Myotonic Dystrophy type 1 (DM1) is an autosomal multisystem disorder manifested due to unstable CTG nucleotide repeat expansion within the 3'-untranslated region of the dystrophia myotonica protein kinase ( DMPK ) gene. Although progress towards understanding of molecular pathogenesis in muscle and heart has been made, the pathways that affect the brain in DM1 is fundamentally unknown. In addition, the congenital DM1 manifest even more complicated brain abnormalities. Despite the wealth of existing cellular and animal models, iPSCs based studies are being fostered as they replicate the human model more closely to the disease. In view of this context, we set out to characterize the differentiation potential of congenital DM1 patient derived iPSC lines towards neuronal cells. Using neurogenin2 (NGN2) induced direct reprogramming of iPSCs into neurons and chemically defined media-induced neural induction protocol, we find that congenital DM1 mutant iPSC derived neurons exhibited precocious differentiation, as evidenced by their expression of pan-neuronal markers TUJ1 and Map2, along with increased processes extension and neurite length. Moreover, unbiased RNA sequencing analyses and qPCR validation revealed precocious and enhanced expression of several neurogenic transcription factors including, Ascl1, NeuroG2, and NeuroD1. Furthermore, immunofluorescence imaging of MBNL1 and MBNL2, RNA-splicing factors, displayed enhanced nuclear aggregations, a hallmark of the DM1 disease, in the mutant lines. Moreover, investigation of RNA splicing events identified mis-splicing in many important genes/transcripts including RMST, ANK3 and MBD1 during the neural conversion of congenital DM1 lines. These studies reveal novel paradigms that may contribute to neurological pathogenesis in CDM1 patients. These studies also provide a strong foundation for future mechanistic investigation aimed at understanding CDM1 pathology and may open new avenues for the development of gene therapy approaches for individuals with DM1.
Congenital toxoplasmosis (CT) is a vertically transmitted infection with a variable clinical spectrum, ranging from asymptomatic infection at birth to severe neurological and ocular sequelae. While the classic triad of hydrocephalus, intracranial calcifications, and chorioretinitis is well characterized, isolated neonatal hyperbilirubinemia as the initial presenting feature is uncommon and may delay diagnosis. We report a case of CT in a Chinese neonate who presented with jaundice and was subsequently found to have subclinical active chorioretinitis, cerebral edema, and bilateral central auditory pathway dysfunction. The case also illustrates therapeutic challenges related to the availability of first-line anti-parasitic agents. A 9-day-old term male infant was admitted for persistent jaundice. He was born at 39 + 4 weeks' gestation, with a prenatal history notable only for maternal cat exposure and treated hypothyroidism. Initial serological testing at the referring hospital revealed positive Toxoplasma gondii IgM and IgG. After transfer, two consecutive blood metagenomic next-generation sequencing (mNGS) tests detected T. gondii DNA (reads: 6 and 7). The combination of negative first-trimester maternal serology, postpartum maternal IgM/IgG positivity, neonatal IgM positivity, and repeated detection of T. gondii DNA in neonatal blood strongly supported congenital toxoplasmosis. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein, while CSF mNGS was negative, possibly reflecting low pathogen burden or compartmentalized infection. Further evaluation demonstrated bilateral active chorioretinitis on fundoscopic examination, abnormal brainstem auditory evoked potentials consistent with bilateral central auditory pathway dysfunction, and brain MRI showing cerebral edema with punctate hemorrhages. Due to initial unavailability of pyrimethamine, azithromycin followed by trimethoprim-sulfamethoxazole was administered; however, no clear improvement in CSF inflammatory indices was observed during this period. After initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid, the patient demonstrated rapid clinical improvement and radiological resolution of brain lesions on follow-up MRI, with marked improvement of chorioretinal scars. Clinicians should consider congenital toxoplasmosis in neonates with unexplained jaundice, even in the absence of classic clinical manifestations. Comprehensive multi-organ evaluation, including neuroimaging, ophthalmologic examination, and auditory testing, is essential for early disease characterization. Standard pyrimethamine-sulfadiazine-folinic acid therapy may be associated with better clinical and radiological outcomes and should be used when available. Long-term multidisciplinary follow-up is necessary to monitor potential sequelae.
The objective of this scoping review is to answer the question, "What is the existing evidence on nurses' educational needs in caring for adults with congenital heart disease?" by identifying and summarizing research and grey literature on the educational needs of nurses who care for this population. The scoping review will use the Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) for reporting. Five databases will be searched: Medline, Embase, CINAHL, ERIC, and Scopus. Grey Matters, Google, and thesis and dissertation databases will be used to identify relevant grey literature. All types of published articles and non-empirical research will be included with no temporal, geographical, or language restrictions. Two independent reviewers will screen titles and abstracts, engage in full-text screening, and perform data extraction in Covidence. Any disagreements will be resolved through a third reviewer. The results of the scoping review will be analyzed using descriptive statistics and narrative analysis. The results will be reported using tables and figures. Findings will be disseminated through a manuscript and at conferences. The findings of this scoping review aim to inform future research and interventions on the nursing care of adults with congenital heart disease. The scoping review was registered on Open Science Framework (https://osf.io/4t5hr) on December 5, 2025.
Macrodactyly is a rare, non-hereditary congenital anomaly characterized by progressive enlargement of digits due to overgrowth of bone, fat, nerve, or soft tissue. It is typically diagnosed and treated in childhood. If left untreated, it may persist into adulthood, resulting in significant functional impairment and cosmetic deformity. We report a 51-year-old female with congenital macrodactyly affecting the left thumb, index, and middle fingers. She experienced progressive enlargement of these digits since birth and reduced function in her left hand. Clinical examination revealed marked hypertrophy, complete loss of function in the left index finger, and partial movement in the thumb and middle finger. Surgical management included amputation of the left index finger, debulking of the thumb and middle finger, and carpal tunnel release. Postoperatively, the patient demonstrated significant improvement in hand function, reduced digit size, and satisfactory cosmetic results. Adult-onset presentation of macrodactyly is rare, but individualized surgical treatment can lead to substantial improvement.
Sensory experience is critical for cortical maturation, but the cellular consequences of its absence remain poorly understood in humans. Using in vivo sub-millimeter 3 T and 7 T MRI and ultra-high-gradient diffusion MRI, we investigated the effects of congenital blindness on the human early visual cortex. Blind individuals showed reduced R2* and MTsat-markers of iron and myelin-along with increased diffusivity, orientation dispersion, and reduced neurite density in the gray and superficial white matter. Cortical thickness was increased in blind individuals and associated with lower myelin and iron, questioning the long-standing assumption that increased thickness primarily reflects disrupted pruning. Our results provide no direct evidence for disrupted pruning. However, they suggest reduced myelination and oligodendrogenesis as key effects of congenital blindness and highlight the critical role of sensory input in shaping and stabilizing cortical circuits.
Right ventricular (RV) function is crucial in the prognosis of adults with congenital heart disease (ACHD). However, its relationship with exercise capacity (EC) and quality of life (QoL) in ACHD remains underexplored. Despite the established benefits of physical activity in CHD, there is limited knowledge regarding the cardiac effects of exercise training in ACHD. To assess the relationship between RV function, comprehensively evaluated using two-dimensional multiplane echocardiography (2D MPE), and both EC and QoL in adults with various types of CHD. Additionally, to investigate the effect of a 16-week home-based aerobic and strength exercise program on these parameters. Fifty-five ACHD underwent transthoracic echocardiographic assessment of RV function, including conventional parameters and longitudinal RV strain, both measured from four RV walls using 2D MPE. The patients also completed a cardiopulmonary exercise test and a QoL questionnaire, and were randomized to either conventional care or a 16-week home-based rehabilitation program combining aerobic interval cycle training and dynamic strength exercises, followed by retesting. At baseline, RV function correlated with EC, measured by percent-predicted peak oxygen consumption. Moreover, significant correlations were observed between RV and QoL parameters, including physical functioning, general health perception and visual analogue scale score. EC, muscle strength and QoL improved following the exercise program, while 39% of patients in the intervention group were non-adherent. RV function correlates with EC and QoL in a diverse ACHD population. ACHD patients should be encouraged to engage in regular exercise, and exercise training should be integrated into CHD treatment.
To investigate the incidence, anatomical distribution, severity and concordance of congenital malformations (CMs) in twin pregnancies according to both zygosity and chorionicity in a cohort selected to minimize non-embryological confounding factors. This was a retrospective single-center cohort study including twin pregnancies evaluated at a fetal medicine referral center (Fetal Medicine Unit, Di Venere Hospital, Bari, Italy) between 1 January 2016 and 31 December 2025. Pregnancies conceived via assisted reproductive technology and those complicated by major maternal metabolic or systemic conditions or abnormalities attributable to secondary hemodynamic complications of monochorionic pregnancy were excluded. Chorionicity was determined on first-trimester ultrasound. Zygosity was established by invasive prenatal molecular testing when available or by standard clinical criteria; molecular confirmation was obtained for almost all pregnancies with structural CMs. CMs were classified according to anatomical district, severity (major vs minor) and concordance. Analyses were performed at pregnancy level. Based on descriptive evidence of anatomical clustering, logistic regression analysis was performed using monozygosity as the exposure variable and cardiac and/or central nervous system (CNS) malformations as the outcome. Among 936 twin pregnancies evaluated, 564 met the inclusion criteria. Overall, CMs were identified in 102 (18.1%) pregnancies, including 57 (55.9%) major and 45 (44.1%) minor anomalies. The overall prevalence of CMs was broadly comparable between twin types. CMs were predominantly discordant between cotwins across all groups. Monozygotic pregnancies demonstrated a distinct non-random anatomical distribution pattern characterized by enrichment of cardiac anomalies, particularly conotruncal defects, and CNS anomalies, particularly neural tube defects. When pregnancies were analyzed according to zygosity alone, cardiac and CNS anomalies accounted for over half of major CMs in monozygotic twins compared with approximately one-quarter in dizygotic twins. Logistic regression analysis confirmed an association between monozygosity and cardiac and/or CNS malformations (odds ratio, 4.13 (95% CI, 1.02-16.68); P = 0.047). Monozygosity was not associated with an increased overall prevalence of CMs but with selective anatomical clustering and a predominance of discordant phenotypes. These findings support the concept that monozygotic twinning may influence early developmental patterning rather than simply increasing the overall risk of malformation. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.
Congenital complete atrioventricular block (CCAVB) is a rare autoimmune mediated disorder with a guarded prognosis, particularly when associated with extreme prematurity and severe bradycardia. Recent advances in neonatal care for extremely premature infants with delivery at level IV neonatal intensive care unit and novel pediatric pacing technologies, have significantly reduced morbidity and mortality in this unique patient population. We present 2 cases of CCAVB in extremely premature neonates, who were successfully managed with epicardial pacing using a novel miniaturized pacemaker.
The procedural sedation for young children, especially in infants under 3 months old, and those with congenital heart disease (CHD) is relatively challenging and risky. This study compares the efficacy and safety of intranasal dexmedetomidine and oral chloral hydrate for sedation in these special populations and identifies the risk factors that influencing sedation success. This retrospective study included infants with CHD aged under 3 months who underwent outpatient sedation for transthoracic echocardiography (TTE) from January 2023 to January 2024. Sedation was administered as either intranasal dexmedetomidine (Dex) 2 μg/kg or oral chloral hydrate (50 mg/kg). Failure to achieve adequate sedation with the initial dose was defined as initial sedation failure. Ultimate sedation failure was determined if TTE examination remained incomplete despite rescue interventions. Data including heart rate (HR), pulse oxygen saturation (SpO2), sedation onset time, discharge time, and adverse reactions were collected. The primary outcomes were the initial sedation success rate. The groups were compared using propensity score matching (PSM) analysis. While the secondary outcome was the risk factors that influencing initial and overall sedation success. A total of 383 patients were included in the final analysis. The initial sedation success rate and the overall success rate were higher in the Dex 2 μg/kg group than in the chloral hydrate group before and after PSM. The sedation onset time and the discharge time in the Dex 2 μg/kg group was significantly shorter than those in the chloral hydrate group. The decline of HR in the Dex 2 μg/kg group was greater than that in the chloral hydrate group both before and after PSM. No severe adverse reactions occurred. Children with low body weight and prolonged fasting time were independent risk factors that influencing sedation success rate. Compared with oral chloral hydrate, the use of intranasal dexmedetomidine of 2 μg/kg was related to a significantly higher success rate of sedation without increasing severe adverse events in infants with CHD aged under 3 months. Prolonged fasting time and low body weight may significantly affect sedation success.
11β-hydroxylasedeficiency (11β-OHD) is a rare form of congenital adrenal hyperplasia caused by biallelic pathogenic variants in the CYP11B1 gene. It leads to impaired cortisol synthesis, resulting in increased adrenocorticotropic hormone stimulation and consequent accumulation of steroid precursors, which are diverted to androgen synthesis. In addition, the accumulation of 11-deoxycorticosterone, which is a potent mineralocorticoid, causes hyporeninemic hypokalemic hypertension. We report the clinical, hormonal, and genetic profiles of five children with 11β-OHD, emphasising phenotypic variability, a median 2-year diagnostic delay, the crucial role of hormonal profile in diagnosis, and management challenges, including post-treatment central precocious puberty. Two novel CYP11B1 variants were identified in two unrelated patients. Hydrocortisone replacement resolved hypertension in only one of the three hypertensive patients; others required spironolactone. Early differentiation of 11β-OHD from 21-hydroxylase deficiency is critical to prevent hypertension-related morbidity.
Neglected congenital talipes equinovarus (CTEV) presents a formidable challenge in pediatric orthopedics, characterized by rigid soft-tissue contractures and adaptive bony changes that occur when the deformity remains untreated past the walking age. While neonatal clubfoot is successfully managed via the Ponseti method, delayed presentations require interventions that can address fixed skeletal remodeling without the morbidity of extensive posteromedial releases. This report analyzes a single case of a child with neglected CTEV treated with the Joshi's external stabilizing system (JESS), following the patient from the pre-operative state through a 3-year follow-up period. A 3.5-year-old female presented with an uncorrected, unilateral, neglected idiopathic clubfoot. The clinical examination revealed a rigid, non-reducible deformity with a Pirani score of 6.0 and a Dimeglio score of 18 (Grade IV). Severe equinus, varus, cavus, and forefoot adduction were present, complicated by a large lateral-border callosity. Treatment involved the surgical application of the JESS fixator using a three-stage frame assembly. A protocol of fractional differential distraction was initiated postoperatively, distracting the medial side at twice the rate of the lateral side (1 mm/day vs. 0.5 mm/day) over 6 weeks, followed by a 6-week static stabilization phase. By the 3-year follow-up, the patient achieved a painless, plantigrade, and functional foot with significantly improved radiological indices. The talocalcaneal angles in both anteroposterior and lateral views normalized, and the patient demonstrated excellent range of motion compared to historical outcomes of open soft-tissue procedures. This case underscores JESS as a versatile, minimally invasive, and effective modality for managing the complex biomechanical demands of neglected clubfoot in low-resource and delayed-presentation settings.
Fetal intervention via vesicoamniotic shunt (VAS) in congenital lower urinary tract obstruction (cLUTO) aims to improve survival and mitigate pulmonary hypoplasia. Today, early VAS is increasingly utilized to preserve renal function. However, appropriate patient selection, VAS-associated complications and long-term management remain challenging. To investigate surgical management of the urethra and its outcome in cLUTO patients with early and late VAS. We performed a single-center retrospective cohort study in cLUTO patients with prenatal intervention between 01/2017 and 12/2022. VAS was performed in 42 patients, of which 21 received early VAS at <17 weeks and 18 cases late VAS at ≥17 weeks of gestation. In three patients, the exact time-point of VAS was unknown. Urethral hypoplasia and PUV (posterior urethral valves) with concomitant urethral hypoplasia were more frequent in early VAS (early VAS: 43 % versus late VAS: 6 %). In the late VAS group, PUV was the prevailing pathology (61 %). After birth, more patients with late VAS had a urethral caliber allowing spontaneous voiding or urethral catheter placement (early VAS: 0 % versus late VAS: 28 %). In the early VAS group, 83 % of initial endoscopies were unsuccessful compared to 29 % in late VAS (p < 0.001). The Cox model showed that the likelihood of ever having a successful endoscopy was significantly higher at a faster rate in late VAS [2.26 (1.02; 4.97) p = 0.04], compared to early VAS. Six early VAS cases required repeat endoscopies, which was not the case in the late VAS group. Our results show an association of early VAS with a decreased number of successful endoscopic interventions/evaluations. It remains highly speculative whether this is due to the severity of the underlying condition or a hypoplastic urethra as a result of early bypass in pregnancy. Based on our experience, we put forward an algorithm to guide attending pediatric urologists and surgeons. Our study's limitations are its retrospective design, small sample size, reliance on information provided by caregivers regarding urinary diversion and voiding at the last follow-up and the variation in follow-up durations. Our data suggests that early VAS patients are less likely to undergo a successful endoscopic intervention/evaluation and if so, to a later time. To reduce the risk of iatrogenic urethral stenosis from early urethral instrumentation and allow the infant to thrive, we propose urinary diversion via tubes or vesicostomy until endoscopy and/or complex reconstructive procedures are feasible.
Paediatric cardiac catheterization is pivotal in the diagnosis and management of patients with congenital heart disease. Although cardiac referral centres exist, access to cardiac surgery remains limited in low-income countries. The study aimed to describe the demographic and clinical profile, determine adverse outcomes, and identify predictors of complications among children undergoing cardiac catheterization at a state hospital in Johannesburg, Gauteng. A retrospective cohort study was performed on children aged 0-18 years with congenital heart disease who presented for cardiac catheterisation between January 2018 and December 2022. Patient data was obtained from the cardiac catheterisation laboratory, anaesthetic records and the paediatric cardiac database. Descriptive and multivariate regression data analysis were performed. A total of 597 paediatric cardiac catheterization procedures were analysed. The median (IQR) age was 1.8 (0.8-4.0) years with 52% males. Two-thirds, 397 (66%), were on anti-failure treatment and 236 (40%) had pulmonary hypertension. The Catheterisation RISk score for Paediatrics (CRISP) score was significantly associated with complications AOR 1.21 (95% CI 1.10-1.33; p < 0.001). Age <1 year was predictive of complications AOR 1.83 (95% CI 1.11-3.01; p = 0.018). The presence of a congenital syndrome was also associated with increased odds of complications AOR 1.72 (95% CI 1.10-2.67; p = 0.016). Peri-operative administration of inotropes AOR 18.3 (95% CI 6.05-70.0; p < 0.001), beta blockers AOR 2.43 (95% CI 1.28-4.54; p = 0.006), and prostin AOR 0.25 (95% CI 0.07-0.80; p = 0.025) were associated with complications. Mortality in this cohort was 5 (0.8%). Pulmonary hypertension was not associated with increased perioperative complications. The current study demonstrates that paediatric cardiac catheterisation procedures in a high-burden, resource-limited South African setting are associated with a diverse patient population, including a significant proportion with pulmonary hypertension and those receiving anti-failure therapy. Despite these challenges, the overall incidence of severe adverse outcomes including mortality remained low, supporting the feasibility and safety of these interventions when managed by an experienced multidisciplinary team.
Nonsyndromic cleft lip with or without palate (nCL/P) is a common congenital anomaly with a complex genetic basis. Previous whole-exome sequencing of Malagasy case-parent trios identified variants in several craniofacial development genes, including SEPTIN9, SKI, WNT5B, GPC4, and MSX1, enriched on East Asian ancestry segments. To assess functional contributions, we used Xenopus laevis embryos to evaluate the effects of individual and combined perturbations of candidate genes. Neither single-gene depletion nor ectopic expression of candidate genes induced orofacial clefts, although some craniofacial malformations were observed. In contrast, double knockdown of SEPTIN9 and MSX1 reproducibly produced orofacial clefts. These defects were rescued by co-injection of wild type human SEPTIN9 and MSX1 mRNAs, but not by variant alleles such as SEPTIN9 p.Glu370Lys and MSX1 p.Glu84Val. Our findings reveal a functional interaction between SEPTIN9 and MSX1 in craniofacial morphogenesis and provide experimental evidence for digenic inheritance in nCL/P. This work underscores the importance of ancestry-enriched variant combinations in the etiology of complex congenital anomalies.
Deep sternal wound complications following cardiac surgery are well described in adults; however, perioperative characteristics and outcomes in pediatric patients remain poorly defined due to the rarity of the indication. This study evaluates the pediatric subgroup within a 30-year, single-surgeon sternal wound reconstruction experience. A retrospective review of a prospectively maintained database of 584 consecutive patients undergoing sternal wound reconstruction from 1995 to 2024 was performed. Patients younger than 18 years were compared with adults aged 18 years or older. Six patients (1.0%) were younger than 18 years (mean age: 5.67±5.92 y) versus 578 adults (mean 64.74±12.48 y, P<0.0001). Two of the 6 pediatric patients required cardiac transplantation and one required reconstruction for congenital sternal absence. Pediatric patients were essentially free of the metabolic comorbidities that characterize adult patients undergoing reconstruction following CABG or valve surgery. Bilateral pectoralis major advancement flaps were the primary strategy in both groups; one pediatric patient additionally required an omental flap. Median total length of stay was 54.5 days [IQR: 17-104.5] versus 18 days in adults (P=0.1100). No pediatric patient experienced wound dehiscence, seroma, hematoma, infectious complication, reoperation, or 30-day mortality. All 6 pediatric patients (100%) had no postoperative complications versus 55.71% of adults (P=0.0376). Two patients died more than 30 days after reconstruction from underlying cardiac disease; no death was attributed to reconstruction. The markedly prolonged pediatric length of stay likely reflected the complexity of underlying congenital or transplant-related cardiac recovery rather than reconstructive failure. In this 30-year single-surgeon series, pediatric sternal wound reconstruction was rare but feasible. Standardized pectoralis-based techniques achieved zero 30-day mortality and no wound-related complications across a heterogeneous pediatric cohort, providing benchmark data for this underrepresented population. Early multidisciplinary coordination between cardiac and plastic surgery services remains essential.
Congenital anomalies of the urogenital system frequently coexist with renal abnormalities due to their shared origin from the intermediate mesoderm. Skeletal anomalies may also be associated, reflecting overlapping embryological development of mesodermal derivatives. Such multisystem involvement can pose a diagnostic challenge, particularly when identified incidentally. We report a 15-year-old female who presented with abdominal swelling and pain, later diagnosed as an umbilical hernia. During radiological evaluation, incidental findings of right renal agenesis, scoliosis, and a bicornuate uterus were identified. The patient underwent successful surgical management of the umbilical hernia. This case highlights the importance of recognizing coexisting anomalies and adopting an integrated approach in evaluation and management. This case highlights the need for a systematic, bidirectional evaluation when a congenital anomaly is identified, particularly involving the renal, genital, and skeletal systems. A syndromic perspective is essential to avoid missed diagnoses, facilitate appropriate follow-up, and anticipate long-term implications in such patients.
Sprengel's deformity (SD) is a rare congenital condition in children characterized by failure of caudal descent, resulting in a high scapula, a cosmetic deformity with functional limitation of the shoulder movements. It is frequently associated with vertebral and other anomalies. A retrospective case series of six children aged <17 years diagnosed with SD over 10 years presented to our tertiary care referral center was included in our study. The exclusion criteria were adults with Sprengel and children with syndromic SD due to their different spectrum of possible intervention, timing of surgery, and their outcomes. Clinical assessment using Cavendish, Rigault systems, and radiological evaluation using plain radiographs, Computerized tomographic scan, and magnetic resonance imaging were performed. Surgical management by Woodward's procedure was undertaken in a 9-year-old case. The outcomes were assessed based on cosmetic improvement, shoulder abduction, and its complications. Current concepts of SD in diagnosis, different radiographic indices, and various surgical options from the systematic review were discussed. The study included six children aged 2-9 years. Four patients had associated omo-vertebral anomalies, five had congenital spinal anomalies, and three had scoliosis. Cavendish Grade ranged from II to IV. Woodward's surgical corrective procedure resulted in significant improvement in shoulder abduction and cosmetic appearance. No major neurovascular complications were observed. Early diagnosis and appropriate surgical intervention in moderate-to-severe SD provide satisfactory cosmetic and functional outcomes. A comprehensive evaluation for associated anomalies is essential for optimal management.
Currently, invasive diagnostic studies are needed to determine the underlying pathology of urinary tract dilation. In this study, we demonstrate that the urinary proteome can be utilized to differentiate between ureteropelvic junction obstruction and vesicoureteral reflux, which are the two most common diagnoses underlying congenital urinary tract dilation. These markers may have the potential to differentiate between obstructive and non-obstructive causes of urinary tract dilation. From a prospectively maintained urinary biorepository in which urine samples from the bladder were collected via catheterization just prior to surgical intervention, urinary proteins of two clinical cohorts of ureteropelvic junction obstruction (n=102) and vesicoureteral reflux (n=122) were analyzed by mass spectrometry. Following quantitation of protein expression, a panel of predictive proteins was identified, and predictive models were generated (via logistic regression and bootstrap, and decision tree analysis). Gene ontology and network analysis was performed using the Ingenuity Pathways Analysis software. A total of 878 proteins present in all subjects were quantified. 125 proteins were differentially expressed with an absolute fold change > 1.3. Both the feature selection via logistic regression and bootstrap (AUC 0.98 accuracy 93%) and decision tree (AUC 0.91, accuracy 86%) models demonstrated good classification performance. Pathways analysis of the differentially expressed proteins provided insight into the different biological processes that occur in the two groups. This study demonstrates differing expression of select urinary proteins between patients with ureteropelvic junction obstruction and vesicoureteral reflux. There is potential for the urinary proteome to be leveraged as a non-invasive method to distinguish between obstructive and nonobstructive causes of congenital urinary dilation.
Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital anomaly affecting around 0.4-0.8% of the population, but limited mortality data exist. We characterized trends and disparities in AAOCA-related mortality in the United States from 1999 to 2023. We queried the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research multiple-cause-of-death database for AAOCA-related deaths among all age groups. Age-adjusted mortality rates (AAMR) per 1,000,000 population with 95% confidence interval, stratified by year, sex, race, regions, and urbanization status, were abstracted. Annual percent changes were computed by Joinpoint regression. From 1999 to 2023, there were 6665 AAOCA-related deaths. Overall AAMR fell insignificantly from 1.1 in 1999 to 0.9 by 2001, rose to 1.1 in 2008, declined significantly to 0.5 by 2020, and then increased to 0.8 by 2023. Male AAMRs exceeded females (1999: 1.3 vs 0.9; 2023: 1.2 vs 0.4). Racially, from 1999-2020 to 2021-2023, non-Hispanic (NH) Blacks exhibited the highest AAMR (1.8 vs 1.5), trailed by NH Whites (0.8 vs 0.6) and Hispanics (0.5 vs 0.6). Regionally, AAMRs from 1999 to 2020 were 0.9 in the Northeast, Midwest, and South, and 0.8 in the West. Moreover, both urban and rural AAMRs were 0.9. Among age groups, <44 years mortality declined, with the steepest drop in 15-44 years, while mortality for >45 years plateaued. Although AAOCA mortality declined overall, especially in children and young adults, it remains high among men, NH Blacks, and Midwest residents. Its recent rebound underscores the need for early detection, risk stratification, and surveillance for timely interventions.
The detailed molecular mechanisms and disease risk factors for heart failure, especially in the Japanese population, remain to be identified. In this study, we developed a trans-omics approach integrating multi-omics data to explore potential disease risk factors on a genome-wide scale. We functionally annotated the single-nucleotide polymorphisms (SNPs) investigated in a Japanese heart failure genome-wide association study using the epigenome data of cis-regulatory elements and regulome data of the transcription factor-binding regions identified in vascular endothelial cells. rs3176334, located in the promoter region of CDKN1A, and rs12437763, located in an enhancer, were identified as candidate heart failure-associated SNPs in the Japanese population. Furthermore, the downstream genes regulated by the enhancer containing rs12437763 were predicted to be multiple C2 and trans-membrane domain containing two (MCTP2) and nuclear receptor subfamily two group F member two (NR2F2), both of which are known causative genes for congenital heart disease. These candidate variants are potential risk factors for heart failure in the Japanese population.