On-Pump versus Off-Pump Complete Arterial Revascularization Using Bilateral Internal Mammary Arteries and the T-Graft Technique: Clinical and Angiographic Results for 3,445 Patients in 13 Years of Follow-Up.

BACKGROUND: This is an investigation of complete arterial coronary artery bypass grafting (CACABG) using bilateral internal mammary arteries (IMA) and the T-graft technique either on- or off-pump as a routine approach to treat coronary artery disease. METHODS: Between January 2000 and December 2012, 3,445 patients underwent on-pump (n = 2,216) or off-pump (n = 1,229) CACABG. A 30-day follow-up was performed prospectively, a long-term follow-up by a questionnaire, and coronary angiography in selected patients. RESULTS: End points at 30 days were death, myocardial infarction, stroke, repeat revascularization, renal replacement, reoperation, sternal wound infection and atrial fibrillation. FitzGibbon A patency rates were 89.8 vs. 91.4% (p = 0.464) with consecutive percutaneous coronary intervention in the grafted area of 1.8 vs. 1.1% (p = 0.693) on- vs. off-pump, and no reoperation in the grafted area in both groups. CONCLUSION: CACABG by use of skeletonized bilateral IMA with the T-graft technique performed either on- or off-pump is a safe and effective approach.

The Mosaic porcine bioprosthesis: role of age on clinical performance in aortic position.

BACKGROUND: The Mosaic bioprosthesis is a third-generation stented porcine bioprosthesis combining physiologic fixation and α-amino oleic acid antimineralization treatment to improve durability and hemodynamic function. This single-center study reports on the performance of the Mosaic bioprosthesis in patients 65 years of age or less and patients older than 65 years at implantation. METHODS: Between 1994 and 1999, 88 younger patients (mean age, 58 years) and 167 older patients (mean age, 72 years) were enrolled in this prospective nonrandomized clinical trial. Follow-up visits were performed after 30 days, 6 months, and annually. Cumulative follow-up was 751 patient-years in the younger group and 1223 patient-years in the older group. RESULTS: Mean systolic gradient increased significantly to 17.0 and 14.7 mm Hg in younger and older patients, respectively, at their latest follow-up (P < .001). Effective orifice area values decreased significantly to 1.8 and 1.6 cm(2) (P < .001). Overall, effective orifice area values were significantly higher in younger patients (P < .001). Transvalvular regurgitation increased over time (P < .001) but remained mild or less in more than 95% of the patients. Freedom from adverse events at latest follow-up in younger and older patients, respectively, were as follows: structural valve deterioration, 85.7% and 86.2% (P < .05); endocarditis, 87.5% and 98.5% (P < .01); valvular thrombosis, 98.8% and 97.1% (not significant); and explantation, 68.9% and 77.9% (P < .01). CONCLUSIONS: Hemodynamic performance is similar in both groups. In the younger patients the incidence of structural valve disease, endocarditis, valve-related reoperation, and explantation is higher. The incidence in structural valve deterioration in the younger patients tends to be similar or lower compared with that seen in the literature.

Clinical results of the Medtronic Mosaic porcine bioprosthesis up to 13 years.

BACKGROUND: The Mosaic bioprosthesis is a third-generation stented porcine bioprosthesis combining physiologic fixation and alpha-amino oleic acid (AOA) antimineralisation treatment to improve haemodynamic performance and durability. This single-centre study reports the clinical results, including haemodynamic performance, of the Mosaic bioprosthesis after implant in aortic or mitral position. METHODS: Between February 1994 and October 1999, 255 patients with aortic valve replacement (AVR; mean age: 67 years, range: 23-82 years) and 47 patients with mitral valve replacement (MVR; mean age: 67 years, range: 41-84 years) were enrolled in this prospective non-randomised clinical trial. Follow-up visits were performed 30 days and 6 months after implant and annually thereafter. The cumulative follow-up was 1976.2 patient-years (pt-yrs) after AVR (median: 8.3 years, maximum: 14.0 years) and 336.9 pt-yrs after mitral valve replacement (MVR) (median: 8.2 years, maximum: 13.3 years). RESULTS: After AVR, mean systolic gradient and effective orifice area at 4, 8 and 13 years follow-up were 13.3+/-5.6, 15.5+/-7.7 and 16.0+/-7.2 mmHg and 1.8+/-0.5, 1.8+/-0.5 and 1.7+/-0.4 cm(2). After MVR, respective data were 4.7+/-2.1, 4.3+/-1.2 and 5.0 mmHg (only one recording) and 2.2+/-0.7, 2.3+/-0.6 and 1.8 cm(2). Transvalvular regurgitation at 13-year follow-up was mild or less in both the AVR and MVR patients. Thirteen-year survival was 63.1+/-4.5% in the AVR group and 51.2+/-13.6% in the MVR group. Early mortality after AVR and MVR was 1.2% and 0.0%, respectively; late mortality was 3.2%pt-yr(-1) and 3.3%pt-yr(-1), including a valve-related/unexplained mortality of 1.1%pt-yr(-1) and 0.9%pt-yr(-1). Freedom from adverse events in the AVR and MVR group was permanent neurological event: 97.4+/-1.2% and 96.0+/-3.9%; valvular thrombosis: 97.8+/-1.1% and 100%; structural valve deterioration: 84.8+/-7.8% and 93.8+/-6.1%; explant: 73.3+/-7.3% and 89.3+/-6.5%. CONCLUSIONS: The Mosaic bioprosthesis demonstrates excellent clinical performance and safety after 13 years of follow-up. Continued follow-up will determine whether this new design will provide increased durability.

Fibrillar collagen type I stimulation of apolipoprotein B secretion in Caco-2 cells is mediated by beta1 integrin.

Caco-2 cells spontaneously differentiate into enterocyte-like cells and secrete apolipoprotein B (apoB) lipoproteins. We evaluated the effect of different extracellular matrix proteins on lipoprotein secretion by these cells. Caco-2 cells grown on human amnion connective tissue (HACT) secreted twice as much apoB as control cells on Transwells, but secreted similar amounts of apoA1. Cells cultured on fibrillar collagen type I secreted increased amounts of apoB similar to the cells cultured on HACT, but cells cultured on non-fibrillar collagen type I, type IV collagen or laminin-1 did not. The increased secretion was nullified by a function inhibiting anti-integrin beta1 monoclonal antibody. Therefore, interactions between type I collagen and beta1 integrins augment apoB secretion by Caco-2 cells. Cells on HACT formed a more uniform columnar epithelium with lipid droplets polarized to the basolateral membrane. We also studied the effect of extracellular matrix proteins on transepithelial resistance (TER) of differentiated Caco-2 cells. TER in cells cultured on HACT was similar to that on Transwells, but cells on laminin-1 and collagen IV exhibited higher TER. Thus, various extracellular matrix proteins regulate apoB secretion and TER differently. This new observation that extracellular matrix proteins can enhance apoB secretion in Caco-2 cells could be useful to explore the modulation of lipid transport by these proteins.

Hemodynamic performance of the Medtronic Mosaic porcine bioprosthesis up to ten years.

BACKGROUND: The Mosaic bioprosthesis (Medtronic, Minneapolis, MN) is a third-generation stented porcine bioprosthesis combining physiologic fixation and amino oleic acid antimineralization treatment to improve hemodynamic performance and durability. The findings of this single-center experience with this valve were evaluated to determine the clinical and hemodynamic performance. METHODS: Between February 1994 and October 1999, we enrolled 255 patients with aortic valve replacement (AVR) with a mean age of 67 years (range, 23 to 82 years) and 47 patients with mitral valve replacement (MVR) with a mean age of 67 years (range, 41 to 84 years) in this post-United States Food and Drug Administration approval prospective and nonrandomized clinical trial. Patients were followed-up, including serial echocardiographic assessment, within 30 days, at 6 months, and annually thereafter. The cumulative follow-up was 1540 patient-years for AVR (mean, 6.1 years; maximum, 10 years) and 250 patient-years for MVR (mean, 5.4 years, maximum; 10 years). RESULTS: Early mortality after AVR (<30 days) was 0.8%; late mortality per patient-year was 3.5%, including a valve-related/unexplained mortality of 1.1%. Early mortality after MVR (<30 days) was 0.0%; late mortality per patient-year was 2.8%, including a valve-related/unexplained mortality of 1.2%. Median postoperative gradient and effective orifice area for all valves after AVR were (early, n = 252; 5 years, n = 161; 9 years, n = 43) 13.7, 12.3, and 11.7 mm Hg and 1.9, 1.8, and 1.8 cm2 at early, 5 years, and 9 years, respectively. With MVR respective data were (early, n = 46; 5 years, n = 25; 7 years, n = 13) 4.6, 4.1, and 3.9 mm Hg and 1.8, 2.2, and 2.3 cm2. At 10 years, freedom from adverse events in the AVR group and MVR group was, respectively, thromboembolism, 86.6% +/- 6.6% and 86.3% +/- 9.8%; permanent neurologic event, 91.2% +/- 6.8% and 90.9% +/- 8.7%; valve thrombosis, 98.2% +/- 0.8% and 100%; structural valve deterioration, 87.1% +/- 6.7% and 100%. CONCLUSIONS: Our midterm results demonstrate clinical safety and good performance of the Mosaic bioprosthesis. Continued follow-up will determine if this new design will provide increased durability.

Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.

Bringing interdisciplinary and multicultural team building to health care education: the downstate team-building initiative.

PURPOSE: To evaluate the impact of the Downstate Team-Building Initiative (DTBI), a model multicultural and interdisciplinary health care team-building program for health professions students. METHOD: A total of 65 students representing seven health disciplines participated in DTBI's first three years (one cohort per year since implementation). During the 18-session curriculum, students self-evaluated their group's progress through Tuckman's four team-development stages (FORMING, STORMING, NORMING, PERFORMING) on an 11-point scale. Students completed matched pre- and postintervention program evaluations assessing five variables: interdisciplinary understanding, interdisciplinary attitudes, teamwork skills, multicultural skills, and team atmosphere. After participation, students completed narrative follow-up questionnaires investigating impact one and two years after program completion. RESULTS: Each year's team development curve followed a similar logarithmic trajectory. Cohort 1 remained in team development stage 3 (NORMING) while Cohorts 2 and 3 advanced into the final stage-PERFORMING. A total of 34 matched pre- and postintervention evaluations showed significant change in all major variables: Team atmosphere and group teamwork skills improved most (48% and 44%, respectively). Interdisciplinary understanding improved 42%. Individual multicultural skills (defined by ability to address racism, homophobia, and sexism) started at the highest baseline and improved the least (13%). Group multicultural skills improved 36%. Of 23 responses to the follow-up surveys, 22 (96%) stated DTBI was a meaningful educational experience applicable to their current clinical surroundings. CONCLUSIONS: DTBI successfully united students across health discipline, ethnicity, socioeconomic class, gender, and sexual orientation into functioning teams. The model represents an effective approach to teaching health care team building and demonstrates benefits in both preclinical and clinical years of training.