The cytoplasmic tail of the rabies virus G protein is an essential domain controlling death/survival in human neuronal cells

Poster presentation

Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability

OBJECTIVES: To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC). METHODS: Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6-8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC). RESULTS: ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs. CONCLUSIONS: ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results. Key Points • ROI size and positioning influence tumour ADC measurements in rectal cancer • ROI size and positioning influence interobserver variability of tumour ADC measurements • ADC measurements of the whole tumour volume provide the most reproducible results • Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment • Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response

Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability

OBJECTIVES: To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC). METHODS: Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6-8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC). RESULTS: ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs. CONCLUSIONS: ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results. Key Points • ROI size and positioning influence tumour ADC measurements in rectal cancer • ROI size and positioning influence interobserver variability of tumour ADC measurements • ADC measurements of the whole tumour volume provide the most reproducible results • Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment • Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response

Role of the urinary concentrating process in the renal effects of high protein intake

Role of the urinary concentrating process in the renal effects of high protein intake. High protein diet is known to increase glomerular filtration rate (GFR) and induce kidney hypertrophy. The mechanisms underlying these changes are not understood. Since the mammalian kidney comprises different nephron segments located in well-delineated zones, it is conceivable that the hypertrophy does not affect all kidney zones and all nephron segments uniformly. The present experiments were designed to study the chronic effects of high or low isocaloric protein diets (HP = 32% or LP = 10% casein, respectively) on kidney function and morphology in Sprague-Dawley rats. HP diet induced significant increases in kidney mass, GFR, free water clearance, and maximum urine concentrating ability. Kidney hypertrophy was characterized by: 1. a preferential increase in thickness of the inner stripe of the outer medulla (IS) (+ 54%, P < 0.001, while total kidney height, from cortex to papillary tip, increased only by 18%); 2. a marked hypertrophy of the thick ascending limbs (TAL) in the inner stripe (+40% epithelium volume/unit tubular length, P < 0.05) but not in the outer stripe nor in the cortex; 3. an increase in heterogeneity of glomeruli between superficial (S) and deep (D) nephrons (D/S = 1.47 in HP vs. 1.17 in LP, P < 0.05). In contrast, normal kidney growth with age and kidney hypertrophy induced by uninephrectomy were not accompanied by preferential enlargement of IS structures. The morphologic changes induced by high protein intake parallel those we previously reported in rats fed a normal diet (25% protein) but in which the operation of the urine concentrating mechanism was chronically stimulated by ADH infusion or by reduction in water intake. This similarity and the dramatic increase in free water reabsorption induced by HP diet suggest that high protein intake affects kidney function and morphology by increasing the level of operation of the urine concentrating process. The preferential increase in TAL epithelium disclosed in this study, and the recent demonstration by others of a decreased salt concentration in the early distal tubule of HP rats raises the possibility that the protein-induced increase in GFR is mediated by a depression of tubuloglomerular feedback resulting from an increased salt transport in the medullary TAL in relation with an increase in free water generation

Strengthening Peer Mentoring Relationships for New Mothers: A Qualitative Analysis

(1) Background: The transition to motherhood can be challenging, especially for first-time mothers, and can accompany maternal distress. Social support—such as that offered by peers— can be important in assisting mothers to manage such distress. Although primiparous mothers often seek out and value peer support programs, few researchers have investigated factors that may influence the strength of relationships in non-professional maternal peer support programs. Insight into these factors can be key to enhancing the success of future peer support interventions. (2) Methods: Reflexive thematic analysis was applied to data gathered from 36 semi-structured interviews conducted with 14 primiparous mothers and 17 peer mentors in a peer support program. (3) Results: Four themes related to successful mentorship were identified: expectations of peer relationship, independence of peer mentor, contact, and similarities. (4) Conclusions: For primiparous mothers who are developing their support network, these factors appear important for promoting close and effective peer support relationships. Interventions that harness the dynamics between these factors may contribute to more successful peer support relationships and mental health outcomes for participants

Gross tumour volume delineation in anal cancer on T2-weighted and diffusion-weighted MRI - Reproducibility between radiologists and radiation oncologists and impact of reader experience level and DWI image quality

Abstract Purpose To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality. Methods and materials We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients. Four readers (Senior and Junior Radiologist; Senior and Junior Radiation Oncologist) independently delineated GTVs, first on T2W-MRI only and then on DWI (with reference to T2W-MRI). Maximum Tumour Diameter (MTD) was calculated from each GTV. Mean GTVs/MTDs were compared between readers and between T2W-MRI vs. DWI. Interobserver agreement was calculated as Intraclass Correlation Coefficient (ICC), Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). DWI image quality was assessed using a 5-point artefact scale. Results Interobserver agreement between radiologists vs. radiation oncologists and between junior vs. senior readers was good–excellent, with similar agreement for T2W-MRI and DWI (e.g. ICCs 0.72–0.94 for T2W-MRI and 0.68–0.89 for DWI). There was a trend towards smaller GTVs on DWI, but only for the radiologists (P = 0.03–0.07). Moderate-severe DWI-artefacts were observed in 11/25 (44%) cases. Agreement tended to be lower in these cases. Conclusion Overall interobserver agreement for anal cancer GTV delineation on MRI is good for both radiologists and radiation oncologists, regardless of experience level. Use of DWI did not improve agreement. DWI artefacts affecting GTV delineation occurred in almost half of the patients, which may severely limit the use of DWI for radiotherapy planning if no steps are undertaken to avoid them

Outcomes and potential impact of a virtual hands-on training program on MRI staging confidence and performance in rectal cancer

Objectives: To explore the potential impact of a dedicated virtual training course on MRI staging confidence and performance in rectal cancer. // Methods: Forty-two radiologists completed a stepwise virtual training course on rectal cancer MRI staging composed of a pre-course (baseline) test with 7 test cases (5 staging, 2 restaging), a 1-day online workshop, 1 month of individual case readings (n = 70 cases with online feedback), a live online feedback session supervised by two expert faculty members, and a post-course test. The ESGAR structured reporting templates for (re)staging were used throughout the course. Results of the pre-course and post-course test were compared in terms of group interobserver agreement (Krippendorf’s alpha), staging confidence (perceived staging difficulty), and diagnostic accuracy (using an expert reference standard). // Results: Though results were largely not statistically significant, the majority of staging variables showed a mild increase in diagnostic accuracy after the course, ranging between + 2% and + 17%. A similar trend was observed for IOA which improved for nearly all variables when comparing the pre- and post-course. There was a significant decrease in the perceived difficulty level (p = 0.03), indicating an improved diagnostic confidence after completion of the course. // Conclusions: Though exploratory in nature, our study results suggest that use of a dedicated virtual training course and web platform has potential to enhance staging performance, confidence, and interobserver agreement to assess rectal cancer on MRI virtual training and could thus be a good alternative (or addition) to in-person training. // Clinical relevance statement: Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training/teaching. This study shows promising results for a virtual web-based training program, which could be a good alternative (or addition) to in-person training. // Key Points: • Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training and teaching. • Using a dedicated virtual training course and web-based platform, encouraging first results were achieved to improve staging accuracy, diagnostic confidence, and interobserver agreement. • These exploratory results suggest that virtual training could thus be a good alternative (or addition) to in-person training

Independent validation of CT radiomics models in colorectal liver metastases:predicting local tumour progression after ablation

Objectives:Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). Materials and methods: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2–8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. Results: The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5–139). The median time to LTP was 8 months (range 2–22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30–0.64) in the internal cohort and 0.50 (95%CI 0.38–0.62) in the external cohort, compared to 0.78 (95%CI 0.65–0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29–0.63) and 0.39 (95%CI 0.28–0.52), and the clinical model 0.51 (95%CI 0.34–0.68) and 0.51 (95%CI 0.39–0.63) in the internal and external cohort, respectively. Conclusion: The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. Clinical relevance statement: Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. </p

Five-year analysis on the long-term effects of dabrafenib plus trametinib (D + T) in patients with BRAF V600–mutant unresectable or metastatic melanoma

Background: First-line treatment with D+T demonstrated prolonged progression-free survival (PFS) and overall survival (OS) in patients with BRAF V600–mutant unresectable or metastatic melanoma. With 5 years of follow-up, we report survival and describe characteristics of patients in the phase 3 COMBI-d and COMBI-v trials with long-term benefit. Methods: Pooled 5-year landmark data for patients treated with D+T in the phase 3 COMBId (NCT01584648) and COMBI-v (NCT01597908) trials were analyzed. The trials enrolled patients with previously untreated BRAF V600E/K–mutant unresectable or metastatic melanoma. Patients received D 150 mg twice daily plus T 2 mg once daily vs either D + placebo (COMBI-d) or vemurafenib (COMBI-v). The primary endpoints were PFS in COMBI-d and OS in COMBI-v. Results: The pooled population included 563 patients who received D+T (COMBI-d, n = 211; COMBI-v, n = 352)