New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function

Objectives: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. Design: Cross-sectional study. Setting: Tertiary paediatric cardiac centre. Methods: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. Results: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s 2 vs 1.56 (0.53) m/s 2, p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = -0.65, p<0.001 and r = -0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). Conclusions: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.published_or_final_versio

Pericardial effusion after open heart surgery for congenital heart disease

Objectives: To determine the prevalence and time course of pericardial effusion after open heart surgery for congenital heart diseases and to identify predisposing risk factors. Design and patients: Prospective assessment of development of pericardial effusion in 336 patients (163 males) undergoing open heart surgery for congenital heart disease by serial echocardiography on days 5, 7, 14, 21, and 28 postoperatively. Setting: Tertiary paediatric cardiac centre. Results: The prevalence of pericardial effusion was 23% (77 of 336). Of the 77 patients who developed effusion, 43 (56%) had moderate to large effusions and 18 (23%) were symptomatic. Patients who had a large amount of effusion were more likely to be symptomatic than those with only a small to moderate amount (47.4% v 15.5%, p = 0.01). The mean (SD) onset of pericardial effusion was 11 (7) days after surgery, with 97% (75 of 77) of cases being diagnosed on or before day 28 after surgery. The prevalence of effusion after Fontan-type procedures (60%, 6 of 10) was significantly higher than that after other types of cardiac surgery: repair of left to right shunts (22.1%, 43 of 125), repair of lesions with right ventricular outflow tract obstruction (22.6%, 19 of 84), arterial switch operation (6.7%, 1 of 15), and miscellaneous procedures (25%, 8 of 32) (p = 0.037). Univariate analyses showed that female patients (p = 0.009) and those receiving warfarin (p = 0.002) had increased risk of postoperative pericardial effusion. A greater pericardial drain output in the first four hours after surgery also tended to be significant (p = 0.056). Multivariate logistic regression similarly identified warfarin treatment (β = 1.73, p = 0.009) and female sex (β for male = -0.63, p = 0.037) as significant determinants. Conclusions: Pericardial effusion occurs commonly after open heart surgery for congenital heart disease. Serial echocardiographic monitoring up to 28 days postoperatively is indicated in selected high risk patients such as those with symptoms of postpericardiotomy syndrome and those given warfarin.published_or_final_versio

Homeobox b5(Hoxb5) regulates the expression of Forkhead box D3 gene (Foxd3) in neural crest

Patterning of neural crest (NC) for the formation of specific structures along the anterio-posterior (A-P) body axis is governed by a combinatorial action of Hox genes, which are expressed in the neuroepithelium at the time of NC induction. Hoxb5 was expressed in NC at both induction and migratory stages, and our previous data suggested that Hoxb5 played a role in the NC development. However, the underlying mechanisms by which Hoxb5 regulates the early NC development are largely unknown. Current study showed that both the human and mouse Foxd3 promoters were bound and trans-activated by Hoxb5 in NC-derived neuroblastoma cells. The binding of Hoxb5 to Foxd3 promoter in vivo was further confirmed in the brain and neural tube of mouse embryos. Moreover, Wnt1-Cre mediated perturbation of Hoxb5 signaling at the dorsal neural tube in mouse embryos resulted in Foxd3 down-regulation. In ovo, Foxd3 alleviated the apoptosis of neural cells induced by perturbed Hoxb5 signaling, and Hoxb5 induced ectopic Foxd3 expression in the chick neural tube. This study demonstrated that Hoxb5 (an A-P patterning gene) regulated the NC development by directly inducing Foxd3 (a NC specifier and survival gene).postprin

Identification and characterization of tropomyosin 3 associated with granulin-epithelin precursor in human hepatocellular carcinoma

Background and Aim: Granulin-epithelin precursor (GEP) has previously been reported to control cancer growth, invasion, chemo-resistance, and served as novel therapeutic target for cancer treatment. However, the nature and characteristics of GEP interacting partner remain unclear. The present study aims to identify and characterize the novel predominant interacting partner of GEP using co-immunoprecipitation and mass spectrometry. Methods and Results: Specific anti-GEP monoclonal antibody was used to capture GEP and its interacting partner from the protein extract of the liver cancer cells Hep3B. The precipitated proteins were analyzed by SDS-PAGE, followed by mass spectrometry and the protein identity was demonstrated to be tropomyosin 3 (TPM3). The interaction has been validated in additional cell models using anti-TPM3 antibody and immunoblot to confirm GEP as the interacting partner. GEP and TPM3 expressions were then examined by real-time quantitative RT-PCR in clinical samples, and their transcript levels were significantly correlated. Elevated TPM3 levels were observed in liver cancer compared with the adjacent non-tumorous liver, and patients with elevated TPM3 levels were shown to have poor recurrence-free survival. Protein expression of GEP and TPM3 was observed only in the cytoplasm of liver cancer cells by immunohistochemical staining. Conclusions: TPM3 is an interacting partner of GEP and may play an important role in hepatocarcinogenesis. © 2012 Lam et al.published_or_final_versio

The impact of cardiovascular disease and chronic kidney disease on life expectancy and direct medical cost in a 10-year diabetes cohort study

Objective: The relative effects of various cardiovascular diseases (CVD) and varying severity of chronic kidney disease (CKD) on mortality risk, direct medical cost and life expectancy in patients with diabetes mellitus (DM) are unclear. The aim of this study was to evaluate these associations. / Research Design and Methods: This was a retrospective cohort study that included 208,792 adults with diabetes stratified into 12 disease status groups with varying combinations of heart disease, stroke, moderate CKD (eGFR:30-59ml/min/1.73m2) and severe CKD (eGFR: <30ml/min/1.73m2) in 2008-2010. The effect of risk mortality, annual direct medical costs and life expectancy were assessed using Cox regression, Gamma generalized linear with log link function, and flexible parametric survival models. / Results: Over a median follow-up of 8.5 years (1.6 million patient-years), 50,154 deaths were recorded. Mortality risks for patients with only a single condition among heart disease, stroke and moderate CKD were similar. The mortality risks were 1.75 times, 2.63 times and 3.58 times greater for patients with one, two and all three conditions (consisting of stroke, heart disease and moderate CKD), compared with patients without these diseases, suggesting an independent and individually additive effect for any combination. A similar trend was observed in annual public healthcare costs with 2.91, 3.90 and 3.88 fold increased costs for patients with one, two and three conditions, respectively. Increases in the number of conditions reduced life expectancy greatly, particularly in younger patients. Reduction in life expectancy for a 40-year-old with one, two and three conditions were 20, 25, 30 years for men and 25, 30, 35 years for women. A similar trend of greater magnitude was observed for severe CKD. / Conclusion: The effect of heart diseases, stroke, CKD and the combination of these conditions on all-cause mortality and direct medical costs are independent and cumulative. CKD, especially severe CKD, appears to have a particularly significant impact on life expectancy and direct medical costs in patients with diabetes. These finding supports the importance of preventing both CVD and CKD in patients with DM

Effectiveness of BNT162b2 after extending the primary series dosing interval in children and adolescents aged 5–17

Extended intervals between the first and second doses of mRNA Covid-19 vaccines may reduce the risk of myocarditis in children and adolescents. However, vaccine effectiveness after this extension remains unclear. To examine this potential variable effectiveness, we conducted a population-based nested case-control study of children and adolescents aged 5–17 years who had received two doses of BNT162b2 in Hong Kong. From January 1 to August 15, 2022, 5396 Covid-19 cases and 202 Covid-19 related hospitalizations were identified and matched with 21,577 and 808 controls, respectively. For vaccine recipients with extended intervals [≥28 days, adjusted odds ratio 0.718, 95% Confidence Interval: 0.619, 0.833] there was a 29.2%-reduced risk of Covid-19 infection compared to those with regular intervals (21–27 days). If the threshold was set at eight weeks, the risk reduction was estimated at 43.5% (aOR 0.565, 95% CI: 0.456, 0.700). In conclusion, longer dosing intervals for children and adolescents should be considered

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring

OBJECTIVE: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech). METHODS: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined. RESULTS: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15–0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06–0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16–0.28). No significant effect modification was identified. CONCLUSION: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty

Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of fallot

The 6th Korea-Japan-China Pediatric Heart Forum, Seoul, Korea, 26-27 March 2010

Meta-analysis of pulmonary valve replacement after operative repair of tetralogy of fallot

The present meta-analysis aimed to determine the outcomes and effect on right ventricular (RV) function of surgical pulmonary valve replacement (PVR) in patients after repair of tetralogy of Fallot. The reported outcomes of surgical PVR in children and adults after tetralogy of Fallot repair were from relatively small observational studies. The PubMed database was searched from its inception to April 2009. Observational studies reporting on the following outcomes measures after surgical PVR were reviewed: early and late all-cause mortalities, the redo-PVR rate, and changes in the indexed RV volumes, ejection fraction, and QRS duration after PVR. Of the 305 citations screened, 15 met the criteria and were analyzed. The pooled early mortality rate (n = 595) was 2.1% (95% confidence interval [CI] 1.1% to 4.0%). The late mortality rate was 0.5%/patient-year (95% CI 0.2% to 0.8%/patient-year), and the redo-PVR rate was 1.9%/patient-year (95% CI 1.3% to 2.5%/patient-year). Data on RV volumes and ejection fractions were available from 5 studies (n = 141). The pooled mean difference in the indexed RV end-diastolic and end-systolic volume was -63 ml/m 2 (95% CI -55 to -72) and -37 ml/m 2 (95% CI -30 to -45), respectively. No significant changes in the pooled mean difference of the RV ejection fraction (95% CI -1% to 3%) or QRS duration (95% CI -10 to 1 ms) were observed. In conclusion, surgical PVR in patients after tetralogy of Fallot repair has been associated with low early and late mortality and significant decreases in RV volumes but no changes in the RV ejection fraction or QRS duration. © 2010 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Systematic review and meta-analysis of pulmonary valve replacement in children and adults after surgical repair of tetralogy of fallot

Oral Presentation: FP8-03OBJECTIVES: Reported outcomes of surgical PVR in children and adults after TOF repair were based on relatively small observational studies. This systematic review and meta-analysis aimed to determine the outcomes and impact on right ventricular (RV) function of surgical pulmonary valve replacement (PVR) in patients after repair of tetralogy of Fallot (TOF). METHODS: The PubMed database was searched from its inception to April 2009. Observational studies reporting on the following outcomes measures after surgical PVR were reviewed: early and late all-cause mortalities, redo-PVR rate, and changes in indexed RV volumes, ejection fraction (EF), and QRS duration after PVR. RESULTS: Of the 305 citations screened, 15 met the criteria and were analyzed. Pooled early mortality (n=595) was 2.1% (95% CI, 1.1 to 4.0%). Late mortality rate was 0.5%/patient-year (95% CI, 0.2 to 0.8%/patient-year) and redo-PVR rate was 1.9%/patient-year (95% CI, 1.3 to 2.5%/patient-year). Data on RV volumes and ejection fractions were available from 5 studies (n=141). Pooled mean differences of indexed RV end-diastolic and end-systolic volumes were -64ml/m2 (95% CI, -55 to -72ml/m2) and -37ml/m2 (95% CI, -30 to -45ml/m2), respectively. No significant changes in pooled mean difference of RV EF (95% CI, -3 to 1%) and QRS duration (95%CI, -1 to 12ms) were observed. CONCLUSIONS: Surgical PVR in patients after TOF repair is associated with low early and late mortalities and significant decrease in RV volumes, but with no changes in RV EF or QRS duration.The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association. Taipei, Taiwan, 15-18 April 2010