The Royal Liverpool University Hospital (RLUH) is a major teaching and research hospital located in the city of Liverpool, England. It is the largest and busiest hospital in Merseyside and Cheshire, and has the largest emergency department of its kind in the UK.A major redevelopment of the hospital began in 2013 and was scheduled for completion in 2017, but construction problems and the 2018 collapse of main contractor Carillion pushed the estimated completion date back to the autumn of 2022.Alongside Broadgreen Hospital and Liverpool University Dental Hospital, the hospital is managed by the Liverpool University Hospitals NHS Foundation Trust and is associated with the University of Liverpool, Liverpool John Moores University and the Liverpool School of Tropical Medicine.
PURPOSE:The RHONE-X study (ClinicalTrials.gov identifier, NCT04432831) evaluated long-term safety and tolerability (primary end points), and efficacy (exploratory end points) of faricimab, a dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) inhibitor, using a treat-and-extend (T&E) protocol in patients with diabetic macular edema (DME). DESIGN:Global phase 3, multicenter, nonrandomized, 2-year open-label extension study of the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) studies. PARTICIPANTS:Of 1622 patients who completed YOSEMITE and RHINE, 1474 patients (91%) were included in the RHONE-X trial. METHODS:Patients transitioned from faricimab every 8 weeks (Q8W), faricimab T&E, or aflibercept 2.0 mg Q8W in YOSEMITE and RHINE to the RHONE-X study without requiring monthly initiation doses. All received faricimab T&E at up to 16-week intervals based on best-corrected visual acuity (BCVA) and central subfield thickness (CST), per YOSEMITE and RHINE criteria. Patients attended every month during the initial 4-month masked period, then only for T&E dosing visits (open-label arm). Analysis windows were defined for the RHONE-X study years 1, 1.5, and 2 to account for visit asynchronicity. MAIN OUTCOME MEASURES:The primary end point was incidence and severity of ocular and nonocular adverse events (AEs). Exploratory end points included change from baseline BCVA and CST, proportion of patients with absence of DME (CST < 325 μm), and treatment durability. RESULTS:Overall, 1204 patients (82%) completed the RHONE-X trial. The incidence of AEs leading to treatment discontinuation (1.5%) and rates of intraocular inflammation (1.3%) were low. Overall, faricimab T&E maintained visual and anatomic improvements achieved in YOSEMITE and RHINE. Adjusted mean BCVA improvements from YOSEMITE and RHINE baseline to the end of the RHONE-X trial were +10.1 letters (faricimab T&E), +11.4 letters (faricimab T&E [prior Q8W]), and +9.5 letters (faricimab T&E [prior aflibercept]); CST reductions were -198.3 μm, -202.5 μm, and -204.9 μm, respectively. At study end, more than 90% of patients achieved DME absence, regardless of prior treatment. Median number of injections over the RHONE-X trial (2 years) were 7 (faricimab T&E), 8 (faricimab T&E [prior Q8W]), and 8 (faricimab T&E [prior aflibercept]). By the RHONE-X trial completion, approximately 80% of patients received faricimab at ≥Q12W intervals. CONCLUSIONS:Faricimab, a dual Ang-2 and VEGF-A inhibitor, provided long-term safety, efficacy, and durability in patients with DME treated using a T&E regimen. Sustained visual and anatomic improvements were observed, with extended dosing intervals and reduced treatment burden. Faricimab was well tolerated, with a safety profile consistent with the YOSEMITE and RHINE trials. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Abstract Psoriasis affects approximately 2% of the global population, with significant associated medical and psychological comorbidity (Meeuwis KA, de Hullu JA, Massuger LF et al. Genital psoriasis: a systematic literature review on this hidden skin disease. Acta Derm Venereol 2011; 91: 5–11). Anogenital psoriasis occurs in isolation in 2–5% of cases but more commonly coexists with other psoriasis subtypes (29–64%), particularly flexural psoriasis. It is often associated with increased psychosexual burden, especially in women [Beck KM, Yang EJ, Sanchez IM et al. Treatment of genital psoriasis: a systematic review. Dermatol Ther (Heidelb) 2018; 8: 509–25]. The reported prevalence of anogenital psoriasis varies due to heterogeneous studies, variable or absent validated disease outcome measurements, under-recognition, and reluctance of patients and clinicians to discuss genital involvement. This suggests the true burden is likely underestimated, and the condition is undertreated with limited evidence-based physical and psychological management options. A UK-wide clinician survey was carried out to explore real-world practice and perceptions of flexural and genital psoriasis. Patient focus groups were formed to study the acceptability and relevance of current practice. The online clinician survey of 21 questions was circulated to UK dermatologists and dermatology specialist nurses through associated dermatology networks. Ethical approval was obtained for focus groups for patients aged > 18 years, clinically diagnosed with anogenital psoriasis by a dermatologist, with or without any subtype of psoriasis, and on any treatment modality. Patients provided informed consent for participation in virtual interviews. A grant of £9590 was provided by the UK Dermatology Clinical Trials Network for patient participation, future publication and dissemination costs. Clinicians recognized the psychological impact of anogenital psoriasis. The analysis demonstrated barriers to assessment and limited standardization of treatment regimens, despite clinician awareness. Focus group analysis identified nine overarching themes describing the lived experience of anogenital psoriasis, highlighting substantial diagnostic, psychosocial and therapeutic challenges. This novel clinician–patient anogenital psoriasis study highlights the need for robust research, incorporating physical and psychosocial outcomes for holistic evidence-based management and enhanced education to reduce stigma for this high-burden, under-represented condition.
Abstract Background Early evidence suggests acceptable outcomes occur at GRWR ≤ 0.6% when portal pressure modulation is employed. However, the minimum safe GRWR achievable in standard-practice without portal interventions needs review. The traditional 0.8% threshold may be unnecessarily restrictive. Methods We analysed 2,506 consecutive LDLT-cases performed without routine portal-pressure-modulation, comprising 1,868 modified right, 308 extended right, 71 standard right, 111 left lobe, and 114 left lateral grafts. Of these, 1,892 had complete follow-up data. Minimum safe GRWR was determined using survival-based inflection-point analysis and Kruskal-Wallis testing at 0.1% increments. Three thresholds (0.6%, 0.7%, 0.8%) were compared using Mann-Whitney U tests. Stratified analysis evaluated whether GRWR remained predictive after adjusting for absolute graft weight. Multivariate logistic regression included MELD score, recipient age, and graft weight. Results Overall survival was 81.0%. A critical inflection occurred at 0.7% GRWR: patients below 0.7% achieved 71.4% survival (n=105), while those at 0.7% or higher achieved 81.5% survival (n=1,787), a 10.1 percentage-point improvement (p=0.010). The 0.8% threshold provided no additional safety; survival below 0.8% was 77.6% (n=272) versus 81.5% at 0.8% or higher (n=1,620), a nonsignificant 4.0 percentage-point difference (p=0.123). The 0.7-0.8% range achieved 82.9% survival (n=152) with lower complication rates at five-year follow-up. Stratified analysis showed GRWR lost predictive value after adjusting for graft weight (all p>0.05), while graft weight remained significant (p=0.023). Conclusions For centres using standard techniques without portal pressure modulation, GRWR of 0.7% represents an evidence-based minimum threshold, offering 10.1 percentage-point survival benefit over lower values (p=0.010). The 0.8% threshold is unnecessarily restrictive (p=0.123).
