Intraoperative intracardiac thrombus in liver transplantation: A 9-year retrospective review focusing on treatment and outcomes.

This study characterizes incidence and outcomes surrounding intracardiac thrombosis (ICT) during liver transplantation over 9 years at a single center before and after the routine use of transesophageal echocardiography (TEE). Adult liver transplantation patients from 2011 to 2020 were divided into eras based on routine TEE use. ICTs were identified by querying anesthetic records for search terms. Descriptive statistics included counts and proportions for baseline recipient, donor, intraoperative, and postoperative characteristics. Outcome data were based on date of hospital discharge and date of death. The incidence of ICT increased in the TEE era (2016-2020) compared with the pre-TEE era (2011-2015; 3.7% [25/685] vs. 1.9% [9/491]; p < 0.001). Patients with ICT had significantly higher Model for End-Stage Liver Disease-sodium (MELD-Na) scores, pretransplant hospitalization, malignancy, drug-induced liver injury, hypertension, deep vein thrombosis, reperfusion syndrome, transfused platelets and cryoprecipitate, and use of hemostatic medications. A higher proportion of patients in the ICT group underwent simultaneous liver-kidney transplantation. The patients with ICT were similar, except patients in the pre-TEE era had higher MELD-Na scores and incidences of hepatitis C virus and lower incidences of encephalopathy. In the pre-TEE era, all ICTs presented as intraoperative cardiac arrest, and the 30-day mortality in the setting of ICT was 66.7% (6/9). During the TEE era, 80% of ICTs were diagnosed incidentally or attributed to hemodynamic instability (p = 0.002). The 30-day mortality rate was 36% (9/25) in the TEE era (p = 0.25). ICT incidence increased in the TEE era, yet the mortality rate was lower, suggesting that routine intraoperative TEE may lead to the early detection of ICT prior to hemodynamic collapse.

Profound Intraoperative Hypotension Associated With Transfusion via the Belmont Fluid Management System.

This retrospective observational case series conducted at 2 large academic centers over a 4-year period consists of 15 cases of profound hypotension in surgical patients immediately after initiation of the Belmont Fluid Management System for rapid transfusion of blood products. Halting the infusion and administering vasoactive agents led to resolution of hypotension. Repeat transfusion with the Belmont system resulted in repeat hypotension unless counteracted with vasopressors. No etiology was elucidated. This represents the largest documented association of acute hypotensive transfusion reaction with any rapid infusion system in surgical patients.

CDK6 kinase activity is required for thymocyte development.

Cyclin-dependent kinase-6 (CDK6) is required for early thymocyte development and tumorigenesis. To mechanistically dissect the role of CDK6 in thymocyte development, we generated and analyzed mutant knock-in mice and found that mice expressing a kinase-dead Cdk6 allele (Cdk6(K43M)) had a pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells (Lin⁻Sca-1⁺c-Kit⁺ [LSK]). In contrast, mice expressing the INK4-insensitive, hyperactive Cdk6(R31C) allele displayed excess proliferation in LSK and thymocytes. However, this is countered at least in part by increased apoptosis, which may limit progenitor and thymocyte expansion in the absence of other genetic events. Our mechanistic studies demonstrate that CDK6 kinase activity contributes to Notch signaling because inactive CDK6 kinase disrupts Notch-dependent survival, proliferation, and differentiation of LSK, with concomitant alteration of Notch target gene expression, such as massive up-regulation of CD25. Further, knockout of CD25 in Cdk6(K43M) mice rescued most defects observed in young mice. These results illustrate an important role for CDK6 kinase activity in thymocyte development that operates partially through modulating Notch target gene expression. This role of CDK6 as a downstream mediator of Notch identifies CDK6 kinase activity as a potential therapeutic target in human lymphoid malignancies.

Abdominal Organ Transplantation: Noteworthy Literature in 2018.

A PubMed search revealed 1382 articles on pancreatic transplantation, 781 on intestinal transplantation, more than 7200 on kidney transplantation, and more than 5500 on liver transplantation published between January 1, 2018, and December 31, 2018. After narrowing the list down to human studies, 436 pancreatic, 302 intestinal, 1920 liver, and more than 2000 kidney transplantation studies were screened for inclusion in this review.

ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus.

Tobacco contains a variety of carcinogens as well as the addictive compound nicotine. Nicotine addiction begins with the binding of nicotine to its cognate receptor, the nicotinic acetylcholine receptor (nAChR). Genome-wide association studies have implicated the nAChR gene cluster, CHRNA5/A3/B4, in nicotine addiction and lung cancer susceptibility. To further delineate the role of this gene cluster in lung cancer, we examined the expression levels of these three genes as well as other members of the nAChR gene family in lung cancer cell lines and patient samples using quantitative reverse transcription-PCR. Overexpression of the clustered nAChR genes was observed in small-cell lung carcinoma (SCLC), an aggressive form of lung cancer highly associated with cigarette smoking. The overexpression of the genomically clustered genes in SCLC suggests their coordinate regulation. In silico analysis of the promoter regions of these genes revealed putative binding sites in all three promoters for achaete-scute complex homolog 1 (ASCL1), a transcription factor implicated in the pathogenesis of SCLC, raising the possibility that this factor may regulate the expression of the clustered nAChR genes. Consistent with this idea, knockdown of ASCL1 in SCLC, but not in non-SCLC, led to a significant decrease in expression of the alpha 3 and beta 4 genes without having an effect on any other highly expressed nAChR gene. Our data indicate a specific role for ASCL1 in regulating the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. This regulation may contribute to the predicted role that ASCL1 plays in SCLC tumorigenesis.