Effects of body size on operative, intermediate, and long-term outcomes after coronary artery bypass operation.

BACKGROUND: To investigate the role of body size, if any, on operative and longer term outcomes following coronary artery surgery. METHODS: A total of 3,560 consecutive patients undergoing coronary artery bypass grafting from 1991 to 1997, including 2,401 (67%) males and a mean +/- SD age of 63 +/- 10 years were ranked based on their body mass index (BMI). The association in these patients of preoperative, long-term, and economic data with variations in BMI were studied using regression analyses. Long-term survival was studied using 5-year Kaplan-Meier survival analysis. RESULTS: Operative mortality, myocardial infarction, cerebrovascular accidents, blood transfusions, and length of hospital stay were all increased in the smallest patients (BMI < or = 24 kg/m2). Obesity did not increase adverse operative outcomes except for a greater rate of sternal wound infections occurring with increasing severity of obesity. Direct variable costs were lowest in patients clustered around normal BMI, with cost increasing similarly at low and high extremes. This effect was correlated with similar BMI effects on ventilatory and intensive care requirements. Excluding operative mortality, 5-year survival trends were similarly worse for the smallest (BMI < or = 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI > or = 30 to BMI < 34) did not affect long-term survival. CONCLUSIONS: Among study patients, immediate operative outcomes were adversely affected by small body size, which reflected older age (66 +/- 10 years) and an exaggerated adverse impact of cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass lead to better operative outcomes in the obese. Long-term outcomes were, however, suboptimal in severely obese patients although that group was the youngest (60 +/- 10 years). In addition to their large body habitus, other factors, including substantial prevalence of diabetes, insulin dependence and hypertension, probably played a significant role in the poor long-term outcome in the severely obese.

Predictors of gastrointestinal complications in cardiac surgery.

Gastrointestinal problems are infrequent but serious complications of cardiac surgery, with high rates of morbidity and mortality. Predictors of these complications are not well developed, and the role of fundamental variables remains controversial. In a retrospective review of our cardiac surgery experience from July 1991 through December 1997 we found that postoperative gastrointestinal complications were diagnosed in 86 of 4,463 consecutive patients (1.9%). We categorized these 86 patients into 2 groups--Surgical and Medical--according to the method of treatment used for their complications. In the Medical group, 9 of 52 patients (17%) died; in the Surgical group, 17 of 34 (50%) died. By logistic multivariate analysis, we identified 8 parameters that predicted gastrointestinal complications: age greater than 70 years, duration of cardiopulmonary bypass, need for blood transfusions, reoperation, triple-vessel disease, New York Heart Association functional class IV, peripheral vascular disease, and congestive heart failure. Postoperative re-exploration for bleeding was a predictor specific to the Surgical group. Use of an intraaortic balloon pump was markedly higher in the Gastrointestinal group than in the Control group (30% vs 10%, respectively), as was the use of inotropic support in the immediate postoperative period (27% vs 5.6%). Our results suggest that intra-abdominal ischemic injury is a likely contributing factor in most gastrointestinal complications. In turn, the ischemia is probably caused by hypoperfusion due to low cardiac output, hypotension due to blood loss, and intra-abdominal atheroemboli. The derived models are useful for identifying patients whose risk of gastrointestinal complications after cardiac surgery may be reduced by clinical measures designed to counter these mechanisms.

Resource utilization in coronary artery bypass operation: does surgical risk predict cost?

BACKGROUND: Current healthcare trends may render financial risk of cardiac operation a key component of clinical decision making. It has been suggested, based on large cohorts of patients stratified by clinical risk, that the cost of operation can be predicted from models of clinical risk since length of stay (LOS) is highly correlated to clinical risk, and LOS is correlated to hospital costs and charges. Direct correlation of actual surgical costs with surgical risk are lacking. METHODS: Variable direct costs, LOS, and The Society of Thoracic Surgeons predicted mortality risk [STS risk (%)] were collected and analyzed in 628 consecutive patients undergoing coronary artery bypass grafting (CABG) at our institution in 1997. RESULTS: Cost of CABG had a near-normal distribution, and cost in 21 outlier patients (cost > two standard deviations above the mean) was an average 5.3 times normal (median cost). For individual patients, cost was well correlated to LOS (R2 = 0.48) but not with STS risk (R2 = 0.12). LOS was also poorly predicted by STS risk (R2 = 0.09). However, despite its poor prediction of cost, STS risk was an unbiased estimator over the entire population. A result manifested, when patients were grouped into similar risk (<1%, 1-2%, 2+ -3%, 3+ -5%, 5+ -10%, and >10%) cohorts, by high correlation between cost and STS risk (R2 = 0.99), cost and LOS risk (R2 = 0.99), and LOS and STS risk (R2 = 0.97). CONCLUSIONS: Our data demonstrated that, in large CABG cohorts, surgical risk models can accurately predict cost of CABG. However, despite a trend for increasing cost with increasing STS risk, surgical risk models based on preoperative data are poor predictors of cost in individual patients. Use of these models should be limited to analysis of cost trends in cardiac operation, but not for predicting financial risk in individual patients during clinical decision making.

Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma.

Normal bronchial epithelial cells (NBECs) are at risk for damage from inhaled and endogenous oxidative species and from epoxide metabolites of inhaled polycyclic aromatic hydrocarbons. Epidemiological and in vitro data suggest that interindividual variation in this risk may result from variation in NBEC expression of enzymes that inactivate reactive species by conjugating them to glutathione. Quantitative competitive reverse transcription-PCR was used to measure mRNA levels of glutathione transferases (GSTs) and glutathione peroxidases (GSHPxs) in primary NBECs from subjects with or without bronchogenic carcinoma. Mean expression levels (mRNA/10(3) beta-actin mRNA) in NBECs from 23 subjects without bronchogenic carcinoma compared to those from 11 subjects with bronchogenic carcinoma respectively (in parentheses) were: mGST (26.0, 6.11), GSTM3 (0.29, 0.09), combined GSTM1,2,4,5 (0.98, 0.60), GSTT1 (0.84, 0.76), GSTP1 (287, 110), GSHPx (140, 62.1), and GSHPxA (0.43, 0.34). Levels of GSTP1, GSTM3, and GSHPx were significantly (P < 0.05) lower in NBECs from subjects with bronchogenic carcinoma. Further, the gene expression index formed by multiplying the values for mGST x GSTM3 x GSHPx x GSHPxA x GSTP1 had a sensitivity (90%) and specificity (76%) for detecting NBECs from bronchogenic carcinoma subjects that was better than any individual gene. In cultured NBECs derived from eight individuals without bronchogenic carcinoma and incubated under identical conditions such that environmental effects were minimized, the mean level of expression and degree of interindividual variation for each gene evaluated was less than that observed in primary NBECs. Data from these studies support the hypotheses that (a) interindividual variation in risk for bronchogenic carcinoma results in part from interindividual variation in NBEC expression of antioxidant genes; (b) gene expression indices will better identify individuals at risk for bronchogenic carcinoma than individual gene expression values; and (c) both hereditary and environmental exposures contribute to the level of and interindividual variation in gene expression observed in primary NBECs. Many epidemiological studies have been designed to evaluate risk associated with polymorphisms or gene expression levels of putative susceptibility genes based on measurements in surrogate tissues, such as peripheral blood lymphocytes. Based on data presented here, it will be important to include the assessment of NBECs in future studies. Measurement of antioxidant gene expression in NBECs may identify the 5-10% of individuals at risk for bronchogenic carcinoma. Bronchoscopic sampling of NBECs from smokers and ex-smokers then will allow susceptible individuals to be entered into surveillance and/or chemoprevention studies.

Anatomic considerations of a modified anterior approach to the cervicothoracic junction.

The results of a study on 30 adult human cadavers showed that the anterior aspect of T-3 can be easily exposed through a modified anterior approach to the cervicothoracic spinal junction. Anterior exposure of T-4 caused significant tension on the brachiocephalic vein in 57%; in 7% the vein actually tore. The location of the vital structures is as follows: the left brachiocephalic vein is at T-1 and T-2 in 80%; the aortic arch is at T-2 and T-3 in 90%; the right recurrent laryngeal nerve reaches the tracheoesophageal groove at the level of C-6 in 50%; the thoracic duct empties into the systemic venous system from C-7 to T-2. Adequate exposure of the low cervical to the upper thoracic spine can be obtained with this approach. Preoperative computed tomographic evaluation of the location of the left brachiocephalic vein with respect to the vertebral levels is recommended.

The gene expression index c-myc x E2F-1/p21 is highly predictive of malignant phenotype in human bronchial epithelial cells.

Recent methodological developments allow expression measurement of many genes simultaneously, thereby revealing patterns of gene expression that can be related to phenotype. We hypothesized that through the use of such methods we could identify patterns of gene expression associated with the malignant phenotype in human bronchial epithelial cells (BEC). To test this hypothesis, a recently developed quantitative reverse transcriptase polymerase chain reaction method was used to assess simultaneously expression of 15 genes mechanistically associated with cell-cycle control (c-myc, E2F-1, p21, rb, PCNA, cyclin D2, cyclin D3, cyclin E, cdc2, CDK2, CDK4, mad, max p21, max p22, and p53) in normal cell cultures from five individuals and in nine different malignant BEC lines. Relative to the mean expression levels in cultured normal cell populations, expression of c-myc, E2F-1, PCNA, cyclin E, and CDK4 messenger RNA (mRNA) were significantly increased and expression of p21 and p53 mRNA were significantly decreased in one or two, but not all three subtypes (squamous, adenocarcinoma and small cell) of carcinoma cell lines evaluated. No single cell-cycle control gene discriminated all three subtypes from normal cell populations. In contrast, the gene expression index c-myc x E2F-1/p21 separated all carcinoma cell lines from all normal cell populations initially evaluated. This malignancy index was validated in an additional three cultured normal BEC and three carcinoma cell lines, as well as three pairs of matched primary normal bronchial epithelial and primary bronchogenic carcinoma samples, and three pairs of matched primary normal lung parenchyma and primary bronchogenic carcinoma tissue. Again, the c-myc x E2F-1/ p21 index successfully discriminated all cultured and primary normal from malignant samples and thereby had a predictive value of 1 (no false positives and no false negatives). We hypothesize that because of functional mutations in cell-cycle regulatory genes (e.g., p53 and/or rb), cells lose the ability to maintain a pattern of gene expression mechanistically associated with normal, division-limited homeostatic equilibrium. Because the c-myc x E2F-1/p21 gene expression index has high specificity for malignant tissue, it will allow confirmation that there is a significant amount of tumor tissue present in small (e.g., fine-needle) biopsy specimens prior to evaluating them for expression of other genes, such as those involved in chemoresistance or radioresistance. In addition, the goal of most gene therapy efforts is to alter levels of gene expression quantitatively. This index and others derived in a similar manner may better define potential gene therapy targets as well as response of targeted genes to therapy.

Preliminary results of neoadjuvant paclitaxel and carboplatin in the treatment of early stage non-small cell lung cancer.

The purpose of this study is to determine the feasibility of delivering neoadjuvant paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin to patients with clinical early stage (stage I and II) non-small cell lung cancer. Although neoadjuvant chemotherapy appears to prolong survival in patients with stage IIIA non-small cell lung cancer, several studies have demonstrated an increase in perioperative mortality associated with this approach. This study is designed to address whether three cycles of paclitaxel (200 mg/m2/3 hour, day 1) and carboplatin (area under the concentration-time curve 5, day 2) can be given preoperatively to patients with clinical stage I and II non-small cell lung cancer and to assess the associated toxicities, pathologic response rate, disease-free survival, and overall survival of this group of patients. Thus far, five patients have been enrolled. Three have successfully undergone resection, with no perioperative complications noted. One patient had a pathologic complete remission and two had pathologic partial remissions. Preliminary results indicate that this approach is well tolerated and results in major tumor response.

Safety profile of cefprozil.

The clinical and laboratory safety of cefprozil was analyzed with data from 4,227 patients who received the drug in North American and European clinical efficacy trials. Of these patients, 3,016 adults and children received capsules or tablets, while 1,211 patients (mostly children) were treated with cefprozil suspension. Cefprozil was used in single-daily or twice-daily dosing regimens for treatment of infections of the upper and lower respiratory tracts, sinuses, middle ear, urinary tract, and skin and skin structure. The incidence of adverse clinical events and laboratory abnormalities was similar to that associated with use of other oral cephalosporins. Gastrointestinal adverse effects were the predominant adverse clinical event, although the incidence of diarrhea with cefprozil was much lower than that with cephalosporins that are less well absorbed. The data confirm the safety of cefprozil in both adult and pediatric patients.

Cefprozil versus cefaclor in the treatment of mild to moderate skin and skin-structure infections. The Cefprozil Multicenter Study Group.

In a multicenter study, 598 patients with skin or skin-structure infections were randomly assigned to receive 500 mg of cefprozil once daily (or 20 mg/kg once daily) or 250 mg of cefaclor three times daily (or 20 mg/kg daily in three equal doses) for 5 to 10 days. Treatment was evaluated in 212 cefprozil-treated patients and in 210 cefaclor-treated patients. The patients were aged 2 to 99 years (mean, 28 years) and their primary diagnoses were impetigo (in 99 patients), pyoderma (in 98), superficial abscess (in 70), and cellulitis (in 64). A satisfactory clinical response was found in 93% of the cefprozil-treated patients and in 92% of the cefaclor-treated patients, the pathogens were eradicated in 91% and 89%, and overall treatment was rated effective in 87% of both groups. Adverse clinical events were reported by 5% of the patients in both groups; one cefprozil-treated patient and three cefaclor-treated patients withdrew from treatment because of adverse events. It is concluded that cefprozil administered once daily is as effective and safe as cefaclor administered three times daily in the treatment of mild to moderate skin and skin-structure infections.

A noncomparative study of cefprozil at two dose levels in the treatment of acute uncomplicated bacterial sinusitis.

The efficacy and safety of cefprozil at two dose levels were evaluated in 110 patients with acute uncomplicated bacterial sinusitis in an uncontrolled, noncomparative, Phase II trial. Ninety patients received 250 mg of cefprozil (low-dose group) and 20 patients received 500 mg of cefprozil (high-dose group) every 12 hours for ten days. Evaluable patients had symptoms consistent with acute sinusitis, pathogens isolated at pretreatment susceptible to cefprozil, and a radiograph positive for sinusitis within 48 hours before treatment. A satisfactory clinical response was achieved in 34 of 39 evaluable patients (87%) in the low-dose group and in all 16 evaluable patients (100%) in the high-dose group. Pathogens were eradicated in 35 of 39 patients (90%) in the low-dose group and in 15 of 16 patients (94%) in the high-dose group. A total of 140 of 155 pathogens (90%) isolated pretreatment were susceptible to cefprozil. Six patients (7%) in the low-dose group and one patient (5%) in the high-dose group reported at least one adverse clinical event.

Cefprozil versus cefaclor in the treatment of acute and uncomplicated urinary tract infections. Cefprozil Multicenter Study Group.

Cefprozil is a new oral cephalosporin with an in vitro spectrum of activity that includes the pathogens most commonly associated with acute and uncomplicated urinary tract infections (UTIs). A multicenter, randomized study was conducted to compare the clinical efficacy and safety of cefprozil, administered once daily, with cefaclor, administered three times a day, for ten days in patients 2 years of age or older who had acute and uncomplicated UTIs. The rate of satisfactory clinical response in evaluable patients was 87% in the cefprozil group and 84% in the cefaclor group. The patient bacteriologic response rates were also similar: 83% for cefprozil and 85% for cefaclor. The overall effective response rate for both cefprozil and cefaclor was 77%. Both drugs were well tolerated, with no difference in the incidence of drug-related adverse events. Because of its efficacy and once-daily dosing regimen, cefprozil may be an alternative to currently available oral antibiotics in the treatment of UTIs.

Probability of rupture of an abdominal aortic aneurysm after an unrelated operative procedure: a prospective study.

It has been assumed by some authors that patients with abdominal aortic aneurysms may be at increased risk of rupture after unrelated operations. From July 1986 to December 1989, 33 patients (29 men, 4 women) with a known abdominal aortic aneurysm underwent 45 operations. Twenty-eight patients had an infrarenal abdominal aortic aneurysm, and five patients had a thoracoabdominal aneurysm. The abdominal aortic aneurysm ranged in transverse diameter from 3.0 to 8.5 cm (average 5.6 cm). Twenty-seven patients underwent a single operation, and six patients had two or more (range of 1 to 6). Operations performed were abdominal (13); cardiothoracic (9); head/neck (2); other vascular (11); urologic (7); amputation (2); breast (1). General anesthesia was used in 29 procedures, spinal/epidural in 6, and regional/local in 10. One postoperative death occurred from cardiopulmonary failure. One patient died of a ruptured abdominal aortic aneurysm at 20 days after coronary artery bypass (1/33 patients [3%]; 1/45 operations [2%]). Fourteen patients had repair of their abdominal aortic aneurysm at a later date, an average of 18 weeks after operation. Four patients had abdominal aortic aneurysm considered too small to warrant resection (average 3.6 cm). Four patients were considered at excessive risk for elective repair. The five thoracoabdominal aneurysm were not repaired. Four patients are awaiting repair. During this same 40-month period, two other patients, not known to have an abdominal aortic aneurysm, died of a ruptured abdominal aortic aneurysm after another operative procedure, at 21 days and 77 days. All three ruptured abdominal aortic aneurysms were 5.0 cm or greater in transverse diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamics alter arterial low-density lipoprotein metabolism.

We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels.

Hemodynamic consequences of Foley catheter control in experiment penetrating cardiac wounds.

Insertion of the Foley catheter has been recommended to control bleeding from penetrating cardiac wounds. Potential complications from this maneuver include enlargement of the tear in the myocardium or further impediment to cardiac function by the balloon. This study was done to evaluate the hemodynamic consequences of the balloon catheter when it was used to control bleeding in cardiac stab wounds created in pigs. A significant decrease in cardiac function occurred with control of the bleeding by the balloon catheter. This effect was dependent on the size of the balloon and cardiac location.

Hemodynamic effects on endothelial cell monolayer detachment from vascular prostheses.

The establishment of an early blood-contacting endothelialized surface may improve the graft-host relationship. This study evaluated the adherence of indium 111-radiolabeled endothelial cells that were cultured to confluence on fibronectin-treated polyester elastomer (Hytrel) grafts that were perfused for two hours on a pulse duplicator apparatus under high- and low-shear conditions. Perfusate samples were serially assayed for radioactivity. After perfusion, grafts were sectioned into four segments and assayed for retained radioactivity. All graft segments were hematoxylin stained and examined under light microscopy for evaluation of cell density. Excellent endothelial cell adherence (90%) was observed under both hemodynamic conditions at 120 minutes, with most losses occurring within the first 15 minutes. No differences were seen between high- and low-shear conditions or proximal vs distal graft segments.