Immunocompetence of nestling great tits in relation to rearing environment and parentage

Theoretical models of host-parasite coevolution assume a partially genetic basis to the variability in susceptibility to parasites among hosts, for instance as a result of genetic variation in immune function. However, few empirical data exist for free-living vertebrate hosts to support this presumption. In a cross-fostering experiment with nestling great tits, by comparing nestlings of the same origin we investigated (i) the variance in host resistance against an ectoparasite due to a common genetic origin, (ii) the effect of ectoparasite infestation on cell-mediated immunity and (iii) the variance in cell-mediated immunity due to a common genetic origin. Ectoparasitic hen fleas can impair the growth of nestling great tits and nestling growth was therefore taken as a measure of host susceptibility. A common origin did not account for a significant part of the variation in host susceptibility to fleas. There was no significant overall effect of fleas on nestling growth or cell-mediated immunity, as assessed by a cutaneous hypersensitivity response. A common rearing environment explained a significant part of the variation in cell-mediated immunity among nestlings, mainly through its effect on nestling body mass. The variation in cell-mediated immunity was also related to a common origin. However, the origin-related variation in body mass did not account for the origin-related differences in cell-mediated immunity. The results of the present study thus suggest heritable variation in cell-mediated immunity among nestling great tits. [References: 49]

American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer

Purpose To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. Results The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. Recommendations For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels � 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration–approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the American Society of Hematology and has been published jointly by invitation and consent in both Journal of Clinical Oncology and Blood.

American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer

Purpose: To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods: An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. Results: The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. Recommendations: For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management

Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. Use of the World Health Organization 2004/International Society of Urological Pathology 1998 grading nomenclature and recent molecular studies highlight certain unique features of bladder urothelial neoplasms in young patients, particularly in patients below 20 years of age. In this meta-analysis and review, the clinical, pathologic, and molecular features and risk factors of bladder urothelial neoplasms in patients 40 years or less are presented and analyzed according to decades of presentation. Similar to older patients, bladder urothelial neoplasms in patients 40 years or younger occur more common in male patients, present mainly with gross painless hematuria, and are more commonly located at bladder trigone/ureteral orifices, but in contrast have a greater chance for unifocality. Delay in diagnosis of bladder urothelial neoplasms seems not to be uncommon in younger patients probably because of its relative rarity and the predominance of benign causes of hematuria in this age group causing hesitancy for an aggressive work-up. Most tumors in patients younger than 40 years were low grade. The incidence of low-grade tumors was the lowest in the first 2 decades of life, with incremental increase of the percentage of high-grade tumors with increasing age decades. Classification according to the World Health Organization 2004/International Society of Urological Pathology grading system identified papillary urothelial neoplasms of low malignant potential to be relatively frequent among bladder tumors of young patients particularly in the teenage years. Similar to grade, there was marked predominance of low stage tumors in the first 2 decades of life with gradual inclusion of few higher stage and metastatic tumors in the 2 older decades. Bladder urothelial neoplasms occurring in patients <20 years of age lack or have a much lower incidence of aberrations in chromosome 9, FGFR3, p53, and microsatellite instability and have fewer epigenetic alterations. Tumor recurrence and deaths were infrequent in the first 2 decades and increased gradually in each successive decade, likely influenced by the increased proportion of higher grade and higher stage tumors. Our review of the literature shows that urothelial neoplasms of the bladder occurring in young patients exhibit unique pathologic and molecular features that translate to its more indolent behavior; this distinction is most pronounced in patients <20 years. Our overall inferences have potential implications for choosing appropriate noninvasive diagnostic and surveillance modalities, whenever feasible, and for selecting suitable treatment strategies that factor in quality of life issues vital to younger patients.