of quality of life. Nevertheless, no prediction about the long-term goals of TDA can be made yet. The SWISSspine registry proofs to be an excellent tool for collection of observational data in a nationwide framework whereby advantages and deficits of its design must be considered. It can act as a model for similar projects in other health-care domains.