In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (Odds Ratio [OR] 1.8), Roux-en-hepaticojejunostomy (OR 1.4), and a history of major abdominal surgery (OR 1.4). For biliary anastomotic strictures, risk factors were ABO-incompatibility (OR 1.4), blood loss >1 liter (OR 1.4), and previous abdominal surgery (OR 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher Comprehensive Complication Index (CCI®) scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival despite available effective treatments.

Skin wound healing represents a dynamic and intricate biological process involving the coordinated efforts of various cellular and molecular components to restore tissue integrity and functionality. Among the myriads of cellular events orchestrating wound closure, fibroblast migration and the regulation of fibrosis play pivotal roles in determining the outcome of wound healing. In recent years, probiotic therapy has emerged as a promising strategy for modulating wound healing and fibrosis. Here, we aim to investigate the effect of bacterial probiotics on cell migration and anti-fibrotic response of human dermal fibroblast (HDFs). Probiotic mixture BioK was co-cultured with HDFs in vitro to assess its impact on fibroblast migration, gene expression, and protein production associated with important processes in wound healing. Gene expression was investigated by transcriptomic analysis and confirmed by RT-qPCR. Protein levels of the identified genes were evaluated by ELISA. The role of lactic acid, produced by BioK, in mediating pH-related effects on fibroblast activity was further examined. We observed that BioK effectively promoted HDFs migration in vitro, which was found to be related to the up-regulation of genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathways such as Paxillin, PI3K, PKC and ITG-β1. Interestingly, we also found that BioK down-regulated the expression of Nox-4, α-SMA and Col-I in TGF-Smad signaling pathways, which are involved in the differentiation of fibroblasts to myofibroblasts, and extracellular matrix type I collagen production, demonstrating its potential in reducing formation of fibrosis and scars. One of the acting factors for such down-regulation was identified to be BioK-produced lactic acid, which is known to lower the surrounding pH and to play a major role in fibroblast activity and wound healing. This study demonstrates BioK’s beneficial effects on fibroblast migration and its potential to mitigate fibrosis through pH modulation and pathway-specific gene regulation. These findings enhance our understanding of probiotic action on wound healing and offer promising therapeutic insights for the reduction of scar formation. Not applicable.

Wound infections pose a significant challenge in healthcare, and traditional antibiotic treatments often result in the development of resistant pathogens. Addressing this gap, ProGel is introduced, a living hydrogel created by entrapping probiotic Lactobacillus plantarum as a therapeutic component within a gelatin matrix. With a double‐syringe system, ProGel can be easily mixed and applied, conforming swiftly to any wound shape and forming hydrogel in situ. It also demonstrates robust mechanical and self‐healing properties owing to the Schiff‐base bonds. ProGel sustains more than 80% viability of the entrapped L. plantarum while restricting their escape from the hydrogel. After a week of storage, more than 70% viability of the entrapped L. plantarum is preserved. Importantly, ProGel exhibits broad‐spectrum antimicrobial efficacy against pathogens commonly associated with wound infections, i.e., Pseudomonas aeruginosa (7Log reduction), Staphylococcus aureus (3‐7Log reduction), and Candida albicans (40–70% reduction). Moreover, its cytocompatibility is affirmed through coculture with human dermal fibroblasts. The effectiveness of ProGel is further highlighted in more clinically relevant tests on human skin wound models infected with P. aeruginosa and S. aureus , where it successfully prevents the biofilm formation of these pathogens. This study showcases an injectable living hydrogel system for the management of complex wound infections.

Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.