Corticosteroid-Induced Osteoporosis in Daily Practice: Pathophysiology, Clinical Importance, Prevention and Intervention Strategies

Glucocorticoid-induced osteoporosis is a serious disease that strikes millions of people world-wide every year. Nevertheless much debate is still going on about the preferred strategies to be followed and the magnitude of the problem. Therefore, the first aim of this thesis was to review the current strategies to identify the patient at risk and the options available for prevention and treatment of this serious skeletal disease. In addition we tried to obtain insight in the magnitude of the population at risk in The Netherlands. We also studied the effects of inhaled glucocorticoids on bone mineral density and markers of bone turnover. The second aim was focused on the prevention and treatment of glucocorticoid-induced osteoporosis. First of all the acute effect of etidronate on markers of bone turnover was studied in glucocorticoid treated patients. Subsequently, in two separate studies the effects of etidronate in the prevention and treatment of glucocorticoid-induced osteoporosis was investigated

Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis

INTRODUCTION: In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit.METHODS: Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D3 (25 (OH)-D) concentrations, were meta-analysed.RESULTS: Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001).CONCLUSIONS: This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill

Conventional hemodynamic resuscitation may fail to optimize tissue perfusion: An observational study on the effects of dobutamine, enoximone, and norepinephrine in patients with acute myocardial infarction complicated by cardiogenic shock

Aim: To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Methods and Results: Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥2.5 L.min-1.m-2 or mixed-venous oxygen saturation (SvO 2) ≥70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm-2; p10.3 mm.mm-2; mortality 72% vs. 17%, p = 0.003). Conclusion: This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock

Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. Methods: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline

Preoperative right heart hemodynamics predict postoperative acute kidney injury after heart transplantation

Purpose: Acute kidney injury (AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed to determine their predictive properties for postoperative AKI severity within 30 days after HTx. Methods: From 1984 to 2016, all consecutive HTx recipients (n = 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC). Results: Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg, p trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47, p trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31, p trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity [adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32), p = 0.029; of PAPi 0.85 (0.75–0.96), p = 0.008]. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models’ predictive accuracy. Conclusions: Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors

Acute effects of etidronate on glucocorticoid-induced bone degradation

OBJECTIVES: To study the acute short-term effects on the biochemical parameters of calcium and bone homeostasis in post-menopausal women treated with a high dose of prednisone alone or with additional etidronate, before and during 5 days of treatment. METHODS: Serum calcium, phosphorus, creatinine, alkaline phosphatase activity, osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH), 25-hydroxyvitamin D and urinary excretion of calcium over 24 h were measured before and during 5 days of treatment in 14 post-menopausal women treated with a high dose of prednisone (60 mg/day) alone (group A) or combined with cyclical etidronate (group B). RESULTS: Significant differences from baseline were found in osteocalcin and urinary excretion of calcium in both groups and for ICTP in group B. Significant differences between groups were calculated at day 5 of the study for osteocalcin, ICTP and 24 h urine calcium excretion (P < 0.01). Urinary excretion of calcium over 24 h increased in group A (+14.7%; P < 0.05) and decreased in group B (-22.1%; P < 0.01). Osteocalcin levels decreased in group A (- 38.1%) and increased in group B (+27.4%; both P < 0.01). ICTP decreased only in group B (-19.4%; P < 0.01). CONCLUSIONS: The results are consistent with the fact that etidronate is acutely able to prevent bone resorption due to corticosteroids. The increase in osteocalcin in the etidronate-treated group is a new feature. A direct or indirect (PTH, 1,25 vitamin D?) stimulatory effect of etidronate on the osteoblast cannot be excluded

Preoperative right heart hemodynamics predict postoperative acute kidney injury after heart transplantation

Purpose: Acute kidney injury (AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed to determine their predictive properties for postoperative AKI severity within 30 days after HTx. Methods: From 1984 to 2016, all consecutive HTx recipients (n = 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC). Results: Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg, p trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47, p trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31, p trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity [adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32), p = 0.029; of PAPi 0.85 (0.75–0.96), p = 0.008]. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models’ predictive accuracy. Conclusions: Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors

The effects of infusions of dobutamine (median 60 minutes), enoximone (median 85 minutes), and norepinephrine (median 75 minutes) on parameters of macro- and microcirculation.

<p>Abbreviations: HR, heart rate; MAP, mean arterial pressure; CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; MPAP, mean pulmonary artery pressure; CI, cardiac index; SVR, systemic vascular resistance; SvO₂, mixed-venous oxygen saturation; delta-T, central-peripheral temperature gradient; PCD, perfused capillary density.</p><p>Values represent median [interquartile range]. The p-value in the last column represents differences among groups. Asterisks indicate statistical significance versus baseline:</p><p>*, p<0.05;</p><p>**, p<0.01.</p><p>P-values>0.05 (NS, non-significant) are not shown.</p>a<p>A pulmonary artery catheter was present in 27/33 (82%) of the measurements.</p

Thirty-day mortality according to final perfused capillary density.

<p>In the subgroup of patients (n = 18) with low perfused capillary density (ie, ≤10.3 mm.mm⁻²), 13 patients died, whereas in the subgroup of patients (n = 12) with preserved capillary density (ie, >10.3 mm.mm⁻²) 2 patients died (p = 0.003).</p

Changes in perfused capillary density following infusions of dobutamine (median 60 minutes), enoximone (median 85 minutes), and norepinephrine (median 75 minutes) at the individual patient level.

<p>↑, increase of parameter following inotropic therapy in terms of percentage relative to baseline. The reference value of perfused capillary density is indicated by the red dashed line (ie, 10.3 mm.mm⁻²). Values greater than this reference are to be considered as preserved capillary density, values below or equal to this reference reflect impaired capillary density <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103978#pone.0103978-denUil1" target="_blank">[5]</a>.</p