There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV) in South ...Korea. This hospital-based retrospective study compared MERS-CoV-positive and MERS-CoV-negative patients. A total of seven positive patients and 55 negative patients with a median age of 43 years (P = 0.845) were included. No statistical differences were observed with respect to their sex and the presence of comorbidities. At the time of admission, headache (28.6% vs. 3.6%; odds ratio OR, 10.60; 95% confidence interval CI, 1.22–92.27), myalgia (57.1% vs. 9.1%; OR, 13.33; 95% CI, 2.30–77.24), and diarrhea (57.1% vs. 14.5%; OR, 7.83; 95% CI, 1.47–41.79) were common among MERS-CoV-positive patients. MERS-CoV-positive patients were more likely to have a low platelet count (164 ± 76.57 vs. 240 ± 79.87) and eosinophil (0.27 ± 0.43 vs. 2.13 ± 2.01; P = 0.003). Chest radiography with diffuse bronchopneumonia was more frequent in MERS-CoV-positive patients than in negative patients (100% vs. 62.5%; P = 0.491). The symptoms of headache, myalgia, and diarrhea, as well as laboratory characteristics, including low platelet counts and eosinophil, and chest X-ray showing diffuse bronchopneumonia might enhance the ability to detect patients in South Korea infected with MERS-CoV.
Background
Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic ...criteria.
Purpose
To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients.
Study Type
Retrospective observational study.
Subject
A total of 418 treatment‐naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment.
Field Strength/sequence
T1W GRE in‐ and opposed‐phase, T2W FSE, DWI, and T1W 3D‐GRE dynamic contrast‐enhanced sequences at 1.5 T and 3 T.
Assessment
Six radiologists with 7–22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI‐RADS) version 2018.
Statistical Tests
Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c‐index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR‐5.
Results
The 15‐point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha‐fetoprotein and platelet). It showed good discrimination in the derivation (c‐index, 0.946) and validation cohorts (c‐index, 0.907). Using a risk score of 12 as a cut‐off, this system yielded higher sensitivity than LR‐5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299).
Data Conclusion
A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI‐RADS without significant compromise in specificity.
Evidence Level
3
Technical Efficacy
Stage 2.
Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, ...surveillance using magnetic resonance imaging (MRI) with liver‐specific contrast showed markedly higher sensitivity in detecting early‐stage HCC than US. This study aimed to compare the cost‐effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost‐effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality‐adjusted life‐years (QALYs), between MRI and US, with a 20‐year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus–associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost‐effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost‐effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life‐years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost‐effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver‐specific contrast may be more cost‐effective than US in patients with virus‐associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on ...treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor ...activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1–10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.
Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult ...location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment.
A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT.
The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients' survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%).
SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.
Background & Aims
We aimed to compare the performance of gadoxetic acid‐enhanced abbreviated MRI (AMRI)‐based surveillance and ultrasound‐only surveillance in high‐risk patients for hepatocellular ...carcinoma (HCC).
Methods
Prospectively recruited high‐risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid‐enhanced MRI (CMRI) and ultrasound at 6‐months intervals were retrospectively analysed. AMRI consisted of diffusion‐weighted, T2‐weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI‐only (AAA), and ultrasound‐only (US) were compared using generalized estimating equations. Image quality was assessed.
Results
In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early‐stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% 12/43; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% 967/1012; P = 0.01) and not significantly different from US (96.3% 975/1012; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% 1004/1055; P = 0.01) and the US approach (93.6% 987/1055; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach.
Conclusions
In high‐risk patients, AMRI‐based surveillance approaches had higher sensitivities than ultrasound‐only surveillance for early‐stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI‐only or ultrasound‐only approach.
The quality of fermented soybeans can be determined by diverse metabolites produced by microorganisms. Mass spectrometry-based metabolomic approach was applied to investigate the differences in ...volatile and non-volatile metabolite profiles of fermented soybeans by different microorganisms e.g., molds, yeasts, lactic acid bacteria (LAB), and other bacteria. The partial least squares-discriminant analysis (PLS-DA) for volatile metabolites profiles indicated that the fungi group (mold/yeast) was clearly discriminated from the bacteria group (bacteria/LAB). The metabolic pathways related to the formation of volatile metabolites also differed according to microorganisms. In particular, the formation of branched-chain aliphatic alcohols and esters increased in the fungi group, while that of volatiles derived from fatty acids was superior in the bacteria group. In addition, we could determine the microorganism-specific metabolites using a correlation network analysis. This study can provide the fundamental knowledge on the metabolic differences according to the type of microorganisms in fermented soybeans.
•Volatile metabolite profiles differed according to starters in fermented soybeans.•The formation of branched-chain alcohols and esters was more activated in fungi.•Higher levels of volatile metabolites from fatty acids were found in bacteria.•Microorganism-specific metabolites were determined by correlation network analysis.
We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor ...thrombosis (PVTT).
A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy.
Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%).
Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.
Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are ...expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.
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