Systematic review for non-surgical interventions for the management of late radiation proctitis

Chronic radiation proctitis produces a range of clinical symptoms for which there is currently no recommended standard management. The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy. Synonyms for radiation therapy and for the spectrum of lower gastrointestinal radiation toxicity were combined in an extensive search strategy and applied to a range of databases. The included studies were those that involved interventions for the non-surgical management of late radiation proctitis. Sixty-three studies were identified that met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy. However, these studies could not be compared. If the management of late radiation proctitis is to become evidence based, then, in view of its episodic and variable nature, placebo controlled studies need to be conducted to clarify which therapeutic options should be recommended. From the current data, although certain interventions look promising and may be effective, one small or modest sized study, even if well-conducted, is insufficient to implement changes in practice. In order to increase recruitment to trials, a national register of cases with established late radiation toxicity would facilitate multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study

Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age 50 chromosomes (n=44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1; 22)(p13; q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9; 11)(p22; q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes

Value assessment and pricing capabilities-how to profit from value

Value is a key concept for researchers and practitioners in the fields of strategy, marketing, and pricing. In the strategy literature, value is closely related to competitive advantage and profit, in the marketing literature value is the cornerstone of the marketing management process, in the pricing literature value represents the customer's willingness to pay. The aim of this article is to bridge the gap between marketing, pricing and strategy research through a compilation of five short essays that focus on value assessment and pricing capabilities. This article argues that value assessment and pricing capabilities provide the foundation for value creation and value appropriation in business-to-business markets, highlights their implications for profiting from value created and delivered, and outlines important areas for future research