New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest.

BACKGROUND: Abnormalities on magnetic resonance imaging scans are common both before and after surgery for congenital heart disease in early infancy. The aim of this study was to prospectively investigate the nature, timing, and consequences of brain injury on magnetic resonance imaging in a cohort of young infants undergoing surgery for congenital heart disease both with and without cardiopulmonary bypass. METHODS AND RESULTS: A total of 153 infants undergoing surgery for congenital heart disease at <8 weeks of age underwent serial magnetic resonance imaging scans before and after surgery and at 3 months of age, as well as neurodevelopmental assessment at 2 years of age. White matter injury (WMI) was the commonest type of injury both before and after surgery. It occurred in 20% of infants before surgery and was associated with a less mature brain. New WMI after surgery was present in 44% of infants and at similar rates after surgery with or without cardiopulmonary bypass. The most important association was diagnostic group (P<0.001). In infants having arch reconstruction, the use and duration of circulatory arrest were significantly associated with new WMI. New WMI was also associated with the duration of cardiopulmonary bypass, postoperative lactate level, brain maturity, and WMI before surgery. Brain immaturity but not brain injury was associated with impaired neurodevelopment at 2 years of age. CONCLUSIONS: New WMI is common after surgery for congenital heart disease and occurs at the same rate in infants undergoing surgery with and without cardiopulmonary bypass. New WMI is associated with diagnostic group and, in infants undergoing arch surgery, the use of circulatory arrest.

The impact of cutaneous neurofibromas on quality of life and mental health in neurofibromatosis type 1.

The skin manifestations of neurofibromatosis 1 significantly reduce health-related quality-of-life. However, data on the utility of existing surveys in capturing neurofibromatosis 1 skin treatment outcomes are lacking. This quantitative study examined the relationship between clinician-rated severity and visibility and patient-rated itch and quality-of-life (QoL) to (1) establish baseline levels of skin- and condition-specific-related QoL, itch, depression and anxiety; (2) identify patient concerns to inform the development and evaluation of skin interventions; and (3) compare the sensitivity of different QoL measures. Validated scales included Skindex-29, Dermatology Life Quality Index (DLQI), Neurofibromatosis 1-adult quality-of-life (NF1-AdQOL) questionnaire, and the Hospital Anxiety and Depression Scale (HADS). We recruited 100 participants (response rate: 95%). Of these, 42% reported itch and 23% had probable clinical anxiety. Our cohort had higher levels of anxiety and total HADS scores compared to a control population. Using multivariate regression analysis, increasing visibility significantly predicted poorer QoL using the Skindex-29, NF1-AdQOL, and DLQI (p < 0.05); and itch significantly predicted worse QoL in Skindex-29 and NF1-AdQOL (p < 0.05). The highest mean scoring questions in Skindex-29 and NF1-AdQOL concerned worry about worsening skin disease and embarrassment. The highest mean scoring questions in DLQI were regarding itch, pain, and embarrassment. Items asking specifically about cutaneous neurofibromas (cNF) scored higher than comparable skin-specific questions (t-test p value <0.05). In summary, this study provides insights into the factors contributing to impaired QoL, anxiety, and mood in NF1 patients with cutaneous neurofibromas. Key factors identified for use in cNF measures include visibility, itch, anxiety, embarrassment, fears of worsening skin disease, and cNF-specific questions.

Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins.

BACKGROUND: Enteroviruses are routinely detected with molecular methods within large cohorts that are at risk of type 1 diabetes. We aimed to examine the association between enteroviruses and either islet autoimmunity or type 1 diabetes. METHODS: For this systematic review and meta-analysis, we searched PubMed and Embase for controlled observational studies from inception until Jan 1, 2023. Cohort or case-control studies were eligible if enterovirus RNA or protein were detected in individuals with outcomes of islet autoimmunity or type 1 diabetes. Studies in pregnancy or other types of diabetes were excluded. Data extraction and appraisal involved author contact and deduplication, which was done independently by three reviewers. Study quality was assessed with the Newcastle-Ottawa Scale and National Health and Medical Research Council levels of evidence. Pooled and subgroup meta-analyses were done in RevMan version 5.4, with random effects models and Mantel-Haenszel odds ratios (ORs; 95% CIs). The study is registered with PROSPERO, CRD42021278863. FINDINGS: The search returned 3266 publications, with 897 full texts screened. Following deduplication, 113 eligible records corresponded to 60 studies (40 type 1 diabetes; nine islet autoimmunity; 11 both), comprising 12077 participants (5981 cases; 6096 controls). Study design and quality varied, generating substantial statistical heterogeneity. Meta-analysis of 56 studies showed associations between enteroviruses and islet autoimmunity (OR 2·1, 95% CI 1·3-3·3; p=0·002; n=18; heterogeneity χ2/df 2·69; p=0·0004; I2=63%), type 1 diabetes (OR 8·0, 95% CI 4·9-13·0; p<0·0001; n=48; χ2/df 6·75; p<0·0001; I2=85%), or within 1 month of type 1 diabetes (OR 16·2, 95% CI 8·6-30·5; p<0·0001; n=28; χ2/df 3·25; p<0·0001; I2=69%). Detection of either multiple or consecutive enteroviruses was associated with islet autoimmunity (OR 2·0, 95% CI 1·0-4·0; p=0·050; n=8). Detection of Enterovirus B was associated with type 1 diabetes (OR 12·7, 95% CI 4·1-39·1; p<0·0001; n=15). INTERPRETATION: These findings highlight the association between enteroviruses and islet autoimmunity or type 1 diabetes. Our data strengthen the rationale for vaccine development targeting diabetogenic enterovirus types, particularly those within Enterovirus B. Prospective studies of early life are needed to elucidate the role of enterovirus timing, type, and infection duration on the initiation of islet autoimmunity and the progression to type 1 diabetes. FUNDING: Environmental Determinants of Islet Autoimmunity, European Association for the Study of Diabetes, JDRF, Australian National Health and Medical Research Council, and University of New South Wales.