Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation.

Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the four core genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect, and last, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.

The Impact of Local Programmatic Decisions on Outcomes in Transplant-Listed Adults With Congenital Heart Disease.

BACKGROUND: We investigated variables impacting waitlist times and negative waitlist outcomes in adults with congenital heart disease (ACHD) who were waiting for orthotopic heart transplant (OHT) after the 2018 allocation change. METHODS: Adult candidates for OHT who were listed between 10/18/2018 and 12/31/2022 in the United Network for Organ Sharing database were categorized as ACHD vs non-ACHD. Waitlist time and time to upgrade for those upgraded into status 1-3 were compared by using rank-sum tests. Death/delisting for deterioration was assessed by using Fine-Gray subdistribution hazard ratios (SHRs). RESULTS: Of 15,424 OHT candidates, 589 (3.8%) were ACHD. ACHD vs non-ACHD candidates had less urgent status at initial listing (4.2% vs 4.7% listed at status 1; 17.2% vs 23.7% listed at status 2; P < 0.001), but not final listing (5.9% vs 7.6% final status 1; 35.6% vs 36.8% final status 2; P < 0.001). ACHD vs non-ACHD candidates upgraded into status 1 (65.0 vs 30.0 days; P = 0.09) and status 2 (113.0 vs 64.0 days; P = 0.003) spent longer times on the waitlist. ACHD vs non-ACHD candidates spent longer times waiting for an upgrade into status 1 (51.4 vs 17.6 days; P = 0.027) and status 2 (76.7 vs 34.7 days; P = 0.003). Once upgraded, there was no difference between groups in waitlist time to status 1 (9.7 vs 5.5 days = 0.66). ACHD vs non-ACHD candidates with a final status of 1 (20.0% vs 8.6%; SHR 2.47 [95%CI = 1.19-5.16]; P = 0.02) and 2 (8.9% vs 2.3%; SHR 3.59 [95%CI = 2.18-5.91]; P < 0.001) experienced higher rates of death and deterioration. CONCLUSIONS: ACHD candidates have longer waitlist times, have lower priority status at initial listing, wait longer for upgrades, and have higher mortality rates at the same final status as non-ACHD candidates, suggesting that they are being upgraded too late.

Incidence, risk factors, and outcomes of postoperative stroke in combined heart-lung transplantation: A retrospective cohort study of the UNOS registry.

Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend = .07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR] = 2.63, 95%CI = [1.13-6.11]) and pre-transplant implantable defibrillator (aOR = 2.86, 95%CI = [1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.

Machine Learning from Veno-Venous Extracorporeal Membrane Oxygenation Identifies Factors Associated with Neurological Outcomes.

BACKGROUND: Neurological complications are common in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) support. We used machine learning (ML) algorithms to identify predictors for neurological outcomes for these patients. METHODS: All demographic, clinical, and circuit-related variables were extracted for adults with VV-ECMO support at a tertiary care center from 2016 to 2022. The primary outcome was good neurological outcome (GNO) at discharge defined as a modified Rankin Scale of 0-3. RESULTS: Of 99 total VV-ECMO patients (median age = 48 years; 65% male), 37% had a GNO. The best performing ML model achieved an area under the receiver operating characteristic curve of 0.87. Feature importance analysis identified down-trending gas/sweep/blender flow, FiO2, and pump speed as the most salient features for predicting GNO. CONCLUSION: Utilizing pre- as well as post-initiation variables, ML identified on-ECMO physiologic and pulmonary conditions that best predicted neurological outcomes.

Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples.

Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. Although these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare 12 cell type quantification tools and evaluate their performance while using each of 10 separate reference profiles. Specifically, we have run each tool on over 4000 samples with known cell type proportions, spanning both immune and stromal cell types. A total of 12 of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single-cell data. A final 3728 clinical samples have been collected from the Framingham cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool Estimating the Proportions of Immune and Cancer cells (EPIC) produces the highest correlation, whereas Gene Expression Deconvolution Interactive Tool (GEDIT) produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. We find that optimal reference depends on the tool used, and report suggested references to be used with each tool. Most tools return results within minutes, but on large datasets runtimes for CIBERSORT can exceed hours or even days. We conclude that deconvolution methods are capable of returning high-quality results, but that proper reference selection is critical.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial.

BACKGROUND: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). METHODS: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. RESULTS: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). CONCLUSION: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Epidemiology of ischemic stroke and hemorrhagic stroke in venoarterial extracorporeal membrane oxygenation.

BACKGROUND: While venoarterial extracorporeal membrane oxygenation (V-A ECMO) provides lifesaving support for cardiopulmonary failure, complications may increase mortality, with few studies focusing on ischemic/hemorrhagic stroke. We aimed to determine the trends and associations of stroke incidence and mortality, and their risk factors, including the effects of annual case volumes of ECMO centers. METHODS: Retrospective analysis was performed on the Extracorporeal Life Support Organization (ELSO) registry, including adult V-A ECMO patients from 534 international centers between 2012 and 2021, excluding extracorporeal cardiopulmonary resuscitation. Temporal trend analyses were performed for stroke incidence and mortality. Univariate testing, multivariable regression, and survival analysis were used to evaluate the associations of stroke, 90-day mortality, and impact of annual center volume. RESULTS: Of 33,041 patients, 20,297 had mortality data, and 12,327 were included in the logistic regression. Between 2012 and 2021, ischemic stroke incidence increased (p < 0.0001), hemorrhagic stroke incidence remained stable, and overall 90-day mortality declined (p < 0.0001). Higher 24-h PaO2 and greater decrease between pre-ECMO PaCO2 and post-cannulation 24-h PaCO2 were associated with greater ischemic stroke incidence, while annual case volume was not. Ischemic/hemorrhagic strokes were associated with increased 90-day mortality (both p < 0.0001), while higher annual case volume was associated with lower 90-day mortality (p = 0.001). Hazard of death was highest in the first several days of V-A ECMO. CONCLUSION: In V-A ECMO patients between 2012 and 2021, 90-day mortality decreased, while ischemic stroke incidence increased. ELSO centers with higher annual case volumes had lower mortality, but were not associated with ischemic/hemorrhagic stroke incidence. Both ischemic/hemorrhagic strokes were associated with increased mortality.

Lower Oxygen Tension and Intracranial Hemorrhage in Veno-venous Extracorporeal Membrane Oxygenation.

INTRODUCTION AND METHODS: We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring. RESULTS: Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01). CONCLUSION: In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients.

What Factors Are Associated With Arterial Line-Related Limb Ischemia in Patients on Extracorporeal Membrane Oxygenation? A Single-Center Retrospective Cohort Study.

OBJECTIVES: The primary purpose of this study was to identify factors associated with the development of arterial line-related limb ischemia in patients on extracorporeal membrane oxygenation (ECMO). The authors also sought to characterize and report the outcomes of patients who developed arterial line-related limb ischemia. DESIGN: Retrospective cohort study. SETTING: A single academic tertiary referral ECMO center. PARTICIPANTS: Consecutive patients who were treated with ECMO over 6 years. INTERVENTIONS: Use of arterial line. MEASUREMENTS AND MAIN RESULTS: A total of 278 consecutive ECMO patients were included, with 19 (7%) patients developing arterial line-related limb ischemia during the ECMO run. Postcannulation Sequential Organ Failure Assessment (SOFA) (adjusted odds ratio [aOR] 1.20, 95% CI 1.08-1.32), Acute Physiology and Chronic Health Evaluation-II (aOR 0.84, 95% CI 0.74-0.95), and adjusted Vasopressor Dose Equivalence (aOR 1.03, 95% CI 1.01-1.05) scores were independently associated with the development of arterial line-associated limb ischemia. A SOFA score of ≥17 at the time of ECMO cannulation had an 80% sensitivity and 87% specificity for predicting arterial line-related limb ischemia. CONCLUSIONS: Arterial line-related limb ischemia is much more common in ECMO patients than in the typical intensive care unit setting. The SOFA score may be useful in identifying which patients may be at risk for arterial line-related limb ischemia. As this was a single-center retrospective study, these results are inherently exploratory, and prospective multicenter studies are necessary to validate these results.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

BACKGROUND: Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. METHODS: We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. RESULTS: We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. CONCLUSIONS: Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

Costs and Readmissions Associated with Type A Aortic Dissections at High- and Low-Volume Centers.

BACKGROUND: Costs and readmissions associated with type A aortic dissection repairs are not well understood. We investigated statewide readmissions, costs, and outcomes associated with the surgical management of type A aortic dissection repairs at low- and high-volume centers. METHODS: We identified all adult type A aortic dissection patients who underwent operative repair in the Maryland Health Services Cost Review Commission's database (2012-2020). Hospitals were stratified into high- (top quartile of total repairs) or low-volume centers. RESULTS: Of the 249 patients included, 193 (77.5%) were treated at a high-volume center. Patients treated at high- and low-volume centers had no differences in age, sex, race, primary payer, or severity (all p > 0.5). High- compared to low-volume centers had a greater proportion of patients transferred in (71.5% vs. 17.9%, p < 0.001). High-volume centers also had longer lengths of stay (12 vs. 8 days, p < 0.001), similar inpatient mortality (13.0% vs. 16.1%, p = 0.6), and similar proportion of patients readmitted (54.9% vs. 51.8%, p = 0.7). High-volume centers had greater index admission costs ($114,859 vs. $72,090, p < 0.001) and similar readmission costs ($48,367 vs. $42,204, p = 0.5). At high-volume centers, transferred patients compared to direct admissions had greater severity of illness (p = 0.05), similar mortality (p = 0.53), and greater lengths of stay (p = 0.05). CONCLUSIONS: High-volume centers had a greater number of patients transferred from other institutions compared to low-volume centers. High-volume centers were associated with increased index admission resource utilization, with transfer patients having higher illness severity and greater resource utilization, yet similar mortality, compared to direct admission patients.

Temporary Mechanical Circulatory Support for Transcatheter Aortic Valve Replacement.

INTRODUCTION: This study aimed to characterize the use of temporary mechanical circulatory support (tMCS) among patients undergoing transcatheter aortic valve replacement (TAVR) using a nationally representative database. MATERIALS AND METHODS: The 2012-2018 National Inpatient Sample was queried for adult patients who underwent isolated TAVR. The tMCS group was comprised of those who required extracorporeal membrane oxygenation, percutaneous ventricular assist device, or intra-aortic balloon pump during index hospitalization. We evaluated temporal trends in the utilization of tMCS using Cuzick's test. Furthermore, a multivariable logistic regression was used to identify factors associated with tMCS use and its impact on in-hospital mortality, selected complications, and nonhome discharge. RESULTS: Of an estimated 215,925 patients who underwent TAVR, 3085 (1.4%) required tMCS during their hospital course. The most common modality of tMCS was intra-aortic balloon pump (49%), followed by extracorporeal membrane oxygenation (27%) then percutaneous ventricular assist device (18%). Seven percent of tMCS patients were supported by > 1 device. The annual incidence of tMCS usage decreased over the study period, from 3% in 2012 to 1% in 2018 (P-trend < 0.01). Nonelective admission, congestive heart failure, coagulopathy, and liver disease were strong independent predictors of requiring tMCS. Patients requiring tMCS had a 31.8% in-hospital mortality rate (adjusted odds ratio = 23, 95% confidence interval 18.5-28.5), longer length of stay (9 d versus 3, P < 0.001), and higher costs ($84,600 versus $48,100, P < 0.001) than those who did not. CONCLUSIONS: The use of tMCS during TAVR has decreased over time but remains associated with a 23-fold increased mortality rate and significant clinical and resource utilization burden.

Massive left atrial thrombus evades multimodality imaging as a myxoma in a bicaval heart transplant recipient.

Intracardiac masses are an extremely rare and poorly described complication following a bicaval heart transplantation. We describe the case of an asymptomatic 62-year-old male with a large left atrial mass found incidentally on transthoracic echocardiography 6 years post-transplant. A battery of additional imaging tests was ordered including transesophageal echocardiography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and T1 and T2 magnetic resonance imaging. Although imaging biomarkers were generally nonspecific, the mass was most consistent with a cardiac myxoma. However, intraoperative findings confirmed by pathology revealed a massive organizing thrombus. The patient had an uneventful recovery after surgical removal of the mass. Our case highlights a very rare phenomenon in heart transplant recipients which remains a unique diagnostic challenge even with current advances in imaging.

Mild hypothermia and neurologic outcomes in patients undergoing venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of cerebral reperfusion injury after prolonged hypoperfusion and immediate restoration of systemic blood flow. We aimed to examine the impact of mild hypothermia during the first 24 h post-ECMO on neurological outcomes in VA-ECMO patients. METHODS: This was a retrospective study of adult VA-ECMO patients from a tertiary care center. Mild hypothermia was defined as 32-36°C during the first 24 h post-ECMO. The primary outcome was a good neurological function at discharge measured by a modified Rankin Scale ≤3. Multivariable logistic regression analysis was performed for primary outcome adjusting for pre-specified covariates. RESULTS: Overall, 128 consecutive patients with VA-ECMO support (median age: 60 years and 63% males) were included. Within the first 24 h of VA-ECMO cannulation, we found a median of 71 readings per patient (interquartile range 45-88). Eighty-eight patients (68.8%) experienced mild hypothermia within the first 24 h while 18 of those 88 patients (14.2%) had a mean temperature <36°C. ECMO indications included post-cardiotomy shock (39.8%), cardiac arrest (29.7%), and cardiogenic shock (26.6%). Duration of mild hypothermia, but not mean temperature, was independently associated with increased odds of good neurological outcome at discharge (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.04-1.31, p = .01) after adjusting for age, the severity of illness, post-ECMO systemic hemorrhage, post-cardiotomy shock, acute brain injury, and mean 24-h PaO2 . Neither duration of mild hypothermia (OR = 0.93, CI = 0.84-1.03, p = .17) nor mean temperature (OR = 0.78, CI = 0.29-2.08, p = .62) was significantly associated with mortality. Similarly, duration of mild hypothermia (p = .47) and mean 24-h temperature (p = .76) were not significantly associated with the frequency of systemic hemorrhages. CONCLUSIONS: In this single-center study, a longer duration of mild hypothermia during the first 24 h of ECMO support was significantly associated with improved neurological outcomes. Mild hypothermia was not associated with an increased risk of systemic hemorrhage or improved survival.

Changes in Donor Utilization and Outcomes for Patients Bridged With Durable Left Ventricular Assist Device.

We studied the impact of the 2018 heart allocation policy change on donor characteristics and posttransplant outcomes of left ventricular assist device (LVAD)-bridged heart transplant (HT) recipients. Left ventricular assist device-bridged adult HT recipients from October 2014 to October 2022 in the United Network for Organ Sharing database were categorized into old allocation policy (OAP) and new allocation policy (NAP) cohorts. Baseline characteristics, posttransplant outcomes, and subgroup analyses of unstable and stable LVAD-bridged recipients were assessed. The study included 7,384 HT recipients; 4,345 (58.8%) were transplanted in the OAP era and 3,039 (41.2%) in the NAP era. Old allocation policy recipients were most frequently status 1A at transplantation (71.1%), whereas NAP recipients were most frequently status 3 (40.0%), and status 4 (31.9%). Median donor sequence number (DSN) was higher in the NAP versus OAP era (9 vs. 3, p < 0.001). On multivariable analysis, NAP recipients had 20% higher 1 year mortality compared to OAP (adjusted hazard ratio [aHR] = 1.20 [95% confidence interval {CI}: 1.04-1.40], p = 0.01). Status 1 or 2 recipients had 28% higher 1 year mortality compared to status 1A (aHR = 1.28 [95% CI: 1.01-1.63], p = 0.04). Status 1 and 2 LVAD-supported recipients had higher mortality following the 2018 allocation change, indicating the need for closer surveillance of LVAD-bridged patients who may decompensate on the waitlist.

Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant With Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used for critically ill candidates with excellent outcomes, but data on this strategy in older recipients remain limited. We compared outcomes of no BTT, mechanical ventilation (MV)-only BTT, and ECMO BTT in recipients of greater than or equal to 65 years. Lung-only recipients of greater than or equal to 65 years in the United Network for Organ Sharing database between 2008 and 2022 were included and stratified by bridging strategy. Of the 9,936 transplants included, 226 (2.3%) were MV-only BTT and 159 (1.6%) were ECMO BTT. Extracorporeal membrane oxygenation BTT recipients were more likely to have restrictive disease pathology, had higher median lung allocation score, and spent fewer days on the waitlist (all p < 0.001). Compared to no-BTT recipients, ECMO BTT recipients were more likely to be intubated or on ECMO at 72 hours posttransplant and had longer hospital lengths of stay (all p < 0.001). Extracorporeal membrane oxygenation BTT recipients had increased risk of 3 years mortality compared to both no-BTT (adjusted hazard ratio [aHR] = 1.48 [95% confidence interval {CI}: 1.14-1.91], p = 0.003) and MV-only recipients (aHR = 1.50 [95% CI: 1.08-2.07], p = 0.02). Overall, we found that ECMO BTT in older recipients is associated with inferior posttransplant outcomes compared to MV-only or no BTT, but over half of recipients remained alive at 3 years posttransplant.

Risk Factors for Nondiagnostic Imaging in a Real-World Deployment of Artificial Intelligence Diabetic Retinal Examinations in an Integrated Healthcare System: Maximizing Workflow Efficiency Through Predictive Dilation.

OBJECTIVE: In the pivotal clinical trial that led to Food and Drug Administration De Novo "approval" of the first fully autonomous artificial intelligence (AI) diabetic retinal disease diagnostic system, a reflexive dilation protocol was used. Using real-world deployment data before implementation of reflexive dilation, we identified factors associated with nondiagnostic results. These factors allow a novel predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori to maximize efficiency and patient satisfaction. METHODS: Retrospective review of patients who were assessed with autonomous AI at Johns Hopkins Medicine (8/2020 to 5/2021). We constructed a multivariable logistic regression model for nondiagnostic results to compare characteristics of patients with and without diagnostic results, using adjusted odds ratio (aOR). P < .05 was considered statistically significant. RESULTS: Of 241 patients (59% female; median age = 59), 123 (51%) had nondiagnostic results. In multivariable analysis, type 1 diabetes (T1D, aOR = 5.82, 95% confidence interval [CI]: 1.45-23.40, P = .01), smoking (aOR = 2.86, 95% CI: 1.36-5.99, P = .005), and age (every 10-year increase, aOR = 2.12, 95% CI: 1.62-2.77, P < .001) were associated with nondiagnostic results. Following feature elimination, a predictive model was created using T1D, smoking, age, race, sex, and hypertension as inputs. The model showed an area under the receiver-operator characteristics curve of 0.76 in five-fold cross-validation. CONCLUSIONS: We used factors associated with nondiagnostic results to design a novel, predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori. This new workflow has the potential to be more efficient than reflexive dilation, thus maximizing the number of at-risk patients receiving their diabetic retinal examinations.

Outcomes of Lung Transplant Candidates Aged ≥70 Years During the Lung Allocation Score Era.

BACKGROUND: With the increasing age of lung transplant candidates, we studied waitlist and posttransplantation outcomes of candidates ≥70 years during the Lung Allocation Score era. METHODS: Adult lung transplant candidates from 2005 to 2020 in the United Network for Organ Sharing database were included and stratified on the basis of age at listing into 18 to 59 years old, 60 to 69 years old, and ≥70 years old. Baseline characteristics, waitlist outcomes, and posttransplantation outcomes were assessed. RESULTS: A total of 37,623 candidates were included (52.3% aged 18-59 years, 40.6% aged 60-69 years, 7.1% aged ≥70 years). Candidates ≥70 years were more likely than younger candidates to receive a transplant (81.9% vs 72.7% [aged 60-69 years] vs 61.6% [aged 18-59 years]) and less likely to die or to deteriorate on the waitlist within 1 year (9.1% vs 10.1% [aged 60-69 years] vs 12.2% [aged 18-59 years]; P < .001). Donors for older recipients were more likely to be extended criteria (75.7% vs 70.1% [aged 60-69 years] vs 65.7% [aged 18-59 years]; P < .001). Recipients ≥70 years were found to have lower rates of acute rejection (6.7% vs 7.4% [aged 60-69 years] vs 9.2% [aged 18-59 years]; P < .001) and prolonged intubation (21.7% vs 27.4% [aged 60-69 years] vs 34.5% [aged 18-59 years]; P < .001). Recipients aged ≥70 years had increased 1-year (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.06-1.33]; P < .001), 3-year (aHR, 1.28 [95% CI, 1.18-1.39]; P < .001), and 5-year mortality (aHR, 1.29 [95% CI, 1.21-1.38]; P < .001) compared with recipients aged 60 to 69 years. CONCLUSIONS: Candidates ≥70 years had favorable waitlist and perioperative outcomes despite increased use of extended criteria donors. Careful selection of candidates and postoperative surveillance may improve posttransplantation survival in this population.

Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes.

BACKGROUND: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. METHODS: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression. RESULTS: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression. CONCLUSIONS: Prolonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population.