Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Inadequate dietary calcium and vitamin D intakes in renal-transplant recipients in Ireland.

OBJECTIVE: To quantify the dietary calcium and vitamin D intake in adult renal-transplant recipients attending at a large teaching hospital in Ireland for follow-up. SETTING: Outpatient renal-transplant follow-up clinic. SUBJECTS: Fifty-nine adult renal transplant recipients (58% male) with a mean age of 46 years, a median transplant duration of 6 years, and a mean estimated glomerular filtration rate (eGFR) of 50 mL/min per 1.73 m2. Fifty-three percent were at National Kidney Foundation stage 3 chronic kidney disease, and 14% had stage 4 chronic kidney disease. INTERVENTION: This cross-sectional, observational study used a tailored food frequency questionnaire specific for calcium and vitamin D intake in Irish adults, which was completed during a face-to-face interview with each subject. MAIN OUTCOME MEASURE: The main outcome measure was the average daily dietary and supplemented calcium and vitamin D intake. RESULTS: The median interquartile range (IQR) dietary calcium intake was 820 mg/day (range, 576-1,177 mg/day), and was similar in men and women (recommended intake > or = 1,000 mg/day in adult men and nonmenopausal adult women, > or = 1,500 mg/day in menopausal women). Five participants received calcium supplementation. Overall, 59% of men and 64% of women had total calcium intakes below the recommended amounts. The median IQR estimated dietary vitamin D intake was 5.2 microg/day (range, 2.4-6.4 microg/day) in women, and 4.6 microg/day (range, 2.2-6.6 microg/day) in men (recommended intake, > or = 10 microg/day). Six subjects received vitamin D supplementation. Total vitamin D intakes were suboptimal in 91% of men and 87% of women. Dietary calcium and vitamin D intakes significantly correlated with each other, but neither was significantly related to eGFR category, and was similarly low in both presumed menopausal women and in the initial year posttransplantation. CONCLUSION: These findings suggest that dietary and total calcium and vitamin D intakes in adult renal-transplant patients are in many cases inadequate.     

Incidence of malnutrition in adult patients at Groote Schuur Hospital, 1984

In order to determine nutritional status and the incidence of malnutrition 700 consecutive adult medical (395) and surgical (305) patients admitted to Groote Schuur Hospital between January and November 1984 were studied. Significant depletion in body weight was observed in 20% of all patients, fat depletion in 30% and muscle depletion in 15%; 40% were hypo-albuminaemia. Intergroup analysis demonstrated that malnutrition was more common in medical than surgical patients, and in non-white patients 38% of coloureds and 42% of blacks were fat depleted. Since malnutrition is associated with enhanced mortality and morbidity rates from any disease state, the results indicate that, particularly in non-white patients, nutritional support should be given greater emphasis in overall patient care.     

RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis.

To address the controversy of whether TNFalpha can compensate for RANKL in osteoclastogenesis in vivo, we used a TNFalpha-induced animal model of inflammatory arthritis and blocked RANKL/RANK signaling. TNFalpha increased osteoclast precursors available for RANK-dependent osteoclastogenesis. RANK signaling is not required for the TNFalpha-stimulated increase in CD11b(hi) osteoclast precursors but is essential for mature osteoclast formation. INTRODUCTION: Although critical roles of TNFalpha in inflammatory arthritis and RANKL in bone resorption have been firmly established, a central controversy remains about the extent to which TNFalpha can compensate for RANKL during osteoclastogenesis and the stage at which RANK signaling is required for osteoclastogenesis. Here, we used the human TNFalpha transgenic mouse model (TNF-Tg) of erosive arthritis to determine if there are both RANK-dependent and -independent stages of osteoclastogenesis in TNFalpha-induced erosive arthritis. MATERIALS AND METHODS: Osteoclastogenesis and osteoclast precursor (OCP) frequency were analyzed using histology, fluorescence-activated cell sorting (FACS), and cell culture from (1) TNF-Tg mice treated with the RANKL antagonist, RANK:Fc, or (2) TNF-Tg X RANK -/- mice generated by crossing TNF-Tg mice with RANK-/- mice. RESULTS: Treatment of TNF-Tg mice, which have increased OCPs in their spleens, with RANK:Fc dramatically reduced osteoclast numbers on the surface of their arthritic joints and within their bones, but did not decrease CD11b(hi) OCP numbers in their spleens. Long-term RANK:Fc administration alleviated joint erosion. Furthermore, TNF-Tg x RANK -/- mice had severe osteopetrosis, no osteoclasts, and no joint erosion, but increased CD11b(hi) precursor numbers that failed to form mature osteoclasts in vitro. CONCLUSION: RANK signaling is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis but not for the TNFalpha-induced increase in CD11b(hi) OCP that subsequently can differentiate into osteoclasts in inflamed joints.