A JAFROC study of nodule detection performance in CT images of a thorax acquired during PET/CT

Purpose Two types of CT images (modalities) are acquired in PET/CT: for attenuation correction (AC) and diagnosis. The purpose of the study was to compare nodule detection and localization performance between these two modalities. Methods CT images, using both modalities, of an anthropomorphic chest phantom containing zero or more simulated spherical nodules of 5, 8, 10 and 12 mm diameters and contrasts −800, −630 and 100 HU were acquired. An observer performance study using nine observers interpreting 45 normal (zero nodules) images and 47 abnormal images (1–3 nodules; average 1.26) was conducted using the free-response receiver operating characteristic (FROC) paradigm. Data were analysed using an R software package implemented jackknife alternative FROC (JAFROC) analysis. Both empirical areas under the equally weighted AFROC curve (wAFROC) and under the highest rating inferred ROC (HR-ROC) curve were used as figures of merit (FOM). To control the probability of Type I error test alpha was set at 0.05. Results Nodule detection as measured by either FOM was significantly better on the diagnostic quality images (2nd modality), irrespective of the method of analysis, [reader averaged inter-modality wAFROC FOM difference = −0.07 (−0.11,−0.04); reader averaged inter-modality HR-ROC FOM difference = −0.05 (−0.09, −0.01)]. Conclusion Nodule detection was statistically worse on images acquired for AC; suggesting that images acquired for AC should not be used to evaluate pulmonary pathology. Keywords PET/CT; Nodule detection; JAFRO

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Maternal obesity is associated with a reduction in placental taurine transporter activity

BACKGROUND/OBJECTIVES: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m(−)(2)) than in women of ideal weight (BMI 18.5–24.9 kg m(−)(2)) and explored potential regulatory factors. SUBJECTS/METHODS: Placentas were collected from term (37–42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19–49 kg m(−)(2). TauT activity was measured as the Na(+)-dependent uptake of (3)H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity. RESULTS: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19–49 kg m(−)(2); P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity. CONCLUSIONS: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome