Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs

Journal of Clinical Immunology - Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe...     

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake,Blood Flow,Neural Activity,and Cognitive Function During Normo- and Hypoglycemia

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.     

Abdominal obesity and alcohol use modify the impact of genetic risk for incident advanced liver disease in the general population

Background & Aims

Genetic variants, abdominal obesity and alcohol use are risk factors for incident liver disease (ILD). We aimed to study whether variants either alone or when aggregated into genetic risk scores (GRSs) associate with ILD, and whether waist-hip ratio (WHR) or alcohol use interacts with this risk.

Methods

Our study included 33 770 persons (mean age 50 years, 47% men) who participated in health-examination surveys (FINRISK 1992–2012 or Health 2000) with data on alcohol use, WHR and 63 genotypes associated with liver disease. Data were linked with national health registers for liver-related outcomes (hospitalizations, malignancies and death). Exclusions were baseline clinical liver disease. Mean follow-up time was 12.2 years. Cox regression analyses between variants and ILD were adjusted for age, sex and BMI.

Results

Variants in PNPLA3, IFNL4, TM6SF2, FDFT1, PPP1R3B, SERPINA1 and HSD17B13 were associated with ILD. GRSs calculated from these variants were not associated with WHR or alcohol use, but were exponentially associated with ILD (up to 25-fold higher risk in high versus low score). The risk of ILD in individuals with high GRS and high WHR or alcohol use compared with those with none of these risk factors was increased by up to 90-fold. GRSs provided new prognostic information particularly in individuals with high WHR.

Conclusions

The effect of multiple genetic variants on the risk of ILD is potentiated by abdominal obesity and alcohol use. Simple GRSs may help to identify individuals with adverse lifestyle who are at a particularly high risk of ILD.     

Persistent organic pollutants associate with liver disease in a Finnish general population sample

Background and Aims

Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease.

Methods

This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression.

Results

Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04–0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05–0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21–2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07–2.68, p < 0.05 respectively).

Conclusions

Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease.     

The Swedish version of EMPATHIC-30 translation and initial psychometric evaluation

Background

One way to measure quality of care is by measuring satisfaction of provided care among patients and their families. EMpowerment of PArents in THe Intensive Care 30 (EMPATHIC-30) is a self-reported questionnaire grounded on the principles of FCC aiming to measure parents' satisfaction with paediatric intensive care. There is lack of Swedish questionnaires measuring satisfaction with paediatric intensive care based on family-centered care principles.

Aim

The aim was to translate the instrument EMpowerment of PArents in THe Intensive Care 30 (EMPATHIC-30) into the Swedish language and evaluate psychometrically the Swedish version in a paediatric intensive care context.

Methods

The instrument EMPATHIC-30 was translated and adapted to Swedish context, thereafter, assessed by expert panels consisting of nurses (panel one; n = 4; panel two; n = 24) and parents (n = 8) with experience in paediatric intensive care. Construct validity, item characteristics and reliability were tested in a cohort of 97 parents whose child had been treated for at least 48 h at two out of four Paediatric Intensive Care Unit (PICUs) in Sweden. Parents whose child died during hospitalisation were excluded.

Results

The Swedish version of EMPATHIC-30 showed an acceptable internal consistency with Cronbach's alpha coefficient for the total scale 0.925. Cronbach's alpha on the domain level varied between 0.548–0.792 with the lowest coefficient in the domain Organisation. Inter-scale correlation revealed acceptable correlations for both subscales (0.440–0.743) and between total scale and subscales (0.623–0.805), which demonstrated good homogeneity for the instrument in its entirety. One problem regarding the domain Organisation and especially the item “It was easy to contact the pediatric intensive care unit by telephone” was revealed, which indicated that the item needs to be reformulated or that the factor structure needs to be further evaluated.

Conclusion

The findings from the current study indicated that the Swedish version of EMPATHIC-30 has acceptable psychometric properties and can be used in Swedish PICUs. Using EMPATHIC-30 in clinical practice can give an indication of the overall quality of family-centered care at the PICU.     

Combined use of the ELF test and CLivD score improves prediction of liver-related outcomes in the general population

Background and Aims

Effective and feasible population screening strategies are needed for the early detection of individuals at high risk of future severe liver-related outcomes. We evaluated the predictive performance of the combination of liver fibrosis assessment, phenotype profile, and genetic risk.

Methods

Data from 5795 adults attending the Finnish Health 2000 Survey were linked with healthcare registers for liver-related outcomes (hospitalization, hepatocellular cancer, and death). Fibrosis was assessed using the enhanced liver fibrosis (ELF) test, phenotype profile by the chronic liver disease (CLivD) risk score, and genetic risk by a validated Polygenic Risk Score (PRS-5). Predictive performance was assessed by competing-risk analyses.

Results

During a median 13-year follow-up, 64 liver-related outcome events were recorded. ELF, CLivD score, and PRS-5 were independently associated with liver-related outcomes. The absolute 10-year risk of liver-related outcomes at an ELF value of 11.3 ranged from 0.3% to 33% depending on the CLivD score. The CLivD score added 51% of new predictive information to the ELF test and improved areas under the curve (AUCs) from 0.91, 0.81, and 0.71 for ELF alone to 0.95, 0.85, and 0.80, respectively, for ELF combined with the CLivD score at 1, 5, and 10 years. The greatest improvement was for 10-year predictions (delta-AUC 0.097, p < .0001). Adding PRS-5 did not significantly increase predictive performance. Findings were consistent in individuals with obesity, diabetes, or alcohol risk use, and regardless of whether gamma-glutamyltransferase was used in the CLivD score.

Conclusion

A combination of ELF and CLivD score predicts liver-related outcomes significantly better than the ELF test alone.     

Obesity and metabolic state are associated with increased healthcare resource and medication use and costs: a Finnish population-based study

The European Journal of Health Economics - To characterize healthcare resource (HCRU) and medication use and associated costs in individuals with obesity compared with individuals with normal...     

Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation

Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4⁺CD8⁺ double-positive (DP) thymocytes and the CD4⁺ or CD8⁺ single-positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n = 7) were compared regarding the expression of 34 molecules using cytometry by time-of-flight (CyTOF). In addition, FACS-sorted thymic eosinophils were co-cultured with autologous CD3/CD28-stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X-shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil-thymocyte co-cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.