Objectives In complex conditions such as cirrhosis, management of urgent issues can leave little time for patient education. However, efforts such as sodium restriction and lactulose titration require an informed patient. We aimed to understand and improve patient knowledge about disease self-management. Study 150 outpatients with cirrhosis in a tertiary hepatology clinic were given a survey to test disease self-management knowledge. Patients were then provided education using a concise booklet, and three months later were invited to participate in a follow-up survey. Demographic and clinical correlates of baseline knowledge were analyzed with linear regression, and t-test for matched pairs was used to compare knowledge scores before and after the educational intervention. Results Only 53% of the 15 questions were answered correctly in the baseline survey. The most commonly missed items related to diet, such as the sodium content of sea salt, as well as the safety of medications such as acetaminophen and statins. The level of patient knowledge was not associated with age, gender, etiology or severity of liver disease, or length of time followed in the clinic. After the educational intervention, 115/150 (77%) returned the follow-up survey. In this group, the median knowledge score improved from 53% to 67% (p<0.001), and improvement occurred across all domains tested. Conclusions Cirrhosis patients lack the knowledge required to effectively manage their disease. A simple educational intervention may improve patient knowledge. Further studies are needed to determine whether improved knowledge translates into better outcomes.

Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity. It has been claimed that obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form of cell death. In addition, obatoclax has been shown to inhibit lysosomal function, but the mechanism of this has not been elucidated. We have evaluated the mechanism of action of obatoclax in eight ovarian cancer cell lines. Consistent with its function as a BH3 mimetic, obatoclax induced apoptosis in three cell lines. However, in the remaining cell lines another form of cell death was evident because caspase activation and PARP cleavage were not observed. Obatoclax also failed to show synergy with carboplatin and paclitaxel, chemotherapeutic agents which we have previously shown to be synergistic with authentic Bcl-2 family antagonists. Obatoclax induced a profound accumulation of LC-3 but knockdown of Atg-5 or beclin had only minor effects on the activity of obatoclax in cell growth assays suggesting that the inhibition of lysosomal function rather than stimulation of autophagy may play a more prominent role in these cells. To evaluate how obatoclax inhibits lysosomal function, confocal microscopy studies were conducted which demonstrated that obatoclax, which contains two basic pyrrole groups, accumulates in lysosomes. Studies using pH sensitive dyes demonstrated that obatoclax induced lysosomal alkalinization. Furthermore, obatoclax was synergistic in cell growth/survival assays with bafilomycin and chloroquine, two other drugs which cause lysosomal alkalinization. These studies explain, for the first time, how obatoclax inhibits lysosomal function and suggest that lysosomal alkalinization contributes to the cytotoxic activity of obatoclax.

Background: Limited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification. Methods: Three hundred twenty-nine EAC cases were available in Tissue Microarrays (TMA) format. A discovery cohort of 166 EAC cases were stained immunohistochemically for range of adaptive immune (CD3, CD4, CD8 and CD45RO) and immune checkpoint biomarkers (ICOS, IDO-1, PD-L1, PD-1). A validation cohort of 163 EAC cases was also accessed. A digital pathology analysis approach was used to quantify biomarker density. Results: CD3, CD4, CD8, CD45RO, ICOS and PD-1 were individually predictive of better overall survival (OS) (Log rank p = < 0.001; p = 0.014; p = 0.001; p = < 0.001; p = 0.008 and p = 0.026 respectively). Correlation and multivariate analysis identified high CD45RO/ICOS patients with significantly improved OS which was independently prognostic (HR = 0.445, (0.223-0.886), p = 0.021). Assessment of CD45RO and ICOS high cases in the validation cohort revealed an associated with improved OS (HR = 0.601 (0.363-0.996), p = 0.048). Multiplex IHC identified cellular co-expression of high CD45RO/ICOS. High CD45RO/ICOS patients have significantly improved OS. Conclusions: Multiplexing identifies true cellular co-expression. These data demonstrate that co-expression of immune biomarkers are associated with better outcome in EAC and may provide evidence for immunotherapy treatment stratification.

Implementation of QI measures incorporating automatic reminders of surveillance status for providers can significantly increase the rate of HCC surveillance among cirrhosis patients.

BackgroundBariatric surgery leads to changes in mental health, quality of life and social functioning, yet these outcomes differ among individuals. In this study, we explore patients’ psychosocial experiences following bariatric surgery and elucidate the individual-level factors that may drive variation in psychosocial outcomes.MethodsEleven semi-structured focus groups with Michigan Bariatric Surgery Collaborative (MBSC) patients (n = 77). Interviews were audio recorded, transcribed verbatim, and analyzed using a grounded theory approach. Data on participant demographic characteristics were abstracted from the MBSC clinical registry.ResultsMost focus group participants were female (89%), white (64%), and married (65%). We identified three major themes: (1) change in self-perception; (2) change in perception by others; and (3) change in relationships. Each theme includes 3 sub-themes, demonstrating a range of positive and negative psychosocial experiences. For example, weight loss led to increased self-confidence among many participants while others described a loss of self-identity. Some noted improved relationships with family or friends while others experienced worsening or even loss of relationships due to perceived jealousy.ConclusionWeight loss following bariatric surgery leads to complex changes in self-perception and inter-personal relationships, which may be proximal mediators of commonly assessed mental health outcomes such as depression. Individuals considering bariatric surgery may benefit from anticipatory guidance about these diverse experiences, and post-surgical longitudinal monitoring should include evaluation for adverse psychosocial events.