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BACKGROUND: Congenital Myasthenic Syndromes (CMS) are rare genetic diseases, which share as a common denominator muscle fatigability due to failure of neuromuscular transmission. A distinctive clinical feature of presynaptic CMS variants caused by defects of the synthesis of acetylcholine is the association with life-threatening episodes of apnea. One of these variants is caused by mutations in the SLC5A7 gene, which encodes the sodium-dependent HC-3 high-affinity choline transporter 1 (CHT1). To our knowledge there are no published cases of this CMS type in Latin America. CASE PRESENTATION: We present two cases of CHT1-CMS. Both patients were males presenting with repeated episodes of apnea, hypotonia, weakness, ptosis, mild ophthalmoparesis, and bulbar deficit. The first case also presented one isolated seizure, while the second case showed global developmental delay. Both cases, exhibited incomplete improvement with treatment with pyridostigmine. CONCLUSIONS: This report emphasizes the broad incidence of CMS with episodic apnea caused by mutations in the SLC5A7 gene and the frequent association of this condition with serious manifestations of central nervous system involvement.

His-bundle pacing has demonstrated feasibility in numerous adult studies to reverse and prevent pacing-induced cardiomyopathy, however, is met with higher capture thresholds with deployment sheaths designed for adults with his-bundles in the typical location. To describe 24 pediatric and adult congenital patients post-physiologic pacing. Patients at the University of Minnesota Masonic Childrens Hospital with congenital complete heart block or congenital heart disease and atrioventricular block presented for pacemaker placement between November 2019 and January 2021. Twenty-four patients had attempted his-bundle placement using either Medtronics C315 or C308 sheaths and 3830 leads except for 3 patients who had Boston Scientifics His system with the Shape 3 sheath and 7842 leads. Twenty-four total patients underwent physiologic pacing (23 his-bundle, 13 female, 11 male) with median age of 14 years (range 8-39 years) with median weight of 51 kg (range 21.2-81 kg) with five right-sided implants performed. Twelve patients had congenital heart disease including atrioventricular canal defects, tetralogy of Fallot, and ventricular septal defect repairs (nine patients with ventricular septal defect repairs). Twelve patients had selective His-bundle pacing (six with congenital heart disease). Median threshold to capture was 0.5 V at 0.4 ms (range 0.4 to 1.1 V at 0.4 ms), impedance 570 ohms (range 456-1140 ohms), and sensing median of 9.7 mV (range 1.5-13.8 mV if present). The median follow-up time was 610 days (range 240-760 days). No complications occurred peri-procedurally or during follow-up. His-bundle pacing is feasible in pediatric and congenital heart disease patients.

INTRODUCTION: Brace treatment is common to address radiological dysplasia in infants with developmental dysplasia of the hip (DDH); however, it is unclear whether bracing provides significant benefit above careful observation by ultrasound. If observation alone is non-inferior to bracing for radiological dysplasia, unnecessary treatment may be avoided. Therefore, the purpose of this study is to determine whether observation is non-inferior to bracing for infants with radiological dysplasia. METHODS AND ANALYSIS: This will be a multicentre, global, randomised, non-inferiority trial performed under the auspices of a global prospective registry for infants and children diagnosed with DDH. Patients will be included if they present with radiological dysplasia (centred hip, alpha angle 43-60°, percent femoral head coverage greater than 35% measured on ultrasound) of a clinically stable hip under 3 months old. Patients will be excluded if they present with clinical hip instability, have received prior treatment or have known/suspected neuromuscular, collagen, chromosomal or lower-extremity congenital abnormalities or syndromic-associated hip abnormalities. Patients will be enrolled and randomised to undergo observation alone or brace treatment with a Pavlik harness for a minimum of 6 weeks. Follow-up visits will occur at 6 weeks, 1 year and 2 years post-enrolment. The primary outcome will be the norm-referenced acetabular index measured on the 2-year radiograph with a 3° non-inferiority margin. A total of 514 patients will be included.The study is anticipated to start in April 2024 and end in September 2028.The primary outcome will be compared between arms with a mixed-effects model with a random intercept for study centre, and a single covariate for the treatment group. If the lower bound of the 95% CI lies within 3° of the mean, we will treat this as evidence for non-inferiority. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the lead sites ethics board (University of British Columbia, Childrens and Womens Research Ethics Board). Ethics approval will be obtained from the local ethics committees or institutional review boards at each institution prior to patient enrolment. It is intended that the results of this study shall be published in peer-reviewed journals and presented at suitable conferences. TRIAL REGISTRATION NUMBER: NCT05869851.

BackgroundOxygen saturation (Spo2) screening has not led to earlier detection of critical congenital heart disease (CCHD). Adding pulse oximetry features (ie, perfusion data and radiofemoral pulse delay) may improve CCHD detection, especially coarctation of the aorta (CoA). We developed and tested a machine learning (ML) pulse oximetry algorithm to enhance CCHD detection.Methods and resultsSix sites prospectively enrolled newborns with and without CCHD and recorded simultaneous pre- and postductal pulse oximetry. We focused on models at 1 versus 2 time points and with/without pulse delay for our ML algorithms. The sensitivity, specificity, and area under the receiver operating characteristic curve were compared between the Spo2-alone and ML algorithms. A total of 523 newborns were enrolled (no CHD, 317; CHD, 74; CCHD, 132, of whom 21 had isolated CoA). When applying the Spo2-alone algorithm to all patients, 26.2% of CCHD would be missed. We narrowed the sample to patients with both 2 time point measurements and pulse-delay data (no CHD, 65; CCHD, 14) to compare ML performance. Among these patients, sensitivity for CCHD detection increased with both the addition of pulse delay and a second time point. All ML models had 100% specificity. With a 2-time-points+pulse-delay model, CCHD sensitivity increased to 92.86% (P=0.25) compared with Spo2 alone (71.43%), and CoA increased to 66.67% (P=0.5) from 0. The area under the receiver operating characteristic curve for CCHD and CoA detection significantly improved (0.96 versus 0.83 for CCHD, 0.83 versus 0.48 for CoA; both P=0.03) using the 2-time-points+pulse-delay model compared with Spo2 alone.ConclusionsML pulse oximetry that combines oxygenation, perfusion data, and pulse delay at 2 time points may improve detection of CCHD and CoA within 48 hours after birth.RegistrationURL: https://www.clinicaltrials.gov/study/NCT04056104?term=NCT04056104&rank=1; Unique identifier: NCT04056104.

BackgroundGlanzmann's thrombasthenia (GT) is a congenital platelet disorder affecting approximately 1:1 000 000 people globally and characterized by impaired platelet aggregation and clot retraction. Autosomal recessive, loss-of-function, variants in ITGA2B or ITGB3 of the αIIbβ3 receptor cause the disease in humans. A cat affected by Glanzmann's and macrothrombocytopenia was presented to the UC Davis VMTH.Hypothesis/objectivesSevere thrombopathia in this cat has an underlying genetic etiology.AnimalsA single affected patient, 2 age-matched clinically healthy controls, and a geriatric population (n = 20) of normal cats.MethodsPhysical examination and clinical pathology tests were performed on the patient. Flow cytometry and platelet aggregometry analyses for patient phenotyping were performed. Patient and validation cohort gDNA samples were extracted for Sanger sequencing of a previously identified ITGA2B (c.1986delC) variant. Reverse transcriptase PCR was performed on patient and healthy control PRP samples to verify ITGA2B variant consequence.ResultsA novel c.1986_1987insCC autosomal recessive variant in ITGA2B was identified. This variant was absent in a population of 194 unrelated cats spanning 44 different breeds. Complete loss of ITGA2B transcript and protein expression was verified by RT-PCR and flow cytometry, explaining the underlying etiology of GT, and likely macrothrombocytopenia, in this cat.Conclusions and clinical importanceThis study emphasizes the role of precision medicine in cardiovascular disease of cats and identified yet another variant that may be of utility for screening in the feline population. This study provides a small-volume, standardized, successful protocol for adequate platelet RNA isolation and subsequent molecular assessment of gene expression in cats.

ObjectiveOur objective was to gauge adherence to nationally endorsed protocols in implementation of pulse oximetry (POx) screening for critical congenital heart disease (CCHD) in infants after mandate by all states and to assess associated characteristics.Study designBetween March and October 2019, an online questionnaire was administered to nurse supervisors who oversee personnel conducting POx screening. The questionnaire used eight questions regarding performance and interpretation of screening protocols to measure policy consistency, which is adherence to nationally endorsed protocols for POx screening developed by professional medical societies. Multilevel linear regression models evaluated associations between policy consistency and characteristics of hospitals and individuals, state of hospital location, early versus late mandate adopters, and state reporting requirements.ResultsResponses from 189 nurse supervisors spanning 38 states were analyzed. Only 17% received maximum points indicating full policy consistency, and 24% selected all four options for potential hypoxia that require a repeat screen. Notably, 33% did not recognize ≤90% SpO2 as an immediate failed screen and 31% responded that an infant with SpO2 of 89% in one extremity will be rescreened by nurses in an hour rather than receiving an immediate physician referral. Lower policy consistency was associated with lack of state reporting mandates (beta = -1.23 p = 0.01) and early adoption by states (beta = -1.01, p

IntroductionPeople 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.MethodsThis large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)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).ResultsIn general linear models lower plasma Aβ42/40 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.DiscussionPlasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest.HighlightsPlasma 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.

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow at well-resourced centers. Studies to evaluate the clinical value and cost-effectiveness of these techniques are needed. For techniques that enhance the value of care for congenital heart disease patients, resources will need to be allocated for education and training to promote widespread implementation.

BackgroundWhile obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS.ObjectiveTo characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis.MethodsMultimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2 ± 6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants.ResultsA sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status.ConclusionsInsomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.

Diagnosis of portosystemic shunts (PSS) in dogs often requires multiple diagnostic tests, and available clinicopathologic tests have limitations in sensitivity and specificity. The objective of this study was to train and validate a machine learning model (MLM) that can accurately predict the presence of a PSS utilizing routinely collected demographic data and clinicopathologic features. Dogs diagnosed with PSS or control dogs tested for PSS but had the condition ruled out (non-PSS) were identified. Dogs were included if a complete blood count and serum chemistry panel were available from PSS diagnostic testing. Dogs with a PSS were subcategorized as having a single intrahepatic PSS, a single extrahepatic PSS, or multiple extrahepatic PSS. An extreme gradient boosting (XGboost) MLM was trained with data from 70% of the cases, and MLM performance was determined on the test set, comprising the remaining 30% of the case data. Two MLMs were created. The first was designed to predict the presence of any PSS (PSS MLM), and the second to predict the PSS subcategory (PSS SubCat MLM). The trained PSS MLM had a sensitivity of 94.3% (95% CI 90.1-96.8%) and specificity of 90.5% (95% CI 85.32-94.0%) for dogs in the test set. The area under the receiver operator characteristic curve (AUC) was 0.976 (95% CI; 0.964-0.989). The mean corpuscular hemoglobin, lymphocyte count, and serum globulin concentration were most important in prediction classification. The PSS SubCat MLM had an accuracy of 85.7% in determining the subtype of PSS of dogs in the test set, with variable sensitivity and specificity depending on PSS subtype. These MLMs have a high accuracy for diagnosing PSS; however, the prediction of PSS subclassification is less accurate. The MLMs can be used as a screening tool to increase or decrease the index of suspicion for PSS before confirmatory diagnostics such as advanced imaging are pursued.

Background: Congenital shoulder dislocation due to shoulder girdle malformation is called true congenital shoulder dislocation. It is an extremely rare disorder as compared with traumatic dislocation or secondary to brachial plexus injury. Case presentation: We report a case of atraumatic true congenital shoulder dislocation, one of the few reported cases across the world. The baby was born of a preterm caesarean section at 30 weeks of gestation, ruling out any perinatal trauma. The baby presented with a lateral shoulder crease and reduced movements of the affected upper limb. The diagnosis was confirmed with radiographs and a sonography that ruled out physeal injury. Treatment involved prompt closed reduction and stabilization by swathing in an adducted internally rotated position for two weeks. Conclusion: Owing to the rarity of this condition, the case is being reported to be archived with a handful of other such cases. [ABSTRACT FROM AUTHOR]

Introduction: Children with cervical or cervicothoracic congenital scoliosis are limited in their ability to compensate for the main curve of the deformity because there are only a few mobile segments in their cervical spine. Over the years, we have frequently observed coronal atlantoaxial dislocation (CAAD) in a lateral direction (from left to right or vice versa) in these patients. It was anticipated that CAAD might compensate for the horizontal position of the head, and it is hypothesized that CAAD depends on the degree of scoliotic deformity. Thus, the aim of our study was to investigate whether there is a correlation between CAAD and scoliosis parameters in these patients. Methods: Retrospective analysis was performed based on CAT scans and preoperative X-rays of patients with cervical and cervicothoracic scoliosis with an apex between C4 and T6. Seventeen patients, with a mean age of 7.25 years, who were 9 girls and 8 boys, and who were treated between 2006 and 2022 were included. Cobb's angle of the main curve (CA-MC), Cobb's angle of the secondary curve (CA-SC), and T1-, C2- and UEV (upper end vertebra) tilt were measured on whole-spine radiographs in the standing position. The CAAD was measured via coronal CAT scan reconstruction and defined as the difference in the distances of the lateral masses to the midline of the axis. Pearson's linear correlation coefficients (r) were determined using SPSS to evaluate correlations between CAAD and the measured parameters. p < 0.05 indicated statistical significance. Results: CAAD toward the convex region in patients with scoliosis was typically observed; the mean CAAD was 3 mm ± 3.7 mm. The mean CA-MC was 46° ± 13°, the mean CA-SC was 16° ± 9.6°, the mean T1 tilt was 17° ± 8.8°, the mean C2 tilt was 9°± 8.8°, and the mean UEV tilt was 24° ± 7.2°. There was a strong linear correlation between CAAD and CA-MC (r = 0.784, p < 0.001), C2 tilt (r = 0.745; p < 0.001), and UEV tilt (r = 0.519; p = 0.033). There was no correlation between CAAD and either CA-SC or T1 tilt. Discussion: Children with cervical or cervicothoracic scoliosis tend to have a CAAD toward the convexity of the scoliosis that correlates to CA-MC, C2-tilt, and UEV-tilt. CAAD may be seen as a compensatory mechanism to keep the head in a horizontal position. Severe or progressive CAAD may result in destruction of the atlantoaxial joint, including severe complaints, thus necessitating close follow-up and possibly early surgical treatment. Moreover, CAAD might be a useful additional radiographic parameter to be checked in future scoliosis studies. Key Points: Children with cervical or cervicothoracic scoliosis may have CAAD toward the convexity of scoliosis. The CAAD in this group of patients strongly depended on the CA-MC, C2 tilt, and UEV tilt but not on the CA-SC or T1 tilt. Close clinical and radiographic follow-up examinations are mandatory for these patients to evaluate if and when correction and fixation within the scoliotic deformity should be performed to prevent these patients from further damage within the atlantoaxial joint. CAAD might be an additional radiographic parameter to be used in future studies dealing with scoliosis. [ABSTRACT FROM AUTHOR]

Objective: To describe 3 cases of midline congenital upper lip sinus (MCULS) and review current literature to inform risk of intracranial involvement in the context of this rare congenital facial anomaly. Materials and Methods: A limited case series with chart review is presented. A literature search was conducted to review proposed theories of the embryology of MCULS and to determine the relative frequency of cephalic extension. Results: Including the 3 new cases presented herein, there have been 42 cases of MCULS described in the literature over the past 53 years. Thirty-nine cases (93%) underwent surgical excision, with 2 of these cases (4.7%) demonstrating cephalic extension of the fistula tract beyond the maxillary crest with termination at the anterior skull base. However, 95% (37/39) of surgically excised MCULS cases demonstrated a more limited depth of extension, with termination of the tract at or below the anterior nasal spine. Conclusions: The MCULS anomaly is rare, with fewer than 50 cases reported in the literature. Only 2 cases have been described with extension of the MCULS superior to the anterior nasal spine and into the nasal septum. It is the authors' opinion that preoperative neuroimaging is not routinely required for MCULS. However, if extension of the sinus tract beyond the anterior nasal spine is noted intraoperatively, the surgeon should consider aborting the case and obtaining appropriate neuroimaging. [ABSTRACT FROM AUTHOR]

Background: Choanal atresia is a congenital anomaly characterized by an absence of the nasal choanae due to Failure to recanalize the nasal fossae during embryogenesis. Instances involving unilateral Choanal atresia may go unidentified for extended periods. Bilateral choanal atresia presenting in adulthood is an infrequent occurrence. Case Presentation: A case of bilateral choanal atresia in a female 24-year-old presenting to our otolaryngology department's out clinics with long-standing nasal obstruction, mouth breathing, and anosmia. She underwent endoscopic choanoplasty to reestablish patency of the posterior choana. Follow-up after one month revealed patent posterior choana. Conclusion: Bilateral choanal atresia requires early surgical intervention in infants for survival. Adult presentations are rare. Nasal endoscopy and CT help determine the surgical approach. Endoscopic trans-nasal Chonaolplasty is typically the standard treatment. [ABSTRACT FROM AUTHOR]

A one-year-old male intact American bulldog was presented for evaluation of previously diagnosed pulmonary stenosis. Echocardiography identified ultra-severe stenosis with an instantaneous trans-pulmonary pressure gradient of 240 mmHg. Angiography confirmed the presence of an anomalous coronary artery with a prepulmonic course of the left coronary artery arising from a single right coronary ostium consistent with a type R2A coronary anomaly. A trans-pulmonary stent was successfully placed transvenously with diameter sizing based on coronary compression testing. No coronary compression was present on postimplantation angiography. A marked reduction in the pressure gradient was obtained on postoperative echocardiography (reduction to 68 mmHg), despite selecting a stent diameter less than the pulmonary annulus diameter. This is the first report of the use of coronary compression testing in transvenous trans-pulmonic stent implantation in a dog with a type R2A coronary artery anomaly. Selection of a stent diameter less than the pulmonary annulus diameter conveyed a clinically relevant reduction in the trans-pulmonic pressure gradient while avoiding coronary compression in this case. [ABSTRACT FROM AUTHOR]

Dogs with severe pulmonary stenosis (PS) are routinely treated with balloon valvuloplasty. Success and safety of these procedures require an accurate assessment of the pulmonary valve annulus (PVA) diameter for proper balloon catheter selection. PVA diameter is assessed with angiography (PVA-Ang) and transthoracic echocardiography (PVA-TTE), and both may impact procedural planning for balloon valvuloplasty. The objective of this study was to describe the relationship between PVA-Ang and PVA-TTE in dogs with PS. Observational, retrospective study of 59 client-owned dogs. Medical records of dogs diagnosed with PS were reviewed. Images from selective right ventricular angiography and transthoracic echocardiography were reviewed. The PVA diameters were measured at the time of angiography (PVA-Ang) and by a single operator for this study (PVA-TTE). Image quality scores were assigned to echocardiographic images of the PVA based on visualization of PVA margins and valve leaflet hinge points. In 41/59 (70%) dogs, the diameter of the PVA-Ang was larger than the PVA-TTE, and the (range 0.1 to 8.4 mm) worse echocardiographic image quality, the difference in measurement between modalities increased. Dogs with poor echocardiographic image quality had greater differences (range −7.7 to 8.4 mm) between PVA-Ang and PVA-TTE compared to those with excellent image quality (range −2.2 to 3.8 mm), and the absolute differences between poor (median 2.8 mm, range 1.5–8.4 mm) and excellent (median 1.4 mm, 0.2–3.8 mm) image quality were significant (P=0.005). Diameters of PVA-Ang are greater than PVA-TTE in most dogs, and these differences are most apparent with worse echocardiographic image quality. These differences may be clinically relevant to interventional procedure planning. [ABSTRACT FROM AUTHOR]

Background and Objectives: In clinical practice, neutropenia is frequently accompanied by other cytopenia; isolated non-chemotherapy-induced severe neutropenia is less frequent and its differential diagnosis can be challenging. In this real-world study with data collected over a 5-year period in a tertiary referral hospital, we primarily sought to identify underlying causes of isolated severe neutropenia (<0.5 × 109/L). Secondly, we aimed to analyze its management and outcomes. Materials and Methods: From 444,926 screened patients, after exclusion of patients with chemotherapy, radiotherapy, hematological neoplasms, additional cytopenia, and benign ethnic neutropenia, we identified and analyzed data from 70 patients (0.015%) with isolated severe neutropenia. We thus confirmed that the occurrence of isolated severe neutropenia is a rare event, even in a tertiary hospital. Results: The median age at diagnosis was 34 years (range 1–81) and 65% were female. Acute neutropenia was more frequently observed (n = 46/70, 65.7%); the main underlying causes in this group were drugs (n = 36/46, 78%) followed by infections (n = 10/46, 21.7%). We identified 24 (34.3%) patients with chronic neutropenia. The majority of them (n = 12/24, 50%) had an idiopathic form (CIN), 8/24 (33%) were autoimmune (AIN), and 4/24 (17%) were congenital. Conclusions: This study demonstrates the rarity and heterogeneity of isolated severe neutropenia and the steps to consider in its diagnostic work-up and management. Epidemiological characteristics, diagnostic work-up, and management including hospitalizations are described. Due to the high frequency of metamizole-induced neutropenia observed in this study, we want to raise awareness about its use, since this complication generates frequent hospitalizations even in young, otherwise healthy patients. Furthermore, recurrent infections in chronic forms of idiopathic neutropenia were quite common, suggesting a difference in phenotypes and need for therapy consideration depending on the clinical course. [ABSTRACT FROM AUTHOR]

Objective: Shone's complex comprises of a combination of congenital cardiac anomalies causing obstructions in the left ventricle's inflow and outflow tracts. This systematic review aims to evaluate the clinical features and surgical outcomes of Shone's complex. Methods: An electronic literature search of PubMed and Scopus was performed to identify relevant studies related to the presentation, management, and outcomes of Shone's complex. Two reviewers independently performed selection. Data on study characteristics, participant demographics, interventions, outcomes, and follow-up durations were extracted and analyzed. Results: A total of 691 papers were identified, with 18 studies included in the final analysis. The majority of the studies (n = 12) focused on the pediatric age group. The most common clinical presentations were coarctation of the aorta (n = 17) and mitral stenosis (n = 12). Surgical interventions often involved staged approaches, prioritizing outflow before inflow obstructions. Mitral valve repair was preferred over replacement due to better long-term outcomes (n = 8). Biventricular repair was recommended due to improved postoperative outcomes, but often needed reoperations. Reoperations were common, primarily due to recurrent coarctation (n = 10), subaortic stenosis (n = 8), and mitral valve dysfunction (n = 7). Pulmonary hypertension (n = 10) and arrhythmias (n = 11) were significant complications. Most patients were in modified Ross/NYHA functional class 1 on follow-up. Mortality rates ranged from 4 to 28%, with better outcomes associated with early and strategic surgical interventions. Conclusion: Early diagnosis and biventricular repair were associated with better outcomes while transplantation was often an eventuality. Standardized diagnostic criteria, long-term follow-up, and consensus guidelines are needed to improve the management of this congenital heart disease. [ABSTRACT FROM AUTHOR]

Background: Congenital toxoplasmosis occurs when a pregnant woman becomes infected with Toxoplasma gondii (T. gondii) for the first time. Treatment typically involves antimicrobial medications, with spiramycin commonly used to prevent transmission. However, spiramycin's effectiveness is limited due to poor placental penetration. Clindamycin, another antibiotic, can cross the placenta but reaches the fetus at only half the maternal concentration. Encapsulating the drug in chitosan-coated niosomes (Cs-Nio) could enhance its effectiveness by targeting specific organs and ensuring sustained release. To address the challenges of using clindamycin, a niosome-coated chitosan system was investigated for treating congenital toxoplasmosis caused by the VEG strain of T. gondii in an animal model. Methods: Pregnant mice were infected with VEG strain of T. gondii on the 12th day of pregnancy, followed by treatment with various drugs across six groups. The treatments included chitosan-coated niosomes loaded clindamycin (Cs-Nio-Cli) and other controls. Parasitological evaluations (microscopic examination and real-time PCR), along with histopathological and immunological assessments were conducted to assess treatment efficacy. Finally, statistical analysis was conducted using GraphPad Prism 8.0 and SPSS 26, comparing test and control groups with T test and Mann–Whitney test. A p ≤ 0.05 was considered statistically significant. Results: The study found that treatment with Cs-Nio-Cli significantly reduced the number of T. gondii cysts in the brain and eyes (97.59% and 92.68%, respectively) compared to the negative control group. It also mitigated inflammatory changes, prevented cell death, and reduced vascular cuffs in the brain. In addition, Cs-Nio-Cli treatment decreased bleeding, placental thrombosis, and inflammatory cell infiltration in the placenta while improving eye tissue health by reducing retinal folds and bleeds. Immunologically, nanoclindamycin treatment resulted in lower TNF-α cytokine levels and higher IL-10 levels, indicating an enhanced anti-inflammatory response. Conclusions: Although Cs-Nio-Cli demonstrates promise in reducing the transmission of congenital toxoplasmosis and mitigating the effects of congenital toxoplasmosis, additional research is necessary to determine the optimal treatment regimens for the complete eradication of the parasite in the fetus. [ABSTRACT FROM AUTHOR]

Purpose: To determine prevalence of musculoskeletal complaints (MSCs) in adults with major congenital upper limb differences (CoULD) compared to able-bodied controls, and to examine associations of MSCs and disability with various biopsychosocial factors. Materials and methods: Questionnaire-based cross-sectional study assessing MSCs, disability (using the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH)), general and mental health status, physical work demands, and upper extremity range of motion. Results: Seventy-one individuals with CoULD (participation rate: 41%) and 71 controls matched on age, gender, and education were included (49% female, mean age 28.9 years). Year prevalence of MSCs was significantly higher in the CoULD group (35%) than in the control group (18%). The CoULD group was less often employed and had lower scores on all measures of upper limb range of motion and hand grip. MSCs were associated with higher DASH scores and higher reported work demands. Disability was associated with female gender, more joints with limited range of motion, unemployment, and lower general and mental health. Factors associated with disability did not differ between groups. Conclusions: MSCs are a frequent problem in young adults with major CoULD. To prevent or reduce MSC and disability, clinicians and researchers should be aware of the associated factors. Implications for rehabilitation: The year prevalence of musculoskeletal complaints (MSCs) in those with major congenital upper limb differences (CoULD) was approximately double to that of the control group, implying a potential relationship between CoULD and MSCs. Rehabilitation professionals should develop personalized strategies to manage work demands in those with CoULD, considering the association between MSCs and higher reported work demands. Recognizing the impact of a negatively perceived body image on mental health, clinicians should integrate psychological counseling into rehabilitation treatments to support mental well-being and improve overall quality of life in those with CoULD. Rehabilitation professionals should educate individuals with CoULD about the potential associations between upper limb work demands, MSCs, and disability. [ABSTRACT FROM AUTHOR]

Maxillonasal dysplasia, known as Binder's syndrome, is a rare congenital deformity characterised by distinctive facial features, including a malformed midface and nose, as well as abnormal positions of the nasal bones. In addition, maxillary hypoplasia, or a shorter upper jaw, and nasal abnormalities may manifest as a flattened nose. Many cases of this condition are associated with other malocclusions, and those affected can be easily identified. Individuals with Binder's syndrome typically present with an undeveloped upper jaw, a projecting lower jaw, a smaller nose, a flat nasal bridge, and midfacial hypoplasia. This is the first case report describing a physiotherapy method for maxillonasal dysplasia. Hereby, the authors present a case report of a six-month-old male child with Binder's syndrome who exhibited delayed developmental milestones and physical anomalies. The child's mother had a complicated pregnancy, culminating in an emergency caesarean section due to preterm premature rupture of membranes. The infant, born with Binder's syndrome and a cleft palate, displayed poor head control, an inability to roll, and reluctance to engage in sensory interactions. Examination revealed bilateral cortical thumbs, hip joint abnormalities, and heightened sensitivity to touch. Magnetic Resonance Imaging (MRI) findings indicated semilobar Holoprosencephaly (HPE) and dysgenesis of the corpus callosum. Physiotherapeutic interventions focused on parent education and home exercise programs targeting developmental milestones. Over the course of two months, the infant showed significant progress in head control and rolling. Furthermore, after four months of training, the child gained sitting control. The present case underscores the importance of early intervention and parental involvement in optimising outcomes for children with Binder's syndrome. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Meckel's diverticulitis (MD) mimics acute appendicitis with right lower abdominal pain. Clinicians must consider MD in acute abdomen cases to avoid diagnostic delays. Perforated MD can lead to serious complications. Timely use of advanced imaging and surgical assessment is essential for accurate diagnosis and management. Meckel's diverticulum (MD) is a gastrointestinal congenital anomaly that signifies a persistent remnant of the omphalomesenteric duct. While frequently asymptomatic, its complications vary widely, ranging from mild and painless to potentially life‐threatening conditions. This is a case of a 4‐year‐old female patient with sudden abdominal pain and tenderness, with an elusive cause before surgery. The definitive diagnosis of a perforated MD was established during diagnostic laparoscopy due to worsening symptoms. Detecting MD and its potential complications requires a high degree of suspicion. Once recognized, prompt management is essential to prevent further complications. Although perforation is uncommon in MD, its symptoms can mimic acute appendicitis, confusing emergency settings. This article underscores the significance of diagnosing MD, despite its rarity, and emphasizes the necessity for swift treatment upon identification. [ABSTRACT FROM AUTHOR]

Purpose: To report on the occurrence of postoperative visual axis opacification (VAO) in children younger than 5 years of age operated for cataract in Sweden, and to analyse correlations with age at surgery and surgical method. Methods: Data were derived from the Swedish Pediatric Cataract Register (PECARE). All children operated on between 1 January 2007 and 31 December 2020 were included. Follow‐ups at 1, 2 and 5 years of age were analysed. Results: Cataract surgery were performed on 770 eyes belonging to 549 children (n = 282 boys, 51.4%); 327/770 (42.5%) of the children underwent surgery before 3 months of age and 216/770 (28%) before 6 weeks of age. Data on 881 follow‐up visits were registered. At the follow up‐visits at 1, 2 and 5 years of age, VAO was present in 154/349 (44.1%), 41/323 (12.7%) and 25/208 (12%). The majority of the children with VAO underwent cataract surgery before age 6 months, with a predominance before age 2 months. Primary IOL was implanted in 601/770 (78%) of eyes; 40.8% had an acrylic one‐piece lens, 31.8% had a bag‐in‐the‐lens IOL, 21.9% were aphakic and 5.2% had an acrylic three‐piece lens. Implantation of a bag‐in‐the‐lens IOL was related to a significantly lower occurrence of VAO compared to other types of IOL, including aphakia (p < 0.0002). Conclusion: Our results are in accordance with the literature. Primary bag‐in‐the‐lens IOL implantation before 2 years of age seems adequate and safe, with a low occurrence of VAO, and can thus be continued as routine in Sweden. [ABSTRACT FROM AUTHOR]

The etiologies of podocyte dysfunction that lead to pediatric nephrotic syndrome (NS) are vast and vary with age at presentation. The discovery of numerous novel genetic podocytopathies and the evolution of diagnostic technologies has transformed the investigation of steroid-resistant NS while simultaneously promoting the replacement of traditional morphology-based disease classifications with a mechanistic approach. Podocytopathies associated with primary and secondary steroid-resistant NS manifest as diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, and collapsing glomerulopathy. Molecular testing, once an ancillary option, has become a vital component of the clinical investigation and when paired with kidney biopsy findings, provides data that can optimize treatment and prognosis. This review focuses on the causes including selected monogenic defects, clinical phenotypes, histopathologic findings, and age-appropriate differential diagnoses of nephrotic syndrome in the pediatric population with an emphasis on podocytopathies. [ABSTRACT FROM AUTHOR]

Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure. [ABSTRACT FROM AUTHOR]

Background: Childhood blindness remains a neglected issue in eye care within low-income countries, with congenital and juvenile cataracts being the most common treatable causes. This study aims to investigate the factors influencing the management of congenital and juvenile bilateral cataracts, provide data on general outcomes and postoperative findings, and discuss treatment in a low-income country context. Methods: In this prospective study, data from clinical care were continuously entered into a database, and one follow-up examination of a cohort of 91 patients with congenital and juvenile bilateral cataracts in Kinshasa, Democratic Republic of the Congo, was conducted. Multiple factors that affect the first clinical presentation, the clinical management, and outcome were investigated. Results: Most patients (88.5%) who received medical treatment were identified by cataract finders. A patient's presentation time was independent of the parent's education, social status, income, and sex of the child. The median age at first presentation was 5.8 years (ranging from 0 days to 17.3 years). The best visual acuity outcomes were achieved by patients who underwent surgery during early childhood. According to WHO grades and on an eye level basis, 51.1% (93 out of 182 eyes) showed improvement, while 34.6% (63 eyes) had unchanged results post-surgery. Among the cases without improvement, 76.2% were blind prior to surgery. Postoperative findings were observed in 56% of the patients, with secondary cataracts being the most common, affecting 26.37% of the operated eyes. Conclusions: Optimal management of childhood cataracts involves early identification, efficient hospital infrastructure, high-quality medical care, and long-term follow up. In sub-Saharan Africa, this approach must be adapted to the context of available resources, which differs significantly from those in high- and middle-income countries. [ABSTRACT FROM AUTHOR]

Introduction: Despite being invasive, direct measurements remain the gold standard to measure intra-cranial pressure (ICP) in patients with craniosynostosis. However, there has been persistent effort to develop non-invasive modalities to measure ICP, possibly avoiding some of the risks of direct measurements. Here, we conduct a systematic review of the evidence behind various non-invasive modalities to monitor ICP in patients with craniosynostosis. Methods: A systematic review was conducted using PubMed, Cochrane, and Web of Science databases to identify studies describing the use of non-invasive ICP measurements in patients with craniosynostosis. Studies were included if they assessed a non-invasive method of ICP monitoring against a direct/invasive ICP monitoring technique in patients with craniosynostosis. Non-English and non-human studies were excluded. Results: A total of 735 studies were screened, of which 52 were included in the study. Nine methods of non-invasive ICP measurement were identified, with varying sensitivities and specificities in detecting elevated ICP. Specifically, optical coherence tomography (OCT), and ocular ultrasonography demonstrated ability to accurately measure ICP when compared to direct measurements. Conclusion: Here, we present the first systemic-review of the current literature surrounding non-invasive modalities to measure ICP in patients with craniosynostosis. While direct measurement remains the gold-standard, multiple reviewed modalities have shown promise in accurately measuring ICP. Of these, OCT has the most rigorous evidence supporting its use. Ocular sonography has also shown promise, albeit without as robust evidence supporting its use. Regardless, further investigation is required before any modality is able to obviate the need for invasive, direct measurements. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Chagas disease (ChD) affects approximately 7 million people in Latin America, with benznidazole being the most commonly used treatment.Data from a retrospective cohort study in Argentina, covering January 1980 to July 2019, was reanalysed to identify and characterize benznidazole‐related adverse drug reactions (ADRs).The study included 518 patients: 449 children and 69 adults (median age in children: 4 years; adults: 25 years; age ranges: 1 month–17.75 years and 18–59 years, respectively). The median benznidazole doses received were 6.6 mg/kg/day for at least 60 days in children and 5.6 mg/kg/day for a median of 31 days in adults. Overall, 29.34% (152/518) of patients developed benznidazole‐related ADRs, with an incidence of 25.83% (116/449) in children and 52.17% (36/69) in adults (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.19–0.54, P < .001). The incidence rate was 177 cases per 1000 person‐years (95% CI = 145–214) in children and 537 per 1000 person‐years (95% CI = 360–771) in adults. There were 240 ADRs identified, primarily mild to moderate. Severe ADRs occurred in 1.11% (5/449) of children and 1.45% (1/69) of adults. The skin was the most affected system. A total of 10.23% (53/518) of patients discontinued treatment. More adults than children discontinued treatment (OR = 3.36, 95% CI = 1.7–6.4, P < .001).Although 29.34% of patients experienced ADRs, most were mild to moderate, indicating a manageable safety profile for benznidazole. While optimized dosing schedules and new drugs are needed, avoiding benznidazole solely due to safety concerns is not justified. [ABSTRACT FROM AUTHOR]

Background: Currently, the treatment outcomes for complex congenital arteriovenous malformations (AVMs) remain unsatisfactory. This article reports on the utilization of an abdominal aortic stent graft, in conjunction with embolization techniques, for managing acute heart failure triggered by complex congenital arteriovenous malformations in the lower limb. Case Presentation: We present a case involving a patient with congenital AVMs in the lower limb, who had suffered from prolonged swelling in the left lower limb and recently developed symptoms of heart failure. At the age of 67, the patient was definitively diagnosed with a complex congenital AVMs in the lower limb. This article delves into the practical experiences and limitations encountered in employing an abdominal aortic stent graft, coupled with embolization, to address acute heart failure caused by complex congenital AVMs in the lower limb. Conclusions: Our article presents the initial report on the challenges and limitations encountered in treating acute heart failure triggered by complex congenital AVMs in the lower limb, utilizing a combination of abdominal aortic stent graft placement and embolization techniques. [ABSTRACT FROM AUTHOR]

Congenital lacrimal drainage anomalies have several syndromic and non-syndromic associations reported in the literature. While the information is exhaustive, it may not be useful if someone wants to know the associations based on individual lacrimal anomalies quickly. For example, if someone wants to know the systemic associations of supernumerary punctum, it entails scanning of all the syndromes to note which of them reported the specific anomaly. Besides, several new associations have been reported in the last four years. Hence, the need was felt for a separate categorization in a catalogue form to access all the associations immediately, in an alphabetical order, and easily reference them. The present exercise allowed us to catalogue 73 systemic associations of CNLDO, 37 for punctal agenesis, 20 for punctal dysgenesis, 17 for congenital lacrimal fistulas, 9 for canalicular wall dysgenesis, and three each for supernumerary punctum and pediatric functional epiphora. [ABSTRACT FROM AUTHOR]

Background: Crossed fused renal ectopia (CFRE) is a common congenital anomaly where one kidney is positioned abnormally on the opposite side of the midline, often fused with the other kidney. However, single ureter draining crossed fused renal ectopia is a rare occurrence. Case report: Here, we report a case of crossed fused renal ectopia with a single ureter in a 46-year-old Nepali male who presented with history of lithuria. Computed tomography revealed that the left kidney was situated on the right side and fused with the right kidney. The renal pelvises of both kidneys were fused, and a single ureter, located on the right side, was draining both kidneys into the bladder. The patient was advised to have regular follow-ups. Conclusion: Crossed fused renal ectopia with a single ureter represents a rare renal anomaly. Asymptomatic patients can typically be managed conservatively. Regular follow-up is recommended to monitor renal function, calculus formation, infections, and malignant changes. [ABSTRACT FROM AUTHOR]

Introduction: Congenital rubella syndrome (CRS) is associated with severe birth defects, that lead to disability in later life. Hence, early detection and intervention are needed to prevent permanent disability and mortality in children with CRS. We evaluated the time to diagnosis or correction intervention related to survival rate using survival analysis. Methodology: A retrospective cohort study was conducted to evaluate the follow-up of CRS-confirmed cases from 2011–2018 at a national referral hospital in Jakarta, Indonesia. Parents of eligible children who registered in the national CRS registry as laboratory-confirmed CRS cases were contacted through phone calls or home visits and interviewed about the current situation of their child’s health. We also obtained clinical data from the medical records. Results: Fifty children, age 4 to 14 years, identified with laboratory-confirmed CRS were included in this study. Half (54%) of these children were female. All were born from mothers with no previous rubella vaccination history. Ophthalmic abnormalities such as congenital cataracts (88%) were the most common birth defect. Multiple congenital abnormalities including congenital heart disease, ocular abnormalities, and auditory defects were identified in 52% of the children. Based on Kaplan-Meier analysis, 50% of children were diagnosed at four months. Ophthalmic corrections such as cataract surgery were performed earlier than heart or auditory correction, with 50% of children undergoing eye correction one month after the diagnosis. Conclusions: There is a vital need to implement CRS surveillance in Indonesia to know the burden of CRS and reinforce the preventive actions, including vaccination against rubella. [ABSTRACT FROM AUTHOR]

We describe cases of three infants who developed acquired colonic atresia presumed secondary to significant systemic cardiovascular compromise and in the absence of necrotizing enterocolitis. An acquired colonic atresia may present as feed intolerance and should be investigated with a lower gastrointestinal contrast study. We would also recommend routine lower gastrointestinal contrast study prior to stoma closure in an infant with history of significant cardiovascular compromise, even in the absence of significant widespread colonic inflammation such as necrotizing enterocolitis. [ABSTRACT FROM AUTHOR]

Pediatric cholesteatomas (PC) have multifactorial aetiology, spread aggressively and there are high chances of residual/ recurrent disease after treatment. The surgical technique to manage this entity has been debatable. This study was done to (i) enumerate the presentation of PC and the surgical techniques adopted (ii) analyse the outcomes viz., residual/ recurrence rates and hearing results. A cross sectional record based study was done on 618 cases of PC operated between 1983 and 2015, at a centre dedicated to otology and lateral skull base surgery. The data which was maintained on the basis of clinical and peri- operative findings was analysed. Otorrhea (59.2%) and hearing loss (54.2%) were the common symptoms. The surgeries done were: canal wall up (CWU) (44.3%), canal wall down (CWD) (41.1%), modified bondy's mastoidectomy (5.7%), radical mastoidectomy (4.9%), trans canal excision (1.8%) and subtotal petrosectomy (2.3%). The residual and recurrence rates were 12.6% and 7.9% respectively. A significant difference between the pre and post operative hearing was observed. The mean improvement in air bone gap was 7.7db. Residual/ recurrent disease were higher in CWU as compared to CWD group. The surgery should be individualised so that the patient remains disease free. [ABSTRACT FROM AUTHOR]

Branchial arch anomalies are considered congenital defects that can occur during fetal development. They may present as cysts, sinuses, or fistulae. Anomalies of the second branchial arch are the most common. The existence of bilateral complete fistulae is exceptionally rare. In this case report, a 5-year-old boy presented with recurrent episodes of bilateral neck swelling and watery discharge from openings on the anterolateral sides of his neck since birth. He was diagnosed with bilateral branchial fistulae after confirmation via a contrast-enhanced CT scan. Surgery was performed to entirely excise the fistula tracts bilaterally. Additionally, a bilateral tonsillectomy was performed to help prevent recurrence. [ABSTRACT FROM AUTHOR]

Congenital earlobe clefts are the most common lower auricular malformations. They represent a unique reconstructive challenge. The goal of surgery includes restoration of a natural lobular contour and volume as well as a fine surgical scar. Several surgical techniques have been described, most of which only address the cleft deformity but not the soft tissue deficiency. We hereby describe a technique which addresses both the cleft and improves soft tissue deficiency through a conchal cartilage graft. [ABSTRACT FROM AUTHOR]

Having health insurance is associated with better access to healthcare and lower rates of comorbidity in the general population, but data are limited on insurance's impact on adults with congenital heart disease (ACHD). The Congenital Heart Survey To Recognize Outcomes, Needs and well-beinG (CH STRONG) was conducted among ACHD in three locations from 2016 to 2019. We performed multivariable logistic regression to determine the associations between health insurance and both access to healthcare and presence of comorbidities. We also compared health insurance and comorbidities among ACHD to similarly-aged individuals in the Behavioral Risk Factor Surveillance System (BRFSS) as a proxy for the general population. Of 1354 CH STRONG respondents, the majority were ≤ 30 years old (83.5%), and 8.8% were uninsured versus 17.7% in the BRFSS (p < 0.01). Compared to insured ACHD, uninsured were less likely to report regular medical care (adjusted odds ratio [aOR] 0.2, 95% confidence interval [CI] 0.1–0.3) and visited an emergency room more often (aOR 1.6, CI 1.0–2.3). Among all ACHD reporting disability, uninsured individuals less frequently received benefits (aOR 0.1, CI 0.0–0.3). Depression was common among uninsured ACHD (22.5%), but insured ACHD had lower rates of depression than insured in the BRFSS (13.3% vs. 22.5%, p < 0.01). In conclusion, rates of insurance were higher among ACHD compared to the general population. Nonetheless, uninsured ACHD inconsistently accessed healthcare and benefits. Further studies are needed to determine if insurance ameliorates the risk of morbidity as ACHD age. [ABSTRACT FROM AUTHOR]

Fetal echocardiography may be performed because of noncardiac indications (the pregnancy is identified as high risk for fetal cardiac disease), or because of fetal cardiac indications (abnormal fetal heart at the time of a screening ultrasound). Considering recent improvements in fetal cardiac screening over the past decade, the goal of this single institution study was to reconsider the importance of performing fetal echocardiography purely for screening (noncardiac) indications. We performed a retrospective analysis to review screening and fetal cardiac indications and fetal cardiac findings for fetal echocardiograms performed at UCLA between 2015 and 2019. Fetal heart disease was identified in 391 (15%) of 2592 pregnancies in this study. Among these 391 cases, 227 (58%) occurred in low-risk pregnancies (without screening indications). While 79% of the cases of fetal cardiac disease were referred with fetal cardiac indications, 21% of the cases were referred with exclusively screening indications. Fetal cardiac disease was discovered on fetal echocardiograms in 4% of pregnancies referred for exclusively screening indications, but the frequency of fetal cardiac disease following normal fetal cardiac screening has decreased from 6% in 2015 to 3% in 2019. In our population, we recommend continued referral for fetal echocardiography for pregnancies identified as high risk for CHD. However, as fetal cardiac screening continues to improve, referral for fetal echocardiography following normal fetal cardiac screening will have diminishing value and yield. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the alterations in extraocular muscles (EOMs) by magnetic resonance imaging (MRI) among patients diagnosed with Duane retraction yndrome (DRS) and congenital fibrosis of the extraocular muscles (CFEOM), who present with various cranial nerve anomalies in an attempt to enhance the clinical diagnostic process. Methods: A case–control study was conducted to evaluate 27 patients with DRS and 14 patients with CFEOM. All patients underwent MRI scans of the brainstem and orbital examination. Neurodevelopmental assessments were conducted through MRI, and maximum cross-sectional area and volumes of EOMs were obtained. Three types of models were constructed using machine learning decision tree algorithms based on EOMs to predict disease diagnosis, cranial nerve abnormalities, and clinical subtypes. Results: Patients with bilateral CN VI abnormalities had smaller volumes of LR, MR, and IR muscles compared to those with unilateral involvement (P < 0.05). Similarly, patients with CFEOM and unilateral third cranial nerve abnormalities had a smaller maximum cross-section of the affected eye's SR compared to the contralateral eye (P < 0.05). In patients with both CN III and CN VI abnormalities, the volume of SR was smaller than in patients with CN III abnormalities alone (P < 0.05). The prediction model using EOMs volume showed a diagnostic precision of 82.5% for clinical cases and 60.1% for predicting cranial nerve abnormalities. Nonetheless, the precision for identifying clinical subtypes was relatively modest, at only 41.7%. Conclusion: The distinctive volumetric alterations in EOMs among individuals exhibiting distinct cranial nerve anomalies associated with DRS or CFEOM provide valuable diagnostic insights into to Congenital Cranial Neurodevelopmental Disorders (CCDDs). MRI analysis of EOMs should thus be regarded as a crucial diagnostic modality. [ABSTRACT FROM AUTHOR]

Enterocytes and liver cells fulfill important metabolic and barrier functions and are responsible for crucial vectorial secretive and absorptive processes. To date, genetic diseases affecting metabolic enzymes or transmembrane transporters in the intestine and the liver are better comprehended than mutations affecting intracellular trafficking. In this review, we explore the emerging knowledge on intracellular trafficking defects and their clinical manifestations in both the intestine and the liver. We provide a detailed overview including more investigated diseases such as the canonical, variant and associated forms of microvillus inclusion disease, as well as recently described pathologies, highlighting the complexity and disease relevance of several trafficking pathways. We give examples of how intracellular trafficking hubs, such as the apical recycling endosome system, the trans‐Golgi network, lysosomes, or the Golgi‐to‐endoplasmic reticulum transport are involved in the pathomechanism and lead to disease. Ultimately, understanding these processes could spark novel therapeutic approaches, which would greatly improve the quality of life of the affected patients. [ABSTRACT FROM AUTHOR]

To report a case of active retinochoroiditis in a neonate treated with intravitreal clindamycin as an adjuvant therapy. A 10-day-old infant presented with active retinochoroiditis lesions in both eyes along with hepatosplenomegaly, abdominal distension, and thrombocytopenia. The mother had a history of fever in the third trimester for which she received symptomatic treatment. The infant was treated with systemic anti-toxoplasma therapy along with intravitreal clindamycin in the severely affected eye. There was a significant faster resolution in the retinochoroiditis lesions, which eventually lead to better anatomical and visual outcomes. Active screening and timely intervention of the neonates who are born to mothers with fever during pregnancy can go a long way in preventing unlikely outcomes due to congenital toxoplasma retinochoroiditis. Intravitreal clindamycin can be considered as an adjuvant therapy in selected cases. [ABSTRACT FROM AUTHOR]

Currently, nearly 90% of patients with congenital heart disease (CHD) reach adulthood in relatively good health. Structured transition programs have emerged to support adolescents and young adults in transitioning to adult care structures, improve their autonomy, and limit healthcare ruptures. The TRANSITION-CHD randomized controlled trial aimed to assess the impact of a transition program on health-related quality of life (HRQoL) in adolescents and young adults with CHD. From January 2017 to February 2020, 200 subjects with a CHD, aged 13–25 years, were enrolled in a prospective, controlled, multicenter study and randomized in two balanced groups (transition program vs. standard of care). The primary outcome was the change in PedsQL self-reported HRQoL score between baseline and 12-month follow-up, using an intention-to-treat analysis. The secondary outcomes were the change in disease knowledge, physical health (cardiopulmonary fitness, physical activity), and mental health (anxiety, depression). The change in HRQoL differed significantly between the transition group and the control group (mean difference = 3.03, 95% confidence interval (CI) = [0.08; 5.98]; p =.044; effect size = 0.30), in favor of the intervention group. A significant increase was also observed in the self-reported psychosocial HRQoL (mean difference = 3.33, 95% CI = [0.01; 6.64]; p =.049; effect size = 0.29), in the proxy-reported physical HRQoL (mean difference = 9.18, 95% CI = [1.86; 16.51]; p =.015; effect size = 0.53), and in disease knowledge (mean difference = 3.13, 95% CI = [1.54; 4.72]; p <.001; effect size = 0.64). The TRANSITION-CHD program improved HRQoL and disease knowledge in adolescents and young adults with CHD, supporting the generalization and systematization of similar preventive interventions in pediatric and congenital cardiology. [ABSTRACT FROM AUTHOR]

Introduction: Pyeloplasty is the definitive management of ureteropelvic junction obstruction (UPJO). One of the challenging questions is when to perform pyeloplasty. We studied if improvement post-pyeloplasty in the first 3 months of life could show greater improvement in hydronephrosis than surgery at an older age. Patients and Methods: Patients with postnatally diagnosed UPJO and underwent pyeloplasty in the first year of life were retrospectively reviewed. We excluded patients with concomitant vesicoureteral reflux, and patients who had pyeloplasty because of UTI or missed follow-up. Patients were divided into two groups, according to the age at pyeloplasty, before and after the age of 3 months. We collected patients' demographics, anteroposterior diameter of the renal pelvis (APD), SFU grade, renogram data, perioperative data (surgery duration, hospital stay, and ureteral stent duration) and postoperative ultrasound changes. The percentage of change of APD (Δ%APD) was calculatedusing the formula: Δ%APD = [ (initial APD-last APD)/initial APD] *100. Results: We included 90 patients (93 renal units). 36 patients had pyeloplasty during the first 3 months of life and 57 patients at 3 -12 months. Patients' characteristics were similar in both groups except APD which was higher when pyeloplasty was done < 3 months of age (p = 0.02). Both groups had comparable perioperative parameters. After almost similar follow-up period of both groups. The Δ%APD was 58% when pyeloplasty was done < 3 months compared to 33% when was performed > 3 months (p = 0.009). Using Kaplan–Meier analysis, APD significantly improved when pyeloplasty was performed before the age of 3 months (p = 0.001). Conclusion: Early pyeloplasty, in the first 3 months of life, showed a significant improvement of APD postoperatively than those had surgery later. It is unclear if this will relate to less loss of renal function yet certainly this would be suspected and feel this finding provides some evidence for early intervention. [ABSTRACT FROM AUTHOR]

Maternal diabetes mellitus is among the most frequent environmental contributors to congenital birth defects, including heart defects and craniofacial anomalies, yet the cell types affected and mechanisms of disruption are largely unknown. Using multi-modal single cell analyses, here we show that maternal diabetes affects the epigenomic landscape of specific subsets of cardiac and craniofacial progenitors during embryogenesis. A previously unrecognized cardiac progenitor subpopulation expressing the homeodomain-containing protein ALX3 showed prominent chromatin accessibility changes and acquired a more posterior identity. Similarly, a subpopulation of neural crest-derived cells in the second pharyngeal arch, which contributes to craniofacial structures, displayed abnormalities in the epigenetic landscape and axial patterning defects. Chromatin accessibility changes in both populations were associated with increased retinoic acid signaling, known to establish anterior-posterior identity. This work highlights how an environmental insult can have highly selective epigenomic consequences on discrete cell types leading to developmental patterning defects.

A common feature of congenital heart disease is the presence of right ventricular outflow tract (RVOT) obstruction that can range from mild to severe and can lead to atresia of the pulmonary valve, in extreme conditions. RVOT abnormalities can frequently be corrected surgically or via interventional means. However, most of these patients will ultimately develop pulmonary valve insufficiency and eventual right ventricular dilation, which will require a pulmonary valve replacement at some point in their life to mitigate the detrimental effects of pulmonary valve regurgitation (PVR) on the right ventricle (RV). The evolution from the studies done by Philip Bonhoeffer to implant a pulmonary valve via transcatheter means, have provided a bedrock for transcatheter pulmonary valve replacement (TPVR). Yet, several areas of unmet need for a demographic of patients still exist. Here, we discuss the clinical unmet needs in children under 20 Kg and expand the use of hybrid and other TPVR approaches along with the current indications and contraindications for pulmonary valve replacement. The constraints and limitations from commercially available pulmonary valves will be discussed from a clinical standpoint. Finally, we explore the use of hybrid and periventricular delivery of transcatheter pulmonary valves in younger patients.

Abstract Background Congenital shoulder dislocation due to shoulder girdle malformation is called true congenital shoulder dislocation. It is an extremely rare disorder as compared with traumatic dislocation or secondary to brachial plexus injury. Case presentation We report a case of atraumatic true congenital shoulder dislocation, one of the few reported cases across the world. The baby was born of a preterm caesarean section at 30 weeks of gestation, ruling out any perinatal trauma. The baby presented with a lateral shoulder crease and reduced movements of the affected upper limb. The diagnosis was confirmed with radiographs and a sonography that ruled out physeal injury. Treatment involved prompt closed reduction and stabilization by swathing in an adducted internally rotated position for two weeks. Conclusion Owing to the rarity of this condition, the case is being reported to be archived with a handful of other such cases.

Abstract Background A blind ending ureteric remnant in a duplicated urinary system is extremely rare, and most of these anomalies go unrecognized as they are asymptomatic. We describe a unique case of a blind ending ureteric remnant presenting with neurological claudication in the lower limb secondary to sacral nerve root radiculopathy which was managed by robotic excision. Case presentation A 61-year-old male presented with radiating pain in the left gluteal region for the past 2 years, which persisted despite multiple conservative treatments. Extensive evaluation for the pain revealed a blind ending ureteric remnant in a partially duplicated system, which contained multiple calculi and caused the compression of the adjacent sacral nerve roots. The patient was subsequently taken up for excision of the remnant, which was performed robotically, after which the symptoms resolved completely. Conclusion Blind ending ureteric duplications are rare anomalies that mostly go unrecognized as they are asymptomatic. Rarely, these anomalies may produce clinically relevant symptoms and result in diagnostic dilemmas, meriting intervention.