Citations

Abstract Background Data on efficacy of hepatitis-B vaccine (HBV) in patients with inflammatory bowel disease (IBD) is limited. Our aim was to review the literature and perform meta-analysis of available studies to quantify efficacy of HBV in patients with IBD. Methods We conducted a comprehensive search of several databases (inception to July 2020) to identify studies evaluating efficacy of HBV in patients with IBD. Random effects model was used to calculate the pooled rates and I2 percentage values were used to assess the heterogeneity. Results A total of 14 studies (2375 patients) were included. Four data sets were available from 2 studies that compared HBV response in patients with IBD against healthy controls. The pooled odds ratio of HBV response in IBD patients was 0.13 (95% CI, 0.05–0.33, P = 0.001). The pooled proportion of adequate immune response (AIR) was 64% (95% CI, 55–72.1, P = 0.003) from 13 data sets, and effective immune response (EIR) was 39.7% (95% CI, 30.7–49.5, P = 0.04) from 10 data sets. Conclusion Patients with IBD on immunosuppression demonstrated significantly reduced HBV response as compared with general population.

Abstract Background: Clinical use of breast cancer risk prediction requires simplified models. We evaluate a simplified version of the validated Rosner–Colditz model and add percent mammographic density (MD) and polygenic risk score (PRS), to assess performance from ages 45–74. We validate using the Mayo Mammography Health Study (MMHS). Methods: We derived the model in the Nurses' Health Study (NHS) based on: MD, 77 SNP PRS and a questionnaire score (QS; lifestyle and reproductive factors). A total of 2,799 invasive breast cancer cases were diagnosed from 1990–2000. MD (using Cumulus software) and PRS were assessed in a nested case–control study. We assess model performance using this case–control dataset and evaluate 10-year absolute breast cancer risk. The prospective MMHS validation dataset includes 21.8% of women age <50, and 434 incident cases identified over 10 years of follow-up. Results: In the NHS, MD has the highest odds ratio (OR) for 10-year risk prediction: ORper SD = 1.48 [95% confidence interval (CI): 1.31–1.68], followed by PRS, ORper SD = 1.37 (95% CI: 1.21–1.55) and QS, ORper SD = 1.25 (95% CI: 1.11–1.41). In MMHS, the AUC adjusted for age + MD + QS 0.650; for age + MD + QS + PRS 0.687, and the NRI was 6% in cases and 16% in controls. Conclusion: A simplified assessment of QS, MD, and PRS performs consistently to discriminate those at high 10-year breast cancer risk. Impact: This simplified model provides accurate estimation of 10-year risk of invasive breast cancer that can be used in a clinical setting to identify women who may benefit from chemopreventive intervention. See related commentary by Tehranifar et al., p. 587

Abstract ONC201, a bitopic DRD2 antagonist and allosteric ClpP agonist, has shown encouraging efficacy in H3 K27M-mutant glioma. Given that the thalamus has the highest extra-striatal expression of DRD2, we performed an integrated preclinical and clinical analysis of ONC201 in thalamic H3 K27M-mutant glioma. ONC201 was effective in mouse intra-uterine electroporation (IUE)-generated H3 K27M-mutant gliomas, with an in vitro IC50 of 500 nM and 50% prolongation of median survival in vivo (p=0.02, n=14). We analyzed thalamic H3 K27M-mutant glioma patients treated with ONC201 on active clinical trials as of 5/22/19 enrollment (n=19 recurrent and 10 post-radiation, non-recurrent; 5–70 years old). As of 12/18/2019, PFS6 and OS12 are 26.3% and 36.8%, respectively, in the recurrent group. For non-recurrent patients, with median follow up of 21.9 months (8.6–26.6) from diagnosis, median PFS or OS have not been reached. This surpasses historical OS of 13.5 months. Best response by RANO includes 1 CR, 3 PR, 4 SD, 8 PD for recurrent patients and 2 PR, 4 SD, 1 PD for non-recurrent patients (4 on-trial patients experienced regressions that are yet unconfirmed responses). Median duration of response for recurrent patients is 14.0 months (2.0–33.1). Furthermore, H3 K27M cell-free tumor DNA in plasma and CSF correlated with MRI response. In summary, single agent ONC201 administered at recurrence, or adjuvantly following radiation, demonstrates promising clinical efficacy in thalamic H3 K27M-mutant glioma patients who currently have no effective treatments following radiation. Investigations are ongoing to assess whether micro-environmental DRD2 expression explains the early exceptional responses in thalamic H3 K27M-mutant glioma.

Abstract Background and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) has limitations of inadequate sampling and false-negative results for malignancy. It has been performed using conventional smear (CS) cytology with rapid on-site evaluation (ROSE) with reasonable diagnostic accuracy. An alternative to ROSE is liquid-based cytology (LBC). Commonly used LBC techniques include precipitation-based (SurePath™) and filtration-based (ThinPrep®, CellPrep®). Data regarding the diagnostic efficacy of LBC compared with CS are limited. Methods Multiple databases were searched through March 2020 to identify studies reporting diagnostic yield of EUS-guided CS and LBC in pancreatic lesions. Pooled diagnostic odds and rates of performance for the cytologic diagnoses of benign, suspicious, and malignant lesions were calculated. Diagnostic efficacy was evaluated by pooled rates of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Nine studies with a total of 1308 patients were included in our final analysis. Pooled diagnostic odds of CS cytology were 1.69 (CI 1.02–2.79) and 0.39 (CI 0.19–0.8) for malignant lesions when compared to filtration-based and precipitation-based LBC techniques, respectively. For CS, precipitation-based and filtration-based LBC, pooled diagnostic accuracy was 79.7 %, 85.2 %, 77.3 %, sensitivity was 79.2 %, 83.6 %, 68.3 %, and specificity was 99.4 %, 99.5 %, 99.5 %, respectively. Conclusions The precipitation-based LBC technique (SurePath™) had superior diagnostic odds for malignant pancreatic lesions compared with CS cytology in the absence of ROSE. It showed superior accuracy and sensitivity, but comparable specificity and PPV. Diagnostic odds of CS cytology in the absence of ROSE were superior to the filtration-based LBC technique (ThinPrep®, Cellprep®) for diagnosing malignant pancreatic lesions.