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.

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.

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.

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.

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.

The effects of acuity circle policy on racial disparity in liver transplantation.

BACKGROUND: A new deceased donor liver allocation policy using an acuity circle-based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. METHODS: We conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post-acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. RESULTS: Acuity circle-policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post-liver transplantation mortality and liver graft failure in both periods. CONCLUSION: Although the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.

Association Between Catheter Ablation for Nonparoxysmal Atrial Fibrillation and Functional Mitral Regurgitation in Patients With Heart Failure With Preserved Ejection Fraction.

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n = 112; moderate, n = 40; severe, n = 1), and these were decreased to 70 (25%) significantly 1 year after AFCA (mild, n = 64; moderate, n = 6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1 year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p = 0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1 year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function.

Utilization of hepatitis C virus infected donors in heart transplant recipients with elevated MELD-XI score.

BACKGROUND: The advent of direct-acting antivirals has helped to increase the safe utilization of organs from hepatitis C virus positive (HCV+) donors. However, the outcomes of heart transplantation (HT) using an HCV+ donor are unclear in recipients with underlying liver disease represented by an elevated model for end-stage liver disease excluding international normalized ratio (MELD-XI). METHODS: The United Network of Organ Sharing database was queried from Jan 2016 to Dec 2021. Post-transplant outcomes stratified by recipient MELD-XI score (low <10.37, medium, 10.38-13.39, and high >13.4) was compared between patients with HT from HCV+ (N = 792) and patients with HT from HCV-negative donors (N = 15,266). RESULTS: The median MELD-XI score was comparable (HCV+, 12.1, vs. HCV-negative, 11.8, p = .37). In the HCV+ group, donors were older (33 vs. 31 years, p < .001). Ischemic time of donor hearts (3.48 vs. 3.28 h, p < .001) and travel distance (250 vs. 157 miles, p < .001) were longer in HCV+ group. In the Kaplan Meier analysis with a median follow-up of 750 days, survival was comparable between the two groups (2-year survival, MELD-XI Low: HCV+, 92.4 ± 3.6% vs. HCV-negative, 91.1 ±.8%, p = .83, Medium: HCV+ 89.2 ± 4.3% vs. HCV-negative, 88.2 ± 1.0%, p = .68, and High: HCV+, 84.9 ± 4.5% vs. HCV-negative, 84.6 ± 1.1%, p = .75) In multivariate Cox hazard models, HCV donors were not associated with mortality in each MELD-XI subgroup (Low: adjusted hazard ratio (aHR), 1.02, p = .94; Medium: aHR, .95, p = .81; and High: aHR, .93, p = .68). CONCLUSION: Utilization of HCV+ hearts was not associated with an increased risk of adverse outcomes in recipients with an elevated MELD- XI score.

Non-operative management of cirrhotic patients with acute calculous cholecystitis: How effective is it?

INTRODUCTION: Nonoperative management (NOM) of acute calculous cholecystitis (ACC) in patients with cirrhosis was proposed. We examined the outcomes of cirrhotic patients with ACC treated with cholecystectomy compared to NOM. METHODS: We analyzed the 2017-Nationwide Readmissions Database including cirrhotic patients with ACC. Patients were stratified: cholecystectomy, percutaneous cholecystostomy (PCT), and antibiotics only. PRIMARY OUTCOMES: complications, failure of NOM. SECONDARY OUTCOMES: mortality, length of stay (LOS), and charges. RESULTS: 3454 patients were identified. 1832 underwent cholecystectomy, 360 PCT, and 1262 were treated with antibiotics. PCT patients had higher mortality 16.9% vs. the antibiotics group 10.9% vs. cholecystectomy group 4.2%. PCT patients had longer LOS, but lower charges compared to the operative group. Failure of NOM was 28.2%. On regression, PCT was associated with mortality. CONCLUSION: ACC remains a morbid disease in cirrhosis patients. One in three failed NOM, had longer LOS, and higher mortality. Further studies are warranted to identify predictors of NOM failure. LEVEL OF EVIDENCE: Level III, prognostic.

Systemic immune-inflammation index as a predictor of prognosis after carotid artery stenting compared with C-reactive protein.

BACKGROUND: Immune-inflammatory processes are highly associated with the progression of atherosclerosis. The systemic immune-inflammation index (SII) is a potential predictor for clinical outcomes in patients with stroke and ischemic heart disease. Therefore, this study aimed to investigate whether SII can accurately predict the short- and long-term prognoses in patients who underwent carotid artery stenting (CAS) compared to that with C-reactive protein (CRP). METHODS: This study was a single-center retrospective investigation. Overall, 129 patients who underwent CAS were categorized into tertiles based on their SII levels. We primarily investigated the long-term major adverse cardiac and cerebrovascular events (MACCE) and secondarily the in-hospital and long-term stroke incidence, as well as all-cause death. RESULTS: The in-hospital stroke rate tended to increase with a rise in SII (P = 0.13). Over the 5-year follow-up period, the Kaplan-Meier overall incidence of MACCE was 9.3%, 16.3%, and 39.5% in the lowest to highest tertiles, respectively (log-rank trend test, P<0.001). The rates of stroke and MACCE during the long-term follow-up were significantly higher with increasing SII. Cox regression analysis showed that the highest tertile of SII (>647) was a predictor of the incidence of long-term stroke (hazard ratio (HR), 21.3; 95% confidence interval (CI), 2.41-188; P = 0.006) and MACCE (HR, 3.98; 95% CI, 1.80-8.81; P<0.001). However, after adjusting for both SII and CRP, only SII remained a significant independent predictor, whereas CRP became less relevant. The receiver operating characteristic curve analysis of long-term MACCE showed that the area under the curve (AUC) for SII (AUC, 0.72; 95% CI, 0.60-0.84; P<0.001) was greater than that of CRP (AUC, 0.64; 95% CI, 0.51-0.77; P = 0.040). CONCLUSION: SII was shown to be an independent predictor of long-term prognosis in patients who underwent CAS and was suggested to be superior to CRP as an inflammatory prognosis predictor.

Complex Abdominal Wall Reconstruction with Biologic Mesh for Ventral/Umbilical Hernias in Patients with Cirrhosis: Technique and Outcomes.

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

Outcomes of Bebtelovimab Therapy in Patients With Solid Organ Transplantation With Mild and Moderate COVID-19.

Solid organ transplant recipients (SOTRs) are at greater risk of poorer outcomes from coronavirus disease 2019 (COVID-19) as compared to the general population. Because of significant drug-drug interactions between nirmatrelvir-ritonavir and immunosuppressive agents as well as logistical challenges of outpatient administration of remdesivir, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) monoclonal antibodies (mAbs) had been the mainstay of outpatient treatment of COVID-19 among SOTRs, with bamlanivimab, casirivimab-imdevimab, and sotrovimab having been previously granted emergency use authorization by the Food and Drug Administration (FDA). The challenge with the ongoing use of these monoclonal antibodies is the loss of efficacy against emerging variants of SARS-CoV-2. Bebtelovimab, which retained efficacy against early subvariants of Omicron, was granted emergency use authorization by the Food and Drug Administration when Omicron BA.4 and BA.5 became the predominant variants in the United States. However, the study based on which bebtelovimab was authorized by the FDA did not include SOTRs. The only available safety and efficacy data on these patients are from retrospective studies. In our retrospective analysis of 62 SOTRs who received bebtelovimab infusion between May 11, 2022, and October 11, 2022, 28 had a kidney transplant, 18 had a liver transplant, 10 had a heart transplant, and six had multi-organ transplants (liver/kidney: 4, heart/kidney: 2). None of the patients reported infusion-associated adverse reaction. Only one (1.6%) patient developed progression of COVID-19, requiring subsequent treatment with remdesivir, steroids, and oxygen supplementation. The rate of need for intensive care and death from COVID-19 during the 30-day follow-up period was 0%.

Use of Donor Hearts ≥50 Years Old for Septuagenarians in Heart Transplantation.

BACKGROUND: The impact of using donors ≥50 years old on heart transplantation outcomes of septuagenarians is unknown, which may have a potential to expand the donor pool. METHODS: From January 2011 to December 2021, 817 septuagenarians received donor hearts <50 years old (DON<50) and 172 septuagenarians received donor hearts ≥50 years old (DON≥50) in the United Network for Organ Sharing database. Propensity score matching was performed using recipient characteristics (167 pairs). The Kaplan-Meier method and Cox proportional hazards model were used to analyze death and graft failure. RESULTS: The number of heart transplants in septuagenarians has been increasing (54 per year in 2011 to 137 per year in 2021). In a matched cohort, the donor age was 30 years in DON<50 and 54 years in DON≥50. In DON≥50, cerebrovascular disease was the main cause of death (43%), whereas head trauma (38%) and anoxia (37%) were the causes in DON<50 (P < .001). The median heart ischemia time was comparable (DON<50, 3.3 hours; DON≥50, 3.2 hours; P = .54). In matched patients, 1- and 5-year survival rates were 88.0% (DON<50) vs 87.2% (DON≥50) and 79.2% (DON<50) vs 72.3% (DON≥50), respectively (log-rank, P = .41). In the multivariable Cox proportional hazards models, donors ≥50 years old were not associated with death in matched (hazard ratio, 1.05; 95% CI, 0.67-1.65; P = .83) and nonmatched groups (hazard ratio, 1.11; 95% CI, 0.82-1.50; P = .49). CONCLUSIONS: The use of donor hearts older than 50 years can be an effective option for septuagenarians, thereby potentially increasing organ availability without compromising outcomes.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology. AIM: To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States. METHODS: WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020. RESULTS: Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001). CONCLUSION: During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Risk Factors for Frequent Infections in Patients With Extremely Severe Motor and Intellectual Disabilities.

BACKGROUND: At our institution, patients of all ages with extremely severe motor and intellectual disabilities (ESMID) receive comprehensive management similar to intensive care for "extremely ill patients." Some patients with ESMID develop frequent infections that are difficult to manage. The purpose of this study was to identify risk factors for frequent infections in these patients. METHODS: Thirty-seven patients with ESMID who were treated for infections at our institution between September 2018 and August 2019 were retrospectively investigated. Frequent infection was defined as three or more episodes of infection and antimicrobial treatment in one year. Infection status and potential risk factors for frequent infections (patient background factors, severity score, hematological parameters, anthropometry index, and parenteral nutritional status) were examined in univariate and multivariate analyses. RESULTS: Frequent infections occurred in 11 of the 37 patients (29.7%) during the study period, including respiratory and urinary tract infections. Univariate and multivariate analyses suggested hypoalbuminemia (p<0.01) and hypertriglyceridemia (p<0.01) were independent risk factors for frequent infections. CONCLUSIONS: Hypoalbuminemia and hypertriglyceridemia may be risk factors for frequent infections in patients with ESMID.