| 1. |
- Björkman, Kristoffer, et al.
(författare)
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Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
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Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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| 2. |
- Böhmer, Jens, 1981, et al.
(författare)
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Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.
- 2023
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874 .- 1432-2277. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.
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| 3. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 4. |
- Sundström, Emilia, 1985-
(författare)
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Inherited arrhythmogenic channelopathies and implantable cardioverter defibrillator treatment : national and age-related perspectives
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Long QT syndrome (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada syndrome (BrS), and short QT syndrome are hereditary diseases caused by mutations in genes coding for cardiac ion channels. Patients carrying these mutations may be at risk of symptoms such as syncope and sudden cardiac death (SCD). To prevent symptoms, patients need to be managed properly and this management may include prophylactic medical treatment, and the use of an implantable cardioverter defibrillator (ICD) for high-risk patients. ICD treatment has previously been shown to prevent SCD, but it also carries a risk of complications and inappropriate shocks. In these studies, we investigated ICD treatment in patients with inherited arrhythmogenic channelopathies with a focus on individual risk assessment and ICD harm.Methods: Studies I–III are observational studies that use registries to identify patients and medical records to collect data. Studies I and III are performed with a descriptive approach that focus on phenotype, genotype, and medical treatment (Study I) and the diagnostic process and treatment over time (Study III). In Study II, we use Kaplan Meier analyses and incidence rates to assess risk scores and ICD harm. Study IV is a systematic review based on a systematic search and screening process. The data, which are synthesized without meta-analysis, are from published original works.Results: In Studies I and II, we present data on 109 Swedish LQTS patients with a first ICD implantation between 1992 and 2013 at a median age of 39 years (range, 5–78 years). Most patients received ICD treatment after aborted cardiac arrest (n=45, 41%) and after syncope despite receiving prophylactic medical treatment, i.e., beta-blockers (n=31, 29%). However, 10 patients (9%) received ICD treatment despite being asymptomatic and 17 patients (16%) after syncope without ongoing beta-blocker treatment. The incidence rate of a first appropriate shock was 4.3 per 100 person-years. Concerning ICD harm, the incidence rate of inappropriate shocks was 3.0 per 100 person-years and the corresponding rate of complications was 7.6 per 100 person-years. Using risk scores previously proposed to our cohort, we found that the patients who received appropriate shocks still had zero points (i.e., the lowest score) from the risk score.In Study III, 39 Swedish pediatric patients had either BrS (n=7) or CPVT (n=32). Of the 32 CPVT patients, 18 (56%) had been misdiagnosed at first; however, since 2010 only two patients received an initial misdiagnosis. The treatment in CPVT patients changed over time in accordance with current guidelines.In Study IV, the database search (4318 references) rendered a final inclusion of 40 references, including 741 children and adolescents with inherited arrhythmogenic channelopathies. Of the patients affected by ICD harm, 20% (148/741) had inappropriate shocks and 23% (145/624) had other complications. In LQTS and CPVT patients, the percentage of patients with ICD harm was lower in studies published from 2015, than before.Conclusion: These studies illustrate both the difficulty in pre-ICD risk stratification and its important role due to high combined rates of ICD harm. ICD treatment is an important treatment option for high-risk patients with inherited arrhythmogenic channelopathies. We found improvements in how patients have been managed over time and identified the need for future research addressing benefit and harm from ICD treatment among children and adolescents.
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| 5. |
- Gio-Batta, Monica, et al.
(författare)
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Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age : Findings from a Swedish Birth Cohort
- 2022
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; , s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age.Methods: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass.Results: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12).Conclusions: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.
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| 6. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Differences between Arterial and Venous Umbilical Cord Plasma Metabolome and Association with Parity
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Umbilical cord blood is frequently used in health monitoring of the neonate. Results may be affected by the proportion of arterial and venous cord blood, the venous blood coming from the mother to supply oxygen and nutrients to the infant, and the arterial carrying waste products from the fetus. Here, we sampled arterial and venous umbilical cords separately from 48 newly delivered infants and examined plasma metabolomes using GC-MS/MS metabolomics. We investigated differences in metabolomes between arterial and venous blood and their associations with gestational length, birth weight, sex, and whether the baby was the first born or not, as well as maternal age and BMI. Using multilevel random forest analysis, a classification rate of 79% was achieved for arteriovenous differences (p = 0.004). Several monosaccharides had higher concentrations in the arterial cord plasma while amino acids were higher in venous plasma, suggesting that the main differences in the measured arterial and venous plasma metabolomes are related to amino acid and energy metabolism. Venous cord plasma metabolites related to energy metabolism were positively associated with parity (77% classification rate, p = 0.004) while arterial cord plasma metabolites were not. This underlines the importance of defining cord blood type for metabolomic studies.
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| 7. |
- Johansson Kostenniemi, Urban, 1987-, et al.
(författare)
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MeningiSSS : A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis
- 2020
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 586-595
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.
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| 8. |
- Ranta, S., et al.
(författare)
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High need for intensive care in paediatric acute myeloid leukaemia: A population-based study
- 2022
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:11, s. 2235-2241
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Tidskriftsartikel (refereegranskat)abstract
- Aim Risk of treatment-related life-threatening toxicity is high in childhood acute myeloid leukaemia (AML), and access to intensive care units (ICU) is crucial. We explored the ICU admission rate and outcome after intensive care in childhood AML in Sweden. Methods Patients diagnosed between 2008 and 2016 were identified from the Swedish Childhood Cancer Registry (SCCR), a national quality registry. Data from SCCR was cross-referenced with clinical questionnaire data from paediatric oncology centers and the Swedish Intensive Care Registry (SIR), another national quality registry. Results According to combined data, 46% of the children (58/126) were admitted to ICU, 17% (21/126) within 1 month from diagnosis. Overall, ICU mortality per admission was 12% and 6% during first-line treatment. There was a discrepancy between admission rate from the clinical questionnaires and SCCR (29%; 36/126 children) and SIR (44%; 55/126) All deaths during first-line treatment occurred at or after ICU care. Conclusion Although admission rate under AML treatment was high, the treatment-related mortality under first-line treatment was low. No child died under first-line treatment without admission to ICU, suggesting good availability. The discrepancy between the two registries, SCCR and SIR, highlights the need for future validation of registry data.
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| 9. |
- Grönberg, Annika, 1970-
(författare)
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Predictors of long-term glycemic control, pancreatic function and BMI trajectory in children with type 1 diabetes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The maintenance of normal metabolic control underpins all management of insulin dependent diabetes whether in terms of preserved beta-cell function, body composition, or family support. The hypothesis of this work was that preserved C-peptide predicts better glycemic control and lowers risk of severe hypoglycemia. It was additionally investigated whether Body Mass Index (BMI) and family structure contributes to the prediction of long-term glycemic control. Objectives: This thesis aimed to 1) identify the factors associated with residual C peptide production at least 10 years after diagnosis, 2) evaluate the association of BMI trajectory and long-term glycemic control, 3) identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course, and 4) investigate the relations of family structure at diagnosis and long-term glycemic control. Methods: Data from four cohorts were used: In the Uppsala cohort, measurement of long-term residual C-peptide was undertaken using ultrasensitive C-peptide ELISA in 73 children and adolescents <25 years, BMI trajectory prior diagnosis was evaluated in 295 children, while family structure at diagnosis was evaluated in 215 children in relation to glycemic control. In the Linköping cohort, stimulated C-peptide was assessed by mixed meal tolerance test in 50 children. Results: The cohort studies showed that better early glycemic control predicted long term residual C-peptide and that long term residual C-peptide, in turn, was protective against severe hypoglycemia. Additionally, BMI trajectory was predicted by BMI prior to the presentation of type 1 diabetes. There was no association with glycemic outcome. Children living in a whole family had a lower probability of long-term dysglycemia. Conclusions: Residual C-peptide is important for better glycemic control and to reduce complications in children with type 1 diabetes. Family structure, but not BMI trajectory, contributes to the prediction of long-term glycemic control. However, more research is needed to understand how to preserve the beta-cell function in children and to target and support families in those children with early deteriorating glycemic control to reduce future complications.
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| 10. |
- Gio-Batta, Monica, et al.
(författare)
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Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
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