BACKGROUND: The Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented.
METHODS: The proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4-10 of the CUX1 gene.
CONCLUSIONS: Our review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.

Genome-wide association studies and experimental mouse models implicate the MIB1 and GATA6 genes in congenital heart disease (CHD). Their close physical proximity and conserved synteny suggest that these two genes might be involved in analogous cardiac developmental processes. Heterozygous Gata6 loss-of-function mutations alone or humanized Mib1 mutations in a NOTCH1-sensitized genetic background cause bicuspid aortic valve (BAV) and a membranous ventricular septal defect (VSD), consistent with MIB1 and NOTCH1 functioning in the same pathway. To determine if MIB1-NOTCH and GATA6 interact in valvular and septal development, we generated compound heterozygote mice carrying different Mib1 missense (Mib1K735R and Mib1V943F) or nonsense (Mib1R530X) mutations with the Gata6STOP/+ heterozygous null mutation. Combining Mib1R530X/+ or Mib1K735R/+ with Gata6STOP/+ does not affect Gata6STOP/+ single mutant phenotypes. In contrast, combining Mib1V943F/+ with Gata6STOP/+ decreases the incidence of BAV and VSD by 50%, suggesting a suppressive effect of Mib1V943F/+ on Gata6STOP/+. Transcriptomic and functional analyses revealed that while the EMT pathway term is depleted in the Gata6STOP/+ mutant, introducing the Mib1V943F variant robustly enriches this term, consistent with the Mib1V943F/+ phenotypic suppression of Gata6STOP/+. Interestingly, combined Notch1 and Gata6 insufficiency led to a nearly fully penetrant VSD but did not affect the BAV phenotype, underscoring the complex functional relationship between MIB1, NOTCH, and GATA6 in valvular and septal development.

Morgagni hernia (MH) is a rare form of congenital diaphragmatic hernia, typically occurring predominantly on the right side and exhibiting a higher prevalence in females. Usually diagnosed incidentally, MH may coexist with congenital heart defects, chest wall abnormalities and certain genetic syndromes such as Down syndrome. A 4-year-old boy with Down syndrome underwent simultaneous repair of MH and closure of a ventricular septal defect (VSD). A vertical midline sternotomy was performed, and the VSD was repaired using the right atrium approach. Subsequently, MH repair was conducted. Three weeks after the surgery, this patient developed a complete heart block, which lead to the implantation of a VVI pacemaker.

UNASSIGNED: We developed a hybrid technique for repairing post-myocardial infarction (MI) ventricular septal defect (VSD) that combines infarct exclusion with patch and a nitinol-mesh septal occluder device (SOD) to provide a scaffold to support the damaged septal wall. Here, we compare outcomes of patients with post-MI VSD repaired using patch only or hybrid patch/SOD.
UNASSIGNED: Patients undergoing post-MI VSD repair at our institution from 2013 to 2022 who received patch alone or patch/SOD repair were analyzed. Primary outcome was survival to hospital discharge. Clinical outcomes and echocardiograms were also analyzed.
UNASSIGNED: Over a 9-year period, 24 patients had post-MI VSD repair at our institution with either hybrid patch/SOD (n = 10) or patch only repair (n = 14). VSD size was 18 ± 5.8 mm for patch/SOD and 17 ± 4.6 mm for patch only. In the patch/SOD repair cohort, average size of SOD implant was 23.6 ± 5.6 mm. Mild left ventricular dysfunction was present prerepair and was unchanged postrepair in both groups; however, moderate-to-severe right ventricular (RV) dysfunction was common in both groups before repair. RV function worsened or persisted as severe in 10% of hybrid versus 54% of patch-only patients postrepair. Tricuspid annular systolic excursion and RV:left ventricle diameter ratio, quantitative metrics of RV function, improved after patch/SOD repair. No intraoperative mortality occurred in either group. Postoperative renal, hepatic, and respiratory failure requiring tracheostomy was common in both groups. Survival to hospital discharge in both cohorts was 70%.
UNASSIGNED: Post-MI VSD repair with patch/SOD has comparable short-term outcomes with patch alone. Addition of a SOD to patch repair provides a scaffold that may enhance the repair of post-MI VSD with patch exclusion.

To evaluate the accuracy of transthoracic echocardiography (TTE) and cardiac computed tomography angiography (CTA) in detecting the size and location of ventricular septal defects (VSD) in infants.
Data from 258 infants diagnosed with VSD between January 2020 and December 2022 were retrospectively analyzed. All infants underwent both TTE and cardiac CTA. The accuracy of these imaging modalities was assessed by comparing their findings with intraoperative observations of VSD size and location.
Intraoperatively, the average VSD size was 6.1 ± 2.5 mm. The defects were classified as committed VSD (Type 1) in 45 patients, noncommitted VSD (Type 2) in 198 patients, inlet VSD (Type 3) in 12 patients, and muscular VSD (Type 4) in 3 patients. Echocardiography estimated the average VSD size at 5.6 ± 2.7 mm, with 42 patients identified as Type 1, 203 as Type 2, 10 as Type 3, and 3 as Type 4. Cardiac CTA estimated the average size at 5.9 ± 3.2 mm, with 48 patients identified as Type 1, 196 as Type 2, 11 as Type 3, and 3 as Type 4. The accuracy rates of TTE and cardiac CTA in diagnosing VSD location were 98.1% and 98.8%, respectively. A survey of surgeons indicated that 80% believe both TTE and cardiac CTA are essential preoperative evaluations.
TTE accurately diagnoses the size and location of VSD, while cardiac CTA serves as a valuable complementary method to TTE. Most surgeons advocate for the combined use of these examinations for preoperative assessment.

BACKGROUND: For patients with large and deep-seated recurrent complex pilonidal sinuses, the use of traditional open excision or flap reconstruction surgery may lead to high surgical difficulty, significant local damage, numerous complications, slow healing, and a high risk of recurrence. This article reports a case of recurrent complex pilonidal sinus and discusses the advantages of Bascom II combined with VSD treatment involving the preservation of tissue bridges.
METHODS: The patient, a 31-year-old male, presented with recurrent swelling, pain, and purulent discharge from the sacrococcygeal region for over a year. Upon physical examination, extensive lumps and sinus tracts were observed in the lumbosacral tail area, with the lesion extending from L4 to the tip of the coccyx. Under general anesthesia, a segmental resection was performed, and the lumbosacral mass lesion was excised, preserving normal tissue bridges. The mature sinus tract at the upper part of the coccyx was removed, and Bascom II reconstruction surgery was performed. In the late stage at the site of lumbar sacral lesion excision, VSD was applied to promote wound healing.
CONCLUSIONS: The combination of Bascom II with lesion tunnel-like removal can reduce the damage, elevate gluteal cleft, and lower the recurrence rate. Subsequently, with the addition of VSD, it can accelerate the elimination of necrotic tissue, reduce infection risk, and expedite wound healing.
CONCLUSIONS: This case explores the advantages and characteristics of combining various techniques in the treatment of recurrent complex pilonidal sinuses, emphasizes the utility of VSD as an adjunctive therapy for large lesions.

BACKGROUND: Carcinogenic risk assessment studies have been repeatedly improved and are still being debated to find a goal. Evaluation might be changed if new approaches would be applied to some chemicals which means that new approaches may change the final assessment. In this paper, the risk assessment of a chemical, in particular the proper carcinogenicity, is examined using the long-banned food additive, 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, AF-2, as a case study.
RESULTS: First, Ames tests were carried out using strains TA1535, TA100, TA1538, and TA98 and their nitroreductase-deficient strains YG7127, YG7128, YG7129, and YG7130. The results showed that mutagenic activity was reduced by about 50% in the nitroreductase-deficient strains, indicating that part of the mutagenic activity shown in Ames test was due to bacterial metabolism. Second, in vivo genotoxicity tests were conducted, including the one that had not been developed in 1970\'s. Both a micronucleus test and a gene mutation assay using transgenic mice were negative. Third, assuming it is a genotoxic carcinogen, the virtual safety dose of 550 μg/day was calculated from the TD50 in rats with a probability of 10-5.
CONCLUSIONS: AF-2 has been shown to be carcinogenic to rodents and has previously been indicated to be genotoxic in vitro. However, the present in vivo genotoxicity study, it was negative in the forestomach, a target organ for cancer, particularly in the gene mutation assay in transgenic mice. Considering the daily intake of AF-2 in the 1970s and its virtually safety dose, the carcinogenic risk of AF-2 could be considered acceptable.

UNASSIGNED: Post-infarction ventricular septal defects remain one of the most feared complications after myocardial infarction with high mortality rates. In special cases, surgical or interventional treatment strategies are technically not feasible and do not always lead to a good outcome.
UNASSIGNED: A 58-year-old male patient in cardiogenic shock with a very large ventricular septal (VSD) defect (4.9 cm × 5 cm) due to myocardial infarction was presented in our department. Acute stabilization was achieved using peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Neither surgical nor interventional therapy was considered as a sufficient option due to the unsuitable anatomy of the VSD and the patient was listed for heart transplantation. After 2 weeks on ECMO, bleeding and infectious complications occurred. Due to organ shortage, urgent implantation of the bioprosthetic total artificial heart (TAH) Aeson device (CARMAT) remained the only useful strategy to achieve a mid- or long-term bridge to transplantation. After successful implantation and good recovery with the Aeson device, the patient was transplanted 4 weeks after implantation.
UNASSIGNED: Post-infarction ventricular septal defects are highly challenging and are commonly associated with a poor prognosis. The implantation of the new Aeson TAH device is a promising therapeutic option, allowing a safe and long-term bridging to heart transplantation.

Infective endocarditis (IE) is life-threatening and can lead to complications if left untreated. A 56-year-old gentleman presented with acute delirium, fever and rigor. Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (S. aureus) was isolated in the blood culture and the PR interval was prolonged on the electrocardiogram (ECG). However, the transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) at presentation were unremarkable with no evidence of intracardiac vegetations. Despite expedient intravenous antibiotics, an acquired ventricular septal defect (VSD) developed, which required urgent cardiothoracic surgical repair. It is imperative to consider early surgical interventions and the use of anti-toxin antibiotics in PVL-positive S. aureus IE.

Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation.