A retrospective analysis of the duration of mechanical ventilation in Scandinavian paediatric heart centres.

AIM: Early extubation after cardiac surgery shortens paediatric intensive care unit (PICU) length of stay (LOS) and decreases complications from mechanical ventilation (MV). We explored the duration of MV in Scandinavian paediatric heart centres. METHODS: We retrospectively reviewed the MV duration and PICU LOS of 696 children operated for atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot (TOF) or total cavopulmonary connection (TCPC) in four Scandinavian centres in 2015-2016. Neonates (n = 90) were included regardless of heart surgery type. RESULTS: Patients with ASD were extubated at a median of 3.25 h (interquartile range [IQR] 2.00-4.83), followed by patients with TCPC (median 5.00 h, IQR 2.60-16.83), VSD (median 7.00 h, IQR 3.69-22.25) and TOF (median 18.08 h, IQR 6.00-41.38). Neonates were not extubated early (median 94.42 h, IQR 45.03-138.14). Although MV durations were reflected in PICU LOS, this was not as apparent among those extubated within 12 h. The Swedish centres had shortest MV durations and PICU LOS. Extubation failed in 24/696 (3.4%) of patients. CONCLUSION: Scandinavian paediatric heart centres differed in the duration of postoperative MV. Deferring extubation up to 12 h postoperatively did not markedly prolong PICU LOS.

Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring.

Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00-2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29-10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers.

Lipid profiles of patients with manifest coronary versus peripheral atherosclerosis - Is there a difference?

AIM: Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations, PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. METHODS: A cohort of 274 statin-naïve patients with either newly diagnosed imaging proven PAD (n = 89) or stable CAD (n = 185) was characterized using nuclear magnetic resonance- and liquid chromatography-tandem mass spectrometry-based advanced lipid and lipoprotein analysis. An independent cohort of 1239 patients with PAD and CAD was used for validation. RESULTS: We found a significant difference in markers of inflammation as well as ceramide and phosphatidylcholine levels between patients with PAD and CAD. In contrast, basic lipid markers including total cholesterol, LDL cholesterol, HDL cholesterol, lipoprotein(a) or detailed lipoprotein profiles did not differ significantly between patients with PAD and CAD. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent of body composition, from the status of smoking or type 2 diabetes mellitus, and also from apolipoprotein C-III and other inflammatory parameters which were different between CAD and PAD. CONCLUSION: The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid patterns but not in lipoprotein characteristics.

A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer.

Epithelial ovarian cancer (EOC) generally responds well to oncological treatments, but the eventual development of a refractory disease is a major clinical problem. Presently, there are no prognostic blood-based biomarkers for the stratification of EOC patients at the time of diagnosis. We set out to assess and validate the prognostic utility of a novel two-lipid signature, as the lipidome is known to be markedly aberrant in EOC patients. The study consisted of 499 women with histologically confirmed EOC that were prospectively recruited at the university hospitals in Turku (Finland) and Charité (Berlin, Germany). Lipidomic screening by tandem liquid chromatography-mass spectrometry (LC-MS/MS) was performed for all baseline serum samples of these patients, and additionally for 20 patients of the Turku cohort at various timepoints. A two-lipid signature, based on the ratio of the ceramide Cer(d18:1/18:0) and phosphatidylcholine PC(O-38:4), showed consistent prognostic performance in all investigated study cohorts. In the Turku cohort, the unadjusted hazard ratios (HRs) per standard deviation (SD) (95% confidence interval) were 1.79 (1.40, 2.29) for overall and 1.40 (1.14, 1.71) for progression-free survival. In a Charité cohort incorporating only stage III completely resected patients, the corresponding HRs were 1.59 (1.08, 2.35) and 1.53 (1.02, 2.30). In linear-mixed models predicting progression of the disease, the two-lipid signature showed higher performance (beta per SD increase 1.99 (1.38, 2.97)) than cancer antigen 125 (CA-125, 1.78 (1.13, 2.87)). The two-lipid signature was able to identify EOC patients with an especially poor prognosis at the time of diagnosis, and also showed promise for the detection of disease relapse.

Pediatric traumas and neighborhood socioeconomic characteristics: A population based study.

BACKGROUND: Identifying pediatric populations at risk for traumas would enable development of emergency medical services and emergency departments for children. Elucidation of the nature of socioeconomic differences in the incidence of pediatric out-of-hospital emergencies is needed to overcome inequities in child health. METHODS: We retrieved all ambulance contacts during 17.12.2014-16.12.2018 involving children (0-15 years) in Helsinki, Finland and separated traumatic and nontraumatic emergencies. We compared the incidences of these emergencies in the pediatric population with socioeconomic markers of the scene of the emergency and of the residential area of the child. RESULTS: Of 11,742 ambulance contacts involving children 4113 (35.0%) were traumatic. Traumatic emergencies occurred more often in neighborhoods with lower median income/household (P=0.043) and were more common in children living in areas with lower median income/inhabitant (P=0.001), higher unemployment (P<0.001), and lower education (P<0.001). The associations were weaker for traumatic than nontraumatic emergencies. Higher proportion of a pediatric population in a residential area (P=0.005) had a protective effect. Exclusion of clinically unnecessary ambulance responses did not change the results. CONCLUSION: Traumatic emergencies in children are more common in areas with lower socioeconomic status. The possible protective effect of urban planning merits further studies. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: II.

Viral infections and immune reconstitution interaction after pediatric allogenic hematopoietic stem cell transplantation.

Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Although immune suppression plays a central role, the literature shows conflicting results on interplay between post-transplant immune reconstitution (IR) and viral infections. Methods: We prospectively studied viral infections and IR in 30 pediatric patients undergoing allogenic HSCT, with a follow-up time of 24 months. In total, 1337 blood (CMV, EBV, HHV-6, ADV and BKV) and urine (BKV and JCV) virus samples were analyzed. IR including B-cells (CD19+), T cells (CD3+, CD4+, CD8+) and NK-cells were measured. Clinical outcomes included overall survival (OS), non-relapse mortality (NRM), graft-versus-host disease (GVHD) and occurrence of blood culture positive bacterial infections. Results: We found BKV reactivation to be most frequent, 47% of the children had viremia and 77% viruria. The frequencies of CMV, HHV-6 and adeno viremia were 37%, 37% and 6%, respectively. Viremias beyond 3 months post-HSCT were uncommon. Factors such as GVHD, use of steroids, EBV and CMV infections and pre-transplant irradiation affected IR. No specific viral infection or IR related factor was associated to OS or NRM. Conclusions: Viral infections and IR interact in a bi-directional manner. Accordingly, close follow-up of both IR and viral loads is warranted.

The Role of KCNQ1 Mutations and Maternal Beta Blocker Use During Pregnancy in the Growth of Children With Long QT Syndrome.

OBJECTIVE: Two missense mutations in KCNQ1, an imprinted gene that encodes the alpha subunit of the voltage-gated potassium channel Kv7.1, cause autosomal dominant growth hormone deficiency and maternally inherited gingival fibromatosis. We evaluated endocrine features, birth size, and subsequent somatic growth of patients with long QT syndrome 1 (LQT1) due to loss-of-function mutations in KCNQ1. DESIGN: Medical records of 104 patients with LQT1 in a single tertiary care center between 1995 and 2015 were retrospectively reviewed. METHODS: Clinical and endocrine data of the LQT1 patients were included in the analyses. RESULTS: At birth, patients with a maternally inherited mutation (n = 52) were shorter than those with paternal inheritance of the mutation (n = 29) (birth length, -0.70 ± 1.1 SDS vs. -0.2 ± 1.0 SDS, P < 0.05). Further analyses showed, however, that only newborns (n = 19) of mothers who had received beta blockers during pregnancy were shorter and lighter at birth than those with paternal inheritance of the mutation (n = 29) (-0.89 ± 1.0 SDS vs. -0.20 ± 1.0 SDS, P < 0.05; and 3,173 ± 469 vs. 3,515 ± 466 g, P < 0.05). Maternal beta blocker treatment during the pregnancy was also associated with lower cord blood TSH levels (P = 0.011) and significant catch-up growth during the first year of life (Δ0.08 SDS/month, P = 0.004). Later, childhood growth of the patients was unremarkable. CONCLUSION: Loss-of-function mutations in KCNQ1 are not associated with abnormalities in growth, whereas maternal beta blocker use during pregnancy seems to modify prenatal growth of LQT1 patients-a phenomenon followed by catch-up growth after birth.

Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis.

Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients with growth hormone deficiency and maternally inherited gingival fibromatosis. We report that patients from three unrelated families harbor either of two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), in KCNQ1, a gene previously implicated in the long QT interval syndrome. Kcnq1 is expressed in hypothalamic GHRH neurons and pituitary somatotropes. Co-expressing KCNQ1 with the KCNE2 ß-subunit shows that both KCNQ1 mutants increase current levels in patch clamp analyses and are associated with reduced pituitary hormone secretion from AtT-20 cells. In conclusion, our results reveal a role for the KCNQ1 potassium channel in the regulation of human growth, and show that growth hormone deficiency associated with maternally inherited gingival fibromatosis is an allelic disorder with cardiac arrhythmia syndromes caused by KCNQ1 mutations.