Gabriela Katharina Muschitz

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9 years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7 years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4 pmol/L) and aBMD values at the total hip (0.989 vs 0.971 g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

The Impact of Vitamin D, Calcium, Protein Supplementation, and Physical Exercise on Bone Metabolism After Bariatric Surgery: The BABS Study

Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m(2) after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced.

Sclerostin Levels and Changes in Bone Metabolism After Bariatric Surgery

CONTEXT The role of sclerostin as a key regulator of bone formation remains unknown after Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (SG). OBJECTIVES The study objectives were evaluation of sclerostin and Dickkopf-1 (DKK-1) serum levels after surgery and correlations with bone turnover markers (P1NP, CTX), parathyroid hormone (iPTH) and areal bone mineral density (BMD), changes at total body, lumbar spine and total hip. DESIGN AND SETTING This was a prospective observational single-center two-arm study in premenopausal women with acute adipositas over 24 months. PARTICIPANTS Participants were 52 premenopausal women (40 ± 8 years, BMI 43.4) after RYGB and 38 premenopausal women (41 ± 7 years, BMI 45.7) after SG. MAIN OUTCOME MEASURES Prior to surgery and 1, 3, 6, 9, 12, 18, and 24 months after surgery sclerostin, DKK-1, CTX, P1NP levels and BMD were measured. RESULTS Sclerostin, CTX and (to a lesser extent) P1NP increased after surgery and remained elevated during the entire study period (P < 0.001). DKK-1 declined during months 3-9 (P < 0.005) and then remained unchanged, serum phosphate continuously increased (P < 0.001), iPTH remained within the upper normal limit. Sclerostin increases were significantly positively correlated with CTX and P1NP increases and negatively correlated with BMD loss. BMD independently declined regardless of RYGB and SG. Elevations of sclerostin, CTX, P1NP, and phosphate, but not DKK-1 and iPTH, were significant discriminating factors for BMD loss (AUC 0.920). CONCLUSION Rapid and sustained increases of sclerostin, CTX, and to a lesser extent, P1NP cause an increase in bone metabolism and result in BMD loss at all skeletal sites.

Predisposing factors for candidemia in patients with major burns

BACKGROUND Despite advances in surgery and critical care, candidemia remains a significant cause of morbidity and mortality in patients with extensive burns. METHODS A retrospective single-center cohort study was performed on 174 patients admitted to the Burn Intensive Care Unit of the General Hospital of Vienna (2007-2013). An AIC based model selection procedure for logistic regression models was utilized to identify factors associated with the presence of candidemia. RESULTS Twenty (11%) patients developed candidemia on median day 16 after ICU admission associated with an increased overall mortality (30% versus 10%). Statistical analysis identified the following factors associated with proven candidemia: younger age (years) odds ratio (OR):0.96, 95% confidence interval (95% CI):0.92-1.0, female gender (reference male) OR:5.03, 95% CI:1.25-24.9, gastrointestinal (GI) complications requiring surgery (reference no GI complication) OR:20.37, 95% CI:4.25-125.8, non-gastrointestinal thromboembolic complications (reference no thromboembolic complication) OR:17.3, 95% CI:2.57-170.4 and inhalation trauma (reference no inhalation trauma) OR:7.96, 95% CI:1.4-48.4. CONCLUSIONS Above-mentioned patient groups are at considerably high risk for candidemia and might benefit from a prophylactic antifungal therapy. Younger age as associated risk factor is likely to be the result of the fact that older patients with a great extent of burn body surface have a lower chance of survival compared to younger patients with a comparable TBSA.

Non-occlusive mesenteric ischaemia: The prevalent cause of gastrointestinal infarction in patients with severe burn injuries

BACKGROUND Gastrointestinal complications occur frequently in intensive care patients with severe burns. Intestinal infarction and its deleterious consequences result in high mortality despite rapid surgical intervention. Our objective was to evaluate the aetiology of gastrointestinal infarction in intensive care patients with severe burns. STUDY DESIGN We retrospectively evaluated all of the severe-burn victims at the burn unit of the Medical University of Vienna from 01/2002 to 06/2012 for whom a gastrointestinal infarction was diagnosed during their inpatient stay on computed-tomography, in the context of acute laparotomy, or upon autopsy by aetiology. RESULTS After a severe thermal injury, 17 patients suffered a gastrointestinal infarction during their stay. In 82% of those patients, non-occlusive mesenteric ischaemia (NOMI) was identified as the cause of the gastrointestinal infarction. Patients with an embolic infarction tended to be older (78.0years embolism vs. 53.4 NOMI, mean, p<0.01), with a lower abbreviated burn severity index (8.7 embolism vs. 10.4 NOMI, mean, p<0.02) and a smaller total body surface area burned (20% embolism vs. 48% NOMI, mean, p<0.01) than those with a non-occlusive mesenterial ischaemia. No patients with an embolic infarction or any of the females in the entire gastrointestinal infarction group survived this event, resulting in a mortality rate of 100% for the embolic infarction group and female group. The decisive factor for surviving a NOMI was age (median age: male survivors 28years vs. nonsurvivors 66years (of this median, males=72years and females=60years), p<0.02). CONCLUSION The results of our study clearly demonstrate that in severe-burn intensive care patients, non-occlusive mesenteric ischaemia is the most frequent cause of gastrointestinal infarction and that the decisive factor for survival is the patients age.

Early and Sustained Changes in Bone Metabolism After Severe Burn Injury

CONTEXT Severe burn injury causes a massive stress response, consecutively heightened serum levels of acute phase proteins, cortisol, and catecholamines with accompanying disturbance in calcium metabolism. OBJECTIVE Evaluation of early and prolonged changes of serum bone turnover markers (BTMs) and regulators of bone metabolism. DESIGN Longitudinal observational design. SETTING University clinic. PATIENTS A total of 32 male patients with a median age of 40.5 years and a median burned total body surface area of 40% (83% patients with full thickness burn injury). INTERVENTIONS None. MAIN OUTCOME MEASURES Comparison of changes of BTM/regulators of bone metabolism in the early (d 2–7) and prolonged (d 7–56) phases after trauma. RESULTS All investigated BTM/regulators significantly changed. During the early phase, pronounced increases were observed for serum type 1 collagen cross-linked C-telopeptide, intact N-terminal propeptide of type I procollagen, sclerostin, Dickkopf-1, bone-specific alkaline phosphatase, fibroblast growth factor 23, and intact parathyroid hormone levels, whereas 25-hydroxyvitamin D, albumin, serum, and ionized calcium levels decreased. Changes of osteoprotegerin, osteocalcin, and phosphate were less pronounced but remained significant. In the prolonged phase, changes of intact N-terminal propeptide of type I procollagen were most pronounced, followed by elevated sclerostin, osteocalcin, bone-specific alkaline phosphatase, and lesser changes for albumin levels. Calcium and ionized calcium levels tardily increased and remained within the limit of normal. In contrast, levels of intact parathyroid hormone, fibroblast growth factor 23, C-reactive protein, and to a lesser extent serum type 1 collagen cross-linked C-telopeptide and phosphate levels declined significantly during this phase of investigation. CONCLUSIONS Ongoing changes of BTM and regulators of bone metabolism suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure in male patients with severe burn injuries.

Vitamin D levels and comorbidities in ambulatory and hospitalized patients in Austria

SummaryVitamin D in its hormonal active form, 1,25-dihydroxyvitamin D (calcitriol), has a major impact on bone turnover by regulating calcium and phosphate homoeostasis. By binding the active vitamin D hormone to the vitamin D receptor (VDR), it acts as a nuclear transcription factor (Bouillon et al., Endocr Rev 29(6):726–776, 2008). The discovery that almost all tissues and cells in the body express the VDR and that several tissues possess the enzymatic capability to convert 25-hydroxyvitamin D (25(OH)-D3; cholecalciferol) to the active form, suggests that vitamin D fulfills various extra-osseous functions (Bouillon et al., Endocr Rev 29(6):726–776, 2008; Holick, N Engl J Med 357(3):266–281, 2007). For example, VDR ensures adequate intestinal calcium absorption by regulating the synthesis of several calcium transport proteins in the duodenum (Bouillon et al., Endocr Rev 29(6):726–776, 2008). Additionally, vitamin D is important for proper muscle function, and some studies suggest it may contribute to prevent type 1 diabetes mellitus, certain autoimmune diseases, hypertension, and several types of cancer (Holick, N Engl J Med 357(3):266–281, 2007).

Long-term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture†

Severe burn injury triggers massive alterations in stress hormone levels with a dose‐dependent hypermetabolic status including increased bone resorption. This study evaluated bone microarchitecture measured by noninvasive high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Changes of serum bone turnover markers (BTM) as well as regulators of bone signaling pathways involved in skeletal health were assessed. Standardized effect sizes as a quantitative measure regarding the impact of serum changes and the prediction of these changes on bone microarchitecture were investigated. In total, 32 male patients with a severe burn injury (median total body surface area [TBSA], 40.5%; median age 40.5 years) and 28 matched male controls (median age 38.3 years) over a period of 24 months were included. In patients who had sustained a thermal injury, trabecular and cortical bone microstructure showed a continuous decline, whereas cortical porosity (Ct.Po) and pore volume increased. Initially, elevated levels of BTM and C‐reactive protein (CRP) continuously decreased over time but remained elevated. In contrast, levels of soluble receptor activator of NF‐κB ligand (sRANKL) increased over time. Osteocalcin, bone‐specific alkaline phosphatase (BALP), intact N‐terminal type 1 procollagen propeptide (P1NP), and cross‐linked C‐telopeptide (CTX) acutely reflected the increase of Ct.Po at the radius (R2 = 0.41), followed by the reduction of trabecular thickness at the tibia (R2 = 0.28). In adult male patients, early and sustained changes of markers of bone resorption, formation and regulators of bone signaling pathways, prolonged inflammatory cytokine activities in conjunction with muscle catabolism, and vitamin D insufficiency were observed. These alterations are directly linked to a prolonged deterioration of bone microstructure. The probably increased risk of fragility fractures should be of clinical concern and subject to future interventional studies with bone‐protective agents.

Clinical significance of Candida colonization of central vascular catheters in patients with major burns requiring intensive care

Dear Editor, Patients with thermal injury are vulnerable to local and systemic infections. Candida spp. were the second most common pathogens isolated from catheter tips in European countries (9.1 %) [1]. Although several studies were performed to evaluate the clinical relevance of Candida spp. colonization of intravascular catheters, burn patients were only rarely studied [2–5]. Patients suffering from severe burns with an Abbreviated Burn Severity Index (ABSI) C6, a length of ICU stay C24 h, a survival of more than 7 days and central venous catheter (CVC) tip culture yielding C15 colony-forming units of Candida spp. met the general inclusion criteria for this study. Patients were categorized into two groups based on their final outcome. Group I consisted of subjects with ‘‘poor outcome’’ (patients with positive CVC tip cultures for Candida spp. that suffered from subsequent or catheter related candidemia); Group II consisted of subjects with ‘‘good outcome’’ (patients with positive CVC tip cultures for Candida spp. that did not suffer from subsequent or catheter-related candidemia) (Table 1). Candidemia was defined as the presence of at least one positive blood culture for any Candida spp. Catheter-related candidemia was defined as detection of the same Candida sp. from the CVC tip and blood culture, obtained 48 h before to 48 h after CVC removal. Subsequent candidemia was defined as the occurrence of candidemia C48 h after CVC removal. Tip cultures, screening for fungal or bacterial pathogens, are always performed when a CVC is removed. A total of 38/194 (20 %) patients met the inclusion criteria for the present study (Table 1). Of these,

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study

OBJECTIVES The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.