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Patients with renal graft failure can develop human leukocyte antigen (HLA) sensitization when returning to dialysis. There is no consensus on which factors could be associated with an increased risk of this kind of sensitization after graft loss. To try to identify some of these factors, a retrospective observational study was performed in our center. Demographic and transplant-related data were collected: HLA mismatches, changes in calculated panel reactive antibody percentage over time, the immunosuppression withdrawal schedule during the first year on hemodialysis (HD), among others. Patients who developed anti-HLA antibodies after 1 year on HD had a greater number of total HLA mismatches (4.15 ± 1.3 vs 3.3 ± 1.1; P = .001), HLA-DR (1.35 ± 0.7 vs 0.7 ± 0.6; P = .001) and HLA-A mismatches (1.70 ± 0.5 vs 1.27 ± 0.7; P = .004) than patients who never developed anti-HLA antibodies. When we only analyzed patients who develop ≥98% calculated panel reactive antibody versus those who persist without anti-HLA antibodies, these differences were more evident (5.2 ± 1.1 MM vs 3.3 ± 1.1 MM; P < .001). The timing of discontinuation of immunosuppression did not influence sensitization. Thus, we have observed that HLA mismatches influence HLA sensitization after graft failure at least during the first year on HD. This study supports the importance of prioritizing HLA matching in patients who may require >1 graft over the years and being aware of the potential importance of HLA mismatches on sensitization on HD., Competing Interests: Declaration of competing interest All the authors declared no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used to identify GCA in cases of apparently isolated PMR., Materials and Methods: 45 patients with isolated PMR and 29 patients with PMR/GCA overlap were included. Blood samples were collected before starting glucocorticoids for all patients. Serum biomarkers reflecting systemic inflammation (interleukin-6 (IL-6), CXCL9), vascular remodelling (MMP-2, MMP-3, MMP-9) and endothelial function (sCD141, sCD146, ICAM-1, VCAM-1, vWFA2) were measured by Luminex assays., Results: Patients with GCA had higher serum levels of sCD141 (p=0.002) and CXCL9 (p=0.002) than isolated PMR. By contrast, serum levels of MMP-3 (p=0.01) and IL-6 (p=0.004) were lower in GCA than isolated PMR. The area under the curve (AUC) was calculated for sCD141, CXCL9, IL-6 and MMP-3. Separately, none of them were >0.7, but combinations revealed higher diagnostic accuracy. The CXCL9/IL-6 ratio was significantly increased in patients with GCA (p=0.0001; cut-off >32.8, AUC 0.76), while the MMP-3/sCD141 ratio was significantly lower in patients with GCA (p<0.0001; cut-off <5.3, AUC 0.79). In patients with subclinical GCA, which is the most difficult to diagnose, sCD141 and MMP-3/sCD141 ratio demonstrated high diagnostic accuracy with AUC of 0.81 and 0.77, respectively., Conclusion: Combined serum biomarkers such as CXCL9/IL-6 and MMP-3/sCD141 could help identify GCA in patients with isolated PMR. It could allow to select patients with PMR in whom complementary examinations are needed., Competing Interests: Competing interests: MS: AbbVie consulting, Argenx consulting, Boehringer Ingelheim consulting, GSK consulting, Novartis consulting and research grant, Roche–Chugai consulting, CSL Vifor consulting, Fresenius consulting. BB: Roche–Chugai personal fees for consulting, Boehringer Ingelheim consulting. AR: Novartis research grant, Novartis consulting, AbbVie consulting, Boehringer Ingelheim consulting, Chugai consulting., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum interleukin-17 concentration that correlates with red blood cell destruction parameters, namely lactate dehydrogenase and bilirubin levels. A decrease in circulating Treg, notably effector Treg, associated with a functional deficiency, as represented by their decrease capability to inhibit Teff proliferation, were also observed. Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions. Transcriptomic profiling of Treg revealed activation of the tumor necrosis facto (TNF)-α pathway, which was linked to increased serum TNF-α concentrations that were twice as high as in controls. Treg transcriptomic profiling also suggested that post-translational mechanisms possibly accounted for Foxp3 downregulation and Treg dysfunctions. Since TNF-α participates in the rupture of immune tolerance during wAIHA, its inhibition could be of interest. To this end, the effects of fostamatinib, a SYK inhibitor, were investigated in vitro, and we showed that besides the inhibition of erythrocyte phagocytosis by monocytes, fostamatinib is also able to dampen TNF-α production, thus appearing as a promising multitargeting therapy in wAIHA (clinicaltrials gov. Identifier: NCT02158195).

Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited disease due to heterozygous loss-of-function mutations on the BMP9/10 pathway ( ENG, ACVRL1 or MADH4 mainly). HHT endothelial cells are prone to lose their quiescence, leading to progressive appearance of numerous telangiectases on skin and mucosa (complicated by epistaxis and anemia), and to larger arteriovenous malformations in lungs, liver and brain. HHT is also associated with T lymphocyte abnormalities, which are currently poorly understood. We quantified by flow-cytometry the main T lymphocyte circulating subsets in 40 HHT patients and 20 matched healthy controls. Immunostaining was done on 2 HHT skin telangiectases. Disruptions in T lymphocyte homeostasis was observed, characterized by increases in subsets known to promote angiogenesis: Th2 (1.38% vs 1.15%, p=0.021), Th17 (0.32% vs 0.22%, p=0.019 2) and Treg (4.94% vs 3.51%, p= 0.027). T angiogenic lymphocytes (Tang), defined as CD3+CD31+CXCR4+ T cells, were at similar levels in both groups, but the proportion of VEGF-A+ Tang after stimulation was higher in the HHT group compared to controls (68.2% vs 44.9%, p=0.012). The global HHT T lymphopenia predominantly affected the effector memory T-helper cells (200 vs 270 cells/mm 3 , p=0.017), and the lymphocytic infiltrate around HHT telangiectases consisted of memory T-helper cells. The Th17 circulating subset was positively correlated with the monthly epistaxis duration (r coefficient: +0,431, p=0.042), prospectively assessed. HHT T-helper lymphocytes are affected by several pro-angiogenic changes, potentially resulting from their recruitment by abnormal endothelial cells. They could constitute a biologically relevant source of VEGF-A and a valuable therapeutic target in HHT., Competing Interests: 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., (Copyright © 2023 Guilhem, Ciudad, Aubriot-Lorton, Greigert, Cladière, Leguy-Seguin, Audia, Samson and Bonnotte.)

In recent years, the demand of healthier food products and products made with natural ingredients has increased overwhelmingly, led by the awareness of human beings of the influence of food on their health, as well as by the evidence of side effects generated by different ingredients such as some additives. This is the case for several artificial colorants, especially azo colorants, which have been related to the development of allergic reactions, attention deficit and hyperactivity disorder. All the above has focused the attention of researchers on obtaining colorants from natural sources that do not present a risk for consumption and, on the contrary, show biological activity. The most representative compounds that present colorant capacity found in nature are anthocyanins, anthraquinones, betalains, carotenoids and chlorophylls. Therefore, the present review summarizes research published in the last 15 years (2008-2023) in different databases (PubMed, Scopus, Web of Science and ScienceDirect) encompassing various natural sources of these colorant compounds, referring to their obtention, identification, some of the efforts made for improvements in their stability and their incorporation in different food matrices. In this way, this review evidences the promising path of development of natural colorants for the replacement of their artificial counterparts.

Beyond their nutritional benefits, vitamins could decrease the risk of chronic diseases due to their potent antioxidant capacity. The present work is aimed at reviewing the state of the art regarding (1) the vitamins involved in oxidative stress prevention in accordance with the requirements established by the European Food Safety Authority (EFSA) and (2) the foods of plant origin that are sources of those vitamins and have potential benefits against oxidative stress in humans. According to the European regulations based on EFSA scientific evidence, riboflavin, vitamin C, and vitamin E are those vitamins subjected to the approved health claim "contribute to the protection of cells from oxidative stress". Scientific studies conducted in humans with some natural food sources of riboflavin (almonds, wheat germ, mushrooms, oat bran), vitamin C (guava, kale, black currant, Brussels sprouts, broccoli, orange), and vitamin E (hazelnuts, almonds, peanuts, pistachio nuts, extra virgin olive oil, dates, rye) have been performed and published in the literature. However, no food of plant origin has obtained a favorable EFSA opinion to substantiate the approval of health claims related to its potential properties related to oxidative stress prevention. Further studies (concretely, well-controlled human intervention studies) must be carried out in accordance with EFSA requirements to provide the highest level of scientific evidence that could demonstrate the potential relationship between foods of plant origin and antioxidant capacity. This review could be useful for the scientific community to study the application of health claims referring to the antioxidant capacity potentially exerted by foods of plant origin.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity., Materials and Methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed., Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 ( HMOX1 ; T/T genotype OR 9.9 p  < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p  = 0.04 and T/T genotype OR 12.9, p  < 0.0001), and rs713400 (eQTL for TMPRSS2 ; C/T + T/T genotype OR 1.86, p  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 ( CD69 ; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p  = 0.01), rs2660 ( OAS1 ; A/G genotype OR 0.6, p  = 0.08), rs896 ( VIPR1 ; T/T genotype OR 0.4, p  = 0.02) and rs33980500 ( TRAF3IP2 ; C/T + T/T genotype OR 0.3, p  = 0.01) were associated with lower risk of viremia., Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population., Competing Interests: FA, has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, FAES, Farmalíder, Ferrer, Galenicum, GlaxoSmithKline, Gilead, Italfarmaco, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva and Zambon. IG-Á reports grants from Instituto de Salud Carlos III, during the course of the study; personal fees from Lilly and Sanofi; personal fees and non-financial support from BMS; personal fees and non-financial support from Abbvie; research support, personal fees and non-financial support from Roche Laboratories; research support from Gebro Pharma; non-financial support from MSD, Pfizer and Novartis, not related to the submitted work. The remaining 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., (Copyright © 2023 Roy-Vallejo, Fernández de Córdoba-Oñate, Delgado-Wicke, Triguero-Martínez, Montes, Carracedo-Rodríguez, Zurita-Cruz, Marcos-Jiménez, Lamana, Galván-Román, Villapalos García, Zubiaur, Ciudad, Rabes, Sanz, Rodríguez, Villa, Rodríguez, Marcos, Hernando, Díaz-Fernández, Abad, de los Santos, Rodríguez Serrano, García-Vicuña, Suárez Fernández, P. Gomariz, Muñoz-Calleja, Fernández-Ruiz, González-Álvaro Cardeñoso and the PREDINMUN-COVID Group.)

Wild edible fruits, neglected by the development of commercial agriculture, have recently aroused as a good source of natural colorants and bioactive compounds. These novel uses could cover the recent demand for healthier foods with functional properties. Prunus avium, Fragaria vesca and Vaccinium myrtillus wild fruits were characterized by individual anthocyanin profile and color CIELAB parameters, as well as phenolic fraction. In addition, some bioactivities were evaluated. In P. avium cyanidin-O-deoxyhexosyl-pentoside was the representative anthocyanin, in F. vesca pelargonidin-3-O-glucoside and in V. myrtillus delphinidin-O-hexoside. The three wild edible fruits showed interesting antioxidant activity especially in OxHLIA assays. V. myrtillus was the fruit with the best results for the bacterial growth inhibition, while F. vesca with better fungal growth inhibition. These results evidenced the richness of these wild fruits in bioactive compounds and pigments with antioxidant capacity, therefore, their potential use as natural colorants for healthier food products design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Wild Vitex agnus-castus (VAC) is a Mediterranean plant that is rich in bioactive metabolites. This study aimed to validate, for the first time, the beneficial use of VAC fruits and fruit decoctions (VFDs) through in vitro and in vivo trials. Forty-one volatile components were detected in VAC fruits, with 1,8-cineole (30.3%) comprising the majority. The antioxidant activity of VFD was measured by using different in vitro methods (EC 50 of 0.16 mg/mL by β-carotene bleaching inhibition assay) and by measuring the DNA protection power. Using the disc diffusion assay, the antimicrobial activity of VFD was evaluated, and it exhibited a noticeable anticandidal activity. VFD did not cause any toxicity or mortality in rats treated with doses > 200 mg/kg. Using the acetic acid writhing test, the antinociceptive activity of VFD was measured. Our results showed that VFD at 200 mg/kg exhibited a higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). Its gastroprotective ability was assessed by HCl/ethanol-induced gastric lesions, which were remarkably inhibited (84.62%) by intraperitoneal administration of VFD. This work helps to validate the popular use of VAC to treat nociceptive, inflammatory, and gastric disorders and encourages researchers to further investigate the identification of pharmacological compounds from this species.

Introduction: The pathogenesis of Giant Cell Arteritis (GCA) relies on vascular inflammation and vascular remodeling, the latter being poorly controlled by current treatments., Methods: This study aimed to evaluate the effect of a novel cell therapy, Human Monocyte-derived Suppressor Cells (HuMoSC), on inflammation and vascular remodeling to improve GCA treatment. Fragments of temporal arteries (TAs) from GCA patients were cultured alone or in the presence of HuMoSCs or their supernatant. After five days, mRNA expression was measured in the TAs and proteins were measured in culture supernatant. The proliferation and migration capacity of vascular smooth muscle cells (VSMCs) were also analyzed with or without HuMoSC supernatant., Results: Transcripts of genes implicated in vascular inflammation ( CCL2 , CCR2 , CXCR3 , HLADR ), vascular remodeling ( PDGF , PDGFR ), angiogenesis (VEGF) and extracellular matrix composition ( COL1A1 , COL3A1 and FN1 ) were decreased in arteries treated with HuMoSCs or their supernatant. Likewise, concentrations of collagen-1 and VEGF were lower in the supernatants of TAs cultivated with HuMoSCs. In the presence of PDGF, the proliferation and migration of VSMCs were both decreased after treatment with HuMoSC supernatant. Study of the PDGF pathway suggests that HuMoSCs act through inhibition of mTOR activity. Finally, we show that HuMoSCs could be recruited in the arterial wall through the implication of CCR5 and its ligands., Conclusion: Altogether, our results suggest that HuMoSCs or their supernatant could be useful to decrease vascular in flammation and remodeling in GCA, the latter being an unmet need in GCA treatment., Competing Interests: MS: Roche–Chugai consulting, AbbVie consulting, Boehringer Ingelheim consulting, Novartis consulting and research grant, VIFOR Pharma consulting; BB: Roche–Chugai personal fees for consulting, Boehringer Ingelheim consulting; CC-G: Horus and Bayer grant, Novartis and Bayer honoraria and Novartis, Bayer, Thea, Horus, Alcon and Allergan medical advisory board; P-HG: Allergan, Bayer and Novartis travel expenses, Novartis and Bayer honoraria; MCC: GlaxoSmithKline consulting, CSL Vifor consulting, AbbVie consulting, Janssen consulting, Astrazeneca consulting, Kiniksa Pharmaceuticals research grant; GE-F: GlaxoSmithKline consulting, Janssen consulting. The remaining 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., (Copyright © 2023 Samson, Genet, Corbera-Bellalta, Greigert, Espígol-Frigolé, Gérard, Cladière, Alba-Rovira, Ciudad, Gabrielle, Creuzot-Garcher, Tarris, Martin, Saas, Audia, Bonnotte and Cid.)

Background: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation., Methods: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected., Results: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib., Conclusions: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials., Clinical Trials Registration: EudraCT: 2020-001156-18., Competing Interests: Potential conflicts of interest. P. R. has received grant support and honoraria from Gilead and MSD; consulting fees from AbbVie SL; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from ViiV and Gilead Sciences; and support for attending meetings and/or travel from AbbVie and GSK (ViiV). J. V. has received scholarships and honorarium as speaker for Gilead Sciences. M. S. has received honoraria from Gilead; has developed educational material for MSD and ViiV Healthcare; and has served on advisory boards for MSD and Gilead. A. M. B. reports grants or contracts from GSK, Moderna, and Janssen (paid to institution); advisory fees from Janssen and Pfizer (paid to author); participation on a data and safety monitoring board (DSMB) for Pfizer, Janssen, and Medical Developments International (paid to author); payment or honoraria for lectures, presentations, manuscript writing, or educational events from Gilead and Pfizer (paid to author); and speaker’s fees from Janssen (paid to author). J. R. A. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Merck (paid to author); support for attending meetings and/or travel from MSD (paid to author); and consulting fees, advisory fees, and speaker’s fees from Gilead, Merck, Pfizer, Sobi, GSK, MSD, Serono, Lilly, and Roche (paid to author); he is also a member of the Infectious Diseases and Clinical Microbiology Society COVID-19 treatment guidelines. A. G. L. reports payment or honoraria for presentation from Gilead Sciences, and support for attending meetings and/or travel from Angelini Pharma España. A. J. C. reports grants or contracts from ISCIII, Ministry of Innovation and Science of Spain (PI21/01507, PI18/00136, CM19/00243, ICI21/00065), and Vaccelerate (Clinical trial name: EU-Covat-1 Aged); payment or honoraria for a course on clinical investigation (paid to institution) from AbbVie, and participation on a DSMB or advisory board for AMR Insights (paid to institution). C. G. reports consulting fees, participation on a DSMB or advisory board, and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Amgen, Daiichi Sankyo, Ferrer, and Sanofi; and support for attending meetings and/or travel from Sanofi and Ferrer. L. S. reports grants or contracts from Novartis and Boehringer, and support for attending meetings and/or travel from Novartis. M. R.-M. reports support for attending meetings and/or travel from Roche Farma SA. M. N. M. reports support for attending meetings and/or travel and payment/honoraria for presentations and educational events from Gilead. M. V. A. reports grants or contracts from Gilead and ViiV (paid to institution); payment or honoraria for lectures and educational events for Gilead and Janssen (paid to author and institution); payment or honoraria for educational events from ViiV and MSD (paid to institution); and support for attending meetings and/or travel from Angelini, Gilead, and Janssen (paid to author). P. G.-R. P. reports support for attending meetings and/or travel from Gilead and Angelini. P. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Sanofi (paid to author). R. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead, ViiV, Merck Sharp & Dohme, and Theratechnologies (paid to author); payment for expert testimony from Gilead and ViiV (paid to author); support for attending meetings and/or travel from Gilead and Janssen (paid to author); and participation on a DSMB or advisory board for ViiV (paid to author). S. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Pfizer, Gilead, Roche, Sobi, and MSD (paid to author), and participation on DSMBs or advisory boards for Pfizer, Gilead, and MSD (paid to author). V. E. reports consulting fees from Gilead, Janssen, and MSD (paid to author); payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead and Janssen (paid to author); support for attending meetings and/or travel from Gilead (paid to author); and participation on DSMBs or advisory boards for Gilead, Janssen, and Synairgen (paid to author). None of the listed potential conflicts are related to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Living donor kidney transplant is the best treatment for end-stage kidney disease, posing minimal perioperative morbimortality for the donor, although long-term consequences are subject of debate if donor acceptance widens. We present a retrospective observational study analyzing clinical, demographic, and analytical variables throughout the follow-up period of 60 kidney donors whose procedures were performed between 1985 and 2021 at our hospital. Donors were divided according to their previous high blood pressure status, analyzing kidney function and other clinical parameters throughout follow-up. There were no statistically significant differences, although there was a trend toward a higher uric acid levels and lower high-density lipoprotein cholesterol in predonation patients with hypertension, not yielding an excess of end-stage kidney disease between groups at the end of the follow-up. We also analyzed the evolution of estimated glomerular filtration rate (eGFR), dividing patients into tertiles, which resulted in none of the parameters associating a higher rate of progression. All donors had an eGFR >71 mL/min/1.73 m 2 at the time of donation. Over time, a decline in eGFR <60 mL/min/m/1.73 m 2 was observed in 26 patients (53.6%), measured by Chronic Kidney Disease Epidemiology Collaboration estimation and in 55.4% of the total (31 patients) by Modification of Diet in Renal Disease. At our center, kidney donors with adequate predonation eGFR, although presenting a reduction in postnephrectomy eGFR, remain stable afterward, with none of them reaching an eGFR <30 mL/min/1.73 m 2 . We found no differences in the impact of high blood pressure on long-term eGFR, nor predictive factors influencing the rate of eGFR decline. Studies with larger number of patients are needed to confirm these results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Introduction: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection., Patients and Methods: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not., Results: Thirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021)., Conclusion: This study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: This work aims to evaluate whether a clinical examination and measurement of N-terminal pro-brain natriuretic peptide can predict poor prognosis in outpatients with heart failure., Patients and Methods: We carried out a retrospective study from 2010 to 2018 in 238 patients diagnosed with heart failure. At baseline, we evaluated the presence of pulmonary rales and bilateral leg edema (clinical congestion) together with N-terminal pro-brain natriuretic peptide ≥ 1500 pg/mL (hemodynamic congestion). Patients were classified into 4 groups depending on their congestion pattern: no congestion (G1) (n = 50); clinical congestion (G2) (n = 43); hemodynamic congestion (G3) (n = 73); and clinical and hemodynamic congestion (G4) (n = 72). The primary outcome was all-cause mortality at one year of follow-up., Results: A total of 238 patients were included. The mean age was 82 years, 61.8% were women, and 20.7% had reduced left ventricular ejection fraction. Thirty patients died in the first year of follow-up (12.6%). After controlling for confounding variables (sex, recent discharge for heart failure, estimated glomerular filtration rate, and left ventricular ejection fraction), the independent risk of death in each group compared to G1 as the reference group was: G2: HR 4.121 (95%CI 1.131-15.019); G3: HR 2.511 (95%CI 1.007-6.263); and G4: HR 7.418 (95%CI 1.630-33.763)., Conclusion: Congestion in outpatients with heart failure correlates with prognosis. Patients with both clinical and hemodynamic congestion had the highest risk of all-cause death at one year., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Traditional farmers' varieties of tomato grown under extensive farming techniques are considered delicious and healthy foods and are preferred by local consumers. Tomatoes are an important component of a healthy diet, as they provide essential micronutrients, including minerals, which are vital to healthy development, disease prevention, and wellbeing. Given the considerable dietary intake of tomatoes and the scarcity of information about the bioaccessibility of inorganic constituents in this fruit, this study was carried out to evaluate the content and bioaccessibility of minerals (macro- and microelements) in tomato farmers' varieties widely cultivated in northeastern Portugal homegardens. Among the macroelements, K stood out as the most abundant mineral in the studied varieties, followed by Mg, Ca, and Na. Regarding the microelements, while the yellow tomato had higher concentrations of Fe and Cu, the round tomato had more Zn and Mn. The in vitro bioaccessibility assessment showed that, among the macroelements, Mg was more bioaccessible than Ca and K when all the tomato varieties were considered together. Among the microelements, Cu seemed to be the most bioaccessible. Although the contribution of a 100 g serving of the studied tomato farmers' varieties to the dietary reference intakes (DRIs) of minerals is relatively low, this food could contribute to reaching these mineral requirements, as it is included in the diet of most of the population, especially in Mediterranean regions.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort., Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata., Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age., Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients., Competing Interests: 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., (Copyright © 2022 Roy-Vallejo, Cardeñoso, Triguero-Martínez, Chicot Llano, Zurita, Ávalos, Barrios, Hernando, Ortiz, Rodríguez-García, Ciudad Sañudo, Marcos, García Castillo, Fontán García-Rodrigo, González, Méndez, Iturrate, Sanz-García, Villa, Sánchez-Azofra, Quicios, Arribas, Álvarez Rodríguez, Patiño, Trigueros, Uriarte, Martín-Ramírez, Arévalo Román, Galván-Román, García-Vicuña, Ancochea, Muñoz-Calleja, Fernández-Ruiz, de la Cámara, Suárez Fernández, González-Álvaro, Rodríguez-Serrano and the PREDINMUN-COVID Group.)

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020)., (© 2022. The Author(s).)

Background: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry., Methods: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients. For the present analysis, we used the Spanish cohort, and the primary outcome was any thromboembolism (TE)/acute coronary syndrome (ACS)/cardiovascular death during the first year of follow-up., Results: 729 AF patients were included (57.1% male, median age 75 [IQR 67-81] years, median CHA 2 DS 2 -VASc and HAS-BLED of 3 [IQR 2-5] and 2 [IQR 1-2], respectively). 548 (75.2%) patients received OAC alone (318 [43.6%] on VKAs and 230 [31.6%] on DOACs). After 1 year, the use of OAC alone showed lower rates of any TE/ACS/cardiovascular death (3.0%/year; p < 0.001) compared to other regimens, and non-use of OAC alone (HR 4.18, 95% CI 2.12-8.27) was independently associated with any TE/ACS/cardiovascular death. Balancing the effects of treatment, the NNTnet to provide an overall benefit of OAC therapy was 24. The proportion of patients on OAC increased at 1 year (87% to 88.1%), particularly on DOACs (33.6% to 39.9%) (p = 0.015), with low discontinuation rates., Conclusions: In this contemporary cohort of AF patients, OAC therapy was associated with better clinical outcomes at 1 year and positive NNTnet. OAC use slightly increased during the follow-up, with low discontinuation rates and higher prescription of DOACs., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Recently developed cell-based therapies have shown potential for graft-versus-host disease (GvHD) mitigation. Our team previously developed a protocol to generate human monocyte-derived suppressor Cells (HuMoSC), a subpopulation of CD33+ suppressor cells of monocytic origin. CD33+HuMoSC successfully reduced xenoGvHD severity in NOD/SCID/IL-2Rγc -/- (NSG) mice. While CD33+ HuMoSC culture supernatant inhibits T cell activation and proliferation, the recovery of CD33+ HuMoSC immunosuppressive cells and the subsequent production of their supernatant is limited. An attractive solution would be to use both the CD33+ and the large number of CD14+ cells derived from our protocol. Here, we assessed the immunoregulatory properties of the CD14+HuMoSC supernatant and demonstrated that it inhibited both CD4 and CD8 T cell proliferation and decreased CD8 cytotoxicity. In vivo , injection of CD14+HuMoSC supernatant reduced xenoGvHD in NSG mice. Furthermore, CD14+HuMoSC supernatant maintained its immunoregulatory properties in an inflammatory environment. Proteomic and multiplex analyses revealed the presence of immunosuppressive proteins such as GPNMB, galectin-3 and IL-1R(A) Finally, CD14+HuMoSC supernatant can be produced using good manufacturing practices and be used as complement to current immunosuppressive drugs. CD14+HuMoSC supernatant is thus a promising therapy for preventing GvHD. ., Competing Interests: 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., (Copyright © 2022 Gérard, Thébault, Lamarthée, Genet, Cattin, Brazdova, Janikashvili, Cladière, Ciudad, Ouandji, Ghesquière, Greigert, Tinel, Adotevi, Saas, Samson, Audia and Bonnotte.)

Extrusion cooking allows the development of value-added products from pulses, such as gluten-free snacks with added functional properties. The main objective of this study was to evaluate the changes induced by the extrusion process on the carbohydrate fraction (total carbohydrates, soluble sugars and oligosaccharides, dietary fiber, and arabinoxylans) of novel flour formulations based on chickpeas and rice enriched with different dietary fiber sources. Moreover, the influence of the addition of fiber-rich ingredients, such as Fibersol ® and passion fruit, on the analyzed compounds was also evaluated. Sucrose was the main soluble sugar found in analyzed formulations, and raffinose was the prevalent oligosaccharide, followed by stachyose. The content of total α-galactosides tended to be higher after extrusion cooking. As a consequence of the extrusion treatment, the content of total and soluble dietary fiber was statistically increased in most of the analyzed samples. In general, no significant changes were observed in total arabinoxylan content as a consequence of the extrusion process, while the content of water-soluble arabinoxylans was significantly increased in extruded formulations. It was observed that the content of total available carbohydrates, stachyose, and water-soluble arabinoxylans were significantly influenced by the addition of passion fruit, Fibersol ® , and both. The incorporation of these ingredients in gluten-free formulations based on chickpeas and rice allows one to obtain suitable functional formulations for the development of innovative, gluten-free, extruded snack-type products, which could be an interesting alternative for people with celiac disease.

Objectives: To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab., Methods: Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab ( n  = 20) or glucocorticoids ( n  = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T-cell (Teff) proliferation and polarisation into Th1 and Th17 cells., Results: Treg (CD4 + CD25 high FoxP3 + ) frequency in total CD4 + T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P  < 0.001) and increased after treatment with tocilizumab but worsened after treatment with glucocorticoids alone. Treg lacking exon 2 of FoxP3 were increased in GCA patients when compared to controls (23% vs. 10% of total Treg, P  = 0.0096) and normalised after treatment with tocilizumab + glucocorticoids but not glucocorticoids alone. In GCA patients, Treg were unable to control Teff proliferation and induced ˜50% increase in the amount of IL-17 + Teff, which was improved after in vitro blockade of the IL-6 pathway by tocilizumab., Conclusion: This study reports quantitative and functional disruptions in the regulatory immune response of GCA patients and demonstrates that, unlike glucocorticoids, tocilizumab improves Treg immune response., Competing Interests: Maxime Samson has received travel fees and personnel fees for symposium and boards from Roche–Chugaï, and consulting fees from AbbVie. Bernard Bonnotte serves as a board member for Roche–Chugaï. Catherine CREUZOT‐GARCHER has received a grant from Horus and Bayer, honoraria from Novartis and Bayer and serves as a medical advisory board member for Novartis, Bayer, Thea, Horus, Alcon and Allergan. Pierre‐Henry Gabrielle has received travel expenses from Allergan, Bayer and Novartis, and honoraria from Novartis and Bayer., (© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3 + CD4 - TCRγδ - TCRVα7.2 + CD161 + phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy. MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αβ-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032). In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance-mostly represented by a regulatory T-cell defect-allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells by their antigen-presenting functions. Moreover, the activation of the classical complement pathway participates to platelet opsonization and also to their destruction by complement-dependent cytotoxicity. Platelet destruction is also mediated by a FcγR-independent pathway, involving platelet desialylation that favors their binding to the Ashwell-Morell receptor and their clearance in the liver. Cytotoxic T cells also contribute to ITP pathogenesis by mediating cytotoxicity against megakaryocytes and peripheral platelets. The deficient megakaryopoiesis resulting from both the humoral and the cytotoxic immune responses is sustained by inappropriate levels of thrombopoietin, the major growth factor of megakaryocytes. The better understanding of ITP pathogenesis has provided important therapeutic advances. B cell-targeting therapies and thrombopoietin-receptor agonists (TPO-RAs) have been used for years. New emerging therapeutic strategies that inhibit FcγR signaling, the neonatal Fc receptor or the classical complement pathway, will deeply modify the management of ITP in the near future., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Immunosuppressive cell-based therapy is a recent strategy for controlling Graft- versus -Host Disease (GvHD). Such cells ought to maintain their suppressive function in inflammatory conditions and in the presence of immunosuppressive agents currently used in allogeneic hematopoietic cell transplantation (allo-HCT). Moreover, these therapies should not diminish the benefits of allo-HCT, the Graft- versus -Leukemia (GvL) effect. We have previously reported on a novel subset of human monocyte-derived suppressor cells (HuMoSC) as a prospective approach for controlling GvHD.Objective., The objective of this study was to explore the therapeutic relevance of the HuMoSC in clinical conditions., Methods: Immune regulatory functions of HuMoSC were assessed in inflammatory conditions and in the presence of immunosuppressants. The therapeutic efficiency of the association of HuMoSC with immunosuppressants was evaluated in an experimental model of GvHD induced by human PBMC in NOD/SCID/IL2-Rγ c -/- (NSG) mice., Interestingly, the inhibitory functions of HuMoSC against T lymphocytes and their ability to polarize Treg are preserved, in vitro , in inflammatory environments and are not affected by immunosuppressive agents. In vivo , the association of HuMoSC-based treatment with an immunosuppressive drug showed a synergistic effect for controlling GvHD. Furthermore, HuMoSC control GvHD while preserving GvL effect in a xeno-GvHD conditioned mouse model with cell neoplasm (CAL-1). HuMoSC are generated according to good manufacturing practices (GMP) and we demonstrated that these cells tolerate long-term preservation with unaltered phenotype and function.Conclusion., HuMoSC-based therapy represents a promising approach for controlling GvHD and could be quickly implemented in clinical practice., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

The food industry is increasingly innovating and applying new processing technologies and ingredients to develop novel food products that meet the consumers' demand. In this study, the effect of extrusion (at 140 °C and 160 °C) was evaluated in different lentil flours formulations enriched with nutritional yeast, in terms of α-galactosides (raffinose, stachyose, verbascose), inositol phosphates (IPs), trypsin inhibitors and lectins content. The content of α-galactosides and IPs was determined by high performance liquid chromatography. Trypsin inhibitor activity (TIA) was evaluated using a small-scale quantitative assay. The lectin content was analyzed using a haemagglutination assay and a Competitive Indirect Enzyme-linked immunosorbent assay. Extrusion promoted a significant increase, up to 85% in total α-galactosides content. After extrusion, IPs content was significantly decreased and TIA as well as lectins content had a reduction higher than 90%. Extrusion demonstrated to have a beneficial effect by increasing desirable prebiotic compounds and decreasing non-nutritional factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Carbapenemase-producing Enterobacteriaceae (CPE) has become a significant problem in terms of public health and clinical outcome., Objective: To assess the epidemiology, treatment and mortality in patients with infection due to CPE., Material and Methods: A retrospective analysis of 163 patients with CPE infection was carried out in a university hospital from July 2013 to October 2015., Results: A total of 163 patients were included over the study period. Klebsiella pneumoniae was isolated in 95.1% of cases, and most of carbapenemases belonged to the OXA-48 group (93.0%). Acquisition was nosocomial in 124 cases (77.0%), healthcare-associated in 30 (18.6%), and 7 cases (4.3%) were community-acquired. The most frequent infections identified in this study were urinary tract (48.4%) and respiratory (19.5%) infections. Approximately half of the patients received antibiotic monotherapy. The 30-day mortality rate was 23.3%. Multivariate analysis revealed that the presence of septic shock at diagnosis (OR 4.2; IC 95% 1.5-11) was independently associated with an increase in death during the first month, unable to identify association with inappropriate antibiotic treatment., Discussion: Further studies are needed to clarify whether antibiotic treatment of EPC infections should be combined or if monotherapy might be sufficient in mild infections.

In this work, the chemical and physical profile of 5 different bread types (Multicereal bread, Bavaria wheat bread, Wholemeal bread, Rye and Oat bread) were analysed in depth, namely the nutritional profile, individual fatty acids and soluble sugars through GC-FID and HPLC-RI, respectively, as well as the mineral profile, including micro and macroelements. Furthermore, a texture profile analysis was carried out in addition to the measurement of the crust colour. Each bread type showed a distinct profile, with Wholemeal and Bavaria having the lowest calories, and Oat the highest. Multicereal showed the highest amount of unsaturated fatty acids, while Wholemeal and Rye scored the least sodium amounts. The hardest bread was Rye and the easiest to chew were Oat and Bavaria breads. The latter was also the one with the darkest crumb of all the analysed breads. This work shows that bread can be baked to meet the needs and particularities of various kinds of diets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Recurrent infective endocarditis (IE) is a major complication of patients surviving a first episode of IE. This study sought to analyse the current state of recurrent IE in a large contemporary cohort., Methods: 1335 consecutive episodes of IE were recruited prospectively in three tertiary care centres in Spain between 1996 and 2015. Episodes were categorised into group I (n=1227), first-IE episode and group II (n=108), recurrent IE (8.1%). After excluding six patients, due to lack of relevant data, group II was subdivided into IIa (n=87), reinfection (different microorganism), and IIb (n=15), relapse (same microorganism within 6 months of the initial episode)., Results: The cumulative burden and incidence of recurrence was slightly lower in the second decade of the study (2006-2015) (7.17 vs 4.10 events/100 survivors and 7.51% vs 3.82, respectively). Patients with reinfections, compared with group I, were significantly younger, had a higher frequency of HIV infection, were more commonly intravenous drug users (IVDU) and prosthetic valve carriers, had less embolic complications and cardiac surgery, with similar in-hospital mortality. IVDU was found to be an independent predictor of reinfection (HR 3.92, 95% CI 1.86 to 8.28).In the relapse IE group, prosthetic valve endocarditis (PVE) and periannular complications were more common. Among patients treated medically, those with PVE had a higher relapse incidence (4.82% vs 0.43% in native valve IE, p=0.018). Staphylococcus aureus and PVE were independent predictors of relapse (HR 3.14, 95% CI 1.11 to 8.86 and 3.19, 95% CI 1.13 to 9.00, respectively) and in-hospital-mortality was similar to group I. Three-year all-cause mortality was similar in recurrent episodes compared with single episodes., Conclusion: Recurrent IE remains a frequent late complication. IVDU was associated with a fourfold increase in the risk of reinfection. PVE treated medically and infections caused by S. aureus increased the risk of relapse. In-hospital and long-term mortality was comparable among groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Wheat is an important cereal with a key role in human nutrition. In this study, dietary fiber (DF) and arabinoxylans of different durum ( Triticum turgidum ssp. Durum L.) and bread ( Triticum aestivum L.) wheat flours were analyzed in order to point out their potential nutritional and health claims allege according to the current European regulation (Regulation (EU) No 432/2012). Moreover, other bioactive compounds (phenolics and tocopherols) were quantified as a first approach to their phytochemical composition in the analyzed wheat varieties. DF was analyzed following AOAC enzymatic-gravimetric methods; arabinoxylans and total phenols were quantified by colorimetric methods; tocopherols were determined by HPLC; antioxidant activity was evaluated using three different in vitro assays. Insoluble DF was the prevailing fraction in all analyzed samples. Water extractable arabinoxylans were higher in durum wheat flours. Whole flours contained higher total phenolics compounds. Alpha-tocopherol was the major isoform. Whole flours showed higher antioxidant properties. According to the obtained results, it is possible to allege all approved health claims referred to wheat, since all analyzed samples, especially whole flour and bran fraction, showed potential health benefits, as functional ingredients or functional foods, related with their phytochemical composition.