Comparison of an inhomogeneous orthotropic and isotropic material models used for FE analyses

Finite element (FE) analysis has been widely used to study the behaviour of bone or implants in many clinical applications. One of the main factors in analyses is the realistic behaviour of the bone model, because the behaviour of the bone is strongly dependent on a realistic bone material property assignment. The objective of this study was to compare isotropic and orthotropic inhomogeneous material models used for FE analyses of the "global" proximal femur and "small" specimens of the bone (cancellous and cortical). Our hypothesis was that realistic material property assignment (orthotropy) is very important for the FE analyses of small bone specimens, whereas in global FE analyses of the proximal femur, this assignment can be omitted, if the inhomogeneous material model was used. The three-dimensional geometry of the "global" proximal femur was reconstructed using CT scans of a cadaveric femur. This model was implemented into an FE simulation tool and various bone material properties, dependant on bone density, were assigned to each element in the models. The "small" specimens of cortical and cancellous bone were created in the same way as the model of the proximal femur. The results obtained from FE analyses support our above described hypothesis.     

Recurrent pregnancy loss and frequency of eight antiphospholipid antibodies and genetic thrombophilic factors in Czech women

PROBLEM: The aim of this study was to investigate frequencies of eight antiphospholipid antibodies (aPLs) in serum, four genetic thrombophilic factors and their mutual relation in 206 patients with repeated pregnancy loss (RPL). METHOD OF STUDY: Enzyme-linked immunosorbent assay was used for detection of aPLs against ph-serine, ph-ethanolamine, ph-inositol, DL-glycerol, phosphatidic acid, anti-annexin V, cardiolipin, and beta2-GPI. FV 1691G>A (Leiden mutation), FII 20210G>A mutation, MTHFR 677C>T and MTHFR 1298A>C variant genotypes were determined using a melting curve analysis of the PCR amplification product detected by the fluorescence resonance energy transfer. Genotypic distribution and allelic frequencies were calculated. Correlation between aPLs and thrombophilic factors was tested by chi-square and Fisher exact test. RESULTS: Our results show significantly increased prevalence of aPLs against ph-inositol (17-19.6% dependent on number of spontaneous miscarriages) and against ph-serine (18-25%). aPLs in IgG prevail. In 96% of the studied group, at least one risk factor was found (either aPLs positivity or thrombophilic factor). Both aPLs and thrombophilic factors were present in 43%. In the group of women with three or more RPLs, strong positive correlation of aPLs positivity and thrombophilic risk factors was observed. CONCLUSION: Antiphospholipide antibodies and genetic thrombophilic factors are important risk factors in the pathogenesis of RPL. Both autoantibodies against various kinds of phospholipides and genetic thrombophilic factors must be studied together in diagnosis of RPL for appropriate treatment.     

European data on stem cell mobilization with plerixafor in patients with nonhematologic diseases: an analysis of the European consortium of stem cell mobilization

BACKGROUND: Plerixafor with granulocyte–colony‐stimulating factor (G‐CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty‐three patients with germ cell tumor (n = 11), Ewing sarcoma (n = 6), Wiscott‐Aldrich disease (n = 5), neuroblastoma (n = 4), and other nonhematologic diseases (n = 7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G‐CSF (n = 21) or after chemotherapy and G‐CSF (n = 12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 × 10⁶/kg body weight (b.w.) CD34+ cells (median, 5.0 × 10⁶/kg b.w. CD34+ cells; range, 2.0 × 10⁶‐29.5 × 10⁶/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 × 10⁶/kg b.w. CD34+ cells (range, 0.9 × 10⁶‐1.8 × 10⁶/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 × 10⁶/kg b.w. (range, 2.3 × 10⁶‐6.7 × 10⁶/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9‐12) and 15 (range, 10‐25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G‐CSF or chemotherapy and G‐CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients.     

Angiomatoid change in polyps of the nasal and paranasal regions: an underrecognized and commonly misdiagnosed lesion—report of 45 cases

We present 45 patients with angiomatoid polyps of the nasal and paranasal regions (APNPRs), which are underrecognized lesions which may cause considerable diagnostic difficulties. There were 32 men and 13 women in our series. The average age at diagnosis was 49 years in men and 54.3 years in women. Locations were known in 41 cases and included the nasal septum (14), maxillary sinus (12), ethmoid sinuses (5), lateral wall of the nasal cavity (5), sphenoid sinus (1), and nasal cavity, not otherwise specified (4). X-ray or computed tomography was performed in 19 cases and revealed bone erosions/deviations in four cases. Initial misdiagnoses submitted by referring pathologists were reported in 20/32 of the consultation cases. Our study confirms that APNPRs are benign lesions which often recur and sometimes multiple recurrences are seen. APNPRs sometimes cause severe changes of the skeletal bones especially in recurrent lesions. Awareness of the above described features and familiarity with the clinical presentation of APNPRs is the best way to avoid a misdiagnosis.     

Prognostic significance of mutation profile at diagnosis and mutation persistence during disease remission in adult acute myeloid leukaemia patients

In this multi-centre study, we analysed the prognostic impact of mutations in 19 genes associated with myeloid malignancies in 258 newly diagnosed acute myeloid leukaemia patients (aged 19–70 years) undergoing intensive therapy. We identified five patient groups with different prognostic risks and different benefits from allogeneic hematopoietic stem cell transplantation (alloHSCT) within the intermediate cytogenetic risk group patients (n = 184). The most adverse prognosis was observed in patients with DNMT3A and FLT3-ITD co-mutation, whose survival could be significantly improved with alloHSCT. In contrast, the most favourable prognosis without any further benefit from alloHSCT was identified in patients with mutations in NPM1 or CEBPA, after exclusion of the unfavourable prognostic groups defined by mutations in DNMT3A, RUNX1 or genes from chromatin/spliceosome group. An additional analysis of 113 diagnosis-remission paired samples revealed that persistence of non-DNMT3A mutations (above 2% VAF) represented a further negative prognostic factor. The proposed model offers a possible molecular stratification and treatment guidance for intermediate cytogenetic risk group patients.     

PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0·76) and OS (97–99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4–6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.