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1.
J Ren Nutr ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521380

RESUMO

OBJECTIVE: While diet plays a key role in chronic kidney disease (CKD) management, the potential for diet to impact CKD prevention in the general population is less clear. Using a priori knowledge, we derived disease-related dietary patterns (DPs) through reduced rank regression (RRR) and investigated associations with kidney function, separately focusing on generally healthy individuals and those with self-reported kidney diseases, hypertension, or diabetes mellitus. METHODS: Eight thousand six hundred eighty-six participants from the population-based Cooperative Health Research in South Tyrol study were split into a group free of kidney disease, hypertension and diabetes (n = 6,133) and a group with any of the 3 conditions (n = 2,553). Diet was assessed through the self-administered Global Allergy and Asthma Network of Excellence food frequency questionnaire and DPs were derived through RRR selecting food frequency questionnaire-derived sodium, potassium, phosphorus, and protein intake as mediators. Outcomes were creatinine-based estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, CKD and microalbuminuria. Multiple linear and logistic models were used to assess associations between RRR-based DPs and kidney outcomes separately in the 2 analytic groups. RESULTS: We identified 3 DPs, where high adherence reflected high levels of all nutrients (DP1), high potassium-phosphorus and low protein-sodium levels (DP2), and low potassium-sodium and high protein-phosphorus levels (DP3), respectively. We observed heterogeneous associations with kidney outcomes, varying by analytic group and sex. Kidney outcomes were much more strongly associated with DPs than with single nutrients. CONCLUSION: RRR is a feasible approach to estimate disease-related DPs and explore the combined effects of nutrients on kidney health. Heterogeneous associations across kidney outcomes suggest possible specificity to kidney function or damage. In individuals reporting kidney disease, hypertension or diabetes, specific dietary habits were associated with better kidney health, indicating that disease-specific dietary interventions can be effective for disease control.

2.
Healthcare (Basel) ; 12(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255053

RESUMO

The COVID-19 pandemic has increased the vulnerability of adults to mental health effects, and the study of protective factors has become crucial. Cognitive reserve (CR) is a well-known protective factor against cognitive decline and several health factors; however, its protective effect on mental health during the pandemic has been rarely addressed. Thus, this study explored, through a mixed-method design, the effect of CR on perceived distress and PTSD-like symptoms in middle-aged participants who have survived severe COVID-19 and a matched control group. A total of 432 participants filled out self-report measures of CR, PTSD, depression, and anxiety, and were also asked to provide narration about their COVID-19-related experience. COVID-19 significantly affected the chances of reporting different mental health symptoms; levels of CR played a protective role in reducing their severity. Moreover, adults with higher CR seemed to be more realistic, focusing less on positive emotions, and elaborating more on the sense of anxiety when describing their experience: this might be an indication of a lower use of suppression to regulate emotions. Practical implications of these findings and future directions have been also discussed.

3.
EBioMedicine ; 96: 104791, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37734204

RESUMO

BACKGROUND: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures. Furthermore, metabolomics profiling during acute disease can be influenced by confounding factors such as indications, medical treatments, and lifestyles. METHODS: We employed metabolomic profiling to cluster infection-free individuals and assessed their relationship with COVID severity and influenza incidence/recurrence. FINDINGS: We identified a metabolomic susceptibility endotype that was strongly associated with both severe COVID (ORICUadmission = 6.7, p-value = 1.2 × 10-08, ORmortality = 4.7, p-value = 1.6 × 10-04) and influenza (ORincidence = 2.9; p-values = 2.2 × 10-4, ßrecurrence = 1.03; p-value = 5.1 × 10-3). We observed similar severity associations when recapitulating this susceptibility endotype using metabolomics from individuals during and after acute COVID infection. We demonstrate the value of using metabolomic endotyping to identify a metabolically susceptible group for two-and potentially more-IDs that are driven by increases in specific amino acids, including microbial-related metabolites such as tryptophan, bile acids, histidine, polyamine, phenylalanine, and tyrosine metabolism, as well as carbohydrates involved in glycolysis. INTERPRETATIONS: These metabolites may be identified prior to infection to enable protective measures for these individuals. FUNDING: The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) and metabolomic profiling were supported by the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health.


Assuntos
COVID-19 , Doenças Transmissíveis , Influenza Humana , Humanos , Metaboloma , Estudos Prospectivos , Influenza Humana/epidemiologia , Metabolômica , Doenças Transmissíveis/etiologia
4.
JPEN J Parenter Enteral Nutr ; 47(6): 698-699, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37408135
5.
JPEN J Parenter Enteral Nutr ; 47(5): 614-623, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36974618

RESUMO

BACKGROUND: Gastric residual volume (GRV) measurement to detect gastrointestinal (GI) dysfunction is a common diagnostic procedures in critical care, albeit still not well standardized being operator-, patient-, and tube-dependent. Our aim was to describe current practice of GRV measurements and its association with clinical outcomes in critically ill patients. METHODS: This was a secondary analysis of an international prospective observational cohort study (intestinal-specific organ function assessment). Eligibility criteria were defined as ≥1 GRV measurement during the 7-day study period. Data collection included GRV measurement practices, tube diameters and volumes, symptoms of GI dysfunction, and clinical outcomes. The primary aim was to describe current practices of GRV measurements, and the secondary aim was to test the association of high (>200 ml) vs. low GRV with symptoms of GI dysfunction and clinical outcomes using generalized linear regression and survival models. RESULTS: Two hundred fifty-eight patients with 2422 GRV measurements on 875 study days were analyzed. GRV was mainly measured via passive drainage twice daily using large diameter tubes. There was no significant association between tube size or measurement technique and high GRV. High GRV occurred in 34% of patients and was associated with other GI symptoms and with increased disease severity but not with 28-day or 90-day mortality, intensive care unit-free and ventilator-free days. CONCLUSION: There was substantial variability of GRV measurement techniques, but this had no impact on the amount of GRV. High GRV was not associated with mortality or ventilator-free days but may serve as a marker of GI dysfunction and disease severity.


Assuntos
Estado Terminal , Gastroenteropatias , Humanos , Estado Terminal/terapia , Estudos Prospectivos , Volume Residual , Nutrição Enteral/métodos , Estômago
6.
JAMA Surg ; 158(3): 235-244, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630120

RESUMO

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Selênio , Adulto , Humanos , Masculino , Idoso , Feminino , Selenito de Sódio/uso terapêutico , Selenito de Sódio/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Anti-Inflamatórios , Método Duplo-Cego
7.
JPEN J Parenter Enteral Nutr ; 47(2): 220-235, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36495215

RESUMO

Patients receiving extracorporeal membrane oxygenation (ECMO) inherit substantial disease-associated metabolic, endocrinologic, and immunologic modifications. Along with the technical components of ECMO, the aforementioned alterations may affect patients' needs and feasibility of adequate macronutrient and micronutrient supply and intake. Thus, patients receiving ECMO are at increased risk for iatrogenic malnutrition and require targeted individual medical nutrition therapy (MNT). However, specific recommendations for MNT in patients receiving ECMO are limited and, with some exceptions, based on an evidence base encompassing general patients who are critically ill. Consequently, clinician decision-making for MNT in patients receiving ECMO is unguided, which may further increase nutrition risk, culminating in iatrogenic malnutrition and ultimately affecting patient outcomes. The purpose of this article is to provide educational background and highlight specific points for MNT in adult patients receiving ECMO, which might serve as evidence-based guidance to develop institutional standard operating procedures and nutrition protocols for daily clinical practice.


Assuntos
Oxigenação por Membrana Extracorpórea , Desnutrição , Adulto , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Nutrição Enteral/métodos , Estado Nutricional , Estado Terminal/terapia , Doença Iatrogênica
8.
JPEN J Parenter Enteral Nutr ; 46(8): 1748-1749, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36342666
9.
Crit Care ; 26(1): 321, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261854

RESUMO

BACKGROUND: Cell stress promotes degradation of mitochondria which release danger-associated molecular patterns that are catabolized to N-formylmethionine. We hypothesized that in critically ill adults, the response to N-formylmethionine is associated with increases in metabolomic shift-related metabolites and increases in 28-day mortality. METHODS: We performed metabolomics analyses on plasma from the 428-subject Correction of Vitamin D Deficiency in Critically Ill Patients trial (VITdAL-ICU) cohort and the 90-subject Brigham and Women's Hospital Registry of Critical Illness (RoCI) cohort. In the VITdAL-ICU cohort, we analyzed 983 metabolites at Intensive Care Unit (ICU) admission, day 3, and 7. In the RoCI cohort, we analyzed 411 metabolites at ICU admission. The association between N-formylmethionine and mortality was determined by adjusted logistic regression. The relationship between individual metabolites and N-formylmethionine abundance was assessed with false discovery rate correction via linear regression, linear mixed-effects, and Gaussian graphical models. RESULTS: Patients with the top quartile of N-formylmethionine abundance at ICU admission had a significantly higher adjusted odds of 28-day mortality in the VITdAL-ICU (OR, 2.4; 95%CI 1.5-4.0; P = 0.001) and RoCI cohorts (OR, 5.1; 95%CI 1.4-18.7; P = 0.015). Adjusted linear regression shows that with increases in N-formylmethionine abundance at ICU admission, 55 metabolites have significant differences common to both the VITdAL-ICU and RoCI cohorts. With increased N-formylmethionine abundance, both cohorts had elevations in individual short-chain acylcarnitine, branched chain amino acid, kynurenine pathway, and pentose phosphate pathway metabolites. CONCLUSIONS: The results indicate that circulating N-formylmethionine promotes a metabolic shift with heightened mortality that involves incomplete mitochondrial fatty acid oxidation, increased branched chain amino acid metabolism, and activation of the pentose phosphate pathway.


Assuntos
Estado Terminal , Cinurenina , Adulto , Feminino , Humanos , Aminoácidos de Cadeia Ramificada , Ácidos Graxos , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Metabolômica/métodos , N-Formilmetionina , Ensaios Clínicos como Assunto
11.
Metabolites ; 12(3)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35323650

RESUMO

Pharmacological interventions are essential for the treatment and management of critical illness. Although women comprise a large proportion of the critically ill, sex-specific pharmacological properties are poorly described in critical care. The sex-specific effects of vitamin D3 treatment in the critically ill are not known. Therefore, we performed a metabolomics cohort study with 1215 plasma samples from 428 patients from the VITdAL-ICU trial to study sex-specific differences in the metabolic response to critical illness following high-dose oral vitamin D3 intervention. In women, despite the dose of vitamin D3 being higher, pharmacokinetics demonstrated a lower extent of vitamin D3 absorption compared to men. Metabolic response to high-dose oral vitamin D3 is sex-specific. Sex-stratified individual metabolite associations with elevations in 25(OH)D following intervention showed female-specific positive associations in long-chain acylcarnitines and male-specific positive associations in free fatty acids. In subjects who responded to vitamin D3 intervention, significant negative associations were observed in short-chain acylcarnitines and branched chain amino acid metabolites in women as compared to men. Acylcarnitines and branched chain amino acids are reflective of fatty acid B oxidation, and bioenergesis may represent notable metabolic signatures of the sex-specific response to vitamin D. Demonstrating sex-specific pharmacometabolomics differences following intervention is an important movement towards the understanding of personalized medicine.

12.
Kidney Blood Press Res ; 47(5): 341-353, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35196662

RESUMO

BACKGROUND: Post-transplant hypomagnesemia is commonly observed among patients prescribed calcineurin inhibitor (CNIs). METHODS: We conducted a retrospective single-center analysis (2000-2013, N = 726) to examine the association of hypomagnesemia with long-term patient and allograft outcomes in kidney transplant recipients. A median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year posttransplant was calculated. RESULTS: For every increase in Mg of 0.1 mg/dL, the risk for either graft loss or death, overall mortality, and death with a functioning graft increased by 11%, 14%, and 12%, respectively (p < 0.01). In a multivariate model, patients with median Mg level ≥1.7 mg/dL had a reduced overall survival rate (HR 1.57, 95% CI: 1.04-2.38, p = 0.033) compared to those with median Mg level <1.7 mg/dL. This association was observed in subgroups of patients above 60 years old, in those who had a slow graft function (SGF) and in females. CONCLUSIONS: Posttransplant hypomagnesemia is associated with better patient and allograft survival up to 10 years posttransplant. This relationship remained significant after accounting for baseline allograft function, presence of SGF and CNI trough levels.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Magnésio , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Sci Rep ; 11(1): 23194, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853395

RESUMO

Procalcitonin is a biomarker of systemic inflammation and may have importance in the immune response. The metabolic response to elevated procalcitonin in critical illness is not known. The response to inflammation is vitally important to understanding metabolism alterations during extreme stress. Our aim was to determine if patients with elevated procalcitonin have differences in the metabolomic response to early critical illness. We performed a metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D3 or placebo. Mixed-effects modeling was used to study changes in metabolites over time relative to procalcitonin levels adjusted for age, Simplified Acute Physiology Score II, admission diagnosis, day 0 25-hydroxyvitamin D level, and the 25-hydroxyvitamin D response to intervention. With elevated procalcitonin, multiple members of the short and medium chain acylcarnitine, dicarboxylate fatty acid, branched-chain amino acid, and pentose phosphate pathway metabolite classes had significantly positive false discovery rate corrected associations. Further, multiple long chain acylcarnitines and lysophosphatidylcholines had significantly negative false discovery rate corrected associations with elevated procalcitonin. Gaussian graphical model analysis revealed functional modules specific to elevated procalcitonin. Our findings show that metabolite differences exist with increased procalcitonin indicating activation of branched chain amino acid dehydrogenase and a metabolic shift.


Assuntos
Colecalciferol/uso terapêutico , Metabolismo Energético , Inflamação/metabolismo , Pró-Calcitonina/metabolismo , Vitaminas/uso terapêutico , Idoso , Estado Terminal/terapia , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Inflamação/sangue , Inflamação/terapia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Metabolômica , Pessoa de Meia-Idade , Efeito Placebo , Pró-Calcitonina/sangue
14.
Ren Fail ; 43(1): 1240-1249, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34433378

RESUMO

BACKGROUND: Hyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome. METHODS: We conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated. RESULTS: Patients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0-1.7, p < 0.05 for every increase of 1 mg/dL in UA level). CONCLUSION: Hyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.


Assuntos
Rejeição de Enxerto/patologia , Hiperuricemia/complicações , Transplante de Rim/mortalidade , Ácido Úrico/sangue , Adulto , Idoso , Aloenxertos/fisiopatologia , Feminino , Rejeição de Enxerto/sangue , Sobrevivência de Enxerto/fisiologia , Humanos , Hiperuricemia/sangue , Israel/epidemiologia , Nefropatias/sangue , Nefropatias/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
15.
Ann Intensive Care ; 11(1): 103, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213685

RESUMO

BACKGROUND: Bibliometric analyses show gender bias against women in scientific publications and citations. We hypothesized that a metric of an individual senior author's inclusivity of women as first authors in critical care publications would predict gender inequality. METHODS: Using PubMed and Web of Science, we conducted a bibliometric analysis of original research publications in critical care from 2008 to 2018 in 11 specialty and general journals. Gender for first and senior authors was assigned by a gender determination application, and manually if needed. For all senior authors we defined the novel Female First Author Index (FFA-index) = #Female first authors in publications by an individual senior author/Total # publications by that senior author. We produced a novel interactive web-based application using the R package Shiny to increase potential utilization of the FFA-index. RESULTS: Of 7370 publications, 30.4% had female first authors and 15.5% had female senior authors. After adjustment for impact factor, journal, year of publication, number of authors, country, and gender determination accuracy, female senior authorship was associated with a 1.9-fold increase in female first authorship [OR = 1.85 (95% CI 1.62, 2.11); p < 0.001] compared with male senior authorship. The mean (SD) FFA-index for all individual senior authors was 30.5 (42.9); with a significant difference in FFA-index between male and female senior authors (27.6 versus 42.5, respectively; p < 0.001). The interactive web-based application (FFA-index App) produces the same FFA-index output as our study results. CONCLUSIONS: Female representation at prominent authorship positions in critical care publications is still far from achieving gender parity. By creating an authorship index score, we propose a frame of reference for the advancement of female first authorship.

16.
Ann Vasc Surg ; 75: 461-470, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33831518

RESUMO

BACKGROUND: We aimed to determine the correlation between the functional status at discharge in non-cardiac vascular surgery patients and the out-of-hospital mortality. METHODS: We performed a retrospective cohort study including adult non-cardiac vascular surgery patients (open, endovascular and venous procedures) surviving hospitalization in Boston, Massachusetts, USA. The exposure of interest was functional status determined by a licensed physical therapist at hospital discharge and rated based on qualitative categories adapted from the Functional Independence Measure. The primary outcome was all cause 90-day mortality after hospital discharge. The secondary outcome was readmission within 30days. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS: This cohort included 2318 patients (male 51%; mean age 61 ± 17.7). After evaluation by a physiotherapist, 425 patients scored the lowest functional status, 631 scored moderately low, 681 moderately high and 581 scored the highest functional status. The lowest functional status was associated with a 3.41-fold increased adjusted odds for 90-day mortality (95%CI, 1.70-6.84) compared to patients with the highest functional status. When excluding venous intervention patients, the adjusted odds ratio was 6.76 (95%CI, 2.53-18.12) for the 90-day mortality post-discharge. The adjusted odds for readmission within 30-days was 1.5-fold increase in patients with the lowest functional status (95%CI, 1.04-2.20). CONCLUSIONS: In vascular surgery patients surviving hospitalization, functional status is strongly associated with out-of-hospital mortality and readmission rate. Future trials could provide evidence if improvement of functional status could prevent adverse outcomes in the postoperative setting.


Assuntos
Procedimentos Endovasculares/efeitos adversos , Estado Funcional , Alta do Paciente , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/diagnóstico , Doenças Vasculares/mortalidade , Procedimentos Cirúrgicos Vasculares/mortalidade
17.
Sci Rep ; 11(1): 3951, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597589

RESUMO

Metabolism differs in women and men at homeostasis. Critically ill patients have profound dysregulation of homeostasis and metabolism. It is not clear if the metabolic response to critical illness differs in women compared to men. Such sex-specific differences in illness response would have consequences for personalized medicine. Our aim was to determine the sex-specific metabolomic response to early critical illness. We performed a post-hoc metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D3 or placebo. Using mixed-effects modeling, we studied sex-specific changes in metabolites over time adjusted for age, Simplified Acute Physiology Score II, admission diagnosis, day 0 25-hydroxyvitamin D level, and 25-hydroxyvitamin D response to intervention. In women, multiple members of the sphingomyelin and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time compared to men. Further, multiple representatives of the acylcarnitine, androgenic steroid, bile acid, nucleotide and amino acid metabolite classes had significantly negative Bonferroni corrected associations over time compared to men. Gaussian graphical model analyses revealed sex-specific functional modules. Our findings show that robust and coordinated sex-specific metabolite differences exist early in critical illness.


Assuntos
Metabolismo Basal/fisiologia , Metaboloma/genética , Metaboloma/fisiologia , Idoso , Idoso de 80 Anos ou mais , Colecalciferol/administração & dosagem , Estado Terminal , Feminino , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Caracteres Sexuais , Fatores Sexuais , Deficiência de Vitamina D/tratamento farmacológico
18.
Clin Nutr ; 40(4): 2053-2060, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33087250

RESUMO

BACKGROUND & AIMS: It is unclear if intervention can mitigate the dramatic alterations of metabolic homeostasis present in critical illness. Our objective was to determine the associations between increased 25-hydroxyvitamin D levels following high dose vitamin D3 and more favorable metabolomic profiles in critical illness. METHODS: We performed a post-hoc metabolomics study of the VITdAL-ICU randomized double-blind, placebo-controlled trial. Trial patients from Medical and Surgical Intensive Care Units at a tertiary university hospital with 25-hydroxyvitamin D level ≤20 ng/mL received either high dose oral vitamin D3 (540,000 IU) or placebo. We performed an analysis of 578 metabolites from 1215 plasma samples from 428 subjects at randomization (day 0), day 3 and 7. Using mixed-effects modeling, we studied changes in metabolite profiles in subjects receiving intervention or placebo relative to absolute increases in 25-hydroxyvitamin D levels from day 0 to day 3. RESULTS: 55.2% of subjects randomized to high dose vitamin D3 demonstrated an absolute increase in 25-hydroxyvitamin D ≥ 15 ng/ml from day 0 to day 3. With an absolute increase in 25-hydroxyvitamin D ≥ 15 ng/ml, multiple members of the sphingomyelin, plasmalogen, lysoplasmalogen and lysophospholipid metabolite classes had significantly positive Bonferroni corrected associations over time. Further, multiple representatives of the acylcarnitine and phosphatidylethanolamine metabolite classes had significantly negative Bonferroni corrected associations over time with an absolute increase in 25-hydroxyvitamin D ≥ 15 ng/ml. Changes in these highlighted metabolite classes were associated with decreased 28-day mortality. CONCLUSIONS: Increases in 25-hydroxyvitamin D following vitamin D3 intervention are associated with favorable changes in metabolites involved in endothelial protection, enhanced innate immunity and improved mitochondrial function.


Assuntos
Colecalciferol/administração & dosagem , Estado Terminal/terapia , Metabolômica , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Estado Terminal/mortalidade , Método Duplo-Cego , Feminino , Humanos , Unidades de Terapia Intensiva , Lisofosfolipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Plasmalogênios/sangue , Esfingomielinas/sangue , Resultado do Tratamento , Vitamina D/sangue
19.
Clin Nutr ; 40(2): 590-599, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32624243

RESUMO

BACKGROUND & AIMS: Despite the presumed importance of preventing and treating micronutrient and mineral deficiencies, it is still not clear how to optimize measurement and administration in critically ill patients. In order to design future comparative trials aimed at optimizing micronutrient and mineral management, an important first step is to gain insight in the current practice of micronutrient, phosphate and magnesium monitoring and administration. METHODS: Within the metabolism-endocrinology-nutrition (MEN) section of the European Society of Intensive Care Medicine (ESICM), the micronutrient working group designed a survey addressing current practice in parenteral micronutrient and mineral administration and monitoring. Invitations were sent by the ESICM research department to all ESICM members and past members. RESULTS: Three hundred thirty-four respondents completed the survey, predominantly consisting of physicians (321 [96.1%]) and participants working in Europe (262 [78.4%]). Eighty-one (24.3%) respondents reported to monitor micronutrient deficiencies through clinical signs and/or laboratory abnormalities, and 148 (44.3%) reportedly measure blood micronutrient concentrations on a routine basis. Two hundred ninety-two (87.4%) participants provided specific data on parenteral micronutrient supplementation, of whom 150 (51.4%) reported early administration of combined multivitamin and trace element preparations at least in selected patients. Among specific parenteral micronutrient preparations, thiamine (146 [50.0%]) was reported to be the most frequently administered micronutrient, followed by vitamin B complex (104 [35.6%]) and folic acid (86 [29.5%]). One hundred twenty (35.9%) and 113 (33.8%) participants reported to perform daily measurements of phosphate and magnesium, respectively, whereas 173 (59.2%) and 185 (63.4%) reported to routinely supplement these minerals parenterally. CONCLUSION: The survey revealed a wide variation in current practices of micronutrient, phosphate and magnesium measurement and parenteral administration, suggesting a risk of insufficient prevention, diagnosis and treatment of deficiencies. These results provide the context for future comparative studies, and identify areas for knowledge translation and recommendations.


Assuntos
Cuidados Críticos/métodos , Deficiências Nutricionais/diagnóstico , Desnutrição/diagnóstico , Avaliação Nutricional , Nutrição Parenteral/métodos , Adolescente , Adulto , Criança , Estado Terminal/terapia , Suplementos Nutricionais , Feminino , Humanos , Magnésio/análise , Deficiência de Magnésio/diagnóstico , Masculino , Micronutrientes/análise , Micronutrientes/deficiência , Pessoa de Meia-Idade , Estado Nutricional , Fosfatos/análise , Fosfatos/deficiência , Padrões de Prática Médica , Inquéritos e Questionários , Adulto Jovem
20.
Kidney Blood Press Res ; 45(6): 982-995, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152728

RESUMO

BACKGROUND: Hypomagnesemia is frequently seen after transplantation and is particularly associated with the use of calcineurin inhibitors (CNIs). METHODS: We conducted a retrospective, single-center analysis (2000-2013, N = 726) to explore the relationship between hypomagnesemia and long-term allograft outcome in kidney transplant recipients. For this study, a median serum magnesium (Mg) level of all measured Mg levels from 1 month to 1 year after renal transplantation was calculated. RESULTS: For every increase in Mg by 0.1 mg/dL, the GFR decreased by 1.1 mL/min at 3 years posttransplant (p < 0.01) and by 1.5 mL/min at 5 years posttransplant. A median blood Mg level of ≥1.7 was found to be an independent predictor of a GFR <60 mL/min at 3 years posttransplant. The odds of having a GFR <60 mL/min 3 years posttransplant was almost 2-fold higher in the high Mg group than in the low Mg group. CONCLUSIONS: Hypomagnesemia from 1 to 12 months after renal transplantation is associated with a better allograft function up to 5 years posttransplant. This relationship was found to hold true after accounting for baseline allograft function and the presence of slow graft function.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Deficiência de Magnésio/sangue , Magnésio/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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