The Albumin-Bilirubin score (ALBI) has been established to predict outcomes after hepatectomy. However, the relative value of ALBI and Model for End-Stage Liver Disease (MELD) in predicting post-hepatectomy liver failure and mortality has not been adequately evaluated. Therefore, the aim of this study was to validate and compare ALBI and MELD with respect to post-hepatectomy liver failure and mortality. Patients undergoing major hepatectomy (≥3 segments) or partial hepatectomy (≤2 segments) were identified in the 2014 to 2017 American College of Surgeons NSQIP Procedure Targeted Participant Use File. Univariable and multivariable analyses were performed for 30-day post-hepatectomy liver failure (PHLF) and mortality. Predictive accuracy was assessed using a receiver operator characteristic curve and calculating the area under the curve (AUC). For 13,783 patients, median ALBI was -2.6, and median MELD score was 6.9. Severe PHLF (grade B to C) and mortality rates were 2.9% and 1.8%, respectively. Multivariable analyses revealed ALBI grade 2/3 to be a stronger predictor than MELD ≥10 with respect to severe PHLF (odds ratio [OR] 2.30; 95% CI, 1.95 to 2.73; p < 0.001 vs OR 1.00; 95% CI, 0.78 to 1.23; p = 0.99) and mortality (OR 3.35; 95% CI, 2.49 to 4.52; p < 0.001 vs OR 1.73; 95% CI, 1.36 to 2.20; p < 0.001). ALBI also had better discrimination compared with MELD for severe PHLF (AUC 0.67 vs AUC 0.60) and mortality (AUC 0.70 vs AUC 0.58) in patients with hepatocellular carcinoma. ALBI is a powerful predictor of PHLF and mortality. Compared with MELD, ALBI is more accurate, especially in patients with hepatocellular carcinoma.

Through retrospective review of consecutive charts, we compare the short-term and long-term clinical outcomes after robotic-assisted right colectomy with intracorporeal anastomosis (RIA) (n=89) and laparoscopic right colectomy with extracorporeal anastomosis (LEA) (n=135). Cohorts were similar in demographic characteristics, comorbidities, pathology, and perioperative outcomes (conversion, days to flatus and bowel movement, and length of hospitalization). The RIA cohort experienced statistically significant: less blood loss, shorter incision lengths, and longer specimen lengths than the LEA cohort. Operative times were significantly longer for the RIA group. No incisional hernias occurred in the RIA group, whereas the LEA group had 5 incisional hernias; mean follow-up was 33 and 30 months, respectively. RIA is effective and safe and provides some clinical advantages. Future studies may show that, in obese and other technically challenging patients, RIA facilitates resection of a longer, consistent specimen with less mesentery trauma that can be extracted through smaller incisions.

Topoisomerase IB (Top1) is a key eukaryotic nuclear enzyme that regulates the topology of DNA during replication and gene transcription. Anticancer drugs that block Top1 are either well-characterized interfacial poisons or lesser-known catalytic inhibitor compounds. Here we describe a new class of cytotoxic redox-stable cationic Au³⁺ macrocycles which, through hierarchical cluster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or inhibitors of Top1. Two pivotal enzyme inhibition assays prove that the compounds are true catalytic inhibitors of Top1. Inhibition of human topoisomerase IIα (Top2α) by 3 was 2 orders of magnitude weaker than its inhibition of Top1, confirming that 3 is a type I-specific catalytic inhibitor. Importantly, Au³⁺ is essential for both DNA intercalation and enzyme inhibition. Macromolecular simulations show that 3 intercalates directly at the 5′-TA-3′ dinucleotide sequence targeted by Top1 via crucial electrostatic interactions, which include π–π stacking and an Au···O contact involving a thymine carbonyl group, resolving the ambiguity of conventional (drug binds protein) vs unconventional (drug binds substrate) catalytic inhibition of the enzyme. Surface plasmon resonance studies confirm the molecular mechanism of action elucidated by the simulations.

Ischemia reperfusion injury (IRI) during liver transplantation increases morbidity and contributes to allograft dysfunction. There are no therapeutic strategies to mitigate IRI. We examined a novel hypothesis: caspase 1 and caspase 11 serve as danger-associated molecular pattern (DAMPs) sensors in IRI. By performing microarray analysis and using caspase 1/caspase 11 double-knockout (Casp DKO) mice, we show that the canonical and non-canonical inflammasome regulators are upregulated in mouse liver IRI. Ischemic pre (IPC)- and post-conditioning (IPO) induce upregulation of the canonical and non-canonical inflammasome regulators. Trained immunity (TI) regulators are upregulated in IPC and IPO. Furthermore, caspase 1 is activated during liver IRI, and Casp DKO attenuates liver IRI. Casp DKO maintained normal liver histology via decreased DNA damage. Finally, the decreased TUNEL assay-detected DNA damage is the underlying histopathological and molecular mechanisms of attenuated liver pyroptosis and IRI. In summary, liver IRI induces the upregulation of canonical and non-canonical inflammasomes and TI enzyme pathways. Casp DKO attenuate liver IRI. Development of novel therapeutics targeting caspase 1/caspase 11 and TI may help mitigate injury secondary to IRI. Our findings have provided novel insights on the roles of caspase 1, caspase 11, and inflammasome in sensing IRI derived DAMPs and TI-promoted IRI-induced liver injury.