Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma

Dietary diversity and Depression: Cross-sectional and longitudinal analyses in Spanish adult population with Metabolic Syndrome. Findings from PREDIMED-PLUS Trial.

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between Dietary Diversity (DD) and depressive symptoms. Design: An energy-adjusted Dietary Diversity Score (DDS) was assessed using a validated food-frequency questionnaire and was categorized into quartiles (Q). The variety in each food group was classified into 4 categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II>=18. Linear and logistic regression models were used. Setting: Spanish older adults with Metabolic Syndrome. Participants: A total of 6625 adults aged (55-75 years) from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; Odds Ratio (OR) Q4 vs Q1= 0.76 (95% confidence interval (CI): 0.64, 0.90). This was driven by high diversity compared to low diversity (C3 vs. C1) of vegetables [OR (95%CI) = 0.75 (0.57, 0.93)], cereals [OR (95%CI) = 0.72 (0.56-0.94)] and proteins [OR (95%CI) = 0.27 (0.11, 0.62)]. In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 y- of follow-up, except for DD in vegetables C4 vs C1= [β (95%CI) = 0.70 (0.05, 1.35)]. Conclusions: According to our results, DD is associated with the presence of depressive symptoms but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up period) are needed to confirm these findings

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Rare Diseases: Needs and Impact for Patients and Families: A Cross-Sectional Study in the Valencian Region, Spain

Families with rare diseases (RDs) have unmet needs that are often overlooked by health professionals. Describing these needs and the impact of the disease could improve their medical care. A total of 163 surveys were obtained from patients visiting primary care centres in the Valencian Region (Spain), during 2015–2017, with a confirmed or suspected diagnosis of RD. Of the 84.7% with a confirmed diagnosis, 50.4% had a diagnostic delay exceeding one year, and it was more prevalent among adults (62.2%). Families with paediatric patients were in a worse economic situation, with lower incomes and higher monthly disease-related expenses (€300 on average). These expenses were incurred by 66.5% of families and were mainly for medication (40.3%). Among them, 58.5% reported not being able to afford adjuvant therapies. The disease had an impact on 73.1% of families, especially on their routine and emotional state. Expenses, needs, and impacts were more frequent among families of patients with a history of hospitalisation or deterioration. Patients with delayed diagnosis had a higher consumption of drugs prior to diagnosis. People affected by RDs in the Valencian Region need therapies to improve their autonomy and emotional state. Health professionals should be aware of these needs

A five-component infection control bundle to permanently eliminate a carbapenem-resistant Acinetobacter baumannii spreading in an intensive care unit

Contains fulltext : 236719.pdf (Publisher’s version ) (Open Access

A five-component infection control bundle to permanently eliminate a carbapenem-resistant Acinetobacter baumannii spreading in an intensive care unit

none19Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection outbreaks are difficult to control and sometimes require cohorting of CRAB-positive patients or temporary ward closure for environmental cleaning. We aimed at controlling the deadly 2018 CRAB outbreak in a 12 bed- intensive care unit (ICU) including 9 beds in a 220 m2 open space. We implemented a new multimodal approach without ward closure, cohorting or temporarily limiting admissions. Methods: A five-component bundle was introduced in 2018 including reinforcement of hand hygiene and sample extension of screening, application of contact precautions to all patients, enhanced environmental sampling and the one-time application of a cycling radical environmental cleaning and disinfection procedure of the entire ICU. The ICU-CRAB incidence density (ID), ICU alcohol-based hand rub consumption and antibiotic use were calculated over a period of 6 years and intervention time series analysis was performed. Whole genome sequencing analysis (WGS) was done on clinical and environmental isolates in the study period. Results: From January 2013, nosocomial ICU-CRAB ID decreased from 30.4 CRAB cases per 1000 patients-days to zero cases per 1000 patients-days. Our intervention showed a significant impact (-2.9 nosocomial ICU-CRAB cases per 1000 bed-days), while no influence was observed for antibiotic and alcohol-based hand rub (AHR) consumption. WGS demonstrated that CRAB strains were clonally related to an environmental reservoir which confirms the primary role of the environment in CRAB ICU spreading. Conclusion: A five-component bundle of continuous hand hygiene improvement, extended sampling at screening including the environment, universal contact precautions and a novel cycling radical environmental cleaning and disinfection procedure proved to be effective for permanently eliminating CRAB spreading within the ICU. Cohorting, admission restriction or ICU closure were avoided.noneMeschiari M.; Lopez-Lozano J.-M.; Di Pilato V.; Gimenez-Esparza C.; Vecchi E.; Bacca E.; Orlando G.; Franceschini E.; Sarti M.; Pecorari M.; Grottola A.; Venturelli C.; Busani S.; Serio L.; Girardis M.; Rossolini G.M.; Gyssens I.C.; Monnet D.L.; Mussini C.Meschiari, M.; Lopez-Lozano, J. -M.; Di Pilato, V.; Gimenez-Esparza, C.; Vecchi, E.; Bacca, E.; Orlando, G.; Franceschini, E.; Sarti, M.; Pecorari, M.; Grottola, A.; Venturelli, C.; Busani, S.; Serio, L.; Girardis, M.; Rossolini, G. M.; Gyssens, I. C.; Monnet, D. L.; Mussini, C

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma

Dietary quality changes according to the preceding maximum weight: a longitudinal analysis in the PREDIMED-Plus randomized trial

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55-75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program.The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research Grant 2013–2018, 340918) to M.Á.M.-G and the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by J.S.-S. and J.Vid., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332), the Especial Action Project entitled: Implementación y evaluación de una intervención intensive sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the Recercaixa Grant to J.S.-S. (2013ACUP00194), Grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a Grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN Grant, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants (FOLIUM, PRIMUS, SYNERGIA, and LIBERI) from Balearic Islands Health Research Institute (IDISBA), funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). Cristina Bouzas received a Fernando Tarongí Bauzà Grant. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results

Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial.

To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Spanish older adults with metabolic syndrome (MetS). A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings