Bulk transcriptome analysis Observations Validations Highlights Liver organoids from patients with BA exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures. Beta-amyloid accumulation was observed around the bile ducts in BA livers. Exposure to beta-amyloid induced aberrant morphology in control organoids. Beta-amyloid accumulation represents a novel finding with pathobiological implications and diagnostic potential for BA.

Aneurysm expansion rate >5.5 mm/y is a significant rupture predictor in addition to size compared with aneurysm morphology and other demographic factors. Aneurysm size >6.5 mm and hyperlipidemia are determining factors of expansion rate. These may have implications in selection of patients for surgery. Better control of hyperlipidemia may alleviate the risk of rupture.

Liver diseases constitute an important medical problem, and a number of these diseases, termed cholangiopathies, affect the biliary system of the liver. In this review, we describe the current understanding of the causes of cholangiopathies, which can be genetic, viral or environmental, and the few treatment options that are currently available beyond liver transplantation. We then discuss recent rapid progress in a number of areas relevant for decoding the disease mechanisms for cholangiopathies. This includes novel data from analysis of transgenic mouse models and organoid systems, and we outline how this information can be used for disease modeling and potential development of novel therapy concepts. We also describe recent advances in genomic and transcriptomic analyses and the importance of such studies for improving diagnosis and determining whether certain cholangiopathies should be viewed as distinct or overlapping disease entities.

Background: Large, chronic full thickness macular holes which failed previous treatments are difficult to manage and even left untreated due to poor prognosis. A retrospective review of consecutive cases with chronic (at least 1 year) full thickness macular holes and internal limiting membrane (ILM) free flap transposition with tuck technique, after previously failed vitrectomy. Methods: This was a retrospective and interventional study conducted in a single centre by a single surgeon. Patients with full thickness macular hole for at least 1 year and at least one previously failed vitrectomy with ILM peeling were recruited. A 25G vitrectomy with ILM free flap transposition was done without assistance of PFCL, viscoelastic or autologous blood. The free flap was manually tucked into the macular hole free space and gas fluid exchange was performed with 20% SF6 as tamponade. The patients were postured prone for 2 weeks postoperatively. Best corrected visual acuity, macular hole duration, previous surgeries, optical coherence tomography (OCT) appearance, hole size and closure rate were recorded. Results: 8 consecutive patients were included from May 2016 to Feb 2018. Transposition surgery was performed an average of 1481 days (SD 1096) after diagnosis of macular hole and average of 1226 days (SD 1242) after first vitrectomy. Macular hole mean size was 821 μm (SD 361.3), preoperative VA was logMAR 1.038 (SD 0.19), postoperative VA was logMAR 0.69 (SD 0.19) at 3 months. There were 1.13 lines gained and a significant improvement of logMAR 0.33 (p = 0.0084) at 6 months. Hole closure was seen in 7 out of 8 eyes (87.5%). The OCT with failed closure showed ILM flap within a flat hole, however no overlying neurosensory layers was seen. The duration from diagnosis to surgery was 2349 days in this case. Conclusion: Free flap ILM transposition tuck without the use of additional intraoperative tamponade is an effective technique in treating large chronic macular holes with previously failed primary macular hole surgeries.