To develop a new nanoparticle formulation for a proteasome inhibitor Carfilzomib (CFZ) to improve its stability and efficacy for future in vivo applications.

CFZ-loaded ternary polypeptide nanoparticles (CFZ/tPNPs) were prepared by using heptakis(6-amino-6-deoxy)-β-cyclodextrin(hepta-hydrochloride) (HaβCD) and azido-poly(ethylene glycol)-block-poly(L-glutamic acid sodium salt) (N

-PEG-PLE). The process involved ternary (hydrophobic/ionic/supramolecular) interactions in three steps 1) CFZ was entrapped in the cavity of HaβCD by hydrophobic interaction, 2) the drug-cyclodextrin inclusion complexes were mixed with N

-PEG-PLE to form polyion complex nanoparticles, and 3) the nanoparticles were modified with fluorescent dyes (AFDye 647) for imaging and/or epithelial cell adhesion molecule (EpCAM) antibodies for cancer cell targeting. CFZ/tPNPs were characterized for particle size, surface charge, drug release, stability, intracellular uptake, proteasome inhibition, and in vitro cytotoxicity.

tPNPs maintained an average particle size of 50nm after CFZ entrapment, EpCAM conjugation, and freeze drying. tPNPs achieved high aqueous solubility of CFZ (>1mg/mL), sustained drug release (t

 = 6.46h), and EpCAM-mediated cell targeting, which resulted in increased intracellular drug accumulation, prolonged proteasome inhibition, and enhanced cytotoxicity of CFZ in drug-resistant DLD-1 colorectal cancer cells.

tPNPs improved stability and efficacy of CFZ in vitro, and these results potentiate effective cancer treatment using CFZ/tPNPs in future vivo studies.

tPNPs improved stability and efficacy of CFZ in vitro, and these results potentiate effective cancer treatment using CFZ/tPNPs in future vivo studies.

OTX008 cost aimed to evaluate the age- and sex-related characteristics in cortical thickness of the tibial diaphysis between non-obese healthy young and elderly subjects as reference data.

The study investigated 31 young subjects (12 men and 19 women; mean age, 25 ± 8 years) and 54 elderly subjects (29 men and 25 women; mean age, 70 ± 6 years). Three-dimensional estimated cortical thickness of the tibial diaphysis was automatically calculated for 5000-9000 measurement points using the high-resolution cortical thickness measurement from clinical computed tomography data. In 12 assessment regions created by combining three heights (proximal, central, and distal diaphysis) and four areas of the axial plane at 90° (medial, anterior, lateral, and posterior areas) in the tibial coordinate system, the standardized thickness was assessed using the tibial length.

As structural characteristics, there were no differences in the medial and lateral thicknesses, while the anterior thickness was greater than the posterior thickness in all groups. The sex-related difference was not shown. As an age-related difference, elderly subjects showed greater or lesser cortical thickness than the young subjects, depending on the regions of the tibia.

Cortical thickness was different depending on sex, age, and regions in the tibia. The results of this study are of clinical relevance as reference points to clarify the causes of various pathological conditions for diseases.

Level 3.

Level 3.

To evaluate the agreement, accuracy, and longitudinal reproducibility of quantitative cartilage morphometry from 2D U-Net-based automated segmentations for 3T coronal fast low angle shot (corFLASH) and sagittal double echo at steady-state (sagDESS) MRI.

2D U-Nets were trained using manual, quality-controlled femorotibial cartilage segmentations available for 92 Osteoarthritis Initiative healthy reference cohort participants from both corFLASH and sagDESS (n = 50/21/21 training/validation/test-set). Cartilage morphometry was computed from automated and manual segmentations for knees from the test-set. #link# Agreement and accuracy were evaluated from baseline visits (dice similarity coefficient DSC, correlation analysis, systematic offset). The longitudinal reproducibility was assessed from year-1 and -2 follow-up visits (root-mean-squared coefficient of variation, RMSCV%).

Automated segmentations showed high agreement (DSC 0.89-0.92) and high correlations (r ≥ 0.92) with manual ground truth for both corFLASH and sagDESS and only small systematic offsets (≤ 10.1%). The automated measurements showed a similar test-retest reproducibility over 1year (RMSCV% 1.0-4.5%) as manual measurements (RMSCV% 0.5-2.5%).

The 2D U-Net-based automated segmentation method yielded high agreement compared with manual segmentation and also demonstrated high accuracy and longitudinal test-retest reproducibility for morphometric analysis of articular cartilage derived from it, using both corFLASH and sagDESS.

The 2D U-Net-based automated segmentation method yielded high agreement compared with manual segmentation and also demonstrated high accuracy and longitudinal test-retest reproducibility for morphometric analysis of articular cartilage derived from it, using both corFLASH and sagDESS.

Despite the large clinical interest in mindfulness, little is known about its effects in patients with brain tumours. Novel delivery methods such as App based Mindfulness training (AMT) may assist in the delivery of mindfulness treatment to this group of patients.

We aimed to determine the feasibility of administering an 8-week mindfulness treatment by AMT in patients operated on for brain tumours in a publically funded hospital. link2 As a secondary aim we collected preliminary data regarding changes in self-reported psychological distress, quality of life and mindfulness capacity.

Uptake was of 40 potentially eligible participants. Of the 20 entering the study, only 10 completed the 8-week post group assessment and only 3 completed the follow-up assessment. There was a positive direction of pre-post change in almost all completers with statistically significant improvement in several mindfulness scales and illness-related quality of life however there was a deterioration in the social/family quality of life domain. The significant variability in individual usage of the AMT appeared to be related more to individual differences rather than tumour histology, progression or treatment. The treatment was well received by those completing the study.

Recruitment and retention feasibility issues were identified. Promising preliminary change and treatment satisfaction scores however suggest that further research with the AMT is warranted. Reduced assessment burden and more regular engagement during treatment is recommended to enhance retention. Large sample sizes however will be needed to address the heterogeneity of this group.

Recruitment and retention feasibility issues were identified. Promising preliminary change and treatment satisfaction scores however suggest that further research with the AMT is warranted. Reduced assessment burden and more regular engagement during treatment is recommended to enhance retention. Large sample sizes however will be needed to address the heterogeneity of this group.

Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients‘ health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1-10 BM over time.

A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes.

At group level, patients‘ physical well-being worsened, whereas emotional well-being improved over 9months. Scores on other HRQoL subscales did not change significantly. link3 Number (1-3 versus 4-10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects.

Our results indicate that even in patients with up to 10BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level.

ClinicalTrials.gov Identifier NCT02953756, November 3, 2016.

ClinicalTrials.gov Identifier NCT02953756, November 3, 2016.

Lung cancer is the leading cause of cancer death and there have been clinical prediction models. This study aimed to evaluate the diagnostic performance of published models and create new models to evaluate the probability of malignant solitary pulmonary nodules (SPNs) in Chinese population.

We consecutively enrolled 2061 patients with SPNs from West China Hospital between January 2008 and December 2016, each SPN was pathologically confirmed. First, four published prediction models, Mayo clinic model, Veterans Affairs (VA) model, Brock model and People’s Hospital of Peking University (PEH) model were validated in our patients. Then, utilizing logistic regression, decision tree and random forest (RF), we developed three new models and internally validated them.

Area under the receiver operating characteristic curve (AUC) values of four published models were as follows Mayo 0.705 (95% CI 0.658-0.752, n = 726), VA 0.64 6 (95% CI 0.598-0.695, n = 800), Brock 0.575 (95% CI 0.502-0.648, n = 550) and PEH 0.675 (95% CI 0.627-0.723, n = 726). Logistic regression model, decision tree model and RF model were developed, AUC values of these models were 0.842 (95% CI 0.778-0.906), 0.734 (95% CI 0.647-0.821), 0.851 (95% CI 0.789-0.914), respectively.

The four published lung cancer prediction models do not apply to our population, and we have established new models that can be used to predict the probability of malignant SPNs.

The four published lung cancer prediction models do not apply to our population, and we have established new models that can be used to predict the probability of malignant SPNs.

Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) can be associated with hemophagocytic lymphohistiocytosis (NK/T-LAHLH), which is a rare and fatal disease with no effective therapy. We evaluated whether etoposide + dexamethasone-based chemotherapy regimens might be useful for treating NK/T-LAHLH.

This retrospective single-center study evaluated clinical data from 37 patients with NK/T-LAHLH who were treated between May 2008 and January 2020.

Among 363 patients with ENKTL, the cumulative incidence of HLH was 11.9%. Among 43 patients with NK/T-LAHLH, 37 patients received etoposide + dexamethasone-based chemotherapy regimens, with an overall response rate of 45.9% for the HLH. The overall response rate was substantially higher for newly diagnosed NK/T-LAHLH than it was for relapsed or refractory NK/T-LAHLH (66.7% vs. 18.8%). The median overall follow-up time was 4months, with overall survival rates of 81.1% at 1month, 62.2% at 2months, 56.8% at 3months, and 34.4% at 6months. Significantly better overall survival (all P < 0.