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BACKGROUND Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. METHODS A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. RESULTS Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score

Background Radiotherapy (RT) might lead to atherosclerotic plaque buildup and coronary artery stenosis of breast cancer (BC) survivors, and coronary artery calcium (CAC) might be a sign of preclinical atherosclerosis. This study explores possible determinants affecting the acceleration of CAC burden in BC patients after adjuvant RT. Methods Female BC patients receiving adjuvant RT from 2002 to 2010 were included. All patients received noncontrast computed tomography (NCCT) of thorax before and after adjuvant RT. Their CAC burden was compared with healthy controls from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The progression of the CAC burden was manifested by the increment of CAC percentiles (%CACinc). Results Ninety-four patients, including both left- and right-side BC, were enrolled in this study. From undergoing the first to second NCCT, the %CACinc in BC patients significantly increased rather than non-BC women. In addition, the %CACinc was significantly higher in left-side than right-side BC patients (p Conclusions A significantly higher accelerated CAC burden in BC patients than non-BC women represents that BC could affect accelerated CAC. A higher risk of accelerated CAC burden was found in left-side than right-side BC patients after adjuvant RT. A decrease of the mean RCA dose could reduce more than 50% of the risk of accelerated CAC burden in BC patients.

Background. Radiation using conventional X-ray is associated with exposure of radiosensitive organs and typically requires the use of protection. This study is aimed at evaluating the use of bismuth shielding for radiation protection in pediatric pelvic radiography. The effects of the anteroposterior and lateral bismuth shielding were verified by direct measurements at the anatomical position of the gonads. Methods. Radiation doses were measured using optically stimulated luminescence dosimeters (OSLD) and CIRS ATOM Dosimetry Verification Phantoms. Gonad radiographs were acquired using different shields of varying material (lead, bismuth) and thickness and were compared with radiographs obtained without shielding to examine the effects on image quality and optimal reduction of radiation dose. All images were evaluated separately by three pediatric orthopedic practitioners. Results. Results showed that conventional lead gonadal shielding reduces radiation doses by 67.45%, whereas dose reduction using one layer of bismuth shielding is 76.38%. The use of two layers of bismuth shielding reduces the dose by 84.01%. Using three and four layers of bismuth shielding reduces dose by 97.33% and 99.34%, respectively. Progressively lower radiation doses can be achieved by increasing the number of bismuth layers. Images obtained using both one and two layers of bismuth shielding provided adequate diagnostic information, but those obtained using three or four layers of bismuth shielding were inadequate for diagnosis. Conclusions. Bismuth shielding reduces radiation dose exposure providing appropriate protection for children undergoing pelvic radiography. The bismuth shielding material is lighter than lead, making pediatric patients more comfortable and less apt to move, thereby avoiding repeat radiography.

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P P = 0.02), age > 50 years old (HR/CI 3.64/2.03–6.54, P P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03–1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04–19.09, P = 0.04) and BMI (HR/CI 1.11/1.03–1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

Type I Chiari malformation (CM-I) consists of downward herniation of the cerebellar tonsils below the foramen magnum and often requires surgical decompression if symptomatic. Spontaneous resolution of CM-I is rare. We present a case of resolved CM-I without surgery in a 6-year-old boy with B-cell lymphoma who was diagnosed with CM-I during lymphoma staging. Cerebrospinal fluid cytology and brain MRI revealed negative CNS involvement but showed CM-I with tonsillar ectopia 19 mm below the foramen magnum. The patient underwent induction chemotherapy including 5 doses of intrathecal chemotherapy. Follow-up MRI demonstrated marked regression of CM-I to less than 6 mm in 3 months, and complete resolution of CM-I was observed in 2 years. To the best of our knowledge, this is the first case of resolved CM-I and syringomyelia following chemotherapy. In this case report, the authors summarize all of the clinical characteristics, the radiological appearance, and the potential causes of resolution based on a review of the literature and propose the mechanisms through which intrathecal chemotherapy contributed to the CM-I and syringomyelia resolution in the present case.

Coronavirus Disease-19 (COVID-19) has been in a global pandemic currently and relating symptoms were reported variously around the world. We reported a previously healthy man of COVID-19 presenting with anosmia as the obvious symptom with relevant radiological findings on brain magnetic resonance imaging.

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small‐molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B‐cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)–mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with (Clin J Am Soc Nephrol. 2011, 6, 1301‐1307) reduced mitochondrial ROS generation; (Am J Physiol‐Renal Physiol. 2011. 301, F1218‐F1230) differentially regulated autophagy and NLRP3 inflammasome; (Clin J Am Soc Nephrol. 2012, 7, 427‐436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and (Free Radic Biol Med. 2013, 61, 285‐297) blunted NLRP3 inflammasome activation through SIRT1‐ and SIRT3‐mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs‐mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.

BACKGROUND AND AIM The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. METHODS Serum anti-HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti-HBV therapy and subsequently during the follow-up period. RESULTS The seropositive rate of anti-HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti-HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992-0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70-0.94; P = 0.005), and hepatitis B e-antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05-0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti-HDV seropositive patients was age (OR/CI: 0.95/0.90-1.00; P = 0.03). The spontaneous clearance rate of serum anti-HDV antibody was 3.0 per 100 person-years with a median follow-up period of 3.5 years (range 2-12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person-years among anti-HDV seropositive patients after a median follow-up period of 6.0 years (range 2-11 years). A baseline anti-HDV titer

Background/Purpose: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. Methods: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. Results: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52–1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65–1.99) were significant factors associated with NFS (p

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

Background One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players. Methods BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers’ group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA. Results TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p p p p Conclusion For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.

OBJECTIVES This study aimed to evaluate the feasibility of automatic Stanford classification of classic aortic dissection (AD) using a 2-step hierarchical neural network. METHODS Between 2015 and 2019, 130 arterial phase series (57 type A, 43 type B, and 30 negative cases) in aortic CTA were collected for the training and validation. A 2-step hierarchical model was built including the first step detecting AD and the second step predicting the probability (0-1) of Stanford types. The model's performance was evaluated with an off-line prospective test in 2020. The sensitivity and specificity for Stanford type A, type B, and no AD (Sens A, B, N and Spec A, B, N, respectively) and Cohen's kappa were reported. RESULTS Of 298 cases (22 with type A, 29 with type B, and 247 without AD) in the off-line prospective test, the Sens A, Sens B, and Sens N were 95.45% (95% confidence interval [CI], 77.16-99.88%), 79.31% (95% CI, 60.28-92.01%), and 93.52% (95% CI, 89.69-96.25%), respectively. The Spec A, Spec B, and Spec N were 98.55% (95% CI, 96.33-99.60%), 94.05% (95% CI, 90.52-96.56%), and 94.12% (95% CI, 83.76-98.77%), respectively. The classification rate achieved 92.28% (95% CI, 88.64-95.04%). The Cohen's kappa was 0.766 (95% CI, 0.68-0.85; p

Sorafenib is currently the first‐line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well‐compensated liver cirrhosis (Child‐Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre‐treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9‐1504 days) with a 1‐year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4‐1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1‐1254 days). The 1‐year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

Background As the COVID-19 epidemic increases in severity, the burden of quarantine stations outside emergency departments (EDs) at hospitals is increasing daily. To address the high screening workload at quarantine stations, all staff members with medical licenses are required to work shifts in these stations. Therefore, it is necessary to simplify the workflow and decision-making process for physicians and surgeons from all subspecialties. Objective The aim of this paper is to demonstrate how the National Cheng Kung University Hospital artificial intelligence (AI) trilogy of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm improves medical care and reduces quarantine processing times. Methods This observational study on the emerging COVID-19 pandemic included 643 patients. An “AI trilogy” of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm on a tablet computer was applied to shorten the quarantine survey process and reduce processing time during the COVID-19 pandemic. Results The use of the AI trilogy facilitated the processing of suspected cases of COVID-19 with or without symptoms; also, travel, occupation, contact, and clustering histories were obtained with the tablet computer device. A separate AI-mode function that could quickly recognize pulmonary infiltrates on chest x-rays was merged into the smart clinical assisting system (SCAS), and this model was subsequently trained with COVID-19 pneumonia cases from the GitHub open source data set. The detection rates for posteroanterior and anteroposterior chest x-rays were 55/59 (93%) and 5/11 (45%), respectively. The SCAS algorithm was continuously adjusted based on updates to the Taiwan Centers for Disease Control public safety guidelines for faster clinical decision making. Our ex vivo study demonstrated the efficiency of disinfecting the tablet computer surface by wiping it twice with 75% alcohol sanitizer. To further analyze the impact of the AI application in the quarantine station, we subdivided the station group into groups with or without AI. Compared with the conventional ED (n=281), the survey time at the quarantine station (n=1520) was significantly shortened; the median survey time at the ED was 153 minutes (95% CI 108.5-205.0), vs 35 minutes at the quarantine station (95% CI 24-56; P Conclusions The AI trilogy improved our medical care workflow by shortening the quarantine survey process and reducing the processing time, which is especially important during an emerging infectious disease epidemic.

Background Cardiac insufficiency is a major cause of mortality in eosinophilic granulomatosis with polyangiitis (EGPA). Despite the dosages-related cardiotoxicity, cyclophosphamide is usually prescribed to induce disease remission in the presence of myocarditis with heart involvement. There is an imperative need of novel medications to efficiently control disease activity and spare the use of cyclophosphamide. Methods A retrospective study was carried out in hospitalized EGPA patients from January 1, 2008 to December 31, 2019, focusing on the use of biologics including benralizumab (BEN, anti-IL-5 receptor), mepolizumab (MEP, anti-IL-5), omalizumab (OMA, anti-IgE) and rituximab (RTX, anti-CD20). Results Sixteen admitted patients, 8 females aged 10 to 70 years (40.4 ± 15.5), had higher disease activities (Birmingham Vasculitis Activity Score 16 to 39, 26.8 ± 6.9), poorer prognostic factors (five-factor score 1 or 2, 1.4 ± 0.5) and elevated eosinophil counts (2,314 to 26,781/µL, 11,108 ± 7,060). BEN, MEP, OMA and RTX were prescribed in one, 2, one and 6 patients, respectively. Ten patients (63%) had myocarditis with impaired left ventricle ejection fraction and cardiac arrhythmia, and 7 received biological therapy without a combined use of cyclophosphamide. One patient obtained MEP with a 100 mg quadri-weekly × 13 regimen at induction for disease relapse. Six patients acquired RTX with a 375 mg/m2 weekly × 4 regimen at induction for refractory activity or relapsing disease, or plus a yearly maintenance schedule in 5. All patients received serial cardiac magnetic resonance imaging, transthoracic echocardiography and 24-hour Holter monitor to evaluate the therapeutic responses in heart involvement. After biological therapy, there were improved cardiac dysfunction, lower eosinophil counts and clinical remission (4 complete, 3 partial) with a relapse-free follow-up (13 to 61 months, 39.1 ± 16.0) after induction. Conclusions In this single-center retrospective study, we observed improved cardiac dysfunction and disease activity after biological therapy in EGPA patients with myocarditis.

Hepatitis C virus (HCV) infections can cause permanent liver-related diseases, including hepatocellular carcinoma (HCC). Low mortality and incidence of HCC have been observed in patients with chronic hepatitis C undergoing direct-acting antiviral therapy. Tumor suppressive let-7 family members are down-regulated in HCC. The present study, therefore, aimed to investigate whether expression levels for the full spectrum of let-7 family members (let-7a, 7b, 7c, 7d, 7e, 7f, 7g, 7i, and miR-98) in the circulatory system are useful as surveillance biomarkers for liver-related diseases to monitor treatment efficacy during HCV infection. To this end, we measured the levels of mature circulating let-7 family members using quantitative reverse transcription-PCR in 236 patients with HCV infection, and 147 age- and sex-matched controls. Using hierarchical cluster analysis and principal component analysis, three clusters were obtained after measuring expression levels of let-7 family members in the patients and controls. Cluster 1 included let-7a/d/e/g, Cluster 2 comprised let-7b and let-7i, and Cluster 3 comprised let-7c/f/miR-98. Let-7b/c/g represented the three clusters and showed the best survival response to liver cancer when analyzed with respect to patient data. Therefore, considering the circulating levels of let7 b/c/g as representatives of the let-7 family may facilitate effective monitoring of liver-related disease.

Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P

Prospective electrocardiography (ECG)-gated cardiac computed tomography angiography (CTA) is widely used for pediatric patients with congenital heart disease (CHD) due to the lower radiation dose compared with the ECG-gated technique. However, functional parameters acquired using ECG-gated cardiac CT to predict pulmonary hypertension (PH) in children with CHD have not yet been reported. This study aimed to investigate the potential of diastolic and systolic right ventricular diameters (RVD) on prospective ECG-gated cardiac CTA to predict PH in children with CHD. A total of 44 children with CHD were divided into two groups: CHD with PH (n = 22) and CHD without PH (n = 22). The association between ECG-gated CTA parameters and PH was evaluated by logistic regression. The receiver operating characteristic curve (ROC) was used to find the best cut-off point for the parameters measured by Youden's index. Patients with higher RVD-BSA [aOR (95% CI) diastolic: 2.76 (1.23–6.23); systolic: 6.15 (1.72–22.06)] had higher risk of PH after adjusting for age and patent ductus arteriosus. The area under the curve (AUC) of D-RVD-BSA was 0.907 and the AUC of S-RVD-BSA was 0.917. Logistic regression showed that patients with D-RVD-BSA over 6.86 or S-RVD-BSA over 5.87 had significantly higher risk of PH after adjustments (aOR = 23.52, 95% CI = 2.89–191.03; aOR = 31.14, 95% CI = 2.75–352.85). In conclusion, in children with CHD, measurements of diastolic or systolic BSA-modified RVDs on prospective ECG-gated CTA are non-invasive markers of PH. BSA-modified D-RVD of 6.86 or BSA-modified S-RVD of 5.87 may be used to identify PH in children with CHD.

// Chia-Yen Dai 1, 2, 3, 4, 5, 6, * , Yi-Shan Tsai 1, * , Wen-Wen Chou 1 , Tawei Liu 1 , Chung-Feng Huang 1, 2, 4 , Shu-Chi Wang 3 , Pei-Chien Tsai 1 , Ming-Lun Yeh 1, 4, 5 , Ming-Yen Hsieh 1 , Ching-I Huang 1, 5 , Shang-Yin Vanson Liu 7 , Jee-Fu Huang 1, 4 , Wan-Long Chuang 1, 4, 6 and Ming-Lung Yu 1, 2, 3, 4, 5, 6, 8 1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 2 Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 3 Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan 8 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan * These authors contributed equally to this work Correspondence to: Ming-Lung Yu, email: fish6069@gmail.com Keywords: miR-125b; HCV; IL-6; STAT3; HCV Received: July 28, 2017 Accepted: December 01, 2017 Published: January 10, 2018 ABSTRACT Background/Aims: MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection. Results: High expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression. The interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays an inducible effect on miR-125b gene expression. STAT3 siRNA or inhibitor could reduce HCV replication. Materials and Methods: HCV replicon cells Con1 (type 1b) and Huh7/Ava5 (type 1b) were treated with 17-hydroxy-jolkinolide B (HJB) or STAT3 siRNA. Cell viability assay and Renilla Luciferase Assay were used. Fragments of the miR-125b-1 promoter were constructed for the luciferase reporter assay. PSMB8, PSMB9, miR-125b-1, and miR-125b-2 expression was determined using TaqMan ® Gene Expression Assays. Western blot analysis was performed to assess protein abundance. Conclusions: This study elucidates a novel pathway for miR-125b in the pathogenesis of chronic HCV infection and suggests it as a possible target for treating HCV infection.

Background/Purpose Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. Methods A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. Results We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. Conclusion In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.

Objectives To investigate the diagnostic value of first-pass myocardial perfusion defects visualised in non-gated high-pitch computed tomography angiography (CTA) in patients admitted to the emergency department (ED) for suspected aortic dissection. Methods We recruited 174 ED patients who underwent high-pitch CTA of the aorta because of suspected aortic dissection. We divided these patients into two groups (diseased and control groups) based on whether their clinical data fulfilled the third universal definition of acute myocardial infarction (AMI), specifically an increase in cardiac troponin (cTn) with at least one of the following: (a) symptoms of ischemia; (b) new ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB); (c) development of pathological Q wave; (d) new loss of viable myocardium or new regional wall motion abnormality; or (e) identification of an intracoronary thrombus by angiography or autopsy. Twenty-two patients with a clinical diagnosis of AMI were placed in the diseased group. Myocardial perfusion defects were evaluated qualitatively and quantitatively on the late arterial phase obtained 50 s post-threshold. Results Of the 22 patients with a final diagnosis of AMI, visually identifiable perfusion defects were observed in 12 patients. The sensitivity, specificity, negative predictive value, and positive predictive value of any perfusion defect for predicting AMI were 54.6%, 94.7%, 93.5%, and 60.0%, respectively. Quantitative analysis indicated that CT attenuation was significantly lower within perfusion defects than within the normal myocardium (67.6 ± 29.5 HU vs. 92.2 ± 19.7 HU; p Conclusions In patients with acute chest pain, the presence of myocardial perfusion defect observed on nongated high-pitch CTA of the aorta can be used to identify individuals with AMI with high specificity, but low sensitivity.

Background/Aims: The purpose of this study is to report our results using a computed tomography (CT)-guided fat transversing coaxial biopsy technique for pancreatic lesion biopsy that avoids major organs and vessels. We retrospectively reviewed the records of patients referred to our department for pancreatic mass biopsy. Patients and Methods: The records of patients (from June 2008 to August 2014) in whom biopsy was performed under CT guidance with a coaxial needle using a fat transversing technique were reviewed. Patient demographic data and biopsy outcomes were collected. We aimed to compare differences between lesion size and biopsy outcome, the independent two-samples t-test was used. Results: A total of 122 patients who underwent 17-G coaxial needle biopsy were included. The mean pancreatic lesion size was 3.2 cm, and in 30 patients it was more than 4 cm. The majority of lesions were located in the head of the pancreas (44.3%). No transorgan biopsies were performed. In most patients, the biopsy was performed via a fat traversing detour route (93.4%), and a successful diagnosis was made based on the biopsy outcome in 96.7% patients. Complications occurred in five patients (4.1%); three of the patients developed a fever, and two developed pancreatitis. All patients recovered with symptomatic treatment. Conclusion: CT-guided coaxial core biopsy of pancreatic lesions using a fat detour route appears to be a safe and effective method for obtaining pancreatic lesion biopsies with a high success rate and low complication rate.

Background & Aims The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. Methods Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. Results HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048–69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057–7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488–17.432). Conclusions DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. Lay summary We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

A 14-year-old girl presented with sudden painless left eye vision loss. Fundus photography showed left central retinal artery occlusion (CRAO) (figure, A). Brain MRI revealed subclinical embolic infarcts (figure, B). Chest CT confirmed multicentric cardiac myxomas (figure, C). Gene testing revealed point mutation in the PRKAR1A gene (figure, D). Carney complex (CNC) is a rare autosomal dominant, multiple neoplasia syndrome with cardio-cutaneous manifestations. Multiple cardiac myxomas are unusual and strongly related to CNC. Cerebral emboli occur in 34% of patients with cardiac myxomas.1 The PRKAR1A gene is located on 17q22-24 and mutated in about 40% of patients with CNC.2

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a morphologically distinctive lesion. Although the clinical course of SANT is benign, its reactive or neoplastic nature remains to be clarified. Furthermore, some investigators have suggested that SANT is related to IgG4 sclerosing lesion or inflammatory pseudotumor with stromal cells positive for Epstein-Barr virus (EBV). In this study, we assessed 22 cases of SANT derived from adult women. Clinical data and follow-up information were obtained by chart review. Immunohistochemical studies for IgG4, IgG, and CD21 stains and in situ hybridization to detect EBV-encoded small RNAs were performed. We also assessed genomic DNA extracted from paraffin-embedded tissue for human androgen-receptor α gene analysis using conventional and methylation-specific polymerase chain reaction methods. The median patient age was 41.5 years (range, 25 to 82 y). Most (77%) patients presented with a single mass that was detected incidentally (59%). The mean size of the lesions was 3.8 cm (range, 1.0 to 9.0 cm). Clinical symptoms correlated with multiple lesions (P=0.043) but not lesional size (P=0.637) or location in the spleen (hilum vs. periphery, P=0.696). None of the cases had evidence of IgG4-related disease or recurred after splenectomy. The mean number of IgG4 cells was 27.7 (range, 4 to 125), and the mean IgG4/IgG ratio was 16.4% (range, 1.6% to 55.7%) with only 2 cases being >40%. Cases with higher IgG4 cells did not correlate with inflammatory pseudotumor-like morphology. No lesions were positive for EBV-encoded small RNAs, and almost all cases with informative results (n=19) showed a polyclonal pattern. We conclude that SANT is a polyclonal, reactive lesion rather than a neoplasm.

Purpose This study aimed to validate standard deviations of lung densities obtained using high-pitch dual-source computed tomography (DSCT) densitometry as indices of bronchopulmonary dysplasia (BPD) severity in premature infants. Methods Data of preterm, late preterm group, and early term groups were evaluated. Mean and median standard deviations (SDmean, SDmedian) of CT lung density (CTLD) were calculated from CT images. Results SDmean of CTLD in infants with severe BPD was significantly higher than that of infants without BPD (198.1 vs. 140.9, respectively; P =.002). Conclusions Study results support using high-pitch DSCT for BPD diagnosis and quantitative evaluation in prematurity.

Measuring bone mineral density (BMD) is important for surveying osteopenia in premature infants. However, the clinical availability of dual-energy X-ray absorptiometry (DEXA) for standard BMD measurement is very limited, and it is not a practical technique for critically premature infants. Developing alternative approaches for DEXA might improve clinical care for bone health. This study aimed to measure the BMD of premature infants via routine chest X-rays in the intensive care unit. A convolutional neural network (CNN) for humeral segmentation and quantification of BMD with calibration phantoms (QRM-DEXA) and soft tissue correction were developed. There were 210 X-rays of premature infants evaluated by this system, with an average Dice similarity coefficient value of 97.81% for humeral segmentation. The estimated humerus BMDs (g/cm3, mean &plusmn, standard) were 0.32 &plusmn, 0.06, 0.37 &plusmn, 0.06, and 0.32 &plusmn, 0.09, respectively, for the upper, middle, and bottom parts of the left humerus for the enrolled infants. To our knowledge, this is the first pilot study to apply a CNN model to humerus segmentation and to measure BMD in preterm infants. These preliminary results may accelerate the progress of BMD research in critical medicine and assist with nutritional care in premature infants.

Background Currently, no standard of care or therapies have been established for patients with advanced HCC. We evaluated the efficacy and safety of conventional transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin (cTACE) and TACE with doxorubicin-loaded drug eluting beads (DEB-TACE). Methods This retrospective study included 273 patients who received cTACE (n = 201) or DEB-TACE. Tumor response, survival, and adverse events were evaluated over a 5-year follow-up period. Results During 5-year follow-up, a greater percentage of patients treated with cTACE died than those treated with DEB-TACE (76.1% vs. 66.7%) (P = 0.045). At the last evaluation, all surviving patients had disease progression and no differences were seen between treatment groups. However, the time to disease progression differed between groups; median time to disease progression was 11.0 months for cTACE and 16.0 months for DEB-TACE (P = 0.019). The median survival time was 37 months in both treatment groups. No significant differences were observed between cTACE and DEB-TACE therapies in subgroups of patients with BCLC stage A or stage B + C either in survival time or time to disease progression (P values > 0.05). No significant differences were observed in survival status or disease progression between cTACE and DEB-TACE in patient subgroups with either tumor number > 5 or with the sum of the diameter of largest five HCC tumors being > 7 cm. Conclusions DEB-TACE demonstrates greater long-term benefits than cTACE in treating treatment-naïve patients with HCC. Results of this long-term study support the use of DEB-TACE in treating HCC.

Introduction Seasonal influenza-associated neurological complications had high mortality and morbidity rates in recent studies. We reported influenza-associated encephalitis/encephalopathy in children during 2014–2017 in Taiwan, focusing on neurological presentations, neuroimaging correlations, and critical care managements. Materials/Subjects During January 1st 2014 to June 30th 2017, pediatric patients reported to the Taiwan Centers for Disease Control surveillance system for severe complicated influenza infections in the hospital were retrospectively reviewed. Children with influenza-associated encephalitis/encephalopathy were inspected for clinical presentations, laboratory data, neuroimaging studies, treatment modalities, and neurological outcomes. Results Ten children with median age 5.9 years were enrolled for analysis. Influenza-associated encephalitis/encephalopathy appeared in the spring and summer, with a delayed peak comparing with the occurrence of pneumonia and septic shock. The neurological symptoms developed rapidly within median 1 day after the first fever episode. All patients had consciousness disturbance. Seven patients (70%) had seizures at initial presentation, and six of them had status epilepticus. Anti-viral treatments were applied in all patients, with median door-to-drug time 0.9 h for oseltamivir and 6.0 h for peramivir. Multi-modality treatments also included steroid pulse therapy, immunoglobulin treatment, and target temperature management, with 85.2% of the major treatments administered within 12 h after admission. Nine of the ten patients recovered without neurological sequelae. Only one patient had epilepsy requiring long-term anticonvulsants and concomitant cognitive decline. Conclusions In highly prevalent area, influenza-associated encephalitis/encephalopathy should be considered irrespective of seasons. Our study suggested the effects of timely surveillance and multi-modality treatments in influenza-associated encephalitis/encephalopathy.

Background and objective During bone drilling, the heat generated by friction depends directly on bone quality and surgical parameters. Excessive bone temperatures may cause thermal necrosis around the pilot hole, weaken the purchase of inserted screws, and in turn reduce the stability of screw fixation. A few studies have addressed the key parameters of drilling, such as the rotation speed of the drill-bit, feed force (axial force), feed rate, tool type, and tip geometry of drill-bits. Nevertheless, in the literature, information on the relationship between bone quality and thermally affected regions is still lacking. This study employed a three-dimensional dynamic elastoplastic finite element model to evaluate the influence of surgical parameters on the bone temperature elevation and assess the risk region of thermal necrosis for different bone qualities as a function of drilling parameters. Methods To ascertain the heat generation rate and the high-risk region of thermal necrosis, the effects of bone quality, feed rate, feed force, and drill-bit diameter on the bone temperature elevation were explained using a three-dimensional dynamic elastoplastic finite element model, which was validated through experimental measurements. Results The bone temperature was affected by the drilling parameters; the maximum temperature was attained at the junction of cancellous and cortical bones. The bone temperature increased with cortical bone thickness, bone density, and drill-bit diameter, and it decreased with the drilling speed and feed force. Conclusions The present model could assess the risk region of thermal necrosis by accurately analyzing the bone temperature elevation for various bone qualities, feed forces, and feed rates. The bone temperature increased with the bone mineral density and cortical bone thickness. The highest bone temperature and maximum necrosis region were found near the junction of cortical and cancellous bones. Increasing the drilling speed or feed force can minimize the bone temperature elevation and the risk range of thermal necrosis.

It has been identified that bisphenol A (BPA) exposure causes developmental toxicity in breast cells. However, the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear. The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer. Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner. Using individual dataset analyses, it was indicated that two BPA-associated gene sets, the visceral obesity pathway, involved in visceral fat deposits and the metabolic syndrome, and the cell cycle pathway, involved in cyclins and cell cycle regulation, were significantly associated with a high grade of aggressiveness and the development of estrogen receptor (ER)-positive breast cancer (between P

The presence of cardiac insufficiency is recognized as a poor prognostic factor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)1, and heart failure is an identified mortality risk factor for eosinophilic granulomatosis with polyangiitis (EGPA)2.

MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.

Cyclosporine (CsA) is an immunosuppressant known for its neurotoxicity, which presents with acute encephalopathy and seizures in the most severe form. However, whether there is age-related neurological susceptibility in pediatric population is poorly defined. The study aims to examine the vulnerability of CsA neurotoxicity among different age groups of pediatric patients in terms of occurrence rate, acute presentations, long-term outcomes, and neuroimaging findings.Pediatric patients (age18 years) who received CsA in a tertiary referral center between July 1, 1988 and August 31, 2011 were retrospectively reviewed for CsA-related encephalopathy. The clinical presentations, demographic data, and laboratory examinations were analyzed through t-test for numerical and Fisher's exact test for categorical variables. Exact logistic regression was used to examine the effect of each variables.Twelve (8%) of the enrolled 146 patients developed CsA-induced encephalopathy. Compared to the non-neurotoxicity group, the neurotoxicity group was significantly younger upon starting CsA (p = 0.008) and had higher percentages of hypertension after CsA treatment (p = 0.01). Regression analysis showed that age6 years (OR 7.6, 95% CI 1.6-51.5; p = 0.007) and hypertension after CsA (OR 6.3, 95% CI 1.4-35.4; p = 0.016) were significantly associated with CsA encephalopathy. Younger children were prone to have more severe seizures in the acute stage and more epilepsy and neuropsychiatric disorders in the future. Follow-up neuroimaging showed parietal cerebral atrophy in all examined children6 years of age.Age-dependent susceptibility of CsA neurotoxicity occurs in children, with severe acute presentations and long-term sequelae in children below 6 years old.

The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. A case–control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene–environment interaction analysis. The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95 % confidence interval (CI) 1.2–3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2–4.0 and 1.5–2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. The results of this betel-related oral cancer study provide the evidence of environment–gene interaction for early prediction and molecular diagnosis.

Hypereosinophilic syndrome (HES), or Löeffler's endocarditis, is a heterogenous group of disorders marked by the sustained overproduction of eosinophils involving different organ systems. Cardiac involvement, recognized as endocardial thickening and left ventricular (LV) mural thrombi, is the major cause for morbidity and mortality. Herein, we present a case with idiopathic HES complicated with severe cardiac involvement, who was treated successfully with corticosteroids. Echocardiography is pivotal in diagnosis and follow-up.

Summary Background Addition of nitroglycerine (NTG) to transcatheter arterial embolization/transarterial chemoembolization (TAE/TACE) has been shown to increase deposition of Lipiodol emulsion in hepatocellular carcinoma (HCC) tumors. The aim of this retrospective study was to evaluate if the addition of nitroglycerin (NTG) to TAE/TACE improved treatment response in HCC. Methods Patients with HCC either received (n = 42) or did not receive (non-NTG) (n = 111) NTG and an emulsion of Lipiodol with or without doxorubicin, followed by embolization with Gelfoam pledgets. Treatment response was monitored using dual-energy computer tomography (CT). Disease progression and overall survival (OS) were monitored. Results The rate of disease progression in the NTG group was 86.5% and in the non-NTG group was 88.6%. Median time to disease progression was 12 months (95% CI; 9.0, 15.0) for the NTG group and 12 months (95% CI; 10.4, 13.6) for the non-NTG groups (P = 0.040). No difference was observed in OS between the NTG (60 months) and the non-NTG groups (41 months) (P = 0.117). Multivariate analysis found that in the NTG group, OS was associated with Cancer of the Liver Italian Program (CLIP) stage I and Barcelona Clinic Liver Cancer (BCLC) stage B. Conclusions Addition of NTG to TAE/TACE did not result in improved OS or disease progression.