Rib fractures at postmortem computed tomography (PMCT) validated against the autopsy

To evaluate the sensitivity of postmortem computed tomography (PMCT) in rib fracture detection validated against autopsy. Fifty-one forensic cases underwent a postmortem CT prior to forensic autopsy. Two image readers (radiologist and forensic pathologist) assessed high resolution CT data sets for rib fractures. Correct recognition rates (CRR), sensitivity and specificity values were calculated over all observations as well as individually for every rib and region. Additionally, for partial rib fractures the sensitivity of autopsy was calculated vice versa. 3876 entries in each study protocol (autopsy, PMCT radiologist and PMCT forensic pathologist) were investigated. A total of 690 fractures (autopsy), 491 (PMCT and radiologist) and 559 (PMCT and forensic pathologist) were detected. The CRR was 0.85. Sensitivity and specificity of PMCT for rib fracture detection were 0.63 (0.58 radiologist, 0.68 forensic pathologist) and 0.97 (both readers 0.97), respectively. Low CRR and sensitivity values were obtained for antero-lateral fractures. Partial rib fractures were better detected by PMCT. PMCT has a rather low sensitivity for rib fracture detection when validated against autopsy and indicates that clinical CT may also demonstrate a reasonable number of false negatives. Partial rib fractures often remain undetected at autopsy.

Bortezomib(Velcade®)-Thalidomide-Dexamethasone (VTD) Is Superior to Thalidomide-Dexamethasone (TD) In Patients with Multiple Myeloma (MM) Progressing or Relapsing After Autologous Transplantation

Introduction: The Thalidomide-Dexamethasone (TD) regimen has provided encouraging results in relapsed MM. To improve results, bortezomib (Velcade) has been added to the combination in previous phase II studies, the so called VTD regimen. In January 2006, the European Group for Blood and Marrow Transplantation (EBMT) and the Intergroupe Francophone du Myélome (IFM) initiated a prospective, randomized, parallel-group, open-label phase III, multicenter study, comparing VTD (arm A) with TD (arm B) for MM patients progressing or relapsing after autologous transplantation. Patients and Methods: Inclusion criteria: patients in first progression or relapse after at least one autologous transplantation, including those who had received bortezomib or thalidomide before transplant. Exclusion criteria: subjects with neuropathy above grade 1 or non secretory MM. Primary study end point was time to progression (TTP). Secondary end points included safety, response rate, progression-free survival (PFS) and overall survival (OS). Treatment was scheduled as follows: bortezomib 1.3 mg/m2 was given as an i.v bolus on Days 1, 4, 8 and 11 followed by a 10-Day rest period (days 12 to 21) for 8 cycles (6 months) and then on Days 1, 8, 15, 22 followed by a 20-Day rest period (days 23 to 42) for 4 cycles (6 months). In both arms, thalidomide was scheduled at 200 mg/Day orally for one year and dexamethasone 40 mg/Day orally four days every three weeks for one year. Patients reaching remission could proceed to a new stem cell harvest. However, transplantation, either autologous or allogeneic, could only be performed in patients who completed the planned one year treatment period. Response was assessed by EBMT criteria, with additional category of near complete remission (nCR). Adverse events were graded by the NCI-CTCAE, Version 3.0.The trial was based on a group sequential design, with 4 planned interim analyses and one final analysis that allowed stopping for efficacy as well as futility. The overall alpha and power were set equal to 0.025 and 0.90 respectively. The test for decision making was based on the comparison in terms of the ratio of the cause-specific hazards of relapse/progression, estimated in a Cox model stratified on the number of previous autologous transplantations. Relapse/progression cumulative incidence was estimated using the proper nonparametric estimator, the comparison was done by the Gray test. PFS and OS probabilities were estimated by the Kaplan-Meier curves, the comparison was performed by the Log-Rank test. An interim safety analysis was performed when the first hundred patients had been included. The safety committee recommended to continue the trial. Results: As of 1st July 2010, 269 patients had been enrolled in the study, 139 in France (IFM 2005-04 study), 21 in Italy, 38 in Germany, 19 in Switzerland (a SAKK study), 23 in Belgium, 8 in Austria, 8 in the Czech republic, 11 in Hungary, 1 in the UK and 1 in Israel. One hundred and sixty nine patients were males and 100 females; the median age was 61 yrs (range 29-76). One hundred and thirty six patients were randomized to receive VTD and 133 to receive TD. The current analysis is based on 246 patients (124 in arm A, 122 in arm B) included in the second interim analysis, carried out when 134 events were observed. Following this analysis, the trial was stopped because of significant superiority of VTD over TD. The remaining patients were too premature to contribute to the analysis. The number of previous autologous transplants was one in 63 vs 60 and two or more in 61 vs 62 patients in arm A vs B respectively. The median follow-up was 25 months. The median TTP was 20 months vs 15 months respectively in arm A and B, with cumulative incidence of relapse/progression at 2 years equal to 52% (95% CI: 42%-64%) vs 70% (95% CI: 61%-81%) (p=0.0004, Gray test). The same superiority of arm A was also observed when stratifying on the number of previous autologous transplantations. At 2 years, PFS was 39% (95% CI: 30%-51%) vs 23% (95% CI: 16%-34%) (A vs B, p=0.0006, Log-Rank test). OS in the first two years was comparable in the two groups. Conclusion: VTD resulted in significantly longer TTP and PFS in patients relapsing after ASCT. Analysis of response and safety data are on going and results will be presented at the meeting.

Modelling Bone Mineral Density in Swiss Breast Cancer Patients Treated with Letrozole, Tamoxifen and Sequences of Letrozole and Tamoxifen in the BIG 1-98 Study (SAKK 21/07).

Background: Bone health is a concern when treating early stage breast cancer patients with adjuvant aromatase inhibitors. Early detection of patients (pts) at risk of osteoporosis and fractures may be helpful for starting preventive therapies and selecting the most appropriate endocrine therapy schedule. We present statistical models describing the evolution of lumbar and hip bone mineral density (BMD) in pts treated with tamoxifen (T), letrozole (L) and sequences of T and L. Methods: Available dual-energy x-ray absorptiometry exams (DXA) of pts treated in trial BIG 1-98 were retrospectively collected from Swiss centers. Treatment arms: A) T for 5 years, B) L for 5 years, C) 2 years of T followed by 3 years of L and, D) 2 years of L followed by 3 years of T. Pts without DXA were used as a control for detecting selection biases. Patients randomized to arm A were subsequently allowed an unplanned switch from T to L. Allowing for variations between DXA machines and centres, two repeated measures models, using a covariance structure that allow for different times between DXA, were used to estimate changes in hip and lumbar BMD (g/cm2) from trial randomization. Prospectively defined covariates, considered as fixed effects in the multivariable models in an intention to treat analysis, at the time of trial randomization were: age, height, weight, hysterectomy, race, known osteoporosis, tobacco use, prior bone fracture, prior hormone replacement therapy (HRT), bisphosphonate use and previous neo-/adjuvant chemotherapy (ChT). Similarly, the T-scores for lumbar and hip BMD measurements were modeled using a per-protocol approach (allowing for treatment switch in arm A), specifically studying the effect of each therapy upon T-score percentage. Results: A total of 247 out of 546 pts had between 1 and 5 DXA; a total of 576 DXA were collected. Number of DXA measurements per arm were; arm A 133, B 137, C 141 and D 135. The median follow-up time was 5.8 years. Significant factors positively correlated with lumbar and hip BMD in the multivariate analysis were weight, previous HRT use, neo-/adjuvant ChT, hysterectomy and height. Significant negatively correlated factors in the models were osteoporosis, treatment arm (B/C/D vs. A), time since endocrine therapy start, age and smoking (current vs. never).Modeling the T-score percentage, differences from T to L were -4.199% (p = 0.036) and -4.907% (p = 0.025) for the hip and lumbar measurements respectively, before any treatment switch occurred. Conclusions: Our statistical models describe the lumbar and hip BMD evolution for pts treated with L and/or T. The results of both localisations confirm that, contrary to expectation, the sequential schedules do not seem less detrimental for the BMD than L monotherapy. The estimated difference in BMD T-score percent is at least 4% from T to L.

Cognitive behavioural therapy for weight gain associated with antipsychotic drugs

BACKGROUND: Overweight and obesity are common concerns in individuals with severe mental disorders. In particular, antipsychotic drugs (AP) frequently induce weight gain. This phenomenon lacks current management and no previous controlled studies seem to use cognitive therapy to modify eating and weight-related cognitions. Moreover, none of these studies considered binge eating or eating and weight-related cognitions as possible outcomes. AIM: The main aim of this study is to assess the effectivity of cognitive and behavioural treatment (CBT) on eating and weight-related cognitions, binge eating symptomatology and weight loss in patients who reported weight gain during AP treatment. METHOD: A randomized controlled study (12-week CBT vs. Brief Nutritional Education) was carried out on 61 patients treated with an antipsychotic drug who reported weight gain following treatment. Binge eating symptomatology, eating and weight-related cognitions, as well as weight and body mass index were assessed before treatment, at 12 weeks and at 24 weeks. RESULTS: The CBT group showed some improvement with respect to binge eating symptomatology and weight-related cognitions, whereas the control group did not. Weight loss occurred more progressively and was greater in the CBT group at 24 weeks. CONCLUSION: The proposed CBT treatment is particularly interesting for patients suffering from weight gain associated with antipsychotic treatment

Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants.

In a multicenter study a new, fully automated Roche Diagnostics Elecsys HBsAg II screening assay with improved sensitivity to HBsAg mutant detection was compared to well-established HBsAg tests: AxSYM HBsAg V2 (Abbott), Architect HBsAg (Abbott), Advia Centaur HBsAg (Bayer) Enzygnost HBsAg 5.0 (Dade-Behring), and Vitros Eci HBsAg (Ortho). A total of 16 seroconversion panels, samples of 60 HBsAg native mutants, and 31 HBsAg recombinant mutants, dilution series of NIBSC and PEI standards, 156 HBV positive samples comprising genotypes A to G, 686 preselected HBsAg positive samples from different stages of infection, 3,593 samples from daily routine, and 6,360 unselected blood donations were tested to evaluate the analytical and clinical sensitivity, the detection of mutants, and the specificity of the new assay. Elecsys HBsAg II showed a statistically significant better sensitivity in seroconversion panels to the compared tests. Fifty-seven out of 60 native mutants and all recombinant mutants were found positive. Among 156 HBV samples with different genotypes and 696 preselected HBsAg positive samples Elecsys HBsAg II achieved a sensitivity of 100%. The lower detection limit for NIBSC standard was calculated to be 0.025 IU/ml and for the PEI standards ad and ay it was <0.001 and <0.005 U/ml, respectively. Within 2,724 daily routine specimens and 6.360 unselected blood donations Elecsys HBsAg II showed a specificity of 99.97 and 99.88%, respectively. In conclusion the new Elecsys HBsAg II shows a high sensitivity for the detection of all stages of HBV infection and HBsAg mutants paired together with a high specificity in blood donors, daily routine samples, and potentially interfering sera.

Remaining rod activity mediates visual behavior in adult Rpe65-/- mice.

Purpose: C57/Bl6, Cpfl1-/- (Cone photoreceptors function loss 1; pure rod function), Gnat1alpha-/- (rod alpha-transducin; pure cone function) and Rpe65-/-;Rho-/- double knock-out mice were studied in order to distinguish the respective contributions of the different photoreceptor (PR) systems that enable light perception and mediate a visual reflex in adult Rpe65-/- mice using a simple behavioural procedure. Methods: Visual function was estimated using a rotating automatized optomotor drum covered with vertical black and white stripes at spatial frequencies of 0.025 to 0.5 cycles per degree (cpd) in both photopic and scotopic conditions. To evaluate the contribution as well as the light intensity threshold of each PR system, we tested the mouse strains with different luminances. Results: Stripe rotation elicits head movements in wild-type (WT) animals in photopic and scotopic conditions depending on the spatial frequency, whereas Cpfl1-/- mice show a reduced activity in the photopic condition and Gnat1alpha-/- mice an almost absent response in the scotopic condition. Interestingly, a robust visual response is obtained with Rpe65-/- knockout mice at 0.075 cpd and 0.1 cpd in the photopic condition. The residual rod function in the Rpe65-/- animals was demonstrated by testing Rpe65-/-;Rho-/- mice that present no response in photopic conditions. Conclusions: The optomotor test is a simple method to estimate the visual function, and to evaluate the respective contributions of rod and cone systems. Using this test, we demonstrate that in Rpe65-/- mice, devoid of functional cones and of detectable 11-cis-retinal protein, rods mimic in part the cone function by mediating vision in photopic conditions.

Plantas autotetraplóides de citros sob tratamento in vitro com colchicina

O objetivo deste trabalho foi obter plantas autotetraplóides de tangerina 'Ponkan', laranja 'Pêra-de-abril' e tangor 'Murcott', que serão usadas em cruzamentos com cultivares diplóides, visando à obtenção de indivíduos triplóides sem sementes. Utilizou-se o método de cultivo in vitro de segmentos de epicótilo em meio com colchicina (0,025, 0,05 e 0,1%), por diversos períodos (1, 2, 3, 7 e 14 dias), com subseqüente regeneração de brotações em meio sem a presença do alcalóide. As brotações foram microenxertadas in vitro e aclimatizadas em estufas. A determinação do nível de ploidia das plantas foi realizada por citometria de fluxo. A colchicina demonstrou ser tóxica aos explantes das três variedades, ocasionando redução significativa no número médio de brotações adventícias e aumento na porcentagem de explantes não-responsivos, em comparação com o controle. Entre as quatro plantas de laranja e uma de tangor obtidas, duas plantas de laranja e a de tangor, demonstraram ser autotetraplóides, apresentando folhas com maior espessura, arredondadas e coloração verde intensa. O método utilizado na duplicação cromossômica, com uso de colchicina, é eficiente em produzir plantas autotetraplóides de citros.

Extraintestinal manifestations in inflammatory bowel disease: frequency and associated risk factors in the nationwide Swiss IBD cohort study (SIBDCS)

Background: Data on the frequency of extraintestinal manifestations (EIM) in Crohnʼs disease (CD) and ulcerative colitis (UC) are scarce. Goal: to evaluate prevalences, forms of EIM and risk factors in a large nationwide IBD cohort. Methods: Data from validated physician enrolment questionnaires of the adult Swiss IBD cohort were analyzed. Logistic regression models were used to identify EIM risk factors. Results: 950 patients were included, 580 (61%) with CD (mean age 43yrs) and 370 (39%) with UC (mean age 49yrs), of these, 249 (43%) of CD and 113 (31%) of UC patients had one to 5 EIM. The following EIM were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), primary sclerosing cholangitis (CD 1%, UC 4%). Logistic regression in CD identified the following items as risk factors for ongoing EIM: active disease (OR 1.95, 95% CI 1.17-3.23, P=0.01), positive IBD family history (OR 1.77, 95% CI 1.07-2.92, P=0.025). No risk factors were identified in UC patients. Conclusions: EIM are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitate their diagnosis and management.

Physical performance limitations in adolescent and adult survivors of childhood cancer and their siblings.

PURPOSE: This study investigates physical performance limitations for sports and daily activities in recently diagnosed childhood cancer survivors and siblings. METHODS: The Swiss Childhood Cancer Survivor Study sent a questionnaire to all survivors (≥ 16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2003 aged <16 years. Siblings received similar questionnaires. We assessed two types of physical performance limitations: 1) limitations in sports; 2) limitations in daily activities (using SF-36 physical function score). We compared results between survivors diagnosed before and after 1990 and determined predictors for both types of limitations by multivariable logistic regression. RESULTS: The sample included 1038 survivors and 534 siblings. Overall, 96 survivors (9.5%) and 7 siblings (1.1%) reported a limitation in sports (Odds ratio 5.5, 95%CI 2.9-10.4, p<0.001), mainly caused by musculoskeletal and neurological problems. Findings were even more pronounced for children diagnosed more recently (OR 4.8, CI 2.4-9.6 and 8.3, CI 3.7-18.8 for those diagnosed <1990 and ≥ 1990, respectively; p=0.025). Mean physical function score for limitations in daily activities was 49.6 (CI 48.9-50.4) in survivors and 53.1 (CI 52.5-53.7) in siblings (p<0.001). Again, differences tended to be larger in children diagnosed more recently. Survivors of bone tumors, CNS tumors and retinoblastoma and children treated with radiotherapy were most strongly affected. CONCLUSION: Survivors of childhood cancer, even those diagnosed recently and treated with modern protocols, remain at high risk for physical performance limitations. Treatment and follow-up care should include tailored interventions to mitigate these late effects in high-risk patients.

Carbono, matéria orgânica leve e fósforo remanescente em diferentes sistemas de manejo do solo

O objetivo deste trabalho foi avaliar os teores de carbono orgânico total (COT), matéria orgânica leve (MOL) e fósforo remanescente (Prem), em áreas de cerrado sob sistema de plantio direto com diferentes cultivos de coberturas do solo, e compará-los aos de áreas sob preparo convencional e pousio. O experimento foi conduzido em campo, em um Latossolo Vermelho, de agosto de 2000 a março de 2007. O delineamento utilizado foi o de blocos ao acaso com parcelas subdivididas, sendo as parcelas constituídas pelos cinco sistemas de manejo do solo avaliados - pousio, preparo convencional e plantio direto com uso dos cultivos de cobertura crotalária (Crotalaria juncea), milheto (Pennisetum americanum) e braquiária (Urochloa brizantha) -, e as subparcelas pelos cultivos de soja e milho. Em março de 2007, coletaram-se amostras de solo das profundidades 0,0-0,025, 0,025-0,05, 0,05-0,10 e 0,10-0,20 m, das quais foram quantificados COT, MOL, estoques de COT e Prem. Em áreas sob plantio direto, o aumento nos teores de MOL pode reduzir a adsorção de fósforo ao solo. Sistemas de manejo que não envolvem revolvimento do solo favorecem o aumento do estoque de carbono orgânico nas camadas superficiais, enquanto o preparo convencional e o plantio direto com uso do milheto como planta de cobertura propiciam a incorporação mais profunda do carbono.

Chemical attributes of a Hapludox soil after nine years of pig slurry application

The objective of this study was to evaluate the pig slurry application effects on chemical attributes of a Hapludox soil managed under no-tillage system. Treatments consisted of 50, 100 and 200 m³ ha-1 per year of pig slurry application, and a control with replacement of P and K exported through harvested grains. Attributes related to soil chemical reaction, exchange complex, and nutrient contents were determined in soil samples collected in the ninth year of experimentation from 0 - 0.025, 0.025 - 0.05, 0.05 - 0.10, 0.10 - 0.20, 0.20 - 0.40 and 0.40 - 0.60 m soil depths. The continuous application of high doses of pig slurry on the Oxisol surface under no-tillage acidifies the soil and increases Al, P, Cu, and Zn contents down to 0.2-m depth, and K levels down to 0.6-m depth.