Chromosome Translocation t(6; 14) With Different Phenotypes and Segregation Patterns: A Report of Two Cases.

Chromosomal rearrangement can disrupt gene function by interfering with coding sequences or their regulatory regions. The breakpoint in these rearrangements can pinpoint the disease-related gene's location. This paper presents two rare cases of chromosomal rearrangement involving chromosome 6 (6p24-25) and chromosome 14 (14q22-23). The first case involves a girl with hearing impairment, inheriting a balanced translocation of chromosomes 6 and 14 from her father. The second case describes a dysmorphic baby boy with congenital bilateral choanal atresia and a tertiary trisomy, involving a translocation between chromosome 6 (6p24) and chromosome 14 (14q22), resulting in a derivative chromosome (14) in addition to the normal complement of chromosomes 6 and 14. The boy's mother had a history of four recurrent miscarriages. However, the origin of this tertiary trisomy in the second case presented could not be delineated because the parents did not consent and declined their blood samples for karyotyping. Parental karyotyping and chromosomal analysis are crucial for investigating recurrent miscarriages, identifying genetic causes, guiding reproductive decisions, and improving successful pregnancy outcomes for affected couples.

A Longitudinal Observation of Antenatal Milk Expression in Mothers of Infants with Congenital Anomalies.

Background: For mothers of infants with congenital anomalies, antenatal milk expression (AME), known as hand expression during late pregnancy, allows mothers to contribute to their newborn's care through colostrum collection. However, research is limited by self-report of AME adherence and colostrum volume. Objective: This study examined the ability of participants to adhere to a recommended protocol on AME for any removal and measurement of colostrum during late pregnancy. Materials and Methods: A prospective, longitudinal, observational design was used. Our recommended protocol involved hand expression of 5 minutes per breast for a total of 10 minutes for each AME session twice per 24 hours for any colostrum from 37 0/7 weeks gestation until birth. Women received AME education, completed milk logs, and attempted AME. The study team verified all colostrum volumes. Results: Nineteen women (10 nulliparous) participated, with 13 (68%) carrying infants with major organ system defects and 6 (32%) carrying infants with congenital heart defects. Most participants (52.6%) completed more than half but fewer than all AME sessions. Seven participants (36.8%) fully adhered, completing two AME sessions daily until hospital admission. Eighteen participants (94.7%) could remove milk (80-100% of the time). The 24-hour colostrum volume (median 0.35 mL, interquartile range [IQR] 0.065-0.845) and the total colostrum volume (median 3.99 mL, IQR 1.35-6.82) from AME varied. Conclusions: Among a small group of women of infants with congenital anomalies, adherence to a recommended protocol is feasible but varied by AME session frequency. Most women could collect colostrum for future infant feeding.

An Intradural Extramedullary Enterogenous Cyst in the Conus Medullaris: A Report of a Rare Presentation.

Intraspinal enterogenous cysts are rare congenital abnormalities that mainly develop in the spinal canal, more commonly in the cervical and thoracic regions, and rarely in the lumbar spine. We present a case of neurenteric (NE) cyst in the conus medullaris and cauda equina junction at the level of L1 in a patient presenting with a nine-year history of progressive lower limb weakness, paresthesia, and muscle wasting. The patient underwent complete resection of the cyst and had no postoperative complications with marked improvement of paresthesia and some localized pain in the lower back manageable by analgesics.

Gastroschisis Prevalence and Co-occurring Malformations Among Danish Live Births During 1994-2021: A Nationwide Register-based Study.

BACKGROUND: Gastroschisis prevalence has increased for decades with corresponding increases in the need for immediate and follow-up care. Such care can be complicated by presence of co-occurring malformations. This study explores prevalence of gastroschisis and co-occurring malformations among a 28-year cohort of Danish live-born infants. METHODS: This retrospective cohort study used data from 1,695,992 infants born in Denmark during 1994-2021 and registered in the neonatal screening program. Infants were identified from the Danish Civil Registration System and Danish National Patient Register accessed through the Danish Biobank Register. Data on co-occurring malformations were ascertained to classify infants as syndromic or non-syndromic (either isolated or with co-occurring major malformations) and on selected infant and parental characteristics. Poisson regression models were used to estimate prevalence and corresponding 95% confidence intervals (CIs). RESULTS: Prevalence (per 10,000 live births) of gastroschisis was 1.64 (CI: 1.45-1.84). Temporal trend analyses showed a statistically significant annual increase of 2.8% (CI: 1.4-3.3). Infants with gastroschisis most often presented as isolated (77.7%; CI: 72.3-82.5), followed by those with co-occurring malformations (21.9%; CI: 17.2-27.3) or a diagnosed syndrome (0.4%, CI: <0.1-2.0). Among infants with co-occurring malformations, cardiovascular (10.9%; CI: 6.8; 12.2) and intestinal (9.0%; CI: 5.9-12.2) malformations were most frequently recorded. Prevalence was higher among infants classified as premature but not influenced by infant sex or parental nativity. CONCLUSION: Gastroschisis prevalence in Denmark increased during 1994-2021, similar to international reports, without increase in co-occurring malformations. Future work with this cohort will characterize healthcare received, comorbidities, and outcomes across the lifespan. LEVELS OF EVIDENCE: Level III (High-quality prospective cohort study).

Increased incidences of cervical ribs in deer indicate extinction risk.

Mammals as a rule have seven cervical vertebrae, a number which remains remarkably conserved. Occasional deviations of this number are usually due to the presence of cervical ribs on the seventh vertebra, indicating a homeotic transformation from a cervical rib-less vertebra into a thoracic rib-bearing vertebra. These transformations are often associated with major congenital abnormalities or pediatric cancers (pleiotropic effects) that are, at least in humans, strongly selected against. Based on data from Late Pleistocene mammoths (Mammuthus primigenius) and woolly rhinoceroses (Coelodonta antiquitatis) from the North Sea, we hypothesized that high incidences of cervical ribs in declining populations are due to inbreeding and/or adverse conditions impacting early pregnancies. In this study, we investigated the incidence of cervical ribs in an extinct Late Pleistocene megaherbivore, giant deer (Megaloceros giganteus) from Ireland and in the extant highly inbred Père David deer (Elaphurus davidianus) and in twenty other extant species. We show that the incidence of cervical ribs is exceptionally high in both the Irish giant deer and the Père David deer and much higher than in extant outbred deer. Our data support the hypothesis that inbreeding and genetic drift increase the frequencies of maladaptive alleles in populations at risk of extinction. The high incidence of cervical ribs indicates a vulnerable condition, which may have contributed to the extinction of megaherbivore species in the Late Pleistocene. We argue that cervical rib frequency may be a good proxy for extinction risk in inbred populations.

Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies.

BACKGROUND: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. METHODS: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. RESULTS: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. CONCLUSION: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

A Comprehensive Review on a Prosthetic Finger Fabrication Approach: Clinical Rest Position (CRP) vs Palms and Fingers Extended (PFE).

Creating effective prosthetic fingers involves precise treatment planning and skilled fabrication to restore aesthetic appearance and passive function. Successful outcomes depend significantly on retention and how closely the prosthesis mimics natural finger contours. We analyzed techniques for fabricating finger prostheses with palms and fingers in clinical rest position (CRP) versus palms and fingers extended (PFE) straight out. The aesthetics and function (passive) were also examined when fabricated in these two physiological conditions. We reviewed 20 articles from national and international journals over 20 years. Most literature focuses on extended posture fabrication, with few addressing CRP. This review article compares the CRP and PFE prosthetic finger fabrication approaches and explains how a prosthetic finger fabricated in a CRP offers superior aesthetic and partial functional outcomes and emerges as a promising alternative to the PFE. The potential impact of these findings on prosthodontics is significant, emphasizing the need for further research to validate these results and the ongoing development in the field.

Autologous micrografting improves regeneration of tissue-engineered urinary conduits in vivo.

Urogenital reconstructive malformation surgery is sometimes hampered by lack of tissue for the repair. We have previously shown that autologous micrografting allows for single-staged scaffold cellularization after surgical implantation. Here, a collagen-based scaffold reinforced with biodegradable mesh and a stent was implanted as a bladder conduit in ten full-grown female minipigs. We aimed to assess short-term regenerative outcomes, safety, and feasibility of implanting tubular urinary micrografted scaffolds versus acellular controls. Five scaffolds were embedded with autologous urothelial micrografts harvested perioperatively. After six weeks, all animals were assessed by cystoscopy, CT-urography, and microanatomical assessment of the urinary conduits. The procedure proved technically feasible within the confines of a regular surgical theater, with duration-times comparable to corresponding conventional procedures. No animals experienced postoperative complications, and all implanted conduits were patent at follow-up. Improved tissue regeneration was observed in the micrografted conduits compared with the acellular controls, including increased luminal epithelialization, increased cell proliferation, decreased cell apoptosis, and increased conduit vascularization. We concluded that single-staged on-site construction and implantation of tissue engineered urinary conduits proved feasible and safe, with improved regenerative potentials in micrografted conduits. This study presents a new approach to urinary conduits, and merits further investigations for advancement towards clinical translation.

Posterior Urethral Valves in a Healthy-Appearing Athletic Adult: A Case Report.

Posterior urethral valves (PUV) are a congenital malformation of the male urethra where the posterior opening connecting to the bladder is covered by membranous folds. Most cases are diagnosed antenatally, with postnatal cases typically diagnosed and surgically repaired within the first years of life. Delayed presentation beyond infancy is rare, with presentation into adulthood being exceedingly rare, especially in the United States. We present a case of an 18-year-old healthy-appearing athletic male who presented with delayed presentation of PUV. This patient with no significant past medical history presented to the emergency room upon referral by his primary care physician, who denoted incidental findings of elevated blood pressure and acute renal failure at his annual physical examination. This led to further investigation, including a full renal blood workup, bilateral renal ultrasound, and voiding cystourethrogram, which revealed severe bilateral hydronephrosis, cortical thinning, and diverticula of the bladder, prompting a diagnosis of PUV. The patient underwent laser valve ablation surgery, although unfortunately, the surgery will prevent symptoms from progressing but is unlikely to reverse the current stage of chronic kidney damage. Even though delayed presentation of PUV is rare, it is important to recognize that patients may have a long history of renal complaints and may have normalized and internalized their symptoms. Physicians should take detailed and holistic medical histories and create a safe, non-judgmental environment to build rapport with young adult patients, ensuring early and effective medical intervention.

[Cryptorchidism: An update of advances in its diagnosis and treatment]. / Criptorquidia: una revisión de los avances más recientes en su diagnóstico y tratamiento.

The absence of one or both testicles in the scrotal position is defined as cryptorchidism. It occurs in 1 - 8 % of full-term newborns and up to 45 % of preterm newborns. Its detection is of great importance due to its association with fertility disorders and the risk of malignancy. The National Endocrinology Committee of the Sociedad Argentina de Pediatría decided to prepare an update document on advances in the diagnosis and treatment of cryptorchidism that contributes to the performance of pediatric practice and allows recognition of conditions that may be accompanied by cryptorchidism, but need more evaluation and referral to a specialist, such as alterations/differences in sexual development, anorchia, genetic syndromes, among others. The first-line treatment is early orchiopexy before 12 to 18 months, always in the hands of pediatric surgeons.

Se define como criptorquidia, o criptorquidismo, a la ausencia de uno o ambos testículos en la posición escrotal. Se presenta en el 1-8 % de los recién nacidos de término y hasta en el 45 % de los pretérmino. Es de gran importancia su detección oportuna por su asociación con alteraciones de la fertilidad y el riesgo de malignidad. El Comité Nacional de Endocrinología de la Sociedad Argentina de Pediatría decidió elaborar un documento de actualización sobre los avances en el diagnóstico y tratamiento de la criptorquidia, útil para la práctica pediátrica y que permita identificar condiciones que puedan acompañarse de criptorquidia, pero que merezcan una evaluación más profunda y derivación al especialista (alteraciones/diferencias en el desarrollo sexual, anorquia, síndromes genéticos). El tratamiento de primera línea es la orquidopexia temprana (antes de los 12 a 18 meses), siempre en manos de cirujanos pediátricos.

The Use of 3D Printing in Fetal Surgery for Surgical Planning: A Scoping Review.

Objectives: We sought to identify in which clinical scenarios 3D printed models are used to plan for fetal surgeries as well as the main purpose and the imaging method utilized for the models. In addition, we describe benefits and shortcomings of the models, as well as potential future improvements. Methods: In this scoping review, data were collected retrospectively from scientific databases (PubMed, Embase, Cochrane CENTRAL, CINAHL, Scopus, and the Web of Science platform) and screened by title, abstract, and full text against strict criteria. The inclusion criteria required the study be performed on a live fetus and involve 3D models used for fetal surgery. The models must have been designed from diagnostic imaging modalities such as CT, MRI, or ultrasound. The articles considered include clinical trials, review articles, cohort studies, case series, case reports, and conference abstracts. Results: Of the initial 742 articles collected, six met the inclusion criteria. Spina bifida and EXIT procedures were the most frequent use cases that inspired surgeons to print models for surgical planning. The ability to view patient-specific anatomy in a 3D handheld model was often touted as providing a great benefit to the surgical team's ability to anticipate intraoperative challenges. Conclusions: Three-dimensional printing models have been applied to plan for fetal surgeries, more specifically, for EXIT procedures and fetoscopic surgical repair of spina bifida. The potential benefits of 3D printing in fetal surgery are enormous.

Rare Right-Sided Posterolateral Diaphragmatic Hernia in an Adult Presenting as an Incarcerated Large Bowel Obstruction: A Case Report.

Introduction: A diaphragmatic hernia (DH) is a defect within a part of the diaphragm that allows intra-abdominal contents to enter the thoracic cavity. Diaphragmatic hernias can be congenital or acquired later in life. The most common congenital DH is the Bochdalek hernia (posterolateral hernia), but the most commonly acquired DH is due to traumatic injury. These hernias are rare in adults and are typically diagnosed incidentally. Surgical repair is the standard of care; however, data regarding the surgical approach is scarce. We report a case of a rare right posterolateral DH in an adult female patient who presented with acute abdominal pain. Case Presentation: A 69-year-old female presented with recurrent epigastric pain that had acutely worsened, nausea, vomiting, and food intolerance. A computed tomography (CT) scan demonstrated a right posterolateral DH containing the hepatic flexure of the colon. The patient was taken urgently to surgery due to concern for strangulation. Reduction of the hernia was attempted laparoscopically but was converted to an open procedure with a subcostal incision due to poor visualization. This approach revealed adequate exposure of the defect and subsequent reduction of the herniated abdominal contents. The defect was easily closed without tension or the use of mesh. The patient was discharged on postoperative day 3. Conclusion: Chronic DH can have severe life-threatening sequelae when left untreated. This case demonstrates the importance of thorough history-taking and raises awareness of missed diaphragmatic injuries in trauma situations. Since patients who present with a symptomatic DH often need urgent repair, it is important for surgeons working in the acute care setting to understand the surgical options available and when mesh placement may benefit the situation. Our case outlines a successful primary defect repair, without mesh, of a right-sided DH in which a minimally invasive technique was attempted but converted to laparotomy for patient safety.

Left atrial mitral valve cord: Unveiling complexity through advanced 3D TEE imaging - A case report.

This case report explores the left atrial mitral valve cord, an extremely rare congenital anomaly. Typically involving mitral valve leaflets and associated with mild mitral regurgitation, it is rarely documented independently. A 51-year-old patient presented with dizziness, and diagnostic challenges arose during transthoracic echocardiography (TTE). Advanced 3-dimensional transesophageal echocardiography (3D TEE) proved invaluable for accurate mapping, revealing a unique, unattached left atrial mitral valve cord.

Clinical presentation and surgical outcomes in patients with Shone's complex: a systematic review.

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.

Prenatal Prognosis of Omphalocele Using Magnetic Resonance Imaging Measurement of Fetal Lung Volumes.

BACKGROUND: Omphalocele is a congenital midline abdominal wall defect resulting in herniation of viscera into a membrane-covered sac. Pulmonary complications, including pulmonary hypoplasia, pulmonary hypertension, and prolonged respiratory support are a leading cause of neonatal morbidity and mortality. OBJECTIVE(S): This study aimed to assess the role of fetal MRI-derived lung volumes and omphalocele defect size as clinical tools to prognosticate postnatal pulmonary morbidity and neonatal mortality in those with a prenatally diagnosed omphalocele (PDO). STUDY DESIGN: This was a retrospective cohort study of all pregnancies with PDO at our fetal center from 2007-2023. Pregnancies with aneuploidy or concurrent life-limiting fetal anomalies were excluded. Using fetal MRI, observed-to-expected total fetal lung volume (O/E TLV) ratios were determined by a previously published method. The transverse diameter of the abdominal defect was also measured. The O/E TLV ratios and abdominal defect measurements were compared with postnatal outcomes. The primary outcome was death at any time. Secondary outcomes included death in the first 30 days of life or before discharge from birth hospitalization, the requirement of respiratory support with intubation and mechanical ventilation, or development of pulmonary hypertension. RESULTS: Of 101 pregnancies with a PDO, 54 pregnancies (53.5%) with prenatally diagnosed omphalocele met inclusion criteria. There was a significant increase in the rate of death when compared between the three O/E TLV classifications: 1/36 (2.8%) in the O/E≥50% group, 3/14 (21.4%) in the O/E 25%-49.9% group, and 4/4 (100%) in the O/E<25% group (P<.001). The rate of intubation increased with the severity of O/E TLV classification, with 27.8% in the O/E≥50% group, 64.3% in the O/E 25%-49.9% group, and 100% in the O/E<25% group (P=.003). The rate of pulmonary hypertension was also higher in the O/E 25%-49.9% (50.0%) and the O/E<25% (50.0%) groups compared to the O/E≥50% group (8.3%, P=.002). There was no association between the transverse diameter of the abdominal wall defect and the primary outcome of death (OR=1.08 95% CI=[0.65-1.78], P=.77). CONCLUSIONS: In our cohort of patients with PDO, O/E TLV<50% is associated with death, need for intubation, prolonged intubation, and pulmonary hypertension. In contrast, omphalocele size demonstrated no prognostic value for these outcomes. The strong association between low fetal lung volume on MRI and poor neonatal outcomes highlights the utility of fetal MRI for estimating postnatal prognosis. Clinicians can utilize fetal lung volumes to direct perinatal counseling and optimize the plan of care.

Association of the national level of human development with the incidence and mortality of congenital birth defects in 2019: A cross-sectional study from 189 countries.

Congenital birth defects (CBD) play a significant role in causing child mortality globally. The incidence and mortality of CBD vary widely across countries, and the underlying causes for this divergence remain incompletely comprehended. We conducted an analysis to investigate the relationship between the incidence and mortality of CBD in 189 countries and their Human Development Index (HDI). In this study, CBD data from 189 countries was used from the Global Burden of Diseases Study (GBD) 2019, and HDI data was collected for the same countries. Later, the relationship between CBD and HDI was analyzed, and the impact of gross national income (GNI) per capita, expected years of schooling, mean years of schooling and life expectancy at birth was quantified using principal component regression. The age-standardized incidence rate (ASIR) varied between 66.57 to 202.24 per 100,000, with a 95% uncertainty interval (UI) of 57.20-77.51 and 165.87-241.48 respectively. The age-standardized mortality rate (ASMR) also showed a rang from 1.38 to 26.53 (14.03-39.90) per 100,000, with the 95%UI of 0.91-2.09 and 14.03-39.90 respectively. Both the incidence and mortality rates of CBD decreased with the increased HDI (incidence: r = -0.38, p < 0.001, mortality: r = -0.77, p < 0.001). Our investigation revealed significant variations in the incidence and mortality of CBD among countries with different development levels. In conclusion, the global incidence and mortality of CBD vary significantly among countries, possibly due to differences in the accessibility of health services.

Choledochal Cyst in the Context of Sickle Cell Disease: A Case Report.

Choledochal cyst is a congenital pathology with an uncommon anomaly associated with common complaints of an abdominal lump and hepatic dysfunction. It may be presented equally in any phase of life, be it childhood, adolescence, or adulthood, and is majorly detected by ultrasonography (USG) on the appearance of primary symptoms in the hepato-biliary system. It has a classical triad consisting of a lump in the upper quadrant on the right side of the abdomen, pain in the upper part of the abdomen, and obstructive jaundice. A few of the clinical features overlap with sickle cell disease. A 30-year-old male patient with sickle cell anemia was diagnosed eight years ago. The patient was diagnosed with a choledochal cyst with the clinical presentation of abdominal pain, nausea, and vomiting, which hampered his routine life. Due to symptomatic recurrence, the patient was subjected to USG (abdomen), which showed a dilated common bile duct (CBD) and dilated intrahepatic biliary radicals. This is a rare case presentation with both sickle cell disease and choledochal cyst, which are symptomatically similar. Based on history, risk factor analysis, and diagnostic findings, the patient was advised to have a Roux-en-Y hepatico-jejunostomy. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) are the investigations of choice, with the better being MRCP. ERCP is a therapeutic and diagnostic modality that helps in the removal of CBD calculus and the placement of a stent. There may be increased bilirubin, showing features of obstructive jaundice in alcoholic stools. In surgical management, which is of total excision of the cyst, there are vital structures in proximity. The patients with these complaints need to be evaluated thoroughly, and detailed clinical examination and proper radiological investigations will be performed. Roux-en-Y hepatico-jejunostomy with cyst excision in toto is the procedure of choice.

Prognostic value of cardiopulmonary exercise test in children with congenital heart defects.

BACKGROUND: Cardiopulmonary exercise testing (CPET) has an important prognostic value in adults with different congenital heart defects (CHDs) and is a useful tool for risk stratification and clinical decision-making. In this retrospective study, we studied the prognostic value of CPET in paediatric patients with CHD. METHODS: 411 CPET performed by paediatric patients with different CHDs were evaluated in this retrospective study. Medical records were reviewed to determine the presence of cardiac events. Participants were classified using the 2018 AHA/ACC guideline for the management of adults with CHD that combines anatomical complexity and current physiological stage. RESULTS: 411 patients with a median age at test of 12 years, 51 patients with simple CHD, 170 patients with moderate complexity CHD and 190 with high complexity CHD underwent CPET. Overall, CPET parameters were lower than the reference values (%predicted VO2peak=75% and %predicted oxygen uptake efficiency slope (OUES)=79%), showing worst exercise capacity in the most complex types of CHD (Group III: %predicted VO2peak=72% and %predicted OUES=75%). Seventy-one patients presented with cardiac events at a median time from CPET to first event of 28 months. Patients with cardiac events had lower exercise performance as compared with patients without cardiac events as determined by the submaximal variables (%predicted OUES: HR=2.6 (1.5-4.4), p<0.001 and VE/VCO2: HR=2.2 (1.4-3.5), p=0.001). CONCLUSION: Reduced exercise capacity at young age is related to a higher probability of future cardiovascular events in paediatric patients with CHD. Submaximal exercise variables can be used instead when maximal exercise cannot be achieved.

Surgical management of the diaphragmatic defect in congenital diaphragmatic hernia: a contemporary review.

Worldwide, 150 children are born each day with congenital diaphragmatic hernia (CDH), a diaphragmatic defect with concomitant abnormal lung development. Patients with CDH with large defects are particularly challenging to treat, have the highest mortality, and are at significant risk of long-term complications. Advances in prenatal and neonatal treatments have improved survival in high-risk patients with CDH, but surgical treatment of large defects lacks standardization. Open repair by an abdominal approach has long been considered the traditional procedure, but the type of defect repair (patch or muscle flap) and patch material (non-absorbable, synthetic or absorbable, biological) remain subjects of debate. Increased experience and improved techniques in minimally invasive surgery (MIS) have expanded selection criteria for thoracoscopic defect repair in cardiopulmonary stable patients with small defects. However, the application of MIS to repair large defects remains controversial due to increased recurrence rates and unknown long-term effects of perioperative hypercapnia and acidosis resulting from capnothorax and reduced ventilation. Current recommendations on the surgical management rely on cohort studies of varying patient numbers and data on the long-term outcomes are sparse. Here, we discuss surgical approaches for diaphragmatic defect repair highlighting advancements, and knowledge gaps in surgical techniques (open surgery and MIS), patch materials and muscle flaps for large defects, as well as procedural adjuncts and management of CDH variants.

Role of genetics and the environment in the etiology of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by failure of diaphragm closure during embryonic development, leading to pulmonary hypoplasia and pulmonary hypertension, which contribute significantly to morbidity and mortality. The occurrence of CDH and pulmonary hypoplasia is theorized to result from both abnormalities in signaling pathways of smooth muscle cells in pleuroperitoneal folds and mechanical compression by abdominal organs within the chest cavity on the developing lungs. Although, the precise etiology of diaphragm maldevelopment in CDH is not fully understood, it is believed that interplay between genes and the environment contributes to its onset. Approximately 30% of patients with CDH possess chromosomal or single gene defects and these patients tend to have inferior outcomes compared with those without genetic associations. At present, approximately 150 gene variants have been linked to the occurrence of CDH. The variable expression of the CDH phenotype in the presence of a recognized genetic predisposition can be explained by an environmental effect on gene penetrance and expression. The retinoic acid pathway is thought to play an essential role in the interactions of genes and environment in CDH. However, apart from the gradually maturing retinol hypothesis, there is limited evidence implicating other environmental factors in CDH occurrence. This review aims to describe the pathogenesis of CDH by summarizing the genetic defects and potential environmental influences on CDH development.