Primary stability of a press-fit cup in combination with impaction grafting in an acetabular defect model

The objectives of this study were to (a) assess primary stability of a press-fit cup in a simplified acetabular defect model, filled with compacted cancellous bone chips, and (b) to compare the results with primary stability of a press-fit cup combined with two different types of bone graft substitute in the same defect model. A previously developed acetabular test model made of polyurethane foam was used, in which a mainly medial contained defect was implemented. Three test groups (N = 6 each) were prepared: Cancellous bone chips (bone chips), tricalciumphosphate tetrapods + collagen matrix (tetrapods + coll), bioactive glass S53P4 + polyethylene glycol-glycerol matrix (b.a.glass + PEG). Each material was compacted into the acetabulum and a press-fit cup was implanted. The specimens were loaded dynamically in the direction of the maximum resultant force during level walking. Relative motion between cup and test model was assessed with an optical measurement system. At the last load step (3000 N), inducible displacement was highest for bone chips with median [25th percentile; 75th percentile] value of 113 [110; 114] µm and lowest for b.a.glass + PEG with 91 [89; 93] µm. Migration at this load step was highest for b.a.glass + PEG with 868 [845; 936] µm and lowest for tetrapods + coll with 491 [487; 497] µm. The results show a comparable behavior under load of tetrapods + coll and bone chips and suggest that tetrapods + coll could be an attractive alternative to bone chips. However, so far, this was found for one specific defect type and primary stability should be further investigated in additional/more severe defects

A method to assess primary stability of acetabular components in association with bone defects

The objectives of this study were to develop a simplified acetabular bone defect model based on a representative clinical case, derive four bone defect increments from the simplified defect to establish a step‐wise testing procedure, and analyze the impact of bone defect and bone defect filling on primary stability of a press‐fit cup in the smallest defined bone defect increment. The original bone defect was approximated with nine reaming procedures and by exclusion of specific procedures, four defect increments were derived. The smallest increment was used in an artificial acetabular test model to test primary stability of a press‐fit cup in combination with bone graft substitute (BGS). A primary acetabular test model and a defect model without filling were used as reference. Load was applied in direction of level walking in sinusoidal waveform with an incrementally increasing maximum load (300 N/1000 cycles from 600 to 3000 N). Relative motions (inducible displacement, migration, and total motion) between cup and test model were assessed with an optical measurement system. Original and simplified bone defect volume showed a conformity of 99%. Maximum total motion in the primary setup at 600 N (45.7 ± 5.6 µm) was in a range comparable to tests in human donor specimens (36.0 ± 16.8 µm). Primary stability was reduced by the bone defect, but could mostly be reestablished by BGS‐filling. The presented method could be used as platform to test and compare different treatment strategies for increasing bone defect severity in a standardized way

Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients

Objective: To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids (VLPD+KA) in comparison with a conventional low-protein diet (LPD) in chronic kidney disease (CKD) patients.Design: Prospective, randomized, controlled clinical study.Setting: Outpatient Clinic of the Nephrology Division of Federal University of São Paulo, Brazil.Subjects: the study involved 24 patients with advanced CKD ( creatinine clearance <25 ml/min) that were randomly assigned to either a VLPD+KA (VLPD+KA group, 12 patients) or to a conventional LPD with 0.6 g/kg/day ( LPD group, 12 patients). the patients were followed for 4 months.Results: Nutritional status was adequately maintained with both diets for the studied period. Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group ( from 0.68 +/- 0.17 to 0.43 +/- 0.12 g/kg/day, P<0.05; from 61.4 +/- 12.8 to 43.6 +/- 14.9 mg/dl, P<0.001; respectively). Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group. Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus (529 +/- 109 to 373 +/- 125 mg/day, P<0.05) associated to the phosphorus-binding effect of the ketoacids. No change in these parameters was found in the LPD group. Serum parathormone increased significantly only in the LPD group (from 241 +/- 138 to 494 +/- 390 pg/ ml, P<0.01). the change in PTH concentration was negatively correlated with changes in ionized calcium concentration ( r = - 0.75, P = 0.02) and positively correlated with changes in serum phosphorus ( r = 0.71, P = 0.03) only in the LPD group.Conclusion: This study indicates that a VLPD+KA can maintain the nutritional status of the patients similarly to a conventional LPD. Besides, an improvement in calcium and phosphorus metabolism and a reduction in serum urea nitrogen were attained only with the VLPD+KA. Thus, VLPD+KA can constitute another efficient therapeutic alternative in the treatment of CKD patients.Sponsorship: This study was supported by CAPES, Oswaldo Ramos Foundation and Fresenius Kabi, Ltda.Universidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

BACKGROUND: Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. METHODS: In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. RESULTS: The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10-1.37; p<0.001)(per 1 kg/m(2) decrement, HR = 1.14; 95% CI, 1.05-1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01-1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00-1.16; p = 0.058). CONCLUSION: The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir

Determinants of the urinary and serum metabolome in children from six European populations

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children