Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.

Esophageal wall defects, including perforations and postoperative leaks, are associated with high morbidity and mortality and pose a significant management challenge. In light of the high morbidity of surgical management or revision, in recent years, endoscopic vacuum therapy (EVT) has emerged as a novel alternative treatment strategy. EVT involves transoral endoscopic placement of a polyurethane sponge connected to an externalized nasogastric tube to provide continuous negative pressure with the intention of promoting defect healing, facilitating cavity drainage, and ameliorating sepsis. In the last decade, EVT has become increasingly adopted in the management of a diverse spectrum of esophageal defects. Its popularity has been attributed in part to the growing body of evidence suggesting superior outcomes and defect closure rates in excess of 80%. This growing body of evidence, coupled with the ongoing evolution of the technology and techniques of deployment, suggests that the utilization of EVT has become increasingly widespread. Here, we aimed to review the current status of the field, addressing the mechanism of action, indications, technique methodology, efficacy, safety, and practical considerations of EVT implementation. We also sought to highlight future directions for the use of EVT in esophageal wall defects.