Cannabinoid treatment did not induce psychopathology and did not impair cognition in cannabis-naïve patients with MS. However, the positive correlation between blood levels of Delta-9-tetrahydrocannabinol and psychopathological scores suggests that at dosages higher than those used in therapeutic settings, interpersonal sensitivity, aggressiveness, and paranoiac features might arise, although greater statistical power would be necessary to confirm this finding.

Background The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway is aberrantly activated in several cancers. Notch signaling maintains cell proliferation, growth, and metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K pathway. Methods This phase I dose-escalation study (NCT01295632) aimed to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and oral MK-0752 (1800 mg once weekly) in patients with solid tumors. No intrapatient dose escalation was permitted. Results 28 patients were treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among 14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis, second episode) was reported. Among 8 evaluable patients receiving ridaforolimus 30 mg, three DLTs were reported (1 each grade 3 stomatitis, grade 3 diarrhea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5 days/week + 1800 mg weekly MK-0752. The most common drug-related adverse events included stomatitis, diarrhea, decreased appetite, hyperglycemia, thrombocytopenia, asthenia, and rash. Two of 15 (13%) patients with head and neck squamous cell carcinoma (HNSCC) had responses: one with complete response (CR) and one with partial response (PR). In addition, one patient experienced stable disease ≥6 months. Conclusions Combined ridaforolimus and MK-0752 showed activity in HNSCC. However, a high number of adverse events were reported at the MTD, which would require careful management during future clinical development.

To evaluate colorectal cancer hepatic metastasis detection and characterization between reduced radiation dose (RD) and standard dose (SD) contrast material-enhanced CT of the abdomen and to qualitatively compare between filtered back projection (FBP) and iterative reconstruction algorithms. Materials and Methods:In this prospective study (from May 2017 through November 2017), 52 adults with biopsy-proven colorectal cancer and suspected hepatic metastases at baseline CT underwent two portal venous phase CT scans: SD and RD in the same breath hold. Three radiologists, blinded to examination details, performed detection and characterization of 2-15-mm lesions on the SD FBP and RD adaptive statistical iterative reconstruction (ASIR)-V 60% series images. Readers assessed overall image quality and lesions between SD FBP and seven different iterative reconstructions. Two nonblinded consensus reviewers established the reference standard using the picture archiving and communication system lesion marks of each reader, multiple comparison examinations, and clinical data.Results: RD CT resulted in a mean dose reduction of 54% compared with SD. Of the 260 lesions (233 metastatic, 27 benign), 212 (82%; 95% confidence interval [CI]: 76%, 86%) were detected with RD CT, whereas 252 (97%; 95% CI: 94%, 99%) were detected with SD (P , .001); per-lesion sensitivity was 79% (95% CI: 74%, 84%) and 94% (95% CI: 90%, 96%) (P , .001), respectively. Mean qualitative scores ranked SD images as higher quality than RD series images, and ASIR-V ranked higher than ASIR and Veo 3.0. Conclusion:CT evaluation of colorectal liver metastases is compromised with modest radiation dose reduction, and the use of iterative reconstructions could not maintain observer performance.

Adaptive statistical iterative reconstruction-V 30% and ASIR-V 60% provided the best combination of qualitative and quantitative performance. Adaptive statistical iterative reconstruction 80% was equivalent qualitatively, but demonstrated inferior spatial resolution and LCD.