Trends of incidence, mortality and survival of multiple myeloma in Spain. A twenty-three-year population-based study.

BACKGROUND: Despite major advances, multiple myeloma remains an incurable disease. Epidemiological data from high-quality population-based registries are needed to understand the heterogeneous landscape of the disease. METHODS: Incidence, mortality and survival in multiple myeloma were comprehensively analyzed in the Girona and Granada population-based cancer registries, over a 23-year study (1994-2016), divided into three periods (1994-2001, 2002-2009 and 2010-2016). Joinpoint regression analysis was used to estimate the annual percentage change in incidence and mortality. Age-standardized net survival was calculated with the Pohar-Perme method. RESULTS: 1957 myeloma patients were included in the study, with a median age of 72 years. Age-standardized incidence and mortality rates decreased over time in both sexes and both rates were higher in males. Five-year age-standardized net survival by period was 27.4% (1994-2001), 38.8% (2002-2009), and 47.4% (2010-2016). Survival improved for all age groups: 32.4%, 74.1% and 78.5% for patients aged 15-49; 27.5%, 44.6%, and 58.5% for those aged 50-69; finally, 24.8%, 25.5%, and 26.3% for the older group. CONCLUSION: Incidence remained overall stable throughout the study, with only a small increase for men. Mortality was progressively decreasing in both sexes. Both incidence and mortality were higher in men. Age plays a critical role in survival, with impressive improvement in patients younger than 70 years, but only a minor benefit in those older than 70.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC).

Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.

[Clinical and analytic diagnostic evaluation of deep venous thrombosis of the lower limbs]. / Valoración diagnóstica clínica y analítica de la trombosis venosa profunda de miembros inferiores.

BACKGROUND: Diagnosis of deep-vein thrombosis (DVT) of lower limbs has changed in recent years. The objective of our study was to analyze the diagnostic accuracy of a combination of clinical and epidemiological data and the D-Dimer plasma levels in this entity. PATIENTS AND METHODS: Clinical (symptoms and signs) and epidemiological data, personal and family history, and D-dimer plasma levels or positivity were reviewed, on the admittance, in 108 patients to whom a phlebography was performed due to a suspected DVT. RESULTS: Phlebography was positive in 76 cases (70.37%). Logistic regression analysis determined a prediction model of the diagnostic of DVI including a combination of both D-dimer plasma levels or positivity and pain along the deep venous involved area. CONCLUSION: Combination of D-dimer testing and pain along the distribution of the deep venous area is useful as an initial diagnostic approach to the DVI of the lower limbs.