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Two hundred and thirty obese subjects (age: 18-77 yr, BMI: 31.1-65.8 kg/m2) were studied before and after a 3-week body mass reduction (BMR) program, coupling restricted energy diet (1200-1500 kcal/day) with low intensity exercise prescription. It involved 5 days per week (consisting of one-hour dynamic aerobic standing and floor exercise plus 30 min of cycloergometer exercise at 60 W or, alternatively, 4 km outdoor leisure walking on flat terrain) and psychological counseling. One-leg standing balance test (OLSB) and stair climbing test (SCT) were employed to assess motor control and maximal lower limb muscle power, respectively. The BMR program induced a significant weight loss (4.1%; p<0.001), a higher reduction of body mass index (BMI) being observed in males than in females (p<0.001). OLSB performance time increased by 20.5% (p<0.001) after treatment, the improvement being evident in both genders. A 20.8% reduction in SCT time (p<0.05) was also observed and corresponded to a 13.2% increase (p<0.001) in average absolute muscle power and 15.0% increase (p<0.001) in specific muscle power (i.e. the power output per kg of body mass), with no differences between genders. In conclusion, in spite of the moderate reduction of body mass after restricted energy diet and low intensity physical conditioning, significant improvements in motor control and performance, likely to ameliorate the execution of simple daily activities, were observed in obese subjects.

Purpose To evaluate the feasibility of a standardized protocol for acquisition and analysis of dynamic contrast material-enhanced (DCE) and dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging in a multicenter clinical setting and to verify its accuracy in predicting glioma grade according to the new World Health Organization 2016 classification. Materials and Methods The local research ethics committees of all centers approved the study, and informed consent was obtained from patients. One hundred patients with glioma were prospectively examined at 3.0 T in seven centers that performed the same preoperative MR imaging protocol, including DCE and DSC sequences. Two independent readers identified the perfusion hotspots on maps of volume transfer constant (K), plasma (v) and extravascular-extracellular space (v) volumes, initial area under the concentration curve, and relative cerebral blood volume (rCBV). Differences in parameters between grades and molecular subtypes were assessed by using Kruskal-Wallis and Mann-Whitney U tests. Diagnostic accuracy was evaluated by using receiver operating characteristic curve analysis. Results The whole protocol was tolerated in all patients. Perfusion maps were successfully obtained in 94 patients. An excellent interreader reproducibility of DSC- and DCE-derived measures was found. Among DCE-derived parameters, v and v had the highest accuracy (are under the receiver operating characteristic curve [A] = 0.847 and 0.853) for glioma grading. DSC-derived rCBV had the highest accuracy (A = 0.894), but the difference was not statistically significant (P > .05). Among lower-grade gliomas, a moderate increase in both v and rCBV was evident in isocitrate dehydrogenase wild-type tumors, although this was not significant (P > .05). Conclusion A standardized multicenter acquisition and analysis protocol of DCE and DSC MR imaging is feasible and highly reproducible. Both techniques showed a comparable, high diagnostic accuracy for grading gliomas. RSNA, 2018 Online supplemental material is available for this article.

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 μg/m2) afterward. This trial included 2 phases: an “explorative phase” addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid–single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an “expansion phase” with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.