Liver fibrosis estimated using extracellular volume fraction obtained from dual-energy CT as a risk factor for hepatocellular carcinoma after sustained virologic response: A preliminary case-control study.

PURPOSE: To assess hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) through clinical data analyses, including evaluation of liver fibrosis using the extracellular volume fraction (ECV) obtained from dual-energy computed tomography (DECT). METHODS: Ninety-two patients (52 men and 40 women; mean age, 69.9 years) with hepatitis C virus infection after SVR underwent DECT of the liver (3-minute equilibrium-phase images) between January 2020 and March 2022. The ECV was calculated by measuring iodine density; fibrous markers, including ECV, fibrosis-4 index, aspartate aminotransferase to platelet ratio index, and platelet count, were statistically analyzed (p < 0.05). The risk factors associated with HCC were analyzed using univariate and multivariate logistic regression analyses. RESULTS: The ECV (26.1 ± 4.6 %) in patients with HCC (n,21) was significantly larger than the ECV (20.7 ± 3.3 %) in patients without HCC (n = 71) (p < 0.001). The cutoff value for the ECV was 24.3 %. The area under the operating characteristic curve of the ECV was 0.857, which was higher than that of the serum fibrosis markers. Older age, SVR achieved with interferon, alpha-fetoprotein level (>5 ng/mL), advanced fibrosis before treatment (>F3), and ECV were associated with HCC according to the univariate analysis. Multivariate analyses showed that ECV was the only factor independently associated with HCC (odds ratio 0.619, 95 % confidence interval 0.482-0.795, p < 0.001). CONCLUSION: Liver fibrosis estimated using ECV can be a predictive marker in patients with HCC after SVR.

A case of focal nodular hyperplasia-like lesion presenting unusual signal intensity on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance image.

Focal nodular hyperplasia (FNH) or FNH-like lesions of the liver are benign lesions that can be mostly diagnosed by hepatobiliary phase gadoxetic acid-enhanced magnetic resonance imaging (MRI). Accurate imaging diagnosis is based on the fact that most FNHs or FNH-like lesions show characteristic hyper- or isointensity on hepatobiliary phase images. We report a case of an FNH-like lesion in a 73-year-old woman that mimicked a malignant tumor. Dynamic contrast-enhanced computed tomography (CT) and MRI using gadoxetic-acid revealed an ill-defined nodule showing early enhancement in the arterial phase and gradual and prolonged enhancement in the portal and equilibrium/transitional phases. Hepatobiliary phase imaging revealed inhomogeneous hypointensity, accompanied by a slightly isointense area compared to the background liver. Angiography-assisted CT showed a portal perfusion defect of the nodule, inhomogeneous arterial blood supply in the early phase, and less internal enhancement in the late phase, accompanied by irregularly shaped peritumoral enhancement. No central stellate scar was identified in any of the images. Imaging findings could not exclude the possibility of hepatocellular carcinoma, but the nodule was pathologically diagnosed as an FNH-like lesion by partial hepatectomy. In the present case, an unusual inhomogeneous hypointensity on hepatobiliary phase imaging made it difficult to diagnose the FNH-like lesions.

Assessment of Arterial Transit Time and Cerebrovascular Reactivity in Moyamoya Disease by Simultaneous PET/MRI.

We investigated the relationship between MRI-arterial spin labeling (ASL) parameters and PET-cerebral blood flow (CBF)/cerebrovascular reactivity (CVR) simultaneously obtained by PET/MRI in Moyamoya disease. Twelve patients underwent 15O-water PET/MRI with the acetazolamide (ACZ) challenge test. PET-CBF and PET-CVR were measured using 15O-water PET. Pseudo-continuous ASL obtained the robust arterial transit time (ATT) and ASL-CBF estimation. ASL parameters were compared with PET-CBF and PET-CVR. Before ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.44, p < 0.0001, and r = 0.55, p < 0.0001, respectively). After ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.56, p < 0.001, and r = 0.75, p < 0.0001, respectively), and ΔASL-CBF was significantly correlated with ΔPET-CBF (r = 0.65, p < 0.0001). Baseline ASL-ATT had strong negative correlations with ΔPET-CBF and PET-CVR (r = -0.72, p < 0.0001, and r = -0.66, p < 0.0001, respectively). Baseline ASL-ATT of MCA territories with CVR <30% (1546 ± 79 ms) was significantly higher than that with CVR > 30% (898 ± 197 ms). ASL-ATT ratio of MCA territories with CVR < 30% (94.0 ± 10.5%) was significantly higher than that with CVR > 30% (81.4 ± 11.3%). ATT correction using multiple postlabeling delays increased the accuracy of ASL-CBF quantitation. Baseline ASL-ATT is a hemodynamic parameter and may represent an efficient alternative to PET-CVR.

Diagnostic performance of abbreviated gadoxetic acid-enhanced magnetic resonance protocols with contrast-enhanced computed tomography for detection of colorectal liver metastases.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) using gadoxetic acid has been shown to have higher accuracy, sensitivity, and specificity for the detection and characterization of hepatic metastases compared with other modalities, the long examination time would limit the broad indication. Several abbreviated enhanced MRI (Ab-MRI) protocols without dynamic phases have been proposed to achieve equivalent diagnostic performance for the detection of colorectal liver metastases. However, an optimal protocol has not been established, and no studies have assessed the diagnostic performance of Ab-MRI combined with contrast-enhanced computed tomography (CE-CT), which is the preoperative imaging of colorectal cancer staging in clinical settings, to determine the best therapeutic strategy. AIM: To compare the diagnostic performance of two kinds of Ab-MRI protocol with the standard MRI protocol and a combination of the Ab-MRI protocol and CE-CT for the detection of colorectal liver metastases. METHODS: Study participants comprised 87 patients (51 males, 36 females; mean age, 67.2 ± 10.8 years) who had undergone gadoxetic acid-enhanced MRI and CE-CT during the initial work-up for colorectal cancer from 2010 to 2021. Each exam was independently reviewed by two readers in three reading sessions: (1) Only single-shot fast spin echo (FSE) T2-weighted or fat-suppressed-FSE-T2-weighted, diffusion-weighted, and hepatobiliary-phase images (Ab-MRI protocol 1 or 2); (2) all acquired MRI sequences (standard protocol); and (3) a combination of an Ab-MRI protocol (1 or 2) and CE-CT. Diagnostic performance was then statistically analyzed. RESULTS: A total of 380 Lesions were analyzed, including 195 metastases (51.4%). Results from the two Ab-MRI protocols were similar. The sensitivity, specificity, and positive and negative predictive values from Ab-MRI were non-inferior to those from standard MRI (P > 0.05), while those from the combination of Ab-MRI protocol and CE-CT tended to be higher than those from Ab-MRI alone, although the difference was not significant (P > 0.05), and were quite similar to those from standard MRI (P > 0.05). CONCLUSION: The diagnostic performances of two Ab-MRI protocols were non-inferior to that of the standard protocol. Combining Ab-MRI with CE-CT provided better diagnostic performance than Ab-MRI alone.

Multiplexed ISSR genotyping by sequencing distinguishes two precious coral species (Anthozoa: Octocorallia: Coralliidae) that share a mitochondrial haplotype.

BACKGROUND: Precious corals known as coralliid corals (Anthozoa: Octocorallia) play an important role in increasing the biodiversity of the deep sea. Currently, these corals are highly threatened because of overfishing that has been brought on by an increased demand and elevated prices for them.The deep sea precious corals Pleurocorallium elatius and P. konojoi are distributed in Japanese waters and have distinct morphological features: (1) the terminal branches of the colony form of P. elatius are very fine, while those of P. konojoi are blunt and rounded, (2) the autozooids of P. elatius are arranged in approximately four rows, while those of P. konojoi are clustered in groups. However, previous genetic analysis using mtDNA and nuclear DNA did not indicate monophyly. Therefore, it is important to clarify their species status to allow for their conservation. METHODOLOGY: We collected a total of 87 samples (60 of Corallium japonicum and 27 of P. konojoi) from around the Ryukyu Islands and Shikoku Island, which are geographically separated by approximately 1,300 km. We used a multiplexed inter-simple sequence repeat (ISSR) genotyping by sequencing (MIG-seq) and obtained 223 SNPs with which to perform STRUCTURE analysis and principle coordinate analysis (PCoA). In addition, two relatively polymorphic mtDNA regions were sequenced and compared. RESULTS: P. elatius and P. konojoi share a same mtDNA haplotype, which has been previously reported. However, MIG-seq analysis clearly distinguished the two species based on PCoA and STRUCTURE analysis, including 5% of species-specific fixed SNPs. CONCLUSION: This study indicated that P. elatius and P. konojoi are different species and therefore both species should be conserved separately. Our findings highlight the importance of the conservation of these two species, especially P. elatius, whose population has been dramatically depleted over the last 100 years. The study also demonstrated the effectiveness and robustness of MIG-seq for defining closely related octocoral species that were otherwise indistinguishable using traditional genetic markers (mtDNA and EF).

Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy.

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.

Evaluation of retained products of conception using pulsed continuous arterial spin-labeling MRI: clinical feasibility and initial results.

OBJECTIVES: We evaluated the vascularity of retained products of conception (RPOC) using arterial spin-labeling magnetic resonance imaging (ASL-MRI) to clarify the clinical feasibility of this approach. MATERIALS AND METHODS: A pulsed-continuous ASL sequence with echo-planar imaging (EPI) acquisitions was used. Ten consecutive patients with RPOC were enrolled. All ASL images were evaluated visually and semiquantitatively and compared with the findings of Doppler ultrasound (US) and dynamic contrast-enhanced MRI (DCE-MRI). RESULTS: The technical success rate was 93.7% (15/16 scans). One failed case was excluded from the analysis. Six patients showed quite high signals over RPOC, while three patients showed no abnormal signals. Doppler US alone failed to detect the hypervascular area in two cases, and ASL-MRI alone failed in three. A significant linear correlation was found between semiquantitative values of ASL-MRI and DCE-MRI. All six patients showing high signals on ASL-MRI underwent follow-up MRI after therapy. High signals in five patients decreased visually and semiquantitatively, while one patient showed signal increases. CONCLUSION: Evaluation of RPOC using ASL-MRI was clinically feasible and response to therapy could be evaluated. However, the clinical advantages over conventional imaging remain unclear and need to be evaluated.

Comparison of gastrointestinal adverse effects of ketoprofen between adult and young cats.

This study elucidated differences in predisposition to the gastrointestinal adverse effects of ketoprofen between young and adult cats. Ketoprofen was administered subcutaneously (2.0 mg/kg, s.c.) once a day for 3 days. The animals were sacrificed 24 hr after final injection to allow examination of gastrointestinal mucosal lesions. Ketoprofen caused gastric lesions in adult cats (>6 months) but not in young cats (<3 months). Ketoprofen caused more severe small intestinal lesions in adult cats than in young cats. In the study of prevention of lipopolysaccharide (LPS)-induced hyperthermia using ketoprofen, young and adult cats of both sexes were administered LPS (0.3 µg/kg, intravenously), and body temperature was measured 24 hr later. Ketoprofen was administered subcutaneously 30 min before LPS injection. LPS-induced hyperthermia was almost completely inhibited by pretreatment with ketoprofen in both adult and young cats. In the pharmacokinetics of ketoprofen, plasma concentrations were analyzed by high-performance liquid chromatography. No significant differences were observed in plasma concentrations of two mirror-image R(-) and S(+) ketoprofen between young and adult cats from 0.5-4 hr after injection. As observed in a previous study using flunixin, the degree of gastrointestinal damage was unrelated to plasma concentrations of ketoprofen. The results of this study demonstrated that ketoprofen is safer for use in young cats than in adult cats from the viewpoint of gastrointestinal adverse effects.

Therapeutic and adverse effects of flunixin-meglumine in adult and young cats.

In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (<3 months old) and adult (>12 months old) cats of both sexes were given LPS (0.3 µg/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.

Soluble dietary fiber protects against nonsteroidal anti-inflammatory drug-induced damage to the small intestine in cats.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. We found that soluble dietary fibers (SDFs), such as pectin, could prevent the formation of small intestinal lesions induced by indomethacin (IND) in cats. To elucidate the mechanism of protection by SDFs, we examined the viscosities of SDFs and the effects of pectin on gastrointestinal absorption of IND and intestinal hypermotility induced by IND. METHODS: Cats were given regular dry food (RFD-Dry) or RFD-Dry supplemented with pectin, guar gum, polydextrose, or mucin twice daily. IND was administered orally once daily for 3 days. Mucosal lesions in the small intestine were examined 24 h after the final dosing of IND. Plasma concentrations of IND were measured by HPLC. GI motilities were measured using a telemetry system in conscious cats implanted with force transducers. Viscosities of the SDFs were measured using a viscosimeter. RESULTS: In cats given RFD-Dry, IND (3 mg/kg) increased motility and produced many lesions in the lower half of the small intestine; the total lesion area (TLA) was 7.5 +/- 2.6 cm(2) (n = 4). Lesions induced by IND were markedly decreased in cats given RFD-Dry supplemented with 3% pectin, guar gum, polydextrose or mucin; TLAs were 0.6 +/- 0.3, 0.0 +/- 0.0, 1.3 +/- 0.8 and 1.6 +/- 0.5 cm(2) (n = 4) (P < 0.05 vs. RFD-Dry alone), respectively. The viscosity (mPa-S) of pectin, guar gum, polydextrose and mucin (3% concentration) was 414, >1,200, 1 and 4, respectively. Pectin did not affect the absorption of IND nor did it inhibit IND-induced intestinal hypermotility. CONCLUSIONS: SDFs protect the small intestine against NSAID-induced damage, probably by compensating a barrier function of the mucin decreased by IND. Viscosities of the SDFs play a role, at least in part, in the protective effects of the SDFs on the small intestine.

A green fluorescent protein fused to rice prolamin forms protein body-like structures in transgenic rice.

Prolamins, a group of rice (Oryza sativa) seed storage proteins, are synthesized on the rough endoplasmic reticulum (ER) and deposited in ER-derived type I protein bodies (PB-Is) in rice endosperm cells. The accumulation mechanism of prolamins, which do not possess the well-known ER retention signal, remains unclear. In order to elucidate whether the accumulation of prolamin in the ER requires seed-specific factors, the subcellular localization of the constitutively expressed green fluorescent protein fused to prolamin (prolamin-GFP) was examined in seeds, leaves, and roots of transgenic rice plants. The prolamin-GFP fusion proteins accumulated not only in the seeds but also in the leaves and roots. Microscopic observation of GFP fluorescence and immunocytochemical analysis revealed that prolamin-GFP fusion proteins specifically accumulated in PB-Is in the endosperm, whereas they were deposited in the electron-dense structures in the leaves and roots. The ER chaperone BiP was detected in the structures in the leaves and roots. The results show that the aggregation of prolamin-GFP fusion proteins does not depend on the tissues, suggesting that the prolamin-GFP fusion proteins accumulate in the ER by forming into aggregates. The findings bear out the importance of the assembly of prolamin molecules and the interaction of prolamin with BiP in the formation of ER-derived PBs.