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Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study.

ABSTRACT: Surgical stress reduces concentrations of most proteins in serum and necessitates a rapid adjustment of hormones dependent on protein binding. Activation of vitamin D by renal 1?-hydroxylation is dependent on protein binding because 1,25-dihydroxyvitamin D (1,25(OH)2D3) is formed after megalin-mediated reabsorption of 25-hydroxyvitamin D (25OHD) bound to vitamin D binding protein (DBP). Postoperative alterations in serum concentrations of DBP and albumin may therefore impair 1,25(OH)2D3 production. Our objective was to determine sex-specific changes in serum concentrations of vitamin D metabolites and sex steroids 2, 6, 24, and 48 hours and 3 weeks postoperatively. Fourteen women and eleven men aged 45 to 77 years without severe comorbidities undergoing unilateral total knee arthroplasty participated in this prospective study in a tertiary center for arthroplasty (trial ID: NCT02336932). The main outcome measures were total and free serum concentrations of 25OHD, 1,25(OH)2D3, 24,25-dihydroxyvitamin-D, DBP, albumin, sex hormone binding globulin (SHBG), calcium, and parathyroid hormone (PTH). Serum albumin and SHBG decreased postoperatively (?albumin48h -18% [-22%; -14%]). Unexpectedly, concentrations of DBP and 25OHD remained unaltered, but 1,25(OH)2D3 declined postoperatively. 1,25(OH)2D3 was 3 weeks after surgery -24% (-40%; -8%) lower than preoperative levels, whereas 24,25-dihydroxyvitamin-D remained unchanged in postmenopausal women. The calculated conversion rate of 25OHD to 1,25(OH)2D3 was strongly associated with serum 25-OHD and PTH preoperatively, whereas serum calcium was most predictive postoperatively. In conclusion, surgery had no effect on serum concentrations of DBP, 25OHD, and PTH, whereas production of 1,25(OH)2D3 was markedly reduced. Further studies are needed to determine duration and putative outcome effects of this postoperative 1,25(OH)2D3 deficit in women, which in part may be due to discordance in CYP27B1 and CYP24A1 activity.

SUBMITTER: Blomberg Jensen M

PROVIDER: S-EPMC6139703 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study.

Blomberg Jensen Martin M Husted Henrik H Bjerrum Poul Jannik PJ Juul Anders A Kehlet Henrik H

JBMR plus 20180522 5

Surgical stress reduces concentrations of most proteins in serum and necessitates a rapid adjustment of hormones dependent on protein binding. Activation of vitamin D by renal 1α-hydroxylation is dependent on protein binding because 1,25-dihydroxyvitamin D (1,25(OH)<sub>2</sub>D<sub>3</sub>) is formed after megalin-mediated reabsorption of 25-hydroxyvitamin D (25OHD) bound to vitamin D binding protein (DBP). Postoperative alterations in serum concentrations of DBP and albumin may therefore impai ...[more]

PMID: 30283909

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Project description:Physical inactivity and a sedentary lifestyle are associated with a chronic low-level inflammatory state which has been implicated in the pathogenesis of cardiovascular disease. There is growing interest in exercise programs as part of surgical 'prehabilitation'. We therefore studied preoperative physical activity levels of patients undergoing elective Coronary Artery Bypass Graft (CABG) surgery, and performed an exploratory analysis of the influence of physical activity on postoperative outcome. The Short Questionnaire to Assess Health (SQUASH) was used to assess physical activity among 100 patients, of mean (SD) age 65.4 (7.6) years. Additionally, handgrip strength was measured, and the get-up-and-go test was conducted. Anxiety, depression, and quality of life were assessed, and a computerised cognitive test battery was used to assess cognitive performance preoperatively, and three months after surgery. Preoperatively, 76% of patients met the recommended national guidelines for physical activity. The incidence of pre-existing medical conditions, and other pre-operative patient features were similar in active and inactive patients. Preoperative physical activity was significantly inversely related to the logistic EuroSCORE. The level of physical activity was also significantly inversely related with preoperative C-reactive protein (CRP) and peak postoperative CRP, but physical activity did not appear to be associated with any adverse postoperative outcomes or extended length of hospital stay. The incidence of postoperative neurocognitive disorder (PNCD) at 3 months postoperatively was 26%. Cognitive performance was not related with physical activity levels. In summary, this was the first study to assess activity levels of cardiac surgical patients with the SQUASH questionnaire. The majority of patients were physically active. Although physical activity was associated with lower levels of inflammation in this pilot study, it was not associated with an improved clinical or cognitive postoperative outcome.

Project description:Postoperative delirium (POD) ranks among the most common complications in surgical patients. Blood-based biomarkers might help identify the patient at risk. This study aimed to assess how serum biomarkers with specificity for vascular and endothelial function and for inflammation are altered, prior to or following surgery in patients who subsequently develop POD. This was a study on a subcohort of consecutively recruited elective non-cardiac as well as cardiac surgery patients (age > 60 years) of the single-center PROPDESC trial at a German tertiary care hospital. Serum was sampled prior to and following surgery, and the samples were subjected to bead-based multiplex analysis of 17 serum proteins (IL-3, IL-8, IL-10, Cripto, CCL2, RAGE, Resistin, ANGPT2, TIE2, Thrombomodulin, Syndecan-1, E-Selectin, VCAM-1, ICAM-1, CXCL5, NSE, and uPAR). Development of POD was assessed during the first five days after surgery, using the Confusion Assessment Method for ICU (CAM-ICU), the CAM, the 4-'A's test (4AT), and the Delirium Observation Scale (DOS). Patients were considered positive if POD was detected at least once during the visitation period by any of the applied methods. Non-parametric testing, as well as propensity score matching were used for statistical analysis. A total of 118 patients were included in the final analysis; 69% underwent non-cardiac surgery, median overall patient age was 71 years, and 59% of patients were male. In the whole cohort, incidence of POD was 28%. The male gender was significantly associated with the development of POD (p = 0.0004), as well as a higher ASA status III (p = 0.04). Incidence of POD was furthermore significantly increased in cardiac surgery patients (p = 0.002). Surgery induced highly significant changes in serum levels of almost all biomarkers except uPAR. In preoperative serum samples, none of the analyzed parameters was significantly altered in subsequent POD patients. In postoperative samples, CCL2 was significantly increased by a factor of 1.75 in POD patients (p = 0.03), as compared to the no-POD cohort. Following propensity score matching, CCL2 remained the only biomarker that showed significant differences in postoperative values (p = 0.01). In cardiac surgery patients, postoperative CCL2 serum levels were more than 3.5 times higher than those following non-cardiac surgery (p < 0.0001). Moreover, after cardiac surgery, Syndecan-1 serum levels were significantly increased in POD patients, as compared to no-POD cardiac surgery patients (p = 0.04). In a mixed cohort of elective non-cardiac as well as cardiac surgery patients, preoperative serum biomarker profiling with specificity for vascular dysfunction and for systemic inflammation was not indicative of subsequent POD development. Surgery-induced systemic inflammation-as evidenced by the significant increase in CCL2 release-was associated with POD, particularly following cardiac surgery. In those patients, postoperative glycocalyx injury might furthermore contribute to POD development.

Project description:BACKGROUND:Elevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. METHODS:We performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). RESULTS:MicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia. CONCLUSIONS:Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

Dataset Information

Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study.

Publications

Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study.

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