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Metabolic syndrome (MetS) profoundly changes the contents of mesenchymal stem cells and mesenchymal stem cells–derived extracellular vesicles (EVs). The anti-inflammatory TGF-β (transforming growth factor-β) is selectively enriched in EVs from Lean but not from MetS pigs, but the functional impact of this endowment remains unknown. We hypothesized that Lean-EVs more effectively induce regulatory T cells in injured kidneys. Five groups of pigs (n=7 each) were studied after 16 weeks of diet-induced MetS and unilateral renal artery stenosis (RAS; MetS+RAS). Two groups of MetS+RAS were treated 4 weeks earlier with an intrarenal injection of either Lean-EVs or MetS-EVs. MetS+RAS had lower renal volume, renal blood flow, and glomerular filtration rate than MetS pigs. Compared with Lean-EVs, MetS-EVs were less effective in improving renal function and decreasing tubular injury and fibrosis in MetS+RAS. Lean-EVs upregulated TGF-β expression in stenotic kidney and increased regulatory T cells numbers more prominently. Furthermore, markedly upregulated anti-inflammatory M2 macrophages reduced proinflammatory M1 macrophages, and CD8 + T cells were detected in stenotic kidneys treated with Lean-EVs compared with MetS-EVs, and renal vein levels of interleukin-1β were reduced. In vitro, coculture of Lean-EVs with activated T cells led to greater TGF-β-dependent regulatory T cells induction than did MetS-EVs. Therefore, the beneficial effects of mesenchymal stem cells–derived EVs on injured kidneys might be partly mediated by their content of TGF-β signaling components, which permitting increased Treg preponderance. Modulating EV cargo and transforming their functionality might be useful for renal repair.

The liver is an immunologically active organ with a tolerogenic microenvironment at a quiescent state. The immunoregulatory properties of the liver appear to be retained after transplantation because liver allografts can reduce alloresponses against other organs that are simultaneously transplanted. Mechanisms of this phenomenon remain unknown. Given the known immunomodulatory properties of mesenchymal stromal cells (MSCs), we hypothesized that liver mesenchymal stromal cells (L‐MSCs) are superior immunomodulators and contribute to liver‐mediated tolerance. L‐MSCs, generated from human liver allograft biopsies, were compared with adipose mesenchymal stromal cells (A‐MSCs) and bone marrow mesenchymal stromal cells (BM‐MSCs). Trilineage differentiation of L‐MSCs was confirmed by immunohistochemistry. Comparative phenotypic analyses were done by flow cytometry and transcriptome analyses by RNA sequencing in unaltered cell cultures. The in vitro functional analyses were performed using alloreactive T cell proliferation assays. The transcriptome analysis showed that the L‐MSCs are different than the A‐MSCs and BM‐MSCs, with significant enrichment of genes and gene sets associated with immunoregulation. Compared with the others, L‐MSCs were found to express higher cell surface levels of several select immunomodulatory molecules. L‐MSCs (versus A‐MSCs/BM‐MSCs) inhibited alloreactive T cell proliferation (22.7% versus 56.4%/58.7%, respectively; P < 0.05) and reduced the frequency of interferon ɤ–producing T cells better than other MSCs (52.8% versus 94.4%/155.4%; P < 0.05). The antiproliferative impact of L‐MSCs was not dependent on cell‐to‐cell contact, could be reversed incompletely by blocking programmed death ligand 1, and required a higher concentration of the competitive inhibitor of indoleamine 2,3‐dioxygenase for complete reversal. In conclusion, L‐MSCs appear to be uniquely well‐equipped immunomodulatory cells, and they are more potent than A‐MSCs and BM‐MSCs in that capacity, which suggests that they may contribute to liver‐induced systemic tolerance.

Background. Anesthetic management of orthotopic liver transplantation (OLT) can be challenging. Management involves responding to sudden hemodynamic shifts, addressing instability, and performing ongoing volume assessment. To best prepare for these perturbations, various monitors are used intraoperatively. We sought to explore the impact of transesophageal echocardiography (TEE) and pulmonary artery catheter (PAC) use on outcomes of patients undergoing OLT. Methods. We retrospectively reviewed records of patients who underwent OLT at a single institution and included all who were monitored intraoperatively with TEE alone, PAC alone, or both methods concurrently (TEE + PAC). We determined whether these groups had differences in length of hospitalization (primary outcome), 30-day mortality rate, and other outcomes. Results. Three hundred eighteen liver transplant operations were included in the study. Patients in the TEE + PAC group had the shortest median length of hospitalization (TEE + PAC, 8.6 days; TEE, 10.3; PAC, 9.1; P = 0.04). The TEE + PAC group also had the lowest 30-day mortality rate (TEE + PAC, n = 1 [1.3%]; TEE, n = 5 [12.8%]; PAC, n = 7 [3.5%]; P = 0.009). However, the TEE + PAC group also had the highest rate of a new postoperative need for dialysis (TEE + PAC, n = 8 [10.3%]; TEE, n = 2 [5.1%]; PAC, n = 1 [0.5%]; P < 0.001). Conclusions. Compared with either TEE alone or PAC alone, intraoperative monitoring with TEE + PAC during OLT was associated with the shortest length of hospitalization and lowest 30-day mortality rate. Transplant anesthesiologists should be aware of the potential benefit on patient mortality and hospital length of stay with concurrent intraoperative TEE + PAC monitoring and the increased need for new postoperative dialysis.

The International Liver Transplantation Society (ILTS) 2019 Annual Congress was held in Toronto, Canada, in May 2019. Members of the ILTS Basic and Translational Research Committee attended all sessions of the meeting and selected the most promising, innovative, and novel research presented. A total of 900 abstracts were presented at the meeting. The percentage of abstracts presented at the ILTS Congress that contains basic or translational research continues to increase, accounting for 15% of all the abstracts in 2019, up from 10% in 2018. Here, we summarize the “what’s hot what’s new” in 5 main themes: liver immunobiology and tolerance, ischemia/reperfusion injury and organ preservation, bioengineering and liver regeneration, hepatic primary tumor biology, and pathophysiology of liver failure.

Abstract Abstract 2692 Background: Massive splenomegaly is occasionally encountered in patients with Non-Hodgkin's Lymphoma (NHL) and can be associated with abdominal symptoms, anemia and thrombocytopenia. The spleen may also be a primary focus of the disease itself. Splenectomy offers the benefit of localized treatment of the disease as well as relief of symptoms from splenomegaly and associated cytopenias. The safety and long term clinical outcomes of splenectomy for massive splenomegaly (>1500 gm) in patients with various histologies of NHL was analyzed. Methods: Data was obtained from clinical records of 90 patients with a diagnosis of NHL who underwent a splenectomy at Mayo Clinic Rochester from January 1998 to December 2007. Demographics, previous treatments, histology, post- surgical complications were collected and analyzed for the entire cohort. Additionally, median overall survival, improvement in symptoms, anemia and thrombocytopenia were analyzed by NHL type. Results: Median age at splenectomy was 67 years (range 42–84 yrs.) and 56 (62%) of patients were male. Average time from diagnosis to splenectomy was 3 months (range 0–217 months). Splenectomy was the first treatment in 56 (62%) patients; the other 34 patients were treated with chemotherapy with an average of two previous regimens. Most patients had involvement outside of the spleen, 65 (72%) with concurrent bone marrow involvement and 35 (50%) with lymph node involvement. Various different NHL histologies were represented: marginal zone (MZ) (34%), mantle cell (MC) (26%), diffuse large B-cell lymphoma (DLBCL) (10%), follicular (FL) (11%), lymphoplasmacytic (LP) (6%) and T cell NOS (4%). With a median follow-up time of 25 months, the median overall survival differed by histology type of NHL (Table 1). Indolent lymphomas such as FL, LP and MZ had more favorable survival compared with more aggressive lymphomas such as DLBCL and T cell NOS. Splenectomy was safe and well tolerated with only one treatment related death. There were no reported post-splenectomy septic events. Two patients did develop a portal vein thrombosis. 95% of patients had relief in pressure and abdominal symptoms post-splenectomy. With the exception of patients with DLBCL and T-cell NHL, a majority of patients had improvement in anemia and thrombocytopenia related to splenomegaly (Table 2). Conclusions: This represents the largest reported series of patients with lymphoma treated with splenectomy. Our results indicate that median overall survival after splenectomy is determined by the underlying type of NHL. Patients with LP, FL, MZ and MCL have a favorable outcomes following splenectomy. Splenectomy remains a safe and effective treatment option for massive splenomegaly in selected patients during the course of their disease management. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2848 Background: Massive splenomegaly (MS) (>1500 grams) is a rare and overtly symptomatic manifestation of myelofibrosis. While splenectomy may provide palliation, the procedure may be technically difficult and lead to high operative risks. We retrospectively analyzed myelofibrosis patients who underwent splenectomy for MS to analyze complications and outcomes. Methods: Retrospective chart review of all patients with myelofibrosis at our institution who underwent splenectomy for MS between 1998 and 2006 was performed. MS was defined as post-operative spleen weight measured to be more than 1500 grams. A total of 63 patients with MS had splenectomy for palliation of pressure symptoms or transfusion requiring cytopenias during that time period. Kaplan Meier statistics and log rank test were used for survival analysis. Results: Mean age of the study patients was 64.9 ± 9.5 years and 56% of those were males. Commonest pre-splenectomy symptoms were left upper quadrant abdominal discomfort (85.7%), fatigue (81%), early satiety (76.2%), anorexia (54%) and weight loss (39.7%). Packed red blood cell and platelet transfusions were required pre-operatively in 36/63 (57.1%) and 10/63 (15.9%) of patients, respectively. Median spleen weight was 2805 (range 1540 – 13085) grams. Perioperative complications occurred in 15 patients (23.8%) including infection (= 4 patients [6.3 %]), thrombosis (= 6 patients [9.5%]), or bleeding (= 9 patients [14.3%]), 2 of which (3.2% of all patients) were fatal. Median post-splenectomy survival (PSS) of these patients was 16.4 (0–110) months and 5 year PSS was 20%. Excluding patients lost to follow up, 43/55 (78.2%), 33/55 (60%) and 26/54 (48.1%) patients were alive at 6 months, 1 year and 2 years after splenectomy, respectively. At 1 year, out of 33 alive patients, 24 (72.7%) patients had relief of pressure symptoms. Out of 36 patients who were red cell transfusion dependent pre-splenectomy, 13 were alive and 6/13 (46.2%) patients were transfusion independent at 1 year. Similarly, out for 10 patients requiring platelet transfusions pre-operatively, 5 were alive and 3/5 (60%) were transfusion independent after 1 year follow up. PSS after splenectomy for MS was decreased in patients that required pre-operative packed red cell transfusions (median 9.3 months vs. 32.1 months, p= 0.033) (Fig 1), but not affected by other factors including age (>64 years), pre-operative thrombocytopenia (<100 × 109/uL), prolonged operative time (>90 minutes) or larger spleen size (>2800 grams). Conclusions: Splenectomy is relatively safe and effective palliative treatment for pressure related symptoms and refractory cytopenias related to MS in patients with myelofibrosis. Pre-operative anemia requiring red cell transfusions may predict advanced disease and is associated with inferior PSS. Disclosures: No relevant conflicts of interest to declare.