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Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

OBJECTIVE Lateral lumbar interbody fusion including anterior-to-psoas oblique lumbar interbody fusion has conventionally relied on pedicle screw placement (PSP) for construct stabilization. Single-position surgery with lumbar interbody fusion in the lateral decubitus position with concomitant PSP has been associated with increased operative efficiency. What remains unclear is the accuracy of PSP with robotic guidance when compared with the more familiar prone patient positioning. The present study aimed to compare robot-assisted screw placement accuracy between patients with instrumentation placed in the prone and lateral positions. METHODS The authors identified all consecutive patients treated with interbody fusion and PSP in the prone or lateral position by a single surgeon between January 2019 and October 2022. All pedicle screws placed were analyzed using CT scans to determine appropriate positioning according to the Gertzbein-Robbins classification grading system (grade C or worse was considered as a radiographically significant breach). Multivariate logistic regression models were constructed to identify risk factors for the occurrence of a radiographically significant breach. RESULTS Eighty-nine consecutive patients (690 screws) were included, of whom 46 (477 screws) were treated in the prone position and 43 (213 screws) in the lateral decubitus position. There were fewer breaches in the prone (n = 13, 2.7%) than the lateral decubitus (n = 15, 7.0%) group (p = 0.012). Nine (1.9%) radiographically significant breaches occurred in the prone group compared with 10 (4.7%) in the lateral decubitus group (p = 0.019), for a prone versus lateral decubitus PSP accuracy rate of 98.1% versus 95.3%. There were no significant differences in BMI between prone versus lateral decubitus cohorts (30.1 vs 29.6) or patients with screw breach versus those without (31.2 vs 29.5). In multivariate models, the prone position was the only significant protective factor for screw accuracy; no other significant risk factors for screw breach were identified. CONCLUSIONS The present data suggest that pedicle screws placed with robotic assistance have higher placement accuracy in the prone position. Further studies will be needed to validate the accuracy of PSP in the lateral position as single-position surgery becomes more commonplace in the treatment of spinal disorders.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Immune checkpoint inhibitor (ICI) myocarditis is a life-threatening condition characterized by lymphocytic myocardial infiltration[1]. Complete heart block (CHB) occurs in 15% of cases and is often fatal[2-4]. The nature and optimal management of this often-malignant condition is poorly understood[5]. Purpose This case series assesses prognostic factors associated with survival at 90 days among people with ICI myocarditis and CHB. Methods The electronic patient record system was used to identify patients admitted with ICI myocarditis. A two-physician review was used to assess the presence of ICI-associated CHB. Wilcoxon rank sum and Spearman’s rank correlation were used for categorical and quantitative variables respectively. Data was analysed using STATA/IC 16.1. The primary outcome was person-day survival 90 days after presenting symptom onset. Results Six patients were included in the final analysis. Mean survival was 47 person days. All had metastatic disease and presented 15 to 32 days after the first ICI infusion. All had muscle weakness. Other common self-symptoms were shortness of breath (4), blurred vision (4), double vision (3), collapse (3), and leg swelling (1). Proximal myopathy (2), fatigable myopathy (1), ptosis (3), and peripheral oedema (1) were present on examination. Raised troponin T and white blood cell count (WBC) were associated with 90-day survival (see Table 1). Nt-pro BNP, AST, and CK levels were raised in all patients. Two patients were tested for anti-striated muscle antibody titres, and both were strongly positive. Increase in QRS duration compared to baseline ECG was associated with lower survival at 90 days. Only one patient had CHB on admission. Steroid dose, IVIG, and plasmapheresis weren’t associated with survival. One patient declined device therapy. One declined permanent pacemaker (PPM) after insertion of transvenous pacemaker (TVP). Both died within 2 weeks. Three people underwent insertion of a transvenous pacemaker (TVP) followed by PPM insertion (table 2). All three eventually died within 100 days. One person received isoproterenol and immunosuppression as a bridge to PPM and survived. One patient was managed initially with TVP but subsequently declined PPM insertion. TVP removal resulted in CHB recurrence, and they died shortly after discharge. One person declined device therapy and died while receiving comfort care. Lead malfunction was frequent. One patient experienced bradycardia arrest with failure of a TVP lead to capture, while another experienced lead dislodgement. Conclusion CHB secondary to ICI is often fatal. It should be considered in patients presenting with symptoms of myositis, raised troponin and increased QRS duration. Despite a small sample size, this study identifies several prognostic factors which can guide both patients and physicians with decision-making. Larger studies are needed to better understand the role of device therapy in this population.

Background and Aims: With distinct mechanisms of action, the combination of tropifexor (TXR) and cenicriviroc (CVC) may provide an effective treatment for NASH. This randomized, multicenter, double-blind, phase 2b study assessed the safety and efficacy of TXR and CVC combination, compared with respective monotherapies. Approach and Results: Patients (N = 193) were randomized 1:1:1:1 to once-daily TXR 140 μg (TXR140), CVC 150 mg (CVC), TXR 140 μg + CVC 150 mg (TXR140 + CVC), or TXR 90 μg + CVC 150 mg (TXR90 + CVC) for 48 weeks. The primary and secondary end points were safety and histological improvement, respectively. Rates of adverse events (AEs) were similar across treatment groups. Pruritus was the most frequently experienced AE, with highest incidence in the TXR140 group (40.0%). In TXR and combination groups, alanine aminotransferase (ALT) decreased from baseline to 48 weeks (geometric mean change: −21%, TXR140; −16%, TXR140 + CVC; −13%, TXR90 + CVC; and +17%, CVC). Reductions in body weight observed at week 24 (mean changes from baseline: TXR140, −2.5 kg; TXR140 + CVC, −1.7 kg; TXR90 + CVC, −1.0 kg; and CVC, −0.1 kg) were sustained to week 48. At least 1-point improvement in fibrosis stage/steatohepatitis resolution without worsening of fibrosis was observed in 32.3%/25.8%, 31.6%/15.8%, 29.7%/13.5%, and 32.5%/22.5% of patients in the TXR140, CVC, TXR140 + CVC, and TXR90 + CVC groups, respectively. Conclusions: The safety profile of TXR + CVC combination was similar to respective monotherapies, with no new signals. TXR monotherapy showed sustained ALT and body weight decreases. No substantial incremental efficacy was observed with TXR + CVC combination on ALT, body weight, or in histological end points compared with monotherapy.

Abstract BTK plays an important role in B cell receptor and Toll-like receptor signaling pathways, which are constitutively active in primary CNS lymphomas, and hence represents an excellent therapeutic target. Ibrutinib, a first-generation BTKi, was evaluated in phase 1/2 trials for R/R PCNSL, SCNSL, and PVRL, showing limited survival benefit. GB5121 is a novel, orally available, covalent BTKi with superior specificity, CNS penetration, and CNS target occupancy in preclinical testing versus other BTKis including ibrutinib. GB5121 is well-suited for evaluation in CNS lymphoma. This is a phase 1b/2 open-label study of GB5121 in adults with R/R PCNSL, isolated SCNSL or PVRL and will be conducted in three parts: phase 1b dose-escalation, expansion, and phase 2. Eligibility criteria for phase 1b dose-escalation and expansion (N≈30 for each) include age ≥18 years, ECOG≤2, R/R PCNSL, R/R SCNSL with CNS-only relapse, or R/R PVRL. Patients with newly diagnosed PCNSL who cannot tolerate standard high-dose methotrexate-based therapies are also eligible. Patients with prior allogeneic stem cell transplant are excluded. A Bayesian optimal interval design will be employed to perform dose escalation to determine the recommended phase 2 dose (RP2D). In the absence of dose-limiting toxicity (DLT), dose levels will increase sequentially according to a modified Fibonacci approach. Safety, tolerability, PK/PD, DLT, maximum tolerated dose, and preliminary therapeutic activity will be assessed to determine the optimal biological dose informing the RP2D. Phase 1b expansion will further explore therapeutic activity and characterize safety and tolerability of GB5121 at the RP2D. Phase 2 will initiate following RP2D determination. This is a single-arm, open-label study to investigate GB5121 safety and efficacy in patients with R/R PCNSL. Adverse events will be graded per CTCAE v5.0. Clinical response will be determined using International Primary CNS Lymphoma Collaborative Group criteria. Progression-free and overall survival will be evaluated. Enrollment begins May 2022 (NCT05242146).