Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy.     

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

On (scientific) integrity: conceptual clarification

The notion of “integrity” is currently quite common and broadly recognized as complex, mostly due to its recurring and diverse application in various distinct domains such as the physical, psychic or moral, the personal or professional, that of the human being or of the totality of beings. Nevertheless, its adjectivation imprints a specific meaning, as happens in the case of “scientific integrity”. This concept has been defined mostly by via negativa, by pointing out what goes against integrity, that is, through the identification of its infringements, which has also not facilitated the elaboration of an overarching and consensual code of scientific integrity. In this context, it is deemed necessary to clarify the notion of “integrity”, first etymologically, recovering the original meaning of the term, and then in a specifically conceptual way, through the identification of the various meanings with which the term can be legitimately used, particularly in the domain of scientific research and innovation. These two steps are fundamental and indispensable for a forthcoming attempt at systematizing the requirements of “scientific integrity”.     

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil

Aim

This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability.

Methods

‘Picual’, ‘Blanqueta’, ‘Sevillana’, ‘Habichuelero’, and ‘Chetoui’ olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells.

Results

Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. ‘Sevillana’ VOO had the highest total bioaccessibility (36%), followed by the ‘Picual’ (19%), ‘Chetoui’ (17%), ‘Habichuelero’ (10%), and ‘Blanqueta’ (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, ‘Chetoui’, and ‘Blanqueta’-BF having the highest radical DPPH scavenging capacity, and ‘Habichuelero’ and ‘Picual’-BF showing protective effects against the peroxyl radical measured by ORAC_FL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells.

Conclusions

Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.

     

Epidemiological trends of sepsis in the twenty-first century (2000–2013): an analysis of incidence,mortality, and associated costs in Spain

Background

Sepsis has represented a substantial health care and economic burden worldwide during the previous several decades. Our aim was to analyze the epidemiological trends of hospital admissions, deaths, hospital resource expenditures, and associated costs related to sepsis during the twenty-first century in Spain.

Methods

We performed a retrospective study of all sepsis-related hospitalizations in Spanish public hospitals from 2000 to 2013. Data were obtained from records in the Minimum Basic Data Set. The outcome variables were sepsis, death, length of hospital stay (LOHS), and sepsis-associated costs. The study period was divided into three calendar periods (2000–2004, 2005–2009, and 2010–2013).

Results

Overall, 2,646,445 patients with sepsis were included, 485,685 of whom had died (18.4%). The incidence of sepsis (events per 1000 population) increased from 3.30 (2000–2004) to 4.28 (2005–2009) to 4.45 (2010–2013) (p?<?0.001). The mortality rates from sepsis (deaths per 10,000 population) increased from 6.34 (2000–2004) to 7.88 (2005–2009) to 7.89 (2010–2013) (p?<?0.001). The case fatality rate (CFR) or proportion of patients with sepsis who died decreased from 19.1% (2000–2004) to 18.4% (2005–2009) to 17.9% (2010–2013) (p?<?0.001). The LOHS (days) decreased from 15.9 (2000–2004) to 15.7 (2005–2009) to 14.5 (2010–2013) (p?<?0.001). Total and per patient hospital costs increased from 2000 to 2011, and then decreased by the impact of the economic crisis.

Conclusions

Sepsis has caused an increasing burden in terms of hospital admission, deaths, and costs in the Spanish public health system during the twenty-first century, but the incidence and mortality seemed to stabilize in 2010–2013. Moreover, there was a significant decrease in LOHS in 2010–2013 and a decline in hospital costs after 2011.

     

Clinical and laboratory factors contributing to uninterpretable beryllium lymphocyte proliferation tests (BeLPT)

Background

The beryllium lymphocyte proliferation test (BeLPT), has become the principal clinical test for detecting beryllium sensitization and chronic beryllium disease. Uninterpretable BeLPT results can occur in a small but significant proportion of tests from poor lymphocyte growth (PG) or over proliferation of lymphocytes (OP). The clinical and laboratory causes of uninterpretable results are not known.

Methods

BeLPT data from the US Department of Energy‐supported Former Worker Screening Program were analyzed for a 10‐year period. Drivers of uninterpretable BeLPTs were investigated using multivariable models and classification techniques.

Results

Three participant attributes were significantly associated with PG, while OP showed no significant associations. Serum lot for the lymphocyte growth medium accounted for 21% of the variation in PG and 16% in OP.

Conclusion

Serum lots influence the likelihood of having uninterpretable BeLPT. To better understand uninterpretable results and possibly reduce their occurrence, additional laboratory‐related factors should be addressed.