Publications by authors named "Naoki Matsumoto"

232 Publications

Large-volume cell-free and concentrated ascites reinfusion therapy improves venous flow in patients with liver cirrhosis.

J Med Ultrason (2001) 2021 Apr 9. Epub 2021 Apr 9.

Ascites Treatment Center, Kanamecho Hospital, 1-11-13 Kanamecho, Toshima-ku, Tokyo, 171-0043, Japan.

Purpose: Hemodynamic change after total paracentesis was investigated because it might lead to various complications. Although cell-free and concentrated ascites reinfusion therapy (CART) is safer and more effective than total paracentesis in theory, hemodynamic change after CART has been never reported. And previous studies did not mention hemodynamics of the venous system.

Methods: We investigated the hemodynamic change, including that of the venous system, before and after CART using color Doppler ultrasonography and fast Fourier transform analysis. Twenty-eight patients with tensive cirrhotic ascites underwent ultrasonography the day before and after total volume CART. The diameter and velocity of the main, right, and left portal vein; inferior vena cava (IVC); and right renal vein were measured using ultrasonography.

Results: A total of 11.8 ± 4.4 L of ascites (range 3.6-20.9 L) was filtered and concentrated to 0.85 ± 0.40 L (range 0.36-1.50 L). The diameter of the IVC increased from median 13.5 ± 5.4 mm (range 4-25 mm) to 18.5 ± 4.1 mm (range 7-29 mm) (p = 0.007). The diameter of the right segmental renal vein significantly increased after KM-CART [from 5.0 ± 1.0 (4-8) mm to 7.0 ± 2.0 (3-10) mm] (p = 0.011). Hemodynamic change of the portal venous system was not significant. The time to the next CART in patients with an IVC diameter ≥ 20 mm and < 20 mm was 86 days and 20.5 days (p = 0.035), respectively.

Conclusion: Tensive ascites results in venous congestion in patients with cirrhotic ascites. CART improved venous flow, but it did not change the hemodynamics of the portal venous system.
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http://dx.doi.org/10.1007/s10396-021-01094-2DOI Listing
April 2021

Plasma Concentration and Pharmacodynamics of Edoxaban in Patients with Nonvalvular Atrial Fibrillation and Acute Heart Failure.

Clin Pharmacokinet 2021 Mar 30. Epub 2021 Mar 30.

Department of Cardiovascular Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

Objective: The objective of this study was to assess the pharmacokinetic and pharmacodynamic profiles and safety of edoxaban in patients with nonvalvular atrial fibrillation (NVAF) who were hospitalized with acute heart failure (AHF).

Methods: The trough plasma concentrations of edoxaban, and the coagulation biomarkers prothrombin fragments 1 and 2 (F1+2) and D-dimer, were determined. Twenty-six patients received edoxaban 60 mg (30 mg when dose adjustment was required) and blood samples were collected immediately before oral edoxaban administration for 7 consecutive days after hospitalization and on the day of discharge.

Results: The mean observation period was 13 (range 7-46) days. Trough plasma concentrations of edoxaban were constant from day 2 onwards. On day 1, the variation was greater owing to the differing intervals between the last edoxaban dose and day 1 blood collection. Trough plasma concentrations were higher in patients with reduced creatinine clearance (≤ 50 mL/min). Median values for F1+2 and D-dimer remained within normal ranges throughout the study. There were no drug discontinuations, and no serious adverse events were reported.

Conclusions: This is the first study of edoxaban pharmacokinetics and pharmacodynamics in patients with NVAF and AHF, and shows that the pharmacokinetic and pharmacodynamic profiles of edoxaban were constant during hospitalization. Thus, even in patients with NVAF and AHF, edoxaban anticoagulation therapy with guided dose adjustment is considered to be a safe and appropriate intervention. In particular, patients with reduced creatinine clearance should adhere to dose adjustment criteria.

Clinical Trial Registration: jRCTs031190006 (Japan Registry of Clinical Trials), 5 April, 2019 retrospectively registered.
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http://dx.doi.org/10.1007/s40262-021-00999-yDOI Listing
March 2021

Renal vein measurement using ultrasonography in patients with cirrhotic ascites and congestive heart failure.

J Med Ultrason (2001) 2021 Apr 25;48(2):225-234. Epub 2021 Mar 25.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.

Purpose: Ascites can cause compression of the inferior vena cava (IVC), leading to increased renal venous pressure and renal congestion. Previously, the left renal vein diameter in liver cirrhosis patients with ascites was measured using computed tomography, showing that enlargement of the left renal vein diameter affects the prognosis. Herein, the diameter and flow velocity of the renal veins were measured using ultrasonography.

Methods: Abdominal ultrasonography was performed on 186 patients. The patients were divided into four groups: normal liver (n = 102), liver cirrhosis (LC) without ascites (n = 37), LC with ascites (n = 30), and congestive liver (n = 17). Ultrasonographic measurements for diameter and flow velocity of the IVC, left renal vein main trunk, and segmental renal vein were performed.

Results: The left renal vein diameter increased in the following order: normal liver, LC, LC with ascites, and congestive liver groups (P < 0.001). IVC flow velocity was lower and left renal vein diameter was larger in the congestive liver and LC with ascites groups. These results suggest that the two groups have different pathological conditions, but the mechanism of renal congestion is similar. In patients with LC, IVC compression due to ascites might cause blood stagnation and renal congestion.

Conclusion: The left renal vein and IVC can be measured using ultrasonography. It might help in furthering our understanding of the pathophysiology of renal congestion in these patients.
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http://dx.doi.org/10.1007/s10396-021-01088-0DOI Listing
April 2021

Predictive value of combined computed tomography volumetry and magnetic resonance elastography for major complications after liver resection.

Abdom Radiol (NY) 2021 Mar 8. Epub 2021 Mar 8.

Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.

Purpose: To retrospectively compare the predictive value of computed tomography volumetry (CTV), magnetic resonance elastography (MRE) of the liver, and their combination for major complications after liver resection.

Methods: We enrolled 108 consecutive patients who underwent anatomical liver resection for liver tumors and preoperative contrast-enhanced CT and MRE. The future liver remnant (FLR) ratio was calculated by CTV, while the liver stiffness measurement (LSM) was obtained by MRE. FLR ratio alone, LSM alone, and combined FLR ratio and LSM were evaluated to predict major complications (Clavien-Dindo grade ≥ IIIa). Univariate and multivariate analyses of hepatic biochemical parameters and imaging data were performed to identify predictors of major complications. Receiver operating characteristic analyses of FLR ratio, LSM, and their combination were performed, and the sensitivity and specificity were calculated.

Results: Twenty-two (20.4%) of the 108 patients experienced major complications. According to multiple regression analysis, the FLR ratio (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.91-0.99, p = 0.040) and LSM (OR 1.72, 95% CI 1.01-2.94, p = 0.047) were independent predictors of major complications. The combined FLR ratio and LSM were predictive of major complications, with an area under the curve (AUC) of 0.818, sensitivity of 68.2%, and specificity of 84.9%. The AUC and specificity for combined FLR ratio and LSM were larger than those for FLR ratio (AUC: 0.711, specificity: 80.2%) and LSM (AUC: 0.793, specificity: 80.2%).

Conclusion: Combined CTV and MRE analysis can improve the AUC and specificity for predicting major complications after anatomical liver resection.
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http://dx.doi.org/10.1007/s00261-021-02991-3DOI Listing
March 2021

Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan.

Viruses 2021 01 29;13(2). Epub 2021 Jan 29.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan.

Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.
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http://dx.doi.org/10.3390/v13020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910831PMC
January 2021

Japanese Man with HCV Genotype 4 Infection and Cirrhosis Who was Successfully Treated by the Combination of Glecaprevir and Pibrentasvir.

Intern Med 2021 Feb 1. Epub 2021 Feb 1.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan.

A 74-year-old man with a history of transfusion at 35 years old in Egypt was referred to our hospital. He was infected with hepatitis C virus (HCV) genotype 4 (GT4), which is a rare HCV GT in Japan, and was also diagnosed with hepatic compensated cirrhosis. We safely treated the patient for 12 weeks with the combination of glecaprevir and pibrentasvir, and a sustained virologic response (SVR) was achieved. This is the first report of HCV GT4 infection in a treatment-naïve Japanese patient with cirrhosis in whom SVR was achieved with the combination treatment of glecaprevir and pibrentasvir.
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http://dx.doi.org/10.2169/internalmedicine.6728-20DOI Listing
February 2021

CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation.

Int Immunol 2021 Apr;33(5):273-280

Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo, Hokkaido, Japan.

CD47, a 50 kDa transmembrane protein, facilitates integrin-mediated cell adhesion and inhibits cell engulfment by phagocytes. Since CD47 blocking promotes engulfment of cancer cells by macrophages, it is important to clarify the mechanism of CD47 signaling in order to develop treatments for diseases involving CD47-overexpressing cancer cells, including breast cancer and lymphoma. Here, we show that CD47 plays an essential role in T-cell lymphoma metastasis by up-regulating basal RhoA activity independent of its anti-phagocytic function. CD47 interacts with AKAP13, a RhoA-specific guanine nucleotide exchange factor (GEF), and facilitates AKAP13-mediated RhoA activation. Our study shows that CD47 has a novel function on the AKAP13-RhoA axis and suggests that CD47-AKAP13 interaction would be a novel target for T-cell lymphoma treatment.
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http://dx.doi.org/10.1093/intimm/dxab002DOI Listing
April 2021

DCIR3 and DCIR4 are widely expressed among tissue-resident macrophages with the exception of microglia and alveolar macrophages.

Biochem Biophys Rep 2020 Dec 18;24:100840. Epub 2020 Nov 18.

Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8562, Japan.

Dendritic cell inhibitory receptor 3 (DCIR3, Clec4a3) and dendritic cell inhibitory receptor 4 (DCIR4, Clec4a1) are C-type lectin receptors that belong to mouse dendritic cell immunoreceptor (DCIR) family. We recently showed that DCIR3 and DCIR4 are co-expressed on inflammatory and patrolling monocytes. In this study, we investigated the expression of DCIR3 and DCIR4 on tissue-resident macrophages. We found that spleen red pulp macrophages, liver Kupffer cells, large and small peritoneal macrophages and small intestinal macrophages expressed both DCIR3 and DCIR4. By contrast, lung alveolar macrophages expressed DCIR3 but not DCIR4 and brain microglia expressed neither DCIR3 nor DCIR4. Considerable part of tissue-resident macrophages are derived from embryonic precursors. We, therefore, examined the expression of DCIR3 and DCIR4 on the embryonic precursors. Yolk-sac macrophages from embryonic day (E) 8.5 embryos expressed both DCIR3 and DCIR4, while DCIR3 and DCIR4 were expressed on subpopulations of fetal liver monocytes from E14.5 embryos. Our results, together with previous data, indicate that the expression of DCIR3 and DCIR4 is widely shared by mononuclear phagocytes, including monocytes and macrophages, and that the expression of DCIR3 and DCIR4 on the embryonic precursors are not always retained by their progenies, suggesting that expression of DCIR3 and DCIR4 on tissue-resident macrophages might be regulated by environment of the tissues where the embryonic precursors differentiate into macrophages.
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http://dx.doi.org/10.1016/j.bbrep.2020.100840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689045PMC
December 2020

Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells.

In Vivo 2020 Nov-Dec;34(6):3301-3308

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background/aim: Hepatitis A virus (HAV) infection is still one of the serious health problems worldwide, despite the existence of effective vaccines for HAV. Zinc compounds have antiviral activities against various DNA and RNA viruses. Therefore, we investigated the effects of zinc compounds on the antiviral activity of interferon against HAV.

Materials And Methods: The effects of zinc compounds with or without interferon on HAV genotype IIIA HA11-1299 replication were examined in human hepatoma Huh7 cells. Cell viability was examined by the MTS assay. Inflammasome associated gene expression was examined by real-time reverse transcription-polymerase chain reaction.

Results: Both zinc sulfate and zinc chloride had an inhibitory effect on HAV replication. Zinc sulfate tended to enhance while zinc chloride significantly enhanced the anti-HAV effect induced by interferon-alpha-2a. Zinc chloride significantly up-regulated mitogen-activated protein kinase 12 (MAPK12) and down-regulated 6 related genes [baculoviral IAP repeat containing 3 (BIRC3), interleukin 1 beta (IL1B), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), prostaglandin-endoperoxide synthase 2 (PTGS2), PYD and CARD domain containing (PYCARD), and tumor necrosis factor (TNF)].

Conclusion: Zinc chloride inhibits HAV replication and has additive effects on the anti-HAV activities of interferon.
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http://dx.doi.org/10.21873/invivo.12168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811611PMC
September 2020

A wheeze recognition algorithm for practical implementation in children.

PLoS One 2020 8;15(10):e0240048. Epub 2020 Oct 8.

Department of Psychosomatic Medicine, Sakai Sakibana Hospital, Osaka, Japan.

Background: The detection of wheezes as an exacerbation sign is important in certain respiratory diseases. However, few highly accurate clinical methods are available for automatic detection of wheezes in children. This study aimed to develop a wheeze detection algorithm for practical implementation in children.

Methods: A wheeze recognition algorithm was developed based on wheezes features following the Computerized Respiratory Sound Analysis guidelines. Wheezes can be detected by auscultation with a stethoscope and using an automatic computerized lung sound analysis. Lung sounds were recorded for 30 s in 214 children aged 2 months to 12 years and 11 months in a pediatric consultation room. Files containing recorded lung sounds were assessed by two specialist physicians and divided into two groups: 65 were designated as "wheeze" files, and 149 were designated as "no-wheeze" files. All lung sound judgments were agreed between two specialist physicians. We compared wheeze recognition between the specialist physicians and using the wheeze recognition algorithm and calculated the sensitivity, specificity, positive predictive value, and negative predictive value for all recorded sound files to evaluate the influence of age on the wheeze detection sensitivity.

Results: The detection of wheezes was not influenced by age. In all files, wheezes were differentiated from noise using the wheeze recognition algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value of the wheeze recognition algorithm were 100%, 95.7%, 90.3%, and 100%, respectively.

Conclusions: The wheeze recognition algorithm could identify wheezes in sound files and therefore may be useful in the practical implementation of respiratory illness management at home using properly developed devices.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240048PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544038PMC
December 2020

Estimating 3-dimensional liver motion using deep learning and 2-dimensional ultrasound images.

Int J Comput Assist Radiol Surg 2020 Dec 3;15(12):1989-1995. Epub 2020 Oct 3.

Yokohama City University Medical Center, Yokohama, Japan.

Purpose: The main purpose of this study is to construct a system to track the tumor position during radiofrequency ablation (RFA) treatment. Existing tumor tracking systems are designed to track a tumor in a two-dimensional (2D) ultrasound (US) image. As a result, the three-dimensional (3D) motion of the organs cannot be accommodated and the ablation area may be lost. In this study, we propose a method for estimating the 3D movement of the liver as a preliminary system for tumor tracking. Additionally, in current 3D movement estimation systems, the motion of different structures during RFA could reduce the tumor visibility in US images. Therefore, we also aim to improve the estimation of the 3D movement of the liver by improving the liver segmentation. We propose a novel approach to estimate the relative 6-axial movement (x, y, z, roll, pitch, and yaw) between the liver and the US probe in order to estimate the overall movement of the liver.

Method: We used a convolutional neural network (CNN) to estimate the 3D displacement from two-dimensional US images. In addition, to improve the accuracy of the estimation, we introduced a segmentation map of the liver region as the input for the regression network. Specifically, we improved the extraction accuracy of the liver region by using a bi-directional convolutional LSTM U-Net with densely connected convolutions (BCDU-Net).

Results: By using BCDU-Net, the accuracy of the segmentation was dramatically improved, and as a result, the accuracy of the movement estimation was also improved. The mean absolute error for the out-of-plane direction was 0.0645 mm/frame.

Conclusion: The experimental results show the effectiveness of our novel method to identify the movement of the liver by BCDU-Net and CNN. Precise segmentation of the liver by BCDU-Net also contributes to enhancing the performance of the liver movement estimation.
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http://dx.doi.org/10.1007/s11548-020-02265-1DOI Listing
December 2020

Clinical significance of spleen stiffness in patients with acute decompensated heart failure.

ESC Heart Fail 2020 Sep 13. Epub 2020 Sep 13.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

Aims: Congestive splenomegaly is a classic sign of organ congestion in acute decompensated heart failure (ADHF). Shear wave elastography (SWE) allows the measurement of spleen stiffness (SS). We hypothesized that SS could quantify the severity of splenic congestion and predict adverse events in ADHF.

Methods And Results: This study included two cohorts: a haemodynamic cohort (62 HF patients) and an outcome cohort (115 ADHF patients). SS was measured by two-dimensional SWE on the same day of right heart catheterization in the haemodynamic cohort. Right atrial pressure (RAP) independently correlated with SS (β = 0.32, P = 0.002). SS was measured in the outcome cohort before discharge. The 115 patients were divided into three groups on the basis of the tertile value of SS. The third tertile SS group had a higher prevalence of severe tricuspid regurgitation, higher N-terminal B-type natriuretic peptide (NT pro-BNP), and larger right ventricular diastolic diameter, than had the first tertile group and the second tertile group. During a median follow-up period of 105 (77-135) days, adverse events occurred in 25 patients (one death and 24 rehospitalizations for HF). The third tertile SS group had a significantly higher rate of adverse events (P < 0.001). A higher SS was independently associated with adverse events after adjusting for conventional validated risk score, liver function test, liver stiffness, and estimated RAP.

Conclusions: The degree of SS at discharge can be used as a marker of residual splenic congestion, which is predictive of adverse events in patients with ADHF.
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http://dx.doi.org/10.1002/ehf2.13001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754734PMC
September 2020

Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease.

Int J Mol Sci 2020 Sep 2;21(17). Epub 2020 Sep 2.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.
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http://dx.doi.org/10.3390/ijms21176384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504211PMC
September 2020

Quantitative Ultrasound Image Analysis Helps in the Differentiation of Hepatocellular Carcinoma (HCC) From Borderline Lesions and Predicting the Histologic Grade of HCC and Microvascular Invasion.

J Ultrasound Med 2021 Apr 25;40(4):689-698. Epub 2020 Aug 25.

Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.

Objectives: Quantitative image analysis is one of the methods to overcome the lack of objectivity of ultrasound (US). The aim of this study was to clarify the correlation between the features from a US image analysis and the histologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and differentiation of HCC smaller than 2 cm from borderline lesions.

Methods: We retrospectively analyzed grayscale US images with histopathologic evidence of HCC or a precancerous lesion using ImageJ version 1.47 software (National Institutes of Health, Bethesda, MD).

Results: A total of 148 nodules were included (borderline lesion, n = 31; early HCC [eHCC], n = 3; well-differentiated HCC [wHCC], n = 16; moderately differentiated HCC [mHCC], n = 79; and poorly differentiated HCC [pHCC], n = 19). A multivariate analysis selected lower minimum gray values (odds ratio [OR], 0.431; P = .003) and a higher standard deviation (OR, 1.880; P = .019) as predictors of HCC smaller than 2 cm. Median (range) minimum gray values of borderline lesions, eHCC, wHCC, mHCC, and pHCC were 29 (0-103), 7 (0-47), 6 (0-60), 10 (0-53), and 2 (0-38), respectively, and gradually decreased from borderline lesions to pHCC (P < 0.001). The multivariate analysis showed a higher aspect ratio (OR, 2.170; P = .001) and lower minimum gray value (OR, 0.475; P = .043) as predictors of MVI. An anechoic area diagnosed by a subjective evaluation was correlated with the minimum gray value (P < .0001). The proportion of the anechoic area gradually increased from eHCC to pHCC (P = .031).

Conclusions: In a US image analysis, HCC smaller than 2 cm had features of greater heterogeneity and a lower minimum gray value than borderline lesions. Moderately differentiated HCC was smoother than borderline lesions, and the anechoic area correlated with histologic grading. Microvascular invasion was correlated with a slender shape and a lower minimum gray value.
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http://dx.doi.org/10.1002/jum.15439DOI Listing
April 2021

Wheeze sound characteristics are associated with nighttime sleep disturbances in younger children.

Asia Pac Allergy 2020 Jul 13;10(3):e26. Epub 2020 Jul 13.

Department of Psychosomatic Medicine, Sakai Sakibana Hospital, Sakai, Japan.

Background: Wheezing is a typical symptom of respiratory conditions. Few objective methods are available for predicting sleep disturbance in young children with wheezing.

Objective: We investigated whether wheezing characteristics, detected by lung-sound analysis, were associated with risk of sleep disturbance.

Methods: We recorded the lung sounds of 66 young children (4-59 months) every morning, for the entire duration of a wheezing episode. On lung-sound analysis, wheezing was displayed as horizontal bars of intensity with corresponding sharp peaks of power. The sharp peak of power was defined as a wheeze band. Wheezing characteristics (e.g., number, frequency, duration, and frequency of maximum intensity of wheeze bands) were analyzed using lung-sound analysis. Patients were divided into 3 groups based on sleep disturbance on the first night after wheezing was recorded: mild group (no sleep disturbance and disappearance of wheezing within 2 days), moderate group (no sleep disturbance but disappearance of wheezing after 3 or more days), and severe group (sleep disturbance and disappearance of wheezing after 3 or more days). Wheezing characteristics on the first morning were compared among the 3 groups based on sleep disturbance on the first night.

Results: The highest frequency, the frequency of maximum intensity, and the number of wheeze bands per 30 seconds were significantly higher in the severe group than in the mild group ( < 0.005, < 0.005, < 0.001, respectively). The number of wheeze bands per 30 seconds was a predictor of nighttime sleep disturbance, with a cutoff value of 11.1. The sensitivity, specificity, and positive- and negative-predictive values were 100%, 65%, 32%, and 100% ( < 0.001), respectively, with an area under the curve of 0.86 ± 0.05.

Conclusions: The number of wheeze bands per 30 seconds on lung-sound analysis was a useful indicator of risk of prolonged exacerbation.
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http://dx.doi.org/10.5415/apallergy.2020.10.e26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402944PMC
July 2020

A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X.

Int J Hematol 2020 Nov 3;112(5):621-630. Epub 2020 Aug 3.

Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Emicizumab shortens activated partial thromboplastin time (aPTT) greater than Factor (F)VIII. Clot waveform analysis triggered by ellagic acid and tissue factor trigger (Elg/TF) provided a useful means of assessing emicizumab activity. Thrombin generation assays (TGA) using this trigger reagent might also overcome the difficulties associated with aPTT by emicizumab. To compare TGA triggered by Elg/TF and other reagents (FXIa, TF) for evaluating emicizumab activity. Emicizumab, FVIII, or FVIII-bypassing agents (BPAs) were incubated with FVIII-deficient plasmas prior to TGA initiated by Elg/TF (0.2 μM/0.5 pM), FXIa (5.21 pM), or TF (PPP-Reagent LOW). Emicizumab, FVIII, or BPAs increased peak thrombin generation (peak-Th) dose-dependently using Elg/TF-trigger and the other triggers. Low responses were evident with FXIa-trigger and the enhanced effects remained below normal levels with Elg/TF-trigger. Experiments using FVIII with emicizumab demonstrated an additive effect on peak-Th using Elg/TF-trigger, and this effect appeared to be less at FVIII  ≥ 40 IU/dl. BPAs with emicizumab appeared to mediate additive effects, although its effects were variable. Parameters of thrombin generation from BPAs and emicizumab with Elg/TF-trigger were improved to normal level compared to low TF-trigger. Elg/TF-TGA could evaluate global coagulation potential during emicizumab prophylaxis including concomitant therapy with FVIII or BPAs.
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http://dx.doi.org/10.1007/s12185-020-02959-xDOI Listing
November 2020

Involvement of the Interferon Signaling Pathways in Pancreatic Cancer Cells.

Anticancer Res 2020 Aug;40(8):4445-4455

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background/aim: To examine interferon (IFN) signaling pathways in human pancreatic cancer cells and their therapeutic application for pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: We examined the effects of IFNα on cytotoxicity, migration, as well as on the levels of toll-like receptor (TLR) signaling pathway-associated genes expression in pancreatic cancer cells. We also examined the additive effects of IFNα and poly(I-C) on tyrosine kinase inhibitor (TKI)-induced cytotoxicity. We performed transcriptome analysis (RNA-Seq) of clinical samples and compared the profile between pancreatic intraepithelial neoplasias (PanINs) and PDACs.

Results: IFNα suppressed cell viability and cell migration, and affected TLR signaling pathways, in pancreatic cancer cells. TLR3 is one of the potential genes involved in IFN-treated pancreatic cancer cells. Furthermore, similar to IFN, extracellular addition of poly(I-C) enhanced TKI-induced cytotoxicity in pancreatic cancer cells. RNA-Seq analysis demonstrated that IFN signaling is one of the potential pathways involved in the progression of PanIN to PDAC.

Conclusion: IFN signaling may be involved in the development of PDAC. Treatments that target the IFN and TLR3 signaling pathways may be therapeutic options against PDAC.
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http://dx.doi.org/10.21873/anticanres.14449DOI Listing
August 2020

Analysis of bioMARKer Distribution and Individual Reproducibility Under Rivaroxaban Treatment in Japanese Patients with Non-Valvular Atrial Fibrillation (R-MARK Study, CVI ARO2).

Int Heart J 2020 Jul 18;61(4):695-704. Epub 2020 Jul 18.

Department of Cardiovascular Medicine, The Cardiovascular Institute.

The "on-therapy range" of direct oral anticoagulants is the 90% interval of drug concentration. Previously, we reported the on-therapy range of rivaroxaban in a single-center cohort. The present study aimed to confirm the range and intraindividual reproducibility in a multicenter cohort.Eligible patients with non-valvular atrial fibrillation under rivaroxaban treatment for prevention of ischemic stroke were enrolled from nine institutes in Tokyo, Japan, between June 2016 and May 2017 (n = 324). The first and second (three months later) blood samples both taken within 1-5 hours after rivaroxaban intake were analyzed (n = 219). Plasma concentration of rivaroxaban (PC-Riv) and prothrombin time (PT) with five reagents were measured.The 90% interval of PC-Riv was 47.3-532.9 ng/mL. The 90% interval of PT measured with RecombiPlasTin 2G was 11.8-22.3 seconds, the widest range among the five reagents examined. PC-Riv reproducibility within a 90% interval was evaluated bidirectionally (first-to-second and second-to-first), and 92.4% of samples were reproducible. The change rate (CR) of PC-Riv between two samplings ranged widely, and high CR (≥54.3%, cutoff for predicting non-reproducibility) was predicted by concomitant drugs (non-dihydropyridine calcium antagonist and thiazide) and mitral regurgitation.We reported the on-therapy range of rivaroxaban in a multicenter cohort. This range was consistent with that of a single-center cohort and was highly reproducible within three months in daily clinical practice. However, caution is necessary regarding several factors that may affect the intraindividual variation of PC-Riv.
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http://dx.doi.org/10.1536/ihj.20-041DOI Listing
July 2020

Noninvasive Assessment of Liver Fibrosis: Current and Future Clinical and Molecular Perspectives.

Int J Mol Sci 2020 Jul 11;21(14). Epub 2020 Jul 11.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan.

Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.
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http://dx.doi.org/10.3390/ijms21144906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402287PMC
July 2020

Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection.

Viruses 2020 05 12;12(5). Epub 2020 May 12.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.
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http://dx.doi.org/10.3390/v12050533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291253PMC
May 2020

Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines.

Int J Mol Sci 2020 May 9;21(9). Epub 2020 May 9.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-associated gene expression levels and compared these gene expression levels in each hepatoma cells treated with or without regorafenib or lenvatinib. In response to regorafenib, nine and 10 genes were upregulated in Huh7 and HepG2 cells, respectively, and only C-X-C motif chemokine ligand 10 was upregulated in both cell lines. A total of 14 and 12 genes were downregulated in Huh7 and HepG2 cells, respectively, and two genes (Fos proto-oncogene, AP-1 transcription factor subunit, and ubiquitin conjugating enzyme E2 N) were downregulated in both cell lines. In response to lenvatinib, four and 16 genes were upregulated in Huh7 and HepG2 cells, respectively, and two genes (interleukin 1 alpha and TLR4) were upregulated in both cells. Six and one genes were downregulated in Huh7 and HepG2, respectively, and no genes were downregulated in both cell lines. In summary, regorafenib and lenvatinib affect TLR signaling pathways in human hepatoma cell lines. Modulation of TLR signaling pathway may improve the treatment of HCC patients with refractory disease.
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http://dx.doi.org/10.3390/ijms21093349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246870PMC
May 2020

Crystal structure of Drosophila Piwi.

Nat Commun 2020 02 12;11(1):858. Epub 2020 Feb 12.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs), and silence transposons in animal gonads. Here, we report the crystal structure of the Drosophila PIWI-clade Argonaute Piwi in complex with endogenous piRNAs, at 2.9 Å resolution. A structural comparison of Piwi with other Argonautes highlights the PIWI-specific structural features, such as the overall domain arrangement and metal-dependent piRNA recognition. Our structural and biochemical data reveal that, unlike other Argonautes including silkworm Siwi, Piwi has a non-canonical DVDK tetrad and lacks the RNA-guided RNA cleaving slicer activity. Furthermore, we find that the Piwi mutant with the canonical DEDH catalytic tetrad exhibits the slicer activity and readily dissociates from less complementary RNA targets after the slicer-mediated cleavage, suggesting that the slicer activity could compromise the Piwi-mediated co-transcriptional silencing. We thus propose that Piwi lost the slicer activity during evolution to serve as an RNA-guided RNA-binding platform, thereby ensuring faithful co-transcriptional silencing of transposons.
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http://dx.doi.org/10.1038/s41467-020-14687-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015924PMC
February 2020

Hepatic hemangioma supplied by abnormal portal vein: A case report.

J Clin Ultrasound 2020 May 13;48(4):231-234. Epub 2019 Nov 13.

Department of Pathology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography.
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http://dx.doi.org/10.1002/jcu.22790DOI Listing
May 2020

Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus.

Int J Med Sci 2019 20;16(10):1366-1370. Epub 2019 Sep 20.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan; (T.K.).

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis including acute liver failure. Hepatitis B infection (HBV) occurs worldwide, with the highest rates in Asian and African countries, and there are several reports that HAV infection may have a more severe clinical course in patients with chronic HBV infection. We previously demonstrated that Japanese miso extracts have inhibitory effects on HAV replication. In the present study, we examined the replication of HAV and HBV in a hepatocyte superinfection model and the inhibitory effects of Japanese miso extracts on both viruses. According to the results, HAV infection inhibited HBV replication in superinfected hepatocytes, and Japanese rice-koji miso extracts had inhibitory effects on HAV replication. Our findings provide useful information for clinicians in managing HAV infection in patients with chronic HBV infection.
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http://dx.doi.org/10.7150/ijms.32795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818197PMC
April 2020

Transient Response of h-BN-Encapsulated Graphene Transistors: Signatures of Self-Heating and Hot-Carrier Trapping.

ACS Omega 2019 Feb 22;4(2):4082-4090. Epub 2019 Feb 22.

Department of Electrical Engineering and Department of Physics, University at Buffalo, the State University of New York, Buffalo, New York 14260, United States.

We use transient electrical measurements to investigate the details of self-heating and charge trapping in graphene transistors encapsulated in hexagonal boron nitride (h-BN) and operated under strongly nonequilibrium conditions. Relative to more standard devices fabricated on SiO substrates, encapsulation is shown to lead to an enhanced immunity to charge trapping, the influence of which is only apparent under the combined influence of strong gate and drain electric fields. Although the precise source of the trapping remains to be determined, one possibility is that the strong gate field may lower the barriers associated with native defects in the h-BN, allowing them to mediate the capture of energetic carriers from the graphene channel. Self-heating in these devices is identified through the observation of time-dependent variations of the current in graphene and is found to be described by a time constant consistent with expectations for nonequilibrium phonon conduction into the dielectric layers of the device. Overall, our results suggest that h-BN-encapsulated graphene devices provide an excellent system for implementations in which operation under strongly nonequilibrium conditions is desired.
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http://dx.doi.org/10.1021/acsomega.8b03259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648290PMC
February 2019

Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization.

J Ultrasound Med 2020 Mar 22;39(3):431-440. Epub 2019 Aug 22.

Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan.

Objectives: We aimed to investigate whether contrast-enhanced ultrasound (CEUS) could be useful for early evaluation of the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC).

Methods: This study retrospectively selected HCCs in which homogeneous retention of iodized oil was confirmed on non-contrast-enhanced computed tomography performed immediately after TACE. Therapeutic responses of HCCs were evaluated by CEUS 1 to 2 days after TACE and by contrast-enhanced computed tomography (CECT) approximately 4 weeks after TACE. We investigated the noninferiority of CEUS 1 to 2 days after TACE to CECT approximately 4 weeks after TACE in terms of the diagnostic accuracy of the therapeutic response to TACE on HCC.

Results: Eighty-nine HCCs were enrolled in this study between April 2014 and June 2016. A complete response was observed in 57 of 89 nodules (64.0%), and an incomplete response was observed in the remaining 32 nodules (36.0%). The accuracy rates for CEUS 1 to 2 days after TACE and CECT approximately 4 weeks after TACE in the therapeutic effect of TACE on HCCs were 83.1% (95% confidence interval, 73.7%-90.2%) and 83.1% (95% confidence interval, 73.7%-90.2%), respectively. The difference in diagnostic accuracy between methods was 0%, which was below the predetermined noninferiority limit of 15%, and CEUS 1 to 2 days after TACE was noninferior to CECT approximately 4 weeks after TACE.

Conclusions: Our results suggest that CEUS is a useful modality for early therapeutic evaluation of TACE for HCC, and we can thus plan the next treatment strategies for HCC within a few days after TACE.
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http://dx.doi.org/10.1002/jum.15118DOI Listing
March 2020

Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease.

Int J Med Sci 2019 2;16(7):909-921. Epub 2019 Jun 2.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing worldwide. Several effective drugs for these diseases are now in development and under clinical trials. It is important to reveal the mechanism of the development of NAFLD and NASH. We investigated the role of arrestin domain-containing protein 3 (ARRDC3), which is linked to obesity in men and regulates body mass, adiposity and energy expenditure, in the progression of NAFLD and NASH. We performed knockdown of endogenous ARRDC3 in human hepatocytes and examined the inflammasome-associated gene expression by real-time PCR-based array. We also examined the effect of conditioned medium from endogenous ARRDC3-knockdown-hepatocytes on the apoptosis of hepatic stellate cells. We observed that free acids enhanced the expression of ARRDC3 in hepatocytes. Knockdown of ARRDC3 could lead to the inhibition of inflammasome-associated gene expression in hepatocytes. We also observed that conditioned medium from endogenous ARRDC3-knockdown-hepatocytes enhances the apoptosis of hepatic stellate cells. ARRDC3 has a role in the progression of NAFLD and NASH and is one of the targets for the development of the effective treatment of NAFLD and NASH.
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http://dx.doi.org/10.7150/ijms.34245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643132PMC
February 2020

Rhamnogalacturonan I galactosyltransferase: Detection of enzyme activity and its hyperactivation.

Plant Physiol Biochem 2019 Sep 4;142:173-178. Epub 2019 Jul 4.

College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan; Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, Kusatsu, Shiga, 525-8577, Japan. Electronic address:

Rhamnogalacturonan I (RG-I), one of the pectic components of the plant cell wall, is composed of a backbone of repeating disaccharide units of rhamnose and galacturonic acid, and side chains, such as galactans, arabinans, and arabinogalactans. The activity of RG-I galactosyltransferase, which transfers galactosyl residues to rhamnosyl residues in the RG-I backbone, has not been detected until now. Here, we detected galactosyltransferase activity in azuki bean epicotyls using fluorogenic RG-I oligosaccharide acceptors. This enzyme prefers oligosaccharides with a degree of polymerization more than 9. The enzyme activity was detected in the Golgi apparatus, which is the site of pectin synthesis. In vitro hyperactivation of this enzyme was also observed. Moreover, enzyme activity was increased up to 40-fold in the presence of cationic surfactants or polyelectrolytes.
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http://dx.doi.org/10.1016/j.plaphy.2019.07.008DOI Listing
September 2019

C1 esterase inhibitor in pediatric cardiac surgery with cardiopulmonary bypass plays a vital role in activation of the complement system.

Heart Vessels 2020 Jan 5;35(1):46-51. Epub 2019 Jul 5.

Department of Anesthesiology, Gunma Children's Medical Center, Gunma, Japan.

Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children's Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann-Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH, and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome.
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http://dx.doi.org/10.1007/s00380-019-01466-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223185PMC
January 2020

Follow-up Results of GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC.

Anticancer Res 2019 Jul;39(7):3855-3862

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy.

Patients And Methods: In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed.

Results: The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years).

Conclusion: Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.
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http://dx.doi.org/10.21873/anticanres.13535DOI Listing
July 2019