Expression, purification and preliminary crystallographic analysis of bacterial transmembrane protein EfeU for iron import.

The bacterial Efe system functions as an importer of free Fe2+ into cells independently of iron-chelating compounds such as siderophores and consisted of iron-binding protein EfeO, peroxidase EfeB, and transmembrane permease EfeU. While we and other researchers reported crystal structures of EfeO and EfeB, that of EfeU remains undetermined. In this study, we constructed expression system of EfeU derived from Escherichia coli, selected E. coli Rosetta-gami 2 (DE3) as an expression host, and succeeded in purification of the proteins which were indicated to form an oligomer by blue native PAGE. We obtained preliminary data of the X-ray crystallography, suggesting that expression and purification methods we established in this study enable structural analysis of the bacterial Efe system.

Potential Association of Blood Transfusion in Deceased Donors With Outcomes of Liver Transplantation in the United States.

BACKGROUND: Donor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). METHODS: From January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan-Meier method and multivariable Cox-hazard model. RESULTS: Among this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). CONCLUSIONS: Donor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection.

Radiation Therapy for Sister Mary Joseph's Nodule: A Review.

Purpose: Umbilical metastasis, known as Sister Mary Joseph's nodule (SMJN), is a manifestation of advanced malignant disease. Patients with SMJN usually require supportive care or palliative systemic chemotherapy. However, with the increasing number of older and infirm patients, radiation therapy for SMJN is needed more frequently. Therefore, we conducted this review to provide insights into radiation treatment for this rare condition. Methods and Materials: We searched PubMed on October 16, 2022, and obtained 275 articles that described SMJN or metastatic tumors within or near the umbilicus, as well as 255 case reports or case series (298 patients) and 20 reviews, original articles, or other study types, 1 of which also described a case. Results: The prognosis of patients with SMJN is extremely poor. However, some patients can survive for more than 2 years. The primary organs of the umbilical metastasis are mainly in the gastrointestinal tract, including the stomach, colon, and pancreas. In addition to these organs, the ovaries, uterine corpus, and breasts are the major organs affected in women. Metastasis may be divided into 4 types according to the tumor location and mechanism of the extension: within the umbilicus, not within although existing near or adjacent to the umbilicus, in the umbilical or paraumbilical hernia sac, and iatrogenic disease. Only 7 reports described patients who received radiation therapy in detail. The patients were divided into 2 groups: a relatively long course and high total dose (approximately 45 Gy) group, and a short course and low total dose group. Conclusions: Umbilical metastasis, known as SMJN, is a rare disease and is divided into 4 types based on the location of the disease and extent mechanism. Although the prognosis of the disease is poor, some patients survive for more than 2 years. Only 7 case reports precisely described radiation therapy. Half of the patients were treated with a short course, whereas the other half were treated with relatively high doses of up to 45 Gy.

The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States.

Background: New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Methods: Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Results: Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P < 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P < 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P < 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P < 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. Conclusions: The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.

Normothermic Machine Perfusion Is Associated With Improvement in Mortality and Graft Failure in Donation After Cardiac Death Liver Transplant Recipients in the United States.

Background: Use of normothermic machine perfusion (NMP) may help to expand the liver transplantation (LT) donor pool by potentially increasing the utilization of donation after circulatory death (DCD) organs. The aim of this study was to assess the impact of NMP on LT from DCD organs. Methods: Data among DCD adult LT recipients in the United Network for Organ Sharing between January 2016 and December 2022 were analyzed. Outcomes were compared between 2 groups: NMP versus non-MP using propensity score matching. Results: During the study period, 4217 DCD LT recipients (NMP: 257 and non-MP: 3960) were identified. compared with non-MP, DCD LT recipients in NMP group were older (median recipient age: 61 versus 59 y, P = 0.013), had lower model for the end-stage liver disease score, longer wait time (126 versus 107 d, P = 0.028), and received organs from older donors (median age: 42 versus 38 y, P < 0.01) with longer preservation time (9.9 versus 5.3 h, P < 0.001). Two-year overall survival (NMP 94.4% versus non-MP 89.7%, P = 0.040) and 2-y graft survival (NMP 91.3% versus non-MP 84.6%, P = 0.017) were better in the NMP group. After propensity score matching, 2-y overall survival (NMP 94.2% versus non-MP 88.0%, P = 0.023) and graft survival (NMP 91.3% versus non-MP 81.6%, P = 0.004) were better in the NMP group. On multivariable cox regression analysis, NMP was an independent factor of protection against mortality (hazard ratio, 0.43; 95% confidence interval: 0.20-0.91; P = 0.029) and against graft failure (hazard ratio, 0.26; 95% confidence interval: 0.11-0.61; P = 0.002). Conclusions: Use of NMP for LT from DCD donors was associated with improved posttransplant patient and graft survival.

Impact of Left Ventricular Unloading on Outcome of Heart Transplant Bridging With Extracorporeal Membrane Oxygenation Support in New Allocation Policy.

BACKGROUND: The new heart allocation policy places veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-supported heart transplant (HT) candidates at the highest priority status. Despite increasing evidence supporting left ventricular (LV) unloading during VA-ECMO, the effect of LV unloading on transplant outcomes following bridging to HT with VA-ECMO remains unknown. METHODS AND RESULTS: From October 18, 2018 to March 21, 2023, 624 patients on VA-ECMO at the time of HT were identified in the United Network for Organ Sharing database and were divided into 2 groups: VA-ECMO alone (N=384) versus VA-ECMO with LV unloading (N=240). Subanalysis was performed in the LV unloading group: Impella (N=106) versus intra-aortic balloon pump (N=134). Recipient age was younger in the VA-ECMO alone group (48 versus 53 years, P=0.018), as was donor age (VA-ECMO alone, 29 years versus LV unloading, 32 years, P=0.041). One-year survival was comparable between groups (VA-ECMO alone, 88.0±1.8% versus LV unloading, 90.4±2.1%; P=0.92). Multivariable Cox hazard model showed LV unloading was not associated with posttransplant mortality after HT (hazard ratio, 0.92; P=0.70). Different LV unloading methods had similar 1-year survival (intra-aortic balloon pump, 89.2±3.0% versus Impella, 92.4±2.8%; P=0.65). Posttransplant survival was comparable between different Impella versions (Impella 2.5, versus Impella CP, versus Impella 5.0, versus Impella 5.5). CONCLUSIONS: Under the current allocation policy, LV unloading did not impact waitlist outcome and posttransplant survival in patients bridged to HT with VA-ECMO, nor did mode of LV unloading. This highlights the importance of a tailored approach in HT candidates on VA-ECMO, where routine LV unloading may not be universally necessary.

Coronavirus Disease 2019 (COVID-19) in Heart Transplant Recipients and Anti-SARS-CoV-2 Monoclonal Antibodies: Experience, Lessons Learnt, and Future Challenges.

Solid organ transplant recipients (SOTRs), including heart transplant (HT) recipients, infected with Coronavirus disease 2019 (COVID-19) are at higher risk of hospitalization, mechanical ventilation, or death when compared with general population. Advances in diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have reduced COVID-19-related mortality rates from ~30% in the early pandemic to <3% in 2022 among HT recipients. We performed a retrospective chart review including adult HT recipients at Westchester Medical Center from January 1, 2020 to December 10, 2022, who received anti-SARS-CoV-2 monoclonal antibodies (mAbs) for treatment of mild-to-moderate COVID-19, and those who received tixagevimab/cilgavimab for preexposure prophylaxis. Additionally, a comprehensive review of the literature involving SOTRs who received mAbs for COVID-19 was conducted. In this largest single-center study in this population, 42 adult HT recipients received casirivimab/imdevimab (36%), sotrovimab (31%), or bebtelovimab (29%) for treatment of mild-to-moderate COVID-19. Among these recipients, no infusion-associated adverse effects, progression of disease, COVID-19-associated hospitalizations, or death were noted. Preexposure prophylaxis with tixagevimab/cilgavimab was given to 63 HT recipients in a dedicated infusion center (40%), inpatient setting (33%), or at time of annual heart biopsy (27%). No immediate adverse events were noted. There were 11 breakthrough infections, all mild. Overall, the data suggests that HT recipients receiving mAbs have reduced rates of hospitalization, need for intensive care unit care, or death. Use of anti-SARS-CoV-2 mAbs in SOTRs is resource intensive and requires a programmatic team approach for optimal administration and to minimize any risk of disparities in their use.

Effect of hyperuricemia on paroxysmal atrial fibrillation after catheter ablation and influence of alcohol consumption.

Background: Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence. Methods: Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n = 114) and control (UA ≤7.0 mg/dL; n = 609) groups and were followed for a median of 24 (12-48) months after ablation. Results: The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p = .017) and a lower incidence of AF-free survival (p = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF-free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12-2.40), female gender (1.91, 1.36-2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14-2.22), and alcohol consumption ≥20 g/day (1.49, 1.03-2.15) (all p < .05). In addition, causal mediation analysis revealed that alcohol consumption of ≥20 g/day directly affected AF recurrence, independent of hyperuricemia. Conclusions: Patients with hyperuricemia may be at a high risk of arrhythmia recurrence after catheter ablation for paroxysmal AF. Although high alcohol consumption may contribute to increased UA levels, the presence of hyperuricemia may independently predict AF recurrence.