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PURPOSE: Major trauma remains a significant cause of morbidity and mortality in the developed and developing world. In 2013, nearly 5 million people worldwide died from their injuries, and almost 1 billion individuals sustained injuries that warranted some type of healthcare, accounting for around 10% of the global burden of disease in general. Behind the statistics, severe trauma takes a major toll on individuals, their families and healthcare systems. Management of the patient with severe trauma requires multiple interventions in a highly time-sensitive context and fragmentation of care, characterised by loss of information and time among disciplines, departments and individuals, both outside the hospital and within it, is frequent. Outcomes may be improved by better streamlining of pre- and intra-hospital care. METHODS: We describe the basis for development of a multi-stakeholder consortium by the European Critical Care Foundation working closely with a number of European Scientific Societies to address and overcome problems of fragmentation in the care of patients with severe trauma. RESULT: The consortium will develop and introduce an information management system adapted to severe trauma, which will integrate continuous monitoring of vital parameters and point-of-care diagnostics. The key innovation of the project is to harness the power of information technologies and artificial intelligence to provide computer-enhanced clinical evaluation and decision-support to streamline the multiple points at which information and time are potentially lost. CONCLUSIONS: The severe trauma management platform thus created could have multiple benefits beyond its immediate use in managing the care of injured patients. ispartof: EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY vol:45 issue:1 pages:39-48 ispartof: location:Germany status: published

Aims: Gait characteristics and balance are altered in diabetic individuals. Little is known about possible treatment strategies. This study evaluated the effect of a specific training program on diabetic patients' gait. Methods: A randomized controlled trial (N = 71) with an intervention (IG) (N = 35), and control group (CG) (N = 36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-oriented strengthening. Controls received no treatment. Results: After intervention the IG increased their habitual walking speed by 0.149 ms(-1) km h(-1)) on tarred terrain and by 0.169 ms(-1) (0.61 km h(-1)) on the cobblestones. This significant treatment effect (p

BACKGROUND: Antimicrobial resistance may compromise the efficacy of antibiotic prophylaxis before surgery. The aim of this study was to measure susceptibility and clonal distribution of coagulase-negative staphylococci (CoNS) colonizing the skin around the surgery access site before and after the procedure. METHODS: From March to September 2004, a series of 140 patients undergoing elective major abdominal surgery were screened for CoNS colonization at admission and 5 days after surgery. All isolates were tested for antibiotic susceptibility and genotyped by pulsed-field gel electrophoresis (PFGE). RESULTS: Colonization rates with CoNS at admission and after surgery were 85% and 55%, respectively. The methicillin-resistant CoNS rate increased from 20% at admission to 47% after surgery (P = 0.001). The PFGE pattern after surgery revealed more patients colonized with identical clones: 8/140 patients (8/119 strains) and 26/140 patients (26/77 strains), respectively (P < 0.001). CONCLUSIONS: Our results suggest rapid recolonization of disinfected skin by resistant nosocomial CoNS. Larger studies, preferably among orthopedic or cardiovascular patients, are required to clarify whether standard antibiotic prophylaxis with first- or second-generation cephalosporins for CoNS infections may be compromised if the patient requires an additional intervention 5 days or more after the initial surgery.

BACKGROUND: Benzimidazoles are often used concomitantly with protease inhibitors in patients with helminthic disease and HIV infection. Low bioavailability and extensive first-pass metabolism make benzimidazoles prone to pharmacokinetic drug interactions. The aim of the present study was to investigate potential drug interactions between the benzimidazoles albendazole and mebendazole and the potent CYP3A4 inhibitor ritonavir. METHODS: Sixteen healthy volunteers were administered a single oral dose of 1,000 mg mebendazole or 400 mg albendazole (2 x n = 8). AUC, C(max), and t(1/2) of mebendazole, albendazole, and albendazole sulfoxide were studied in absence and after short-term (2 doses) and long-term (8 days) treatment with ritonavir 200 mg bid. RESULTS: Pharmacokinetic parameters of albendazole and mebendazole were not changed by short-term administration of ritonavir. However, long-term administration of ritonavir resulted in significant changes in albendazole and mebendazole disposition, with a significant decrease in AUC(0-24) (27 and 43% of baseline for albendazole and mebendazole, respectively) and C(max) (26 and 41% of baseline, respectively). CONCLUSION: The AUC(0-24) of benzimidazoles decreased after long-term use of ritonavir, while no changes in pharmacokinetic profiles were observed under short-term administration. These findings might help to optimize benzimidazole efficacy when used in combination with protease inhibitors.

Summary: We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. Background: Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. Methods: We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. Results: Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20-0.33, p

Protein deficiency is associated with impaired titanium osseointegration. We studied whether systemic treatment with PTH or pamidronate could influence the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. PTH or pamidronate prevented the deleterious effects of protein undernutrition on bone microarchitecture close to the implant and on mechanical fixation. PTH even significantly improved implant osseointegration. Introduction: Protein deficiency is highly prevalent among elderly patients hospitalized in orthopedic wards. Reduced protein intake impairs titanium osseointegration in rats. Whether stimulator of bone formation or inhibitor of bone resorption could improve implant osseointegration under protein deprivation is not known. We studied the effects of systemic treatment with PTH or pamidronate on the resistance to pull-out of titanium rods implanted into rats proximal tibia under normal and isocaloric low protein intake. Materials and Methods: We measured the resistance to pull-out 1-mm -diameter titanium rods implanted into the proximal tibias of 49 adult female rats receiving a normal or an isocaloric low protein diet. After 2 wk on either diet, the implants were inserted, and the rats received PTH(1–34), pamidronate or saline vehicle for 8 wk. The tibias were removed for μCT morphometry, followed by the evaluation of pull-out strength. Results: Pull-out strength was lower in rats fed an isocaloric low protein diet compared with rats fed a normal protein intake (−29%). PTH and pamidronate significantly increased pull-out strength in animals fed a normal or a low protein diet, the effect of PTH being of higher magnitude. The PTH- or pamidronate-mediated increase in pull-out strength was associated with significant increases of relative bone volume, bone-to -implant contact, and trabecular thickness, whereas trabecular spacing was reduced, in the vicinity of the implants. Conclusions: We confirmed that isocaloric low protein intake impairs titanium implant osseointegration. PTH or pamidronate prevented the deleterious effects of protein undernutrition and even significantly improved the implant osseointegration. These results indicate that systemic administration of PTH or pamidronate could be considered for preventing uncemented arthroplasty loosening in protein undernourished patients.

Beside its influence on determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality as evaluated by nanoindentation, increasing elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for 104 wk with daily dose from 0 to 900 mg/kg. Introduction: We previously showed that strontium ranelate treatment improves the mechanical properties of the vertebral body and long bone midshaft in intact rats. The increased energy to failure obtained with strontium ranelate is essentially caused by an increase in plastic energy, suggesting that bone formed during treatment can withstand greater deformation before fracture. In the bone mineral phase, strontium is mainly located in the hydrated shell and could thus potentially influence intrinsic bone tissue quality. Materials and Methods: To study whether strontium ranelate treatment could positively influence intrinsic bone tissue quality (elastic modulus, hardness, and dissipated energy), nanoindentation tests were performed at the level of trabecular nodes and cortex under physiological or dry conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a daily dose of 0, 225, 450, or 900 mg/kg (n = 12 per group). Ex vivo μCT measurements and axial compression tests of adjacent vertebral bodies were also performed. Significance of difference was evaluated using ANOVA. Results: In agreement with previous results, strontium ranelate (900 mg/kg/d) significantly increased versus controls in maximal load (+23%), total energy (+71%), and plastic energy (+143%). At the level of trabecular bone, strontium ranelate treatment resulted in a significant increase in elastic modulus (+15.1%, p < 0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001) versus controls in physiological, but not in dry, conditions. The effect was less pronounced in cortex. Conclusions: These results show for the first time a direct action of strontium ranelate on bone tissue quality. Beside its shown influence on classical determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality. This could contribute to the increase in bone strength and thus be involved in the reduction of fracture risk in postmenopausal osteoporotic patients treated with strontium ranelate.

Background Propofol is commonly used as sedative in newborns and children. Recent experimental studies led to contradictory results, revealing neurodegenerative or neuroprotective properties of propofol on the developing brain. We investigated neurodevelopmental short- and long-term effects of neonatal propofol treatment. Methods 6-day-old Wistar rats (P6), randomised in two groups, received repeated intraperitoneal injections (0, 90, 180 min) of 30 mg/kg propofol or normal saline and sacrificed 6, 12 and 24 hrs following the first injection. Cortical and thalamic areas were analysed by Western blot and quantitative real-time PCR (qRT-PCR) for expression of apoptotic and neurotrophin-dependent signalling pathways. Long-term effects were assessed by Open-field and Novel-Object-Recognition at P30 and P120. Results Western blot analyses revealed a transient increase of activated caspase-3 in cortical, and a reduction of active mitogen-activated protein kinases (ERK1/2, AKT) in cortical and thalamic areas. qRT-PCR analyses showed a down-regulation of neurotrophic factors (BDNF, NGF, NT-3) in cortical and thalamic regions. Minor impairment in locomotive activity was observed in propofol treated adolescent animals at P30. Memory or anxiety were not impaired at any time point. Conclusion Exposing the neonatal rat brain to propofol induces acute neurotrophic imbalance and neuroapoptosis in a region- and time-specific manner and minor behavioural changes in adolescent animals. OA Förderung 2013

Background Neuroblastoma is the most common pediatric solid tumor of the sympathetic nervous system. Development of improved predictive tools for patients stratification is a crucial requirement for neuroblastoma therapy. Several studies utilized gene expression-based signatures to stratify neuroblastoma patients and demonstrated a clear advantage of adding genomic analysis to risk assessment. There is little overlapping among signatures and merging their prognostic potential would be advantageous. Here, we describe a new strategy to merge published neuroblastoma related gene signatures into a single, highly accurate, Multi-Signature Ensemble (MuSE)-classifier of neuroblastoma (NB) patients outcome. Methods Gene expression profiles of 182 neuroblastoma tumors, subdivided into three independent datasets, were used in the various phases of development and validation of neuroblastoma NB-MuSE-classifier. Thirty three signatures were evaluated for patients' outcome prediction using 22 classification algorithms each and generating 726 classifiers and prediction results. The best-performing algorithm for each signature was selected, validated on an independent dataset and the 20 signatures performing with an accuracy > = 80% were retained. Results We combined the 20 predictions associated to the corresponding signatures through the selection of the best performing algorithm into a single outcome predictor. The best performance was obtained by the Decision Table algorithm that produced the NB-MuSE-classifier characterized by an external validation accuracy of 94%. Kaplan-Meier curves and log-rank test demonstrated that patients with good and poor outcome prediction by the NB-MuSE-classifier have a significantly different survival (p < 0.0001). Survival curves constructed on subgroups of patients divided on the bases of known prognostic marker suggested an excellent stratification of localized and stage 4s tumors but more data are needed to prove this point. Conclusions The NB-MuSE-classifier is based on an ensemble approach that merges twenty heterogeneous, neuroblastoma-related gene signatures to blend their discriminating power, rather than numeric values, into a single, highly accurate patients' outcome predictor. The novelty of our approach derives from the way to integrate the gene expression signatures, by optimally associating them with a single paradigm ultimately integrated into a single classifier. This model can be exported to other types of cancer and to diseases for which dedicated databases exist.

OBJECTIVES The aim of this study was to test whether adenosine triphosphate sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart. BACKGROUND The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However the mechanisms that govern the expression of their subunits (e.g. potassium inward rectifier [Kir] 6.2) in adult pathologies are mostly unknown. METHODS We collected biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2 FOXO1 FOXO3 and hypoxia inducible factor [HIF] 1a) were measured respectively by Western blotting immunohistochemistry and quantitative real time polymerase chain reaction and submitted to statistical analysis. RESULTS In all heart chambers Kir6.2 mRNA correlated with HIF 1a mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their respective mRNAs. The HIF 1a mRNA related in the left ventricle to aortic pressure in the left atrium to left atrial pressure and in all heart chambers to a decreased Kir6.2 protein/mRNA ratio. Interestingly in the left heart Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at low venous PO(2). In the left ventricle the Kir6.2 protein/mRNA ratio was also significantly higher at low venous PO(2) suggesting that tissue hypoxia might stabilize the Kir6.2 protein. CONCLUSIONS Results suggest that post transcriptional events determine Kir6.2 protein expression in the left ventricle of patients with severe mitral dysfunction and low venous PO(2). Mechanical stress mainly affects transcription of HIF 1a and Kir6.2. This study implies that new therapies could aim at the proteasome for stabilizing the left ventricular Kir6.2 protein.

Aims/hypothesis Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients. Methods This was a randomised controlled trial (n = 71) with an intervention (n = 35) and control group (n = 36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening (twice weekly over 12 weeks). Controls received no treatment. Individuals were allocated to the groups in a central office. Gait, balance, fear of falls, muscle strength and joint mobility were measured at baseline, after intervention and at 6-month follow-up. Results The trial is closed to recruitment and follow-up. After training, the intervention group increased habitual walking speed by 0.149 m/s (p

Background Peripheral neuropathy is recognised to be the most symptomatic complication of diabetes and is also linked to postural instability. This study investigates balance instability in diabetic patients with and without peripheral neuropathy. Methods Quiet standing balance was investigated using an accelerometric-based method in 24 diabetic patients (12 with and 12 without peripheral neuropathy) and compared with 12 control subjects. Accelerations were measured at lumbar and ankle levels using three accelerometers. Two standing conditions of 30 s were evaluated (i.e., eyes opened, eyes closed). The range and root mean square values were calculated on the anterior posterior component of lumbar and ankle accelerations and for the medial lateral component of lumbar accelerations. Differences between parameters were compared between groups using ANOVA and post hoc comparisons. Findings The diabetic patients with peripheral neuropathy show higher-range and root mean square values compared with those of control subjects and diabetic patients without peripheral neuropathy. Significant differences between groups have been detected for anterior posterior range of lumbar acceleration, which was significantly higher for diabetic patients with peripheral neuropathy, compared with those of others groups. Significant higher values for diabetic patients with peripheral neuropathy were also detected for anterior posterior range and root mean square of ankle accelerations compared with control subjects. Visual deprivation shows an increase in accelerometric parameters for each group. Interpretation This study is the first to investigate the balance instability of diabetic patients using accelerometers. Results confirm that diabetic patients with peripheral neuropathy have greater postural instability with higher acceleration values than those of control group and diabetic patients without peripheral neuropathy.

AIM: To identify clinical factors associated with gait alterations in patients with Type 2 diabetes. METHODS: A sample of 76 diabetic patients underwent clinical examination and an outdoor gait assessment on tarred and cobblestoned terrains. We calculated respective differences in gait speed (performance measure) and gait variability (fall risk index) on changing terrains. Associations with clinical factors were investigated using correlation coefficients and linear regression analysis. RESULTS: The mean walking speed on the tarred pathway was 4.5 +/- 0.6 km/h and 3.9 +/- 0.8 km/h on the cobblestone pathway (P < 0.001). The CVGCT increased from 2.6 +/- 0.9% on the tarred pathway to 5.1 +/- 2.8% on the cobblestone pathway (P < 0.001). Regression analysis showed that 36% of the decrease in gait speed was explained proportionally by the mean of maximal isometric lower limb strength (22.2%; P ≤ 0.01), fear of falls (7.4%; P ≤ 0.01) and participants' perceived vibration threshold (6.4%; P ≤ 0.01). Moreover, mean maximal isometric strength explained 11.8% (P ≤ 0.01) of the increase of the coefficient of variation of the gait cycle time when participants changed from tarred terrain to cobblestones. CONCLUSION: This study indicated that both physiological (strength and proprioception) and cognitive-behavioural factors (fear of falls) should be considered when treating diabetic patients with gait alterations. Therapists should apply these findings when developing specific fall prevention and treatment programmes.

The aim of this prospective study was to examine the determinants of growth failure and the association with neurodevelopmental outcome in infants undergoing open-heart surgery. In 107 infants undergoing open-heart surgery for congenital heart disease (CHD), we evaluated weight at birth, at surgery, and at one year of age (expressed as z-scores). Neurodevelopmental status was assessed before surgery and at one year of age. Median age at surgery was 3.9 months (range: 0.1-10.2). Mean [+/-standard deviation (S.D.)] weight z-score at birth was -0.27 (+/-1.45), before surgery -1.34 (+/-1.45) (P3 (OR 3.22, P

Objectives: To study the impact of a teaching intervention on the rate of central venous catheter-related bloodstream infections (CRBSI) in intensive care patients. Design: Prospective before/after interventional cohort study on medical and surgical intensive care units. Setting: University hospital with five adult intensive care units. Patients: All patients with a central venous catheter on the five ICUs from September to December 2003 (baseline period) and from March to July 2004 (intervention period). Interventions: Educational program with teaching of hand hygiene, standards of catheter care, and preparation of intravenous drugs. Measurements and Main Results: The primary outcome variable was the rate of CRBSIs per 1000 catheter days during a baseline period of 4 months and an intervention period of 5 months. The secondary outcome variable was compliance with hand hygiene. Of the patients, 499 patients with 6200 catheter days in the baseline period and 500 patients with 7279 catheter days were monitored in the intervention period. The incidence density of CRBSI decreased from 3.9 per 1000 catheter days in the preintervention phase to 1.0 per 1000 catheter days in the intervention phase (p

Human rhinovirus type C is a recently discovered species that has been associated with respiratory tract infections of unusual severity in some cases. However, the precise type of diseases associated with this new human rhinovirus needs to be investigated. In the present report, we used adapted real-time PCR assays to screen different clinical specimens collected from a 14-month-old boy presenting an acute lower respiratory tract disease complicated by a severe pericarditis. RT-PCR identified picornavirus RNA in the bronchoalveolar lavage (BAL) specimen, pericardial fluid, plasma and stools. This supported the existence of a disseminated viral infection that extended to the pericardial space. 5'UTR and VP1 sequence analysis performed directly from the BAL sample allowed genotyping of the virus as a human rhinovirus C. This observation highlights the need for adapted diagnostic tools and the potential for the new rhinovirus species C to cause complications, including pericarditis.

The gastrointestinal (GI) tract forms from the endoderm (which gives rise to the epithelium) and the mesoderm (which develops into the smooth muscle layer, the mesenchyme, and numerous other cell types). Much of what is known of GI development has been learned from studies of the endoderm and its derivatives, because of the importance of epithelial biology in understanding and treating human diseases. Although the necessity of epithelial-mesenchymal cross talk for GI development is uncontested, the role of the mesoderm remains comparatively less well understood. The transformation of the visceral mesoderm during development is remarkable; it differentiates from a very thin layer of cells into a complex tissue comprising smooth muscle cells, myofibroblasts, neurons, immune cells, endothelial cells, lymphatics, and extracellular matrix molecules, all contributing to the form and function of the digestive system. Understanding the molecular processes that govern the development of these cell types and elucidating their respective contribution to GI patterning could offer insight into the mechanisms that regulate cell fate decisions in the intestine, which has the unique property of rapid cell renewal for the maintenance of epithelial integrity. In reviewing evidence from both mammalian and nonmammalian models, we reveal the important role of the visceral mesoderm in the ontogeny of the GI tract.

Der LH (Luteinisierendes Hormon)-Rezeptor spielt die entscheidende Rolle in dem komplexen Prozess der Geschlechtsdifferenzierung. Dabei kann er sowohl Ursache für eine vorzeitige als auch für eine ausbleibende Pubertätsentwicklung sein.

We describe four infants with ornithine transcarbamylase (OTC) deficiency, who developed arterial and venous thromboses prior to undergoing liver transplantation. These patients prompted a retrospective chart review of children with inborn errors of metabolism associated with hyperammonemia seen at our institution between 1998 and 2008; no additional cases with thrombosis were detected. Data abstracted from medical records include patient demographics, details about thrombus, treatment, associated risk factors and metabolic abnormalities. OTC deficiency was diagnosed during the first week of life in all patients (median age – 4 days; age range 1–7 days). Thrombotic complications developed prior to liver transplant in all patients (median age - 63 days; age range 6–71 days). One patient had arterial thrombus; the rest developed venous thromboses. Possible risk factors for thrombosis are summarized in the table below. Risk factors Patient 1 Patient 2 Patient 3 Patient 4 Indwelling catheter at the site of thrombus Yes Yes Yes Yes Hyperammonemia (>94 mmol/L) Yes No Yes Yes Low plasma arginine ( Table 1. Patient characteristics that are potential risk factors for thrombosis * AT III - Anti-thrombin III Multiple pro-thrombotic risk factors were present. Hyperammonemia was seen in 3 patients and low plasma arginine level was present in all patients around the time of thrombosis. As L-arginine is a substrate for nitric oxide synthesis, arginine deficiency leads to low nitric oxide levels. Recent studies have linked nitric oxide insufficiency to platelet hyperaggregability, thrombosis and endothelial damage. Infants with OTC deficiency, indwelling vascular catheters, hyperammonemia and low plasma arginine may be at increased risk for thrombosis. Further studies in patients with OTC deficiency, to evaluate the role of hyperammonemia and low plasma arginine in thrombogenesis are warranted.