Summary Background Genetic disorders and congenital anomalies are the leading causes of infant mortality. Diagnosis of most genetic diseases in neonatal and paediatric intensive care units (NICU and PICU) is not sufficiently timely to guide acute clinical management. We used rapid whole-genome sequencing (STATseq) in a level 4 NICU and PICU to assess the rate and types of molecular diagnoses, and the prevalence, types, and effect of diagnoses that are likely to change medical management in critically ill infants. Methods We did a retrospective comparison of STATseq and standard genetic testing in a case series from the NICU and PICU of a large children's hospital between Nov 11, 2011, and Oct 1, 2014. The participants were families with an infant younger than 4 months with an acute illness of suspected genetic cause. The intervention was STATseq of trios (both parents and their affected infant). The main measures were the diagnostic rate, time to diagnosis, and rate of change in management after standard genetic testing and STATseq. Findings 20 (57%) of 35 infants were diagnosed with a genetic disease by use of STATseq and three (9%) of 32 by use of standard genetic testing (p=0·0002). Median time to genome analysis was 5 days (range 3–153) and median time to STATseq report was 23 days (5–912). 13 (65%) of 20 STATseq diagnoses were associated with de-novo mutations. Acute clinical usefulness was noted in 13 (65%) of 20 infants with a STATseq diagnosis, four (20%) had diagnoses with strongly favourable effects on management, and six (30%) were started on palliative care. 120-day mortality was 57% (12 of 21) in infants with a genetic diagnosis. Interpretation In selected acutely ill infants, STATseq had a high rate of diagnosis of genetic disorders. Most diagnoses altered the management of infants in the NICU or PICU. The very high infant mortality rate indicates a substantial need for rapid genomic diagnoses to be allied with a novel framework for precision medicine for infants in NICU and PICU who are diagnosed with genetic diseases to improve outcomes. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, and National Center for Advancing Translational Sciences.

Health care inequities among racial and ethnic groups remain prevalent. For people with type 1 diabetes who require increased medical access and care, disparities are seen in access to care and health outcomes. This article reports on a study by the T1D Exchange Quality Improvement Collaborative evaluating differences in A1C, diabetic ketoacidosis (DKA), severe hypoglycemia, and technology use among racial and ethnic groups. In a diverse cohort of nearly 20,000 children and adults with type 1 diabetes, A1C was found to differ significantly among racial and ethnic groups. Non-Hispanic Blacks had higher rates of DKA and severe hypoglycemia and the lowest rate of technology use. These results underscore the crucial need to study and overcome the barriers that lead to inequities in the care and outcomes of people with type 1 diabetes.Health inequities among racial and ethnic groups persist in both children and adults. Individuals with chronic conditions such as type 1 diabetes require increased medical access and care. Yet, there are disparities in access to care and health outcomes (1). The incidence of type 1 diabetes is increasing in the United States across all populations, and most significantly among Hispanic youths, but despite the higher incidence, health disparities continue to worsen among specific racial and ethnic groups (2,3). Mean A1C levels were found to be higher in Hispanics and non-Hispanic Blacks with type 1 diabetes compared with non-Hispanic Whites in the largest U.S. study to date, which included $11,000 youths and young adults in the T1D Exchange clinic network and registry (4). Non-Hispanic Blacks and Hispanics have been reported to perform fewer blood glucose checks per day than Non-Hispanic Whites (5,6). One study evaluating A1C trajectories over time in $16,000 youths from Australia, Europe, and the United States found that minority groups were more likely to have increasing A1C levels over time compared with Non-Hispanic Whites, specifically in the T1D Exchange and Diabetes-Patienten-Verlaufsdokumentation registries (7).

Analyses suggest an associated increase in T1D self-management behaviors in youths with increased sleep duration. These findings highlight the importance of assessing sleep in clinical practice, and encourage further research to examine effective strategies to address sleep hygiene as part of routine diabetes management.

Congenital parenchymal lung malformations have an estimated incidence at 1:25,000-1:35,000 births. We present a case of this rare congenital abnormality in a 38 year-old male, review the current literature with discussion of proposed causes, malignant potential, and management strategies. A 38-year-old white male presented with a 4-day history of chronic stable hemoptysis. Social history was notable for a 50-pack-year active smoking history and remote heavy alcohol consumption. Physical examination was normal. Chest radiograph revealed an ill defined right lower lobe infiltrate. Chest computed tomography demonstrated an irregular, thin-walled, cystic lesion with adjacent nodularity and calcifications. The patient received a right lower lobectomy. Pathologic specimen demonstrated a 10-cm, mostly thin-walled cyst with features suggestive of a congenital cyst adenomatoid malformation and areas of adenocarcinoma (mixed subtype with acinar and bronchioloalveolar patterns). Congenital cyst adenomatoid malformations have recently been renamed as congenital pulmonary airway malformations and are the most common type of congenital parenchymal lung malformations. Individuals typically present with recurrent pulmonary infections, pneumothorax, or hemoptysis. The development is controversial but believed to be a result of arrested development of the fetal bronchial tree during the sixth and seventh week of fetal development. Defects in thyroid transcription factor 1 have also been proposed. With the increasing use and image resolution of ultrasound in modern obstetric practice, congenital pulmonary airway malformations rarely go undetected into adulthood. Management remains controversial; however, most authors agree with early surgical excision.

ImportanceIn preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes.ObjectiveTo determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022.InterventionsParticipants were randomly assigned 1:1 to once-daily oral verapamil (n = 47) or placebo (n = 41) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care.Main Outcomes and MeasuresThe primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes.ResultsAmong 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial. In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95% CI, 0.01 to 0.27 pmol/mL]; P = .04). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, −0.3% [95% CI, −1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment.Conclusions and RelevanceIn children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT04233034