Influence of Access, Anticoagulant, and Bleeding Definition on Outcomes of Primary Percutaneous Coronary Intervention: Early Experience of an US Academic Center.

Background We aimed to carry out comparison of different bleeding avoidance strategies in doing primary percutaneous coronary intervention (PPCI) using either radial or femoral as access of choice and either bivalirudin or unfractionated heparin as anticoagulant of choice. In this analysis, we analyzed the influence of major bleeding definition on bleeding outcomes as well. Methods We did a retrospective analysis of 139 patients with ST-segment elevation myocardial infarction (STEMI) who had PPCI in our academic center from January 2010 till October 2013. The primary outcome at 30 days was a composite of death from any cause or stent thrombosis or non-coronary artery bypass grafting (CABG) related major bleeding (CathPCI Registry definition) and secondary outcomes were individual components of primary outcome and the hospital length of stay. Results There was no significant difference among different access/anticoagulant combinations with regards to primary outcome (22% in radial/bivalirudin vs. 5% in radial/heparin vs. 17% in femoral/bivalirudin vs. 28% in femoral/heparin group; p = 0.2) as well as its individual components except the hospital length of stay (2.56 vs. 3 vs. 3.97 vs. 4.4 days each; p < 0.0001). The overall rate of major bleeding was 11.5%. When we use HORIZON-AMI bleeding definition, it went up to 25 % due to one particular component (p < 0.004). Conclusions This single center observational study doing PPCI did not show any superiority of one bleeding avoidance strategy over others with regard to primary outcome and its individual components except the hospital length of stay. It also shows the importance of bleeding definition on bleeding outcomes.

Comparison of two Macintosh laryngoscope blades in 300 patients.

BACKGROUND: There are two forms of Macintosh laryngoscope blade. Compared with the standard blade, the English blade is longer, its curve is more continuous across the entire length of the blade, the flange of the blade continues much closer to the blade tip, and the height of the flange is shorter. METHOD: We studied 300 patients to compare the ease of laryngoscopy with each type of Macintosh laryngoscope blade. In a random crossover design, after induction of anaesthesia and neuromuscular block, the two blades were inserted in turn, and the views of the glottis at laryngoscopy (Cormack and Lehane scores) were compared. RESULTS: There was a difference in the view of the glottis in 80 patients. Among these patients, the view was better for the English blade for 63 patients and the standard blade was better for 17 patients. Laryngoscopy was difficult (grade 3 or 4) for at least one blade in 42 of 300 patients (14%). In these 42 patients, there was a difference in the score between the blades in 28 patients; the view was better for the English blade in 25 patients (60%) and for the standard blade in three patients (7%). The view was significantly better for the English blade than for the standard blade (P<0.001; 95% confidence interval 45-74%). CONCLUSIONS: In patients in whom laryngoscopy was unexpectedly difficult, the English blade provided a better glottic view significantly more frequently than the standard blade.

Risk assessment of slow or no-reflow phenomenon in aortocoronary vein graft percutaneous intervention.

Slow or no-reflow phenomenon (SNR) complicates 10%-15% of cases of percutaneous intervention (PCI) in aortocoronary saphenous vein grafts (SVG). At present, there are no uniform, effective strategies to predict or prevent this common and potentially serious complication. The purpose of our study was to characterize variables correlated with the risk of SNR in SVG PCI in the era of stenting and glycoprotein IIb/IIIa receptor inhibitors. We identified 2,898 consecutive patients who had PCI, of whom 163 underwent PCI of at least one SVG. The clinical and angiographic characteristics of patients who developed SNR (SNR group) were compared with those who did not (no-SNR group). A total of 23 patients experienced SNR and 140 did not. Using a stepwise multivariate logistic regression analysis, four independent predictors for SNR were detected: probable thrombus (OR 6.9; 95% CI, 2.1-23.9; P = 0.001), acute coronary syndromes (OR 6.4; 95% CI, 2.0-25.3; P = 0.003), degenerated vein graft (OR 5.2; 95% CI, 1.7-16.6; P = 0.003), and ulcer (OR 3.4; 95% CI, 0.99-11.6; P = 0.04). The risk of developing SNR could be estimated according to the number of predictors found: low-grade risk (1%-10%) if < or = one variable was present, moderate risk (20%-40%) if two variables were present, and high risk (60%-90%) if three or more variables were present. We identified and quantified current risk factors for SNR and concluded that the risk of developing SNR during PCI in SVG can be predicted by simple clinical and angiographic variables obtained before PCI. This information may be useful when the risk of PCI has to be balanced against alternative strategies such as medical therapy or redo-bypass surgery or in the selection of those patients that will most benefit from the use of protection devices during PCI.

Characterization of fortilin, a novel antiapoptotic protein.

Apoptosis is meticulously controlled in living organisms. Its dysregulation has been shown to play a key role in a number of human diseases, including neoplastic, cardiovascular, and degenerative disorders. Bcl-2 family member proteins and inhibitors of apoptosis proteins are two major negative regulators of apoptosis. We report here the characterization of novel antiapoptotic protein, fortilin, which we identified through yeast two-hybrid library screening. Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide highly conserved from mammals to plants. Fortilin is structurally unrelated to either Bcl-2 family member proteins or inhibitors of apoptosis proteins. Northern blot analysis showed the fortilin message to be ubiquitous in normal tissue but especially abundant in the liver, kidney, and small intestine. Western blot analysis using anti-fortilin antibody showed more extensive expression in cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from normal tissue (HEK293). Immunocytochemistry using HeLa cells transiently expressing FLAG-tagged fortilin and immunohistochemistry using human breast ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is predominantly localized in the nucleus. Functionally, the transient overexpression of fortilin in HeLa cells prevented them, in a dose-dependent fashion, from undergoing etoposide-induced apoptosis. Consistently, U2OS cells stably expressing fortilin protected the cells from cell death induced by etoposide over various concentrations and durations of exposure. In addition, fortilin overexpression inhibited caspase-3-like activity as assessed by the cleavage of fluorogenic substrate benzyloxycarbonyl-DEVD-7-amido-4-(trifluoromethyl)coumarin. Furthermore, the antisense depletion of fortilin from breast cancer cell line MCF-7 was associated with massive cell death. These data suggest that fortilin represents a novel antiapoptotic protein involved in cell survival and apoptosis regulation.

Percutaneous intervention in saphenous venous grafts: in-stent restenosis lesions are safer than de novo lesions.

BACKGROUND: The histological appearance of stenosis in de novo saphenous venous grafts (DNSVG) consists of diffuse atherosclerosis that contains blood elements, necrotic debris and limited fibrocollagenous tissue. The friable nature of these lesions complicates percutaneous intervention (PCI) procedures. On the other hand, in-stent restenosis (ISR) of SVG is due primarily to atherosclerotic plaque or fibromuscular hyperplasia, with thrombus formation playing a secondary role. The purpose of this study is to compare the results of PCI in these two types of SVG lesions. METHODS: We reviewed our institutional interventional database from March 1996 through February 2000 and identified all consecutive patients who underwent PCI of at least one SVG. One hundred and ten patients were identified: 89 undergoing DNSVG intervention and 21 patients with ISR lesions. RESULTS: Acute coronary syndromes, degenerated and thrombus-containing lesions were more common in the DNSVG group. "Slow-, no-reflow" complicated 20% of the DNSVG lesions compared to none of the ISR lesions (p = 0.02). Post-procedural myocardial infarction was higher in the DNSVG group (13.5% versus 0%; p = 0.1) and correlated significantly with the occurrence of "slow-, no-reflow" (r = 0.43; p = 0.0001). Utilizing statistical modeling to adjust for baseline differences between the groups, ISR lesions were associated with a low risk of procedural complications (r = 0.22; p = 0.03). CONCLUSION: This study demonstrates that in this relatively high-risk population, PCI is safer in ISR lesions than in de novo SVG lesions.

Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon.

Slow or no reflow (SNR) complicates 10-15% of cases of percutaneous intervention (PI) in saphenous vein bypass graft (SVG). To date there have been limited options for the prevention and treatment of this common and potentially serious complication. We evaluated the procedural outcome of 143 consecutive SVG interventions. We compared patients who received pre-intervention intra-graft adenosine boluses with those who did not. In addition we examined the efficacy of adenosine boluses to reverse slow-no reflow events. Angiograms were reviewed and flow graded (TIMI grade) by film readers blinded to the use of any intraprocedural drug or clinical history. Seventy patients received intragraft adenosine boluses before percutaneous intervention (APPI), 73 received no preintervention adenosine (NoAPPI). There were no significant angiographic differences between the two groups at baseline. A total of 20 patients experienced SNR. The incidence of SNR was similar in the two groups (APPI = 14.2% vs. NoAPPI = 13.6%, P = 0.9). SNR was treated with repeated, rapid boluses (24 microg each) of intra-graft adenosine. Reversal of SNR was observed in 10 of 11 patients (91%) who received high doses of adenosine (>/=5 boluses, mean 7.7 +/- 2.6) and in 3 of 9 (33%) of those who received low doses (<5 boluses, mean 1.5 +/- 1.2). Final TIMI flow was significantly better in the high dose than in the low dose group (final TIMI 2.7 +/- 0.6 vs. 2 +/- 0.8, P = 0.04). No significant untoward complications were observed during adenosine infusion. These findings suggest that SNR after PI in SVG is not prevented by pre-intervention adenosine, but it can be safely and effectively reversed by delivery of multiple, rapid and repeated boluses of 24 microg of intra-graft adenosine.

Causes of early reintervention after successful coronary artery stenting.

Acute reintervention was performed in 26 of 1,620 patients after coronary stenting (1.6%). Half of the patients had stent thrombosis and the other half residual anatomic problems. The mean time for reintervention was shorter in patients with stent thrombosis. All patients with stent thrombosis had a sudden recurrence of chest pain. Electrocardiographic changes were more common with stent thrombosis. Composite end point occurred in 10 patients (77%) with stent thrombosis versus 5 (39%) in the other group (p = 0.04).

Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of "no reflow" phenomenon.

Percutaneous intervention in acute myocardial infarction has been associated with a high incidence of "no reflow," ranging from 11% to 30%, with an increased risk of complications. The role of intracoronary adenosine for the prevention of this phenomenon has not been evaluated fully. We studied the procedural outcomes of 79 patients who underwent percutaneous intervention in the context of acute myocardial infarction. Twenty-eight patients received no intracoronary adenosine, and 51 received intracoronary adenosine boluses (24-48 microg before and after each balloon inflation). Eight patients who were not given adenosine experienced no reflow (28.6%) and higher rates of in-hospital death, while only three of 51 patients (5.9%; P = 0.014) in the adenosine group experienced no reflow. No untoward complications were noted during adenosine infusion. Intracoronary adenosine bolus administration during percutaneous intervention in the context of acute myocardial infarction is easy and safe and may significantly lessen the incidence of no reflow, which may improve the outcome of this procedure.

Timing of coronary stent thrombosis in patients treated with prophylactic tirofiban.

BACKGROUND: Acute and subacute stent thromboses (ASST) are the major thrombotic complications of coronary stenting. The time course of ASST seems to be related to the type of antithrombotic therapy (four days in patients treated with aspirin and coumadin compared to 12 hours with the use of aspirin and ticlopidine). In this report, we compared the timing of ASST in patients treated with aspirin, ticlopidine/clopidogrel, heparin and tirofiban with that in patients treated with the same drugs but without tirofiban. METHODS: Retrospective analysis of the Hermann intervention database between January 1997 and October 1999 was performed. We identified 13 patients who required reintervention in the first week after a successful coronary stenting ( 1 stent). Four patients were treated with tirofiban (Group 1) and 9 were not (Group 2). RESULTS: The median time from stent deployment to ASST was 7 hours (interquartile range, 2.5Eth 33 hours) in group 2 compared to 84.5 hours (interquartile range, 56Eth 124.5 hours) in group 1. The mean time from stent deployment to ASST was 90.3 +/- 43.1 hours in group 1 versus 12.8 +/- 15.3 hours in group 2 (p = 0.0005). All episodes of ASST occurred 3 days in patients treated with tirofiban, whereas they occurred in the first 2 days in all patients not treated with tirofiban. CONCLUSION: Prophylactic tirofiban treatment delays the time to stent thrombosis after successful coronary artery stent implantation for more than two days. Patients at high risk for stent thrombosis treated with short-acting glycoprotein IIb/IIIa platelet receptor inhibitors may warrant close follow-up during the first week after stenting.

Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen.

MCL1 (ML1 myeloid cell leukemia 1), a Bcl-2 (B- cell lymphoma-leukemia 2) homologue, is known to function as an anti-apoptotic protein. Here we show in vitro and in vivo that MCL1 interacts with the cell cycle regulator, proliferating cell nuclear antigen (PCNA). This finding prompted us to investigate whether MCL1, in addition to its anti-apoptotic function, has an effect on cell cycle progression. A bromodeoxyuridine uptake assay showed that the overexpression of MCL1 significantly inhibited the cell cycle progression through the S-phase. The S-phase of the cell cycle is also known to be regulated by PCNA. A mutant of MCL1 that lacks PCNA binding (MCL1(Delta)(4A)) could not inhibit cell cycle progression as effectively as wild type MCL1. In contrast, MCL1(Delta)(4A) retained its anti-apoptotic function in HeLa cells when challenged by Etoposide. In addition, the intracellular localization of MCL1(Delta)(4A) was identical to that of wild type MCL1. An in vitro pull-down assay suggested that MCL1 is the only Bcl-2 family protein to interact with PCNA. In fact, MCL1, not other Bcl-2 family proteins, contained the PCNA-binding motif described previously. Taken together, MCL1 is a regulator of both apoptosis and cell cycle progression, and the cell cycle regulatory function of MCL1 is mediated through its interaction with PCNA.

[Transition of branched-chain amino acids and tyrosine ratio (BTR) in the blood of acute hepatitis patients].

The molar ratio of branched-chain amino acids to tyrosine (BTR) correlates well with the Fischer ratio, and can be measured in a short period of time. It is regarded as the method of analysis that will eventually replace the Fischer ratio. But clinical significance of BTR in terms of acute liver disorders has not been examined thoroughly as of yet. In this study, we measured BTR of 34 patients with acute hepatitis, and examined the transition of the acute period of acute hepatitis and its recovery process. Thirty-four patients diagnosed with acute viral hepatitis became subjects of examination (16 patients of A type, 15 patients of B type, 1 patient of C type, 2 patients of non-A, non-B, non-C type). Out of the 34 patients, 11 were in serious stages (HPT under 40%), including 3 in fulminant condition. By using preserved serum obtained during the acute period (within 1 week of the highest transaminase value), recovery period (within 4 weeks), and treatment period (3 months and later), measurements were conducted with Diacolor:BTR (enzymatic analysis, ONO Pharmaceutical Co., Ltd.), and the results were compared with those of 50 healthy subjects (25 men, 25 women). BTR correlated well with the Fischer ratio for chronic hepatic patients, and with albumin (Alb), PT, and ICGR15 as well, proving that it is useful as an indicator of hepatic reserve ability. But BTR has not been thoroughly examined as it relates to acute liver disorders. In this study, BTR fell in the acute period, correlating with the serious period, proving that it is a useful indicator. For acute liver damage, BTR supports conventional indicators (Alb, Ch-E, HGF, etc.) for assessing serious damage. Also, it has been suggested that measuring the passage of BTR could be the indicator of true recovery, including amino acid metabolism for liver disorders.

Intracoronary adenosine administered during rotational atherectomy of complex lesions in native coronary arteries reduces the incidence of no-reflow phenomenon.

Rotational atherectomy (RA) of complex, calcified lesions has been associated with a high incidence of no reflow ranging from 6%-15% and concomitant myocardial necrosis with adverse prognostic implications. There are no uniform strategies for preventing this complication. The role of intracoronary adenosine for the prevention of this phenomenon during RA has not been fully evaluated. We studied the procedural outcome of 122 patients who underwent RA of complex native coronary artery lesions. Fifty-two patients received no adenosine but a variety of other agents. Seventy patients received intracoronary adenosine boluses (24 to 48 microgram prior to and after each RA run). There was no difference in the type of lesion studied, run time, or Burr to artery ratio (0.6-0.7) between the two groups. Six patients without adenosine experienced no reflow (11.6%), with resultant infarction in the target artery territory, while only 1 of 70 patients (1.4%, P - 0.023) in the adenosine group experienced no reflow. No untoward complications were observed during adenosine infusion. Intracoronary adenosine bolus administered during rotational atherectomy is easy, safe, and may significantly reduce the incidence of no reflow, which may improve the 30-day outcome of this procedure.

The effects of the lateral position on cardiopulmonary function during laparoscopic urological surgery.

UNLABELLED: Laparoscopic urological surgery is usually performed transperitoneally with retroperitoneal insufflation of carbon dioxide (CO2) in the lateral position. We studied whether a difference in the side of lateral position affected hemodynamic and pulmonary functions during pneumoperitoneum. Fifteen patients (eight in the right and seven in the left lateral position) undergoing elective laparoscopic urological surgery were studied under general anesthesia. Hemodynamic variables and blood gas data were recorded. Before insufflation, mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) in the right lateral position were higher than those in the left lateral position. Pneumoperitoneum increased MAP, MPAP, CVP, PCWP, and cardiac index but decreased systemic vascular resistance in the right lateral position. Similar changes occurred during pneumoperitoneum in the left lateral position, but the changes were less than those in the right lateral position. The respiratory index (PaO2/PAO2), intrapulmonary shunt, and SpO2 did not change during pneumoperitoneum in either lateral position. Changing the side of the lateral position affected hemodynamic function but did not affect pulmonary oxygenation during pneumoperitoneum. IMPLICATIONS: The right and left lateral positions produced different hemodynamic changes during laparoscopic urological surgery. The increases in preload and cardiac index and the decrease in systemic vascular resistance were greater in the right than in the left lateral position. Respiratory changes were not affected differently between the right and left lateral positions.