Single-center experience with early liver transplantation for acute alcohol-related hepatitis-Limitations of the SALT score and directions for future study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.

The Superficial Femoral Artery: An Alternative Access for Percutaneous Endovascular Aneurysm Repair.

BACKGROUND: The aim of this study was to report the results of percutaneous endovascular aortic aneurysm repair (PEVAR) using the superficial femoral artery (SFA) for large bore vessel access. METHODS: We reviewed all PEVAR procedures at our institution over an 18-month period, identifying all patients who underwent PEVAR with the use of one or both SFAs for endograft delivery with dual ProGlide large bore access closure. Indications for use of the SFA instead of the common femoral artery (CFA) included morbid obesity, CFA vessel wall disease, and scarring from previous CFA surgery. RESULTS: In total, 158 percutaneous access closures were performed in 79 patients. Ten patients had one or both SFAs used. We accessed a total of 13 SFAs: 6 for the endograft main body (size range 18- to 20-French) and 7 for the limb (14- to 16-French). The freedom from open conversion was 84.6%. In comparison, of 145 CFA accesses (in 76 patients) there were 9 conversions (93.7% success). Of the 13 SFAs accessed, there were no major access site complications (pseudoaneurysm, access site bleed, limb ischemia, or need to return to the operating room). All SFAs accessed remained patent at the latest follow-up (range 1-13 months, median 8 months). CONCLUSIONS: Our preliminary case series suggests that, in the absence of a healthy or percutaneously accessible CFA, a healthy SFA may be considered for PEVAR access. While likely carrying a higher risk of open conversion, this technique, when combined with intraoperative duplex ultrasound (both before and after the procedure) and with meticulous ultrasound-guided vascular access, appears safe for up to 20-French device diameters.

Defective signal joint recombination in fanconi anemia fibroblasts reveals a role for Rad50 in V(D)J recombination.

V(D)J recombination of immunoglobulin loci is dependent on the immune cell-specific Rag1 and Rag2 proteins as well as a number of ubiquitously expressed cellular DNA repair proteins that catalyze non-homologous end-joining of DNA double-strand breaks. The evolutionarily conserved Rad50/Mre11/Nibrin protein complex has a role in DNA double-strand break-repair, suggesting that these proteins, too, may participate in V(D)J recombination. Recent findings demonstrating that Rad50 function is defective in cells from patients afflicted with Fanconi anemia provide a possible mechanistic explanation for previous findings that lymphoblasts derived from these patients exhibit subtle defects in V(D)J recombination of extrachromosomal plasmid molecules. Here, we describe a series of findings that provide convincing evidence for a role of the Rad50 protein complex in V(D)J recombination. We found that the fidelity of V(D)J signal joint recombination in fibroblasts from patients afflicted with Fanconi anemia was reduced by nearly tenfold, compared to that observed in fibroblasts from normal donors. Second, we observed that antibody-mediated inhibition of the Rad50, Mre11, or Nibrin proteins reduced the fidelity of signal joint recombination significantly in wild-type cells. The latter finding was somewhat unexpected, because signal joint rejoining in cells from patients with Nijmegen breakage syndrome, which results from mutations in the Nibrin gene, occurs with normal fidelity. However, introduction of anti-Nibrin antibodies into these cells reduced the fidelity of signal joint recombination dramatically. These data reveal for the first time a role for the Rad50 complex in V(D)J recombination, and demonstrate that the protein product of the disease-causing allele responsible for Nijmegen breakage syndrome encodes a protein with residual DNA double-strand break repair activity.