The role of health-related quality of life in early discontinuation of chemotherapy for breast cancer

To examine the role of health-related quality of life (HRQOL) in early treatment discontinuation among women enrolled in a breast cancer clinical trial. A total of 464 women were enrolled in the Eastern Cooperative Oncology Group randomized controlled trial of adjuvant regimens comparing six cycles of cytoxan, adriamycin and 5-flurouricil (5-FU) with a 16-week regimen (weekly therapy with cytoxan, adriamycin, vincristine, methotrexate, and 5-FU) among women with lymph node positive breast cancer. One hundred sixty-four women participated in the HrQL substudy using the Breast Chemotherapy Questionnaire, which was designed to measure HRQOL in women receiving chemotherapy. Changes in global HRQOL score were examined over time as a predictor of early treatment discontinuation using generalized estimation equations (GEE) modeling and Cox proportional hazards regression. We considered early treatment discontinuation as a longitudinal binary variable determined at each time point HRQOL was measured. The results of multivariate GEE model fitting indicated that declines in HRQOL (p=0.04), older age (p=0.02), higher degree of nausea (p=0.02), higher degree of neurosensory toxicity (0.03) and lower degrees of hair loss (p=0.004) were correlated with early treatment discontinuation. We then fitted a proportional hazard regression model for time to early discontinuation with HRQOL score as a time-dependent covariate. The results were identical. Declines in HRQOL during therapy predicted early treatment discontinuation even after accounting for age and chemotherapy-related side effects. In the age of ever more aggressive treatments for breast cancer, women's perception of the impact of these treatments on their lives will become more important.     

The association of time of day and serum testosterone concentration in a large screening population

OBJECTIVE: To assess testosterone patterns during clinical hours in a large population of men participating in a national screening programme for prostate cancer, as the effect of time of day on serum testosterone concentration is unclear and largely reported in small studies. SUBJECTS AND METHODS: Testosterone levels were measured in 3006 men attending the national Prostate Cancer Awareness Week screening programme. Blood samples were obtained between 06.00 and 18.00 hours, whenever men presented for screening. All men completed questionnaires on age, comorbidities, height and weight. Testosterone levels were compared based on four periods, i.e. T1, 06.00-10.00 (632 men), T2, 10.00-12.00 (812), T3, 12.00-14.00 (388), and T4, 14.00-18.00 hours (1174). RESULTS: The mean (sd, range) age of the men was 60.3 (9.9, 40-94) years and the mean (sd) testosterone level was 415.2 (190.9) ng/dL. There was no change in mean (sd) testosterone levels over T1, T2 and T3, at 444.9 (206.2), 433.5 (195.8) and 434.4 (181.2) ng/dL, respectively, but levels at T4, at 380.4 (176.4) ng/dL, were lower by approximately 13% (P < 0.05). Advancing age, diabetes and obesity were associated with lower testosterone levels. The percentage of men with biochemical hypogonadism (<300 ng/dL) did not change across all four periods. CONCLUSIONS: Testosterone levels in older men are stable throughout the morning and early afternoon, declining only modestly thereafter. Further case-controlled studies are needed to confirm these findings.     

Duodenal- jejunal bypass sleeve: a totally endoscopic device for the treatment of morbid obesity

Morbid obesity affects over 15 million people in the United States. Nonsurgical management produces sustained weight loss in less than 5% of patients. Despite associated comorbidities, less than 1% of obese patients seek surgical intervention. Less invasive procedures have been developed with varying success. The Endobarrier( trade mark) (GI Dynamics(trade mark), Watertown, MA) duodenal-jejunal bypass sleeve is a totally endoscopically delivered device designed to produce weight loss in the morbidly obese. We describe the first placement of a duodenal-jejunal bypass sleeve in a patient in the United States. A blinded, randomized, prospective clinical trial was approved by the Food and Drug Administration to evaluate safety and efficacy of a novel device for weight loss in the obese. The first patient enrolled was a 36-year-old woman with body mass index of 45.2. After informed consent, endoscopic placement of the device under general anesthesia was performed using fluoroscopy to confirm positioning. The device was placed without complications. At conclusion of the 3-month study period, the device was removed endoscopically. Total weight lost by the patient was 9.09 kg. Described herein is the first deployment of the duodenal-jejunal bypass sleeve in North America. The device is delivered in a totally endoscopic manner in morbidly obese patients. In our patient, total weight loss at 3 months was 9.09 kg. Continued follow-up and enrollment is ongoing to demonstrate patient safety and efficacy. Additional studies are being performed to elucidate mechanism of weight loss and future clinical applications of this device.     

Synchrotron X‐ray analyses demonstrate phosphate‐bound gadolinium in skin in nephrogenic systemic fibrosis

Background Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to gadolinium (Gd)‐based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many patients with NSF contain micron‐sized insoluble Gd‐containing deposits. However, the precise composition and chemical nature of these particles is unclear. Objectives To clarify the precise chemical structure of the Gd‐containing deposits in NSF tissues. Methods Autopsy skin tissues from a patient with NSF were examined in situ using synchrotron X‐ray fluorescence (SXRF) microscopy and extended X‐ray absorption fine structure (EXAFS) spectroscopy and in correlation with light microscopy and the results of scanning electron microscopy/energy dispersive spectroscopy analyses. Results The insoluble Gd deposits were shown to contain Gd no longer coordinated by GBCA chelator molecules but rather in a sodium calcium phosphate material. SXRF microscopy shows a clear correlation between Gd, Ca and P. EXAFS spectroscopy shows a very different spectrum from the GBCAs, with Gd–P distances at 3·11 Å and 3·72 Å as well as Gd–Gd distances at an average of 4·05 Å, consistent with a GdPO₄ structure. Conclusions This is the first direct evidence for the chemical release of Gd from GBCA in human tissue. This supports the physical–chemical, clinical and epidemiological data indicating a link between stability and dose of GBCA to the development of NSF.     

Agenesis of the Inferior Vena Cava in H Syndrome Due to a Novel SLC29A3 Mutation

We present a 10‐year‐old girl with typical clinical features of H syndrome. Complete agenesis of the inferior vena cava was found on echocardiography and radiologic studies. Mutation analysis of the SLC29A3 gene revealed a novel nonsense mutation. This unique case extends the clinical and mutation spectrum associated with H syndrome and underlines the importance of routine cardiac screening in this disorder.