Short-term outcomes of craniotomy for malignant brain tumors in the elderly.

BACKGROUND: Disparity in resection rates for malignant brain tumors in elderly patients is partially attributed to a belief that advanced age is associated with an increased risk of postoperative morbidity and mortality. The objective of this study was to investigate the effect of advanced age (≥75 years) on 30-day outcomes in patients with primary and metastatic brain tumors who underwent craniotomy for definitive resection of a malignant brain tumor. METHODS: The authors conducted prospective analyses of the American College of Surgeons' National Surgical Quality-Improvement Project (NSQIP) database from 2006 to 2010 of 970 patients aged ≥40 years who underwent craniotomy for definitive resection of neoplasm. Preoperative and intraoperative characteristics and 30-day outcomes were stratified by age. By using propensity scores, 134 patients (aged ≥75 years) were matched to 134 patients ages 40 to 74 years. Logistic regression was used to predict adverse postoperative outcomes. RESULTS: The median length of hospital stay was 5 days; the rate of minor and major complications were 5.9% and 13.1%, respectively; 5.7% of patients returned to the operating room; and 4.3% of patients died within 30 days. Advanced age did not increase the odds for poorer short-term outcomes. CONCLUSIONS: Advanced age did not increase the risk of poor outcomes after surgical resection of primary or metastatic intracranial tumors when analyses were controlled for other risk factors. These results suggest that age should not be used, in isolation, as an a priori factor to discourage pursuing craniotomy.

Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients.

Oxidative abnormalities precede clinical and pathological manifestations of Alzheimer's disease and are the earliest pathological changes reported in the disease. The olfactory pathways and mucosa also display the pathological features associated with Alzheimer's disease in the brain. Olfactory neurons are unique because they can undergo neurogenesis and are able to be readily maintained in cell culture. In this study, we examined neuronal cell cultures derived from olfactory mucosa of Alzheimer's disease and control patients for oxidative stress responses. Levels of lipid peroxidation (hydroxynonenal), N(epsilon)-(carboxymethyl)lysine (glycoxidative and lipid peroxidation), and oxidative stress response (heme oxygenase-1) were measured immunocytochemically. We found increased levels for all the oxidative stress markers examined in Alzheimer's disease neurons as compared to controls. Interestingly, in one case of Alzheimer's disease, we found hydroxynonenal adducts accumulated in cytoplasmic lysosome-like structures in about 20% of neurons cultured, but not in neurons from control patients. These lysosome-like structures are found in about 100% of the vulnerable neurons in brains of cases of Alzheimer's disease. This study suggests that manifestations of oxidative imbalance in Alzheimer's disease extend to cultured olfactory neurons. Primary culture of human olfactory neurons will be useful in understanding the mechanism of oxidative damage in Alzheimer's disease and can even be utilized in developing therapeutic strategies.

Effect of smoking on the perioperative outcomes of patients who undergo elective spine surgery.

STUDY DESIGN: Retrospective analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement database. OBJECTIVE: We assessed whether preoperative cigarette smoking and smoking duration predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. SUMMARY OF BACKGROUND DATA: Prior studies have assessed the association of smoking and long-term outcomes for a number of spine surgery procedures, with conflicting findings. The association between smoking and 30-day outcomes for spine surgery is unknown. METHODS: A total 14,500 adults, classified as current (N = 3914), prior (N = 2057), and never smokers. Using propensity scores, current and prior smokers were matched to never smokers. Logistic regression was used to predict adverse postoperative outcomes. The relationship between pack-years and adverse outcomes was tested. Sensitivity analyses were conducted limiting the study sample to patients who underwent spine fusion (N = 4663), and using patient subgroups by procedure. RESULTS: In unadjusted analyses, prior smokers were significantly more likely to have prolonged hospitalization (1.2, 95% confidence interval [CI]: 1.1-1.3) and major complications (1.3, 95% CI: 1.1-1.6) compared with never smokers. No association was found between smoking status and adverse outcomes in adjusted, matched patient models. Current smokers with more than 60 pack-years were more likely to die within 30 days of surgery (3.0, 95% CI, 1.1-7.8), compared with never smokers. Sensitivity analyses confirmed these findings. CONCLUSION: The large National Surgical Quality Improvement population was carefully matched for a wide range of baseline comorbidities, including 29 variables previously suggested to influence perioperative outcomes. Although previous studies conducted in subgroups of spine surgery patients have suggested a deleterious effect for smoking on long-term outcomes in patients undergoing spine surgery, our analysis did not find smoking to be associated with early (30 d) perioperative morbidity or mortality.

Preoperative anemia and perioperative outcomes in patients who undergo elective spine surgery.

STUDY DESIGN: Analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. OBJECTIVE: To assess whether preoperative anemia predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. SUMMARY OF BACKGROUND DATA: Prior studies have assessed the association of anemia with outcomes in various noncardiac surgical procedures. The association between preoperative anemia and 30-day outcomes for spine surgery is unknown. METHODS: A total of 24,473 adults, classified as having severe (N = 88), moderate (N = 314), mild (N = 5477), and no anemia. Using propensity scores, patients with severe, mild, and moderate anemia were matched with patients with no anemia. Logistic regression was used to predict adverse postoperative outcomes. Sensitivity analyses were conducted limiting the study sample to patients who did not receive intra- or postoperative transfusion and to patients with and without preoperative cardiovascular comorbidities. RESULTS: Patients with all levels of anemia had significantly higher risk of nearly all adverse outcomes than nonanemic patients in unadjusted and propensity-matched models. Patients with moderate and mild anemia were more likely to have prolonged length of hospitalization, experience 1 or more complications, and expire within 30 days of surgery compared with nonanemic patients. The association between anemia and adverse outcomes was found independently of intra- and postoperative transfusions, and was not more pronounced in patients with preoperative cardiovascular comorbidities. CONCLUSION: All levels of anemia were significantly associated with prolonged length of hospitalization and poorer operative or 30-day outcomes in patients undergoing elective spine surgery. Our findings, using a large multi-institutional sample of prospectively collected data, suggests that anemia should be regarded as an independent risk factor for perioperative and postoperative complications that deserves attention prior to elective spine surgery.

Hepatic autoregulation: response of glucose production and gluconeogenesis to increased glycogenolysis.

The effect of increased glycogenolysis, simulated by galactose's conversion to glucose, on the contribution of gluconeogenesis (GNG) to hepatic glucose production (GP) was determined. The conversion of galactose to glucose is by the same pathway as glycogen's conversion to glucose, i.e., glucose 1-phosphate --> glucose 6-phosphate --> glucose. Healthy men (n = 7) were fasted for 44 h. At 40 h, hepatic glycogen stores were depleted. GNG then contributed approximately 90% to a GP of approximately 8 micromol.kg(-1).min(-1). Galactose, 9 g/h, was infused over the next 4 h. The contribution of GNG to GP declined from approximately 90% to 65%, i.e., by approximately 2 micromol.kg(-1).min(-1). The rate of galactose conversion to blood glucose, measured by labeling the infused galactose with [1-(2)H]galactose (n = 4), was also approximately 2 micromol.kg(-1).min(-1). The 41st h GP rose by approximately 1.5 micromol.kg(-1).min(-1) and then returned to approximately 9 micromol.kg(-1).min(-1), while plasma glucose concentration increased from approximately 4.5 to 5.3 mM, accompanied by a rise in plasma insulin concentration. Over 50% of the galactose infused was accounted for in blood glucose and hepatic glycogen formation. Thus an increase in the rate of GP via the glycogenolytic pathway resulted in a concomitant decrease in the rate of GP via GNG. While the compensatory response to the galactose administration was not complete, since GP increased, hepatic autoregulation is operative in healthy humans during prolonged fasting.

Pseudoarthrosis of the cervical spine: a comparison of radiographic diagnostic measures.

STUDY DESIGN: A retrospective review was conducted. OBJECTIVE: To compare the accuracy of two objective radiographic techniques in identifying nonunion after anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: The accuracy of diagnostic methods for detecting pseudarthrosis has been poorly documented. Radiographic criteria mentioned in the literature include perceived motion or change in the Cobb angles between the involved segments on flexion-extension views. METHODS: The participants in this study were 27 patients with 29 cervical fusions ranging from one to three levels. Patients were examined and radiographs obtained. The mean follow-up period was 39 months. Two measurements were obtained from lateral flexion-extension radiographs: Cobb angle and the distance between the tips of the spinous processes of the surgically managed levels. The measurements were obtained independently by three physicians in a blinded fashion. RESULTS: The reliability among the observers, as measured by Cronbach's alpha, was 0.95 for the spinous process method and 0.74 for the Cobb angle method. A measurement of more than 2 mm between spinous processes was noted in patients with a known pseudarthrosis. The Pearson correlation between pseudarthrosis and use of the spinous process method was 0.77 ( < 0.001). The Pearson correlation between pseudarthrosis and use of the Cobb angle method was 0.28 ( > 0.10). The area under the receiver operating characteristic curve for the spinous process method was found to be 0.980, as compared with 0.662 for the Cobb angle method, for the measurement of pseudarthrosis. CONCLUSIONS: Measurement of the change in distance between spinous processes is more reproducible and accurate than the Cobb method for making the diagnosis of pseudarthrosis. The authors believe that the measurement of distances between spinous processes on lateral flexion-extension radiographs should be used as a method for evaluating radiographic fusion in patients with pseudarthrosis.

Oxidative damage in the olfactory system in Alzheimer's disease.

Increased oxidative damage is a prominent and early feature of vulnerable neurons in Alzheimer's disease (AD). However, while damage to proteins, sugars, lipids, nucleic acids and organelles such as lysosomes, mitochondria, and endoplasmic reticulum are evident, the source of increased reactive oxygen species has not been determined. Furthermore, a major limitation in further determining the source, as well as finding a means to arrest damage, is the paucity of cellular models directly homologous to AD since the vulnerable neurons of the brain in AD cannot be studied in vitro. Here, we examined the olfactory epithelium in situ to see if neurons there exhibit a similar pathological oxidative balance to vulnerable neurons in AD. In biopsy specimens, (eight AD and three controls) we found that neurons, and also the surrounding epithelial cells, show an increase in oxidative damage for a subset of the markers increased in the brain of cases of AD. Lipid peroxidation and heme oxygenase-1, a stress response protein, were increased, while nucleic acid or protein oxidation, demonstrated in vulnerable neurons in AD, were not increased. These findings highlight the systemic nature of oxidative abnormalities in AD, but that different cell types may express this abnormality by a different array of oxidative stress markers, supporting the potential for using olfactory neurons or other cells derived from AD patients in culture to understand the mechanistic basis for increased oxidative damage in AD and as a model to screen compounds for therapeutic intervention.

Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation.

Biochemical studies show that phosphorylated tau, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule deficiency in Alzheimer's disease (AD). However, although this issue is one of the most important aspects to further understanding the cell biology of AD, no quantitative examination of microtubule diminution in AD and its relationship with PHFs has been performed. To examine this issue directly, we undertook a morphometric study of brain biopsy specimens from AD and control cases. Ultrastructural analysis of neurons was performed to compare the microtubule assembly state in neurons of diseased and control cases and to examine the effect of PHF accumulation. We found that both number and total length of microtubules were significantly and selectively reduced in pyramidal neurons from AD in comparison to control cases (P = 0.000004) but that this decrement in microtubule density was surprisingly unrelated to PHFs (P = 0.8). Further, we found a significant age-dependent decrease in microtubule density with aging in the control cases (P = 0.016). These findings suggest that reduction in microtubule assembly is not dependent on tau abnormalities of AD and aging.