Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD.

Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated. Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting. Design: Observational study. Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection. Results: The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26-1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3-8] versu 8 [5-16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09-1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14-3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30-2.24], p < 0.001), and platelet count <50 × 109/l (HR = 1.69 [95% CI = 1.3-2.2], p < 0.001). BM blasts >20% (HR = 1.57 [95% CI = 1.19-2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35-2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51-0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996-0.998], p = 0.016) protected from it. Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.

Author Correction: Validating a breast cancer score in Spanish women. The MCC-Spain study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Relation of CUN-BAE Index with Body Mass Index and Waist Circumference in Adults Aged 50 to 85 Years: The MCC-Spain Study.

Backgound: Traditional anthropometrics such as body mass index (BMI) or waist circumference (WC) do not fully capture the complex biology of body fat (BF) in the elderly. The Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index, based on BMI, is proposed as a better indicator of BF. However, its relation with BMI is not clear. The aim was to compare the agreement between CUN-BAE, BMI, and WC in those aged ≥50 years. Methods: A cross-sectional sample of 3153 Caucasian healthy adults was taken from the MCC-Spain study. The Pearson's correlation and its 95% confidence interval (CI), adiposity distribution, and Kappa Index (95%CI) were calculated. Results: The correlation of CUN-BAE with WC is 0.18 (95%CI 0.14-0.21) and that with BMI is moderate (r 0.58; 95%CI 0.55-0.60), but both increased strongly by sex. Agreement (normal weight/overweight/obesity) of CUN-BAE with BMI is 7% and with WC is 18%. Conclusions: The correlation and the degree of agreement of CUN-BAE with BMI and WC are low in individuals aged over 50, but it is higher by sex. Thus, this different criterion of obesity may have clinical applications. More studies with a gold standard are needed to evaluate the CUN-BAE in elderly adults.

The Value of Adding Surveillance Cultures to Fluoroquinolone Prophylaxis in the Management of Multiresistant Gram Negative Bacterial Infections in Acute Myeloid Leukemia.

Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13-0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38-0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.

Psychological Distress, Family Support and Employment Status in First-Year University Students in Spain.

Mental disorders are consistently and closely related to psychological distress. At the start of the university period, the relationship between a student's psychological distress, family support, and employment status is not well-known. The aims of this study were: To determine the prevalence of psychological distress in first-year university students and to analyze its relationship with family support and the student's employment status. Data from 4166 first-year university students from nine universities across Spain were considered. The prevalence of psychological distress was obtained using the GHQ-12, a valid and reliable screening tool to detect poor mental health. To analyze the relationship between psychological distress, family support, and employment status, logistic regression models were fitted. Regarding the prevalence found, 46.9% of men and 54.2% of women had psychological distress. In both genders, psychological distress levels increased as family support decreased. Among women, psychological distress was associated with their employment status. The prevalence of psychological distress among first-year university students in Spain is high. In addition, family support, and employment status for women, could be factors to take into account when developing psychological distress prevention strategies at the beginning of the university period.

Drug use, family support and related factors in university students. A cross-sectional study based on the uniHcos Project data / Consumo de drogas ilegales, apoyo familiar y factores relacionados en estudiantes universitarios. Un estudio transversal basado en datos del Proyecto uniHcos

Objective: To assess the prevalence of illegal drug use in college students on any previous occasion, during the previous year and the previous month, and to analyze the relationship between illegal drug use and family support and other factors. Methods: A cross-sectional study using data from students participating in the uniHcos project (n = 3767) was conducted. The prevalence and age of onset of consumption of cannabis, non-prescription sedatives, stimulants and depressants was evaluated. Polyconsumption was also assessed. The independent variables were: family support, age, residence, and employment status. To determine the factors related to drug use multivariate logistic regression models stratified by gender were fitted. Results: Differences between men and women in prevalence of illegal drug use except non-prescription sedatives were observed. In both genders, less family support was associated with higher consumption of all drugs, except depressants, and with polyconsumption. To be studying and looking for work was related to cannabis and stimulant use and to polyconsumption among women, but only to cannabis use among men. Conclusions: These results support the notion that the start of university studies is a particularly relevant stage in the onset of illegal drug use and its prevention, and that consumption may be especially associated with family support

Objetivo: Evaluar la prevalencia del consumo de drogas ilegales en estudiantes universitarios y analizar la relación entre dicho consumo, el apoyo familiar y otros factores. Método: Se realizó un diseño transversal basado en datos de participantes en el proyecto uniHcos (n = 3767). Se evaluaron la prevalencia y la edad de inicio del consumo de cannabis, tranquilizantes sin receta, estimulantes y depresores, y el policonsumo. Como variables independientes se consideraron el apoyo familiar, la edad, la residencia y la situación laboral. Para la determinación de los factores asociados al consumo de drogas se ajustaron modelos de regresión logística estratificados por sexo. Resultados: Se observaron diferencias entre hombres y mujeres en la prevalencia del consumo de todas las drogas ilegales, excepto tranquilizantes sin receta. En ambos sexos, cuanto peor apoyo familiar, mayor consumo de todas las drogas, excepto depresores y policonsumo. Encontrarse estudiando y buscando trabajo se relacionó con el consumo de cannabis, estimulantes y policonsumo en las mujeres, y solo con cannabis en los hombres. Conclusiones: Los resultados de este estudio aportan nueva evidencia a favor de que el inicio de la etapa universitaria es un momento de especial relevancia en el inicio del consumo de drogas ilegales y su prevención, pudiendo este consumo estar especialmente relacionado con el apoyo familiar

Drug use, family support and related factors in university students. A cross-sectional study based on the uniHcos Project data.

OBJECTIVE: To assess the prevalence of illegal drug use in college students on any previous occasion, during the previous year and the previous month, and to analyze the relationship between illegal drug use and family support and other factors. METHODS: A cross-sectional study using data from students participating in the uniHcos project (n = 3767) was conducted. The prevalence and age of onset of consumption of cannabis, non-prescription sedatives, stimulants and depressants was evaluated. Polyconsumption was also assessed. The independent variables were: family support, age, residence, and employment status. To determine the factors related to drug use multivariate logistic regression models stratified by gender were fitted. RESULTS: Differences between men and women in prevalence of illegal drug use except non-prescription sedatives were observed. In both genders, less family support was associated with higher consumption of all drugs, except depressants, and with polyconsumption. To be studying and looking for work was related to cannabis and stimulant use and to polyconsumption among women, but only to cannabis use among men. CONCLUSIONS: These results support the notion that the start of university studies is a particularly relevant stage in the onset of illegal drug use and its prevention, and that consumption may be especially associated with family support.

Net contribution and predictive ability of the CUN-BAE body fatness index in relation to cardiometabolic conditions.

BACKGROUND: The CUN-BAE (Clínica Universidad de Navarra-Body adiposity estimator) index is an anthropometric index based on age, sex and body mass index (BMI) for a refined prediction of body fatness in adults. CUN-BAE may help detect metabolically unhealthy individuals with otherwise normal weight according to BMI or waist circumference (WC). The aim of this study was to evaluate whether CUN-BAE, independent of its components (BMI, age and sex), was associated with cardiometabolic conditions including arterial hypertension, diabetes mellitus and metabolic syndrome (MetS). METHODS: The ENRICA study was based on a cross-sectional sample of non-institutionalized men and women representative of the adult Spanish population. Body weight, height, and WC were measured in all participants. The residual of CUN-BAE (rCUN-BAE), i.e. the part of the index not explained by its components, was calculated. The associations of CUN-BAE, rCUN-BAE, BMI and WC with hypertension, diabetes and MetS were analysed by multivariate logistic regression, and the Akaike information criterion (AIC) was calculated. RESULTS: The sample included 12,122 individuals. rCUN-BAE was associated with hypertension (OR 1.14, 95% CI 1.07-1.21) and MetS (OR 1.48, 1.37-1.60), but not with diabetes (OR 1.05, 0.94-1.16). In subjects with a BMI < 25 kg/m2, CUN-BAE was significantly associated with all three outcome variables. CUN-BAE was more strongly associated with the cardiometabolic conditions than BMI and WC and fit similar AICs. CONCLUSIONS: The CUN-BAE index for body fatness was positively associated with hypertension, diabetes and MetS in adults independent of BMI or WC. CUN-BAE may help to identify individuals with cardiometabolic conditions beyond BMI, but this needs to be confirmed in prospective settings.

PGC-1α as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer.

Colorectal cancer is a significant public health concern. As a multistage and multifactorial disease, environmental and genetic factors interact at each stage of the process, and an individual's lifestyle also plays a relevant role. We set out to review the scientific evidence to study the need to investigate the role of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) gene as a biomarker of the physical activity's (PA) effect on colorectal cancer. PA is a protective factor against colorectal cancer and usually increases the expression of PGC-1α This gene has pleiotropic roles and is the main regulator of mitochondrial functions. The development of colorectal cancer has been associated with mitochondrial dysfunction; in addition, alterations in this organelle are associated with colorectal cancer risk factors, such as obesity, decreased muscle mass, and the aging process. These are affected by PA acting, among other aspects, on insulin sensitivity and oxygen reactive species/redox balance. Therefore, this gene demands special attention in the understanding of its operation in the consensual protective effect of PA in colorectal cancer. A significant amount of indirect evidence points to PGC-1α as a potential biomarker in the PA-protective effect on colorectal cancer. The article focuses on the possible involvement of PGC-1α in the protective role that physical activity has on colorectal cancer. This is an important topic both in relation to advances in prevention of the development of this widespread disease and in its therapeutic treatment. We hope to generate an initial hypothesis for future studies associated with physical activity-related mechanisms that may be involved in the development or prevention of colorectal cancer. PGC-1α is highlighted because it is the main regulator of mitochondrial functions. This organelle, on one hand, is positively stimulated by physical activity; on the other hand, its dysfunction or reduction increases the probability of developing colorectal cancer. Therefore, we consider the compilation of existing information about the possible ways to understand the mechanisms of this gene to be highly relevant. This study is based on evidence of PGC-1α and physical activity, on PGC-1α and colorectal cancer, on colorectal cancer and physical activity/inactivity, and the absence of studies that have sought to relate all of these variables. Cancer Prev Res; 11(9); 523-34. ©2018 AACR.

Possible role of chondroitin sulphate and glucosamine for primary prevention of colorectal cancer. Results from the MCC-Spain study.

A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28-0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47-1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62-0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.

Validating a breast cancer score in Spanish women. The MCC-Spain study.

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations.

Alterations in PGC1α expression levels are involved in colorectal cancer risk: a qualitative systematic review.

BACKGROUND: Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected to be involved in this type of tumorigenesis, as supported by an accumulating body of research evidence. However, little is known about how mitochondrial alterations contribute to tumorigenesis. Mitochondrial biogenesis is a fundamental cellular process required to maintain functional mitochondria and as an adaptive mechanism in response to changing energy requirements. Mitochondrial biogenesis is regulated by peroxisome proliferator-activated receptor gamma coactivator 1-α (PPARGC1A or PGC1α). In this paper, we report a systematic review to summarize current evidence on the role of PGC1α in the initiation and progression of CRC. The aim is to provide a basis for more comprehensive research. METHODS: The literature search, data extraction and quality assessment were performed according to the document Guidance on the Conduct of Narrative Synthesis in Systematic Reviews and the PRISMA declaration. RESULTS: The studies included in this review aimed to evaluate whether increased or decreased PGC1α expression affects the development of CRC. Each article proposes a possible molecular mechanism of action and we create two concept maps. CONCLUSION: Our systematic review indicates that altered expression of PGC1α modifies CRC risk. Most studies showed that overexpression of this gene increases CRC risk, while some studies indicated that lower than normal expression levels could increase CRC risk. Thus, various authors propose PGC1α as a good candidate molecular target for cancer therapy. Reducing expression of this gene could help to reduce risk or progression of CRC.

The role of EZH2 in overall survival of colorectal cancer: a meta-analysis.

Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis. The role of the gene EZH2 in colorectal cancer survival is uncertainly, the aim of this study is clear this relationship. Relevant literaure was searched from electronic databases. A meta-analysis was performed with elegible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with colorectal cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38-0.84) We performed bias analysis according Egger and Begg,s test and we did not find publication bias. EZH2 overexpression indicates a better prognosis for colorectal cancer.

Características clínicas, anatomopatológicas y moleculares en casos de cáncer colorrectal según localización tumoral y grado de diferenciación / Clinical, anatomopathological and molecular characteristics of colorectal cancer by tumor location and degree of differentiation

Objetivos: El cáncer colorrectal (CCR) presenta elevada incidencia y mortalidad con diferentes tendencias según localización anatómica y otras características anatomopatológicas que parecen vinculadas a cambios tanto a la exposición a factores de riesgo como al diagnóstico siendo esencial una adecuada filiación tumoral para valorar el efecto de dichos factores en la aparición, diagnóstico y progresión de la enfermedad. El objetivo fue describir las características clínicas y anatomopatológicas de pacientes diagnosticados de CCR en el Área de Salud de León en función de la localización tumoral y del grado de diferenciación. Métodos: Se estudió una serie de 408 casos de entre 25 y 85 años con diagnóstico confirmado de CCR, recogiéndose información de características clínicas y anatomopatológicas y de los biomarcadores analizados en la rutina clínica. Se realizó análisis univariable y bivariable según el grado de diferenciación y la localización tumoral. Resultados: El tamano tumoral disminuye desde colon proximal a recto (Colon Proximal = 5,13 cm: Colon Distal = 4,09cm: Recto = 3,17cm; p< 0,001) siendo el TNM también mayor en zonas proximales. Los adenocarcinomas mucinosos son más frecuentes en tumores pobremente diferenciados que en bien diferenciados (23,1% vs 5,5%). Las invasiones linfática, venosa y peritumoral son más frecuentes con menor grado de diferenciación. Conclusiones: La distribución del estadio tumoral en función de la localización tiene estadios TNM más avanzados en zonas proximales, lo que podría asociarse a una menor detección precoz en dichos casos. La asociación entre invasión venosa y linfática con el grado de diferenciación es poco conocida requiriéndose estudios que aclaren su posible interés pronóstico.

Aims: Colorectal cancer (CRC) has a high incidence and mortality, with different patterns depending on anatomical location and other pathological characteristics that appear linked to changes in exposure risk factors exposure as well as the diagnosis. All these make it essential to determine the source of the tumour to properly assess the effect of these factors in the development, diagnosis and progression of the disease. The aim was to describe the clinical and anatomical-pathological characteristics of patients diagnosed with CRC in the Health Area of Leon (ASL) based on their location and degree of tumour differentiation. Methods: Information was collected on the clinical and pathological characteristics, including biological markers analysed in clinical routine of 408 patients between 25 and 85 years with a confirmed diagnosis of CRC, and residents in ASL at least six months before diagnosis. Univariate and bivariate analyses were performed according to the degree of differentiation and tumour location. Results: Tumour size decreases from the colon to the rectum from location decline proximal colon to the rectum (Proximal Colon = 5.13cm; Distal Colon = 4.09cm; Rectum = 3.17cm, P< 0.001), with the TNM stage also being higher in proximal areas. Mucinous adenocarcinomas are more frequent in poorly differentiated than in well differentiated tumours (23.1% vs 5.5%). Lymphatic, venous and peri-tumour invasions are more common in poorly differentiated tumours. Conclusions: The distribution in accordance with the location has more advanced TNM stages in the proximal areas, which could be related to the poorer early diagnosis in proximal areas. The association between venous and lymphatic invasion with the degree of differentiation is poorly understood, and requires studies to clarify their possible prognostic interest.