Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome.

INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials. METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aß)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years). RESULTS: In general linear models lower plasma Aß42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory. DISCUSSION: Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest. Highlights: Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.

Parents of children with Down syndrome reflect on their postnatal diagnoses, 2003-2022.

A 2003 survey revealed the scope of mothers' dissatisfaction with their postnatal support following a diagnosis of Down syndrome (DS). Substantial proportions of mothers reported that providers conveyed diagnoses with pity, emphasized negative aspects of DS, and neglected to provide adequate materials explaining DS. This study follows up on the 2003 survey by assessing whether parents' experiences have improved. Four DS nonprofit organizations, which participated in the original study, distributed a mixed-methods survey to families who have had children with DS between 2003 and 2022. Quantitative analysis assessed correlations among responses and differences between the 2003 and 2022 survey groups. Open-ended responses were qualitatively analyzed. Compared to the 2003 findings, parents' perceptions of their postnatal care have not improved (N = 89). Parents are increasingly likely to report that their providers pitied them, omitted positive aspects of DS, and provided insufficient materials describing DS. Substantial proportions of parents reported fear (77%) and anxiety (79%), only 24% described receiving adequate explanatory materials, and parents were 45% likelier to report that physicians discussed negative aspects of DS than positive aspects. Qualitatively, substantial numbers of parents recounted insensitive conduct by providers. These results suggest that despite interventions, parents' experiences of postnatal diagnoses of DS have not improved over time. Certain provider behaviors-such as describing positive aspects of DS and providing comprehensive explanatory materials-can reduce fear and anxiety, pointing to directions for reform.

Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population.

Results of inaugural international Down Syndrome Societal Services and Supports survey.

PURPOSE: We previously designed the Down Syndrome Societal Services and Supports Survey (DS-4S) to measure country-specific supports for people with Down syndrome (DS) across multiple life domains (healthcare, education, policy, independence, and community inclusion). We now report and analyze the results. METHODS: We partnered with international DS consortia, who distributed the DS-4S to 154 cumulative members representing over 100 countries. Organizations were included if they had a holistic focus on the lives of people with DS and if at least 50% of their members either have DS or are family members of people with DS. Factor analysis was used to analyze the results. RESULTS: We received survey responses from 55 different organizations in 50 countries who met inclusion criteria. Each country had complete data for at least 4 of the 5 domains. The lowest 5 scores were from countries in Africa and Asia; the highest 5 scores were in Europe and North America. CONCLUSION: The responses to the DS-4S stratified countries within each surveyed domain. The DS-4S can now be used to track countries' progress over time and to determine which countries have best practices that might be replicated. We will publish the results and update them biennially at www.DownSyndromeQualityOfLife.com.

Alzheimer's drugs, APPlication for Down syndrome?

Accumulation of the amyloid ß (Aß) peptide, derived from Aß precursor protein (APP), is a trait of Down syndrome (DS), as is early development of dementia that resembles Alzheimer's disease (AD). Treatments for this AD in DS simply do not. New drug therapies for AD, e.g., Lecanemab, are monoclonal antibodies designed to clear amyloid plaques composed of Aß. The increasingly real ability to target and dispose of Aß favors the use of these drugs in individuals with AD in DS, and, perhaps as earlier intervention for cognitive impairment. We present pertinent similarities between DS and AD in adult DS subjects, discuss challenges to target APP metabolites, and suggest that recently developed antibody treatments against Aß may be worth investigating to treat AD in DS.

Compromised femoral and lumbovertebral bone in the Dp(16)1Yey Down syndrome mouse model.

Down syndrome (DS), affecting ∼1 in 800 live births, is caused by the triplication of human chromosome 21 (Hsa21). Individuals with DS have skeletal features including craniofacial abnormalities and decreased bone mineral density (BMD). Lowered BMD can lead to increased fracture risk, with common fracture points at the femoral neck and lumbar spine. While the femur has been studied in DS mouse models, there is little research done on the vertebrae despite evidence that humans with DS have affected vertebrae. Additionally, it is important to establish when skeletal deficits occur to find times of potential intervention. The Dp(16)1Yey DS mouse model has all genes triplicated on mouse chromosome 16 orthologous to Hsa21 and displayed deficits in long bone, including trabecular and cortical deficits in male but not female mice, at 12 weeks. We hypothesized that the long bone and lumbovertebral microarchitecture would exhibit sexually dimorphic deficits in Dp(16)1Yey mice compared to control mice and long bone strength would be diminished in Dp(16)1Yey mice at 6 weeks. The trabecular region of the 4th lumbar (L4) vertebra and the trabecular and cortical regions of the femur were analyzed via micro-computed tomography and 3-point bending in 6-week-old male and female Dp(16)1Yey and control mice. Trabecular and cortical deficits were observed in femurs from male Dp(16)1Yey mice, and cortical deficits were seen in femurs of male and female Dp(16)1Yey mice. Male Dp(16)1Yey femurs had more deficits in bone strength at whole bone and tissue-estimate level properties, but female Dp(16)1Yey mice were also affected. Additionally, the L4 of male and female Dp(16)1Yey mice show trabecular deficits, which have not been previously reported in a DS mouse model. Our results indicate that skeletal deficits associated with DS occur early in skeletal development, are dependent on skeletal compartment and site, are sex dependent, and potential interventions should likely begin early in skeletal development of DS mouse models.

The functional roles of S-adenosyl-methionine and S-adenosyl-homocysteine and their involvement in trisomy 21.

The one-carbon metabolism pathway is involved in critical human cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. In the homocysteine-methionine cycle S-adenosyl-methionine (SAM) and S-adenosyl-homocysteine (SAH) are synthetized, and their levels are finely regulated to ensure proper functioning of key enzymes which control cellular growth and differentiation. Here we review the main biological mechanisms involving SAM and SAH and the known related human diseases. It was recently demonstrated that SAM and SAH levels are altered in plasma of subjects with trisomy 21 (T21) but how this metabolic dysregulation influences the clinical manifestation of T21 phenotype has not been previously described. This review aims at providing an overview of the biological mechanisms which are altered in response to changes in the levels of SAM and SAH observed in DS.

Pulmonary Hypertension in Developmental Lung Diseases.

Diverse genetic developmental lung diseases can present in the neonatal period with hypoxemic respiratory failure, often associated with with pulmonary hypertension. Intractable hypoxemia and lack of sustained response to medical management should increase the suspicion of a developmental lung disorder. Genetic diagnosis and lung biopsy are helpful in establishing the diagnosis. Early diagnosis can result in optimizing management and redirecting care if needed. This article reviews normal lung development, various developmental lung disorders that can result from genetic abnormalities at each stage of lung development, their clinical presentation, management, prognosis, and differential diagnoses.

Transient abnormal myelopoiesis requiring advanced neonatal intensive care treatment.

AIM: Five to thirty percent of neonates with trisomy 21 develop transient abnormal myelopoiesis (TAM) with a high mortality rate. The aim of the study was to identify contributing factors that determine mortality and need for chemotherapy in this patient group. METHODS: Six-year, single-centre, retrospective study of neonatal TAM cases requiring admission to intensive care. Data were collected from electronic patient records, laboratory and genetic results. The odds ratio was calculated to assess the likelihood of neonates with certain clinical characteristics having short-term mortality and needing chemotherapy. RESULTS: Twenty-one neonates were studied with a mortality rate of 28%. Neonates requiring inotropic support (OR 19, 95% CI: 0.9-399, p = 0.05) and inhaled nitric oxide (iNO) (OR 13, 95% CI: 1.4-124.3, p = 0.03) were less likely to survive to discharge. Neonates needing mechanical ventilation (OR 14, 95% CI: 1.1-185.5, p = 0.04), or a white cell count >50 × 109/L (OR 27, 95% CI: 1.2-605.7, p = 0.04) were more likely to receive chemotherapy. CONCLUSION: A high mortality rate was identified in TAM neonates with symptomatic pulmonary hypertension (PH) needing active treatment strategies, such as inotropes and iNO. The presence of PH should be considered in the clinical management, prognosis and parental counselling.

Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21.

AIM: In this study, we compared the ratio of second trimester fetal biometric measurements to nasal bone length (NBL) in fetuses with normal karyotype and trisomy 21 to determine their diagnostic prognostic value. MATERIALS AND METHODS: The study included 148 pregnant women who obtained second-trimester ultrasonographic fetal anatomy and had amniocentesis (AS) for fetal karyotyping. The fetal karyotype results divided the groups into normal and trisomy 21 fetuses. Age, obstetric history, first and/or second trimester screening test risk ratios, fetal biometric measurements, and NBL mm, median (MoM) multiples, and percentile values were recorded and compared between groups. RESULTS: BPD/NBL ratios above 9.26 predict trisomy 21 in fetuses with 77.6% sensitivity and 86.1% specificity (p = 0.001). HC/NBL ratios above 34.50 predict trisomy 21 in fetuses with 77.8% sensitivity and 88.8% specificity (p = 0.001). FL/NBL ratios above 6.02 predict trisomy 21 in fetuses with 69.6% sensitivity and 72.2% specificity (p = 0.001). HL/NB ratios above 6.56 predict trisomy 21 in fetuses with 95.5% sensitivity and 47.2% specificity (p = 0.001). The NBL MoM value demonstrated a high diagnostic accuracy for normal-karyotype fetuses (p = 0.021). CONCLUSION: We found that BPD/NBL, HC/NBL, FL/NBL, and HL/NBL ratios differed between fetuses with a normal karyotype and those with trisomy 21, specifically the HC/NBL ratio, which predicted trisomy 21 with good diagnostic accuracy. In identifying normal-karyotype fetuses, the NBL MoM was highly accurate.

Comparison of power spectra from overnight electroencephalography between patients with Down syndrome and matched control subjects.

Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full-night in-laboratory polysomnography from 100 patients with Down syndrome, and 100 age- and sex-matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)-180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0-10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25-4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5-12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude-the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome.

Prenatal aneuploidy screening in a low-risk Hispanic population: price elasticity and cost-effectiveness.

BACKGROUND: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursement for procedures in which the International Classification of Diseases, Tenth Edition, code for serum aneuploidy screening used by certain communities was stipulated. This change led to a substantial number of patients who went without aneuploidy screening for approximately 3 years. OBJECTIVE: This study aimed to determine the change in use and cost-effectiveness of prenatal aneuploidy serum screening in a low-risk Hispanic Medicaid population in Massachusetts. STUDY DESIGN: We conducted a retrospective chart review of Spanish-speaking pregnant patients younger than 35 years of age who underwent aneuploidy serum screening at a Massachusetts community health center. The study compared the aneuploidy serum screening rates for the periods before and after May 2016 when the Massachusetts Medicaid program, MassHealth, temporarily discontinued reimbursement for the screening. Based on these rates, we developed a Markov cohort simulation model to assess the economic value of reimbursed aneuploidy screening vs nonreimbursed or limited screening. Clinical outcomes included trisomy 21, live births, and therapeutic abortions for a trisomy 21 diagnosis. Economic outcomes included discounted quality-adjusted life years and lifetime medical costs, net health benefit, and incremental cost-effectiveness ratios. RESULTS: Before the MassHealth policy change, 69% (55/80) of pregnant individuals selected quad or sequential screens in comparison with only 9% (10/112) who selected screens after the policy change. Traditional aneuploidy serum screening in a low-risk (aged <35 years) Hispanic population was considered to be cost-saving (ie, led to lower incremental costs and higher incremental benefits when compared with nonreimbursed or limited screening). CONCLUSION: From a United States healthcare payer perspective, aneuploidy serum screening for Hispanic pregnant individuals under 35 years of age is economically advantageous when compared with limited screening.

Outcomes and characteristics in term infants with necrotising enterocolitis and CHD.

BACKGROUND: CHD is a significant risk factor for the development of necrotising enterocolitis. Existing literature does not differentiate between term and preterm populations. Long-term outcomes of these patients are not well understood. The aim was to investigate the baseline characteristics and outcomes of term normal birth weight infants with CHD who developed necrotising enterocolitis. METHODS: A retrospective review was performed of infants from a single tertiary centre with CHD who developed necrotising enterocolitis of Bell's Stage 1-3, over a ten-year period. Inclusion criteria was those born greater than 36 weeks' gestation and birth weight over 2500g. Exclusion criteria included congenital gastro-intestinal abnormalities. Sub-group analysis was performed using Fisher's exact test. RESULTS: Twenty-five patients were identified, with a median gestational age of 38 weeks. Patients with univentricular physiology accounted for 32% (n = 8) and 52% of patients (n = 13) had a duct-dependent lesion. Atrioventricular septal defect was the most common cardiac diagnosis (n = 6, 24%). Patients with trisomy 21 accounted for 20% of cases. Mortality within 30 days of necrotising enterocolitis was 20%. Long-term mortality was 40%, which increased with increasing Bell's Stage. In total, 36% (n = 9) required surgical management of necrotising enterocolitis, the rate of which was significantly higher in trisomy 21 cases (p < 0.05). CONCLUSION: Not previously described in term infants is the high rate of trisomy 21 and atrioventricular septal defect. This may reflect higher baseline incidence in our population. Infants with trisomy 21 were more likely to develop surgical necrotising enterocolitis. Mortality at long-term follow-up was high in patients with Bell's Stage 2-3.

Correlation between telomere shortening in maternal peripheral blood and fetal aneuploidy.

BACKGROUND: This study aimed to assess whether maternal telomere length is a more accurate predictor of trisomy 21 than maternal age while also exploring the factors influencing maternal and fetal telomere length. METHODS: Forty mothers with fetuses carrying extra maternal copies of chromosome 21 were defined as trisomy 21 cases, and 18 mothers with normal karyotype fetuses were defined as controls. Telomere lengths of maternal blood lymphocytes and amniotic fluid cells were determined using real-time polymerase chain reaction. Fetal and maternal telomere lengths were compared between the two groups. Moreover, we analyzed the factors influencing maternal and fetal telomere length in the trisomy 21 pedigree. A logistic regression model was used to analyze the correlation between maternal telomere length and trisomy 21 risk. In addition, receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using maternal telomere length as an indicator of trisomy 21 risk. RESULTS: The study revealed that both maternal and fetal telomere lengths were significantly shorter in trisomy 21 cases than in the controls. In the trisomy 21 group, the maternal age, occupation, and nationality showed no significant correlation with their telomere length; fetal telomere length exhibited a positive correlation with maternal telomere length. Furthermore, maternal telomere length shortening is associated with trisomy 21 (OR = 0.311; 95% CI, 0.109-0.885, P < 0.05). The results of ROC curve analysis indicated that a combined assessment of maternal age and maternal telomere length predicted fetal chromosome trisomy more effectively than a single assessment (area under the curve 0.808, 95% CI, 0.674-0.941, P < 0.001). CONCLUSION: Maternal age combined with maternal telomere length proved to be a superior predictor of trisomy risk. Additionally, maternal telomere length was found to influence fetal telomere length.

Enhancing Speech Rehabilitation in a Young Adult with Trisomy 21: Integrating Transcranial Direct Current Stimulation (tDCS) with Rapid Syllable Transition Training for Apraxia of Speech.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed toward examining post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and Trisomy 21 (T21, Down syndrome). This N-of-1 randomized trial examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) over 10 sessions of anodal tDCS (1.5 mA, 25 cm) over Broca's area with the cathode over the contralateral region was compared to 10 sessions of sham-tDCS and four control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSW production progressively improved (gain of 40%) under tDCS (sham-tDCS and control sessions showed < 20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. Speech accuracy under tDCS was correlated with Wernicke's area activation (P3 current source density), which in turn was correlated with the activation of the left supramarginal gyrus and the Sylvian parietal-temporal junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated speech sound acquisition in a young adult with T21 and CAS, possibly through activating brain regions required for phonological working memory.

Follow-up of children with Down syndrome and sleep disordered breathing and the effects of treatment on actigraphically recorded sleep, quality of life, behaviour, and daytime functioning.

Children with Down syndrome are at increased risk of obstructive sleep disordered breathing, which has deleterious effects on daytime functioning. We aimed to examine the effects of treatment of sleep disordered breathing on sleep quality and daytime functioning in children with Down syndrome, and hypothesised that these would be improved. Thirty-four children completed a baseline study and a follow-up 2 years later. Measures at both time points included 7 days of actigraphy and parents completed a number of questionnaires assessing sleep, behaviour, daytime functioning, and quality of life. All children had overnight polysomnography at baseline; 15 children (44%) were treated. At baseline the treated group had more severe sleep disordered breathing compared with the untreated group: obstructive apneoa-hypopnoea index 29.3 ± 38.2 events/h versus 3.3 ± 5.2 events/h (p < 0.01). Actigraphy showed no significant differences in total sleep time, sleep efficiency, sleep schedules from baseline to follow up in either group. The sleep disturbance (p < 0.01) and total problems (p < 0.05) scales on the OSA-18 and the sleep disordered breathing subscale on the Paediatric Sleep Problem Survey Instrument (p < 0.01) improved in the treated children. There were no changes in any measure in the untreated children. Treatment of sleep disordered breathing improves symptoms, sleep disturbance and quality of life in children with Down syndrome, but has no demonstrable impact on actigraphic sleep measures or daytime behaviour or function. In contrast, children who were not treated, despite having less severe disease at baseline, had increased sleep disruption and no change in quality of life.

Myeloid Proliferations Associated with Down Syndrome: Clinicopathologic Characteristics of Forty Cases from Five Large Academic Institutions.

INTRODUCTION: The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically similar to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS. Differentiating TAM and ML-DS is challenging but clinically critical. METHODS: We performed a retrospective review of ML-DS and TAM cases collected from five large academic institutions in the USA. We assessed clinical, pathological, immunophenotypical, and molecular features to identify differentiating criteria. RESULTS: Forty cases were identified: 28 ML-DS and 12 TAM. Several features were diagnostically distinct, including younger age in TAM (p < 0.05), as well as presentation with clinically significant anemia and thrombocytopenia in ML-DS (p < 0.001). Dyserythropoiesis was unique to ML-DS, as well as structural cytogenetic abnormalities aside from the constitutional trisomy 21. Immunophenotypic characteristics of TAM and ML-DS were indistinguishable, including the aberrant expression of CD7 and CD56 by the myeloid blasts. DISCUSSION: The findings of the study confirm marked biological similarities between TAM and ML-DS. At the same time, several significant clinical, morphological, and genetic differences were observed between TAM and ML-DS. The clinical approach and the differential diagnosis between these entities are discussed in detail.

Long-Term Outcomes in Patients With Trisomy 21 and Obstructive Sleep Apnea.

OBJECTIVE: To better understand the long-term health implications of obstructive sleep apnea (OSA) on patients with Trisomy 21 (T21) and the role of sleep surgery as a therapeutic intervention. STUDY DESIGN: Retrospective large database review. SETTING: The prevalence of OSA is as high as 75% in patients with T21. We sought to examine the cardiovascular, neurological, and endocrinological outcomes of patients with T21 10 years after their diagnosis of OSA. METHODS: TriNetX, an electronic medical record database, was queried for health outcomes in patients with T21 after diagnosis of OSA. The group was further analyzed to identify those who underwent sleep surgery, including hypoglossal nerve stimulation, palatopharyngoplasty, or adenotonsillectomy. RESULTS: Ten years after diagnosis, patients with OSA and T21 had a significantly higher incidence of death, myocardial infarction, cerebral infarction, heart failure, cardiac arrhythmia, ischemic heart disease, atrial fibrillation, essential hypertension, pulmonary hypertension, diabetes mellitus, and Alzheimer's disease compared to patients with T21 alone. Patients with OSA and T21 who underwent sleep surgery had significantly reduced incidence of adverse health outcomes compared to patients using continuous positive airway pressure. CONCLUSION: Our findings suggest that patients with T21 and OSA are at higher risk of poor health outcomes, which may require closer monitoring for earlier diagnosis and management of comorbid conditions. Sleep surgery is a suitable treatment modality for mitigating the risk of adverse outcomes in this population and should be considered in patients who are eligible surgical candidates.

Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions.

A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.

Outcomes of atrioventricular septal defects with and without down syndrome: analysis of the national inpatient database.

BACKGROUND: Controversial data exist about the impact of Down syndrome on outcomes after surgical repair of atrioventricular septal defect. AIMS: (A) assess trends and outcomes of atrioventricular septal defect with and without Down syndrome and (B) determine risk factors associated with adverse outcomes after atrioventricular septal defect repair. METHODS: We queried The National Inpatient Sample using International Classification of Disease codes for patients with atrioventricular septal defect < 1 year of age from 2000 to 2018. Patients' characteristics, co-morbidities, mortality, and healthcare utilisation were evaluated by comparing those with versus without Down syndrome. RESULTS: In total, 2,318,706 patients with CHD were examined; of them, 61,101 (2.6%) had atrioventricular septal defect. The incidence of hospitalisation in infants with atrioventricular septal defect ranged from 4.5 to 7.5% of all infants hospitalised with CHD per year. A total of 33,453 (54.7%) patients were associated with Down syndrome. Double outlet right ventricle, coarctation of the aorta, and tetralogy of Fallot were the most commonly associated with CHD in 6.9, 5.7, and 4.3% of patients, respectively. Overall atrioventricular septal defect mortality was 6.3%. Multivariate analysis revealed that prematurity, low birth weight, pulmonary hypertension, and heart block were associated with mortality. Down syndrome was associated with a higher incidence of pulmonary hypertension (4.3 versus 2.8%, p < 0.001), less arrhythmia (6.6 versus 11.2%, p < 0.001), shorter duration for mechanical ventilation, shorter hospital stay, and less perioperative mortality (2.4 versus 11.1%, p < 0.001). CONCLUSION: Trends in atrioventricular septal defect hospitalisation had been stable over time. Perioperative mortality in atrioventricular septal defect was associated with prematurity, low birth weight, pulmonary hypertension, heart block, acute kidney injury, and septicaemia. Down syndrome was present in more than half of atrioventricular septal defect patients and was associated with a higher incidence of pulmonary hypertension but less arrhythmia, lower mortality, shorter hospital stay, and less resource utilisation.