specimen-collection-and-analysis-of-the-duodenal-microbiome

Specimen Collection and Analysis of the Duodenal Microbiome

Shifts in the microbiome have been correlated with the physiology and pathophysiology of many organ systems both in humans and in mouse models. The gut ...

University of California, Los Angeles

Intestinal stem cell organoid transplantation generates functional intestinal neomucosa and has been used therapeutically to improve nutrient absorption and cure bile acid malabsorption in rats. We hypothesized that intestinal organoids can be harvested and transplanted to generate intestinal neomucosa in a large animal model.

Intestinal stem cell organoid transplantation generates neomucosa in dogs.

Although it is the only curative treatment for polycystic liver disease (PLD), orthotopic liver transplantation (OLT) has been reserved for severely symptomatic, malnourished, or refractory patients who are not candidates for palliative disease-directed interventions (DDI). Data on the effect of previous DDIs on post-transplant morbidity and mortality are scarce. We analyzed the outcomes after OLT for PLD recipients, and determined the effects of previous palliative surgical intervention on post-transplantation morbidity and mortality.

A 20-year experience with liver transplantation for polycystic liver disease: does previous palliative surgical intervention affect outcomes?

Data on complications requiring reoperation after orthotopic liver transplantation (OLT) are limited. We sought to describe the spectrum of reoperative complications after OLT, evaluate the associations with graft and patient survival, and identify predictors of need for reoperation.

Reoperative complications after primary orthotopic liver transplantation: a contemporary single-center experience in the post-model for end-stage liver disease era.

The Milan criteria have been the cornerstone of selection policies for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) globally for over two decades. Many groups have proposed the transplantation of patients with larger and more numerous tumors achieving comparable results. Many of these use radiologic morphometric criteria as surrogates for explant pathology to predict outcomes. Several other indices have been developed both within and beyond Milan incorporating biological indices as well as dynamic markers of response to pre-transplant locoregional treatments and waiting time. These have allowed for successful expansion of transplant selection criteria without compromising outcomes with limited organ supplies. In this review we will discuss the predictors of outcome in patients beyond Milan criteria.

Predictors of outcome after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria.

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).

Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.

Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the binary EAD (AUROC=0.68) definition and Model for Early Allograft Function (MEAF, AUROC=0.70) in the single-center derivation cohort (DC, n=2008). We sought to externally validate L-GrAFT, and compare its prognostic performance to EAD and MEAF.

Article	Year
Intestinal stem cell organoid transplantation generates neomucosa in dogs. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract\| PubMed ID: 19165549	2009
A 20-year experience with liver transplantation for polycystic liver disease: does previous palliative surgical intervention affect outcomes? Journal of the American College of Surgeons\| PubMed ID: 25065361	2014
Reoperative complications after primary orthotopic liver transplantation: a contemporary single-center experience in the post-model for end-stage liver disease era. Journal of the American College of Surgeons\| PubMed ID: 25127506	2014
Predictors of outcome after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria. International journal of surgery (London, England)\| PubMed ID: 32707331	2020
Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring. Nature communications\| PubMed ID: 32895384	2020
Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction. Journal of hepatology\| PubMed ID: 32976864	2020

Vatche G. Agopian

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