TLR10 (CD290) Is a Regulator of Immune Responses in Human Plasmacytoid Dendritic Cells.

TLRs are the most thoroughly studied group of pattern-recognition receptors that play a central role in innate immunity. Among them, TLR10 (CD290) remains the only TLR family member without a known ligand and clearly defined functions. One major impediment to studying TLR10 is its absence in mice. A recent study on TLR10 knock-in mice demonstrated its intrinsic inhibitory role in B cells, indicating that TLR10 is a potential drug target in autoimmune diseases. In this study, we interrogated the expression and function of TLR10 in human plasmacytoid dendritic cells (pDCs). We have seen that primary human pDCs, B cells, and monocytes constitutively express TLR10. Upon preincubation with an anti-TLR10 Ab, production of cytokines in pDCs was downregulated in response to stimulation with DNA and RNA viruses. Upon further investigation into the possible mechanism, we documented phosphorylation of STAT3 upon Ab-mediated engagement of TLR10. This leads to the induction of inhibitory molecule suppressor of cytokine signaling 3 (SOCS3) expression. We have also documented the inhibition of nuclear translocation of transcription factor IFN regulatory factor 7 (IRF7) in pDCs following TLR10 engagement. Our data provide the (to our knowledge) first evidence that TLR10 is constitutively expressed on the surface of human pDCs and works as a regulator of their innate response. Our findings indicate the potential of harnessing the function of pDCs by Ab-mediated targeting of TLR10 that may open a new therapeutic avenue for autoimmune disorders.

Outcomes of Impella 5.0 and 5.5 for cardiogenic shock: A single-center 137 patient experience.

BACKGROUND: This study evaluated the outcomes of patients with cardiogenic shock (CS) supported with Impella 5.0 or 5.5 and identified risk factors for in-hospital mortality. METHODS: Adults with CS who were supported with Impella 5.0 or 5.5 at a single institution were included. Patients were stratified into three groups according to their CS etiology: (1) acute myocardial infarction (AMI), (2) acute decompensated heart failure (ADHF), and (3) postcardiotomy (PC). The primary outcome was survival, and secondary outcomes included adverse events during Impella support and length of stay. Multivariable logistic regression was performed to identify risk factors for in-hospital mortality. RESULTS: One hundred and thirty-seven patients with CS secondary to AMI (n = 47), ADHF (n = 86), and PC (n = 4) were included. The ADHF group had the highest survival rates at all time points. Acute kidney injury (AKI) was the most common complication during Impella support in all 3 groups. Increased rates of AKI and de novo renal replacement therapy were observed in the PC group, and the AMI group experienced a higher incidence of bleeding requiring transfusion. Multivariable analysis demonstrated diabetes mellitus, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine were independent predictors of in-hospital mortality, but the etiology of CS did not impact mortality. CONCLUSIONS: This study demonstrates that Impella 5.0 and 5.5 provide effective mechanical support for patients with CS with favorable outcomes, with nearly two-thirds of patients alive at 180 days. Diabetes, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine are strong risk factors for in-hospital mortality.

Extracorporeal life support after surgical repair for acute type a aortic dissection: A systematic review and meta-analysis.

BACKGROUND: The use of extracorporeal life support (ECLS) in patients after surgical repair for acute type A aortic dissection (ATAAD) has not been well documented. METHODS: We performed a systematic review and meta-analysis to assess the outcomes of ECLS after surgery for ATAAD with data published by October 2023 in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The protocol was registered in PROSPERO (CRD42023479955). RESULTS: Twelve observational studies met our eligibility criteria, including 280 patients. Mean age was 55.0 years and women represented 25.3% of the overall population. Although the mean preoperative left ventricle ejection fraction was 59.8%, 60.8% of patients developed left ventricle failure and 34.0% developed biventricular failure. Coronary involvement and malperfusion were found in 37.1% and 25.6%, respectively. Concomitant coronary bypass surgery was performed in 38.5% of patients. Regarding ECLS, retrograde flow (femoral) was present in 39.9% and central cannulation was present in 35.4%. In-hospital mortality was 62.8% and pooled estimate of successful weaning was 50.8%. Neurological complications, bleeding and renal failure were found in 25.9%, 38.7%, and 65.5%, respectively. CONCLUSION: ECLS after surgical repair for ATAAD remains associated with high rates of in-hospital death and complications, but it still represents a chance of survival in critical situations. ECLS remains a salvage attempt and surgeons should not try to avoid ECLS at all costs after repairing an ATAAD case.

Outcomes in Patients With LVADs Undergoing Simultaneous Heart-Kidney Transplantation.

BACKGROUND: Multiple studies have shown better outcomes for simultaneous heart-kidney transplant (sHKT) than for isolated orthotopic heart transplant (iOHT) in recipients with chronic kidney disease (CKD). However, outcomes in patients supported by durable left ventricular assist devices (LVADs) have not been well studied. METHODS: Patients with durable LVADs and stage 3 or higher CKD (eGFR < 60 mL/min/1.73 m2) undergoing iOHT or sHKT between 2008 and 2020 were identified from the United Network for Organ Sharing registry. A Kaplan-Meier survival analysis with associated log-rank test was conducted to compare post-transplant survival rates. Multivariable modeling was used to identify risk-adjusted predictors of 1 year post-transplant mortality. RESULTS: We identified 4375 patients; 366 underwent sHKT, and 4009 underwent iOHT. The frequency of sHKT increased during the study period. The 1-year post-transplant survival rate was worse in patients after sHKT than in patients after iOHT (80.3% vs 88.3%; P < 0.001) and persisted up to 5 years post-transplant (P = 0.001). sHKT recipients were more likely to require dialysis after transplantation and had longer hospital lengths of stay (P < 0.001). Multivariable analysis showed that sHKT remained an independent risk factor for mortality at 1 year (OR 1.58; P = 0.002). CONCLUSIONS: sHKT is becoming more common in patients with durable LVADs. Compared with iOHT, patients with sHKTs have worse short- and long-term survival rates and are more likely to require post-transplant dialysis.

Revascularization Strategies for Multivessel Coronary Artery Disease in the Elderly Population.

BACKGROUND: Prospective trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for the treatment of multivessel coronary disease (MVCAD) have included mostly younger patients. We compared treatment strategies in the elderly population. MATERIALS AND METHODS: We performed a propensity-score-matched comparison of patients ≥75 y who underwent isolated CABG or PCI for MVCAD between 2011 and 2018, excluding those with prior cardiac surgery and/or significant left main disease. The primary outcome was 5-year Kaplan Meier survival, and secondary outcomes included readmissions and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Propensity-matching yielded 536 patients (266 PCI and 266 CABG). Rates of complete revascularization of all stenotic lesions were higher in the CABG arm (86.8% versus 21.8%; P < 0.001). Thirty-d mortality was similar between cohorts, though PCI recipients had shorter hospital stay and greater likelihood of discharge to home. Unadjusted one- (89.1% versus 88.4%) and 5-year (73.8% versus 60.1%) survival were both higher in patients who underwent CABG (P = 0.0332). Patients undergoing CABG had reduced, but nonsignificant cumulative incidence of all-cause hospital readmission and MACCE at 5 y. Subgroup analysis of patients 80 y or older revealed similar late survival benefit with CABG when compared to PCI. Among patients undergoing CABG, there did not appear to be any 5-year benefits from multi-arterial grafting. CONCLUSIONS: Despite longer hospitalization and higher rate of nonhome discharge, CABG was associated with improved late survival over PCI in the elderly population. Cardiac surgeons should be included in the multidisciplinary evaluation of older patients with MVCAD.

Fate of the Kidneys in Patients with Post-Operative Renal Failure After Cardiac Surgery.

BACKGROUND: This study evaluates the clinical and renal-related outcomes in patients with acute renal failure (ARF) following cardiac surgery. METHODS: Index adult cardiac operations at a single institution from 2010-2018 were reviewed. Patients requiring dialysis pre-operatively were excluded. ARF was stratified as either creatinine rise (≥3-times baseline or ≥4.0 mg/dL) or post-operative dialysis. Outcomes included mortality, rates of progression to dialysis, and renal recovery. Multivariable Cox regression was used for risk-adjustment. RESULTS: A total of 10,037 patients, including 6,275 (62.5%) isolated coronary artery bypass grafting (CABG), 2,243 (22.3%) isolated valve, and 1,519 (15.1%) CABG plus valve cases, were included. Post-operative ARF occurred in 346 (3.5%) patients, with 230 (66.5%) requiring dialysis. Survival was significantly reduced in patients with ARF at 30-days (97.9 versus 70.8%, P <0.001), 1-year (94.9 versus 48.0%, P <0.001), and 5-years (86.2 versus 38.2%, P <0.001) with more profound reductions in those requiring dialysis, findings which persisted after risk-adjustment. Progression to subsequent dialysis in the creatinine rise group was rare (n = 1). The median time to dialysis initiation in the dialysis group was 5 days (IQR 2-12 days) with a median time of dialysis dependence of 72 days (IQR 38-1229 days). Of those patients requiring postoperative dialysis, 30.9% demonstrated renal recovery. CONCLUSIONS: Post-operative ARF and in particular the need for dialysis are associated with substantial reductions in survival that persist during longitudinal follow-up. This occurs despite the finding that patients experiencing creatinine rise only rarely progress to dialysis, and that nearly one-third of patients requiring post-operative dialysis recover renal function.

HVAD versus heartmate III bridge to heart transplantation: Waitlist and posttransplant outcomes.

BACKGROUND: This study compared outcomes of patients bridged with either the Heartware HVAD or Heartmate 3 (HM3) device to orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing registry was queried to perform two separate analyses of adult, isolated OHT candidates bridged with HVAD or HM3. First, waitlist outcomes were compared among patients waitlisted 1/1/2015-3/20/2020. Second, posttransplant survival was compared among those transplanted 1/1/2015-3/20/2020. RESULTS: Two thousand two hundred fifty-five candidates were waitlisted within the study period, 1587 (70.4%) bridged with HVAD and 668 (29.6%) with HM3. At 1 year from waitlisting, cumulative incidence of OHT higher in the HVAD cohort (p < .001). During the same time period, 2643 patients underwent OHT, 2154 (81.5%) with prior HVAD and 489 (18.5%) with HM3. Yearly proportions of patients bridged with HM3 increased across the study period and decreased for HVAD (p < .001). HM3-bridged recipients had shorter waitlist times, longer graft cold ischemic times, and experienced a higher rate of posttransplant dialysis requirement. Unadjusted and risk-adjusted posttransplant mortality rates were similar between both groups. CONCLUSIONS: Posttransplant survival is equivalent regardless of device type used for bridging. However, HM3 patients had lower likelihood of reaching transplantation, which may be a reflection of the recent heart allocation policy changes.

Early T Cell Activation Metrics Predict Graft-versus-Host Disease in a Humanized Mouse Model of Hematopoietic Stem Cell Transplantation.

Acute graft-versus-host disease (GVHD) is a frequent complication of hematopoietic transplantation, yet patient risk stratification remains difficult, and prognostic biomarkers to guide early clinical interventions are lacking. We developed an approach to evaluate the potential of human T cells from hematopoietic grafts to produce GVHD. Nonconditioned NBSGW mice transplanted with titrated doses of human bone marrow developed GVHD that was characterized by widespread lymphocyte infiltration and organ pathology. Interestingly, GVHD was not an inevitable outcome in our system and was influenced by transplant dose, inflammatory status of the host, and type of graft. Mice that went on to develop GVHD showed signs of rapid proliferation in the human T cell population during the first 1-3 wk posttransplant and had elevated human IFN-γ in plasma that correlated negatively with the expansion of the human hematopoietic compartment. Furthermore, these early T cell activation metrics were predictive of GVHD onset 3-6 wk before phenotypic pathology. These results reveal an early window of susceptibility for pathological T cell activation following hematopoietic transplantation that is not simply determined by transient inflammation resulting from conditioning-associated damage and show that T cell parameters during this window can serve as prognostic biomarkers for risk of later GVHD development.

Safety and benefit of ad libitum feeding following laparoscopic pyloromyotomy: retrospective comparative trial.

PURPOSE: In this study, we evaluated the impacts of ad libitum feedings on outcomes following laparoscopic pyloromyotomy in patients with infantile hypertrophic pyloric stenosis. METHODS: Pediatric patients with infantile hypertrophic pyloric stenosis who underwent laparoscopic pyloromyotomy were included. Patients were stratified into ad libitum and structured feeding groups. Primary outcomes were times from surgery completion to goal feeding and discharge. RESULTS: A total of 336 patients were included in the study with 63 patients (18.8%) in the ad libitum feeding group. The ad libitum feeding group experienced significantly shorter times from surgery completion to both goal feedings (10.7 h vs 18.7 h; p < 0.001) and hospital discharge (21.6 h vs 23.1 h; p = 0.008) compared to the structured protocol group. Postoperative emesis (47.% vs 30.8%; p = 0.011) was higher in the ab libitum cohort, but the rates of return to an emergency department and/or readmission (4.8% vs 2.2%; p = 0.26) were similar. CONCLUSION: Ad libitum feeding after pyloromyotomy decreases time to reach goal feeding and hospital discharge. While it may contribute to a higher incidence of emesis, it does not appear to significantly increase hospital readmission. Ad libitum feeding appears to be a safe and beneficial alternative to structured feeding protocols following pyloromyotomy. LEVEL OF EVIDENCE: III.

Geographic disparities in heart transplantation persist under the new allocation policy.

BACKGROUND: This study evaluated the impact of the 2018 heart allocation policy change on geographic disparities in United States orthotopic heart transplantation (OHT). METHODS: The United Network for Organ Sharing registry was queried to measure geographic disparity in OHT rates between pre-policy and post-policy change eras. We performed multilevel Poisson regression to measure region-level OHT rates. We derived an allocation priority-adjusted median incidence rate ratio (MIRR) for each policy era, a measure of median change in OHT rates between regions. RESULTS: 5958.78 waitlist person-years were analyzed, comprising 6596 OHT procedures (3890 pre-policy and 2706 post-policy). Median region-level OHT rate was .94 transplants/person-years before and 1.51 transplants/person-years after the policy change (P < .001). The unadjusted OHT MIRR across regions was 1.29 (95% CI 1.00-1.50) pre-policy change and 1.17 (95% CI 1.00-1.43) post-policy change, suggesting that the region-related variance in OHT rates decreased under the new allocation. After adjustment for allocation priority risk factors, the MIRR pre-policy change was 1.13 (95% CI 1.01-1.32) and post-policy change was 1.15 (95% CI 1.00-1.35). CONCLUSIONS: Geography accounts for ∼10% of the disparity among United States OHT rates. Despite broader heart sharing, the updated allocation policy did not substantially alter the existing geographic disparities among OHT recipients.

Utilization and outcomes of postcardiotomy mechanical circulatory support.

BACKGROUND: This study evaluated the utilization and outcomes of postcardiotomy mechanical circulatory support (MCS). METHODS: This was a retrospective, single institution analysis of adult cardiac surgery cases that required de novo MCS following surgery from 2011 to 2018. Patients that were bridged with MCS to surgery were excluded. The primary outcomes were early operative mortality and longitudinal survival. Secondary outcomes included postoperative complications, and 5-year all-cause readmission. RESULTS: Five hundred and thirty-three patients required de novo postcardiotomy MCS, with the most commonly performed procedure being isolated coronary artery bypass grafting (29.8%). Median cardiopulmonary bypass and cross-clamp times were 185 (IQR 123-260) min and 122 (IQR 81-179) min, respectively. A total of 442 (82.9%) of patients were supported with intra-aortic balloon pump counterpulsation, 23 (4.3%) with an Impella device, and 115 (21.6%) with extracorporeal membrane oxygenation. Three (0.6%) patients had an unplanned ventricular assist device placed. Operative mortality was 29.8%. Longitudinal survival was 56.1% and 43.0% at 1 and 5 years, respectively. Survival was lowest in those supported with ECMO and highest with those supported with an Impella (p < 0.001). Freedom from readmission was 61.4% at 5 years. Postoperative ECMO was an independent predictor of mortality (HR 5.1, 95% CI 2.0-12.9, p < 0.001), but none of the MCS types predicted long-term hospital readmission after risk adjustment. CONCLUSIONS: Postcardiotomy MCS is associated with high operative mortality. Even patients that survive to discharge have compromised longitudinal survival, with nearly only half surviving to 1 year. Close follow-up and early referral to advanced heart failure specialists may be prudent in improving these outcomes.

Impact of various sizing metrics on female donor to male recipient heart transplant outcomes.

BACKGROUND: This study evaluated the impact of various sizing metrics on outcomes of female donor to male recipient orthotopic heart transplantation (OHT). METHODS: We queried the United Network of Organ Sharing database to analyze all isolated, primary adult OHTs from January 1, 2010 to January 20, 020. Patients were stratified by donor-recipient sex pairing. Logistic regression was used to investigate risk-adjusted effects of current size matching criteria (weight ratio, body mass index [BMI] ratio, predicted heart mass [pHM] ratio) on 1-year posttransplant mortality. Kaplan-Meier analysis was used to compare posttransplant survival among cohorts. RESULTS: A total of 22,450 patients were analyzed, of which 3019 (13.4%) underwent female-to-male transplantation. Of sex-matched pairs, female-to-male donation had the lowest proportion of undersized hearts using weight and BMI ratio metrics (10.5% and 5.2%) but had the highest proportion of undersizing using pHM metrics (48.1%) (all p < 0.001). Female-to-male recipients had the lowest rate of unadjusted 1-year survival (90.0%, p = 0.0169), and increased hazards of mortality after risk adjustment (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.01-1.36, p = 0.034). Undersizing using pHM (donor-recipient ratio <0.85) was the only metric found to be associated in increased mortality after risk adjustment (OR: 1.32, 95% CI: 1.02-1.71, p = 0.035). CONCLUSION: Female-to-male heart transplantation has the worst survival of all sex-matching combinations. Although female donors in this cohort are appropriately sized using traditional metrics, half are under-sized using pHM. This, combined with its strong association with mortality, underscores the importance of routine pHM assessment when evaluating female donors for male recipients.

Preoperative troponin levels and outcomes of coronary surgery following myocardial infarction.

BACKGROUND: This study evaluates the impact of peak preoperative troponin level on outcomes of coronary artery bypass grafting (CABG) for non-ST-elevation myocardial infarction (NSTEMI). METHODS: This was a retrospective review of patients undergoing isolated CABG from 2011 to 2018 with the presentation of NSTEMI. Patients were stratified into low- and high-risk groups based on median preoperative peak troponin (1.95 ng/dl). Major adverse cardiac and cerebrovascular events (MACCE) and mortality were compared. Multivariable analysis was performed to model risk factors for MACCE and mortality. RESULTS: This study included 1211 patients, 607 low-risk (≤1.95 ng/dl) and 604 high-risk (>1.95 ng/dl). Patients were well-matched with respect to age and comorbidity. High-risk patients had lower median preoperative ejection fraction (46.5% [interquartile range {IQR}: 35.0%-55.0%] vs. 53.0% [IQR: 40.0%-58.0%]) and higher incidence of preoperative intra-aortic balloon pump (15.9% vs. 8.73%). Intensive care unit and hospital length of stay were longer in the high-risk group, but increasing troponin level was not associated with prolonged intensive care or hospital length of stay (>4 and >14 days, respectively) after risk adjustment. Postoperative complications and 30-day, 1- and 5-year rates of both MACCE and survival were similar between groups. Peak troponin greater than 1.95 ng/dl was not associated with increased hazards for MACCE, mortality, or readmission in multivariable modeling. In subanalysis, neither increasing troponin as a continuous variable nor peak troponin greater than 10.00 ng/ml were associated with increased hazards for these outcomes. CONCLUSIONS: Preoperative troponin levels do not appear to be predictive of short- or long-term outcomes following CABG, and clinical decisions regarding surgical revascularization should not be dictated by these measurements.

Changes in multiorgan heart transplants following the 2018 allocation policy change.

BACKGROUND: This study evaluated the impact of the heart allocation policy change in 2018 on the characteristics and outcomes of multiorgan transplants involving heart allografts. METHODS: Adults undergoing multiorgan heart transplantation from 2010 to 2020 were identified from the United Network for Organ Sharing (UNOS) registry. Transplants were stratified into occurring before versus after the October 2018 heart allocation change. The primary outcome was 1-year survival following transplantation. A Cox proportional hazards model was used to evaluate the risk-adjusted effect of the allocation policy change on outcomes between cohorts. RESULTS: A total of 1832 patients underwent multiorgan heart transplantation during the study period with 245 (13.37%) undergoing heart-lung transplantation, 244 (13.32%) undergoing heart-liver transplantation, and 1343 (73.31%) undergoing heart-kidney transplantation. There was a higher utilization of temporary MCSDs as well as longer ischemic times for all three types of transplantation following the policy change. Heart-lung and heart-liver recipients had a similar 1-year survival before and after the policy change (each p > .05). Renal failure requiring dialysis (29.5% vs. 39.4%, p = .001) as well as 1-year survival (88% vs. 82%; log-rank p = .01) were worse in the heart-kidney cohort after the organ allocation system modification. CONCLUSIONS: This study demonstrates similar trends in multiorgan transplants as has been observed in isolated heart transplants following the allocation change, including more frequent utilization of temporary mechanical support and longer ischemic times. Although outcomes have remained comparable in the new allocation era with heart-lung and heart-liver transplants, heart-kidney recipients have a worse 1-year survival following the change.

Impact of center donor acceptance patterns on utilization of extended-criteria donors and outcomes.

BACKGROUND: This study investigated the impact of transplanting center donor acceptance patterns on usage of extended-criteria donors (ECDs) and posttransplant outcomes following orthotopic heart transplantation (OHT). METHODS: The Scientific Registry of Transplant Recipients was queried to identify heart donor offers and adult, isolated OHT recipients in the United States from January 1, 2013 to October 17, 2018. Centers were stratified into three equal-size terciles based on donor heart acceptance rates (<13.7%, 13.7%-20.2%, >20.2%). Overall survival was compared between recipients of ECDs (≥40 years, left ventricular ejection fraction [LVEF] <60%, distance ≥500 miles, hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV], or ≥50 refusals) and recipients of traditional-criteria donors, and among transplanting terciles. RESULTS: A total of 85,505 donor heart offers were made to 133 centers with 15,264 (17.9%) accepted for OHT. High-acceptance programs (>20.2%) more frequently accepted donors with LVEF <60%, HIV, HCV, and/or HBV, ≥50 offers, or distance >500 miles from the transplanting center (each p < .001). Posttransplant survival was comparable across all three terciles (p = .11). One- and five-year survival were also similar across terciles when examining recipients of all five ECD factors. Acceptance tier and increasing acceptance rate were not found to have any impact on mortality in multivariable modeling. Of ECD factors, only age ≥40 years was found to have increased hazards for mortality (hazard ratio, 1.33; 95% confidence interval [CI], 1.22-1.46; p < .001). CONCLUSIONS: Of recipients of ECD hearts, outcomes are similar across center-acceptance terciles. Educating less aggressive programs to increase donor acceptance and ECD utilization may yield higher national rates of OHT without major impact on outcomes.

Gastrointestinal complications after cardiac surgery: Incidence, predictors, and impact on outcomes.

BACKGROUND: The purpose of this study was to investigate the incidence, predictors, and long-term impact of gastrointestinal (GI) complications following adult cardiac surgery. METHODS: Index Society of Thoracic Surgeons (STS) adult cardiac operations performed between January 2010 and February 2018 at a single institution were included. Patients were stratified by the occurrence of postoperative GI complications. Outcomes included early and late survival as well as other associated major postoperative complications. A subanalysis of propensity score-matched patients was also performed. RESULTS: A total of 10,285 patients were included, and the overall rate of GI complications was 2.4% (n = 246). Predictors of GI complications included dialysis dependency, intra-aortic balloon pump, congestive heart failure, chronic obstructive pulmonary disease, and longer aortic cross-clamp times. Thirty-day (2.6% vs. 24.8%), 1- (6.3% vs. 41.9%), and 3-year (11.1% vs. 48.4%) mortality were substantially higher in patients who experienced GI complications (all p < .001). GI complication was associated with a threefold increased hazard for mortality (hazard ratio = 3.1, 95% confidence interval = 2.6-3.7) after risk adjustment, and there was an association between the occurrence of GI complications and increased rates of renal failure (39.4% vs. 2.5%), new dialysis dependency (31.3% vs. 1.5%), multisystem organ failure (21.5% vs .1.0%), and deep sternal wound infections (2.6% vs. 0.2%; all p < .001). These results persisted in propensity-matched analysis. CONCLUSION: GI complications are infrequent but have a profound impact on early and late survival, and often occur in association with other major complications. Risk factor modification, heightened awareness, and early detection and management of GI complications appear warranted.

The predictive value of preimplant pulmonary function testing in LVAD patients.

BACKGROUND: The predictive value of preoperative pulmonary function testing (PFT) in left ventricular assist device (LVAD) patients remains unknown. This study evaluates the relationship between abnormal PFTs and postimplant outcomes in LVAD patients. METHODS: LVAD implants from January 2004 to December 2018 at a single institution were included. Patients were stratified based on the presence of abnormal preoperative PFTs, and the primary outcome was respiratory adverse events (AE). Secondary outcomes included 1-year overall postimplant survival, and complications including bleeding, renal failure, thromboembolism, and device malfunction. RESULTS: The total of 333 patients underwent LVAD implant, 46.5% (n = 155) with normal PFTs and 53.5% (n = 178) with abnormal PFTs. Patients with abnormal PFTs were noted to have higher rates of respiratory AEs (25.9% vs. 15.1%, p = .049). In multivariable analysis, the impact of PFTs was most significant when forced expiratory volume in 1 s/forced expiratory volume (FEV1/FVC) ratio was less than 0.5 (hazard ratio [HR] 16.32, 95% confidence interval [CI], 1.70-156.78). The rates of other AEs including bleeding, renal failure, right heart failure, and device malfunction were similar. One-year overall postimplant survival was comparable between the groups (56.8% vs. 68.8%, p = .3183), though patients in the lowest strata of FEV1 (<60% predicted) and FEV1/FVC (<0.5) had elevated risk-adjusted hazards for mortality (HR 2.63, 95% CI, 1.51-4.60 and HR 18.92, 95% CI, 2.10-170.40, respectively). CONCLUSIONS: The presence of abnormal preoperative PFTs is not prohibitory for LVAD implantation although it can be used for risk stratification for respiratory AEs and mortality, particularly in patients with severely reduced metrics. The importance of careful patient selection should be underscored in this higher risk patient subset.

Twenty-year survival following orthotopic heart transplantation in the United States.

BACKGROUND: This study evaluated 20-year survival after adult orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing Registry database was queried to study adult OHT recipients between 1987 and 1998 with over 20-year posttransplant follow-up. The primary and secondary outcomes were 20-year survival and cause of death after OHT, respectively. Multivariable logistic regression was used to identify significant independent predictors of long-term survival, and long-term survival was compared among cohorts stratified by number of predictors using Kaplan Meier survival analysis. RESULTS: 20,658 patients undergoing OHT were included, with a median follow-up of 9.0 (IQR, 3.2-15.4) years. Kaplan-Meier estimates of 10-, 15-, and 20-year survival were 50.2%, 30.1%, and 17.2%, respectively. Median survival was 10.1 (IQR, 3.9-16.9) years. Increasing recipient age (>65 years), increasing donor age (>40 years), increasing recipient body mass index (>30), black race, ischemic cardiomyopathy, and longer cold ischemic time (>4 h) were adversely associated with a 20-year survival. Of these 6 negative predictors, presence of 0 risk factors had the greatest 10-year (59.7%) and 20-year survival (26.2%), with decreasing survival with additional negative predictors. The most common cause of death in 20-year survivors was renal, liver, and/or multisystem organ failure whereas graft failure more greatly impacted earlier mortality. CONCLUSIONS: This study identifies six negative preoperative predictors of 20-year survival with 20-year survival rates exceeding 25% in the absence of these factors. These data highlight the potential for very long-term survival after OHT in patients with end-stage heart failure and may be useful for patient selection and prognostication.

Extracorporeal membrane oxygenation bridge to heart transplant: Trends following the allocation change.

BACKGROUND: This study compared outcomes of patients bridged with extracorporeal membrane oxygenation (ECMO) to orthotopic heart transplantation (OHT) following the recent heart allocation policy change. METHODS: The United Network of Organ Sharing Registry (UNOS) database was queried to examine OHT patients between 2010 and 2020 that were bridged with ECMO. Waitlist outcomes and 1-year posttransplant survival were compared between patients waitlisted and/or transplanted before and after the heart allocation policy change. Secondary outcomes included posttransplant stroke, renal failure, and 1-year rejection. RESULTS: A total of 285 waitlisted patients were included, 173 (60.7%) waitlisted under the old policy and 112 (39.3%) under the new policy. New policy patients were more likely to receive OHT (82.2% vs. 40.6%), and less likely to be removed from the waitlist due to death or clinical deterioration (15.0% vs. 41.3%; both p < .001). A total of 165 patients bridged from ECMO to OHT were analyzed, 72 (43.6%) transplanted during the old policy and 93 (56.3%) under the new. Median waitlist time was reduced under the new policy (4 days [interquartile range {IQR}: 2-6] vs. 47 days [IQR: 10-228]). Postoperative renal failure was higher in the new policy group (23% vs. 6%; p = .002), but rates of stroke and 1-year acute rejection were equivalent. One-year survival was lower the new policy but was not significant (79.8% vs. 90.3%; p = .3917). CONCLUSIONS: The UNOS heart allocation policy change has resulted in decreased waitlist times and higher likelihood of transplant in patients supported with ECMO. Posttransplant 1-year survival has remained comparable although absolute rates are lower.

TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses.

Toll-like receptors play a central role in the initiation of adaptive immune responses with several TLR agonists acting as known B cell mitogens. Despite thousands of publications on TLRs, the function of TLR10 remains unknown. We have found that Ab-mediated engagement of TLR10 on primary human B cells suppresses B cell proliferation, cytokine production, and signal transduction. When challenged with either a T independent or T dependent Ag, TLR10 transgenic mice exhibit diminished Ab responses. Adoptive transfer of splenic B cells into B cell-deficient mice revealed that the suppressive effects on Ag-specific humoral immune responses are entirely B cell intrinsic. Our results demonstrate that TLR10 has a functional role within the B cell lineage that is distinct from that of other TLR family members and may provide a potential therapeutic target for diseases characterized by dysregulated B cell activity.