Pediatric endoscopy across multiple clinical settings: Efficiency and adverse events.

BACKGROUND: Endoscopic procedures are becoming increasingly important for the diagnosis and treatment of gastrointestinal disorders during childhood, and have evolved from a more infrequent inpatient procedure in the operating room to a routine outpatient procedure conducted in multiple care settings. Demand for these procedures is rapidly increasing and thus there is a need to perform them in an efficient manner. However, there are little data comparing the efficiency of pediatric endoscopic procedures in diverse clinical environments. We hypothesized that there are significant differences in efficiency between settings. AIM: To compare the efficiency and examine adverse effects of pediatric endoscopic procedures across three clinical settings. METHODS: A retrospective chart review was conducted on 1623 cases of esophagogastroduodenoscopy (EGD) or combined EGD and colonoscopy performed between January 1, 2014 and May 31, 2018 by 6 experienced pediatric gastroenterologists in three different clinical settings, including a tertiary care hospital operating room, community hospital operating room, and free-standing pediatric ambulatory endoscopy center at a community hospital. The following strict guidelines were used to schedule patients at all three locations: age greater than 6 mo; American Society of Anesthesiologists class 1 or 2; normal craniofacial anatomy; no anticipated therapeutic intervention (e.g., foreign body retrieval, stricture dilation); and, no planned or anticipated hospitalization post-procedure. Data on demographics, times, admission rates, and adverse events were collected. Endoscopist time (elapsed time from the endoscopist entering the operating room or endoscopy suite to the next patient entering) and patient time (elapsed time from patient registration to that patient exiting the operating room or endoscopy suite) were calculated to assess efficiency. RESULTS: In total, 58% of the cases were performed in the tertiary care operating room. The median age of patients was 12 years and the male-to-female ratio was nearly equal across all locations. Endoscopist time at the tertiary care operating room was 12 min longer compared to the community operating room (63.3 ± 21.5 min vs 51.4 ± 18.9 min, P < 0.001) and 7 min longer compared to the endoscopy center (vs 56.6 ± 19.3 min, P < 0.001). Patient time at the tertiary care operating room was 11 min longer compared to the community operating room (133.2 ± 39.9 min vs 122.3 ± 39.5 min, P < 0.001) and 9 min longer compared to the endoscopy center (vs 124.9 ± 37.9 min; P < 0.001). When comparing endoscopist and patient times for EGD and EGD/colonoscopies among the three locations, endoscopist, and patient times were again shorter in the community hospital and endoscopy center compared to the tertiary care operating room. Adverse events from procedures occurred in 0.1% (n = 2) of cases performed in the tertiary care operating room, with 2.2% (n = 35) of cases from all locations having required an unplanned admission after the endoscopy for management of a primary GI disorder. CONCLUSION: Pediatric endoscopic procedures can be conducted more efficiently in select patients in a community operating room and endoscopy center compared to a tertiary care operating room.

The Impact of an Emergency Department Upgrade to Level I Trauma Status on the Timeliness of Nontrauma Computed Tomography Scans.

BACKGROUND: Resources such as computed tomography (CT) scanners are sometimes shared when separate adult and pediatric emergency departments (EDs) exist in proximity. OBJECTIVES: To assess the impact of American College of Surgeons Level I trauma verification of an adult ED on the timeliness of nontrauma CT scans in a pediatric and adult ED that share a CT scanner. METHODS: ED patient records were retrospectively reviewed to determine the time from order to completion of nontrauma CT scans. We compared the timeliness of CT scan completion between the year leading up to the adult ED being verified as a Level I Trauma Center (2015), and the 2 subsequent years (2016-2017). RESULTS: The median time for nontrauma CT completion in the adult ED prior to Level I verification was 39 min, compared with 50 min and 49 min for the subsequent 2 years (p < 0.001). Similarly, the median time for completion of nontrauma CT scans in the pediatric ED increased from 33 min to 41 min and 39 min (p < 0.001). The proportion of patients who received CT scans within 30 min from order decreased after adult ED trauma upgrade, from 40% in 2015 to 30% and 32% (p < 0.001) in the 2 subsequent years. The pediatric ED showed similar results, with 48% of patients receiving CT scans within 30 min in 2015, compared with 34% in 2016 and 35% in 2017 (p < 0.001). CONCLUSIONS: Level I trauma verification of the adult ED adversely affected the timeliness of nontrauma CT scans in the EDs.

Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

OBJECTIVES: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved.

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy.

Implications from neurologic assessment of brain protection for total arch replacement from a randomized trial.

OBJECTIVE: The study objective was to perform a randomized trial of brain protection during total aortic arch replacement and identify the best way to assess brain injury. METHODS: From June 2003 to January 2010, 121 evaluable patients were randomized to retrograde (n = 60) or antegrade (n = 61) brain perfusion during hypothermic circulatory arrest. We assessed the sensitivity of clinical neurologic evaluation, brain imaging, and neurocognitive testing performed preoperatively and 4 to 6 months postoperatively to detect brain injury. RESULTS: A total of 29 patients (24%) experienced neurologic events. Clinical stroke was evident in 1 patient (0.8%), and visual changes were evident in 2 patients; all had brain imaging changes. A total of 14 of 95 patients (15%) undergoing both preoperative and postoperative brain imaging had evidence of new white or gray matter changes; 10 of the 14 patients had neurocognitive testing, but only 2 patients experienced decline. A total of 17 of 96 patients (18%) undergoing both preoperative and postoperative neurocognitive testing manifested declines of 2 or more reliable change indexes; of these 17, 11 had neither imaging changes nor clinical events. Thirty-day mortality was 0.8% (1/121), with no neurologic deaths and a similar prevalence of neurologic events after retrograde and antegrade brain perfusion (22/60, 37% and 15/61, 25%, respectively; P = .2). CONCLUSIONS: Although this randomized clinical trial revealed similar neurologic outcomes after retrograde or antegrade brain perfusion for total aortic arch replacement, clinical examination for postprocedural neurologic events is insensitive, brain imaging detects more events, and neurocognitive testing detects even more. Future neurologic assessments for cardiovascular procedures should include not only clinical examination but also brain imaging studies, neurocognitive testing, and long-term assessment.

RMS: a platform for managing cross-disciplinary and multi-institutional research project collaboration.

BACKGROUND: Cross-institutional cross-disciplinary collaboration has become a trend as researchers move toward building more productive and innovative teams for scientific research. Research collaboration is significantly changing the organizational structure and strategies used in the clinical and translational science domain. However, due to the obstacles of diverse administrative structures, differences in area of expertise, and communication barriers, establishing and managing a cross-institutional research project is still a challenging task. We address these challenges by creating an integrated informatics platform to reduce the barriers to biomedical research collaboration. RESULTS: The Request Management System (RMS) is an informatics infrastructure designed to transform a patchwork of expertise and resources into an integrated support network. The RMS facilitates investigators' initiation of new collaborative projects and supports the management of the collaboration process. In RMS, experts and their knowledge areas are categorized and managed structurally to provide consistent service. A role-based collaborative workflow is tightly integrated with domain experts and services to streamline and monitor the life-cycle of a research project. The RMS has so far tracked over 1,500 investigators with over 4,800 tasks. The research network based on the data collected in RMS illustrated that the investigators' collaborative projects increased close to 3 times from 2009 to 2012. Our experience with RMS indicates that the platform reduces barriers for cross-institutional collaboration of biomedical research projects. CONCLUSION: Building a new generation of infrastructure to enhance cross-disciplinary and multi-institutional collaboration has become an important yet challenging task. In this paper, we share the experience of developing and utilizing a collaborative project management system. The results of this study demonstrate that a web-based integrated informatics platform can facilitate and increase research interactions among investigators.

Hormone replacement therapy among postmenopausal women presenting with acute myocardial infarction: insights from the GUSTO-III trial.

BACKGROUND: The role of hormone replacement therapy (HRT) in the prevention of cardiovascular disease has been controversial. In large observational studies, HRT appears to lower cardiovascular disease risk. However, prospective randomized trials do not substantiate this. METHODS: We sought to characterize the use of HRT in women presenting with acute myocardial infarction and to investigate an association between HRT and inhospital or 30-day outcomes among women enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries III (GUSTO-III) trial. Of the 15,059 patients in GUSTO-III, 4124 were women. Menopausal status, HRT use, and clinical outcomes data were prospectively collected. RESULTS: Postmenopausal women taking HRT were significantly younger than those not taking HRT, and US women were more likely to be prescribed HRT than non-US women. While unadjusted 30-day mortality was substantially lower in HRT patients (6.1% vs 12.7%, P < .001), HRT use was not independently predictive of mortality after correcting for baseline differences (χ(2) = 0.15, P = .70). CONCLUSION: Hormone replacement therapy appears to have no early mortality benefit in women sustaining acute myocardial infarction. These findings further challenge the role of HRT in cardiovascular medicine.

Comprehensive left atrial appendage optimization of thrombus using surface echocardiography: the CLOTS multicenter pilot trial.

BACKGROUND: The aim of this study was to determine the ability to identify thrombus within the left atrial appendage (LAA) in the setting of atrial fibrillation (AF) using transthoracic echocardiography (TTE). In AF, the structure and function of the LAA has historically been evaluated using transesophageal echocardiography (TEE). The role of TTE remains undefined. METHODS: The Comprehensive Left Atrial Appendage Optimization of Thrombus (CLOTS) multicenter study enrolled 118 patients (85 men; mean age, 67 +/- 13 years) with AF of >2 days in duration undergoing clinically indicated TEE. On TEE, the LAA was evaluated for mild spontaneous echo contrast (SEC), severe SEC, sludge, or thrombus. Doppler Tissue imaging (DTI) peak S-wave and E-wave velocities of the LAA walls (anterior, posterior, and apical) were acquired on TTE. Transthoracic echocardiographic harmonic imaging (with and without intravenous contrast) was examined to determine its ability to identify LAA SEC, sludge, or thrombus. RESULTS: Among the 118 patients, TEE identified 6 (5%) with LAA sludge and 2 (2%) with LAA thrombi. Both LAA thrombi were identified on TTE using harmonic imaging with contrast. Anterior, posterior, and apical LAA wall DTI velocities on TTE varied significantly among the 3 groups examined (no SEC, mild SEC, severe SEC, sludge or thrombus). An apical E velocity < or = 9.7 cm/s on TTE best identified the group of patients with severe SEC, sludge, or thrombus. An anterior S velocity < or = 5.2 cm/s on TTE best identified the group of patients with sludge or thrombus. CONCLUSIONS: The CLOTS multicenter pilot trial determined that TTE is useful in the detection of thrombus using harmonic imaging combined with intravenous contrast (Optison; GE Healthcare, Milwaukee, WI). Additionally, LAA wall DTI velocities on TTE are useful in determining the severity of LAA SEC and detecting sludge or thrombus.

A novel approach to cancer staging: application to esophageal cancer.

A novel 3-step random forests methodology involving survival data (survival forests), ordinal data (multiclass forests), and continuous data (regression forests) is introduced for cancer staging. The methodology is illustrated for esophageal cancer using worldwide esophageal cancer collaboration data involving 4627 patients.

Comparison of anticoagulant and anti-inflammatory responses using enoxaparin versus unfractionated heparin for transesophageal echocardiography-guided cardioversion of atrial fibrillation.

The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II study compared enoxaparin with unfractionated heparin (UFH) as bridging therapy in patients with atrial fibrillation >2 days in duration who underwent transesophageal echocardiography-guided cardioversion. In the present study, the anticoagulant and anti-inflammatory effects of enoxaparin and UFH were compared at prespecified time points. In a randomized substudy of 155 patients from 17 clinical sites, the anticoagulant activity of enoxaparin (n = 76) was compared with that of UFH (n = 79). Blood samples were drawn at enrollment, on day 2, and on day 4 in the 2 groups. Blood samples were evaluated for anticoagulant activity by measuring the activated partial thromboplastin time, anti-Xa, anti-IIa, and tissue factor pathway inhibitor levels. In addition, levels of coagulation activation (by thrombin antithrombin complex) and inflammation (by highly sensitive C-reactive protein) were measured. The results of this substudy showed that the anti-Xa levels in the 2 groups increased on day 2. Similar increases in anti-Xa were observed on day 4. The anti-Xa levels and tissue factor pathway inhibitor levels were higher in the enoxaparin group compared with the UFH group on days 2 and 4. However, as expected, the anti-IIa levels in the UFH group were higher. In addition, markers of coagulation activation and inflammation were increased in patients with atrial fibrillation. Treatment with enoxaparin significantly decreased thrombin antithrombin complex levels compared with treatment with UFH. Highly sensitive C-reactive protein levels were also decreased after treatment in the 2 groups. In conclusion, the ACUTE II study showed that the use of enoxaparin for bridging therapy in patients with atrial fibrillation who underwent transesophageal echocardiography-guided cardioversion resulted in a more predictable and stronger anticoagulant response than that observed with UFH. Markers of inflammation were also decreased in the 2 groups.

The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion: assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study.

AIMS: To compare the feasibility and safety of transoesophageal echocardiograpy-guided cardioversion (CV) with enoxaparin and unfractionated heparin (UFH) in patients with atrial fibrillation (AF). METHODS AND RESULTS: The Assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II pilot trial compared the safety and efficacy of enoxaparin with UFH in 155 patients with AF who were scheduled for transoesophageal echocardiography (TEE)-guided CV. Safety outcomes over a 5-week period were ischaemic stroke, major or minor bleeding, and death. Efficacy outcomes were length of stay (LOS) and return to normal sinus rhythm (NSR). Of the 76 patients assigned to the enoxaparin group, 72 (94.7%) had a transoesophageal echocardiogram and 63 (82.9%) had early CV, of which 59 (93.7%) were successful. Of the 79 UFH patients, 66 (83.5%) had a transoesophageal echocardiogram and 58 (73.4%) had early CV, of which 54 (98.2%) were successful. There were no significant differences in embolic events, bleeding, or deaths between groups. The enoxaparin group had shorter median LOS compared with the UFH group [3(2-4) vs. 4(3-5)] days; P<0.0001). There was also more NSR at 5 weeks in the enoxaparin group (76 vs. 57%; P=0.013). CONCLUSION: In the ACUTE II trial, there were no differences in safety outcomes between the two strategies. However, the enoxaparin group had a shorter LOS. Thus, the TEE-guided enoxaparin strategy may be considered a safe and effective alternative strategy for AF. The shorter LOS may translate to lower costs using the enoxaparin TEE-guided approach.

Usefulness of atrioventricular delay optimization using Doppler assessment of mitral inflow in patients undergoing cardiac resynchronization therapy.

This study evaluated the utility of atrioventricular (AV) optimization using Doppler echocardiography in patients who undergo cardiac resynchronization therapy (CRT). AV optimization in patients who undergo CRT is performed inconsistently, with few data supporting its utility. Data were collected from 215 patients in New York Heart Association class III or IV heart failure (66% ischemic) who underwent AV optimization <30 days after implantation from 1999 to 2003. All patients arrived with AV delay programmed at the time of their CRT procedures (100 to 120 ms). AV delay was optimized using Doppler mitral inflow data to target stage I diastolic filling. Baseline clinical characteristics, AV delay, and diastolic functional stage were recorded. The mean follow-up period was 23 months. Five hundred patients underwent CRT, 215 of whom underwent AV optimization <30 days after implantation. Baseline mean age was 66 +/- 12 years, left ventricular (LV) ejection fraction 19 +/- 8%, LV end-diastolic dimension 6.5 +/- 1 cm, LV end-systolic dimension 5.5 +/- 1 cm, QRS duration 166 +/- 27 ms, and time to AV optimization 2.5 +/- 4 days. Baseline and final AV delay means were 120 +/- 25 and 135 +/- 40 ms, respectively (p = 0.0001). In 40% of patients (86 of 215), final AV delay settings were >140 ms. Left atrial diameter and AV block predicted patients in whom AV delay settings >140 ms were optimal. There was no difference in mortality in patients with final AV delays of >140 ms. In conclusion, AV optimization in patients who underwent CRT resulted in final AV delay settings of >140 ms in 40% of patients. AV delay optimization based on Doppler echocardiographic determination of optimal diastolic filling is useful and safe in patients who undergo CRT.

Exercise-induced QT/R-R-interval hysteresis as a predictor of myocardial ischemia.

OBJECTIVES: Exercise-induced QT/RR hysteresis exists when, for a given R-R interval, the QT interval duration is shorter during recovery after exercise than during exercise. We sought to assess the association between QT/RR hysteresis and imaging evidence of myocardial ischemia. BACKGROUND: Because ischemia induces cellular disturbances known to decrease membrane action potential duration, we hypothesized a correlation between QT/RR and myocardial ischemia. METHODS: We digitally analyzed 4-second samples of QT duration and R-R-interval duration in 260 patients referred for treadmill exercise stress and rest single photon emission computed tomography myocardial perfusion imaging; a cool-down period was used after exercise. None of the patients were in atrial fibrillation or used digoxin, and none had marked baseline electrocardiographic abnormalities. Stress and rest myocardial perfusion images were analyzed visually and quantitatively to define the extent and severity of stress-induced ischemia. QT/RR hysteresis was calculated using a computerized algorithm. RESULTS: There were 82 patients (32%) who manifested myocardial ischemia by single photon emission computed tomography myocardial perfusion imaging. The likelihood of ischemia increased with increasing QT/RR hysteresis, with prevalence according to quartiles of 20%, 30%, 26%, and 49% (P = .003 for trend). In analyses adjusting for ST-segment changes, exercise capacity, heart rate recovery, and other confounders, QT/RR hysteresis was independently predictive of presence of myocardial ischemia (adjusted odds ratio for 100-point increase of QT/RR hysteresis, 1.61; 95% confidence interval, 1.22-2.12; P = .0008). QT/RR hysteresis was also predictive of severe ischemia. CONCLUSION: Exercise-induced QT/RR hysteresis is a strong and independent predictor of myocardial ischemia and provides additional information beyond that afforded by standard ST-segment measures.

Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial.

BACKGROUND: Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations. CONCLUSIONS: Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

Magnesium as a neuroprotectant in cardiac surgery: a randomized clinical trial.

OBJECTIVE: We sought to evaluate magnesium as a neuroprotectant in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: From February 2002 to September 2003, 350 patients undergoing elective coronary artery bypass grafting, valve surgery, or both were enrolled in a randomized, blinded, placebo-controlled trial to receive either magnesium sulfate to increase plasma levels 1(1/2) to 2 times normal during cardiopulmonary bypass (n = 174) or no intervention (n = 176). Neurologic function, neuropsychologic function, and depression were assessed preoperatively, at 24 and 96 hours after extubation (neurologic) and at 3 months (neuropsychologic, depression). Neurologic scores were analyzed using ordinal longitudinal methods, and neuropsychologic and depression inventory data were summarized by principal component analysis, followed by linear regression analysis using component scores as response variables. RESULTS: Seven (2%) patients had a postoperative stroke, 2 (1%) in the magnesium and 5 (3%) in the placebo group (P = .4). Neurologic score was worse postoperatively in both groups (P < .0001); however, magnesium group patients performed better than placebo group patients (P = .0001), who had prolonged declines in short-term memory and reemergence of primitive reflexes. Three-month neuropsychologic performance and depression inventory score were generally better than preoperatively, with few differences between groups (P > .6); however, older age (P = .0006), previous stroke (P = .003), and lower education level (P = .0007) were associated with worse performance. CONCLUSIONS: Magnesium administration is safe and improves short-term postoperative neurologic function after cardiac surgery, particularly in preserving short-term memory and cortical control over brainstem functions. However, by 3 months, other factors and not administration of magnesium influence neuropsychologic and depression inventory performance.

Efficacy of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation at 6 months: a randomized controlled trial.

BACKGROUND: Electrical cardioversion in patients with atrial fibrillation (AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography (TEE)-guided strategy with a conventional strategy in patients with AF > 2 days' duration undergoing electrical cardioversion over a 6-month follow-up. METHODS: The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six-month follow-up was available in 1034 patients (85%), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. RESULTS: At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group (10 [2%] vs 4 [0.8%]; risk ratio (RR) 2.47, 95% CI 0.78-7.88; P = .11). However, the hemorrhagic rate was significantly lower in the TEE group (23 [4.4%] vs 38 [7.5%]; RR 0.58, 96% CI 0.35-0.97; P = .04). There was no difference between the 2 treatment groups in all-cause mortality (21 [4%] vs 14 [2.8%]; RR 1.48, 95% CI 0.76-2.92; P = .25) and in the occurrence of normal sinus rhythm between the 2 groups (305 [62.2%] vs 280 [58.1%]; P = .51). Sinus rhythm at 6 months was more common in the TEE-guided group, in those patients who had direct current cardioversion (238 [62.5%] vs 151 [53.9%]; P = .03). CONCLUSION: The TEE-guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of > 2 days' duration undergoing electrical cardioversion over a 6-month period.

Utility of transesophageal echocardiography in identification of thrombogenic milieu in patients with atrial fibrillation (an ACUTE ancillary study).

The ACUTE trial randomly assigned patients who had atrial fibrillation (AF) of >2 days' duration to a transesophageal echocardiographically guided or a conventional strategy before cardioversion. In the 571 patients who underwent transesophageal echocardiography (TEE) in the ACUTE trial, we assessed the relative predictive value of baseline data derived by history, transthoracic echocardiography, and TEE for prediction of thrombus and adjudicated embolism (thromboembolism) as a composite end point. TEE was performed at 70 centers in 571 patients, 549 in the transesophageal echocardiographically guided group and 22 crossovers in the conventional group. Six patients (1.1%) who had embolism and 79 (13.8%) who had thrombi were identified in this group. Thrombus was completely resolved in 76.5% of patients who had repeat transesophageal echocardiographic procedures after 31.7 +/- 7.5 days of anticoagulation. For patients who had embolic events, none had a transesophageal echocardiographically identified thrombus; 5 of 6 (83.3%) had >/=1 transesophageal echocardiographic risk factors (including spontaneous echocardiographic contrast, aortic atheroma, patent foramen ovale, atrial septal aneurysm, mitral valve strands), and 4 of 6 (66.66%) had subtherapeutic anticoagulation or no anticoagulation. Clinical, transthoracic echocardiographic, and transesophageal echocardiographic risk factors contributed significantly to the prediction of composite thrombus/embolism. However, transesophageal echocardiographic thromboembolic risk factors were the strongest predictors of thromboembolism and provided statistically significant incremental value (chi-square 38.0, p <0.001) for identification of risk. Thus, in addition to thrombus identification, TEE has significant incremental value in the identification of patients who had high thromboembolic risk. In conclusion, this study supports the role of TEE and anticoagulation monitoring in patients who have atrial fibrillation and is useful for identifying thromboembolic risk factors.

Impact of cardioversion strategy on functional capacity in patients with atrial fibrillation: the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study.

BACKGROUND: The ACUTE Trial studied a transesophageal echocardiography (TEE)-guided strategy compared with a conventional strategy for management of patients with atrial fibrillation undergoing direct current cardioversion. The primary aim was to determine if patient functional capacity, measured by the Duke Activity Status Index (DASI), would differ between treatment strategies. METHODS: The DASI was self-administered at study enrollment and at 8-week follow-up in 1074 (88%) of 1222 total patients. Clinical outcomes associated with enrollment DASI scores and change in follow-up DASI scores were reviewed. RESULTS: There was no difference between the TEE-guided (n = 544) and conventional treatment (n = 530) groups for mean baseline and 8-week DASI scores, adjusting for baseline; however, patients who improved their DASI score were more likely to be in the TEE-guided group (P = .03). Pooled group data showed that the higher the enrollment DASI score, the more it tended to be positively related to maintenance of sinus rhythm (P = .06) at 8 weeks. The lower the enrollment DASI score, the more it was predictive of death (P = .03) and bleeding (P = .01) within 8 weeks. Patients with congestive heart failure (CHF) at enrollment showed greater improvement in DASI scores at 8 weeks compared with patients without CHF (DASI Delta 45.9% vs 31.6%, P < .001). CONCLUSIONS: There was no difference in DASI scores between treatment groups. However, TEE-guided treatment was a predictor of improved DASI at follow-up, and subgroup analysis showed that patients with CHF did show improvement in functional capacity with cardioversion.

1993 2003 gender differences in coronary artery revascularization: has anything changed?

BACKGROUND: Gender differences abound in patients undergoing coronary artery bypass graft (CABG) surgery. Most research was conducted in the early 1 990s. It is unknown if gender differences have diminished over time. RESEARCH OBJECTIVES: To determine whether gender differences exist in the current era of CABG surgery by examining preoperative, intraoperative, and postoperative factors known to affect outcomes. SUBJECTS AND METHODS: In this descriptive, correlational study of all patients undergoing primary, isolated CABG at a large, urban Midwestern healthcare center, data in 1993 and 2003 were analyzed to determine if gender and time differences existed and if there was a time and gender interaction effect. Trained nurses prospectively collected data during the index hospitalization for the institution's Cardiovascular Information Registry. RESULTS: 2,200 patients were studied; women accounted for one-fourth of the sample. Age over 65 years; current smoking; presence of hypertension, cerebrovascular accident; and insulin-dependent diabetes; symptomatic heart failure and chest pain were significantly associated with female gender (all P' s < .001). Intraoperatively, internal mammary arteries were used less as a graft conduit in women (P < .001); gender differences were most pronounced in patients requiring 2 bypass grafts. Postoperatively, cardiac pump failure and median hospital stay were greater in women (both P' s < .001); however, both decreased over time. CONCLUSIONS: Gender differences continue to exist in patients undergoing CABG. Differences do not affect hospital mortality rates but play a role in hospital length of stay and may affect postdischarge recovery. Research targeted at modifiable preoperative factors may improve postoperative recovery.