Publications by authors named "Ilkka P Mattila"

20 Publications

  • Page 1 of 1

Generation of self-reactive, shared T-cell receptor α chains in the human thymus.

J Autoimmun 2021 05 27;119:102616. Epub 2021 Feb 27.

Research Programs Unit, Translational Immunology, and Medicum, University of Helsinki, Haartmaninkatu 3, 00290, Helsinki, Finland.

The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCRα to TCRβ chains with the estimated total TCR diversity of >10. Despite this high diversity, similar or identical TCR chains are found to recur in immune responses. Here, we analyzed the thymic generation of TCR sequences previously associated with recognition of self- and nonself-antigens, represented by sequences associated with autoimmune diabetes and HIV, respectively. Unexpectedly, in the CD4 compartment TCRα chains associated with the recognition of self-antigens were generated in significantly higher numbers than TCRα chains associated with the recognition of nonself-antigens. The analysis of the circulating repertoire further showed that these chains are not lost in negative selection nor predominantly converted to the regulatory T-cell lineage. The high abundance of self-reactive TCRα chains in multiple individuals suggests that the human thymus has a predilection to generate self-reactive TCRα chains independently of the HLA-type and that the individual risk of autoimmunity may be modulated by the TCRβ repertoire associated with these chains.
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http://dx.doi.org/10.1016/j.jaut.2021.102616DOI Listing
May 2021

Characterization of human T cell receptor repertoire data in eight thymus samples and four related blood samples.

Data Brief 2021 Apr 20;35:106751. Epub 2021 Jan 20.

Research Programs Unit, Translational Immunology, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland.

T cell receptor (TCR) is a heterodimer consisting of TCRα and TCRβ chains that are generated by somatic recombination of multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional and potentially autoreactive receptors are removed. During the last years, the development of high-throughput sequencing technology has allowed a large scale assessment of TCR repertoire and multiple analysis tools are now also available. In our recent manuscript, [1], we show highly overlapping thymic TCR repertoires in unrelated individuals. In the current Data in Brief article, we provide a more detailed characterization of the basic features of these thymic and related peripheral blood TCR repertoires. The thymus samples were collected from eight infants undergoing corrective cardiac surgery, two of whom were monozygous twins [2]. In parallel with the surgery, a small aliquot of peripheral blood was drawn from four of the donors. Genomic DNA was extracted from mechanically released thymocytes and circulating leukocytes. The sequencing of TCRα and TCRβ repertoires was performed at ImmunoSEQ platform (Adaptive Biotechnologies). The obtained repertoire data were analysed applying relevant features from immunoSEQ® 3.0 Analyzer (Adaptive Biotechnologies) and a freely available VDJTools software package for programming language R [3]. The current data analysis displays the basic features of the sequenced repertoires including observed TCR diversity, various descriptive TCR diversity measures, and V and J gene usage. In addition, multiple methods to calculate repertoire overlap between two individuals are applied. The raw sequence data provide a large database of reference TCRs in healthy individuals at an early developmental stage. The data can be exploited to improve existing computational models on TCR repertoire behaviour as well as in the generation of new models.
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http://dx.doi.org/10.1016/j.dib.2021.106751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859292PMC
April 2021

Human thymic T cell repertoire is imprinted with strong convergence to shared sequences.

Mol Immunol 2020 11 19;127:112-123. Epub 2020 Sep 19.

Research Programs Unit, Translational Immunology and Medicum, Department of Bacteriology and Immunology, University of Helsinki. Haartmaninkatu 3, 00290 Helsinki, Finland. Electronic address:

A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCRα and TCRβ locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRα nucleotide repertoire was more diverse than TCRβ, with 4.1 × 10 vs. 0.81 × 10 unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRα than in TCRβ repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCRα and TCRβ loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCRα than TCRβ repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.
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http://dx.doi.org/10.1016/j.molimm.2020.09.003DOI Listing
November 2020

Perinatal and perioperative factors associated with mortality and an increased need for hospital care in infants with transposition of the great arteries: A nationwide 11-year population-based cohort.

Acta Obstet Gynecol Scand 2020 12 23;99(12):1728-1735. Epub 2020 Jul 23.

Department of Pediatric Cardiology, Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Introduction: Newborn infants with transposition of the great arteries (d-TGA) need immediate care for an optimal outcome. This study comprised a nationwide 11-year population-based cohort of d-TGA infants, and assessed whether the implementation of a nationwide systematic fetal screening program, or other perinatal, or perioperative factors, are associated with mortality or an increased need for hospital care.

Material And Methods: The national cohort consisted of all live-born infants with simple d-TGA (TGA ± small ventricular septal defect, n = 127) born in Finland during 2004-2014. Data were collected from six national registries. Prenatal diagnosis and perinatal and perioperative factors associated with mortality and length of hospitalization were evaluated.

Results: Preoperative mortality was 7.9%, and the total mortality was 8.7%. The prenatal detection rate increased after introducing systematic fetal anomaly screening from 5.0% to 37.7% during the study period (P < .0001), but the total mortality rate remained unchanged. All prenatally diagnosed infants (n = 27) survived. Lower gestational age (odds ratio 0.68, P = .012) and higher maternal age at birth (odds ratio 1.16, P = .036) were associated with increased mortality in multivariable analysis. Older infant age at time of operation (P = .002), longer aortic clamp time (P < .001), and higher maternal body mass index (P = .027) were associated with longer initial hospital stay. An extended need for hospital care during the first year of life was multi-factorial.

Conclusions: In our cohort, none of the prenatally diagnosed d-TGA infants died. As a result of the limited prenatal detection rates, however, the sample size was insufficient to reach statistical significance. The d-TGA infants born with lower gestational age and to older mothers had increased mortality.
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http://dx.doi.org/10.1111/aogs.13953DOI Listing
December 2020

Identifying the inheritable component of human thymic T cell repertoire generation in monozygous twins.

Eur J Immunol 2020 05 14;50(5):748-751. Epub 2020 Jan 14.

Research Programs Unit, Translational Immunology, University of Helsinki, Helsinki, Finland.

We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.
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http://dx.doi.org/10.1002/eji.201948404DOI Listing
May 2020

Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+ thymocyte stage.

Cell Immunol 2020 01 11;347:104026. Epub 2019 Dec 11.

Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland; Medicum, University of Helsinki, 00014 Helsinki, Finland.

The natural CD25+ FOXP3+ regulatory T cell (Treg) population is generated as a distinct lineage in the thymus, but the details of Treg development in humans remain unclear, and the timing of Treg commitment is also contested. Here we have analyzed the emergence of CD25+ cells at the CD4+CD8+ double positive (DP) stage in the human thymus. We show that these cells share T cell receptor repertoire with CD25+ CD4 single-positive thymocytes, believed to be committed Tregs. They already have a fully demethylated FOXP3 enhancer region and thus display stable expression of FOXP3 and the associated Treg phenotype. Transcriptome analysis also grouped the DP CD25+ and CD4 CD25+ thymocytes apart from the CD25- subsets. Together with earlier studies, our data are consistent with human Treg commitment already at the DP thymocyte stage. We suggest that the most important antigens and signals necessary for human Treg differentiation may be found in the thymic cortex.
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http://dx.doi.org/10.1016/j.cellimm.2019.104026DOI Listing
January 2020

Development of Human Leukocyte Antigen (HLA) Antibodies Against Vascular Homograft Donor in Pediatric Heart Transplant Recipients.

Ann Transplant 2019 Aug 6;24:454-460. Epub 2019 Aug 6.

Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

BACKGROUND The appearance of human leukocyte antigen (HLA) antibodies after solid organ transplantation predisposes recipients to graft dysfunction. In theory, vascular homografts, which are widely used in children with congenital heart defects, may cause allosensitization. MATERIAL AND METHODS In this single-center retrospective study, the presence of pre-existing HLA antibodies in pediatric heart transplant (HTx) recipients with a vascular homograft was evaluated in a cohort of 12 patients. HLA antibodies were screened before and after HTx and positive screening results were confirmed and identified using the Luminex® single antigen bead method. Endomyocardial biopsies (EMB) and coronary angiography studies were re-evaluated to assess the prevalence of acute rejections and coronary artery change in these patients. RESULTS At the time of HTx, 8 patients (67%) had HLA antibodies detected by the Luminex assay, none of which were heart donor specific (DSA). All patients had negative leukocyte crossmatch. One patient developed DSAs against homograft donor prior to HTx. After the HTx, 5 patients (42%) developed DSAs against the heart donor and 4 patients (40%) against the homograft donor. In 2 patients (17%), the antibodies were against both heart and homograft donors. The rejection rate or prevalence of coronary artery vasculopathy did not differ significantly between the homograft cohort and our historical controls. CONCLUSIONS Our results suggest that the prevalence of DSAs against homograft donor prior to HTx is relatively rare. However, almost half of the patients developed DSAs against homograft post-HTx. The clinical importance of these antibodies warrants further studies.
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http://dx.doi.org/10.12659/AOT.917232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698089PMC
August 2019

Congenital diaphragmatic hernia with heart defect has a high risk for hypoplastic left heart syndrome and major extra-cardiac malformations: 10-year national cohort from Finland.

Acta Obstet Gynecol Scand 2018 02 27;97(2):204-211. Epub 2017 Dec 27.

Pediatric Cardiology, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: Congenital diaphragmatic hernia (CDH) has a well-known risk of congenital heart defects with poor prognosis. This study was conducted to determine the national total prevalence and prenatal detection rates of CDH with heart defects and its association with major extra-cardiac malformations and to further evaluate the impact of the heart defect severity on survival.

Material And Methods: A 10-year national cohort was derived from four national registries, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. The study cohort was sorted according to cardiac defect severity.

Results: The total prevalence of CDH with heart defects was 0.6/10 000 births and live birth prevalence 0.3/10 000 live births. Of 145 cases with CDH, 37 (26%) had a concurrent heart defect. The overall prenatal detection rate of heart defects was 41%. The total prevalence (483/10 000) and live birth prevalence (500/10 000) of hypoplastic left heart syndrome were 124 and 250 times higher than in the general population in Finland, respectively. Additional major extra-cardiac malformations were found in 68% of cases. The survival rate for CDH with major heart defects was 11 and 38% with minor heart defects.

Conclusions: The total prevalence of hypoplastic left heart syndrome was significantly higher in CDH patients than in the general population in Finland. Prenatal detection rate for heart defects in CDH patients was 41%. Major extra-cardiac malformations were more common than previously reported. The prognosis of CDH with major heart defects remained poor.
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http://dx.doi.org/10.1111/aogs.13274DOI Listing
February 2018

Left-Sided Reoperations After Arterial Switch Operation: A European Multicenter Study.

Ann Thorac Surg 2017 Sep 12;104(3):899-906. Epub 2017 Jul 12.

Department of Cardiovascular Surgery, German Heart Center Munich Technische Universität München, Munich, Germany.

Background: We sought to report the frequency, types, and outcomes of left-sided reoperations (LSRs) after an arterial switch operation (ASO) for patients with D-transposition of the great arteries (D-TGA) and double-outlet right ventricle (DORV) TGA-type.

Methods: Seventeen centers belonging to the European Congenital Heart Surgeons Association (ECHSA) contributed to data collection. We included 111 patients who underwent LSRs after 7,951 ASOs (1.4%) between January 1975 and December 2010. Original diagnoses included D-TGA (n = 99) and DORV TGA-type (n = 12). Main indications for LSR were neoaortic valve insufficiency (n = 52 [47%]) and coronary artery problems (CAPs) (n = 21 [19%]).

Results: Median age at reoperation was 8.2 years (interquartile range [IQR], 2.9-14 years). Seven patients died early after LSRs (6.3%); 4 patients with D-TGA (5.9%) and 3 patients with DORV TGA-type (25%) (p = 0.02). Median age at last follow-up was 16.1 years (IQR, 9.9-21.8 years). Seventeen patients (16%) required another reoperation, which was more frequent in patients with DORV- TGA type (4 of 9 [45%]) than in patients with D-TGA (13 of 95 [14%]). Late death occurred in 4 patients (4 of 104 [3.8%]). The majority of survivors were asymptomatic at last clinical examination (84 of 100 [84%]).

Conclusions: Reoperations for residual LSRs are infrequent but may become necessary late after an ASO, predominantly for neoaortic valve insufficiency and CAPs. Risk at reoperation is not negligible, and DORV TGA-type anatomy, as well as procedures on the coronary arteries, were significantly associated with a higher morbidity and a lower overall survival. Recurrent reoperations after LSRs may be required.
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http://dx.doi.org/10.1016/j.athoracsur.2017.04.026DOI Listing
September 2017

Surgical options after Fontan failure.

Heart 2016 07 13;102(14):1127-33. Epub 2016 Apr 13.

Department of cardiothoracic surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Objective: The objective of this European multicenter study was to report surgical outcomes of Fontan takedown, Fontan conversion and heart transplantation (HTX) for failing Fontan patients in terms of all-cause mortality and (re-)HTX.

Methods: A retrospective international study was conducted by the European Congenital Heart Surgeons Association among 22 member centres. Outcome of surgery to address failing Fontan was collected in 225 patients among which were patients with Fontan takedown (n=38; 17%), Fontan conversion (n=137; 61%) or HTX (n=50; 22%).

Results: The most prevalent indication for failing Fontan surgery was arrhythmia (43.6%), but indications differed across the surgical groups (p<0.001). Fontan takedown was mostly performed in the early postoperative phase after Fontan completion, while Fontan conversion and HTX were mainly treatment options for late failure. Early (30 days) mortality was high for Fontan takedown (ie, 26%). Median follow-up was 5.9 years (range 0-23.7 years). The combined end point mortality/HTX was reached in 44.7% of the Fontan takedown patients, in 26.3% of the Fontan conversion patients and in 34.0% of the HTX patients, respectively (log rank p=0.08). Survival analysis showed no difference between Fontan conversion and HTX (p=0.13), but their ventricular function differed significantly. In patients who underwent Fontan conversion or HTX ventricular systolic dysfunction appeared to be the strongest predictor of mortality or (re-)HTX. Patients with valveless atriopulmonary connection (APC) take more advantage of Fontan conversion than patients with a valve-containing APC (p=0.04).

Conclusions: Takedown surgery for failing Fontan is mostly performed in the early postoperative phase, with a high risk of mortality. There is no difference in survival after Fontan conversion or HTX.
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http://dx.doi.org/10.1136/heartjnl-2015-309235DOI Listing
July 2016

Long-term outcome after treatment of pulmonary atresia with ventricular septal defect: nationwide study of 109 patients born in 1970-2007.

Eur J Cardiothorac Surg 2016 May 29;49(5):1411-8. Epub 2015 Nov 29.

Division of Pediatric Cardiology and Cardiac and Transplantation Surgery, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Objectives: Treatment of pulmonary atresia with ventricular septal defect (PA + VSD) has evolved during recent decades, but it still remains challenging. This study evaluated 41-year experience of outcome, survival and treatment of PA + VSD patients.

Methods: Patient records and angiograms of 109 patients with PA + VSD born in Finland between 1970 and 2007, and treated at the Children's Hospital, Helsinki University Central Hospital, were retrospectively analysed in this nationwide study.

Results: Of the 109 patients, 66 (61%) had simple PA + VSD without major aortopulmonary collateral arteries (MAPCAs). Although we observed no difference in overall survival between those with or without MAPCAs, the patients without MAPCAs had better probability to achieve repair (64 vs 28%, P < 0.0003). Only 3 patients were treated by compassionate care. Overall survival was affected by the size of true central pulmonary arteries on the first angiogram (P = 0.001) and whether repair was achieved (P < 0.0001). After successful repair, the survival rate was 93% at 1 year, 91% from the second year, and functional capacity as assessed by New York Heart Association (NYHA) I-II remained in 85% of patients alive at the end of follow-up. Palliated patients at 1, 5, 10 and 20 years of age had Kaplan-Meier estimated survival rates of 55, 42, 34 and 20%, respectively. Patients who underwent repair attempts but were left palliated with right ventricle (RV)-pulmonary artery connection and septal fenestration had better survival than the rest of the palliated patients (P = 0.001). Further, the McGoon index improved after implementation of a systemic-pulmonary artery shunt in the overall PA + VSD population (P < 0.0001).

Conclusions: These findings show that achievement of repair and initial size of true central pulmonary arteries affect survival of patients with PA + VSD. Although the overall survival of patients with MAPCAs showed no difference compared with simple PA + VSD patients, they had a higher risk of remaining palliated. However, palliative surgery may have a role in treatment of PA + VSD because the size of pulmonary arteries increased after placement of systemic-pulmonary artery shunt. In addition, subtotal repair by a RV-pulmonary artery connection and septal fenestration improved survival over extracardiac palliation.
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http://dx.doi.org/10.1093/ejcts/ezv404DOI Listing
May 2016

The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase-Associated Lipocalin in Pediatric Heart Surgery.

Pediatr Crit Care Med 2016 Feb;17(2):121-7

1Department of Anesthesiology and Intensive Care Medicine, Peijas Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 2Department of Anesthesiology and Intensive Care Medicine, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3Department onf Pediatric Cardiac and Transplantation Surgery, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 4Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objectives: Plasma neutrophil gelatinase-associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase-associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase-associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase-associated lipocalin concentrations in pediatric heart surgery.

Design: Two separate double-blinded randomized trials.

Setting: PICU at a university-affiliated hospital.

Patients: Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction.

Interventions: First trial (neonate trial), 40 neonates undergoing open-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15).

Measurements And Main Results: Plasma neutrophil gelatinase-associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase-associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase-associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase-associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase-associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001).

Conclusions: Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase-associated lipocalin levels. Neutrophil gelatinase-associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase-associated lipocalin levels as a kidney injury marker in pediatric heart surgery.
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http://dx.doi.org/10.1097/PCC.0000000000000573DOI Listing
February 2016

Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

Pediatr Crit Care Med 2016 Jan;17(1):45-52

1Divisions of Pediatric Cardiology, Anesthesia and Intensive Care, Neonatology, and Cardiac and Transplantation Surgery, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 2Department of Radiology, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objective: Ambient hypoxia impairs the airway epithelial Na transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na transport, Na transporter-gene expression, and short-term lung edema accumulation.

Design: Prospective, observational study.

Setting: Tertiary care medical center responsible for nationwide pediatric cardiac surgery.

Patients: Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (SpO2% ≥ 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (SpO2 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (SpO2 ≤ 85%; n = 39).

Measurements And Main Results: Nasal transepithelial potential difference served as a surrogate measure for epithelial Na transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na transporters (amiloride-sensitive epithelial Na channel and β1- Na-K-ATPase) were not attenuated, but instead α1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia.

Conclusions: The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.
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http://dx.doi.org/10.1097/PCC.0000000000000568DOI Listing
January 2016

Favourable mid-term outcome after heart transplantation for late Fontan failure.

Eur J Cardiothorac Surg 2015 Apr 17;47(4):665-71. Epub 2014 Jul 17.

Department of Cardiothoracic Surgery, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Objectives: Fontan failure (FF) represents a growing and challenging indication for paediatric orthotopic heart transplantation (OHT). The aim of this study was to identify predictors of the best mid-term outcome in OHT after FF.

Methods: Twenty-year multi-institutional retrospective analysis on OHT for FF.

Results: Between 1991 and 2011, 61 patients, mean age 15.0 ± 9.7 years, underwent OHT for failing atriopulmonary connection (17 patients = 27.8%) or total cavopulmonary connection (44 patients = 72.2%). Modality of FF included arrhythmia (14.8%), complex obstructions in the Fontan circuit (16.4%), protein-losing enteropathy (PLE) (22.9%), impaired ventricular function (31.1%) or a combination of the above (14.8%). The mean time interval between Fontan completion and OHT was 10.7 ± 6.6 years. Early FF occurred in 18%, requiring OHT 0.8 ± 0.5 years after Fontan. The hospital mortality rate was 18.3%, mainly secondary to infection (36.4%) and graft failure (27.3%). The mean follow-up was 66.8 ± 54.2 months. The overall Kaplan-Meier survival estimate was 81.9 ± 1.8% at 1 year, 73 ± 2.7% at 5 years and 56.8 ± 4.3% at 10 years. The Kaplan-Meier 5-year survival estimate was 82.3 ± 5.9% in late FF and 32.7 ± 15.0% in early FF (P = 0.0007). Late FF with poor ventricular function exhibited a 91.5 ± 5.8% 5-year OHT survival. PLE was cured in 77.7% of hospital survivors, but the 5-year Kaplan-Meier survival estimate in PLE was 46.3 ± 14.4 vs 84.3 ± 5.5% in non-PLE (P = 0.0147). Cox proportional hazards identified early FF (P = 0.0005), complex Fontan pathway obstruction (P = 0.0043) and PLE (P = 0.0033) as independent predictors of 5-year mortality.

Conclusions: OHT is an excellent surgical option for late FF with impaired ventricular function. Protein dispersion improves with OHT, but PLE negatively affects the mid-term OHT outcome, mainly for early infective complications.
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http://dx.doi.org/10.1093/ejcts/ezu280DOI Listing
April 2015

Resection of the stenotic segment with individually tailored anastomosis for symptomatic congenital tracheal stenosis in infants.

Eur J Cardiothorac Surg 2014 Jun 28;45(6):e215-9. Epub 2014 Mar 28.

Department of Paediatric Cardiac Surgery, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

Objectives: To analyse retrospectively population-based results of congenital tracheal stenosis (CTS) repair in infants in Finland.

Methods: Data on infants who were operated on for CTS in Helsinki Children's Hospital between August 1988 and May 2013 were analysed retrospectively. Fibreoptic bronchoscopy was performed perioperatively and in follow-up of all the surviving patients. The median follow-up time was 7 (range 1-20) years.

Results: Thirteen infants were operated on for CTS. Resection of the stenotic segment with individually tailored anastomosis was used in 12 patients and slide tracheoplasty in 1 patient. The median age at the operation was 2.9 (range 0.2-19) months. Eight (62%) patients had associated cardiovascular defects, which were corrected during the same operation. The median length of stenosis was 35% (range 25-60%) of the total length of the trachea. The median length of time of postoperative mechanical ventilation was 10 (range 5-19) days. The median length of time of intensive care treatment was 15 (range 7-40) days. One patient died from hypoplastic lung tissue and fibrosis, and multiorgan failure. One patient required reoperation, and 3 other patients received balloon bronchodilatations postoperatively. There was no late mortality. All of the 12 survivors had a good outcome.

Conclusion: Resection with individually tailored anastomosis with up to 55% of the stenotic segment of the trachea presented a good long-term outcome.
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http://dx.doi.org/10.1093/ejcts/ezu113DOI Listing
June 2014

Outcome of pediatric heart transplantation recipients treated with ventricular assist device.

Pediatr Transplant 2013 Feb 28;17(1):73-9. Epub 2012 Nov 28.

Department of Pediatrics, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

This study was conducted to evaluate the long-term prognosis of pediatric HTx patients treated with VAD before transplantation. The clinical data of six patients bridged to HTx with Berlin Heart EXCOR pediatric device were analyzed retrospectively. Information about graft function, CA results, and EMB findings as well as appearance DSA was collected. Also, information about growth and cognitive function was analyzed. These findings were compared with age-, gender-, and diagnosis-matched HTx patients. During the median follow-up time of four and half yr after HTx, the prognosis including graft function, number of rejection episodes, and incidence of coronary artery vasculopathy, growth and cognitive development did not differ between VAD-bridged HTx patients compared with control patients. In both groups, one patient developed positive DSA titer after HTx. Our single-center experience suggests that the prognosis of pediatric HTx patients treated with VAD before transplantation is not inferior to that of other HTx patients.
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http://dx.doi.org/10.1111/petr.12028DOI Listing
February 2013

Prevention of postoperative pericardial adhesions in children with hypoplastic left heart syndrome.

Interact Cardiovasc Thorac Surg 2011 Feb 16;12(2):270-2. Epub 2010 Nov 16.

Department of Paediatric Cardiac Surgery, Hospital for Children and Adolescents, University of Helsinki, P.O.B. 281, 00029 Helsinki, Finland.

Reoperations for congenital cardiac defects are associated with an increased surgical risk due to adhesions. We compared the capability of a polytetrafluoroethylene (PTFE) membrane, synthetic polyethyleneglycol hydrogel (PEG), and a combination of them to prevent postoperative pericardial adhesions in patients with hypoplastic left heart syndrome (HLHS). Eighteen consecutive patients with HLHS were included. At the end of the Norwood I operation the cranial and the caudal half of the heart of each patient was randomized to receive a PTFE membrane, a synthetic PEG, a combination of them, or no treatment (control). Tenacity and density of adhesions, epicardial visibility, and adhesions between the heart and the sternum were analyzed semiquantitatively at a subsequent bidirectional Glenn operation. The PTFE membrane significantly decreased adhesion formation between the heart and the sternum (P<0.001). However, the PTFE membrane, with or without synthetic PEG, impaired epicardial visibility (P<0.05) when compared to synthetic PEG or controls. Synthetic PEG alone did not significantly reduce the formation of pericardial adhesions. Tenacity and density of adhesions were not affected by any of the treatment modalities. The PTFE membrane significantly decreases postoperative adhesions between the heart and the sternum, but impairs epicardial visibility. Synthetic PEG does not prevent formation of pericardial adhesions.
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http://dx.doi.org/10.1510/icvts.2010.241448DOI Listing
February 2011

Serum Levels of Natriuretic Peptides in Children before and after Treatment for an Atrial Septal Defect, a Patent Ductus Arteriosus, and a Coarctation of the Aorta-A Prospective Study.

Int J Pediatr 2010 20;2010:674575. Epub 2010 Apr 20.

Department of Pediatrics, University Hospital of Tampere, 33521 Tampere, Finland.

Background and Objectives. We evaluated and compared the influence of treatment for atrial septal defect (ASD), patent ductus arteriosus (PDA), and coarctation of the aorta (CoA) on serum levels of N-terminal proatriopeptide and N-terminal probrain natriuretic peptide. Correlations between peptide levels and echocardiographic measurements were calculated. Patients and Methods. Peptide levels were measured and echocardiography performed before and 6-12 months after treatment in 21 children with ASD, 25 with PDA, 15 with CoA, and 76 control children. Results. ANPN levels were higher than in controls at baseline in all patient groups, and NT-proBNP in patients with ASD and PDA. Both peptide levels were elevated 6 months after treatment and decreased thereafter. Peptide levels were higher in patients with volume than pressure overload. They correlated with echocardiographic measurements. At the 6-month follow-up, dimensions of the originally overloaded ventricle had normalized only in patients with PDA. Conclusions. After intervention, peptide levels decrease but normalization takes over 6 months. The type of correlation between peptide levels and echocardiography varies according to the loading condition. Measurement of peptide levels can be used for monitoring the course of a patient's heart disease.
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http://dx.doi.org/10.1155/2010/674575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859410PMC
July 2011

Left ventricular hypertrophy persists after successful treatment for coarctation of the aorta.

Scand Cardiovasc J 2007 Dec;41(6):370-7

Department of Paediatric, University of Kuopio, Kuopio, Finland.

Objectives: To evaluate cardiac size and function in patients with coarctation of the aorta (CoA) before and after treatment.

Design: Ventricular size and function were examined by 2- and 3-dimensional echocardiography, and concentrations of natriuretic peptides measured in 15 paediatric patients before repair, and one, 6, and 12 months thereafter. Controls comprised 15 children.

Results: Before repair, mitral inflow velocities and left ventricular (LV) size and wall thickness were higher in patients. Thicknesses of interventricular septum and LV posterior wall decreased after repair but increased to initial level one year thereafter. The LV end-diastolic diameter remained larger than in controls despite successful repair. The size of right ventricle increased and levels of natriuretic peptides decreased during follow-up. Levels of natriuretic peptides correlated with the smallest diameter of CoA segment and diastolic indices of LV function.

Conclusion: LV hypertrophy persists and LV size remains larger than in controls after successful repair even in normotensive patients with normal growth of CoA segment. This may be due to remodelling of ventricles and the aorta caused by CoA.
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http://dx.doi.org/10.1080/14017430701397839DOI Listing
December 2007

Hemodynamic improvement is faster after percutaneous ASD closure than after surgery.

Catheter Cardiovasc Interv 2007 Feb;69(3):432-41; discussion 442

Department of Pediatrics, University Hospital of Kuopio, Kuopio, Finland.

Objectives: Hemodynamic effects of surgical and percutaneous closure of atrial septal defect (ASD) were evaluated.

Background: ASD causes volume overload of right ventricle (RV) and is associated with distortion and dysfunction of left ventricle (LV). The amount and timing of hemodynamic changes after ASD closure are not well known.

Methods: The study group consisted of 7 children treated surgically and 17 treated in the catheterization laboratory. In the control group, there were 51 healthy children. RV size and LV end-diastolic and systolic dimensions, volumes, and function were examined by two- and three- dimensional echocardiography and serum concentrations of natriuretic peptides measured prior to ASD closure, and 1, 6, and 12 months thereafter.

Results: In all children with ASD, during the 1-year follow-up, the z score of RV end-diastolic diameter decreased from a median 5.00 SD to 2.25 SD (P < 0.001). Dilatation of RV did not resolve entirely during 1-year follow-up in either treatment group. End-diastolic LV diameter increased from -1.50 to -0.50 SD (P < 0.001). LV size increased slower in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides increased during the first month after ASD closure and normalized thereafter in patients treated percutaneously but remained higher than in controls in patients treated surgically.

Conclusions: During 1-year follow-up after ASD closure, RV size decreases but does not normalize in all patients. The size of the LV normalizes after ASD closure but the increase in LV size is slower in patients treated surgically. Serum levels of ANPN and proBNP are elevated prior to ASD closure but decrease thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically.
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February 2007
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