Puncture Versus Surgical Cutdown Complications of Transfemoral Aortic Valve Implantation (from the Spanish TAVI Registry).

Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 [18%] vs 42 [6.9%]; relative risk [RR] 2.60; 95% confidence interval [CI] 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 [15%] vs 25 [4.1%], RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 [3%] vs 40 [6.6%], RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 [1.5%] vs 21 [3.4%], RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 [15%] vs 31 [5.1%], hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 [1.6%] vs 21 [3.4%], hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population.

Comparison of Different Bone Marrow-Derived Stem Cell Approaches in Reperfused STEMI. A Multicenter, Prospective, Randomized, Open-Labeled TECAM Trial.

BACKGROUND: Stem cell-based therapy has emerged as a potential therapy in acute myocardial infarction (AMI). Although various approaches have been studied, intracoronary injection of bone marrow autologous mononuclear cells (BMMC) and the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize endogenous cells have attracted the most attention. OBJECTIVES: This study compares, for the first time, the efficacy of BMMC injection, G-CSF mobilization, and the combination of both with standard treatment. METHODS: On Day 1 after primary percutaneous coronary intervention, 120 patients were randomized to a 1) intracoronary BMMC injection; 2) mobilization with G-CSF; 3) both (BMMC injection plus G-CSF); or 4) conventional treatment (control group). G-CSF, 10 µg/kg/day subcutaneously, was started Day 1 and maintained for 5 days. BMMC injection was performed on Days 3 to 5. Our primary endpoint was absolute change in 12-month left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV) relative to baseline measured by cardiac magnetic resonance. RESULTS: The mean change in LVEF between baseline and follow-up for all patients was 4 ± 6% (p = 0.006). Change in LVEF and LVESV over time did not differ significantly among the 4 groups. Patients actively treated with any stem cell approach showed similar changes in LVEF and LVESV versus control subjects, with a small but significant reduction in infarct area (p = 0.038). CONCLUSIONS: In our study, 3 different bone marrow-derived stem cell approaches in AMI did not result in improvement of LVEF or volumes compared with standard AMI care (Trial of Hematopoietic Stem Cells in Acute Myocardial Infarction [TECAM]; NCT00984178).

Dual Antiplatelet Therapy for 6 Months vs 12 Months After New-generation Drug-eluting Stent Implantation: Matched Analysis of ESTROFA-DAPT and ESTROFA-2.

INTRODUCTION AND OBJECTIVES: The recommendation for dual antiplatelet therapy following drug-eluting stent implantation ranges from 6 months to 12 months or beyond. Recent trials have suggested the safety of a 6-month dual antiplatelet therapy regimen, yet certain caveats to these studies limit the applicability of this shorter duration dual antiplatelet therapy strategy in real world settings. METHODS: A registry was constructed with consecutive recruitment of patients undergoing new-generation drug-eluting stent implantation and prescribed 6 months of dual antiplatelet therapy. Propensity score matching was undertaken with a historical cohort of patients treated with second-generation drug-eluting stents who received 12 months of dual antiplatelet therapy from the ESTROFA-2 registry. The sample size was calculated using a noninferiority basis and the primary endpoint was the combination of cardiac death, myocardial infarction, revascularization, or major bleeding at 12 months. RESULTS: The analysis included 1286 patients in each group, with no significant differences in baseline characteristics. The primary endpoint occurred in 5.0% and 6.6% in the 6-month and 12-month groups, respectively (P = .001 for noninferiority). The incidence of definite or probable stent thrombosis was 0.5% and 0.7% in the 6-month and 12-month groups, respectively (P = .4). Major bleeding events were lower in the 6-month group than in the 12-month group (0.8% vs 1.4%; P = .2) CONCLUSIONS: In selected patients in this large multicenter study, the safety and efficacy of a 6-month dual antiplatelet therapy regimen after implantation of new-generation drug-eluting stents appeared to be noninferior to those of a 12-month dual antiplatelet therapy regimen.

Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial.

BACKGROUND: The effect of intracoronary adenosine (ADO) on ST-segment elevation myocardial infarction (STEMI) size and adverse remodeling is not well established. METHODS: In a double-blind trial, 201 patients with STEMI were randomized to receive percutaneous coronary intervention (PCI) within 6 hours of symptom onset, 4.5mg ADO or saline immediately prior to reperfusion. Primary end-point: percentage of total myocardial necrotic mass by cardiac magnetic resonance (CMR) 2-7 days post-reperfusion. Secondary end-points: changes in left ventricular volumes and ejection fraction (LVEF) at baseline and at 6 months. RESULTS: Baseline CMR could not be performed in 20 patients. Overall, no significant differences were observed between ADO and placebo regarding infarct size (20.8% vs. 22.5%; p=0.40). However, infarct size was significantly reduced (19.4% vs. 25.7%; p for interaction=0.031) in those with ischemia duration below the median (200 min). CMR at 6 months, performed in 138 patients, did not show statistically significant differences between groups in the rate of LVEF increase (3.3 units (SD 9.6) in ADO group vs. 1.5 units (SD 9) in placebo group; p=0.25). In the subgroup analysis, among patients with ischemia time below 200 min, the increase in LVEF was slightly higher with ADO (3.59% vs. 0.43%; p for interaction=0.06). CONCLUSIONS: Although our study failed to demonstrate that intracoronary administration of ADO prior to PCI limits infarct size, in patients receiving early PCI ADO might enhance myocardial salvage and has a favorable effect on LVEF evolution, which may help to reconcile apparently contradictory results of previous studies. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov (NCT00781404).

A prospective randomized trial of everolimus-eluting stents versus bare-metal stents in octogenarians: the XIMA Trial (Xience or Vision Stents for the Management of Angina in the Elderly).

OBJECTIVES: The aim of this study was to determine whether drug-eluting stents (DES) are superior to bare-metal stents (BMS) in octogenarian patients with angina. BACKGROUND: Patients ≥80 years of age frequently have complex coronary disease warranting DES but have a higher risk of bleeding from prolonged dual antiplatelet therapy. METHODS: This multicenter randomized trial was conducted in 22 centers in the United Kingdom and Spain. Patients ≥80 years of age underwent stent placement for angina. The primary endpoint was a 1-year composite of death, myocardial infarction, cerebrovascular accident, target vessel revascularization, or major hemorrhage. RESULTS: In total, 800 patients (83.5 ± 3.2 years of age) were randomized to BMS (n = 401) or DES (n = 399) for treatment of stable angina (32%) or acute coronary syndrome (68%). Procedural success did not differ between groups (97.7% for BMS vs. 95.4% for DES; p = 0.07). Thirty-eight percent of patients had ≥2-vessel percutaneous coronary intervention, and 66% underwent complete revascularization. Patients who received BMS had shorter stent implants (24.0 ± 13.4 mm vs. 26.6 ± 14.3 mm; p = 0.01). Rates of dual antiplatelet therapy at 1 year were 32.2% for patients in the BMS group and 94.0% for patients in the DES group. The primary endpoint occurred in 18.7% of patients in the BMS group versus 14.3% of patients in the DES group (p = 0.09). There was no difference in death (7.2% vs. 8.5%; p = 0.50), major hemorrhage (1.7% vs. 2.3%; p = 0.61), or cerebrovascular accident (1.2% vs. 1.5%; p = 0.77). Myocardial infarction (8.7% vs. 4.3%; p = 0.01) and target vessel revascularization (7.0% vs. 2.0%; p = 0.001) occurred more often in patients in the BMS group. CONCLUSIONS: BMS and DES offer good clinical outcomes in this age group. DES were associated with a lower incidence of myocardial infarction and target vessel revascularization without increased incidence of major hemorrhage. (Xience or Vision Stent-Management of Angina in the Elderly [XIMA]; ISRCTN92243650).

The Ibero-American transcatheter aortic valve implantation registry with the CoreValve prosthesis. Early and long-term results.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The aim of this study was to describe early experience and long-term follow-up with the CoreValve self-expanding aortic prosthesis at 42 Ibero-American hospitals. METHODS: Multiple centre observational study including 1220 consecutive patients with symptomatic severe aortic stenosis who are not suitable candidates for surgery and underwent transcatheter aortic valve implantation with the self-expanding Medtronic CoreValve System between December 2007 and May 2012. RESULTS: The registry included 1220 consecutive patients with a mean age of 80.8 ± 6.3 years and a mean logistic euroSCORE of 17.8% ± 13%. The procedural success rate was 96.1%. Hospital mortality was 7.3% and combined end-point was 21.3%. Aortic regurgitation after TAVI was present in 24.5% (Sellers grade ≥ 2). The estimated 1-year and 2-year survival rates were 82.1% and 73.4% respectively. The following issues were significant independent risk factors for hospital mortality: acute kidney failure (odds ratio 3.55); stroke (odds ratio 5.72); major bleeding (odds ratio 2.64) and euroSCORE (odds ratio 1.02). Long-term predictors of mortality were diabetes mellitus (hazard ratio 1.59, 95% confidence interval 1.09-2.31), severe chronic obstructive pulmonary disease (hazard ratio 1.85, 95% confidence interval 1.85-2.88), and functional classes NYHA III-IV (hazard ratio 1.31, 95% confidence interval 1.01-1.70). CONCLUSIONS: Transcatheter aortic valve implantation constitutes a safe and viable therapeutic option for high operative risk patients with severe aortic stenosis. Long-term prognosis is conditioned by associate comorbidities.

Comparison of paclitaxel-eluting stents (Taxus) and everolimus-eluting stents (Xience) in left main coronary artery disease with 3 years follow-up (from the ESTROFA-LM registry).

Evidence regarding therapy with drug-eluting stents in the left main coronary artery (LM) is based mostly on trials performed with first-generation drug-eluting stents. The aim of this study was to evaluate long-term clinical outcomes after treatment for unprotected LM disease with paclitaxel-eluting stents (PES) and everolimus-eluting stents (EES). The ESTROFA-LM is a multicenter retrospective registry including consecutive patients with unprotected LM disease treated with PES or EES. A total of 770 patients have been included at 21 centers, 415 with treated PES and 355 with EES. Treatment with 2 stents was more frequent with PES (17% vs 10.4%, p = 0.007), whereas intravascular ultrasound was more frequently used with EES (35.2% vs 26%, p = 0.006). The 3-year death and infarction survival rates were 86.1% for PES and 87.3% for EES (p = 0.50) and for death, infarction, and target lesion revascularization were 83.6% versus 82% (p = 0.60), respectively. Definite or probable thrombosis was 1.6% for PES and 1.4% for EES (p = 0.80). The use of 2 stents, age, diabetes, and acute coronary syndromes were independent predictors of mortality. In the subgroup of distal lesions, the use of intravascular ultrasound was an independent predictor of better outcome. Comparison of propensity score-matched groups did not yield differences between the 2 stents. In conclusion, the results of this multicenter registry show comparable safety and efficacy at 3 years for PES and EES in the treatment of LM disease. The use of bifurcation stenting techniques in distal lesions was a relevant independent predictor for events. The use of intravascular ultrasound appears to have a positive impact on patients treated for LM distal disease.

Intraoperative use of spectral-domain optical coherence tomography during Descemet's stripping automated endothelial keratoplasty.

PURPOSE: To evaluate the intraoperative changes in the donor lenticule, recipient cornea, and the reduction of interface fluid thickness during Descemet's stripping and automated endothelial keratoplasty with EndoGlide™ (Angiotech Pharmaceuticals Inc, Vancouver, Canada) donor insertion, using intraoperative spectral-domain optical coherence tomography. METHODS: Prospective observational case series of patients underwent Descemet's stripping and automated endothelial keratoplasty using the EndoGlide inserter. Spectral-domain optical coherence tomography (iVue; Optovue Inc, Fremont, CA) with a handheld probe was used to image the cornea and anterior chamber. Standardized software was used to measure interface fluid gap, host cornea, and donor lenticule thicknesses during the following surgical stages of Descemet's stripping and automated endothelial keratoplasty: (1) after donor insertion and immediately before full air tamponade; (2) after air tamponade and expression of fluid from venting incisions; (3) at 6 minutes of air tamponade; and (4) at 10 minutes of air tamponade. RESULTS: Ten patients with a mean age of 74.9 ± 11.8 years were recruited. Spectral-domain optical coherence tomography measurements of the interface fluid gap after fluid was expressed through the venting incisions (P < 0.001), at 6 minutes of air tamponade (P < 0.001) and at 10 minutes of air tamponade (P < 0.001 and P = 0.001, respectively), were significantly decreased compared to the measurements immediately before air tamponade. Donor thickness increased significantly at 6 minutes of air tamponade (P = 0.004) but reduced by 10 minutes compared to immediately before air tamponade. CONCLUSION: Significant intraoperative changes in the donor, recipient cornea, and interface fluid thickness occurred following endothelial keratoplasty donor insertion.

Evolution of deep anterior lamellar keratoplasty (DALK).

The concept of selective tissue transplantation was theorized over two centuries ago. However, deep anterior lamellar keratoplasty (DALK) was difficult to perform with the instruments available at that time, and visual acuity results were poor compared to those achieved by full-thickness transplantation. Recently, many technical improvements in surgical instrumentation and advances in eye bank technology have led to the re-emergence of DALK. Now, patients with stromal pathologies not affecting the corneal endothelium can benefit from this surgery, which allows total stromal replacement of the recipient's cornea, leaving an intact recipient Descemet membrane and endothelium. Along with the advances in surgical instrumentation, improvements in surgical techniques and imaging technology have contributed to improved visual outcomes obtained with DALK. DALK is now seen as a viable alternative to penetrating keratoplasty with equivalent visual results and better long-term graft survival.

Umbilical cord lining stem cells as a novel and promising source for ocular surface regeneration.

The stem cells involved in renewal of the corneal epithelium are located in the basal region of the limbus, a narrow transition zone surrounding the cornea. In many ocular surface disorders loss of these stem cells results in partial or complete vision loss. Conventional corneal transplant in these patients is associated with dismal results. Stem cell transplantation offers new hope to such patients. The umbilical cord is emerging as an important source of stem cells that may have potential clinical applications. There are advantages to the use of umbilical cord stem cells as these cells are less immunogenic, non-tumorigenic, highly proliferative and ethically acceptable. In this study, we have confirmed the expression of several putative limbal stem cell markers such as HES1, ABCG2, BMI1, CK15 as well as cell adhesion-associated molecules INTEGRIN-α6, -α9, -ß1, COLLAGEN-IV and LAMININ in our recently characterized CLEC-muc population derived from human umbilical cord. Ex vivo expansion of these cells on a human amniotic membrane substrate formed a stratified cell sheet that similarly expresses some of these molecules as well as cornea-specific cytokeratins, CK3 and CK12. Transplantation of a bioengineered CLEC-muc sheet in limbal stem cell-deficient rabbit eyes resulted in regeneration of a smooth, clear corneal surface with phenotypic expression of the normal corneal-specific epithelial markers CK3, CK12 but not CK4 or CK1/10. Our results suggest that CLEC-muc is a novel stem cell that can be ex vivo expanded for corneal epithelial regeneration in the treatment of various eye diseases.

Comparison of eye-tracking success in laser in situ keratomileusis after flap creation with 2 femtosecond laser models.

PURPOSE: To determine the efficiency of an eye tracker after laser in situ keratomileusis (LASIK) flap creation with 1 of 2 femtosecond laser models. SETTING: Tertiary referral center, Singapore National Eye Center, Singapore. DESIGN: Randomized clinical trial. METHODS: The LASIK flap was created with an IntraLase (Group A) or a VisuMax (Group B) femtosecond laser. An Advanced Control Eye Tracker was initiated 3 times to obtain iris recognition. Eye tracking was considered successful if the eye movements could be followed despite the presence or absence of an opaque bubble layer (OBL). Univariate-multivariate logistic regression analysis was performed. RESULTS: Preoperatively, the mean values (ranges) of the 87 eyes were sphere, -5.64 diopters (D) ± 2.17 (SD) (-9.75 to -0.25 D); cylinder 1.65 ± 1.63 D (-3.75 to 0.00 D); optical zone, 6.34 ± 0.20 mm (5.6 to 7.0 mm); keratometry, 43.48 ± 1.32 D (40.1 to 42.8 D); flap thickness, 109.30 + 5.21 µm (90 to 115 µm). Eye tracking was successful in 38 (90.5%) of 42 eyes in Group A and 43 (95.6%) of 45 eyes in Group B. No specific type of OBL was seen in either group. The LASIK was completed in all eyes. There was a statistically significant association between positive tracking and a smaller optical zone (P=.03). There were no statistically significant differences in eye tracking between the 2 femtosecond lasers. CONCLUSIONS: Eye tracking was achieved in more than 90% of cases after LASIK flap creation with 1 of 2 femtosecond laser models, even in the presence of an OBL.

Thrombosis of second-generation drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2).

OBJECTIVES: This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. BACKGROUND: First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). METHODS: A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. RESULTS: From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). CONCLUSIONS: In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis.

Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial.

BACKGROUND: A catheter-based approach after fibrinolysis is recommended if fibrinolysis is likely to be successful in patients with acute ST-elevation myocardial infarction. We designed a 2x2 randomized, open-label, multicenter trial to evaluate the efficacy and safety of the paclitaxel-eluting stent and tirofiban administered after fibrinolysis but before catheterization to optimize the results of this reperfusion strategy. METHODS AND RESULTS: We randomly assigned 436 patients with acute ST-elevation myocardial infarction to (1) bare-metal stent without tirofiban, (2) bare-metal stent with tirofiban, (3) paclitaxel-eluting stent without tirofiban, and (4) paclitaxel-eluting stent with tirofiban. All patients were initially treated with tenecteplase and enoxaparin. Tirofiban was started 120 minutes after tenecteplase in those patients randomly assigned to tirofiban. Cardiac catheterization was performed within the first 3 to 12 hours after inclusion, and stenting (randomized paclitaxel or bare stent) was applied to the culprit artery. The primary objectives were the rate of in-segment binary restenosis of paclitaxel-eluting stent compared with that of bare-metal stent and the effect of tirofiban on epicardial and myocardial flow before and after mechanical revascularization. At 12 months, in-segment binary restenosis was similar between paclitaxel-eluting stent and bare-metal stent (10.1% versus 11.3%; relative risk, 1.06; 95% confidence interval, 0.74 to 1.52; P=0.89). However, late lumen loss (0.04+/-0.055 mm versus 0.27+/-0.057 mm, P=0.003) was reduced in the paclitaxel-eluting stent group. No evidence was found of any association between the use of tirofiban and any improvement in the epicardial and myocardial perfusion. Major bleeding was observed in 6.1% of patients receiving tirofiban and in 2.7% of patients not receiving it (relative risk, 2.22; 95% confidence interval, 0.86 to 5.73; P=0.14). CONCLUSIONS: This trial does not provide evidence to support the use of tirofiban after fibrinolysis to improve epicardial and myocardial perfusion. Compared with bare-metal stent, paclitaxel-eluting stent significantly reduced late loss but appeared not to reduce in-segment binary restenosis. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00306228.

Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

BACKGROUND: We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). METHODS: Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. RESULTS: No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. CONCLUSIONS: In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy.

In vivo real-time intraocular pressure variations during LASIK flap creation.

PURPOSE: To monitor and compare in vivo real-time intraocular pressure (IOP) in rabbit eyes undergoing LASIK flap creation using microkeratome and femtosecond laser. METHODS: Thirteen rabbit eyes in each group underwent LASIK flap creation using a microkeratome and a femtosecond laser. In vivo real-time IOP profile was measured using a 30-gauge needle with an IOP catheter sensor inserted into the anterior chamber from the limbus during surgery. RESULTS: In vivo real-time IOP monitoring was achieved in all cases, showing IOP variations during different phases of LASIK flap creation from docking of the instrument, start of surgery to the end of procedure, and monitoring the post-LASIK stabilization. IOP fluctuations were significantly lower in corneal flaps made with the femtosecond laser than with the microkeratome during globe suction (81.78+/-10.55 vs. 122.51+/-16.95 mm Hg), cutting (62.25+/-3.28 vs. 141.02+/-20.46 mm Hg), and suction (41.40+/-2.99 vs. 89.30+/-12.15). In contrast, femtosecond laser requires double the time (19+/-2 vs. 10+/-2 seconds for globe suction and 19+/-2 vs. 9+/-2 seconds for cutting) for completion of the procedure. CONCLUSIONS: The authors describe an accurate and reliable setup to measure and record in vivo real-time changes in IOP measurement from the anterior chamber during laser surgery. Femtosecond laser flap creation exerts less extreme IOP fluctuations with improved chamber stability but requires more procedure time than does microkeratome.

One-year follow-up of epithelial corneal cell sheet allografts mounted on platelet poor plasma in rabbits.

PURPOSE: To evaluate the usefulness of epithelial corneal sheets mounted on platelet poor plasma (PPP) for allograft transplantation of rabbits with total limbal stem cell deficiency (LSCD) and to prove its efficacy at 1 year after surgery. METHODS: LSCD was induced in 21 female rabbits by mechanical keratectomy. To configure the grafts, limbal biopsies were taken from male rabbits and cells were cultured on a fibroblast feeder layer grown on clotted autologous PPP. After keratectomy, grafts were sutured over the stroma. Control groups consisted of no implant or an implant of clotted PPP. Rabbits were euthanized at 3 and 12 months. Corneas and cultured sheets were processed for histopathology and immunohistochemistry (K3/12 and K19). Gender analysis was performed at 4 and 7 months. RESULTS: One rabbit had endophthalmitis, and another died of no apparent cause. The rest of the animals treated had no inflammation, showed a stratified epithelium, keratin 3/12 expression, and no expression of keratin 19. At 1 year, seven of eight rabbits showed no LSCD or corneal rejection signs. Y chromosomes were detected at 4 and 7 months postoperatively. All controls showed LSCD signs, erratic epithelium, and minimal cell differentiation; they revealed a slight expression of K3/12 and an expression of K19 in patchy patterns. CONCLUSIONS: Allografts contributed to restoring a healthy eye surface without signs of graft rejection. This technique seems to be a promising procedure for bilateral ocular surface diseases and may be useful for new therapeutic strategies.

Comparison of neointimal hyperplasia with drug-eluting stents versus bare metal stents in patients undergoing intracoronary bone-marrow mononuclear cell transplantation following acute myocardial infarction.

The aims of this study were to assess the safety of drug-eluting stent (DES) use and to compare the incidence of in-stent restenosis (ISR) and neointimal hyperplasia formation according to the type of stent implanted (DES vs bare-metal stents [BMS]) in patients who underwent intracoronary bone marrow mononuclear cell transplantation after acute ST elevation myocardial infarction. Fifty-nine patients with successfully revascularized ST elevation myocardial infarction (37 using BMS and 22 using DES) underwent paired angiographic examinations at baseline and 6 to 9 months after the intracoronary injection of 91 million +/- 56 million autologous bone marrow mononuclear cells. A subgroup of 30 patients also underwent serial intravascular ultrasound examinations. Off-line angiographic assessment showed 4 cases of binary ISR, primarily in BMS (3 cases), and no major adverse cardiac events were associated with stent type (mean follow-up period 41 +/- 10 months). At follow-up, angiographic late luminal loss was significantly lower in patients with DES than in those patients with BMS (0.35 +/- 0.66 vs 0.71 +/- 0.38 mm, p = 0.011). Multivariate analysis identified the use of DES (beta = -0.32, 95% confidence interval [CI] -0.57 to -0.26, p = 0.03) and a smaller baseline reference vessel diameter (beta = 0.29, 95% CI 0.04 to 0.54, p = 0.02) as independent predictors of lower late loss. Moreover, intravascular ultrasound showed a significant reduction of in-stent neointimal hyperplasia formation related to DES use compared with BMS use (Delta neointimal hyperplasia volume 5.4 mm(3) [95% CI 2.7 to 28.1] vs 35.9 mm(3) [95% CI 22.0 to 43.6], p = 0.035). In conclusion, these findings suggest that the use of DES is safe and may prevent ISR and neointimal hyperplasia formation in patients who undergo intracoronary bone marrow mononuclear cell transplantation after a successfully revascularized ST elevation myocardial infarction.