Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.

BACKGROUND & AIMS: There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. METHODS: A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). RESULTS: A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. CONCLUSION: The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.

Outcomes With Single-Site Dual-Lumen Versus Multisite Cannulation for Adults With COVID-19 Respiratory Failure Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To determine whether multisite versus single-site dual-lumen (SSDL) cannulation is associated with outcomes for COVID-19 patients requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization Registry. Propensity score matching (2:1 multisite vs SSDL) was used to control for confounders. PATIENTS: The matched cohort included 2,628 patients (1,752 multisite, 876 SSDL) from 170 centers. The mean ( sd ) age in the entire cohort was 48 (11) years, and 3,909 (71%) were male. Patients were supported with mechanical ventilation for a median (interquartile range) of 79 (113) hours before VV-ECMO support. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was 90-day survival. Secondary outcomes included survival to hospital discharge, duration of ECMO support, days free of ECMO support at 90 days, and complication rates. MAIN RESULTS: There was no difference in 90-day survival (49.4 vs 48.9%, p = 0.66), survival to hospital discharge (49.8 vs 48.2%, p = 0.44), duration of ECMO support (17.9 vs 17.1 d, p = 0.82), or hospital length of stay after cannulation (28 vs 27.4 d, p = 0.37) between multisite and SSDL groups. More SSDL patients were extubated within 24 hours (4% vs 1.9%, p = 0.001). Multisite patients had higher ECMO flows at 24 hours (4.5 vs 4.1 L/min, p < 0.001) and more ECMO-free days at 90 days (3.1 vs 2.0 d, p = 0.02). SSDL patients had higher rates of pneumothorax (13.9% vs 11%, p = 0.03). Cannula site bleeding (6.4% vs 4.7%, p = 0.03), oxygenator failure (16.7 vs 13.4%, p = 0.03), and circuit clots (5.5% vs 3.4%, p = 0.02) were more frequent in multisite patients. CONCLUSIONS: In this retrospective study of COVID-19 patients requiring VV-ECMO, 90-day survival did not differ between patients treated with a multisite versus SSDL cannulation strategy and there were only modest differences in major complication rates. These findings do not support the superiority of either cannulation strategy in this setting.

The relationship between hair pulling style and quality of life.

BACKGROUND: Past research has found different associations between hair pulling (HP) variables and quality of life (QOL), especially after controlling for depression. This study examined HP styles (automatic vs focused) for their associations with QOL and whether depression accounted for these relationships. METHODS: Our sample consisted of 187 adults who met DSM-IV diagnostic criteria for trichotillomania (TTM) or chronic HP (TTM criteria except B and/or C). Clinician-administered interviews were used to diagnose TTM/HP. Participants completed self-report scales for HP style and severity, QOL, and severity of depression. RESULTS: Significant correlations were reported between QOL and the focused style of HP, as well as with interference and distress from HP. Exploratory analyses also revealed a correlation between number of HP sites and QOL. None of the correlations remained significant after controlling for severity of depression. CONCLUSIONS: These results indicate that future research on HP style also should consider the impact of co-occurring depressive symptoms. Interventions addressing both depression and HP should be considered in treatment planning to optimize outcomes.

A Virtual Multi-institution Pediatric Radiology Peer Teaching Conference Improves Knowledge of Educators.

RATIONALE AND OBJECTIVES: Medical education led by peers and near-peers has been shown to benefit both teachers and learners and can be successfully incorporated into radiology education. The authors created a virtual, multi-institution pediatric radiology conference employing peer and near-peer teaching with the goals of improving radiology knowledge and enhancing the educational experience of radiology trainees. MATERIALS AND METHODS: Two radiology residency programs implemented a common pediatric radiology curriculum and joint quarterly virtual peer teaching conference. Conferences featured short teaching sessions led by six to ten radiology trainees and were facilitated by attending pediatric radiologists. Knowledge assessments (KA) consisting of multiple-choice questions inspired by conference learning objectives were sent to peer educators before the conference (pre-conference), directly after the conference (immediate post-conference), and three months after the conference (delayed post-conference). Surveys were distributed to peer educators immediately after conferences to assess conference reception and solicit feedback. Quantitative data was analyzed using ANOVA, Kruskal-Wallis test, and post-hoc Tukey HSD test. RESULTS: Four conferences featured 33 peer educators consisting primarily of first-year (60.6 %), second-year (18.2 %), and third-year (15.2 %) radiology residents. Compared to pre-conference scores, immediate post-conference scores were significantly increased (HSD 13, p = 0.02) and delayed post-conference scores were increased without statistical significance (HSD 5.8, p = 0.29). Almost all survey respondents perceived the conferences as helpful, well-organized, and effective in teaching pediatric radiology. A majority of participants expressed interest in participating in future peer teaching radiology conferences. CONCLUSION: A virtual pediatric radiology peer and near-peer teaching conference held between two radiology residencies improved short-term radiology knowledge of educators and was highly received.

NEO-FFI personality clusters in trichotillomania.

The purpose of this study was to determine whether personality prototypes exist among hair pullers and if these groups differ in hair pulling (HP) characteristics, clinical correlates, and quality of life. 164 adult hair pullers completed the NEO-Five Factor Inventory (NEO-FFI; Costa and McCrae, 1992) and self-report measures of HP severity, HP style, affective state, and quality of life. A latent class cluster analysis using NEO-FFI scores was performed to separate participants into clusters. Bonferroni-corrected t-tests were used to compare clusters on HP, affective, and quality of life variables. Multiple regression was used to determine which variables significantly predicted quality of life. Two distinct personality prototypes were identified. Cluster 1 (n=96) had higher neuroticism and lower extraversion, agreeableness, and conscientiousness when compared to cluster 2 (n=68). No significant differences in demographics were reported for the two personality clusters. The clusters differed on extent of focused HP, severity of depression, anxiety, and stress, as well as quality of life. Those in cluster 1 endorsed greater depression, anxiety, and stress, and worse quality of life. Additionally, only depression and cluster membership (based on NEO scores) significantly predicted quality of life.