Cheungpasitporn, Wisit

Background: Better understanding of the different phenotypes/subgroups of non-U.S. citizen kidney transplant recipients may help the transplant community to identify strategies that improve outcomes among non-U.S. citizen kidney transplant recipients. This study aimed to cluster non-U.S. citizen kidney transplant recipients using an unsupervised machine learning approach; Methods: We conducted a consensus cluster analysis based on recipient-, donor-, and transplant- related characteristics in non-U.S. citizen kidney transplant recipients in the United States from 2010 to 2019 in the OPTN/UNOS database using recipient, donor, and transplant-related characteristics. Each cluster’s key characteristics were identified using the standardized mean difference. Post-transplant outcomes were compared among the clusters; Results: Consensus cluster analysis was performed in 11,300 non-U.S. citizen kidney transplant recipients and identified two distinct clusters best representing clinical characteristics. Cluster 1 patients were notable for young age, preemptive kidney transplant or dialysis duration of less than 1 year, working income, private insurance, non-hypertensive donors, and Hispanic living donors with a low number of HLA mismatch. In contrast, cluster 2 patients were characterized by non-ECD deceased donors with KDPI <85%. Consequently, cluster 1 patients had reduced cold ischemia time, lower proportion of machine-perfused kidneys, and lower incidence of delayed graft function after kidney transplant. Cluster 2 had higher 5-year death-censored graft failure (5.2% vs. 9.8%; p < 0.001), patient death (3.4% vs. 11.4%; p < 0.001), but similar one-year acute rejection (4.7% vs. 4.9%; p = 0.63), compared to cluster 1; Conclusions: Machine learning clustering approach successfully identified two clusters among non-U.S. citizen kidney transplant recipients with distinct phenotypes that were associated with different outcomes, including allograft loss and patient survival. These findings underscore the need for individualized care for non-U.S. citizen kidney transplant recipients.

AbstractBackgroundOur study aimed to characterize kidney retransplant recipients using an unsupervised machine‐learning approach.MethodsWe performed consensus cluster analysis based on the recipient‐, donor‐, and transplant‐related characteristics in 17 443 kidney retransplant recipients in the OPTN/UNOS database from 2010 to 2019. We identified each cluster's key characteristics using the standardized mean difference of >.3. We compared the posttransplant outcomes, including death‐censored graft failure and patient death among the assigned clustersResultsConsensus cluster analysis identified three distinct clusters of kidney retransplant recipients. Cluster 1 recipients were predominantly white and were less sensitized. They were most likely to receive a living donor kidney transplant and more likely to be preemptive (30%) or need ≤1 year of dialysis (32%). In contrast, cluster 2 recipients were the most sensitized (median PRA 95%). They were more likely to have been on dialysis >1 year, and receive a nationally allocated, low HLA mismatch, standard KDPI deceased donor kidney. Recipients in cluster 3 were more likely to be minorities (37% Black; 15% Hispanic). They were moderately sensitized with a median PRA of 87% and were also most likely to have been on dialysis >1 year. They received locally allocated high HLA mismatch kidneys from standard KDPI deceased donors. Thymoglobulin was the most commonly used induction agent for all three clusters. Cluster 1 had the most favorable patient and graft survival, while cluster 3 had the worst patient and graft survival.ConclusionThe use of an unsupervised machine learning approach characterized kidney retransplant recipients into three clinically distinct clusters with differing posttransplant outcomes. Recipients with moderate allosensitization, such as those represented in cluster 3, are perhaps more disadvantaged in the kidney retransplantation process. Potential opportunities for improvement specific to these re‐transplant recipients include working to improve opportunities to improve access to living donor kidney transplantation, living donor paired exchange and identifying strategies for better HLA matching.

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient’s response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review’s findings.

Introduction Premature birth has a causal relationship with hypertension and diabetes, which are significant risk factors for major cardiovascular disease. Nonetheless, little is known whether premature birth portends future risks of acquired heart diseases, for example, ischemic heart disease (IHD), heart failure (HF), and valvular heart disease (VHD). Methods We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to December 2021. Studies with prospective and retrospective cohort designs that reported the association between premature birth and acquired heart disease, including IHD, HF, and VHD, were included. Data from each study were combined with a random-effects model. The results were reported in the hazard ratio (HR) with 95% confidence intervals. Results The selected studies were comprised of 7 studies, with 5 studies involving premature birth and the development of IHD in adulthood and 2 studies involving premature birth and HF. No studies reporting the relationship between premature birth and VHD met our initial inclusion criteria. Our study did not find any association between premature birth and IHD in the adulthood (HR 1.14 95% CI 0.91-1.19, P = .16, I 2 = 51%). We found the association between premature birth and acquired HF (HR 1.53 95% CI 1.08-2.16, P = .01, I 2 = 0) Conclusion Premature birth was not statistically associated with IHD in adulthood, but there was a significant association between preterm and HF.

Background: The utilization of multi-dimensional patient data to subtype hepatorenal syndrome (HRS) can individualize patient care. Machine learning (ML) consensus clustering may identify HRS subgroups with unique clinical profiles. In this study, we aim to identify clinically meaningful clusters of hospitalized patients for HRS using an unsupervised ML clustering approach. Methods: Consensus clustering analysis was performed based on patient characteristics in 5564 patients primarily admitted for HRS in the National Inpatient Sample from 2003–2014 to identify clinically distinct HRS subgroups. We applied standardized mean difference to evaluate key subgroup features, and compared in-hospital mortality between assigned clusters. Results: The algorithm revealed four best distinct HRS subgroups based on patient characteristics. Cluster 1 patients (n = 1617) were older, and more likely to have non-alcoholic fatty liver disease, cardiovascular comorbidities, hypertension, and diabetes. Cluster 2 patients (n = 1577) were younger and more likely to have hepatitis C, and less likely to have acute liver failure. Cluster 3 patients (n = 642) were younger, and more likely to have non-elective admission, acetaminophen overdose, acute liver failure, to develop in-hospital medical complications and organ system failure, and to require supporting therapies, including renal replacement therapy, and mechanical ventilation. Cluster 4 patients (n = 1728) were younger, and more likely to have alcoholic cirrhosis and to smoke. Thirty-three percent of patients died in hospital. In-hospital mortality was higher in cluster 1 (OR 1.53; 95% CI 1.31–1.79) and cluster 3 (OR 7.03; 95% CI 5.73–8.62), compared to cluster 2, while cluster 4 had comparable in-hospital mortality (OR 1.13; 95% CI 0.97–1.32). Conclusions: Consensus clustering analysis provides the pattern of clinical characteristics and clinically distinct HRS phenotypes with different outcomes.

AbstractBackgroundHigh‐power short‐duration (HPSD) atrial fibrillation (AF) ablation with a power of 40–50 W was proved to be safe and effective. Very high‐power short‐duration (vHPSD) AF ablation is a novel method using >50 W to obtain more durable AF ablation. This study aimed to evaluate the efficacy and safety of vHPSD ablation compared with HPSD ablation and conventional power ablation.MethodsA literature search for studies that reported AF ablation outcomes, including short‐term freedom from atrial arrhythmia, first‐pass isolation (FPI) rate, procedure time, and major complications, was conducted utilizing MEDLINE, EMBASE, and Cochrane databases. All relevant studies were included in this analysis. A random‐effects model of network meta‐analysis and surface under cumulative ranking curve (SUCRA) were used to rank the treatment for all outcomes.ResultsA total of 29 studies with 9721 patients were included in the analysis. According to the SUCRA analysis, HPSD ablation had the highest probability of maintaining sinus rhythm. Point estimation showed an odds ratio of 1.5 (95% confidence interval [CI]: 1.2–1.9) between HPSD ablation and conventional power ablation and an odds ratio of 1.3 (95% CI: 0.78–2.2) between vHPSD ablation and conventional power ablation. While the odds ratio of FPI between HPSD ablation and conventional power ablation was 3.6 (95% CI: 1.5–8.9), the odds ratio between vHPSD ablation and conventional power ablation was 2.2 (95% CI: 0.61–8.6). The procedure times of vHPSD and HPSD ablations were comparable and, therefore, shorter than that of conventional power ablation. Major complications were low in all techniques.ConclusionvHPSD ablation did not yield higher efficacy than HPSD ablation and conventional power ablation. With the safety concern, vHPSD ablation outcomes were comparable with those of other techniques.

AbstractBackgroundLeft bundle branch area pacing (LBBAP) has recently become a promising option for the near‐natural restoration of electrical activation. However, the clinical relevance of therapeutic effects in individuals with heart failure with reduced ejection fraction (HFrEF) and dyssynchrony remains unknown.MethodsMEDLINE, EMBASE, and Cochrane databases were searched from inception until June 2022. Data from each study was combined using a random‐effects model, the generic inverse variance method of DerSimonian and Laird, to calculate standard mean differences and pooled incidence ratio, with 95% confidence intervals (CIs).ResultsA total of 772 HFrEF patients were analyzed from 15 observational studies per protocol. The success rate of LBBAP implantation was 94.8% (95% CI 89.9–99.6, I2 = 79.4%), which was strongly correlated with shortening QRS duration after LBBAP implantation, with a mean difference of −48.10 ms (95% CI −60.16 to −36.05, I2 = 96.7%). Over a period of 6–12 months of follow‐up, pacing parameters were stable over time. There were significant improvements in left ventricular ejection fraction (LVEF), left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic diameter (LVEDD), and left ventricular end‐diastolic volume (LVEDV) with mean difference of 16.38% (95% CI 13.13–19.63, I2 = 90.2%), −46.23 ml (95% CI −63.17 to −29.29, I2 = 86.82%), −7.21 mm (95% CI −9.71 to −4.71, I2 = 84.6%), and −44.52 ml (95% CI −64.40 to −24.64, I2 = 85.9%), respectively.ConclusionsLBBAP was associated with improvements in both cardiac function and electrical synchrony. The benefits of LBBAP in individuals with HFrEF and dyssynchrony should be further validated by randomized studies.

AbstractWell‐selected patients with kidney disease and diabetes mellitus who undergo simultaneous kidney‐pancreas transplantation often experience dramatic improvements in quality of life and long‐term survival compared to those who remain on medical therapy. Over the past several years the importance of frailty in the pancreas transplant candidate and recipient populations has grown. More patients with advanced age have entered the waitlist, and complications from prolonged diabetes, even in younger patients, have created increased evidence of risk for frailty. Given these concerns, and the broad challenges facing pancreas transplantation volumes overall, we generated this review to help establish the impact and implications. We summarize the interplay of immunological factors, aging, environmental factors, diabetes mellitus, and chronic kidney disease that put these patients at risk for frailty. We discuss its measurement and recommend a combination of two instruments (both well‐validated and one entirely objective). We describe the outcomes for patients before and after pancreas transplantation who may have frailty, and what interventions can be taken to mitigate its effects. Broader investigation into frailty in the pancreas transplant population is needed to better understand how to select patients for pancreas transplantation and to how manage its consequences thereafter.

Introduction: Posttransplant anemia is a common finding after kidney transplantation. A previous meta-analysis reported an association between anemia and graft loss. However, data on cardiovascular outcomes have not yet been reported. Objective: We conducted an updated meta-analysis to examine the association between posttransplant anemia and outcomes after transplantation including cardiovascular mortality in adult kidney transplant recipients. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2021. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios and 95% CIs. Results: Seventeen studies from August 2006 to April 2019 were included (16 463 kidney transplantation recipients). Posttransplant anemia was associated with overall mortality (pooled risk ratio = 1.72 [1.39, 2.13], I 2 = 56%), graft loss (pooled risk ratio = 2.28 [1.77, 2.93], I 2 = 94%), cardiovascular death (pooled risk ratio = 2.06 [1.35, 3.16], I 2 = 0%), and cardiovascular events (pooled risk ratio = 1.33 [1.10, 1.61], I 2 = 0%). Early anemia (≤6 months), compared with late anemia (>6 months), has higher risk of overall mortality and graft loss with a pooled risk ratio of 2.63 (95% CI 1.79-3.86; I 2 = 0%) and 2.96 (95% CI 2.29-3.82; I 2 = 0%), respectively. Discussion: In addition to increased risk of graft loss, our updated meta-analysis demonstrated that posttransplant anemia was significantly associated with poor outcomes after kidney transplantation including overall mortality, graft loss, cardiovascular death, and cardiovascular events. Future studies are required to assess the effects of treatment strategies for posttransplant anemia on posttransplant outcomes including cardiovascular mortality.