Ribosome dysfunction underlies the pathogenesis of many cancers and heritable ribosomopathies. Here, we investigate how mutations in either ribosomal protein large (RPL) or ribosomal protein small (RPS) subunit genes selectively affect erythroid progenitor development and clinical phenotypes in Diamond-Blackfan anemia (DBA), a rare ribosomopathy with limited therapeutic options. Using single-cell assays of patient-derived bone marrow, we delineated two distinct cellular trajectories segregating with ribosomal protein genotypes. Almost complete loss of erythroid specification was observed in RPS-DBA. In contrast, we observed relative preservation of qualitatively abnormal erythroid progenitors and precursors in RPL-DBA. Although both DBA genotypes exhibited a proinflammatory bone marrow milieu, RPS-DBA was characterized by erythroid differentiation arrest, whereas RPL-DBA was characterized by preserved GATA1 expression and activity. Compensatory stress erythropoiesis in RPL-DBA exhibited disordered differentiation underpinned by an altered glucocorticoid molecular signature, including reduced ZFP36L2 expression, leading to milder anemia and improved corticosteroid response. This integrative analysis approach identified distinct pathways of erythroid failure and defined genotype-phenotype correlations in DBA. These findings may help facilitate therapeutic target discovery.

Background: Medical advancements have encouraged minimally invasive surgical repair of congenital heart defects such as ventricular septal defects (VSDs), and the diagnostic process can now be carried out using non-traditional techniques such as pulse oximetry. This, in turn, has improved clinical outcomes with reduced complication rates post-surgery. However, the variations in type of VSDs, age of patient, comorbidities, and access to closure devices may limit the efficacy of surgical advancements. Methods: Articles were identified amongst Scopus, MEDLINE, and PubMed using various relevant search strings using PRISMA guidelines. Of the 115 articles initially extracted, 10 were eventually reviewed after duplicates and irrelevant studies were removed. Results: Of the 24 eligible articles, 10 papers were selected for analysis. Minimally invasive approaches to VSD repair was associated with satisfactory short-term outcomes when compared to open repair. For diagnosis of congenital VSD, whilst recent advances such as pulse oximetry method and genome analysis are more sensitive, the limited availability and access to such investigatory methods must be recognised. Conclusion: Pulse oximetry and fetal echocardiography are established non-invasive diagnostic tools for VSD. The recent advances in minimally invasive treatment options including periventricular approach and transcatheter techniques have improved patient outcomes, yet at the expense of higher residual rates. Careful patient selection for each technique and follow-up should be planned through multidisciplinary team meetings.

Congenital anomalies of the aortic valve frequently necessitate intervention in childhood. The most common aortic valve pathologies present in childhood are aortic stenosis and insufficiency. Presentation of aortic valve disease depends on severity and presence of concomitant syndromes and valvular disorders. Treatment options are largely categorised as medical, percutaneous repair or surgical repair and replacement. Surgical techniques have been refined over the last few years making this the mainstay of treatment in paediatric cases. Whilst repair is considered in most instances before replacement, there are substantial limitations which are reflected in the frequency of reintervention and restenosis rate. Replacements are typically undertaken with tissue or mechanical prosthesis. The current gold-standard aortic valve replacement surgery is called the Ross procedure—where replacement is undertaken with a competent pulmonic valve and a simultaneous pulmonary homograft.Conclusion: In this review, we aim to outline the various surgical options and discuss efficacy and complications of various interventions. What is Known: • Congenital aortic valve defects repair options medically and surgically What is New: • Comparisons between surgical options for aortic valve repair including efficacy, risks and long-term outcomes.

The ductus arteriosus (DA) connects the pulmonary artery to the aorta to bypass the pulmonary circulation in utero. It normally closes within 24–72 hours after birth due to increased pulmonary resistance from an increase in oxygen partial pressure with the baby’s first breath. Medical treatment can help close the DA in certain situations where closure is delayed. However, in duct-dependent cardiac defects, the presence of the DA is crucial for survival and as such medical and surgical techniques have evolved to prevent closure. This review aims to outline the two main management options for keeping a ductus arteriosus patent. This includes stenting the PDA and shunting via a modified Blalock–Taussig shunt. Whilst both techniques exist, multicentre trials have found equal mortality end points but significantly reduced morbidity with stenting than shunting. This is also reflected by shorter recovery times, reduced requirement for extracorporeal membrane oxygenation (ECMO), and improved quality of life, although stent longevity remains a limiting factor.