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.

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.

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.

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.

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.

Annular geometry and motion in human ischemic mitral regurgitation: novel assessment with three-dimensional echocardiography and computer reconstruction.

BACKGROUND: Annular geometry and motion in functional ischemic mitral regurgitation are incompletely understood. Three-dimensional echocardiography demonstrates saddle-shaped annular geometry, but standard methodology does not enable quantification of annular motion. Therefore, a novel technique using three-dimensional echocardiography and computer software was used to characterize alterations in mitral annular geometry and motion in patients with ischemic mitral regurgitation. METHODS: We developed a computer program to reconstruct the mitral annulus based on spatial coordinates from three-dimensional echocardiography. Data were obtained at end-diastole and end-systole in 7 patients with ischemic mitral regurgitation and 5 normal control subjects. Mitral annular motion was quantified by calculating the displacement area of the annulus between end-diastole and end-systole. RESULTS: Comparison of ischemic mitral regurgitation and control patients revealed differences in annular geometry and motion at end-diastole. Annular perimeter was greater in ischemic mitral regurgitation patients (10.7 +/- 0.7 cm versus 8.6 +/- 0.2 cm in control group; p < 0.03), with increased intertrigonal distance in ischemic mitral regurgitation patients (2.8 +/- 0.3 cm versus 2.1 +/- 0.1 cm; p < 0.06). These changes resulted in increased annular orifice area in ischemic mitral regurgitation patients (9.1 +/- 1.2 cm2 versus 5.7 +/- 0.3 cm2; p < 0.03). Ischemic mitral regurgitation patients had altered annular motion, with reduced movement of the posterior annulus (5.4 +/- 0.7 cm2 versus 8.7 +/- 1.1 cm2; p < 0.03). CONCLUSIONS: Computer analysis of data obtained from three-dimensional echocardiography demonstrates altered annular geometry and motion in patients with ischemic mitral regurgitation. Patients with ischemic mitral regurgitation have annular dilatation, with an increase in anterior and posterior annular perimeters; this is accompanied by an increase in the intertrigonal distance and restriction of annular motion.

Sustained apoptosis in human cardiac allografts despite histologic resolution of rejection.

BACKGROUND: We investigated the occurrence of apoptosis during and after resolution of cardiac allograft rejection. Apoptosis could play different roles in graft survival depending on the target cells; thus, we also determined the cell types involved. METHODS: Endomyocardial biopsy specimens were evaluated during the first 6 months after transplantation as follows: group I, no current or prior rejection; group II, during an episode of moderate rejection; and group III, histologic resolution after an episode of moderate rejection. RESULTS: Groups II and III showed significantly increased apoptotic activity, indicated by increased caspase-8 and caspase-3 activity; however, activated caspase-3 was undetectable in group I. Activated caspase-3 was detected only in groups II and III. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling was detected in groups II and III but not group I and predominantly in inflammatory cells. CONCLUSIONS: Increased caspase activity and apoptosis of infiltrating cells not only occurs during acute cardiac allograft rejection but persists after histologic resolution. Thus, programmed cell death occurs beyond the period of histologic resolution and may play a role in regulation of the rejection process.

Bleeding complications in patients with atrial fibrillation undergoing cardioversion randomized to transesophageal echocardiographically guided and conventional anticoagulation therapies.

In a multicenter randomized trial, we studied a transesophageal echocardiography (TEE) guided strategy with short-term anticoagulation compared with a conventional strategy for patients with atrial fibrillation >2 days' duration and undergoing cardioversion. Composite major and minor bleeding was a predetermined secondary end point of the study. The objective of the study was to assess the incidence, location, and predictors of bleeding in the 2 treatment groups. A total of 1,222 patients were assigned to a TEE guided or conventional strategy and followed over 8 weeks. We present data on major and minor adjudicated bleeding complications for the 2 study groups during the 8-week study period. Composite major and minor bleeding complications occurred in 51 of 1,222 patients (4.2%) and were significantly lower in the TEE guided group compared with the conventional group (2.9 vs 5.5%, p = 0.025). The TEE group had fewer cancellations of cardioversion as a result of bleeding (0% vs 0.7%, p = 0.003). Major (n = 14) and minor (n = 38) bleeding complications were predominantly gastrointestinal (71.4% and 31.6%, respectively) and were associated with warfarin use. Predictors of bleeding included patient age, conventional group assignment, inpatient status, and functional status. Thus, composite major and minor bleeding complications occurred in 4.2% of the 1,222 patients and were significantly lower in the TEE guided group compared with the conventional group. Treatment variables affecting length of anticoagulant therapy in the conventional arm combined with advancing age and functional status are important concerns in patients who undergo cardioversion of atrial fibrillation.

Serum testosterone associates with lower high-density lipoprotein cholesterol in black and white males, 10 to 15 years of age, through lowered apolipoprotein AI and AII concentrations.

High-density lipoprotein cholesterol (HDL-C) concentrations decrease during adolescence in males in association with increasing pubertal maturation and free testosterone (F-T). To determine whether F-T effects lower HDL-C levels by decreasing the amount of cholesterol associated with the major protein moeities associated with HDL-C (apolipoprotein [apo]AI and AII) or by decreasing the concentrations of these proteins, we studied 251 black and 285 white boys, ages 10 to 15 years. In cross-sectional analysis, advancing puberty associated with decreasing HDL-C, apoAI, and apoAII in boys of each ethnic group. The decreases were greater in white (1.49 to 1.24 mmol/L) than black boys (1.68 to 1.53 mmol/L). Backward stepwise regression analyses indicated that F-T was a significant negative predictor of all 3 lipid parameters--HDL-C, apoAI, and apoAII. Ethnic group was associated with HDL-C (blacks higher) and apoAII (whites higher), but not apoAI. The ratio of HDL-C to apo (AI+AII) varied significantly (and negatively) with body mass index (BMI; kg/m(2)), but not with pubertal stage or F-T. Thus, increased F-T appears to explain decreased HDL-C via decreased apoAI and apoAII, not decreases in the amount of cholesterol associated with these proteins.