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Background Methods Results Conclusions Normothermic machine perfusion (NMP) aims to reduce ischemia–reperfusion injury in donor livers and its clinical manifestation, early allograft dysfunction (EAD) by maintaining perfusion and oxygenation. However, there is limited data on which NMP perfusate biomarkers might be associated with such EAD and the role of perfusate hemoglobin has not been assessed.We performed a pilot retrospective analysis of adult donor livers undergoing NMP between 2020 and 2022 at our center. NMP was commenced at the recipient hospital after initial static cold storage. All NMP circuits were primed in the same manner according to the manufacturer's instructions. Livers were stratified by initial perfusate hemoglobin below (≤5.2 mmol/L) or above (>5.2 mmol/L) the median. The association between hemoglobin levels and EAD or recipient peak transaminase levels was assessed.Among 23 livers, eight were considered unsuitable for transplantation, leaving 15 livers for assessment. Higher initial hemoglobin was associated with a lower risk of EAD (0% vs. 55.6%, p = 0.04). Perfusate hemoglobin decreased after NMP initiation (p = 0.003) and negatively correlated with recipient peak transaminase levels (ALT: ρ = −0.72, p = 0.002; AST: ρ = −0.79, p < 0.001). Consistently, higher hemoglobin livers also demonstrated lower perfusate liver enzymes.Perfusate hemoglobin levels decreased during NMP, and lower perfusate hemoglobin levels were associated with a higher incidence of EAD and higher levels of liver injury markers. Maintaining higher hemoglobin levels during NMP may help reduce ischemia–reperfusion injury and prevent or attenuate EAD. Larger prospective studies are needed to validate the findings of this pilot study. [ABSTRACT FROM AUTHOR]

Objective: To present the early results of a new technique for the treatment of renal cell carcinoma with intra‐cardiac tumour extension and Budd–Chiari syndrome. Patients and Methods: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse‐string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. Results: Three of five patients presented with clinical Budd–Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. Conclusion: While we continue to compile longer‐term data for a larger follow‐up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery. [ABSTRACT FROM AUTHOR]

Patients with high model for end‐stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score ≥35 was introduced in February 2016. Waiting list mortality, post‐transplant outcomes and intention‐to‐treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre‐Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre‐Share 35 group (11.7% vs. 52.2%, OR.120 95% CI.044–.328, P <.001). Post‐transplant patient and graft survival were not significantly different between the groups (5‐year patient survival 82% vs. 84%, P =.991, 5‐year graft survival 82% vs. 76%, P =.543). Intention‐to‐treat survival was superior in the Share 35 group (HR.302, 95% CI.149–.614, P <.001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post‐transplant survival and an improvement in intention‐to‐treat survival. [ABSTRACT FROM AUTHOR]

Objective: Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD. Method: We used a murine model of KD (induced by the injection of the Candida albicans water‐soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD. Results: We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up‐regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS‐injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up‐regulate mTOR signaling, confirming that the mTOR pathway is active in human KD. Conclusion: Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high‐risk KD patients. [ABSTRACT FROM AUTHOR]

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning BRM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) is an effective procedure for locoregional control of hepatocellular carcinoma (HCC). Extrahepatic collaterals of left hepatic lobe HCC via the left inferior phrenic and internal mammary arteries are well recognized.3 Super-selective TACE treatment of HCC with extrahepatic collaterals is feasible and safe.4,5 In this case, super-selective TACE via the left inferior phrenic artery was successfully performed to treat a Segment II HCC. [Extracted from the article]