Multidisciplinary management of a pregnant woman with hepatic rupture complicated with HELLP syndrome.

A 32-year-old woman with preeclampsia who presented with persistent severe hypertension and epigastric pain underwent an emergency cesarean section for fetal distress and was diagnosed with hepatic rupture and HELLP (hemolysis, elevated liver enzymes, and a low platelet) syndrome. After the operation, the patient was transferred to the intensive care unit for supportive treatment and management of complications. Diagnosis and treatment decisions were made through multidisciplinary management. The patient received plasma exchange and continuous renal replacement therapy. One week after the operation, the patient developed deep vein thrombosis and received anticoagulant therapy, which triggered rebleeding. Conservative treatment was taken, including halving the dosage of anticoagulant medication and performing a blood transfusion, and the patient's condition gradually stabilized. The patient was discharged 44 days after the operation. Early diagnosis, effective treatment, and multidisciplinary management can help patients with this critical presentation achieve good clinical outcomes.

Multiphase computed tomography angiography derived from computed tomography perfusion data for the differential diagnosis of intracranial aneurysm and infundibular dilation.

Background: As infundibular dilation (ID) is less likely to cause hemorrhage or other clinical sequelae than an intracranial aneurysm (IA) and treating infundibulum itself may put the patient at unnecessary risk for stroke, it is important to distinguish between the ID and IA. Given the limitations of conventional single-phase computed tomography angiography (sCTA) to show small branches of intracranial arteries, the application of multiphase computed tomography angiography (mCTA) for identification seems promising. Our main objective was to evaluate whether using mCTA derived from computed tomography perfusion (CTP) data can improve distinction between IA and ID. Methods: A total of 35 patients diagnosed with IA or ID of the posterior communicating artery at its junction with the internal carotid artery junction (ICA-PComA) by sCTA at the 8th Medical Center of Chinese PLA General Hospital between January 2019 and May 2022 were retrospectively selected. All patients underwent CTP. The simulated mCTA was reconstructed from 0.75 mm CTP data for assessment of vascular branches. All data were processed separately by 2 CTA post-processors; 2 observers diagnosed IA and ID by source and volume rendering (VR) images of sCTA and VR images of mCTA, and compared the diagnostic efficacy of source and VR images of sCTA with VR images of mCTA. Results: The quality of the reconstructed images was more consistent between the 2 post-processors mCTA (K=0.856) than sCTA (K=0.648). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the source image for ID identification were 78.9%, 86.7%, 84.2%, 81.3%, and 80.0% for sCTA, 73.7%, 81.2%, 82.3%, 72.2%, and 77.2% for the VR image of sCTA, and 94.7%, 87.5%, 90.0%, 93.3%, and 91.4% for the VR image based on mCTA, respectively. The net reclassification index (NRI) of mCTA for VR and the source image of sCTA was 0.273 and 0.220, respectively. VR base on mCTA was on average better than VR and the source image of sCTA at differentiating ID from IA (P=0.005 and P=0.001, respectively). Conclusions: Compared to sCTA, mCTA is more helpful in improving the distinction of ID and IA.

Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects.

BACKGROUND: Congenital heart disease (CHD) is the most common human birth defect. Genetic causes for CHD remain largely unknown. GATA transcription factor 5 (GATA 5) is an essential regulator for the heart development. Mutations in the GATA5 gene have been reported in patients with a variety of CHD. Since misregulation of gene expression have been associated with human diseases, we speculated that changed levels of cardiac transcription factors, GATA5, may mediate the development of CHD. METHODS: In this study, GATA5 gene promoter was genetically and functionally analyzed in large cohorts of patients with ventricular septal defect (VSD) (n=343) and ethnic-matched healthy controls (n=348). RESULTS: Two novel and heterozygous DNA sequence variants (DSVs), g.61051165A>G and g.61051463delC, were identified in three VSD patients, but not in the controls. In cultured cardiomyocytes, GATA5 gene promoter activities were significantly decreased by DSV g.61051165A>G and increased by DSV g.61051463delC. Moreover, fathers of the VSD patients carrying the same DSVs had reduced diastolic function of left ventricles. Three SNPs, g.61051279C>T (rs77067995), g.61051327A>C (rs145936691) and g.61051373G>A (rs80197101), and one novel heterozygous DSV, g.61051227C>T, were found in both VSD patients and controls with similar frequencies. CONCLUSION: Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.

Two functional sequence variants of the GATA6 gene promoter in patients with indirect inguinal hernia.

Inguinal hernia is a common surgical disease, majority of which are indirect inguinal hernia (IIH). A positive family history has indicated that genetic factors play important roles in the IIH development. To date, genetic causes and underlying mechanisms for inguinal hernia remain largely unknown. During the embryonic development, GATA transcription factor 6 (GATA6) plays an essential role. Mutations in GATA6 gene and changed GATA6 levels have been associated with human diseases. As GATA6 acts in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the IIH development. In this study, the GATA6 gene promoter was genetically and functionally analyzed in IIH patients and ethnic-matched controls. Eleven DNA sequence variants (DSVs), including four SNPs and seven new variants, within the GATA6 gene promoter were identified. Two heterozygous DSVs, g.22168361C>A and g.22169106C>T, were identified in two IIH patients, but in none of controls. In cultured human fibroblast, these DSVs significantly reduced the GATA6 gene promoter activities. In addition, three heterozygous DSVs were only found in three controls. Five DSVs, including four SNPs and one new variant, were found in both IIH patients and controls with similar frequencies. Therefore, the DSVs within the GATA6 gene promoter may contribute to the IIH development as a risk factor by changing the GATA6 levels.

Two novel and functional DNA sequence variants within an upstream enhancer of the human NKX2-5 gene in ventricular septal defects.

Mortality in patients with congenital heart disease (CHD) is significantly increased even with successful surgeries. The main causes are late cardiac complications, such as heart failure and arrhythmia, probably due to genetic defects. To date, genetic causes for CHD remain largely unknown. NKX2-5 gene encodes a highly conserved homeobox transcription factor, which is essential to the heart development in embryos and cardiac function in adults. Mutations in NKX2-5 gene have been implicated in diverse types of CHD, including ventricular septal defect (VSD). As NKX2-5 is a dosage-sensitive regulator, we have speculated that changed NKX2-5 levels may mediate CHD development by influencing cardiac gene regulatory network. In previous studies, we have analyzed the NKX2-5 gene promoter and a proximal enhancer in VSD patients. In the present study, we further genetically and functionally analyzed an upstream enhancer of the NKX2-5 gene in large cohorts of VSD patients (n=340) and controls (n=347). Two novel heterozygous DNA sequence variants (DSVs), g.17483576C>G and g.17483564C>T, were identified in three VSD patients, but none in controls. Functionally, these two DSVs significantly decreased the activity of the enhancer (P<0.01). Another novel heterozygous DSV, g.17483557Ins, was found in both VSD patients and controls with similar frequencies (P>0.05). Taken together, our data suggested that the DSVs within the upstream enhancer of the NKX2-5 gene may contribute to a small number of VSD. Therefore, genetic studies of CHD may provide insight into designing novel therapies for adult CHD patients.