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Type 1 Gaucher disease (GD1) is a rare, autosomal recessive disorder caused by glucocerebrosidase deficiency. Skeletal manifestations represent one of the most debilitating and potentially irreversible complications of GD1. Although imaging studies are the gold standard, early diagnostic/prognostic tools, such as molecular biomarkers, are needed for the rapid management of skeletal complications. This study aimed to identify potential protein biomarkers capable of predicting the early diagnosis of bone skeletal complications in GD1 patients using artificial intelligence. An in silico study was performed using the novel Therapeutic Performance Mapping System methodology to construct mathematical models of GD1-associated complications at the protein level. Pathophysiological characterization was performed before modeling, and a data science strategy was applied to the predicted protein activity for each protein in the models to identify classifiers. Statistical criteria were used to prioritize the most promising candidates, and 18 candidates were identified. Among them, PDGFB, IL1R2, PTH and CCL3 (MIP-1α) were highlighted due to their ease of measurement in blood. This study proposes a validated novel tool to discover new protein biomarkers to support clinician decision-making in an area where medical needs have not yet been met. However, confirming the results using in vitro and/or in vivo studies is necessary. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX's predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view. [ABSTRACT FROM AUTHOR]

Introduction: Mepact® (mifamurtide) is the first drug approved for the treatment of high-grade resectable non-metastatic osteosarcoma in patients aged 2-30 in the last 20 years. It follows a randomized clinical trial showing a statistically-significant and clinically-relevant decrease in the risk of death without compromising safety. Aim: This study assessed the cost-effectiveness and budget impact of mifamurtide. Methods: The economic evaluation was done on a hypothetical cohort of young patients under the age of 30 with high-grade, non-metastatic, resectable osteosarcoma. Standard chemotherapy without mifamurtide was used as comparator. A Markov model was adapted using Spanish costs and the results of the INT-0133 Phase III study. The analysis has been carried out from the perspective of the Spanish National Health Service, with a time horizon of up to 60 years in the base analysis. Results: The observed greater efficacy of mifamurtide in the trial translates into a gain of 3.03 (undiscounted) and 1.33 (discounted) quality-adjusted life years at an additional cost of €102,000. The estimated budgetary impact of using mifamurtide in 10-100% of the potential population would cost €671,000 and €6.7 million respectively. Conclusion: The cost per quality-adjusted life years gained with mifamurtide in Spain is in the low band (<€100,000) of the iCERs obtained by other orphan drugs and would have a limited and affordable cost in Spain. [ABSTRACT FROM AUTHOR]

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background and Objective: The REACH Registry is the largest worldwide designed to obtain information on cardiovascular risk factor control and preventive treatment in a population who have, or are at risk of having, symptoms of atherothrombosis. The objective of this study is to show the results of cardiovascular events obtained in a sample of the Spanish population at one year follow-up and intervention., Material and Method: The REACH Spain registry is a prospective cohort study of subjects with vascular risk factors (ORF) for atherothrombosis or with symptomatic vascular disease (VD): coronary artery disease (CAD) and/or cerebrovascular disease (CVD) and/or peripheral artery disease (PAD). The main outcome measures were rates of all-cause mortality, cardiovascular (CV) death, and the overall combined CV death, myocardial infarction (MI), or stroke and CV hospitalization at one year follow-up., Results: In Spain 2,516 patients were recruited and 2,252 completed one year follow-up, the mean age was 68,1 (73,8% men), 11,6% of subjects with ORF and 88,5% with VD, 55% with CAD, 33% with CVD and 17% with PAD. The annual rate of all-cause mortality in VD and ORF groups were 3,57% and 1,98% (NS) respectively, while for CV death they were 2,69% and 0,62% (P<.05) and for overall combined CV death myocardial infarction (MI), or stroke and CV hospitalization they were 15,34% and 5,47% (P=.0001). The annual rate of CV death for CAD, CVD and PAD groups were 3,47%, 2,78% and 1,46% respectively, and for the overall combined CV death, myocardial infarction (MI) , or stroke and CV hospitalization they were 18,52%, 13,75% and 14,52%. These event rates increased with the number of symptomatic arterial disease locations from 0,1,2 or 3 for CV death (0,62%, 2,46%, 3,55% and 4,32%, respectively P<.05) and for overall combined CV death myocardial infarction (MI), or stroke and CV hospitalization (5,50%, 4,18%, 20,59% y 19,40%, respectively P<.0001). At one year follow-up, 82,8% of the patients were with at least one antiplatelet drug and 86,2% were receiving lipid-lowering agents., Conclusions: The REACH Spain Registry at one year follow-up in patients with atherothrombotic disease or at risk of having symptoms of atherothrombosis shows a high rate of all-cause mortality and of overall combined major CV events, which is becoming higher as the number of symptomatic arterial disease locations increases.