A credible homogenized finite element model to predict radius fracture in the case of a forward fall.

Fragility fractures that occur after a fall from a standing height or less are almost always due to osteoporosis, which remains underdiagnosed and untreated. Patient-specific finite element (FE) models have been introduced to predict bone strength and strain. This approach, based on structure mechanics, is derived from Quantitative Computed Tomography (QCT), and element mechanical properties are computed from bone mineral densities. In this study, we developed a credible finite element model of the radius to discriminate low-trauma-fractured radii from non-fractured radii obtained experimentally. Thirty cadaveric radii were impacted with the same loading condition at 2 m/s, and experimental surface strain was retrieved by stereo-correlation in addition to failure loads in fracture cases. Finite element models of the distal radius were created from clinical computed tomography. Different density-elasticity relationships and failure criteria were tested. The strongest agreement (simulations-experiments) for average strain showed a Spearman's rank correlation (ρ) between 0.75 and 0.82, p < 0.0001, with a root mean square error between 0.14 and 0.19%. The experimental mean strain was 0.55%. Predicted failure load error (23%) was minimized for derived Pistoia's failure criterion. Numerical failure demonstrated area under the receiver operating characteristic (ROC) curves of 0.76 when classifying radius fractures with an accuracy of 82%. These results suggest that a credible FE modelling method in a large region of interest (distal radius) is a suitable technique to predict radius fractures after a forward fall.

Influence of loading conditions in finite element analysis assessed by HR-pQCT on ex vivo fracture prediction.

Many fractures occur in individuals with normal areal Bone Mineral Density (aBMD) measured by Dual X-ray Absorptiometry (DXA). High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) allows for non-invasive evaluation of bone stiffness and strength through micro finite element (µFE) analysis at the tibia and radius. These µFE outcomes are strongly associated with fragility fractures but do not provide clear enhancement compared with DXA measurements. The objective of this study was to establish whether a change in loading conditions in standard µFE analysis assessed by HR-pQCT enhance the discrimination of low-trauma fractured radii (n = 11) from non-fractured radii (n = 16) obtained experimentally throughout a mechanical test reproducing a forward fall. Micro finite element models were created using HR-pQCT images, and linear analyses were performed using four different types of loading conditions (axial, non-axial with two orientations and torsion). No significant differences were found between the failure load assessed with the axial and non-axial models. The different loading conditions tested presented the same area under the receiver operating characteristic (ROC) curves of 0.79 when classifying radius fractures with an accuracy of 81.5%. In comparison, the area under the curve (AUC) is 0.77 from DXA-derived ultra-distal aBMD of the forearm with an accuracy of 85.2%. These results suggest that the restricted HR-pQCT scanned region seems not sensitive to loading conditions for the prediction of radius fracture risk based on ex vivo experiments (n = 27).

Variabilities in µQCT-based FEA of a tumoral bone mice model.

A finite element analysis based on Micro-Quantitative Computed Tomography (µQCT) is a method with high potential to improve fracture risk prediction. However, the segmentation process and model generation are generally not automatized in their entirety. Even with a rigorous protocol, the operator might add uncertainties during the creation of the model. The aim of this study was to evaluate a µQCT-based model of mice tumoral and sham tibias in terms of the variabilities induced by the operator and sensitivity to operator-dependent variables (such as model orientation or length). Two different operators generated finite element (FE) models from µCT images of 8 female Balb/c nude mice tibias aged 10 weeks old with bone tumors induced in the right tibia and with sham injection in the left. From these models, predicted failure load was determined for two different boundary conditions: fixed support and spherical joints. The difference between the predicted and experimental failure load of both operators was large (-122% to 93%). The difference in the predicted failure load between operators was less for the spherical joints boundary conditions (9.8%) than for the fixed support (58.3%), p < 0.001, whereas varying the orientation of bone tibia caused more variability for the fixed support boundary condition (44.7%) than for the spherical joints (9.1%), p < 0.002. Varying tibia length had no significant effect, regardless of boundary conditions (<4%). When using the same mesh and same orientation, the difference between operators is non-significant (<6%) for each model. This study showed that the operator influences the failure load assessed by a µQCT-based finite element model of the tumoral and sham mice tibias. The results suggest that automation is needed for better reproducibility.

In Vivo Assessment of Elasticity of Child Rib Cortical Bone Using Quantitative Computed Tomography.

Elasticity of the child rib cortical bone is poorly known due to the difficulties in obtaining specimens to perform conventional tests. It was shown on the femoral cortical bone that elasticity is strongly correlated with density for both children and adults through a unique relationship. Thus, it is assumed that the relationships between the elasticity and density of adult rib cortical bones could be expanded to include that of children. This study estimated in vivo the elasticity of the child rib cortical bone using quantitative computed tomography (QCT). Twenty-eight children (from 1 to 18 y.o.) were considered. Calibrated QCT images were prescribed for various thoracic pathologies. The Hounsfield units were converted to bone mineral density (BMD). A relationship between the BMD and the elasticity of the rib cortical bone was applied to estimate the elasticity of children's ribs in vivo. The estimated elasticity increases with growth (7.1 ± 2.5 GPa at 1 y.o. up to 11.6 ± 1.9 GPa at 18 y.o.). This data is in agreement with the few previous values obtained using direct measurements. This methodology paves the way for in vivo assessment of the elasticity of the child cortical bone based on calibrated QCT images.

Identification of HLA-G7 as a new splice variant of the HLA-G mRNA and expression of soluble HLA-G5, -G6, and -G7 transcripts in human transfected cells.

The nonclassical HLA-G primary transcript is alternatively spliced to generate several mRNAs that have the capacity to encode four membrane bound isoforms, namely HLA-G1, -G2, -G3, and -G4 and two soluble isoforms HLA-G5 and -G6. We aimed at defining the capacity of full length and truncated soluble HLA-G transcripts to be translated in human cell lines. Our study of HLA-G alternative transcripts in various human tissues led us to identify a new splice variant of the HLA-G mRNA, named G7, in which open reading frame continues in intron 2. Due to the presence of a stop codon within intron 2, HLA-G7 transcripts retain the capacity to be translated as soluble truncated HLA-G proteins bearing the alpha1 domain linked to two specific aminoacids encoded by intron 2. Expression vectors containing cDNAs encoding HLA-G5, -G6, and -G7 isoforms were transfected into human cell lines. The presence of translated HLA-G5, -G6, and -G7 proteins was detected in protein extracts of transfected cells by Western blot and immunoprecipitation, but only the full length HLA-G5 soluble isoform could be clearly detected as a secreted protein in both transfected cells supernatants and body fluids.

Opinions on renal transplantation and organ donation in high school students in two large northern (Torino) and southern (Napoli) Italian cities.

UNLABELLED: Organ shortage for transplantation has focused attention on educational interventions. Italy is a nonhomogenous country whose cultural and economic differences are reflected in the health-care system: dialysis is mainly public in the north versus private in the south; and transplantation rates display a wide range from 3.4 to 37.8 per million people in 2002. The aim of the present study was to analyze the opinions of population of high school students (last two years) in two large cities: northern (Torino) and southern (Napoli) Italy, as a knowledge base for a randomized controlled trial on the efficacy of educational interventions on renal replacement therapy and organ donation, targeted to high school students. METHODS: This preliminary study included eight public high schools that completed a first and anonymous semistructured questionnaire. Five hundred and eighty nine questionnaires were retrieved in Torino and 539 in Napoli. In both cities most students answered that they would give a kidney to a brother, sister, or partner needing dialysis (Torino: yes 80.6%; no 2.2%, uncertain-blank 17.2%; Napoli: yes 86.1%, no 1.1%; uncertain-blank 12.8%). Only 36.3% of the students in Torino and 37.7% in Napoli answered that they would consent to organ donation, if they had to choose for a strict relative with brain death. Opposition was 28% in Torino and 23.7% in Napoli; 35.7% in Torino and 38.6% in Napoli were blank-uncertain. These data underline the need for detailed information on the opinions of the overall population as basis for tailored educational campaigns.

Kidney vending: opinions of the medical school students on this controversial issue.

BACKGROUND: In this era of globalization, in which different cultural and economic barriers are progressively abated, in the context of the development of rapid information networks such as the Internet, physicians are increasingly challenged by clinical and ethical questions. Kidney vending, banned in some countries, legal or tolerated in others, may be the prototype of the ethical aspects of health-care globalization. METHODS: To test the interest and the opinions of medical school students, a simulated case was proposed to students attending a seminar within the nephrology course fourth year of the Medical School of Torino, san Luigi): an Italian patient comes to the nephrologist's office asking for advice on the possibility to legally buy a kidney in a foreign country. The 43 students attending the lesson answered a semistructured questionnaire (15 boys, 28 girls, of median age 23 years). Attendance was within the usual standards (50 students inscribed per year). From the clinical point of view, 11.6% were favorable to kidney vending, 51.2% were contrary, 37.2% were uncertain. From the ethical point of view, no student was pro, 81.4% were contrary, and 18.6% were uncertain. The open comments underline the importance of patient self-determination and of informed consent. Similar opinions were recorded in a nonstructured question: "What should physician's attitude be, in the face of a choice he/she doesn't share?" CONCLUSION: Students' uncertainties and doubts underline the need to discuss ethical scenarios in the clinical teachings of the medical school.

Preemptive pancreas-kidney transplantation: multidisciplinary follow-up starts too late.

BACKGROUND: Preemptive pancreas-kidney transplantation is increasingly considered at early stages of nephropathy in type 1 diabetics. A multidisciplinary approach is required, but referral to the nephrologist is often delayed. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a dedicated nephrology unit and to test the prevalence of indications for pancreas-kidney transplantation in this population, according to early preemptive criteria (creatinine >/= 2 mg/dL and/or nephrotic syndrome). PATIENTS AND METHODS: The setting of study was the first Italian Nephrology Outpatient Unit dedicated to diabetics during 1991 to 2002. The main biochemical and clinical parameters were analyzed at referral. RESULTS: Ninety type 1 diabetics underwent at least one nephrological visit during the period; 85 had data at referral. The referral pattern was stable: 1991 to June 1996 [22 men, 24 women of median age 36 (18 to 65) years; diabetological follow-up 18.0 (3 to 37) years] and July 1996 to March 2002 [26 men, 18 women median age 40 (18 to 65); diabetological follow-up 21.5 (11 to 36) years]. The main biochemical data at referral were superimposable: serum creatinine: 1.2 (0.6 to 3.2) versus 1.3 (0.6 to 7) mg/dL; proteinuria: 0.9 (0 to 11) versus 1.01 (0.05 to 12.3) g/24 hours. Diabetes follow-up was greater in July 1996 to March 2002 [18 (3 to 37) versus 21.5 (11 to 36) years] suggesting an effect of improvements in diabetic care. At referral 76.6% were macroproteinuric 85.6% had signs of end-organ damage other than nephropathy; and 30.6% had indications for pancreas-kidney grafting (creatinine >/= 2 mg/dL: n = 6 cases; nephrotic syndrome: n = 10; or both n = 10). CONCLUSIONS: One new frontier of transplantation is the need for early multidisciplinary evaluation of type 1 diabetic patients.

Complete reversal of the nephrotic syndrome after preemptive pancreas-kidney transplantation: a case report.

BACKGROUND: Nephrotic syndrome due to diabetic nephropathy is presently considered an indication for pancreas-kidney transplantation even in the absence of severe renal failure. Reversal of the nephrotic syndrome has been reported, but the mechanisms of this effect are unclear. AIM: To describe the renal morphofunctional pattern and the pattern of proteinuria before and after preemptive pancreas-kidney transplantation. METHODS: Methods included quantitative and qualitative assessment of proteinuria as well as renal ultrasound and scintiscan. CASE REPORT: A 42-year-old woman with type 1 diabetes since age 24 had widespread end-organ damage. Renal biopsy (2001) showed a mainly nodular pattern of diabetic nephropathy. Following referral (1999), her serum creatinine ranged from 1.6 to 2.2 mg/dL, with nephrotic range proteinuria (glomerular nonselective, tubular complete). Renal scintiscan revealed bilateral, symmetric, well-perfused kidneys. The functional data before pancreas-kidney graft (February 2003) were: serum creatinine 1.6 mg/dL, creatinine clearance 58 mL/min, serum albumin 2.6 g/dL, proteinuria 9.1 g/d. At hospital discharge (March 2003), the creatinine was 1.2 mg/dL, the creatinine clearance 97 mL/min, the proteinuria 0.676 g/d. Two months later, the creatinine was 1.2 mg/dL and proteinuria 0.421 g/d. A renal scintiscan demonstrated the functional prevalence of the grafted kidney (77% of total function), with vital, almost completely excluded native kidneys (functional contribution, 11.5% each). Proteinuria, ranging from 0.3 to 0.6 g/d, showed a physiological pattern. CONCLUSIONS: Functional exclusion of the native kidneys by renal scintiscan gives morphological support to reversal of the nephrotic syndrome.

Twenty years of renal replacement therapy in a type 1 diabetic patient: advantages of a multiple choice dialysis system.

The prognosis of diabetic patients on renal replacement therapy (RRT) is usually poor. We report on the type 1 diabetic woman with the longest RRT follow-up in our area: over 20 years, half on dialysis, half with a renal graft. CS started RRT at age 27 on peritoneal dialysis (3 years), continued until an underdialysis syndrome developed, was switched to acetate dialysis and, because of poor tolerance, to hemofiltration which with good clinical results, allowing her to become the first Italian patient on home hemofiltration, which continued for 5 years. A cadaver graft lasted for the subsequent decade, despite several complications; afterwards she resumed bicarbonate dialysis, choosing a frequent home hemodialysis schedule. Despite several vascular access problems, her clinical conditions were good enough to candidate her for a second renal transplant, performed 3 years ago. This history of active self-care may draw attention to the advantages of a multiple choice dialysis network.

Maintenance of residual renal function 10 years after the start of hemodialysis: the advantage of tailored schedules?

Maintenance of residual renal clearance is a clinical advantage, protecting against the long-term effects of uremia: although demonstrated in peritoneal dialysis, the strategies in hemodialysis are less clear. This case suggests that dialysis schedules individualized on the basis of renal clearances may help preserve residual function. SB is a 58 year-old male who started dialysis in emergency (creatinine 30.7 mg/dL) in 1993. He had a history of gout, small shrunken kidneys and moderate hypertension. The clinical diagnosis was vasculointerstitial nephropathy. Eighteen months after starting hemodialysis on a conventional thrice weekly schedule, the patient was switched to 2 sessions/week (creatinine clearance increased to 6 ml/min). Thereafter, clearances were checked in alternate months and treatment was tailored to an equivalent renal clearance > or =12 ml/min (1-2 sessions, 2-3.30 hours/week). Ten years after beginning dialysis, he is on a twice weekly schedule (3.30 hours), is normotensive, works full-time and does not want to go on a transplant waiting list.

EPO or not-EPO? An evidence based informed consent.

BACKGROUND: Informed consent is crucial in therapeutic choices; however, the forms presented to patients are often locally developed and information may not be homogeneous. OBJECTIVE: To prepare an evidence-based model for informed consent, applied in the case of erythropoietin therapy (EPO) as a teaching tool for medical students. METHODS: Methodological tools of Evidence-Based Medicine (EBM) were developed within the EBM Course in the Medical School of Torino, Italy, as problem solving and patient information tools (5th year students work in small groups under the supervision of statisticians, epidemiologists and experts of internal medicine--nephrology in this case). RESULTS: Methodological and ethical problems were identified: in the pre-dialysis field, evidence from randomized clinical trials (RCT) is scant; how to use evidence gathered in dialysis? How to deal with implementation? How with the mass media? Do we need to discuss the drug choice with the patients? How to deal with rare and severe side effects?). The "evidence" was searched for on Medline/Embase, by using key-words and free terms. About 680 papers were retrieved and screened. Forms available on the Internet were retrieved and a general scheme was drawn: it included 5 areas: title, aim and targets (patients and family physicians); search strategies and updating; pros and cons of therapy; alternative options; open questions. CONCLUSIONS: EBM may offer valuable tools for systematically approaching patient information; the inclusion of this kind of exercise in the Medical School EBM courses may help enhance the awareness of future physicians of the correct communication with patients.

[Bright disease in Turin and Italy from the middle of the 19th century to the middle of the 20th century]. / La "malattia di Bright" a Torino e in Italia dalla metà dell'Ottocento alla metà del Novecento.

For many years the term nephritis was used to indicate renal diseases (in the sense of Bright s disease) in a larger sense. This review summarizes the history of the concept of glolomerulonephritis from Egyptian Medicine up to the Post-Biopsy Era, in particularly in Turin and in Italy. This study reports an epidemiology survey of Bright s disease in Italy from 1880 up to 1960. Towards the end of the 19th century Bright s disease accounted for 26 deaths/year/105 population (in comparison with more than 200 from tubercolosis) in Italy. At the beginning of the 20th century, Bright s disease was the seventh cause of death in Italy. Moreover, in Italy autopsy studies showed a higher percentage of deaths attributed to Bright s disease (5-7%) in comparison with those obtained from vital studies. In 1960, just before the beginning of renal replacement therapy, Bright s disease accounted for 15.7 deaths/year/105 population. Probably it was difficult to recognize in the real incidence of chronic renal diseases leading to death in the 1960s, and vital studies were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20/year/105 population).

Human maxilla bone response to 30 degrees oriented impacts and comparison with frontal bone impacts.

The aims of this study were to compare the responses of human maxilla and frontal bones under 30 degrees-oriented impacts. Maxilla and frontal bones of the same subject were impacted by a guided horizontal steel cylinder. Linear acceleration time histories and force time histories were plotted and corridors were proposed for maxilla bone response. Sensitivity of head dynamics in regard to impact energy level and localization showed the protection of the intracranial contents by the facial bones crushing. Injury risk curves were established for impact on frontal bone, showing a 50% risk injury for impact energy of 265 J or impact force of 7500 N.

[Costs of dialysis in hospitalised patients with acute or chronic renal failure, according to area of treatment]. / Costi dei trattamenti dialitici condotti in aree operative differenziate in pazienti ospedalizzati, acuti e cronici.

BACKGROUND: In Italy, dialysis reimbursement is regulated by the "Tariffario delle prestazioni ambulatoriali" (G.U. N 216, 14/9/1996), which does not take into account separately the dialysis sessions performed in hospitalised patients. In these cases the dialysis activity is considered within the final DRG (Diagnosis Related Group). Aim of the study was an analysis of production costs of dialysis performed in hospitalised patients, according to the setting in which dialysis is performed (Intensive Care Units (ICUs), other Units, hospital dialysis ward). METHODS: The direct production costs were assessed by the "bottom-up" technique logic (cost definition from the single elements needed for producing the treatment) referring to specific Cost Centres. The main items considered were health-care staff, dialysis supplies and hardware, blood tests, dialysis data recording and transmission. RESULTS: During the year 2000, there were 4,450 treatments performed in 490 patients. They included 924 haemodialyses in ICUs; 2,531 in the nephrology hospital dialysis ward; 602 peritoneal dialysis treatments in ICUs-other wards, 393 in the nephrology ward. Direct cost per haemodialysis treatment ranged from 276.05 E (UF) to 413.46 E (HF) in ICU, from 170.47 E (Bicarbonate Haemodialysis) to 275.36 E (Slow Haemofiltration) in hospital dialysis ward; for peritoneal dialysis between 128.95 E (CAPD in dialysis ward) and 282.10 E (CAPD in ICU/other Units). During the year 2000, the global cost of production was 1,038,346.65 E. CONCLUSIONS: The cost of dialysis in hospitalised patients is high. A dedicated budget is needed to avoid deficits, particularly in highly specialised Units of large referral hospitals.