Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Experiences and Lessons Learned in Developing and Implementing a Population-Based Nutrition and Health Surveillance System in Guatemala 2011­2021

Practice-based experiences documenting development and implementation of nutrition and health surveillance systems are needed. To describe processes, methods, and lessons learned from developing and implementing a population-based household nutrition and health surveillance system in Guatemala. The phases and methods for the design and implementation of the surveillance system are described. Efforts to institutionalize the system in government institutions are described, and illustrative examples describing different data uses, and lessons learned are provided. After initial assessments of data needs and consultations with officials in government institutions and partners in the country, a population-based nutrition surveillance system prototype with complex sampling was designed and tested in 5 Guatemalan Highland departments in 2011. After dissemination of the prototype, government and partners expanded the content, and multitopic nutrition and health surveillance cycles were collected in 2013, 2015, 2016, 2017/18, and 2018/19 providing nationally representative data for households, women of reproductive age (15­49 y), and children aged 0­59 mo. For each cycle, data were to be collected from 100 clusters, 30 households in each, and 1 woman and 1 child per household. Content covered ∼25 health and nutrition topics, including coverage of all large-scale nutrition-specific Interventions; the micronutrient content of fortifiable sugar, salt, and bread samples; anthropometry; and biomarkers to assess annually, or at least once, ∼25 indicators of micronutrient status and chronic disease. Data were collected by 3­5 highly trained field teams. The design was flexible and revised each cycle allowing potential changes to questionnaires, population groups, biomarkers, survey design, or other changes. Data were used to change national guidelines for vitamin A and B-12 interventions, among others, and evaluate interventions. Barriers included frequent changes of high-level government officials and heavy dependence on US funding. This system provides high-quality data, fills critical data gaps, and can serve as a useful model for others.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.

Aortic stenosis prognosis in older patients: frailty is a strong marker of early congestive heart failure admissions : Influence of frailty in aortic stenosis.

PURPOSE: Degenerative aortic stenosis has become a new valvular epidemic in the last few decades due to its high prevalence in the geriatric population. We sought to analyse factors that could influence earlier hospitalization for congestive heart failure in geriatric patients with moderate-severe degenerative aortic stenosis. METHODS: This investigation was an ambispective cohort study of 104 patients aged 70 years or older with moderate-severe aortic stenosis. Epidemiological, geriatric, clinical, echocardiographic and electrocardiographic variables were collected. During the follow-up, the number of admissions for congestive heart failure and the time elapsed from diagnosis to first admission were recorded. RESULTS: A total of 45.2% of the patients were admitted for congestive heart failure, with a median time to first admission of 3 years (95% CI 1.88-4.25). For patients aged 85 years or older, this median was 8.07 months (95% CI 0.05-1.99). The first admission for congestive heart failure was independently related to frailty (HR 4.46, 95% CI: 1.38-14.41), atrial fibrillation (HR 2.19, 95% CI: 1.01-4.73), a high EuroSCORE (HR 1.03, 95% CI: 1.00-1.05), the affected valvular area (HR 0.11, 95% CI: 0.02-0.47), age (HR 1.11, 95% CI: 1.04-1.18) and renal failure (HR 4.13, 95% CI: 1.46-11.63). The median time to admission for frail patients was 1.08 years (95% CI 0.30-1.86). CONCLUSIONS: In geriatric patients with moderate-severe degenerative aortic stenosis, frailty is an independent marker of early congestive heart failure admission with a powerful and important association.

A Comparative Evaluation of Kernel Equating and Test Characteristic Curve Equating.

This study compares the kernel equating (KE) and test characteristic curve (TCC) equating methods using the nonequivalent anchor test equating design. In this Monte Carlo study, four independent variables were examined: sample size, test length, average form discrimination, anchor test reliability, and the percentage of anchor items. For each condition, there were 100 replications. To assess the performance of TCC equating and KE, the differences between the examinee parametric true scores and the equated estimated expected true scores were examined. The equated scores were based on the average across replications for each condition. Generally speaking, both KE and TCC equating produced accurate results, although KE tended to perform better than TCC on the parametric true score scale across conditions. Past research and the current study's results seem to indicate that KE should be strongly considered for most equating situations, particularly in light of its flexibility.

Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats.

The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

An introduction to mixture item response theory models.

Mixture item response theory (IRT) allows one to address situations that involve a mixture of latent subpopulations that are qualitatively different but within which a measurement model based on a continuous latent variable holds. In this modeling framework, one can characterize students by both their location on a continuous latent variable as well as by their latent class membership. For example, in a study of risky youth behavior this approach would make it possible to estimate an individual's propensity to engage in risky youth behavior (i.e., on a continuous scale) and to use these estimates to identify youth who might be at the greatest risk given their class membership. Mixture IRT can be used with binary response data (e.g., true/false, agree/disagree, endorsement/not endorsement, correct/incorrect, presence/absence of a behavior), Likert response scales, partial correct scoring, nominal scales, or rating scales. In the following, we present mixture IRT modeling and two examples of its use. Data needed to reproduce analyses in this article are available as supplemental online materials at http://dx.doi.org/10.1016/j.jsp.2016.01.002.

Familial dilated cardiomyopathy: A multidisciplinary entity, from basic screening to novel circulating biomarkers.

Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited cardiomyopathies over the past decades. Genetic screening of first-degree relatives has revealed that 30-50% of the cases have a familial origin. Similar to other heart diseases, familial dilated cardiomyopathy is characterized by a high genetic heterogeneity that complicates family studies. Cli'nical screening, 12-lead electrocardiogram and transthoracic echocardiogram are recommended for patients and first-degree family members. Magnetic resonance also needs to be considered. Genetic technologies have become fundamental for the clinical management of this disease. New generation sequencing methods have made genetic testing feasible for extensive panels of genes related to the disease. Recently, new imaging modalities such as speckle-tracking, strain and strain rate or magnetic resonance, and circulating biomarkers such as non-coding RNAs, have emerged as potential strategies to help cardiologists in their clinical practice. Imaging, genetic and blood-based techniques should be considered together in the evaluation and testing of familial dilated cardiomyopathy. Here, we discuss the current procedures and novel approaches for the clinical management of familial dilated cardiomyopathy.

Leucemia mieloide crónica en España: sus características de presentación han cambiado. Sección española del registro poblacional EUTOS / Chronic myeloid leukaemia in Spain: Its presentation characteristics have changed. Spanish section of the EUTOS population-based registry

Objetivos. Pretendemos aportar datos más fiables sobre la epidemiología de la leucemia mieloide crónica (LMC) en España que los disponibles hasta la fecha. Material y métodos. El registro poblacional EUTOS, de la European LeukemiaNet, es un registro de casos nuevos de LMC en pacientes ≥ de 18 años de 22 áreas europeas. La sección española incluyó las comunidades autónomas de Madrid, Castilla-La Mancha y Aragón, en el periodo comprendido entre el 1-2-2010 y el 31-12-2012. Resultados. Se registraron 250 casos en 35 meses. La incidencia global fue de 1,08 casos/105 habitantes-año, con predominio masculino (58% de varones) y claras diferencias entre comunidades autónomas. La incidencia estandarizada por edad fue similar (global 1,04, varones 1,31, mujeres 0,81). La mediana de edad fue de 54 años. La incidencia aumentó con la edad, siendo máxima en>65 años, aunque un 31,7% de los casos aparecieron entre los 20 y los 44 años. Un 4% se diagnosticaron en fases avanzadas (2,4% en fase acelerada, 1,6% en crisis blástica), el 56% estaban asintomáticos, el 38% tenían esplenomegalia, y el score Sokal era alto en el 11% (inferior a lo previamente reflejado en la literatura). Conclusiones. La incidencia actual de LMC en España es superior a la previamente descrita y similar a la de los estudios europeos. A diferencia de las descripciones clásicas, la LMC se presenta mayoritariamente de forma asintomática, sin esplenomegalia, con menor leucocitosis y en estadios con mejor pronóstico (AU)

Objectives. To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. Material and methods. The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. Results. A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/105 inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). Conclusions. The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis (AU)

Chronic myeloid leukaemia in Spain: Its presentation characteristics have changed. Spanish section of the EUTOS population-based registry. / Leucemia mieloide crónica en España: sus características de presentación han cambiado. Sección española del registro poblacional EUTOS.

OBJECTIVES: To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. MATERIAL AND METHODS: The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. RESULTS: A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/10(5) inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). CONCLUSIONS: The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis.

Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease that currently lacks genomic and genetic biomarkers to assist in its clinical management. We performed whole-exome sequencing (WES) of three BPDCN cases. Based on these data, we designed a resequencing approach to identify mutations in 38 selected genes in 25 BPDCN samples. WES revealed 37-99 deleterious gene mutations per exome with no common affected genes between patients, but with clear overlap in terms of molecular and disease pathways (hematological and dermatological disease). We identified for the first time deleterious mutations in IKZF3, HOXB9, UBE2G2 and ZEB2 in human leukemia. Target sequencing identified 29 recurring genes, ranging in prevalence from 36% for previously known genes, such as TET2, to 12-16% for newly identified genes, such as IKZF3 or ZEB2. Half of the tumors had mutations affecting either the DNA methylation or chromatin remodeling pathways. The clinical analysis revealed that patients with mutations in DNA methylation pathway had a significantly reduced overall survival (P=0.047). We provide the first mutational profiling of BPDCN. The data support the current WHO classification of the disease as a myeloid disorder and provide a biological rationale for the incorporation of epigenetic therapies for its treatment.

Epigenomic profiling in polycythaemia vera and essential thrombocythaemia shows low levels of aberrant DNA methylation.

AIMS: The purpose of this study was to compare the DNA-methylation signature in classic chronic Philadelphia negative myeloproliferative neoplasms (MPN), polycythaemia vera (PV) and essential thrombocythaemia (ET), in order to obtain a global insight into DNA-methylation changes associated with these malignancies. METHODS: Thirty-five MPN samples from 11 ET JAK2 V617F, 12 ET JAK2 wild type (WT) and 12 PV JAK2 V617F patients as well as 12 from healthy donors were analysed. DNA samples extracted from whole peripheral blood were hybridised to the 'HumanMethylation27 DNA Analysis BeadChip.' RESULTS: All groups showed a very homogeneous methylation pattern. Only the ZNF577 gene showed a differential methylation profile between PV JAK2 V617F positive and controls. This aberrant methylation was correlated with a differential gene expression of ZNF577. No aberrant hypermethylation was found in the SOCS-1 and SOCS-3 genes. CONCLUSIONS: According to our results, an aberrant methylation pattern does not seem to play a crucial role in MPN pathogenesis; nor does it justify phenotypical differences between PV and ET.

The effect of nutritional supplementation on physical activity and exploratory behavior of Mexican infants aged 8-12 months.

BACKGROUND/OBJECTIVES: Physical activity and exploration in infancy affect physical and cognitive development. Nutritional supplementation improves activity in severely malnourished infants, but the evidence in mild-to-moderately malnourished and nutritionally at-risk infants is equivocal. We tested the effect of multiple-micronutrient supplementation on physical activity and exploration in Mexican infants. SUBJECTS/METHODS: Using a quasi experimental design, we analyzed data from a supplementation study that lacked a placebo-control group. We compared infants between 8 and 12 months measured at baseline who had received no supplementation (comparison group, n=78), with infants 8-12 months measured after 4 months of daily supplementation (treatment group, n=109). The treatment consisted of three supplement types: micronutrient powder, syrup (each containing only micronutrients) and a milk-based, fortified-food supplement (FFS; containing micronutrients and macronutrients). We formed the micronutrient-only group (MM) by combining the micronutrient powder and syrup groups. We measured activity and exploration by direct observation and used cluster analysis to form and characterize activity and exploration clusters. We performed logistic regression with activity or exploration cluster as the outcome variable and treatment versus comparison and MM or FFS versus comparison as the predictor variables. RESULTS: Treatment versus comparison increased the odds of being in the high activity (odds ratio (OR)=2.35, P<0.05) and high exploration (OR=1.87, P<0.05) cluster. MM increased the odds of being in the high activity (OR=2.64, P<0.05) cluster and FFS increased the odds (OR=3.16, P<0.05) of being in the high exploration cluster. CONCLUSIONS: Nutritional supplementation benefited activity and exploration in this sample of Mexican infants.

Real-time PCR quantification of haematopoietic chimerism after transplantation: a comparison between TaqMan and hybridization probes technologies.

This study aimed to compare the sensitivity and accuracy of two methods of quantitative real-time polymerase chain reaction (qrt-PCR), in order to determine haematopoietic chimerism (CH): single nucleotide polymorphisms using TaqMan (TM) probes and insertion/deletion polymorphisms using Hybridization (Hyb) probes. A total of 106 samples from 20 patients who underwent allogenic stem cell transplantation (n = 14) or live-donor liver transplantation (n = 6) were studied. The mean level of chimerism was 8.37% for the TM method and 7.73% in the Hyb method, which was not significantly different (P = 0.69). The Pearson correlation coefficient between the two methods was r = 0.91 (P < 0.001). The estimation of the regression line, using the Passing and Balbock method was Intercept A -0.0381 [95% confidence interval (CI) -0.1265 to 0.0296) and Slope B: 1.04609(95% CI 0.9349-1.161). Bland-Altman data showed that the standard deviations, which differed between the two methods (%Hyb-%TM), were 0.98 and -1.28. The accuracy and sensitivity of qrt-PCR chimerism is independent of the method used if the optimization is adequate and satisfies the criteria for adequate study. Real-time PCR, independent of the method adopted, is a very good tool for study levels of CH.

Room temperature reversible hydrogen storage in polyaniline (PANI) nanofibers.

We report for the first time the reversible hydrogen storage behavior at room temperature in polyaniline nanofibers. The rate of hydrogen sorption during the initial run was very rapid and an extended plateau pressure of about 30 bars was obtained from the pressure-composition isotherm profiles of these polyaniline nanofibers. The reversible cycling capacity of approximately 3-4 wt% was demonstrated at room temperature and has been attributed to the unique nanofibrous microstructural and surface properties.