Prognostic factors and predictive models in hot gallbladder surgery: A prospective observational study in a high-volume center.

Backgrounds/Aims: The standard treatment for acute cholecystitis, biliary pancreatitis and intractable biliary colics ("hot gallbladder") is emergency laparoscopic cholecystectomy (LC). This paper aims to identify the prognostic factors and create statistical models to predict the outcomes of emergency LC for "hot gallbladder." Methods: A prospective observational cohort study was conducted on 466 patients having an emergency LC in 17 months. Primary endpoint was "suboptimal treatment," defined as the use of escape strategies due to the impossibility to complete the LC. Secondary endpoints were postoperative morbidity and length of postoperative stay. Results: About 10% of patients had a "suboptimal treatment" predicted by age and low albumin. Postop morbidity was 17.2%, predicted by age, admission day, and male sex. Postoperative length of stay was correlated to age, low albumin, and delayed surgery. Conclusions: Several predictive prognostic factors were found to be related to poor emergency LC outcomes. These can be useful in the decision-making process and to inform patients of risks and benefits of an emergency vs. delayed LC for hot gallbladder.

Development of Neuroregenerative Gene Therapy to Reverse Glial Scar Tissue Back to Neuron-Enriched Tissue.

Injuries in the central nervous system (CNS) often causes neuronal loss and glial scar formation. We have recently demonstrated NeuroD1-mediated direct conversion of reactive glial cells into functional neurons in adult mouse brains. Here, we further investigate whether such direct glia-to-neuron conversion technology can reverse glial scar back to neural tissue in a severe stab injury model of the mouse cortex. Using an adeno-associated virus (AAV)-based gene therapy approach, we ectopically expressed a single neural transcription factor NeuroD1 in reactive astrocytes in the injured areas. We discovered that the reactive astrocytes were efficiently converted into neurons both before and after glial scar formation, and the remaining astrocytes proliferated to repopulate themselves. The astrocyte-converted neurons were highly functional, capable of firing action potentials and establishing synaptic connections with other neurons. Unexpectedly, the expression of NeuroD1 in reactive astrocytes resulted in a significant reduction of toxic A1 astrocytes, together with a significant decrease of reactive microglia and neuroinflammation. Furthermore, accompanying the regeneration of new neurons and repopulation of new astrocytes, new blood vessels emerged and blood-brain-barrier (BBB) was restored. These results demonstrate an innovative neuroregenerative gene therapy that can directly reverse glial scar back to neural tissue, opening a new avenue for brain repair after injury.