Background:Patients with genetic syndromes who undergo surgery to correct congenital heart defects can be at risk for increased morbidity or mortality.Surgical outcomes and postoperative courses following congenital h...Background:Patients with genetic syndromes who undergo surgery to correct congenital heart defects can be at risk for increased morbidity or mortality.Surgical outcomes and postoperative courses following congenital heart surgery in patients with Kabuki-Syndrome(KS)have not been well studied.Objectives:The purpose of this study was to describe the postoperative courses and associated outcomes in the largest set of KS patients undergoing congenital heart surgery to date.Methods:Patients with a confirmed molecular diagnosis of KS and a diagnosis of a CHD admitted to Texas Children’s Hospital between January 1,2000 and January 1,2020 were included(n=20).Demographics and medical histories were collected from the hospitals’electronic health records.Results:Of 20 patients identified with KS and a CHD,15 required surgical correction of their congenital cardiac malformation.Median age and weight at the time of surgery was 2 months and 4.1 kg,respectively.Median duration of hospital stay was 49 days for all surgeries and 151 days for the Norwood procedure.Postoperative infections and pleural effusions were detected and treated in 45.8%and 50%of patients,respectively.There was no in-hospital mortality for any surgery.Median follow up time was 5.6 years;survival at 6 years was 94%.Conclusions:Although KS patients seem to be at increased risk for a more complicated,prolonged postoperative course than that of patients without a genetic syndrome,patients with a diagnosis of a CHD and KS do not appear to be at increased risk of mortality following congenital heart surgery.展开更多
Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these ...Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.展开更多
文摘Background:Patients with genetic syndromes who undergo surgery to correct congenital heart defects can be at risk for increased morbidity or mortality.Surgical outcomes and postoperative courses following congenital heart surgery in patients with Kabuki-Syndrome(KS)have not been well studied.Objectives:The purpose of this study was to describe the postoperative courses and associated outcomes in the largest set of KS patients undergoing congenital heart surgery to date.Methods:Patients with a confirmed molecular diagnosis of KS and a diagnosis of a CHD admitted to Texas Children’s Hospital between January 1,2000 and January 1,2020 were included(n=20).Demographics and medical histories were collected from the hospitals’electronic health records.Results:Of 20 patients identified with KS and a CHD,15 required surgical correction of their congenital cardiac malformation.Median age and weight at the time of surgery was 2 months and 4.1 kg,respectively.Median duration of hospital stay was 49 days for all surgeries and 151 days for the Norwood procedure.Postoperative infections and pleural effusions were detected and treated in 45.8%and 50%of patients,respectively.There was no in-hospital mortality for any surgery.Median follow up time was 5.6 years;survival at 6 years was 94%.Conclusions:Although KS patients seem to be at increased risk for a more complicated,prolonged postoperative course than that of patients without a genetic syndrome,patients with a diagnosis of a CHD and KS do not appear to be at increased risk of mortality following congenital heart surgery.
文摘Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.
