The left gastric vein is associated with some sonographic and clinical markers of disease severity, whereas the absence of portosystemic collaterals or the presence of paraumbilical veins seems to identify cirrhotics with markers predictive of a more favorable clinical course.

Progressive myoclonus epilepsy (PME) of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. We find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influences progenitors' proliferation and modulates neuronal distribution by attracting interneurons to the site of secretion via cell-non-autonomous mechanisms. Similarly, in patient-derived hCOs, low levels of functional CSTB result in an alteration of progenitor's proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as suggested by a proteomic analysis in patients' hCOs. Overall, our study sheds new light on the cellular mechanisms underlying the development of EPM1.

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Background and study aims Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). Patients and methods Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. Results Mean cysts size was 36.7mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45%), serous cystadenoma (18.8%), and mucinous cystadenoma (12.8%). Fifty-eight (11.5%) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p=0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p=0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p<0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28% AEs rate), low-risk (1.4% AE rate, including patients <64 years with other-than-IPMN diagnosis sampled with ≤2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1% AEs rate, including the remaining patients). Conclusion TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

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