UNOS policy change benefits high-priority patients without harming those at low priority.

The heart transplantation policy change (PC) has improved outcomes in high-acuity (Old 1A, New 1-3) patients, but the effect on low-priority (Old 1B/2, New 4-6) patients is unknown. We sought to determine if low-priority patient outcomes were compromised by benefits to high-priority patients by evaluating for interaction between PC and priority status (PS). We included adult first-time heart transplant candidates and recipients from the UNOS registry during a 19-month period before and after the PC. We compared clinical characteristics and performed competing risks and survival analyses stratified by PC and PS. There was a dependence of PC and PS on waitlist death/deterioration with an interaction sub-distribution hazard ratio (adjusted sdHR) of 0.59 (0.45-0.78), p-value < .001. There was a trend toward a benefit of PC on waitlist death/deterioration (adjusted sdHR: 0.86 [0.73-1.01]; p = .07) and an increase in heart transplantation (adjusted sdHR: 1.08 [1.02-1.14], p = .007) for low-priority patients. There was no difference in 1-year post-transplant survival (log-rank p = .22) when stratifying by PC and PS. PC did not negatively affect waitlisted or transplanted low-priority patients. High-priority, post-PC patients had a targeted reduction in waitlist death/deterioration and did not come at the expense of worse post-transplant survival.

Effect of UNOS policy change and exception status request on outcomes in patients bridged to heart transplant with an intra-aortic balloon pump.

BACKGROUND: Intra-aortic balloon pumps (IABP) are used to bridge select end-stage heart disease patients to heart transplant (HT). IABP use and exception requests both increased dramatically after the UNOS policy change (PC). The purpose of this study was to evaluate the effect of PC and exception status requests on waitlist and post-transplant outcomes in patients bridged to HT with IABP support. METHODS: We analyzed adult, first-time, single-organ HT recipients from the UNOS Registry either on IABP at the time of registration for HT or at the time of HT. We compared waitlist and post-HT outcomes between patients from the PRE (October 18, 2016 to May 30, 2018) and POST (October 18, 2018 to May 30, 2020) eras using Kaplan-Meier curves and time-to-event analyses. RESULTS: A total of 1267 patients underwent HT from IABP (261 pre-policy/1006 post-policy). On multivariate analysis, PC was associated with an increase in HT (sub-distribution hazard ratio (sdHR): 2.15, p < .001) and decrease in death/deterioration (sdHR: 0.55, p = .011) on the waitlist with no effect on 1-year post-HT survival (p = .8). The exception status of patients undergoing HT was predominantly seen in the POST era (29%, 293/1006); only four patients in the PRE era. Exception requests in the POST era did not alter patient outcomes. CONCLUSIONS: In patients bridged to heart transplant with an IABP, policy change is associated with decreased rates of death/deterioration and increased rates of heart transplantation on the waitlist without affecting 1-year post-transplant survival. While exception status use has markedly increased post-PC, it is not associated with patient outcomes.

Long-term outcomes in patients with critical limb ischemia and heart failure with preserved or reduced ejection fraction.

The impact of heart failure (HF) on long-term survival in patients with critical limb ischemia (CLI) has not been well described. Outcomes stratified by left ventricular ejection fraction (EF) are also unknown. A single center retrospective chart review was performed for patients who underwent treatment for CLI from 2006 to 2013. Baseline demographics, procedural data and outcomes were analyzed. HF diagnosis was based on appropriate signs and symptoms as well as results of non-invasive testing. Among 381 CLI patients, 120 (31%) had a history of HF and 261 (69%) had no history of heart failure (no-HF). Within the HF group, 74 (62%) had HF with preserved ejection fraction (HFpEF) and 46 (38%) had HF with reduced ejection fraction (HFrEF). The average EF for those with no-HF, HFpEF and HFrEF were 59±13% vs 56±9% vs 30±9%, respectively. The likelihood of having concomitant coronary artery disease (CAD) was lowest in the no-HF group (43%), higher in the HFpEF group (70%) and highest in the HFrEF group (83%) ( p=0.001). Five-year survival was on average twofold higher in the no-HF group (43%) compared to both the HFpEF (19%, p=0.001) and HFrEF groups (24%, p=0.001). Long-term survival rates did not differ between the two HF groups ( p=0.50). There was no difference in 5-year freedom from major amputation or freedom from major adverse limb events between the no-HF, HFpEF and HFrEF groups, respectively. Overall, the combination of CLI and HF is associated with poor 5-year survival, independent of the degree of left ventricular systolic dysfunction.

Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis.

BACKGROUND: It is controversial whether proteinuria is a valid surrogate end point for randomized trials in chronic kidney disease. STUDY DESIGN: Meta-analysis of individual patient-level data. SETTING & POPULATION: Individual patient data for 9,008 patients from 32 randomized trials evaluating 5 intervention types. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least 1 further year of follow-up for the clinical outcome. PREDICTOR: Early change in proteinuria. OUTCOMES: Doubling of serum creatinine level, end-stage renal disease, or death. RESULTS: Early decline in proteinuria was associated with lower risk of the clinical outcome (pooled HR, 0.74 per 50% reduction in proteinuria); this association was stronger at higher levels of baseline proteinuria. Pooled estimates for the proportion of treatment effect on the clinical outcome explained by early decline in proteinuria ranged from -7.0% (95%CI, -40.6% to 26.7%) to 43.9% (95%CI, 25.3% to 62.6%) across 5 intervention types. The direction of the pooled treatment effects on early change in proteinuria agreed with the direction of the treatment effect on the clinical outcome for all 5 intervention types, with the magnitudes of the pooled treatment effects on the 2 end points agreeing for 4 of the 5 intervention types. The pooled treatment effects on both end points were simultaneously stronger at higher levels of proteinuria. However, statistical power was insufficient to determine whether differences in treatment effects on the clinical outcome corresponded to differences in treatment effects on proteinuria between individual studies. LIMITATIONS: Limited variety of interventions tested and low statistical power for many chronic kidney disease clinical trials. CONCLUSIONS: These results provide new evidence supporting the use of an early reduction in proteinuria as a surrogate end point, but do not provide sufficient evidence to establish its validity in all settings.

Purulent Bacterial Pericarditis: Rare Yet Lethal.

Bacterial pericarditis is a rare phenomenon that progresses rapidly and carries high mortality. Patients presenting with new pericardial effusions are often evaluated for concomitant rheumatologic, oncologic, and infectious diseases. We present a complex case of purulent pericarditis with pneumopericardium.

New UNOS allocation system associated with no added benefit in waitlist outcomes and worse post-transplant survival in heart-kidney patients.

BACKGROUND: The 2018 United Network for Organ Sharing (UNOS) heart transplant policy change (PC) sought to improve waitlist risk stratification to decrease waitlist mortality and promote geographically broader sharing for high-acuity patients awaiting heart transplantation. Our analysis sought to determine the effect of the UNOS PC on outcomes in patients waiting for, or who have received, a heart-kidney transplantation. METHODS: We analyzed adult (≥18 years old), first-time, heart-only and heart-kidney transplant candidates and recipients from the UNOS Registry. Patients were divided into pre-PC (PRE: October 18, 2016-May 30, 2018) and post-PC (POST: October 18, 2018-May 30, 2020) groups for comparison. Competing risks analysis (subdistribution and cause-specific hazards analyses) was performed to assess for differences in waitlist death/deterioration or heart transplantation. One-year post-transplant survival was assessed with Kaplan-Meier and Cox analyses. We included an interaction term (policy era × heart ± kidney) in our analyses to evaluate the effect of PC on outcomes in heart-kidney patients. RESULTS: One-year post-transplant survival was similar (p = 0.83) for PRE heart-kidney and heart-only recipients, but worse (p < 0.001) for POST heart-kidney vs heart-only recipients. There was a policy-era interaction between heart-kidney and heart-only recipients (HR 1.92[1.04,3.55], p = 0.038) indicating a detrimental effect of policy on 1-year survival in POST vs PRE heart-kidney recipients. No added beneficial effect of PC on waitlist outcomes in heart-kidney vs heart-only candidates was observed. CONCLUSIONS: There was no added policy-era benefit on waitlist outcomes for heart-kidney candidates when compared to heart-only candidates. POST heart-kidney recipients experienced worse 1-year survival compared to PRE heart-kidney recipients with no policy effect on heart-only recipients.

Effect of the UNOS policy change on rates of rejection, infection, and hospital readmission following heart transplantation.

BACKGROUND: The 2018 adult heart allocation policy sought to improve waitlist risk stratification, reduce waitlist mortality, and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Posttransplant complications are significantly higher in patients on tMCS before transplantation, and early posttransplant complications impact long-term mortality. We sought to determine if policy change affected early posttransplant complication rates of rejection, infection, and hospitalization. METHODS: We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between November 1, 2016, and October 31, 2017, and post-policy (POST) between November 1, 2018, and October 31, 2019. We used a multivariable logistic regression analysis to assess the effect of policy change on posttransplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis. RESULTS: The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p = 0.8), hospitalization (p = 0.69), and hospitalization due to rejection (p = 0.76) and infection (p = 0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p = 0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras. CONCLUSIONS: The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early posttransplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term posttransplant mortality.

Differences in HIV-specific T cell responses between HIV-exposed and -unexposed HIV-seronegative individuals.

HIV-1-specific T lymphocyte responses in individuals exposed to HIV-1 but who remain persistently seronegative (HESNs) have been reported in some but not all previous studies. This study was designed to resolve unequivocally the question of whether HESNs make HIV-1-specific T cell responses. We performed a blind investigation to measure HIV-1-specific T cell responses in both HIV-1-serodiscordant couples and HIV-1-unexposed seronegative controls (HUSNs). We found low-frequency HIV-1-specific T cells in both HESNs and HUSNs but show that the response rates were higher over time in the former (P = 0.01). Furthermore, the magnitudes of the HIV-1-specific T cell responses were significantly higher among responding HESNs than among HUSNs over time (P = 0.002). In both groups, responses were mediated by CD4 T cells. The responses were mapped to single peptides, which often corresponded to epitopes restricted by multiple HLA-DR types that have previously been detected in HIV-1-infected patients. HIV-1-specific T cell responses in HUSNs and some HESNs likely represent cross-reactivity to self or foreign non-HIV-1 antigens. The significantly greater T cell responses in HESNs, including in two who were homozygous for CCR5Δ32, demonstrates that HIV-1-specific T cell responses can be induced or augmented by exposure to HIV-1 without infection.

Early change in proteinuria as a surrogate outcome in kidney disease progression: a systematic review of previous analyses and creation of a patient-level pooled dataset.

BACKGROUND: Proteinuria is a candidate surrogate end point for randomized controlled trials (RCTs) in chronic kidney disease (CKD). There is a reasonably sound biological basis for this hypothesis, but only preliminary empirical evidence currently exists. METHODS: A systematic review and creation of a patient-level dataset of randomized controlled trials (RCTs) in CKD that reported changes in proteinuria and assessed progression of kidney disease as defined by dialysis, transplantation, death, or changes in GFR or creatinine were performed. RESULTS: Systematic review. Seventy RCTs met the eligibility criteria; 17 eligible RCTs contained analyses of proteinuria as a predictor of outcomes; 15 RCTs concluded that greater proteinuria was associated with adverse outcomes. A majority were studies of diabetic or hypertensive kidney disease and tested renin-angiotensin system blockade. Definitions of predictor and outcome variables were too variable to conduct a meta-analysis of group data. Database creation. Over 4 years was required to create the patient-level dataset. The final dataset included 34 studies and > 9000 patients with a variety of CKD types and interventions. CONCLUSIONS: There are a relatively small number of RCTs designed to rigorously test therapies for kidney disease progression. Current analyses of change in proteinuria as a predictor of CKD progression are heterogeneous and incomplete, indicating further evaluation in a pooled individual patient-level database is necessary to advance knowledge in this field.

The National Asthma Survey--New York State: association of the home environment with current asthma status.

OBJECTIVES: The National Asthma Survey--New York State (NYS), a telephone survey of NYS residents, was conducted in 2002-2003 to further understand the burden of asthma among adults and children and to identify health, socioeconomic, behavioral, and environmental factors associated with asthma. METHODS: A total of 1,412 households with at least one member with current asthma and 2,290 control households answered questions about their home environment (e.g., presence of asthma triggers and practices that promote or reduce common asthma triggers). RESULTS; For children younger than 18 years of age, we found statistically significant positive associations between current asthma and the presence of mold (adjusted odds ratio [AOR] = 2.1, 95% confidence interval [CI] 1.3, 3.3), air cleaners (AOR = 1.5, 95% CI 1.1, 2.1), dehumidifiers (AOR = 2.0, 95% CI 1.4, 2.7), and humidifiers (AOR = 1.6, 95% CI 1.1, 2.3). For adults, there were statistically significant positive associations with the presence of mold (AOR = 2.5, 95% CI 1.8, 3.4), air cleaners (AOR = 2.2, 95% CI 1.7, 2.8), and humidifiers (AOR = 1.4, 95% CI 1.1, 1.8). There were no statistically significant associations with the presence of cockroaches, pets, or tobacco smoke, while use of a wood-burning stove or fireplace was significantly more prevalent in control homes. CONCLUSIONS: Asthma guidelines emphasize the importance of reducing triggers in the home as part of a multifaceted approach to asthma control. Despite these guidelines, many asthma triggers (specifically, mold) were as prevalent or more so in the homes of New Yorkers with asthma as compared with control households. Public health interventions in NYS should focus on educating households about potential asthma triggers and their sources and teach methods to prevent, reduce, or eliminate them.

Complications of Pulmonic Valve Endocarditis in Repaired Tetralogy of Fallot.

Transthoracic echocardiography plays a pivotal role in the diagnosis of complications, evaluation of hemodynamics, and management of patients with surgically repaired congenital heart disease. Late complications of surgically corrected tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease, include pulmonary regurgitation (PR), ventricular septal defect (VSD) patch leakage, and residual right ventricular outflow tract obstruction. We present a case of severe PR secondary to Bartonella endocarditis in an adult with a history of repaired TOF in which echocardiography was instrumental in the diagnosis of severe PR, residual VSD, and a right-to-left shunt through an unsuspected patent foramen ovale.