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1.
J Clin Invest ; 134(19)2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39352394

RÉSUMÉ

Infants with biallelic IL7R loss-of-function variants have severe combined immune deficiency (SCID) characterized by the absence of autologous T lymphocytes, but normal counts of circulating B and NK cells (T-B+NK+ SCID). We report 6 adults (aged 22 to 59 years) from 4 kindreds and 3 ancestries (Colombian, Israeli Arab, Japanese) carrying homozygous IL7 loss-of-function variants resulting in combined immunodeficiency (CID). Deep immunophenotyping revealed relatively normal counts and/or proportions of myeloid, B, NK, and innate lymphoid cells. By contrast, the patients had profound T cell lymphopenia, with low proportions of innate-like adaptive mucosal-associated invariant T and invariant NK T cells. They also had low blood counts of T cell receptor (TCR) excision circles, recent thymic emigrant T cells and naive CD4+ T cells, and low overall TCR repertoire diversity, collectively indicating impaired thymic output. The proportions of effector memory CD4+ and CD8+ T cells were high, indicating IL-7-independent homeostatic T cell proliferation in the periphery. Intriguingly, the proportions of other T cell subsets, including TCRγδ+ T cells and some TCRαß+ T cell subsets (including Th1, Tfh, and Treg) were little affected. Peripheral CD4+ T cells displayed poor proliferation, but normal cytokine production upon stimulation with mitogens in vitro. Thus, inherited IL-7 deficiency impairs T cell development less severely and in a more subset-specific manner than IL-7R deficiency. These findings suggest that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin, governs an IL-7-independent pathway of human T cell development.


Sujet(s)
Interleukine-7 , Récepteurs à l'interleukine-7 , Humains , Interleukine-7/immunologie , Interleukine-7/génétique , Interleukine-7/métabolisme , Adulte , Récepteurs à l'interleukine-7/génétique , Récepteurs à l'interleukine-7/immunologie , Récepteurs à l'interleukine-7/métabolisme , Mâle , Femelle , Adulte d'âge moyen , Immunodéficience combinée grave/immunologie , Immunodéficience combinée grave/génétique , Immunodéficience combinée grave/anatomopathologie , Lignage cellulaire/immunologie , Lymphocytes T/immunologie , Sous-unité alpha du récepteur à l'interleukine-7
2.
Sci Rep ; 14(1): 20728, 2024 09 05.
Article de Anglais | MEDLINE | ID: mdl-39237611

RÉSUMÉ

The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.


Sujet(s)
COVID-19 , Polymorphisme de nucléotide simple , SARS-CoV-2 , Indice de gravité de la maladie , Humains , COVID-19/génétique , COVID-19/immunologie , COVID-19/virologie , Mâle , Femelle , Adulte d'âge moyen , SARS-CoV-2/génétique , SARS-CoV-2/immunologie , Sujet âgé , Adulte , Récepteur de type Toll-7/génétique , TYK2 Kinase/génétique , Génotype , Prédisposition génétique à une maladie , 2',5'-Oligoadenylate synthetase/génétique
3.
Proc Natl Acad Sci U S A ; 121(37): e2321794121, 2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39231201

RÉSUMÉ

We report two unrelated adults with homozygous (P1) or compound heterozygous (P2) private loss-of-function variants of V-Rel Reticuloendotheliosis Viral Oncogene Homolog B (RELB). The resulting deficiency of functional RelB impairs the induction of NFKB2 mRNA and NF-κB2 (p100/p52) protein by lymphotoxin in the fibroblasts of the patients. These defects are rescued by transduction with wild-type RELB complementary DNA (cDNA). By contrast, the response of RelB-deficient fibroblasts to Tumor Necrosis Factor (TNF) or IL-1ß via the canonical NF-κB pathway remains intact. P1 and P2 have low proportions of naïve CD4+ and CD8+ T cells and of memory B cells. Moreover, their naïve B cells cannot differentiate into immunoglobulin G (IgG)- or immunoglobulin A (IgA)-secreting cells in response to CD40L/IL-21, and the development of IL-17A/F-producing T cells is strongly impaired in vitro. Finally, the patients produce neutralizing autoantibodies against type I interferons (IFNs), even after hematopoietic stem cell transplantation, attesting to a persistent dysfunction of thymic epithelial cells in T cell selection and central tolerance to some autoantigens. Thus, inherited human RelB deficiency disrupts the alternative NF-κB pathway, underlying a T- and B cell immunodeficiency, which, together with neutralizing autoantibodies against type I IFNs, confers a predisposition to viral, bacterial, and fungal infections.


Sujet(s)
Immunité acquise , Immunité innée , Facteur de transcription RelB , Humains , Facteur de transcription RelB/génétique , Facteur de transcription RelB/métabolisme , Immunité acquise/génétique , Femelle , Mâle , Lymphocytes B/immunologie , Sous-unité p52 de NF-kappa B/génétique , Sous-unité p52 de NF-kappa B/métabolisme , Adulte , Fibroblastes/métabolisme , Fibroblastes/immunologie , Interféron de type I/immunologie , Interféron de type I/métabolisme
4.
J Clin Rheumatol ; 30(7): 264-270, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39264828

RÉSUMÉ

BACKGROUND: Hospital-acquired bacterial infections are associated with high morbidity and mortality rates in patients with systemic lupus erythematosus (SLE). This study aimed to develop and validate predictive models for the risk of hospital-acquired bacterial infections in patients with SLE. METHODS: A historical cohort study was designed for development, and another bidirectional cohort study was used for external validation. The risk of bacterial infection was assessed upon admission and after 5 days of hospitalization. Predictor selection employed the least absolute shrinkage and selection operator (LASSO) techniques. Multiple imputations were used to handle missing data. Logistic regression models were applied, and the properties of discrimination, calibration, and decision curve analysis were evaluated. RESULTS: The development cohort comprised 1686 patients and 237 events (14.1%) from 3 tertiary hospitals. The external validation cohort included 531 patients and 84 infection outcomes (15.8%) from 10 hospital centers in Colombia (secondary and tertiary level). The models applied at admission and after 120 hours of stay exhibited good discrimination (AUC > 0.74). External validation demonstrated good performance among patients from the same tertiary institutions where the models were developed. However, geographic validation at other institutions has been suboptimal. CONCLUSIONS: Two predictive models for nosocomial bacterial infections in patients with SLE are presented. All infection prevention recommendations should be maximized in patients at moderate/high risk. Further validation studies in diverse contexts, as well as clinical impact trials, are necessary before potential applications in research and clinical care.


Sujet(s)
Infection croisée , Lupus érythémateux disséminé , Humains , Lupus érythémateux disséminé/complications , Lupus érythémateux disséminé/épidémiologie , Femelle , Mâle , Infection croisée/épidémiologie , Infection croisée/diagnostic , Infection croisée/prévention et contrôle , Adulte , Colombie/épidémiologie , Infections bactériennes/épidémiologie , Infections bactériennes/diagnostic , Adulte d'âge moyen , Appréciation des risques/méthodes , Études de cohortes , Facteurs de risque , Modèles logistiques
5.
Nature ; 633(8029): 417-425, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39198650

RÉSUMÉ

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.


Sujet(s)
Macrophages , Tuberculose pulmonaire , Facteurs de nécrose tumorale , Adulte , Femelle , Humains , Mâle , Facteur de stimulation des colonies de granulocytes et de macrophages/métabolisme , Homozygote , Cellules souches pluripotentes induites/métabolisme , Cellules souches pluripotentes induites/immunologie , Cellules souches pluripotentes induites/cytologie , Inflammation/immunologie , Interféron gamma/immunologie , Mutation perte de fonction , Poumon/cytologie , Poumon/effets des médicaments et des substances chimiques , Macrophages/cytologie , Macrophages/effets des médicaments et des substances chimiques , Macrophages/immunologie , Macrophages/métabolisme , Macrophages/anatomopathologie , Macrophages alvéolaires/cytologie , Macrophages alvéolaires/effets des médicaments et des substances chimiques , Macrophages alvéolaires/immunologie , Macrophages alvéolaires/microbiologie , Macrophages alvéolaires/anatomopathologie , Mycobacterium tuberculosis/immunologie , Phénotype , Espèces réactives de l'oxygène/métabolisme , Récepteur au facteur de nécrose tumorale de type I/déficit , Récepteur au facteur de nécrose tumorale de type I/génétique , Récepteur au facteur de nécrose tumorale de type I/métabolisme , Stimulation du métabolisme oxydatif , Tuberculose pulmonaire/immunologie , Tuberculose pulmonaire/microbiologie , Tuberculose pulmonaire/génétique , Inhibiteurs du facteur de nécrose tumorale/pharmacologie , Facteurs de nécrose tumorale/déficit , Facteurs de nécrose tumorale/génétique , Adolescent , Jeune adulte
6.
Arch Bronconeumol ; 2024 Jul 10.
Article de Anglais, Espagnol | MEDLINE | ID: mdl-39068054

RÉSUMÉ

INTRODUCTION: Pulmonary function tests are vital for diagnosing lung diseases, assessing treatment responses, and monitoring respiratory health. Recent updates to interpretive standards by the European Respiratory and American Thoracic Societies (ERS/ATS) in 2022 introduced significant changes compared to the 2005 standards. They include incorporating lung volume measurements, non-specific and mixed disorders, introducing z-scores for functional abnormality assessment, reducing severity categories from five to three, and revising criteria for positive bronchodilator responses. METHODS: We conducted a retrospective, multi-center study across four centers using spirometric data spanning from 2002 to 2022. We categorized spirometry results using both the 2005 and 2022 ATS/ERS standards and calculated predicted values following the GLI 2012 equation (Caucasian subset). RESULTS: Among 79,039 subjects, we observed that 23% shifted from an obstructive diagnosis under the 2005 standard to a mixed pattern diagnosis under the 2022 standard, necessitating lung volume assessments. In the evaluation of bronchodilator responses among 59,203 tests, 12.3% of those initially classified as responders were reclassified as non-responders with the new standards. We found variations in severity categorization across age groups, with older patients tending to receive milder severity classifications and younger individuals receiving greater severity classifications under the 2022 standards. CONCLUSIONS: The 2022 document emphasizes early lung volume assessment, potentially leading to increased utilization of more complex tests. Furthermore, the bronchodilator response was predominant in extreme age groups and among individuals with milder spirometric impairments. This shift may impact treatment decisions, potentially initiating medication in milder cases and de-escalating treatment in more severe cases.

7.
Lupus Sci Med ; 11(2)2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39059814

RÉSUMÉ

OBJECTIVE: To explore the potential associations between high-density lipoprotein (HDL) levels and inflammasome components in the context of systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted. A group of 50 patients with SLE and 50 healthy controls matched by sex and similar age ranges were enrolled. Serum HDL cholesterol (HDL-C) and C reactive protein (CRP) levels were quantified. Serum cytokine levels, including IL-1ß and IL-6, were determined by ELISA. The gene expression of inflammasome-related genes in peripheral blood mononuclear cells was measured by quantitative real-time PCR. RESULTS: HDL-C levels were lower in the patients with SLE (p<0.05), and on segregation according to disease activity, those with active SLE had the lowest HDL-C levels. Patients with SLE presented higher concentrations of the serum inflammatory cytokines IL-1ß and IL-6 (p<0.0001) but similar levels of CRP to those in controls. A similar scenario was observed for the gene expression of inflammasome components, where all the evaluated markers were significantly upregulated in the SLE population. These results revealed significant negative correlations between HDL levels and disease activity, serum IL-6 and IL-1ß levels and the mRNA expression of NLRP3, IL-1ß and IL-18. In addition, significant positive correlations were found between disease activity and serum IL-1ß and between disease activity and the mRNA expression of IL-18, and interestingly, significant positive correlations were also observed between active SLE and serum IL-1ß and the mRNA expression of NLRP3. CONCLUSION: Our results suggest that HDL is essential for SLE beyond atherosclerosis and is related to inflammation regulation, possibly mediated by inflammasome immunomodulation.


Sujet(s)
Protéine C-réactive , Inflammasomes , Interleukine-1 bêta , Lupus érythémateux disséminé , Humains , Lupus érythémateux disséminé/immunologie , Lupus érythémateux disséminé/sang , Femelle , Mâle , Études transversales , Adulte , Inflammasomes/immunologie , Adulte d'âge moyen , Interleukine-1 bêta/sang , Protéine C-réactive/analyse , Lipoprotéines HDL/sang , Agranulocytes/immunologie , Agranulocytes/métabolisme , Études cas-témoins , Interleukine-6/sang , Cholestérol HDL/sang , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Cytokines/sang
8.
J Clin Immunol ; 44(7): 163, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39008214

RÉSUMÉ

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.


Sujet(s)
Anticorps neutralisants , Autoanticorps , Cryptococcose , Cryptococcus gattii , Cryptococcus neoformans , Facteur de stimulation des colonies de granulocytes et de macrophages , Humains , Facteur de stimulation des colonies de granulocytes et de macrophages/immunologie , Autoanticorps/sang , Autoanticorps/immunologie , Mâle , Colombie , Femelle , Adulte , Cryptococcus gattii/immunologie , Adulte d'âge moyen , Cryptococcus neoformans/immunologie , Cryptococcose/immunologie , Cryptococcose/diagnostic , Anticorps neutralisants/sang , Anticorps neutralisants/immunologie , Études rétrospectives , Séronégativité VIH/immunologie , Jeune adulte , Sujet âgé
9.
J Exp Med ; 221(8)2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-38869500

RÉSUMÉ

UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.


Sujet(s)
Érythème pernio , Lupus érythémateux disséminé , Récepteur de type Toll-7 , Femelle , Humains , Mâle , Érythème pernio/génétique , Mutation gain de fonction , Cellules HEK293 , Lupus érythémateux cutané/génétique , Lupus érythémateux cutané/anatomopathologie , Lupus érythémateux disséminé/génétique , Protéines de transport membranaire/génétique , Protéines de transport membranaire/métabolisme , Mutation faux-sens , Pedigree , Récepteur de type Toll-7/génétique , Récepteur de type Toll-7/métabolisme , Récepteur de type Toll-8/génétique , Récepteur de type Toll-8/métabolisme , Enfant d'âge préscolaire , Enfant , Jeune adulte , Adulte
10.
Angew Chem Int Ed Engl ; 63(37): e202409524, 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-38923738

RÉSUMÉ

A ruthenium-catalyzed reductive amination via asymmetric transfer hydrogenation (ATH) has been used to perform an efficient dynamic kinetic resolution (DKR) of N-aryl 2-formyl pyrroles decorated with a phosphine moiety positioned at the ortho' position. The strategy relies on the labilization of the stereogenic axis in the substrate facilitated by a transient Lewis acid-base interaction (LABI) between the carbonyl carbon and the phosphorus center. The reaction features broad substrate scope of aliphatic amines and N-aryl pyrrole scaffolds, and proceeds under very mild conditions to afford P,N atropisomers in good to high yields and excellent enantioselectivities (up to 99 % ee) for both diphenyl and dicyclohexylphosphino derivatives.

11.
Biol Trace Elem Res ; 2024 Jun 10.
Article de Anglais | MEDLINE | ID: mdl-38853197

RÉSUMÉ

The study aimed to assess the impact of injectable trace mineral ("ITM"; Multimin90; Fort Collins, CO) supplementation on bacterial infection in cattle. Angus-crossbred steers (n = 32) were organized into two blocks by initial body weight. Steers were maintained on a ryelage and dry-rolled corn-based growing diet without supplementation of Zn, Cu, Mn, and Se for the duration of the study. The steers were transported 6 h, then randomized into three treatment groups: control received sterile saline ("CON"), ITM administered 1 day after transport (6 days before infection, "ITMPRE"), and ITM administered 2 days post infection (dpi) concurrent with antibiotic treatment ("ITMPOST"). Steers were infected with Mannheimia haemolytica on day 0, and all were treated with tulathromycin at 2 dpi. Plasma levels of Zn, Cu, and Se did not differ among treatments (P ≥ 0.74). Liver Se was higher in ITMPRE at 2 dpi (P < 0.05), and both ITM groups had higher liver Se at 5 dpi (P < 0.05) compared to CON. A time × treatment interaction was detected for liver Cu (P = 0.02). Clinical scores were lower (P < 0.05) in ITMPRE on 1 and 8 dpi and ITMPOST on 8 dpi compared to CON. Thoracic ultrasonography scores were lower in ITMPRE at 2 dpi compared to CON (P < 0.05) and ITMPOST (P < 0.1). No treatment effects (P > 0.10) were observed for bacterial detection from bronchoalveolar lavage (BAL) or nasopharyngeal swabs. At 5 dpi, both ITMPRE and ITMPOST showed higher frequencies of γδ T cells and NK cells in BAL compared to CON (P < 0.05). Before infection, leukocytes from ITMPRE steers produced more IL-6 (P < 0.01) in response to stimulation with the TLR agonist, Pam3CSK4. Use of ITM may be an effective strategy for improving disease resistance in feedlot cattle facing health challenges.

12.
PLoS One ; 19(6): e0301860, 2024.
Article de Anglais | MEDLINE | ID: mdl-38833461

RÉSUMÉ

OBJECTIVE: To assess the effectiveness of different machine learning models in estimating the pharmaceutical and non-pharmaceutical expenditures associated with Diabetes Mellitus type II diagnosis, based on the clinical risk index determined by the analysis of comorbidities. MATERIALS AND METHODS: In this cross-sectional study, we have used data from 11,028 anonymized records of patients admitted to a high-complexity hospital in Bogota, Colombia between 2017-2019 with a primary diagnosis of Diabetes. These cases were classified according to Charlson's comorbidity index in several risk categories. The main variables analyzed in this study are hospitalization costs (which include pharmaceutical and non-pharmaceutical expenditures), age, gender, length of stay, medicines and services consumed, and comorbidities assessed by the Charlson's index. The model's dependent variable is expenditure (composed of pharmaceutical and non-pharmaceutical expenditures). Based on these variables, different machine learning models (Multivariate linear regression, Lasso model, and Neural Networks) were used to estimate the pharmaceutical and non-pharmaceutical expenditures associated with the clinical risk classification. To evaluate the performance of these models, different metrics were used: Mean Absolute Percentage Error (MAPE), Mean Squared Error (MSE), Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), and Coefficient of Determination (R2). RESULTS: The results indicate that the Neural Networks model performed better in terms of accuracy in predicting pharmaceutical and non-pharmaceutical expenditures considering the clinical risk based on Charlson's comorbidity index. A deeper understanding and experimentation with Neural Networks can improve these preliminary results, therefore we can also conclude that the main variables used and those that were proposed can be used as predictors for the medical expenditures of patients with diabetes type-II. CONCLUSIONS: With the increase of technology elements and tools, it is possible to build models that allow decision-makers in hospitals to improve the resource planning process given the accuracy obtained with the different models tested.


Sujet(s)
Diabète de type 2 , Dépenses de santé , Apprentissage machine , Humains , Diabète de type 2/économie , Diabète de type 2/traitement médicamenteux , Mâle , Femelle , Études transversales , Adulte d'âge moyen , Colombie/épidémiologie , Sujet âgé , Hospitalisation/économie , Comorbidité , Adulte , Facteurs de risque
13.
Nutrients ; 16(11)2024 May 22.
Article de Anglais | MEDLINE | ID: mdl-38892494

RÉSUMÉ

OBJECTIVE: Medical nutrition therapy provides the opportunity to compensate for muscle wasting and immune response activation during stress and trauma. The objective of this systematic review is to assess the safety and effectiveness of early enteral nutrition (EEN) in adults with sepsis or septic shock. METHODS: The MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and ICTRP tools were searched from inception until July 2023. Conference proceedings, the reference lists of included studies, and expert content were queried to identify additional publications. Two review authors completed the study selection, data extraction, and risk of bias assessment; disagreements were resolved through discussion. Inclusion criteria were randomized controlled trials (RCTs) and non-randomized studies (NRSs) comparing the administration of EEN with no or delayed enteral nutrition (DEE) in adult populations with sepsis or septic shock. RESULTS: Five RCTs (n = 442 participants) and ten NRSs (n = 3724 participants) were included. Low-certainty evidence from RCTs and NRSs suggests that patients receiving EEN could require fewer days of mechanical ventilation (MD -2.65; 95% CI, -4.44-0.86; and MD -2.94; 95% CI, -3.64--2.23, respectively) and may show lower SOFA scores during follow-up (MD -1.64 points; 95% CI, -2.60--0.68; and MD -1.08 points; 95% CI, -1.90--0.26, respectively), albeit with an increased frequency of diarrhea episodes (OR 2.23, 95% CI 1.115-4.34). Even though the patients with EEN show a lower in-hospital mortality rate both in RCTs (OR 0.69; 95% CI, 0.39-1.23) and NRSs (OR 0.89; 95% CI, 0.69-1.13), this difference does not achieve statistical significance. There were no apparent differences for other outcomes. CONCLUSIONS: Low-quality evidence suggests that EEN may be a safe and effective intervention for the management of critically ill patients with sepsis or septic shock.


Sujet(s)
Nutrition entérale , Sepsie , Choc septique , Humains , Nutrition entérale/méthodes , Essais contrôlés randomisés comme sujet , Ventilation artificielle , Sepsie/thérapie , Sepsie/mortalité , Choc septique/thérapie , Choc septique/mortalité , Facteurs temps , Résultat thérapeutique
15.
Transl Anim Sci ; 8: txae075, 2024.
Article de Anglais | MEDLINE | ID: mdl-38764468

RÉSUMÉ

Seventy-two Angus-cross steers (261 ±â€…14 kg) were utilized to determine the effects of supplemental Zn sulfate on growth, trace mineral status, circulating immune cells, and functional innate immune responses. Steers were stratified by weight and implanted with a Component E-S with Tylan implant (Elanco Animal Health, Greenfield, IN) on day 0. Dietary treatments included: control (CON; no supplemental Zn), Zn100 (100 mg supplemental Zn/kg DM), and Zn150 (150 mg supplemental Zn/kg DM). Analyzed dietary concentrations of Zn were 58, 160, and 207 mg Zn/kg DM, respectively. On days 13 and 57, blood from nine steers per treatment was collected for immune analyses (cell phenotyping and response to stimulus). On day 16, implant abscesses were evaluated by palpation and visual appraisal. Sixty percent of steers had abscesses; however, there were no differences in abscess prevalence due to treatment (P = 0.67). Data were analyzed as a split-plot design using the Mixed procedure of SAS 9.4 (Cary, NC) with effects of dietary treatment, abscess, and their interaction. There was a tendency (treatment × abscess; P ≤ 0.09) for steers without abscesses to have greater average daily gain (ADG; treatment × abscess P = 0.06) and gain:feed (G:F; treatment × abscess P = 0.09) from d 14 to 27 in CON and Zn100 while within Zn150 steers without abscesses tended to have lesser ADG and G:F than abscessed steers. There were no other treatment × abscess effects for growth performance, but steers with abscesses tended to have decreased final body weight (P = 0.10) and overall G:F (days 0 to 57; P = 0.08). There was no interaction of treatment and abscess on immune cell populations on days 13 or 58 (treatment × abscess P ≥ 0.11). On day 13, Zn150 steers had increased CD45RO + gamma delta (P = 0.04) T cells. Abscessed steers had increased CD21 + B cells (P = 0.03) and tended to have increased CD21 + (P = 0.07) and CD21 + MHCIIhi (P = 0.07) B cells in circulation. This study shows zinc supplementation and implant abscesses can alter the immune system and growth performance of growing beef steers.

16.
Cureus ; 16(4): e58802, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38784359

RÉSUMÉ

Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due to Gemella species by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due to Gemella species remains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research.

17.
Reumatol. clín. (Barc.) ; 20(4): 218-222, Abr. 2024. ilus
Article de Espagnol | IBECS | ID: ibc-232375

RÉSUMÉ

El uso de anticuerpos específicos en miopatías inflamatorias ha mejorado la caracterización de esta enfermedad identificando distintos fenotipos clínicos. Los pacientes con dermatomiositis y anticuerpos anti-MDA5 muestran síntomas típicos en la piel, un menor compromiso muscular y una prevalencia de enfermedad pulmonar intersticial de hasta el 91%. Además de la enfermedad pulmonar intersticial, se ha identificado el neumomediastino espontáneo como una manifestación pulmonar rara pero potencialmente mortal. Se reportan 2 casos de esta manifestación en pacientes con dermatomiositis anti-MDA5.(AU)


The use of specific antibodies in inflammatory myopathies has improved the characterization of this disease, identifying different clinical phenotypes. Patients with dermatomyositis and anti-MDA5 antibodies display typical skin symptoms, lesser muscular involvement, and a prevalence of interstitial lung disease of up to 91%. Beyond interstitial lung disease, spontaneous pneumomediastinum has been identified as a rare but potentially fatal pulmonary manifestation. Two cases of this complication in patients with anti-MDA5 dermatomyositis are reported.(AU)


Sujet(s)
Humains , Mâle , Femelle , Adulte d'âge moyen , Emphysème médiastinal , Dermatomyosite , Emphysème sous-cutané , Pneumothorax , Pneumopathies interstitielles
18.
Foods ; 13(7)2024 Mar 22.
Article de Anglais | MEDLINE | ID: mdl-38611283

RÉSUMÉ

The total phenolic, flavonoid, and anthocyanin contents were evaluated in 11 cultivars of Argentinian roses of different colors. HPLC-ESI-QTOF/MS was used to identify the components where ellagic and quinic acids, quercetin, and kaempferol glycosylated derivatives were found. The phenolic contents ranged from 78.8 ± 3.2 to 203.4 ± 3.1 mg GAE/g dw, the flavonoid content ranged from 19.1 ± 3.8 to 125.9 ± 6.5 mg QE/g dw, and the anthocyanin content ranged from less than 0.01 to 5.8 ± 0.1 mg CE/g dw. The dark red cultivars exhibited the greatest levels of the analyzed compounds and of the antioxidant activities, even higher than those of certain plants known for their high phenolic contents and antioxidant activity. Moreover, the addition of these extracts decreased the population of L. innocua and P. aeruginosa to undetectable levels 24 h after inoculation. Rose petal extracts, mainly those with a dark red color, can be used as natural additives in food, feed, and cosmetics, as they contain a high proportion of bioactive compounds with antioxidant and antimicrobial effects.

19.
Reumatol Clin (Engl Ed) ; 20(4): 218-222, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38614887

RÉSUMÉ

The use of specific antibodies in inflammatory myopathies has improved the characterization of this disease, identifying different clinical phenotypes. Patients with dermatomyositis (DM) and anti-MDA5 antibodies display typical skin symptoms, lesser muscular involvement, and a prevalence of interstitial lung disease (ILD) of up to 91%. Beyond ILD, spontaneous pneumomediastinum (SN) has been identified as a rare but potentially fatal pulmonary manifestation. Two cases of this complication in patients with anti-MDA5 DM are reported.


Sujet(s)
Dermatomyosite , Hélicase IFIH1 inductrice de l'interféron , Emphysème médiastinal , Femelle , Humains , Mâle , Adulte d'âge moyen , Autoanticorps/sang , Dermatomyosite/complications , Dermatomyosite/immunologie , Hélicase IFIH1 inductrice de l'interféron/immunologie , Emphysème médiastinal/étiologie , Emphysème médiastinal/imagerie diagnostique
20.
J Vis Exp ; (206)2024 Apr 05.
Article de Anglais | MEDLINE | ID: mdl-38647320

RÉSUMÉ

Fuel treatments and other forest restoration thinning practices aim to reduce wildfire risk while building forest resilience to drought, insects, and diseases and increasing aboveground carbon (C) sequestration. However, fuel treatments generate large amounts of unmerchantable woody biomass residues that are often burned in open piles, releasing significant quantities of greenhouse gases and particulates, and potentially damaging the soil beneath the pile. Air curtain burners offer a solution to mitigate these issues, helping to reduce smoke and particulates from burning operations, more fully burn biomass residues compared to pile burning, and eliminate the direct and intense fire contact that can harm soil beneath the slash pile. In an air curtain burner, burning takes place in a controlled environment. Smoke is contained and recirculated by the air curtain, and therefore burning can be conducted under a variety of climatic conditions (e.g., wind, rain, snow), lengthening the burning season for disposal of slash material. The mobile pyrolysis unit that continuously creates biochar was specifically designed to dispose of residual woody biomass at log landings, green wood at landfills, or salvaged logged materials and create biochar in the process. This high-carbon biochar output can be used to enhance soil resilience by improving its chemical, physical, and biological properties and has potential applications in remediating contaminated soils, including those at abandoned mine sites. Here, we describe the general use of this equipment, appropriate siting, loading methods, quenching requirements, and lessons learned about operating this new technology.


Sujet(s)
Charbon de bois , Bois , Bois/composition chimique , Charbon de bois/composition chimique , Pyrolyse , Science forêt/méthodes
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