Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Ann Thorac Surg ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815846

ABSTRACT

BACKGROUND: Stroke affects surgical decision making and outcomes of neonatal cardiac surgery(CHS). We sought to assess the burden of stroke in this population from a large multi-center database. METHODS: We analyzed neonates undergoing CHS with cardiopulmonary bypass from the Pediatric Health Information System database(2004-2022). The cohort was divided into stroke-group which included pre/post-op ischemic, hemorrhagic-subtypes and grade III-IV intraventricular hemorrhages and compared in-hospital and follow-up outcomes to non-stroke group. RESULTS: Of 14,228 neonates, 800(5.6%) had a peri-operative stroke. Stroke-group was more likely to have hypoplastic left-heart syndrome (HLHS)(30.5% vs 20.7%), born pre-term(19.4% vs 11.7%), low-birthweight(17.8% vs 11.9%) and require ECMO(48.8% vs 13.8%)(all, p<0.001). Outcomes comparing stroke vs no-stroke were, mortality:33.1% vs 8.9%, non-home discharge:12.5% vs 6.9%, length of stay:41 vs 24 days, hospitalization-costs:$354,521 vs $180,489(all, p<0.05). Stroke increased odds of mortality by two-fold[OR 2.20(1.75-2.77), p<0.001] after adjusting for ECMO, prematurity among other significant factors. On follow-up, stroke-group had higher incidence of hydrocephalus(9.5% vs 1.3%), cerebral palsy (6.2% vs 1.3%), autism spectrum disorder(7.1% vs 3.5%) and had higher one- and five- year mortality among survivors of index admission(5.3% and 11.3% vs 3.3% and 5.9%, respectively) (all p<0.05). CONCLUSIONS: Neonatal CHS patients born prematurely, diagnosed with HLHS or those requiring ECMO are disproportionately affected by stroke. The occurrence of stroke is marked by significantly higher mortality. Future research should seek to identify factors leading to stroke, in order to increase rescue after stroke and for improvement of long-term outcomes.

2.
J Pediatr ; 268: 113955, 2024 May.
Article in English | MEDLINE | ID: mdl-38340889

ABSTRACT

OBJECTIVE: To assess rates of cardiac surgery and the clinical and demographic features that influence surgical vs nonsurgical treatment of congenital heart disease (CHD) in patients with trisomy 13 (T13) and trisomy 18 (T18) in the United States. STUDY DESIGN: A retrospective study was performed using the Pediatric Health Information System. All hospital admissions of children (<18 years of age) with T13 and T18 in the United States were identified from 2003 through 2022. International Classifications of Disease (ICD) codes were used to identify presence of CHD, extracardiac comorbidities/malformations, and performance of cardiac surgery. RESULTS: Seven thousand one hundred thirteen patients were identified. CHD was present in 62% (1625/2610) of patients with T13 and 73% (3288/4503) of patients with T18. The most common CHD morphologies were isolated atrial/ventricular septal defects (T13 40%, T18 42%) and aortic hypoplasia/coarctation (T13 21%, T18 23%). Single-ventricle morphologies comprised 6% (100/1625) of the T13 and 5% (167/3288) of the T18 CHD cohorts. Surgery was performed in 12% of patients with T13 plus CHD and 17% of patients with T18 plus CHD. For all cardiac diagnoses, <50% of patients received surgery. Nonsurgical patients were more likely to be born prematurely (P < .05 for T13 and T18). The number of extracardiac comorbidities was similar between surgical/nonsurgical patients with T13 (median 2 vs 2, P = .215) and greater in surgical vs nonsurgical patients with T18 (median 3 vs 2, P < .001). Hospital mortality was <10% for both surgical cohorts. CONCLUSIONS: Patients with T13 or T18 and CHD receive surgical palliation, but at a low prevalence (≤17%) nationally. Given operative mortality <10%, opportunity exists perhaps for quality improvement in the performance of cardiac surgery for these vulnerable patient populations.


Subject(s)
Cardiac Surgical Procedures , Heart Defects, Congenital , Trisomy 13 Syndrome , Trisomy 18 Syndrome , Humans , Retrospective Studies , United States/epidemiology , Female , Male , Heart Defects, Congenital/surgery , Heart Defects, Congenital/epidemiology , Cardiac Surgical Procedures/methods , Trisomy 18 Syndrome/surgery , Infant , Child, Preschool , Infant, Newborn , Child , Adolescent , Hospitalization/statistics & numerical data , Chromosomes, Human, Pair 18 , Trisomy , Chromosome Disorders/epidemiology
4.
J Heart Lung Transplant ; 43(1): 32-35, 2024 01.
Article in English | MEDLINE | ID: mdl-37619643

ABSTRACT

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18 year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.


Subject(s)
Lung Transplantation , Tissue and Organ Procurement , Humans , Child , United States , Adolescent , Death , Retrospective Studies , Tissue Donors , Graft Survival
5.
J Thorac Cardiovasc Surg ; 167(5): 1556-1563.e2, 2024 May.
Article in English | MEDLINE | ID: mdl-37414356

ABSTRACT

OBJECTIVES: Ventricular assist devices (VADs) are associated with a mortality benefit in children. Database-driven analyses have associated VADs with reduction of modifiable risk factors (MRFs), but validation with institutional data is required. The authors studied MRF reduction on VAD and the influence of persistent MRFs on survival after heart transplant. METHODS: All patients at the authors' institution requiring a VAD at transplant (2011-2022) were retrospectively identified. MRFs included renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2), hepatic dysfunction (total bilirubin ≥1.2 mg/dL), total parenteral nutrition dependence, sedatives, paralytics, inotropes, and mechanical ventilation. RESULTS: Thirty-nine patients were identified. At time of VAD implantation, 18 patients had ≥3 MRFs, 21 had 1 to 2 MRFs, and 0 had 0 MRFs. At time of transplant, 6 patients had ≥3 MRFs, 17 had 1 to 2 MRFs, and 16 had 0 MRFs. Hospital mortality occurred in 50% (3 out of 6) patients with ≥3 MRFs at transplant vs 0% of patients with 1 to 2 and 0 MRFs (P = .01 for ≥3 vs 1-2 and 0 MRFs). MRFs independently associated with hospital mortality included paralytics (1.76 [range, 1.32-2.30]), ventilator (1.59 [range, 1.28-1.97]), total parenteral nutrition dependence (1.49 [range, 1.07-2.07]), and renal dysfunction (1.31 [range, 1.02-1.67]). Two late mortalities occurred (3.6 and 5.7 y), both in patients with 1 to 2 MRFs at transplant. Overall posttransplant survival was significantly worse for ≥3 versus 0 MRFs (P = .006) but comparable between other cohorts (P > .1). CONCLUSIONS: VADs are associated with MRF reduction in children, yet those with persistent MRFs at transplant experience a high burden of mortality. Transplanting VAD patients with ≥3 MRFs may not be prudent. Time should be given on VAD support to achieve aggressive pre-transplant optimization of MRFs.


Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Kidney Diseases , Child , Humans , Heart-Assist Devices/adverse effects , Retrospective Studies , Heart Transplantation/adverse effects , Risk Factors , Heart Failure/diagnosis , Heart Failure/surgery , Treatment Outcome
6.
J Thorac Cardiovasc Surg ; 167(2): 422-430, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37385525

ABSTRACT

OBJECTIVE: To characterize national experience with surgical aortic valve repair in pediatric patients. METHODS: Patients in the Pediatric Health Information System database aged 17 years or younger with International Statistical Classification of Diseases and Related Health Problems codes for open aortic valve repair from 2003 to 2022 were included (n = 5582). Outcomes of reintervention during index admission (repeat repair, n = 54; replacement, n = 48; and endovascular intervention, n = 1), readmission (n = 2176), and in-hospital mortality (n = 178) were compared. A logistic regression was performed for in-hospital mortality. RESULTS: One-quarter (26%) of patients were infants. The majority (61%) were boys. Heart failure was present in 16% of patients, congenital heart disease in 73%, and rheumatic disease in 4%. Valve disease was insufficiency in 22% of patients, stenosis in 29%, and mixed in 15%. The highest quartile of centers by volume (median, 101 cases; interquartile range, 55-155 cases) performed half (n = 2768) of cases. Infants had the highest prevalence of reintervention (3%; P < .001), readmission (53%; P < .001), and in-hospital mortality (10%; P < .001). Previously hospitalized patients (median, 6 days; interquartile range, 4-13 days) were at higher risk for reintervention (4%; P < .001), readmission (55%; P < .001), and in-hospital mortality (11%; P < .001), as were patients with heart failure (reintervention [6%; P < .001], readmission [42%; P = .050], and in-hospital mortality [10%; P < .001]). Stenosis was associated with reduced reintervention (1%; P < .001) and readmission (35%; P = .002). The median number of readmissions was 1 (range, 0-6) and time to readmission was 28 days (interquartile range, 7-125 days). A regression of in-hospital mortality identified heart failure (odds ratio, 3.05; 95% CI, 1.59-5.49), inpatient status (odds ratio, 2.40; 95% CI, 1.19-4.82), and infancy (odds ratio, 5.70; 95% CI, 2.60-12.46) as significant. CONCLUSIONS: The Pediatric Health Information System cohort demonstrated success with aortic valve repair; however, early mortality remains high in infants, hospitalized patients, and patients with heart failure.


Subject(s)
Aortic Valve Stenosis , Health Information Systems , Heart Failure , Transcatheter Aortic Valve Replacement , Male , Infant , Humans , Child , Female , Aortic Valve/surgery , Aortic Valve/abnormalities , Aortic Valve Stenosis/surgery , Constriction, Pathologic/surgery , Treatment Outcome , Heart Failure/surgery , Patient Readmission , Risk Factors
8.
Transplantation ; 108(3): 750-758, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38062571

ABSTRACT

BACKGROUND: With rates of potential donor heart discard as high as 66% nationally, quality improvement efforts must seek to optimize donor utilization. Whether the timing of donor brain death declaration (BDD) influences organ acceptance is understudied. The authors sought to characterize the impacts of time between donor hospital admission and BDD on heart utilization and posttransplant outcomes. METHODS: All potential heart donors and recipients in the United Network for Organ Sharing database were identified (2006-2021). Admission-to-BDD cohorts were: 1 to 2 d (n = 52 469), 3 to 4 d (n = 44 033), 5 to 7 d (n = 24 509), and 8 to 10 d (n = 8576). Donor clinical characteristics were compared between cohorts, and donor acceptance was assessed using multivariable binary logistic regression. Recipient posttransplant survival was assessed with the Kaplan-Meier method. RESULTS: Donor demographics and comorbidity profiles (diabetes and hypertension) were comparable across cohorts. Anoxia/overdose deaths were more common (10% > 21% > 24% > 18%, respectively) and cardiopulmonary resuscitation requirements were higher (37% > 52% > 58% > 47%) when BDD occurred longer after admission. Renal dysfunction (44% > 44% > 35% > 29%) and inotrope requirements (52% > 25% > 36% > 29%) were lower in the later BDD cohorts. Proportions of hepatic dysfunction (18%-21%) and left ventricular ejection fraction <50% (13%-16%) were clinically equivalent. Donor acceptance differed by admission-to-BDD cohort (36% [1-2 d], 34% [3-4 d], 30% [5-7 d], and 28% [8-10 d]). Admission-to-BDD >4 d was independently associated with lower odds of acceptance on multivariable analysis (odds ratio 0.79, P < 0.001). Recipients experienced equivalent posttransplant survival for all donor admission-to-BDD cohorts ( P = 0.999 adults and P = 0.260 pediatrics). CONCLUSIONS: Heart donors with later BDD were disproportionately discarded despite similar-to-favorable overall clinical profiles, resulting in nearly 3000 fewer transplants during the study. Increased utilization of donors with later BDD and "high-risk" characteristics (eg, anoxia/overdose, cardiopulmonary resuscitation requirement) can improve rates of transplantation without compromising outcomes.


Subject(s)
Drug Overdose , Heart Transplantation , Tissue and Organ Procurement , Adult , Humans , Child , Tissue Donors , Stroke Volume , Brain Death , Ventricular Function, Left , Hypoxia , Retrospective Studies
9.
J Heart Lung Transplant ; 43(3): 461-470, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37863451

ABSTRACT

BACKGROUND: Recently, several centers in the United States have begun performing donation after circulatory death (DCD) heart transplants (HTs) in adults. We sought to characterize the recent use of DCD HT, waitlist time, and outcomes compared to donation after brain death (DBD). METHODS: Using the United Network for Organ Sharing database, 10,402 adult (aged >18 years) HT recipients from January 2019 to June 2022 were identified: 425 (4%) were DCD and 9,977 (96%) were DBD recipients. Posttransplant outcomes in matched and unmatched cohorts and waitlist times were compared between groups. RESULTS: DCD and DBD recipients had similar age (57 years for both, p = 0.791). DCD recipients were more likely White (67% vs 60%, p = 0.002), on left ventricular assist device (LVAD; 40% vs 32%, p < 0.001), and listed as status 4 to 6 (60% vs 24%, p < 0.001); however, less likely to require inotropes (22% vs 40%, p < 0.001) and preoperative extracorporeal membrane oxygenation (0.9% vs 6%, p < 0.001). DCD donors were younger (29 vs 32 years, p < 0.001) and had less renal dysfunction (15% vs 39%, p < 0.001), diabetes (1.9% vs 3.8%, p = 0.050), or hypertension (9.9% vs 16%, p = 0.001). In matched and unmatched cohorts, early survival was similar (p = 0.22). Adjusted waitlist time was shorter in DCD group (21 vs 31 days, p < 0.001) compared to DBD cohort and 5-fold shorter (DCD: 22 days vs DBD: 115 days, p < 0.001) for candidates in status 4 to 6, which was 60% of DCD cohort. CONCLUSIONS: The community is using DCD mostly for those recipients who are expected to have extended waitlist times (e.g., durable LVADs, status >4). DCD recipients had similar posttransplant early survival and shorter adjusted waitlist time compared to DBD group. Given this early success, efforts should be made to expand the donor pool using DCD, especially for traditionally disadvantaged recipients on the waitlist.


Subject(s)
Heart Transplantation , Tissue and Organ Procurement , Adult , Humans , Tissue Donors , Brain Death , Time Factors , Graft Survival , Retrospective Studies , Death
10.
Ann Thorac Surg ; 117(3): 611-618, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37271442

ABSTRACT

BACKGROUND: In pediatric heart transplantation, surgeons historically avoided donors requiring cardiopulmonary resuscitation (CPR), despite evidence that donor CPR does not change posttransplant survival (PTS). This study sought to determine whether CPR duration affects PTS. METHODS: All potential brain-dead donors aged <40 years from 2001 to 2021 consented for heart procurement were identified in the United Network for Organ Sharing database (n = 54,671). Organ acceptance was compared by CPR administration and duration. All recipients aged <18 years with donor CPR data were then identified (n = 5680). Survival analyses were conducted using increasing CPR duration as a cut point to identify the shortest duration beyond which PTS worsened. Additional analyses were performed with multivariable and cubic spline regression. RESULTS: Fifty-one percent of donors (28,012 of 54,671) received CPR. Donor acceptance was lower after CPR (54% vs 66%; P < .001) and across successive quartiles of CPR duration (P < .001). Of the transplant recipients, 48% (2753 of 5680) belonged to the no-CPR group, and 52% (2927 of 5680) belonged to the CPR group. Kaplan-Meier analyses of CPR duration attained significance at 55 minutes, after which PTS worsened (11.1 years vs 9.2 years; P = .025). There was no survival difference between the CPR ≤55 minutes group and the no-CPR group (11.1 years vs 11.2 years; P = .571). A cubic spline regression model confirmed that PTS worsened at more than 55 minutes of CPR. A Cox regression demonstrated that CPR >55 minutes predicted worsened PTS relative to no CPR (HR, 1.51; P = .007) but CPR ≤55 minutes did not (HR, 1.01; P = .864). CONCLUSIONS: Donor CPR decreases organ acceptance for transplantation; however, shorter durations (≤55 minutes) had equivalent PTS when controlling for other risk factors.


Subject(s)
Cardiopulmonary Resuscitation , Heart Transplantation , Humans , Child , Cardiopulmonary Resuscitation/adverse effects , Tissue Donors , Time Factors , Survival Analysis , Graft Survival , Retrospective Studies , Treatment Outcome
11.
Article in English | MEDLINE | ID: mdl-37774778

ABSTRACT

OBJECTIVE: Many pediatric Fontan patients require heart transplant, but this cohort is understudied given the difficulty in identifying these patients in national registries. We sought to characterize survival post-transplant in a large cohort of pediatric patients undergoing the Fontan. METHODS: The United Network for Organ Sharing and Pediatric Health Information System were used to identify Fontan heart transplant recipients aged less than 18 years (n = 241) between 2005 and 2022. Decompensation was defined as the presence of extracorporeal membrane oxygenation, ventilation, hepatic/renal dysfunction, paralytics, or total parenteral nutrition at transplant. RESULTS: Median age at transplant was 9 (interquartile range, 5-12) years. Median waitlist time was 107 (37-229) days. Median volume across 32 center was 8 (3-11) cases. Approximately half (n = 107, 45%) of recipients had 1A/1 initial listing status. Sixty-four patients (28%) were functionally impaired at transplant, 10 patients (4%) were ventilated, and 18 patients (8%) had ventricular assist device support. Fifty-nine patients (25%) had hepatic dysfunction, and 15 patients (6%) had renal dysfunction. Twenty-one patients (9%) were dependent on total parenteral nutrition. Median postoperative stay was 24 (14-46) days, and in-hospital mortality was 7%. Kaplan-Meier analysis showed 1- and 5-year survivals of 89% (95% CI, 85-94) and 74% (95% CI, 81-86), respectively. Kaplan-Meier of Fontan patients without decompensation (n = 154) at transplant demonstrated 1- and 5-year survivals of 93% (95% CI, 88-97) and 88% (95% CI, 82-94), respectively. In-hospital mortality was higher in decompensated patients (11% vs 4%, P = .023). Multivariable analysis showed that decompensation predicted worse post-transplant survival (hazard ratio, 2.47; 95% CI, 1.16-5.22; P = .018), whereas older age at transplant predicted superior post-transplant survival (hazard ratio, 0.89/year; 95% CI, 0.80-0.98; P = .019). CONCLUSIONS: Pediatric Fontan post-transplant outcomes are promising, although early mortality remains high. For nondecompensated pediatric patients at transplant without end-organ disease (>63% of cohort), early mortality is circumvented and post-transplant survival is excellent and similar to all pediatric transplantation.

14.
Pediatr Cardiol ; 2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36811659

ABSTRACT

Patients with heterotaxy syndrome and congenital heart disease (CHD) experience inferior cardiac surgical outcomes. Heart transplantation outcomes are understudied, however, particularly compared to non-CHD patients. Data from UNOS and PHIS were used to identify 4803 children (< 18 years) undergoing first-time heart transplant between 2003 and 2022 with diagnoses of heterotaxy (n = 278), other-CHD (n = 2236), and non-CHD cardiomyopathy (n = 2289). Heterotaxy patients were older (median 5 yr) and heavier (median 17 kg) at transplant than other-CHD (median 2 yr and 12 kg), and younger and lighter than cardiomyopathy (median 7 yr and 24 kg) (all p < 0.001). UNOS status 1A/1 at listing was not different between groups (65-67%; p = 0.683). At transplant, heterotaxy and other-CHD patients had similar rates of renal dysfunction (12 and 17%), inotropes (10% and 11%), and ventilator-dependence (19 and 18%). Compared to cardiomyopathy, heterotaxy patients had comparable renal dysfunction (9%, p = 0.058) and inotropes (46%, p = 0.097) but more hepatic dysfunction (17%, p < 0.001) and ventilator-dependence (12%, p = 0.003). Rates of ventricular assist device (VAD) were: heterotaxy-10%, other-CHD-11% (p = 0.839 vs. heterotaxy), cardiomyopathy-37% (p < 0.001 vs. heterotaxy). The 1-year incidence of acute rejection post-transplant was comparable between heterotaxy and others (p > 0.05). While overall post-transplant survival was significantly worse for heterotaxy than others (p < 0.05 vs. both), conditional 1-year survival was comparable (p > 0.3 vs. both). Children with heterotaxy syndrome experience inferior post-heart transplant survival, although early mortality appears to influence this trend, with 1-year survivors having equivalent outcomes. Given similar pre-transplant clinical status to others, heterotaxy patients are potentially under risk-stratified. Increased VAD utilization and pre-transplant end-organ function optimization may portend improved outcomes.

16.
Pediatr Transplant ; 27(1): e14414, 2023 02.
Article in English | MEDLINE | ID: mdl-36261871

ABSTRACT

BACKGROUND: Both gender- and weight-matching between donor and recipient are thought to impact survival in pediatric heart transplantation, with clinical dogma holding that male donor hearts and "ideal" weight-matching yield superior survival. The composite impacts of gender and weight on post-transplant survival (PTS) are understudied. METHODS: All pediatric (age <18) heart recipients between 1989 and 2021 with the complete recipient and donor gender and weight data were identified in the United Network for Organ Sharing database. Patients were grouped by recipient-donor gender (M & F) and donor-to-recipient weight ratio (DRWR; undersized [<0.8], ideal-sized [0.8-1.5], oversized [>1.5]). RESULTS: A total of 10 697 patients were identified. Among male recipients, PTS was greatest with oversized DRWR from either male or female donors (median 22.4 and 20.6 years; p < .001 vs. others) and lowest for undersized DRWR from either male or female donors (median 13.4 and 13.2 years; p < .001 vs. others). The majority (64%) of male recipients received ideal-sized DRWR, among which female donor hearts yielded superior survival to males (median 18.9 vs. 17.4 years, p = .014). No differences in PTS existed for female recipients on the basis of gender-match, DRWR, and gender/DRWR together (all p > .1). CONCLUSIONS: When considered together, gender and DRWR pairings impact PTS in male-but not female-pediatric heart transplant recipients. For males receiving ideal-sized DRWR organs (most common pairing, >60%), male recipients achieve superior survival when female donor hearts are transplanted. These findings suggest that if weight is being used for size-matching, donor gender should also be considered, particularly for male recipients.


Subject(s)
Heart Transplantation , Tissue Donors , Humans , Child , Male , Retrospective Studies , Heart , Transplant Recipients , Graft Survival
18.
Pediatr Transplant ; 27(3): e14433, 2023 05.
Article in English | MEDLINE | ID: mdl-36345131

ABSTRACT

BACKGROUND: Mechanical ventilation prior to pediatric heart transplantation predicts inferior post-transplant survival, but the impact of ventilation duration on survival is unclear. METHODS: Data from the United Network for Organ Sharing and Pediatric Health Information System were used to identify pediatric (<18 years) heart transplant recipients from 2003 to 2020. Patients ventilated pretransplant were first compared to no ventilation, then ventilation durations were compared across quartiles of ventilation (≤1 week, 8 days-5 weeks, >5 weeks). RESULTS: At transplant, 11% (511/4506) of patients required ventilation. Ventilated patients were younger, had more congenital heart disease, more urgent listing-status, and greater rates of nephropathy, TPN-dependence, and inotrope and ECMO requirements (p < .001 for all). Post-transplant, previously ventilated patients experienced longer ventilation durations, ICU and hospital stays, and inferior survival (all p < .001). Hospital outcomes and survival worsened with longer pretransplant ventilation. One-year and overall survival were similar between the no-ventilation and ≤1 week groups (p = .703 & p = .433, respectively) but were significantly worse for ventilation durations >1 week (p < .001). On multivariable analysis, ventilation ≤1 week did not predict mortality (HR 0.98 [95% CI 0.85-1.43]), whereas ventilation >1 week did (HR: 1.18 [1.01-1.39]). CONCLUSIONS: Longer pretransplant ventilation portends worse outcomes, although only ventilation >1 week predicts mortality. These findings can inform pretransplant prognostication.


Subject(s)
Health Information Systems , Heart Transplantation , Humans , Child , Respiration, Artificial , Length of Stay , Time Factors , Retrospective Studies , Treatment Outcome
19.
Mol Biochem Parasitol ; 238: 111291, 2020 07.
Article in English | MEDLINE | ID: mdl-32479776

ABSTRACT

In free-living and parasitic nematodes, the methylation of phosphoethanolamine to phosphocholine provides a key metabolite to sustain phospholipid biosynthesis for growth and development. Because the phosphoethanolamine methyltransferases (PMT) of nematodes are essential for normal growth and development, these enzymes are potential targets of inhibitor design. The pine wilt nematode (Bursaphelenchus xylophilus) causes extensive damage to trees used for lumber and paper in Asia. As a first step toward testing BxPMT1 as a potential nematicide target, we determined the 2.05 Å resolution x-ray crystal structure of the enzyme as a dead-end complex with phosphoethanolamine and S-adenosylhomocysteine. The three-dimensional structure of BxPMT1 served as a template for site-directed mutagenesis to probe the contribution of active site residues to catalysis and phosphoethanolamine binding using steady-state kinetic analysis. Biochemical analysis of the mutants identifies key residues on the ß1d-α6 loop (W123F, M126I, and Y127F) and ß1e-α7 loop (S155A, S160A, H170A, T178V, and Y180F) that form the phosphobase binding site and suggest that Tyr127 facilitates the methylation reaction in BxPMT1.


Subject(s)
Ethanolamines/chemistry , Helminth Proteins/chemistry , Methyltransferases/chemistry , Nematoda/enzymology , Pinus/parasitology , Plant Diseases/parasitology , Amino Acid Sequence , Animals , Binding Sites , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli/genetics , Escherichia coli/metabolism , Ethanolamines/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Helminth Proteins/genetics , Helminth Proteins/metabolism , Kinetics , Methyltransferases/genetics , Methyltransferases/metabolism , Models, Molecular , Nematoda/genetics , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Substrate Specificity , Thermodynamics
20.
J Thorac Cardiovasc Surg ; 155(3): 897-904, 2018 03.
Article in English | MEDLINE | ID: mdl-29249502

ABSTRACT

OBJECTIVES: Surgery for type A aortic dissection is associated with a high operative mortality, and a variety of predictive risk factors have been reported. We hypothesized that a combination of risk factors associated with organ malperfusion and severe acidosis that are not currently documented in databases would be associated with a level of extreme operative risk that would warrant the consideration of treatment paradigms other than immediate ascending aortic surgery. METHODS: Charts of patients undergoing repair of acute type A aortic dissection between January 1, 1996, and May 1, 2016, were queried for preoperative malperfusion, preoperative base deficit, pH, bicarbonate, cardiopulmonary resuscitation, severe aortic insufficiency, redo status, and preoperative intubation. Multivariable logistic analyses were considered to evaluate interested variables and operative mortality. RESULTS: Between January 1, 1996, and May 1, 2016, 282 patients underwent surgical repair of type A aortic dissection. A total of 66 patients had a calculated base deficit -5 or greater. Eleven of 12 patients (92%) with severe acidosis (base deficit ≥-10) with malperfusion had operative mortality. No patient with severe acidosis with abdominal malperfusion survived. Multivariable analyses identified base deficit, intubation, congestive heart failure, dyslipidemia/statin use, and renal failure as predictors of operative death. The most significant predictor was base deficit -10 or greater (odds ratio, 9.602; 95% confidence interval, 2.649-34.799). CONCLUSIONS: The combination of severe acidosis (base deficit ≥-10) with abdominal malperfusion was uniformly fatal. Further research is needed to determine whether the identification of extreme risk warrants consideration of alternate treatment options to address the cause of severe acidosis before ascending aortic procedures.


Subject(s)
Abdomen/blood supply , Acidosis/mortality , Aortic Aneurysm/surgery , Aortic Dissection/surgery , Ischemia/mortality , Vascular Surgical Procedures/mortality , Acid-Base Equilibrium , Acidosis/diagnosis , Acidosis/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Aortic Dissection/diagnostic imaging , Aortic Dissection/mortality , Aortic Dissection/physiopathology , Aortic Aneurysm/diagnostic imaging , Aortic Aneurysm/mortality , Aortic Aneurysm/physiopathology , Clinical Decision-Making , Computed Tomography Angiography , Female , Humans , Ischemia/diagnostic imaging , Ischemia/physiopathology , Male , Middle Aged , Regional Blood Flow , Risk Assessment , Risk Factors , Severity of Illness Index , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...