A Pilot Clinical Study of Liquid Ubiquinol Supplementation on Cardiac Function in Pediatric Dilated Cardiomyopathy.

BACKGROUND: Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM. METHODS: Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study. RESULTS: Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation. CONCLUSION: Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.

Association between vascular rings and learning performance: A cross-sectional study.

BACKGROUND: Chronic tracheal obstruction has been associated with learning deficits; hence, early surgical intervention has been suggested. AIM: To evaluate the relationship between learning performance and vascular ring caused by an isolated aberrant right subclavian artery. METHODS: Participants included 1,685 undergraduate students (ie, students of medical informatics and medical/public health students) in Central Taiwan. The diagnostic period was from 2005 to 2010. Vascular ring was diagnosed by two-dimensional echocardiographic screening and was validated by esophagogram. The reference group (medical students) was associated with higher learning performance, whereas the comparison group (students of medical informatics and public health) was associated with lower learning performance. Multiple logistic regression was used for analysis. RESULTS: The prevalence of vascular ring among the reference and comparison groups was 0.48 and 2.03%, respectively. The odds ratio for the vascular ring was 4.90 (95% confidence interval: 1.30-18.40) after adjusting for potential confounders. CONCLUSIONS: This study suggests that vascular ring can impact learning efficiency and advocates for larger dedicated studies. © 2017 The Authors Journal of Clinical Ultrasound Published by Wiley Periodicals, Inc. J Clin Ultrasound 45:556-560, 2017.

Improving Image Quality of On-Board Cone-Beam CT in Radiation Therapy Using Image Information Provided by Planning Multi-Detector CT: A Phantom Study.

PURPOSE: The aim of this study was to improve the image quality of cone-beam computed tomography (CBCT) mounted on the gantry of a linear accelerator used in radiation therapy based on the image information provided by planning multi-detector CT (MDCT). METHODS: MDCT-based shading correction for CBCT and virtual monochromatic CT (VMCT) synthesized using the dual-energy method were performed. In VMCT, the high-energy data were obtained from CBCT, while the low-energy data were obtained from MDCT. An electron density phantom was used to investigate the efficacy of shading correction and VMCT on improving the target detectability, Hounsfield unit (HU) accuracy and variation, which were quantified by calculating the contrast-to-noise ratio (CNR), the percent difference (%Diff) and the standard deviation of the CT numbers for tissue equivalent background material, respectively. Treatment plan studies for a chest phantom were conducted to investigate the effects of image quality improvement on dose planning. RESULTS: For the electron density phantom, the mean value of CNR was 17.84, 26.78 and 34.31 in CBCT, shading-corrected CBCT and VMCT, respectively. The mean value of %Diff was 152.67%, 11.93% and 7.66% in CBCT, shading-corrected CBCT and VMCT, respectively. The standard deviation within a uniform background of CBCT, shading-corrected CBCT and VMCT was 85, 23 and 15 HU, respectively. With regards to the chest phantom, the monitor unit (MU) difference between the treatment plan calculated using MDCT and those based on CBCT, shading corrected CBCT and VMCT was 6.32%, 1.05% and 0.94%, respectively. CONCLUSIONS: Enhancement of image quality in on-board CBCT can contribute to daily patient setup and adaptive dose delivery, thus enabling higher confidence in patient treatment accuracy in radiation therapy. Based on our results, VMCT has the highest image quality, followed by the shading corrected CBCT and the original CBCT. The research results presented in this study should be able to provide a route to reach a high level of image quality for CBCT imaging in radiation oncology.

Patterns of failure after use of (18)F-FDG PET/CT in integration of extended-field chemo-IMRT and 3D-brachytherapy plannings for advanced cervical cancers with extensive lymph node metastases.

BACKGROUND: The study is to evaluate the patterns of failure, toxicities and long-term outcomes of aggressive treatment using (18)F-FDG PET/CT-guided chemoradiation plannings for advanced cervical cancer with extensive nodal extent that has been regarded as a systemic disease. METHODS: We retrospectively reviewed 72 consecutive patients with (18)F-FDG PET/CT-detected widespread pelvic, para-aortic and/or supraclavicular lymph nodes treated with curative-intent PET-guided cisplatin-based extended-field dose-escalating intensity-modulated radiotherapy (IMRT) and adaptive high-dose-rate intracavitary 3D-brachytherapy between 2002 and 2010. The failure sites were specifically localized by comparing recurrences on fusion of post-therapy recurrent (18)F-FDG PET/CT scans to the initial PET-guided radiation plannings for IMRT and brachytherapy. RESULTS: The median follow-up time for the 72 patients was 66 months (range, 3-142 months). The 5-year disease-free survival rate calculated by the Kaplan-Meier method for the patients with extensive N1 disease with the uppermost PET-positive pelvic-only nodes (26 patients), and the patients with M1 disease with the uppermost PET-positive para-aortic (31 patients) or supraclavicular (15 patients) nodes was 78.5 %, and 41.8-50 %, respectively (N1 vs. M1, p = 0.0465). Eight (11.1 %), 18 (25.0 %), and 3 (4.2 %) of the patients developed in-field recurrence, out-of-field and/or distant metastasis, and combined failure, respectively. The 6 (8.3 %) local failures around the uterine cervix were all at the junction between IMRT and brachytherapy in the parametrium. The rate of late grade 3/4 bladder and bowel toxicities was 4.2 and 9.7 %, respectively. When compared to conventional pelvic chemoradiation/2D-brachytherapy during 1990-2001, the adoption of (18)F-FDG PET-guided extended-field dose-escalating chemoradiation plannings in IMRT and 3D-brachytherapy after 2002 appeared to provide higher disease-free and overall survival rates with acceptable toxicities in advanced cervical cancer patients. CONCLUSIONS: For AJCC stage M1 cervical cancer with supraclavicular lymph node metastases, curability can be achieved in the era of PET and chemo-IMRT. However, the main pattern of failure is still out-of-field and/or distant metastasis. In addition to improving systemic treatment, how to optimize and integrate the junctional doses between IMRT and 3D-brachytherapy in PET-guided plannings to further decrease local recurrence warrants investigation.

A Matched Influenza Vaccine Strain Was Effective in Reducing the Risk of Acute Myocardial Infarction in Elderly Persons: A Population-Based Study.

The aim of this study was to explore whether matched or mismatched strains of influenza vaccines (IVs) are beneficial at reducing the risk of acute myocardial infarction (AMI) in elderly persons.Data were obtained from the Longitudinal Health Database 2005 (LHID 2005) which is maintained by the National Health Insurance Research Institute in Taiwan. The analytical data included individuals who were vaccinated with mismatched vaccines during the October 2007 to December 2007 season and individuals vaccinated with matched strains during the October 2008 to December 2008 season. All participants were 65 years of age and older. In this analysis, individuals were considered to be exposed if their records showed that they were vaccinated against influenza, and they were considered to be nonexposed if they were not vaccinated during these seasons. A Cox hazard model was used to estimate AMI hazard ratio.This study enrolled 93,051 exposed and 109,007 unexposed individuals. The AMI hazards ratios (HRs) for the men and women exposed to mismatched vaccine (in 2007) were 0.990 (95% confidence interval [CI], 0.745-1.316) and 1.102 (95% CI: 0.803-1.513), respectively. Men exposed to matched vaccines (in 2008) had significant HRs (HR: 0.681; 95% CI: 0.509-0.912) while the HRs in the women were barely significant (HR: 0.737; 95% CI: 0.527-1.029).AMI risk could be particularly reduced in men if the IV matches well with the circulating strains in elderly people 65 years of age and older.

Diagnostic Performance of Combined Contrast-Enhanced Magnetic Resonance Angiography and Phase-Contrast Magnetic Resonance Imaging in Suspected Subclavian Steal Syndrome.

PURPOSE: The study sought to evaluate the efficacy of magnetic resonance imaging (MRI) in patients with suspected subclavian steal syndrome (SSS) using both contrast-enhanced (CE) MR angiography and phase-contrast (PC) MRI. METHODS: Fifteen suspected SSSs from 13 patients were evaluated using CE-MR angiography and PC-MRI. Ten patients also received dynamic CE-MR angiography. RESULTS: All MRI examinations were technically successful. By combining CE-MR angiography with PC-MRI, 10 SSSs were diagnosed in 9 patients. The delay enhancement dynamic technique predicted SSS with a sensitivity, specificity, and accuracy of 57.1%, 100%, and 72.7%, respectively. Without the dynamic technique, affected delay-enhanced arteries were poorly visualized and could be mistaken for occluded vessels. Retrograde vertebral flow by PC-MRI was used to predict ipsilateral SSS with a sensitivity, specificity, and accuracy of 100%, 60%, and 86.7%, respectively. There were 2 false positives including 1 patient with a proximal total occlusion of the affected vertebral artery and another with brachiocephalic steal syndrome rather than SSS. This suggested that retrograde vertebral flow does not always indicate SSS. CONCLUSIONS: CE-MR angiography combined with PC-MRI is efficacious when evaluating SSS in clinical practice.

Simulation analysis of airflow alteration in the trachea following the vascular ring surgery based on CT images using the computational fluid dynamics method.

This study presents a computational fluid dynamics (CFD) model to simulate the three-dimensional airflow in the trachea before and after the vascular ring surgery (VRS). The simulation was based on CT-scan images of the patients with the vascular ring diseases. The surface geometry of the tracheal airway was reconstructed using triangular mesh by the Amira software package. The unstructured tetrahedral volume meshes were generated by the ANSYS ICEM CFD software package. The airflow in the tracheal airway was solved by the ESI CFD-ACE+ software package. Numerical simulation shows that the pressure drops across the tracheal stenosis before and after the surgery were 0.1789 and 0.0967 Pa, respectively, with the inspiratory inlet velocity 0.1 m/s. Meanwhile, the improvement percentage by the surgery was 45.95%. In the expiratory phase, by contrast, the improvement percentage was 40.65%. When the inspiratory velocity reached 1 m/s, the pressure drop became 4.988~Pa and the improvement percentage was 43.32%. Simulation results further show that after treatment the pressure drop in the tracheal airway was significantly decreased, especially for low inspiratory and expiratory velocities. The CFD method can be applied to quantify the airway pressure alteration and to evaluate the treatment outcome of the vascular ring surgery under different respiratory velocities.

Tuberous sclerosis complex associated with heterotopic ossification in a young girl.

Tuberous sclerosis complex (TSC) is a multisystem disorder resulting in hamartomatous lesions. Despite diverse manifestations, skeletal muscular comorbidity is rarely reported in TSC. We report a 2-year-old girl with TSC who suffered from multiple subcutaneous masses over the paraspinal and bilateral scapular areas, which caused disabling pain on any passive movement. Three-dimensional computed tomography scanning revealed multiple calcifications that were consequently diagnosed as fibrodysplasia ossificans progressiva. Such imaging features should be evaluated cautiously to avoid unnecessary surgical intervention and biopsy that may worsen the condition.

[Improving comprehensiveness of information given to pediatric cardiac surgery patients prior to surgery].

BACKGROUND: Cardiac surgery for critical pediatric patients places significant demands on hospital equipment and facilities. Parents of these patients are often under enormous stress due to insufficient knowledge regarding cardiac surgery and postoperative care procedures. This project used appropriate preoperative consultation given by nursing staffs to decrease stress and anxiety in parents of pediatric cardiac surgery patients. PURPOSE: This project worked to enhance the completion rate of preoperative instructions for pediatric cardiac surgery patients and ensure their parents received comprehensive information and knowledge. RESOLUTION: The authors developed a standardized procedure for patient instruction and evaluation. Participants received instructions in the forms of a video presentation and printed handouts. Also, an educational training program was held and the implementation of preoperative patient instructions was made a routine task during nursing handover to enhance the completion rate. RESULTS: The completion rate of patient preoperative instructions to pediatric cardiac surgery rose from 78% to 98%; The cognitive degree of participating parents rose from 52% to 96%. CONCLUSIONS: This intervention effectively increased the completion rate of preoperative instructions for pediatric patients scheduled for cardiac surgery and improved clinical pediatric nursing care practicability and efficiency.

Effects of chronic resistive airway loading on behavioral changes in rats.

Complete vascular ring is a term describing a group of congenital aortic arch abnormalities that is often observed in infancy and leads to tracheoesophageal compression and airway obstruction. We investigated the effects of chronic resistive airway loading on anxiety and learning behavior in Wistar rats. The trachea were obstructed by a circumferential tracheal band to increase respiratory esophageal pressure. All of the rats were subjected to the elevated plus-maze test and the active avoidance test at 2 or 4 weeks after the obstruction surgery. One set of rats received surgical relief of the tracheal obstruction on week 2 or 3 after obstruction. At 4, but not 2, weeks after tracheal obstruction, the rats showed impairment of learning in the active avoidance test and this impairment was prevented by surgical relief of tracheal obstruction performed on week 2, but not week 3. In contrast, anxiety-like behavior in the elevated plus-maze test was not affected at either 2 or 4 weeks after tracheal obstruction. Body weight was not affected by tracheal obstruction and no differences were seen in arterial blood gases after 4 weeks of tracheal obstruction. These results suggest that chronic tracheal obstruction causes learning deficits and that surgical intervention is necessary and should be performed as early as possible to prevent long-term sequelae.

Luteolin attenuates the pulmonary inflammatory response involves abilities of antioxidation and inhibition of MAPK and NFκB pathways in mice with endotoxin-induced acute lung injury.

Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity. Lipopolysaccharide (LPS) is a key mediator of lung injury. This study investigates the protective effects and mechanisms of luteolin in intratracheal instillation of LPS (100µg)-induced ALI in mice. Pretreatment of mice with 70µmol/kg luteolin significantly restores LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood. The histopathological study established 70µmol/kg luteolin pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of polymorphonuclear neutrophils (PMNs) into the lung parenchyma and alveolar spaces. Sufficient evidence for luteolin (35 and 70µmol/kg) suppresses activation and infiltration of PMNs is obtained in expression of surface marker CD11b and Ly6G on cells in bronchoalveolar lavage fluid (BALF) cells and myeloperoxidase activity in lung tissue. Furthermore, luteolin reduces the activity of catalase and superoxide dismutase, and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of TNF-α, KC, and ICAM-1 in the BALF after LPS challenge are also inhibited by luteolin. Moreover, luteolin reduced LPS-induced activation of MAPK and NFκB pathways. Therefore, luteolin is a potential protective antagonists for LPS-induced ALI in mice.

Assessing the impact of polysomy-17 on HER2 status and the correlations of HER2 status with prognostic variables (ER, PR, p53, Ki-67) in epithelial ovarian cancer: a tissue microarray study using immunohistochemistry and fluorescent in situ hybridization.

Although HER2 overexpression and Her2 amplification have been noted in breast and a variety of human cancers, we report here for the first time the impact of polysomy-17 on HER2 status and the correlations between HER2 status and other prognostic factors in patients with epithelial ovarian cancers (EOC).We analyzed HER2, estrogen receptor (ER), progesterone receptor (PR), p53, and Ki-67 protein overexpressions by immunohistochemistry (IHC) and determined Her2 gene amplification by fluorescence in situ hybridization (FISH) in 27 tissue microarray samples from EOC patients.We achieved 100% positive concordance (3/3) and 100% negative concordance (19/19) between HER2 testing by IHC and FISH. Both the total Her2 gene copies and FISH scores increased significantly in a stepwise order through the negative, equivocal, and positive HER2 IHC result categories in all 27 cases (P=0.001, P=0.001), and still increased significantly in 18 nonpolysomy-17 cases (P=0.007 and 0.013) after the exclusion of 9 polysomy-17 cases. HER2 protein expression is inversely correlated with both ER (P=0.002) and PR expressions (P=0.046). Her2 gene amplification is inversely correlated with ER expression (P=0.007) but not with PR expression (P=0.106).This study showed extremely high positive and negative concordances between Her2 FISH and HER2 IHC assays. Polysomy-17 is insufficient for causing a significant impact on the relationship between HER2 testing by IHC and FISH in EOC. ER and PR expressions were inversely correlated with HER2 protein expression. In addition, ER but not PR expression is inversely correlated with Her2 gene amplification.

Identification of the coexisting HER2 gene amplification and novel mutations in the HER2 protein-overexpressed mucinous epithelial ovarian cancer.

BACKGROUND: Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC). METHODS: Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing. RESULTS: The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases. CONCLUSIONS: HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.

The HER2 gene copies per tumor cell either before or after correction for chromosome-17 correlated significantly with HER2 IHC results in epithelial ovarian cancer in a tissue microarray study.

BACKGROUND: HER2 gene amplification and HER2 protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast cancer patients. The purpose of this study is to evaluate the correlation between HER2 protein expressions and the HER2 gene copies per tumor cell either before or after chromosome-17 correction in epithelial ovarian cancer (EOC). METHODS: Adopting 2007 ASCO/CAP guideline recommendations for HER2 testing, 27 tissue microarray (TMA) samples from EOC patients were analyzed by immunohistochemistry (IHC) using Dako, c-erb-B2 antibody and subsequently examined by fluorescence in situ hybridization (FISH) using Abbott/Vysis, PathVysion HER2 DNA Probe Kit. RESULTS: The overall concordance revealed 81.5% between HER2 IHC and HER2 FISH results. Additionally, HER2 gene copies prior to chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P = 0.026), as did the HER2 gene copies after chromosome-17 correction (P = 0.028). On the other hand, HER2 IHC results correlated significantly with both chromosome-17 uncorrected HER2 gene copy numbers (ρ = 0.430, P = 0.025) and chromosome-17 corrected HER2 gene copy numbers (ρ = 0.524, P = 0.027). CONCLUSION: We demonstrated that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC result categories; and tests for the HER2 gene copies per tumor cell either before or after correction for chromosome-17 can be applied as a potentially valuable tool in analyzing the HER2 status in EOC.

Balloon dilatation in management of postoperative airway obstruction due to tracheal bronchus associated with right main bronchial stenosis: emphasizing the role of three-dimensional computed tomography on preoperative evaluation.

Three-dimensional computed tomography (3D-CT) not only allows accurate preoperative delineation of the lesions but also provides precise pathomechanic diagnosis for planning the most effective treatment to avoid respiratory compromise. In a 10-month-old baby girl, who was ventilator-dependent after successful correction of double outlet right ventricle (DORV), flexible fiberoptic bronchoscopy (FFB) revealed the new formation of postoperative airway obstruction over the right main bronchus (RMB) and obstructed right tracheal bronchus (RTB). 3D-CT demonstrated tracheobronchial obstruction (TBO) was caused by the dilated ascending aorta (AAo) and right pulmonary artery (RPA). Sequential treatments including artery pexy of AAo and RPA and balloon dilatation (BD) of the stenotic RTB and RMB had successfully restored the airway patency. The patient was successfully weaned from ventilator 2 days after treatments and has shown no respiratory difficulty thus far. Thus, the impact of preoperative 3D-CT on planning treatment cannot be emphasized.