CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naive for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.We would like to thank all patients and healthy donors who participated in the study. This study has been funded by projects CP14/00198, PI16/01769, and RD16/0025/0013 integrated in the State Plan for Scientific and Technical Research and Innovation and co-funded by ISCIII-Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). N Rallon is a Miguel Servet investigator from the Spanish Carlos III Institute of Health (ISCIII), grant CP14/00198, Madrid, Spain. Maria Angeles Navarrete-Munoz was funded by RD16/0025/0013 and the Intramural Research Scholarship from IIS-FJD. Clara Restrepo was funded by project RD16/0025/0013. M Garcia is a predoctoral student co-funded by CP14/00198 project and the Intramural Research Scholarship from IIS-FJD.S

Higher versus lower nut consumption and changes in cognitive performance over two years in a population at risk of cognitive decline: a cohort study

Background: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function. Objective: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk. Methods: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as Results: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend Conclusion: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted

Impact of COVID-19 pandemic on the PREDIMED-Plus randomized clinical trial: Effects on the interventions, participants follow-up, and adiposity

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity. Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown. Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04]). Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity. Clinical trial registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870. Keywords: COVID-19; Mediterraean diet; PREDIMED-Plus; clinical trial; lockdown; weight-loss. Copyright © 2023 Paz-Graniel, Fitó, Ros, Buil-Cosiales, Corella, Babio, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Vázquez, Daimiel, García-Gavilán, Toledo, Nishi, Sorlí, Castañer, García-Ríos, García de la Hera, Barón-López, Ruiz-Canela, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Fernández-García, Vázquez-Ruiz, Fernández-Carrión, Goday, Peña-Orihuela, Compañ-Gabucio, Schröder, Martínez-Gonzalez and Salas-Salvadó. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial

Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (EGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired EGFR (<60 mL/min/1.73 m2) and micro-to macroalbuminuria (UACR ≥30 mg/g), and reversion of moderately (45 to <60 mL/min/1.73 m2) to mildly impaired GFR (60 to <90 mL/min/1.73 m2) or micro-to macroalbuminuria. Results: After 1 year, EGFR declined by 0.66 and 1.25 mL/min/1.73 m2 in the intervention and control groups, respectively (mean difference, 0.58 mL/min/1.73 m2; 95% CI: 0.15-1.02). There were no between-group differences in mean UACR or micro-to macroalbuminuria changes. Moderately/severely impaired EGFR incidence and reversion of moderately to mildly impaired GFR were 40% lower (HR 0.60; 0.44-0.82) and 92% higher (HR 1.92; 1.35-2.73), respectively, in the intervention group. Conclusions: The PREDIMED-Plus lifestyle intervention approach may preserve renal function and delay CKD progression in overweight/obese adults.This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is cofunded by the European Regional Development Fund (5 coordinated FIS projects leaded by J.S.-S and J.V., 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 intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S.; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to M.Á.M.-G.; the Recercaixa (No. 2013ACUP00194) grant to J.S.-S.; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council – FESNAD (Long-term effects of an energyrestricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) (PI: M.Á.M.-G.); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: D.R.); grant of support to research groups No. 35/2011 (Balearic Islands Gov.; FEDER funds) (J.A.T. and C.B.); the JR17/00022 (ISCIII) grant to O.C.; the Boosting young talent call grant program for the development of IISPV research projects 2019–2021 (Ref.: 2019/IISPV/03 grant to A.D.-L.); the Societat Catalana d’Endocrinologia i Nutrició (SCEN) Clinical-Research Grant 2019 (IPs: J.S.-S. and A.D.-L.). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to A.D.-L

Pro-vegetarian food patterns and cardiometabolic risk in the PREDIMED-Plus study: a cross-sectional baseline analysis

[Purpose]: We explored the cross-sectional association between the adherence to three different provegetarian (PVG) food patterns defined as general (gPVG), healthful (hPVG) and unhealthful (uPVG), and the cardiometabolic risk in adults with metabolic syndrome (MetS) of the PREDIMED-Plus randomized intervention study. [Methods]: We performed a cross-sectional analysis of baseline data from 6439 participants of the PREDIMED-Plus randomized intervention study. The gPVG food pattern was built by positively scoring plant foods (vegetables/fruits/legumes/grains/potatoes/nuts/olive oil) and negatively scoring, animal foods (meat and meat products/animal fats/eggs/fish and seafood/dairy products). The hPVG and uPVG were generated from the gPVG by adding four new food groups (tea and coffee/fruit juices/sugar-sweetened beverages/sweets and desserts), splitting grains and potatoes and scoring them differently. Multivariable-adjusted robust linear regression using MM-type estimator was used to assess the association between PVG food patterns and the standardized Metabolic Syndrome score (MetS z-score), a composed index that has been previously used to ascertain the cardiometabolic risk, adjusting for potential confounders. [Results]: A higher adherence to the gPVG and hPVG was associated with lower cardiometabolic risk in multivariable models. The regression coefficients for 5th vs. 1st quintile were − 0.16 (95% CI: − 0.33 to 0.01) for gPVG (p trend: 0.015), and − 0.23 (95% CI: − 0.41 to − 0.05) for hPVG (p trend: 0.016). In contrast, a higher adherence to the uPVG was associated with higher cardiometabolic risk, 0.21 (95% CI: 0.04 to 0.38) (p trend: 0.019). [Conclusion]: Higher adherence to gPVG and hPVG food patterns was generally associated with lower cardiovascular risk, whereas higher adherence to uPVG was associated to higher cardiovascular risk.This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, 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, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Mechanical and structural adaptations to migration in the flight feathers of a Palaearctic passerine

Current avian migration patterns in temperate regions have been developed during the glacial retreat and subsequent colonization of the ice-free areas during the Holocene. This process resulted in a geographic gradient of greater seasonality as latitude increased that favoured migration-related morphological and physiological (co) adaptations. Most evidence of avian morphological adaptations to migration comes from the analysis of variation in the length and shape of the wings, but the existence of intra-feather structural adjustments has been greatly overlooked despite their potential to be under natural selection. To shed some light on this question, we used data from European robins Erithacus rubecula overwintering in Campo de Gibraltar (Southern Iberia), where sedentary robins coexist during winter with conspecifics showing a broad range of breeding origins and, hence, migration distances. We explicitly explored how wing length and shape, as well as several functional (bending stiffness), developmental (feather growth rate) and structural (size and complexity of feather components) characteristics of flight feathers, varied in relation to migration distance, which was estimated from the hydrogen stable isotope ratios of the summer-produced tail feathers. Our results revealed that migration distance not only favoured longer and more concave wings, but also promoted primaries with a thicker dorsoventral rachis and shorter barb lengths, which, in turn, conferred more bending stiffness to these feathers. We suggest that these intra-feather structural adjustments could be an additional, largely unnoticed, adaptation within the avian migratory syndrome that might have the potential to evolve relatively quickly to facilitate the occupation of seasonal environments.Ministerio de Economía y Competitividad (MINECO)Depto. de Biodiversidad, Ecología y EvoluciónFac. de Ciencias BiológicasTRUEpu