A multiscale model to predict current absolute risk of femoral fracture in a postmenopausal population

Osteoporotic hip fractures are a major healthcare problem. Fall severity and bone strength are important risk factors of hip fracture. This study aims to obtain a mechanistic explanation for fracture risk in dependence of these risk factors. A novel modelling approach is developed that combines models at different scales to overcome the challenge of a large space–time domain of interest and considers the variability of impact forces between potential falls in a subject. The multiscale model and its component models are verified with respect to numerical approximations made therein, the propagation of measurement uncertainties of model inputs is quantified, and model predictions are validated against experimental and clinical data. The main results are model predicted absolute risk of current fracture (ARF0) that ranged from 1.93 to 81.6% (median 36.1%) for subjects in a retrospective cohort of 98 postmenopausal British women (49 fracture cases and 49 controls); ARF0 was computed up to a precision of 1.92 percentage points (pp) due to numerical approximations made in the model; ARF0 possessed an uncertainty of 4.00 pp due to uncertainties in measuring model inputs; ARF0 classified observed fracture status in the above cohort with AUC = 0.852 (95% CI 0.753–0.918), 77.6% specificity (95% CI 63.4–86.5%) and 81.6% sensitivity (95% CI 68.3–91.1%). These results demonstrate that ARF0 can be computed using the model with sufficient precision to distinguish between subjects and that the novel mechanism of fracture risk determination based on fall dynamics, hip impact and bone strength can be considered validated

Multiple loading conditions analysis can improve the association between finite element bone strength estimates and proximal femur fractures: A preliminary study in elderly women

This is a preliminary case-control study on osteopenic/osteoporotic elderly women, testing the association of proximal femur fracture with minimum femoral strength, as derived from finite element (FE) analysis in multiple loading conditions. Fracture cases (n=22) in acute conditions were enrolled among low-trauma fractures admitted in various hospitals in the Emilia Romagna Region, Italy. Women with no history of low-trauma fractures were enrolled as controls (n=33). Patients were imaged with DXA to obtain aBMD, and with a bilateral full femur CT scan. FE-strength was derived in stance and fall configurations: (i) as the minimum strength among those obtained for multiple loading conditions spanning a domain of plausible force directions, and (ii) as the strength associated to the most commonly used single loading conditions. The association of FE-strength and aBMD with fractures was tested with logistic regression models, deriving odds ratios (ORs) and area under the receiver operating characteristic curve (AUC). FE-strength from multiple loading conditions better classified fracture cases from controls (OR per SD change=9.6, 95% CI=3.0-31.3, AUC=0.87 in stance; OR=9.5, 95% CI=2.9-31.2, AUC=0.88 in fall) compared to aBMD (OR=3.6, 95% CI=1.6-8.2, AUC=0.79 for total femur aBMD), while FE-strength results from the most commonly used single loading conditions were similar to aBMD. Only FE-strength from multiple loading conditions remained significant in age- and aBMD-adjusted models (OR=10.5, 95% CI=1.8-61.3, AUC=0.95). In summary, we highlighted the importance of considering different loading conditions to identify bone weakness, and confirmed that femoral FE-strength estimates may add value to aBMD predictions in elderly osteopenic/osteoporotic women

In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates

Erratum: In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: Results of a multicentre observational study (Bone Marrow Transplantation (2013) 48 (908-914) DOI: 10.1038/bmt.2013.66))

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In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates

Search for SARS-CoV-2 RNA in platelets from COVID-19 patients

The frequent finding of thrombocytopenia in patients with severe SARS-CoV-2 infection (COVID-19) and previous evidence that several viruses enter platelets suggest that SARS-CoV-2 might be internalized by platelets of COVID-19. Aim of our study was to assess the presence of SARS-CoV-2 RNA in platelets from hospitalized patients with aconfirmed diagnosis of COVID-19. RNA was extracted from platelets, leukocytes and serum from 24 COVID-19 patients and 3 healthy controls, real-time PCR and ddPCR for viral genes were carried out. SARS-CoV-2 RNA was not detected in any of the samples analyzed nor in healthy controls, by either RT-PCR or ddPCR, while RNA samples from nasopharyngeal swabs of COVID-19 patients were correctly identified. Viral RNA was not detected independently of viral load, of positive nasopharyngeal swabs, or viremia, the last detected in only one patient (4.1%). SARS-CoV-2 entry in platelets is not acommon phenomenon in COVID-19 patients, differently from other viral infections

In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates

In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates