Integrated 3D information for custom-made bone grafts: focus on biphasic calcium phosphate bone substitute biomaterials

none5Purpose: Several studies showed that the sintering temperature of 1250 °C could affect the formation of α-Ca3(PO4)2, which is responsible for the reduction of the hardness value of biphasic calcium phosphate biocomposites, but they did not evaluate the inference of the sintering time at peak temperature on transition of β-Ca3(PO4)2 to α-Ca3(PO4)2. This analysis explored, in an innovative way, inferences and correlations between volumetric microstructure, mechanical properties, sintering temperature, and time at peak temperature in order to find the best sintering conditions for biphasic calcium phosphate composites grafted in severe alveolar bone defects. Methods: Sintered biphasic calcium phosphates (30%-hydroxyapatite/70%-tricalcium phosphate) were tested by microCT imaging for the 3D morphometric analysis, by compressive loading to find their mechanical parameters, and by X-ray diffraction to quantify the phases via Rietveld refinement for different sintering temperatures and times at the peak temperature. Data were analysed in terms of statistical inference using Pearson’s correlation coefficients. Results: All the studied scaffolds closely mimicked the alveolar organization of the jawbone, independently on the sintering temperatures and times; however, mechanical testing revealed that the group with peak temperature, which lasted for 2 hours at 1250 °C, showed the highest strength both at the ultimate point and at fracture point. Conclusion: The good mechanical performances of the group with peak temperature, which lasted for 2 hours at 1250 °C, is most likely due to the absence of the α-Ca3(PO4)2 phase, as revealed by X-ray diffraction. However, we detected its presence after sintering at the same peak temperature for longer times, showing the time-dependence, combined with the temperature-dependence, of the β-Ca3(PO4)2 to α-Ca3(PO4)2 transition.openAlessandra Giuliani; Maria Laura Gatto; Luigi Gobbi; Francesco Guido Mangano; Carlo ManganoGiuliani, Alessandra; Gatto, MARIA LAURA; Gobbi, Luigi; Guido Mangano, Francesco; Mangano, Carl

The role of diagnostic imaging and interventional radiology in liver schistosomiasis: A case report of advanced disease

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Second malignancies after treatment of diffuse large B-cell non-Hodgkin's lymphoma: a GISL cohort study

BACKGROUND: Improved treatment has increased the life expectancy of patients with non-Hodgkin's lymphoma, but few studies have addressed the issue of second cancer in patients treated for diffuse large B-cell lymphoma. The aims of this study were to determine the incidence and time free of second cancers in this subset of patients. DESIGN AND METHODS: We evaluated a cohort of 1280 patients with diffuse large B-cell lymphoma who were first treated between 1988 and 2003. We utilized the central database of the Gruppo Italiano Studio Linfomi, which includes data on demographics, clinical characteristics, laboratory parameters, treatment and follow-up of all patients with non-Hodgkin's lymphoma enrolled in clinical trials. RESULTS: After a median follow-up of 51 months, 48 patients had developed a second cancer: 13 hematologic malignancies and 35 solid tumors. The overall standardized incidence ratio in our cohort (with a median age of 58 years) matched that of the general Italian population. The incidence ratio of second tumors was age related, and the age groups 20-39 and 40-59 years showed an increased risk. Overall, the cumulative incidence of second cancer was 8.2% at 15 years. A multivariate analysis showed that older age at the time of diagnosis of lymphoma had a negative influence on the time free of second tumors. CONCLUSIONS: In our cohort, only young patients showed an increased incidence ratio of second malignancies, while the incidence ratio in patients aged over 59 years matched the incidence in the Italian general population. Demographics, baseline characteristics, laboratory parameters and treatment modalities did not have any significant impact on the incidence ratio of a second cancer

Recipient pre-existing chronic hypotension is associated with delayed graft function and inferior graft survival in kidney transplantation from elderly donors

BackgroundPre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive.MethodsA monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003-2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP ResultsUnivariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p50 years old donor.ConclusionsOur findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure

Absolute monocyte count at diagnosis could improve the prognostic role of early FDG-PET in classical Hodgkin lymphoma patients

Recently published international guidelines suggested that positron emission tomography (PET)-computed tomography (CT) could be utilized for response assessment using the Deauville criteria in fluorodeoxyglucose (FDG)-avid lym- phomas (Meignan et al, 2012). Interim PET (I-PET) scan- ning seems highly predictive of treatment failure in Hodgkin Lymphoma (HL) patients. We recently showed that the absolute monocyte count (AMC) has prognostic value in patients with classical HL (cHL) (Tadmor et al, 2015). Here, we show that the com- bined use of I-PET and AMC at diagnosis enables a more accurate projection of patient outcome in cHL. The present study is an ancillary branch of the analysis reported by Tadmor et al, (2015). Patients with histopatho- logical diagnosis of cHL previously enrolled in the Gruppo Italiano Studio Linfomi trials were eligible if data on all clini- cal and laboratory features and treatments, reported I-PET results, treatment response and follow-up were available. Response was defined according to the revised International Working Group guidelines (Cheson et al, 1999). An absolute lymphocyte count <06 9 10 9 /l and AMC > 075 9 10 9 /l were used as cut-off points. I-PET was performed after 2 cycles of treatment. A positive or negative I-PET was defined by the local investigators’ interpretation of the nuclear physi- cian’s scan report, which was based on a visual qualitative assessment. The principal end-point of the study was the impact of I-PET and AMC on progression-free survival (PFS); their impact on overall survival (OS) was the secondary end-point. Survival functions were estimated using the Kaplan–Meier method. Statistical comparisons between curves were per- formed with log-rank test, and the effect of the covariate was reported as hazard ratios (HR), from Cox regression. All patients had a diagnosis of cHL; 76% of cases had the nodular sclerosis (NS) subtype. Seventy-six patients (64%) were treated with classical ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), and 23 (19%) and 19 (16%) with the more intensive BEACOPP (bleomycin, etoposide, doxoru- bicin, cyclophosphamide, vincristine, procarbazine, pred- nisone) and COPPEBVCAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, bleomycin) regimens (Federico et al, 2009), respectively. Of the entire cohort, 104 patients (88%) achieved complete remission. Twenty-six patients had a positive I-PET (22%) and 28 (24%) had AMC > 075 9 10 9 /l at diagnosis. The median follow-up of the entire cohort was 88 months (range 5–142 months). The estimated 5-year OS was 91% (95% confidence interval [CI]: 84–95%). The 5-year PFS was 80% (95% CI: 71–86%). Patients with positive I-PET showed a worse PFS compared to patients with negative I-PET (51% and 88%, respectively; HR 587 [95% CI: 256–135]). Patients with AMC > 075 9 10 9 /l at diagnosis had a worse PFS compared to patients with AMC ≤ 075 9 10 9 /l (58% and 87%, respectively; HR 373 [95% CI: 161–864]). Multi- ple Cox proportional hazards (PH) regression, adjusted for International Prognostic Score 3–7, confirmed the prognostic role of I-PET (HR 532 [95% CI: 230–123]; P < 0001) and AMC >075 9 10 9 /l (HR 319 [95% CI: 132–768]; P = 0010). Figure 1A, B shows the PFS for I-PET and AMC, and Table I shows the uni- and multivariate Cox PH regres- sion for PFS. The prognostic role of I-PET and AMC on OS was also confirmed. Given the strong predictive value of both I-PET and AMC, we stratified patients by positive or negative I-PET and AMC > 075 9 10 9 /l or ≤075 9 10 9 /l into 3 groups with different levels of risk. The low risk level (negative I- PET and AMC ≤ 075 9 10 9 /l; n = 73, 62%) had a 5-year PFS of 90% (95% CI: 80–96%), the intermediate level (I-PET positive or AMC > 075 9 10 9 /l; n = 36, 51%) had a 5-year PFS of 73% (95% CI: 55–85%), and the high risk level (I-PET positive and AMC > 075 9 10 9 /l; n = 9, 8%) had a 5-year PFS of 17% (95% CI: 1–49%). The log-rank test between the intermediate and low levels and between the high and intermediate levels were significant (P = 0 007, P = 0001, respectively). For OS, the difference between the intermediate and low risk levels tended to narrow (P = 0232), while the difference between the high and inter- mediate levels was significantly different (P < 0001). Fig- ure 1C, D shows the PFS and OS stratified by risk group. The test for trend in PFS and OS was significant (P < 0001). The rationale for using AMC as a prognostic parameter in cHL is relevant because immunohistochemical and molecular data, including the gene expression profile, have identified a key role for monocytes and macrophages in the biology of cHL (Steidl et al, 2010; Porrata et al, 2012; Tan et al, 2012; Koh et al , 2015; Tadmor et al, 2015). It might therefore bepossible that AMC is associated with the number of tumour- associated macrophages (TAMs) in the microenvironment. If so, then it could be considered as a biomarker of reactive cells that is easily detectable in peripheral blood. The FDG- PET scan is currently considered the most precise staging method and may also be used to provide an early prediction of treatment efficacy There is a strong suggestion that reactive cells are respon- sible for the increased FDG uptake at baseline, as they account for 99% of Hodgkin tumours (Gallamini, 2010). Furthermore, early responses to treatment have been sug- gested to demonstrate the elimination of reactive cells, or at least the disappearance of their activity, and are indirect surrogates of tumour chemo-sensitivity (Gallamini & Kostakoglu, 2012). Thus, the FDG-PET scan could be considered a biomarker of the extent and activity of the tumour microenvironment. However, in clinical practice, patients with negative I-PET can rapidly progress during induction treatment, while other patients with positive I-PET may eventually achieve a CR. Therefore, there is a need to further improve the predictive power of I-PET. By combining the AMC at diagnosis with the I-PET results, we showed that it is possible to increase the discriminatory power of I-PET alone in identifying cHL patients with poor PFS and OS. We are fully aware that our study has many weaknesses, such as its retrospective nature, the small number of patients and the lack of use of the Deauville criteria. However, our results suggest that it is pos- sible to further improve the already high predictive power of PET by combining it with a simple and inexpensive surrogate biomarker of reactive cells that are easily detectable in peripheral blood

Secondary malignancies after treatment for indolent non-Hodgkin's lymphoma: a 16-year follow-up study.

Relatively little information is available on the incidence of secondary cancer in non-Hodgkin's lymphoma. The aim of this long-term follow-up study was to determine the incidence, the time free of second tumors, and risk factors for developing secondary cancer in a homogeneous group of patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: We evaluated a total of 563 patients with indolent non-Hodgkin's lymphoma enrolled in Gruppo Italiano Studio Linfomi trials from 1988 to 2003. RESULTS: After a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer: 12 myelodysplastic syndromes/acute myeloid leukemia, and 27 solid tumors. The overall standardized incidence ratio of secondary malignancy in patients with non-Hodgkin's lymphoma was higher than the risk of malignancy in the general population. The standardized incidence ratio was elevated in male patients and in patients under 65 years old at first treatment. Overall, the cumulative incidence of secondary cancer at 12 years was 10.5%, after correction in a competing-risk model. Univariate and multivariate Cox regression analyses showed that older age at the time of diagnosis, male sex, and fludarabine-containing therapy had significant negative impacts on the time free of second tumors. CONCLUSIONS: We have identified subgroups of non-Hodgkin's lymphoma patients with increased standardized incidence ratios of secondary malignancy and variables that have a negative impact on the time free of second tumors. This information could help physicians to select the most appropriate treatments. Finally, taking into account the possible occurrence of secondary neoplasia, long-term monitoring must be considered

Are there sex differences in physiological parameters and reaction time responses to overload in firefighters?

Male and female firefighters work side-by-side in the same in strenuous and risky conditions. Anthropometrics, physiological, and reaction time (mean of reaction time -MRT-, and errors made -E) parameters of 12 Female and 13 Male firefighters were compared. Effect of overload (step test with and without equipment) on the MRT and E were analyzed on 3 trials (T1 = 1-1s, T2 = 0.5-1s, T3 = 0.5-0.5s), compared with a pre-test condition (basal). T-test between males and females was applied to assess differences (p<0.05) in all parameters. ANOVA with repeated measures and Bonferroni on 3 conditions of step test between males and females was applied in reaction time variables. Between MRT and E, in T1, T2 and T3 trials and the 3 test conditions, ANCOVA models with interactions were used. Differences (p<0.05) in anthropometric, physiological and reaction time data emerged across groups, and on the 3rd trials (T3 vs T1 and T2) in reaction time parameters of each group. ANCOVA showed differences (p<0.001) in E among trials. Post hoc showed significant differences in T1vsT3 and T1vsT2. MRT x trial interaction was extremely significant (P<0.001). Implementing fitness and reaction time exercise programs is important to decrease the injury risk and increase work capacity in firefighters with reference to female workers

Absolute monocyte count and lymphocyte-monocyte ratio predict outcome in nodular sclerosis Hodgkin lymphoma: Evaluation based on data from 1450 patients

Objective: To verify whether absolute monocyte count (AMC) and lymphocyte-monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL). Patients and Methods: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007. Results: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm3, and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; P<.001). The overall survival (OS) at 10 years for an AMC of more than 750 cells/mm3 was 78% (70%-85%), and the OS at 10 years for an AMC of 750 cells/mm(3) or less was 88% (84%-90%; P=.01). In multivariate analysis, both AMC and LMR maintained prognostic significance for PFS (hazard ratio [HR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3). Conclusion: This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice

Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: Results of a large multicenter study involving 990 patients

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR &gt;6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients