Linda Sanders

PURPOSE: Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation response. These trials, however, generally lacked rigorous thermal dose prescription and administration. We report the final results of a prospective randomized trial of superficial tumors (</= 3 cm depth) comparing radiotherapy versus HT combined with radiotherapy, using the parameter describing the number of cumulative equivalent minutes at 43 degrees C exceeded by 90% of monitored points within the tumor (CEM 43 degrees C T(90)) as a measure of thermal dose. METHODS: This trial was designed to test whether a thermal dose of more than 10 CEM 43 degrees C T(90) results in improved complete response and duration of local control compared with a thermal dose of </= 1 CEM 43 degrees C T(90). Patients received a test dose of HT </= 1 CEM 43 degrees C T(90) and tumors deemed heatable were randomly assigned to additional HT versus no additional HT. HT was given using microwave spiral strip applicators operating at 433 MHz. RESULTS: One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned. The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7 (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the HT arm. No overall survival benefit was seen. CONCLUSION: Adjuvant hyperthermia with a thermal dose more than 10 CEM 43 degrees C T(90) confers a significant local control benefit in patients with superficial tumors receiving radiation therapy.

To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.

BACKGROUND: Although serotonin has been postulated as an etiologic agent in the development of carcinoid heart disease, no direct evidence for different ambient serotonin levels in cardiac and noncardiac patients has been reported to date. METHODS AND RESULTS: The present study reviews our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite, 5-hydroxyindole acetic acid (5-HIAA). No significant demographic differences existed between the cardiac and noncardiac groups; however, typical carcinoid syndrome symptoms (ie, flushing and diarrhea) were almost threefold more common in the cardiac group (P < .001). Compared with the noncardiac group, heart disease patients demonstrated strikingly higher (P < .0001) mean serum serotonin (9750 versus 4350 pmol/mL), plasma serotonin (1130 versus 426 pmol/mL), platelet serotonin (6240 versus 2700 pmol/mg protein), and urine 5-HIAA (219 versus 55.3 mg/24 h) levels. The spectrum of heart disease among the 19 patients showed a strong right-sided valvular predominance, with tricuspid regurgitation being the most common valvular dysfunction (92% by cardiac catheterization; 100% by echocardiogram). CONCLUSIONS: These data suggest that serotonin plays a major role in the pathogenesis of the cardiac plaque formation observed in carcinoid patients.