Understanding Prognosis: Discrepancy in Prognosis Estimates Between Patients With Cirrhosis and their Hepatologists.

BACKGROUND & AIMS: Patients require a clear understanding of their prognosis to make informed decisions about their care. The aim of this study was to compare the perceptions of prognosis and transplant candidacy between patients with cirrhosis and their hepatologists. METHODS: Patients with cirrhosis and their hepatologists were prospectively recruited at an urban liver transplant center. Patients and hepatologists were asked about transplant candidacy and about how many years patients would live with and without a liver transplant. Agreement between patients and hepatologists was assessed with the weighted kappa statistic. Associations between patient/hepatologists' prognostic estimates and those predicted by patients' Model for End-Stage Liver Disease-Sodium (MELD-Na) score were estimated using the Pearson correlation coefficient. RESULTS: Seventy patients and 6 hepatologists were enrolled in the study. Patients were predominantly male (61.4%) and white (68.6%), with a mean MELD-Na score of 19 ± 9. There was no-slight agreement between patients and hepatologists regarding survival without and with a liver transplant (κ = 0.1 and 0.2, respectively), with patients more optimistic than their hepatologists. There was greater agreement between patients and hepatologists about transplant candidacy (κ = 0.6). There was a negligible association between MELD-Na and patient estimates (r = -0.24, P = .05) but a moderate association between MELD-Na and hepatologist estimates (r = -0.51, P < .001), with higher MELD-Na scores associated with lower predicted survival. CONCLUSIONS: Patients with cirrhosis are more optimistic and less accurate in their predictions of survival compared with hepatologists, although they are more realistic about their transplant candidacy. Aligning patient and provider expectations may increase the likelihood that patients receive value-concordant care.

Glucocorticoid Treatment of Symptomatic Sarcoidosis in 2 Morbidly Obese Patients.

Corticosteroid management for patients with sarcoidosis requires the need for close monitoring to detect and manage any complications that may arise during treatment.

Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease.

Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.

Identification of ovarian cancer metastatic miRNAs.

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2-4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.