Impact of radiation therapy and extent of resection for ependymoma in young children: A population-based study.

BACKGROUND: Young children with posterior fossa ependymoma (PF-EPN) have a worse prognosis than older children, and they have a unique molecular profile (PF-EPN-A subtype). Alternative treatment strategies are often used in these young patients, and their prognostic factors are less clear. METHODS: We characterized the prognostic factors and treatment outcomes of 482 patients between ages 0 and 3 years with the diagnosis of ependymoma identified from the Surveillance, Epidemiology, and End Results registry (1973-2013). RESULTS: Radiation therapy (RT) was delivered to 52.3% of patients, and gross total resection (GTR) was performed in 51.0% of patients. Overall survival (OS) at 10 years was 48.4% with median follow-up of 3.3 years. WHO grade was not predictive of OS. Extent of resection was significant for survival; the 10-year OS with GTR was 61.0%, and with subtotal resection (STR) and biopsy was 38.2% and 35.0%, respectively (P < 0.001). RT significantly benefitted OS for both grades II and III. The 10-year OS for grade II was 50.5% with RT and 43.4% without (P = 0.030); 10-year OS for grade III was 66.0% with RT and 40.0% without (P = 0.002). Multivariate analysis showed significantly improved OS with RT (hazard ratio [HR] 0.601, 95% CI: 0.439-0.820, P = 0.001) and GTR (HR 0.471, 95% CI: 0.328-0.677, P < 0.0001). CONCLUSIONS: Ependymoma outcomes in patients within 0-3 years of age significantly improved with RT and GTR. Histopathologic grading of ependymoma demonstrated no prognostic significance. Given the poor OS for this population and unique genetic profile, future prospective studies with molecular-based stratification should be performed to evaluate additional prognostic factors.

Within-session changes in responding during concurrent variable interval variable ratio schedules.

Rats (Experiment 1) and pigeons (Experiment 2) responded on several concurrent variable interval (VI) variable ratio (VR) schedules. The rate of, but not the time spent, responding in each component usually changed within-sessions. The bias and sensitivity parameters of the generalized matching law (GML) did not change systematically within-sessions. The fit of the GML to the data did not change within-sessions for pigeons, but it was better in the middle than at the beginning or end of the session for some for rats. Both over- and under-matching occurred. These results imply that within-session changes in responding do not usually cause problems for assessing the validity of the GML when subjects respond on concurrent VI VR schedules. The results also suggest that under- and over-matching are not produced by different factors, but rather lie on a continuum.

Criticisms of the satiety hypothesis as an explanation for within-session decreases in responding.

The authors of four papers recently reported that satiation provides a better explanation than habituation for within-session decreases in conditioned responding. Several arguments question this conclusion. First, the contribution of habituation to within-session changes in responding seems clearly established. Information that is consistent with habituation, but that is difficult to reconcile with satiation, is not adequately addressed. Second, the limited evidence offered in support of satiation is ambiguous because the results are just as compatible with habituation as with other satiety variables. Finally, the term satiation is used in an intuitive way that is sometimes contradicted by research about the termination of ingestion. Use of the technical term satiation in a way that differs from its conventional usage will only isolate operant psychology from other areas of psychological research.

Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine.

BACKGROUND: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure. METHODS: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography. RESULTS: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries. CONCLUSIONS: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.

Nail changes associated with scleroderma: a case report.

A case report and literature review on the association of nail changes and scleroderma was presented. The exact etiology of these nail changes seen in scleroderma and of the disease entity itself, has not yet been determined. The current treatment regimen, which is at best supportive, was discussed. Proper treatment of the nail changes depends on a good understanding of what to expect as the disease or condition progresses to its later stages. The extent and severity of the onychodystrophy can be correlated with the duration of the disease. Nonetheless, there are still questions that remain to be answered regarding the nail changes associated with scleroderma. For example, are these nail changes the result of Raynaud's phenomenon and its associated arterial insufficiency, or are they a normal sequelae of the integumentary degeneration so characteristic of scleroderma? Whatever the answer may be, it should be recognized that these changes are a source of clinical concern. Practitioners should take note of this clinical entity and record their findings so that these perplexing questions, as well as many others, may be discussed in the future.

Ventricular fibrillation survivors in whom tachyarrhythmia cannot be induced: outcome related to selected therapy.

Eight-five patients were studied to determine the prognosis of the ventricular tachyarrhythmias at the time of electrophysiologic study. Twenty-five patients (29%) were not inducible when we used a stimulation protocol consisting of up to four extrastimuli delivered at two right ventricular sites. Patients with no inducible arrhythmias were younger (53 vs 59 yrs; p = .06) and had higher ejection fractions (.49 vs .34; p less than .04) than the inducible ventricular fibrillation survivors. Sex, cardiac diagnosis, time from event to electrophysiologic study, and antiarrhythmic therapy at the time of event did not discriminate between those with and those without inducible ventricular tachyarrhythmias. Survival free of recurrent sudden death or ventricular tachycardia was .86 +/- .05 and .95 +/- .05 for patients with and without inducible tachyarrhythmias, respectively (p = .22). Nine of 25 (36%) patients with no inducible arrhythmias developed inducible ventricular tachyarrhythmias when testing was repeated with an antiarrhythmic drug. Ventricular fibrillation survivors not inducible at the time of programmed ventricular stimulation (using a stimulation protocol consisting of four extrastimuli delivered at two right ventricular sites) seem to have a good prognosis. Many "noninducible" patients develop inducible tachyarrhythmias when placed on antiarrhythmic therapy. Because it is possible that these drugs are proarrhythmic, empiric antiarrhythmic therapy should be avoided in these patients.

Reproducibility of arrhythmia induction with intracardiac electrophysiologic testing: patients with clinical sustained ventricular tachyarrhythmias.

In order to characterize the day to day reproducibility of arrhythmias provoked during electrophysiologic stimulation, 114 patients with documented sustained clinical ventricular tachyarrhythmias were studied. Two baseline electrophysiologic tests were performed in the drug-free state and within 6 to 24 hours of one another. There was a significant increment (p less than or equal to 0.02) in the induction of sustained ventricular tachyarrhythmias as the number of programmed extrastimuli increased from one (10% induction) to four (64% induction). Provoked arrhythmias were observed to be more frequently nonreproducible (as reflected in a major change in rate or duration, or both, of an induced ventricular arrhythmia between baseline tests) as the number of extrastimuli increased from one (7%) to four (27%). Nonreproducibility with three and four extrastimuli was not significantly greater than when two extrastimuli were utilized. Electrophysiology-directed drug trials should be interpreted in light of this observed variability in induced arrhythmias.

Application of clinically valid cardiac risk factors to aortic aneurysm surgery.

The operative outcome of 97 consecutive nonruptured infrarenal aortic aneurysms is analyzed regarding clinically identifiable cardiac risk factors. Clinically evident coronary artery disease was present in 45 patients (46%). Operative mortality was 4% (four cardiac deaths) with an additional 4% nonfatal postoperative myocardial infarction rate. All cardiac complications occurred in patients with clinically evident coronary artery disease, while no mortality occurred in 52 patients lacking a preoperative history of myocardial infarction, congestive heart failure, or angina. Preoperative risk factors having a significant negative influence on outcome include a history of prior myocardial infarction and compensated congestive heart failure. Few patients with aneurysms who have clinical evidence of coronary artery disease are indicated for coronary arteriography and bypass prior to aneurysm repair. Furthermore, indications for invasive cardiac screening of the patient with an aneurysm who lacks cardiac symptoms are limited.

Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement.

From 1962-1977, 99 patients, mean age 65 +/- 0.5 years (range 60-81 years) underwent valve replacement for severe calcific aortic valve stenosis. Ninety-three percent of the patients were in New York Heart Association functional class III or IV. The aortic valve gradient was 76 +/- 3 mm Hg and the aortic valve area index was 0.34 +/- 0.01 cm2/m2. Left ventricular systolic pressure was 207 +/- 4 mm Hg, cardiac index was 2.5 +/- 0.1 l/min/m2, left ventricular ejection fraction was 0.57 +/- 0.02 and left ventricular end-diastolic volume index was 108 +/- 60 ml/m2; left ventricular ejection fraction and end-diastolic volume were normal in 63% of the patients. The operative mortality was 16%. Mean follow-up is 55 +/- 4 months. Using life-table analysis, the 10-year survival, excluding cardiac deaths, is 57.5 +/- 7%. Ninety-one percent of the survivors are in functional class I or II. We conclude that the left ventricular function is normal in two-thirds of elderly patients with severe aortic valve stenosis. After valve replacement, the 10-year survival is most encouraging and most of the survivors are functionally improved.

A prospective study of sudden death in "high-risk" bundle-branch block.

We prospectively followed 257 patients with bifascicular and trifascicular conduction-system disease and intact atrioventricular conduction who had undergone His-bundle studies. Forty-seven per cent had associated coronary-artery disease, and 23 per cent primary conduction-system disease. His-ventricular interval was moderately prolonged in 43 per cent and markedly prolonged in 12 per cent. During an average follow-up period of 25 months 50 patients died. However, death was sudden in only 27, and 17 of the sudden deaths were not due to bradyarrhythias. Actuarial analysis showed an overall mortality rate (mean +/- S.E.) of 19 +/- 2.6 per cent at two years, mortality from sudden death being 10 +/- 2.6 per cent. Permanent heart block occurred in 12. No clinical symptoms (including syncope), electrocardiographic findings, electrophysiologic data or their combination identified patients at high risk of sudden death. Sudden death due to bradyarrhythmia is uncommon in patients with bundle-branch block and intact atrioventricular conduction. Therefore, routine prophylactic use of permanent pacemakers in all such patients is inappropriate. Pacemaker implantation should be reserved for those with documented symptomatic bradyarrhythmias.

Frequency and significance of coronary arterial dominance in isolated aortic stenosis.

Myocardial infarction during aortic valve replacement has previously been reported to result from obstruction of a branch of the left main coronary artery by the perfusion cannula. Patients with a dominant left coronary arterial system may be at greater risk. To assess the frequency and significance of a dominant left coronary arterial system the coronary angiograms of 75 consecutive patients more than 34 years of age with isolated aortic stenosis were studied and compared with those of a control group of 150 patients. Among the patients with aortic stenosis, 19 (25 percent) had left dominance, 9 (12 percent) a balanced circulation and 47 (63 percent) a dominant right coronary arterial system. Among control patients, 14 (9 percent) had left dominance 18 (12 percent) a balanced system and 118 (79 percent) right dominance. The increased prevalence of left dominance in patients with aortic stenosis was significant (P less than 0.005). Among patients with aortic stenosis, the left main coronary artery was shorter (P less than 0.01) in those with left dominance (6.2 +/- 1.3 mm [mean +/- standard error]) than in those with right dominance (9.9 +/- 0.7). Sixty-nine patients with aortic stenosis underwent aortic valve replacement. Perioperative myocardial infarction occurred in 4 of 15 (26.7 percent) of those with left dominance and in 4 of 54 (7.4 percent) of those with right dominance or a balanced circulation (P less than 0.05). Perioperative myocardial infarction occurred in all three patients with left dominance and obstructive coronary artery disease. The increased prevalence of a dominant left coronary arterial system in aortic stenosis suggests that this may be part of a developmental complex. Patients with left dominance have a shorter left main coronary artery than patients with right dominance. They also have an increased risk of perioperative myocardial infarction if there is associated obstructive coronary artery disease. Preoperative information about the coronary arterial anatomy and extent of coronary artery disease may be helpful in planning the use of coronary perfusion and other myocardial preservation techniques during surgery in order to reduce the incidence of myocardial infarction.

Left main coronary artery spasm. A potential cause for angiographic misdiagnosis of severe coronary artery disease.

Two patients had catheter-induced spasm of the left main coronary artery during diagnostic coronary arteriography. One patient had no coronary artery disease, and the other had minimal disease of the right coronary artery. Spasm was relieved by nitrates; however, in one patient several doses were needed over 35 minutes. Catheter-induced spasm must be considered in the diagnosis of left main coronary artery disease, particularly on a patient with isolated left main coronary artery disease.