Patients' and physicians' roles in detecting recurrent Hodgkin lymphoma following complete remission.

BACKGROUND: Optimal post-treatment surveillance for patients with Hodgkin lymphoma in first complete remission (CR) is unknown. Guidelines are based on consensus rather than high-quality evidence. It is unknown if routine screening leads to earlier relapse detection or translates into better outcomes. PATIENTS AND METHODS: We identified 258 patients with relapse after CR and determined whether the recurrence was detected as a result of patient-detected symptoms (PT group) or through exams or tests ordered by the physician in the absence of symptoms (MD group). RESULTS: Of 258 recurrences, 182 (71%) were in the PT group. The median time to diagnosis of recurrence was similar in both groups (PT group = 1.65 years; MD group = 1.95 years; P = 0.69). Neither the postrelapse progression-free (PFS, P = 0.26) nor overall survival (OS, P = 0.40) differed significantly between the groups. CONCLUSION: Patients are much more likely to detect recurrence than their physicians employing routine follow-up testing. There is no difference in PFS or OS between patients whose recurrence is self-diagnosed versus those whose recurrence is diagnosed by physician through routine screening. We found no benefit for detection of HL recurrence in asymptomatic patients and thus cannot support the routine use of costly, anxiety-provoking or potentially harmful tests in the absence of symptoms.

Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia.

OBJECTIVE: The pathophysiology of non-traumatic osteonecrosis (ON) or avascular necrosis (AVN) of the femoral head remains poorly understood. Some studies have suggested the contribution of underlying thrombophilia as a mechanism; however, no specific thrombophilic factor has been consistently found in association with the disease. We are presenting data suggesting a role for endothelial cell activation rather than thrombophilia in ON. METHODS: A prospective consecutive cohort of 49 patients with a diagnosis of ON. The disease was considered idiopathic in five and secondary in 44 patients. The investigation included a coagulation and thrombophilia profile, endothelial cell activation and non-specific inflammatory markers as well as a biochemical profile. Statistical analysis using Fisher's exact test was obtained to assess correlation between endothelial cell markers and variables of inflammation. RESULTS: Patients with non-traumatic ON were not found to have a specific underlying thrombophilic factor compared with the general population. Out of 49 patients,19 had elevation of at least one endothelial cell markers. We found that activation of endothelial cell markers was independently correlated to ON but not correlated to the presence of inflammation (P = 1.0000). CONCLUSION: These results suggest that non-traumatic ON is not associated with a specific thrombophilic abnormality in those affected. This study demonstrates a potential association between regional endothelial dysfunction and ON. More studies are needed at a molecular level to further investigate the specific role of endothelium in the physiopathology of ON. A better understanding of the underlying mechanism could lead to potential preventive and therapeutic strategies of this devastating disease.

Coronary artery bypass graft surgery: do women cost more?

BACKGROUND: Coronary artery bypass graft surgery (CABG) in women has been associated with worse clinical outcomes than CABG in men. However, little is known about the impact of sex on the cost of CABG. OBJECTIVE: To examine the impact of sex on hospital course and the cost of CABG. METHODS: Hospital course and cost were examined among 2880 female and 9137 male patients from four Canadian and five American hospitals. Data were obtained from a resource and cost accounting system used by each of the nine hospitals. RESULTS: Among the 12,017 patients who underwent CABG, 24% (n=2880) were women and 76% (n=9137) were men. Women had a significantly longer length of stay (LOS) than did men (10.3+/-0.2 days and 8.9+/-0.08 days, respectively; P<0.0001) and a significantly higher in-hospital mortality than did men (2.6% and 1.5%, respectively; P<0.0001). The total unadjusted cost was higher for women than for men both in Canada (US$11,200+/-268 and US$10,143+/-139, respectively; P<0.0001) and the United States (US$22,715+/-509 and US$19,906+/-269, respectively; P<0.0001). After adjusting for age and comorbid conditions, female sex was associated with a 10% increase in LOS (P<0.0001), a 97% increase in mortality (P=0.0006) and a 7% increase in overall cost (P<0.0001). CONCLUSION: Compared with men, women undergoing CABG had a modestly increased LOS and a higher mortality. Total in-hospital cost was higher for women in each of the nine hospitals studied. Compared with other clinical variables, female sex is a relatively minor determinant of cost. Nevertheless, because of the expected increase in the number of women undergoing CABG in the future, this increased cost may translate into an important economic burden.

Regulation of gene Expression by 1alpha,25-dihydroxyvitamin D3 and Its analog EB1089 under growth-inhibitory conditions in squamous carcinoma Cells.

Analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)2D3) inhibit growth in vitro and in vivo of cells derived from a variety of tumors. Here, we examined the effects of 1alpha,25(OH)2D3 and its analog EB1089 on proliferation and target gene regulation of human head and neck squamous cell carcinoma (SCC) lines SCC4, SCC9, SCC15, and SCC25. A range of sensitivities to 1alpha,25(OH)2D3 and EB1089 was observed, from complete G0/G1 arrest of SCC25 cells to only 50% inhibition of SCC9 cell growth. All lines expressed similar levels of vitamin D3 receptor (VDR) mRNA and protein, and no significant variation was observed in 1alpha,25(OH)2D3-dependent induction of the endogenous 24-hydroxylase gene, or of a transiently transfected 1alpha,25(OH)2D3-sensitive reporter gene. The antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC25 cells were analyzed by screening more than 4,500 genes on two cDNA microarrays, yielding 38 up-regulated targets, including adhesion molecules, growth factors, kinases, and transcription factors. Genes encoding factors implicated in cell cycle regulation were induced, including the growth arrest and DNA damage gene, gadd45alpha, and the serum- and glucocorticoid-inducible kinase gene, sgk. Induction of GADD45alpha protein in EB1089-treated cells was confirmed by Western blotting. Moreover, while expression of proliferating cell nuclear antigen (PCNA) was reduced in EB1089-treated cells, coimmunoprecipitation studies revealed increased association between GADD45alpha and PCNA in treated cells, consistent with the capacity of GADD45alpha to stimulate DNA repair. While 1alpha,25(OH)2D3 and EB1089 modestly induced transcripts encoding the cyclin-dependent kinase inhibitor p21(waf1/cip1), no changes in protein levels were observed, indicating that p21(waf1/cip1) induction does not contribute to the antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC cells. Finally, in partially resistant SCC9 cells, there was extensive loss of target gene regulation (10 of 10 genes tested), indicating that resistance arises from widespread loss of 1alpha,25(OH)2D3-dependent gene regulation in the presence of normal levels of functional VDRs.

Relationship between choice reaction time and the Tower of Hanoi test.

The aim of this study was to examine a possible relation between the speed of information processing, as measured by simple and choice visual RT, and problem-solving, as measured by the Tower of Hanoi test. For 20 normal teenagers, performing all tests, significant correlations were found between choice RT and both measures of performance on the Tower of Hanoi, number of disk moves, and time taken to complete the task. Simple RT was correlated with Completion time but not with the number of moves, while the reverse pattern was discerned for decision time. Choice movement time was also associated with both measures, but simple movement time was not. These results are consistent with the hypothesis of a common neurobiological basis to information-processing speed and executive functions.