Hepatitis C virus eradication ameliorates the prognosis of advanced hepatocellular carcinoma treated with sorafenib.

The risk of hepatocellular carcinoma (HCC) occurrence following hepatitis C virus (HCV) eradication has been previously reported, but the impact of HCV eradication on advanced HCC patient survival remains unclear. Therefore, the present study aimed to evaluate the effect of HCV eradication on the survival outcome of patients with advanced HCC treated with sorafenib. One hundred and three HCV-related advanced HCC patients who were treated with sorafenib were enrolled in this study. Of these, 43 patients were administered antiviral therapy before sorafenib treatment (HCV eradication group), while 60 patients remained HCV-infected (HCV non-eradication group). We analysed the impact of HCV eradication on survival in advanced HCC treated with sorafenib. Median overall survival (OS) was significantly longer in the HCV eradication group than in the HCV non-eradication group (24.0 months vs. 14.1 months; p = 0.001). Although there was no significant difference in the albumin-bilirubin (ALBI) score at the start of treatment between the HCV eradication group and the non-eradication group (p = 0.065), the ALBI score at 2 months after initiation of sorafenib treatment was significantly decreased in the HCV non-eradication group (p < 0.001), but not in the HCV eradication group (p = 0.121). Multivariate logistic analysis revealed HCV eradication (hazard ratio [HR], 0.5; p = 0.006) and ALBI score at the start of treatment (HR, 2.47; p = 0.002) as factors that may contribute to OS. HCV eradication may serve an important role in the survival outcome of advanced HCC patients treated with sorafenib.

Serum α-fetoprotein level at treatment completion is a useful predictor of hepatocellular carcinoma occurrence more than one year after hepatitis C virus eradication by direct-acting antiviral treatment.

Direct-acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved liver function of HCV patients. The risk of hepatocellular carcinoma (HCC) occurrence following HCV eradication has been previously reported, but HCC may have been missed following imaging diagnosis before DAA administration in previous studies. Therefore, the present study aimed to identify definite predictors of HCC occurrence ≥1 year after DAA treatment. Among 956 patients receiving DAAs for HCV infection, 567 patients who achieved sustained virologic response with no history of HCC treatment were enrolled in this study between September 2014 and July 2021. The incidence of HCC in HCV-infected patients ≥1 year following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinical characteristics and blood test results. In the present study, 25 patients developed HCC. The incidence of HCC was 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from the end of treatment with DAAs. Multivariate logistic analysis revealed serum α-fetoprotein level at end of treatment (EOT-AFP) >3.8 ng/ml ≥1 year following treatment with DAAs (HR, 9.7; p < .0001) as an independent factor that may contribute to HCC occurrence following DAA treatment. In conclusion, serum EOT-AFP level may serve an important role in determining the risk of HCC occurrence ≥1 year after DAA treatment. Regular examinations are required even if serum EOT-AFP level is low at treatment completion.

Acute Perimyocarditis in an Adolescent Japanese Male after a Booster Dose of the BNT162b2 COVID-19 Vaccine.

Perimyocarditis is a rare and serious cardiac complication following COVID-19 vaccination. Young males are most at risk after the second dose. With the introduction of the booster (third) dose, some reports have focused on the risk of perimyocarditis after a booster dose. However, no currently available report in Japan has comprehensively described this phenomenon. A healthy 14-year-old Japanese male, who had completed a two-dose primary series of the BNT162b2 (Pfizer-BioNTech) vaccine six months prior, developed fever and chest pain within 24 hours after a homologous booster dose. He was transferred to our institute because of worsening chest pain. A multiplex PCR test showed no evidence of active viral infections, including SARS-CoV-2. Electrocardiography revealed ST-segment elevation in almost all leads, suggesting pericarditis. Echocardiography showed normal systolic function. Laboratory data demonstrated C-reactive protein levels of 8.8 mg/dL and elevated cardiac damage markers (troponin T, 1.9 ng/mL; creatine phosphokinase, 1527 U/L; MB isoenzyme, 120 U/L), suggesting myocarditis. He was diagnosed with perimyocarditis associated with the booster dose, which was confirmed by cardiac magnetic resonance imaging four days after initial symptoms. Chest pain improved spontaneously along with a resolution of electrocardiographic findings and laboratory data within several days. He was discharged eight days after admission. Perimyocarditis is less frequent after a booster dose than after primary doses. In this case, the patient with booster-dose-associated perimyocarditis showed favorable clinical course without severe sequelae. The patient's clinical course was consistent with findings on previous large-scale reports on primary-dose-associated perimyocarditis and case series on booster-dose-associated perimyocarditis.

Occurrence of Torsade de Pointes prior to complete lead connection during pacemaker implantation.

Torsade de Pointes (TdP) can be triggered by a pacing spike on the T-wave, due to pacemaker undersensing. However, it is not widely known that this phenomenon can occur even during pacemaker implantation. An 84-year-old woman underwent pacemaker implantation for the treatment of a complete atrioventricular block with dyspnea. During the procedure, immediately following ventricular lead insertion and before torque wrench tightening, TdP was observed. Ventricular pacing was initiated by inserting the lead into the header of the generator; however, sensing remained unstable. T-waves associated with undersensed PVCs and ventricular pacing occurred simultaneously, resulting in a spike on the T-wave and TdP.

[A case of multiple osteonecrosis caused by acute-on-chronic pancreatitis].

A 61-year-old man was admitted due to alcoholic liver cirrhosis, portal vein thrombosis, hepatocellular carcinoma, and chronic pancreatitis. The patient's portal vein thrombosis improved with anticoagulant therapy. Serum amylase gradually increased, but there was no abdominal pain. The patient was placed under observation. The pain in both ankle and knee joints appeared on nine days after admission. Multiple osteonecrotic lesions of both elbows, both knees and both ankle joints were examined using 99mTc bone scintigraphic examinations. Magnetic resonance of the right ankle joint showed osteonecrosis. The pain of the right ankle joint improved with a decrease of serum amylase. We report that this is a rare case of multiple osteonecrosis caused by exacerbation of chronic pancreatitis.

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides.

The stereoselective cyanoalkylation of electron-deficient olefins with potassium cyanide and alkyl halides was developed based on the utilization of modular chiral 1,2,3-triazolium salts featuring a hydrogen bond-donor ability as catalysts. The reaction involving multiple carbon-carbon bond formations proceeds via the enantioselective conjugate addition of a cyanide ion and the consecutive catalyst-controlled diastereoselective alkylation of intermediary chiral triazolium enolates. Control experiments revealed that the use of a properly tuned chiral triazolium ion as a catalyst and the presence of the cyano functionality in the intermediary enolate are of crucial importance for achieving high levels of acyclic absolute and relative stereocontrol.

Papillary muscle rupture after transcatheter aortic valve implantation.

Catheter-induced mitral regurgitation (MR) caused by mitral papillary muscle rupture can be a fatal complication of transcatheter aortic valve implantation (TAVI). We report a case involving an 89-year-old man who presented with symptomatic severe aortic stenosis. In addition, preoperative echocardiography showed accessory mitral valve tissue. Although moderate MR developed immediately after TAVI, severe MR caused by anterolateral papillary muscle rupture occurred 3 months after TAVI. As only a few case series have been published, our case report adds to the evidence base for this treatment strategy.

Coil Embolization for Coronary Artery Perforation: A Retrospective Analysis of 110 Patients.

OBJECTIVE: Coil embolization (CE) for coronary artery perforation (CAP) has not been thoroughly evaluated. This study aimed to evaluate the extent of myocardial damage and impact on cardiac function after CE for CAP. METHODS: A total of 110 consecutive patients treated with CE for CAP were retrospectively identified. The degree of myocardial damage and impact on cardiac function were evaluated. RESULTS: Forty-nine (44.5%) cases involved chronic total occlusions. A guidewire was the cause of perforation in 97 (88.2%) patients. The success rate of CE was 98.2%. Almost all patients were prescribed either antiplatelet drugs or anticoagulant medication or both. Patients with perforation types III and IV were found to be prone to creatinine kinase (CK) elevation and epicardial main vessel perforation, thereby causing myocardial damage. No changes were noted in the ejection fraction (EF) in patients with type V distal perforation and collateral channel perforation, while patients with perforation of the epicardial main vessel may show impaired cardiac function afterward. CONCLUSIONS: CE is safe and effective for treating CAP, especially when collateral channels and distal vessels are involved. Meanwhile, efforts should be taken to prevent CAP in epicardial main vessels since it may be difficult to treat with CS and cause myocardial damage when bailed out with CE leading to vessel sacrifice. We found that it was not necessary to change the anticoagulant regimen after CE owing to its ability to achieve robust hemostasis.

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus on weekdays.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P < 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.

Clinical effectiveness and adverse events associated with tolvaptan in patients above 90 years of age with acute decompensated heart failure.

With the aging society, the number of very-elderly (VE) patients with acute decompensated heart failure (ADHF) is increasing. Although tolvaptan is recommended for patients with ADHF in whom conventional diuretic therapy is ineffective, few reports exist on VE patients over 90 years of age. Therefore, we aimed to evaluate the clinical effectiveness and adverse events associated with tolvaptan in VE patients with ADHF. From January 2011 to December 2018, we retrospectively studied 180 patients with ADHF who were first administered tolvaptan during hospitalization. Patients were divided into two groups, namely, VE patients who were ≥ 90 years of age (n = 32) and not-VE patients (NVE) who were < 90 years of age (n = 148). The primary effective endpoints were the total urine volume and change in body weight. The safety endpoints evaluated were the incidence of hypernatremia (≥ 150 mEq/L) and worsening renal function (WRF) at any time during hospitalization. The median [interquartile range] patient age was 93 [91-94] years in the VE group and 80 [69-85] years in the NVE group. The mean dose of tolvaptan for the first week of administration was similar between groups (7.9 ± 5.0 mg, VE group; 7.3 ± 3.7 mg, NVE group; p = 0.52). There were no significant differences between the two groups in the total urine volume at 24 h (1901 ± 666 mL, VE group; 2101 ± 1167 mL, NVE group; p = 0.33) and that at 48 h (3707 ± 1274 mL, VE group; 4195 ± 1990 mL, NVE group; p = 0.19) and in the mean change in body weight (- 2.5 ± 2.0 kg, VE group; -2.7 ± 2.4 kg, NVE group; p = 0.70). The median duration of hospitalization was 24 [20-9] and 31 [20-42] days in the VE and NVE groups, respectively (p = 0.67). The incidence of hypernatremia (6.3% (2/32), VE group; 3.4% (5/148), NVE group; p = 0.61) and WRF (25.0% (8/32) VE group; 19.6% (29/148), NVE group; p = 0.31) was similar between the groups. In conclusion, tolvaptan has similar clinical effectiveness in increasing urine volume and decreasing body weight, without increased adverse events, in VE patients with ADHF who were ≥ 90 years of age compared to NVE patients with ADHF.

Computational Prediction of Compound-Protein Interactions for Orphan Targets Using CGBVS.

A variety of Artificial Intelligence (AI)-based (Machine Learning) techniques have been developed with regard to in silico prediction of Compound-Protein interactions (CPI)-one of which is a technique we refer to as chemical genomics-based virtual screening (CGBVS). Prediction calculations done via pairwise kernel-based support vector machine (SVM) is the main feature of CGBVS which gives high prediction accuracy, with simple implementation and easy handling. We studied whether the CGBVS technique can identify ligands for targets without ligand information (orphan targets) using data from G protein-coupled receptor (GPCR) families. As the validation method, we tested whether the ligand prediction was correct for a virtual orphan GPCR in which all ligand information for one selected target was omitted from the training data. We have specifically expressed the results of this study as applicability index and developed a method to determine whether CGBVS can be used to predict GPCR ligands. Validation results showed that the prediction accuracy of each GPCR differed greatly, but models using Multiple Sequence Alignment (MSA) as the protein descriptor performed well in terms of overall prediction accuracy. We also discovered that the effect of the type compound descriptors on the prediction accuracy was less significant than that of the type of protein descriptors used. Furthermore, we found that the accuracy of the ligand prediction depends on the amount of ligand information with regard to GPCRs related to the target. Additionally, the prediction accuracy tends to be high if a large amount of ligand information for related proteins is used in the training.

[A case of pembrolizumab-induced sclerosing cholangitis that was responsive to high-dose steroid therapy].

An 80-year-old woman was treated with pembrolizumab for non-small cell lung carcinoma. The hepatobiliary enzymes of the patient were elevated before the start of the ninth treatment cycle. The patient was diagnosed with pembrolizumab-induced sclerosing cholangitis based on magnetic resonance cholangiopancreatography and liver biopsy. Liver dysfunction improved with steroid therapy, and hepatobiliary enzymes increased again. The patient was treated with methylprednisolone (1000mg/day for 3 days) followed by oral prednisolone (1mg/kg/day). The patient's hepatobiliary enzymes subsequently decreased, and the oral prednisolone was tapered. Another liver biopsy, which showed a decrease in the hepatic CD8+ T cell count, was performed. Liver dysfunction did not recur although steroid therapy was discontinued after 1 year of administration.

The Effectiveness of Target Low-Density Lipoprotein Cholesterol Achieved with Strict Management in Secondary Prevention of Long-Term Coronary Events in Japanese Patients.

BACKGROUND: In the secondary prevention of long-term coronary events, a target value of low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL is recommended as standard management in Japanese guidelines. However, the effectiveness of strict management on lowering LDL-C remains unclear. OBJECTIVES: To clarify whether strict management of LDL-C < 70 mg/dL is more effective in preventing long-term coronary event recurrence than standard management. METHODS: We retrospectively investigated 344 patients with previous percutaneous coronary interventions who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early restenosis period from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C < 70 mg/dL (n = 53), 70 to < 100 mg/dL (n = 130), and ≥ 100 mg/dL (n = 161). Endpoints were acute coronary syndrome (recurrent-ACS) and late coronary revascularization. RESULTS: After follow-up (median 6.0 years), 200 patients (58%) underwent late coronary revascularization, including 94 recurrent-ACS. The incidence of recurrent-ACS was significantly lower in the patients who achieved LDL-C < 70 mg/dL than in those with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.009 and p = 0.001, respectively). There was no significant difference between the patients with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.140). There was also no significant difference in late revascularization between the patients with LDL-C < 70 mg/dL and LDL-C 70 to < 100 mg/dL. In patients with LDL-C < 100 mg/dL (n = 183), LDL-C [hazard ratio (HR) 1.035, p = 0.007] and HbA1c (HR 1.338, p = 0.001) were independently associated with recurrent-ACS. CONCLUSIONS: In Japanese patients, LDL-C was a residual risk for recurrent-ACS even after recommended standard LDL-C lowering management target values had been achieved.

Association with left atrial volume index and long-term prognosis in patients without systolic dysfunction nor atrial fibrillation: an observational study.

The prognostic impact of left atrial size in patients without systolic dysfunction nor atrial fibrillation (AF) has not been fully elucidated in Japan. We retrospectively analyzed data obtained from 4444 consecutive patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in our hospital. Those who presented with a history of myocardial infarctions, severe and moderate valvular diseases, low ejection fraction (< 50%), and documented AF, and without data on LA volume index (LAVI) or tissue Doppler early diastolic mitral annular velocity were excluded. We defined high LAVI as a value > 34 ml/m2. The primary outcome measure was a composite of all-cause death and major adverse cardiac events. A total of 2792 patients were categorized into two groups: 2627 with normal LAVI (94.1%), 165 with high LAVI (5.9%). The median age of patients in the normal and high LAVI groups were 67, and 77 years, respectively (p < 0.001). Prevalence of diabetes mellitus, hypertension, and chronic kidney disease, and left ventricular mass index was higher in the high-LAVI group than normal-LAVI group. After adjusting for confounders, the excess 3-year risk of primary outcome of high-LAVI related to normal-LAVI was significant (hazard ratio 1.44; 95% confidence interval 1.03-1.97, p = 0.032). High-LAVI should be considered a marker of a worse long-term follow-up in patients without systolic dysfunction nor AF.

[A case of hepatic toxocariasis in a patient with hepatitis B].

A 49-year-old man with chronic hepatitis B receiving treatment with entecavir visited a hospital with a complaint of abdominal pain. Computed tomography (CT) showed 2 liver tumors, each measuring 1cm in diameter, 1 in segment 7 and 1 in segment 4. Magnetic resonance imaging (MRI) showed a hypervascular tumor in segment 7 that appeared in a site different from that seen on CT. The liver tumor in segment 4 was not detected by MRI. Two months later, MRI showed a new liver tumor in segment 7/6 and that the liver tumor in segment 7 had increased to 2cm in diameter;blood tests showed eosinophilia. Enzyme-linked immunosorbent assay showed a high serum Toxocara antibody. The patient was diagnosed as having hepatic toxocariasis and was treated with albendazole for 8 weeks. After treatment, MRI showed that the liver tumors disappeared. Eosinophilia, multiple lesions, and the disappearance of the tumors were characteristic findings of visceral larva migrans.

Age- and Body Size-Adjusted Left Ventricular End-Diastolic Dimension in a Japanese Hospital-Based Population.

BACKGROUND: Using the normal values for the East Asian population, we evaluated age- and body size-adjusted left ventricular end-diastolic dimension (LVEDD) and its prognostic impact in a hospital-based population in Japan. Methods and Results: We retrospectively analyzed data obtained from 4,444 consecutive patients who had undergone both transthoracic echocardiography and electrocardiography at Kitano Hospital in 2013. Those who presented with a history of previous episodes of myocardial infarction and severe or moderate valvular disease or with low ejection fraction (<50%) were excluded from the analysis. We calculated LVEDD adjusted by age and body surface area. A total of 3,474 patients were categorized into 3 groups: 401 with large adjusted LVEDD, 2,829 with normal adjusted LVEDD, and 244 with small adjusted LVEDD. Mean patient age in the large, normal, and small adjusted LVEDD groups was 66.6±18.4, 65.6±15.7, and 62.1±15.5 years, respectively (P<0.001). After adjusting for confounding factors, the excess adjusted 3-year risk of primary outcome of large adjusted LVEDD relative to normal LVEDD was significant (HR, 1.40; 95% CI: 1.08-1.78). The risk for primary outcomes of small adjusted LVEDD relative to normal adjusted LVEDD was significantly lower (HR, 0.55; 95% CI: 0.34-0.85). CONCLUSIONS: Adjusted large LVEDD has a deleterious impact on long-term mortality, whereas small LVEDD carried a significantly lower risk.

Enlargement of Deinococcus grandis spheroplasts requires Mg2+ or Ca2.

While the cell wall strictly controls cell size and morphology in bacteria, spheroplasts lack cell walls and can become enlarged in growth medium under optimal conditions. Optimal conditions depend on the bacterial species. We frequently observed extreme enlargement of spheroplasts of the radiation-resistant bacterium Deinococcus grandis in Difco Marine Broth 2216, but not in TGY broth (a commonly used growth medium for Deinococcus). Thorough investigation of media components showed that the presence of Mg2+ or Ca2+ promoted extreme spheroplast enlargement, synthesizing the outer membrane. Our findings strongly suggest that Mg2+ or Ca2+ enlarges spheroplasts, which could change the lipid composition of the spheroplast membrane.

ZrO2 Nanocrystals As Catalyst for Synthesis of Dimethylcarbonate from Methanol and Carbon Dioxide: Catalytic Activity and Elucidation of Active Sites.

The catalytic activity of zirconium oxide (ZrO2) nanocrystals for the reaction of carbon dioxide (CO2) with methanol to form dimethylcarbonate (DMC) was investigated. ZrO2 nanocrystals prepared by hydrothermal synthesis at various temperatures were compared. The size of the ZrO2 nanocrystals monotonically increased with the hydrothermal temperature, according to specific surface area, transmission electron microscope measurements, and their X-ray diffraction peak widths. The ZrO2 nanocrystals prepared by hydrothermal synthesis were found to exhibit high catalytic activity owing to their high surface area and catalytically active surfaces arising from their high crystallinity. Next, adsorbed species generated from CO2 on the ZrO2 surfaces were measured using CO2 temperature-programmed desorption (TPD) and in situ FT-IR spectroscopy. The results confirmed the presence of several kinds of adsorbed species including bidentate bicarbonate (b-HCO3-), bidentate carbonate (b-CO32-), and monodentate carbonate (m-CO32-). The relationship between the amounts of these surface species and the catalytic activity of the ZrO2 was investigated for the first time. The amount of the bidentate species (b-HCO3- and b-CO32-) was found to correlate well with the catalytic activity, demonstrating that the surface sites that afford these species contribute to the catalytic activity for this reaction.

The Accuracy of a Large V Wave in the Pulmonary Capillary Wedge Pressure Waveform for Diagnosing Current Mitral Regurgitation.

BACKGROUND: Large V waves in the pulmonary capillary wedge pressure (PCWP) waveform traditionally indicate severe mitral regurgitation (MR). However, our understanding of MR etiology and hemodynamics has changed in recent decades. OBJECTIVES: We aimed to reevaluate the association between large V waves and current MR to determine whether traditional large V wave criteria remain optimal. METHOD: We reviewed 1,964 right heart catheterizations (RHCs) performed at our institution from 2010 to 2017, and retrospectively selected 126 patients with sinus rhythm who underwent echocardiography within 2 days (0.3 ± 0.5 days) of the RHC. The diagnostic accuracy of 3 traditional criteria for large V waves was assessed, and the optimal cut-off points were determined as those with the maximal Youden indices. RESULTS: Severe MR was observed on echocardiography in 26 (21%) patients, including 15 (58%) with Carpentier classification type II MR and 11 (42%) with type IIIB MR. Large V waves, defined as a difference between the peak V wave and mean PCWP ≥10 mm Hg, had a high specificity of 94% (95% confidence interval: 87-98%), but a low sensitivity of 27% (12-48%) for diagnosing severe MR. The optimal cut-off point for the V wave was 3 mm Hg above the mean PCWP, with a sensitivity of 73% (52-88%) and a specificity of 64% (54-73%). CONCLUSIONS: For diagnosing current MR, the cut-off point for a large V wave should be reduced from that previously employed for rheumatic valvular heart disease. This information may be useful in guiding contemporary transcatheter therapies for MR under RHC monitoring.

Effect of epigallocatechin-3-o-gallate and quercetin on the cryopreservation of cartilage tissue.

The effects of epigallocatechin-3-o-gallate (EGCG) and quercetin on the contents of extracellular matrix (ECM) in porcine cartilage at 4 °C were investigated. The addition of quercetin at 0.01 mM for the incubation of porcine cartilage disks at 4 °C for 2 week could suppress the decrease in ECM and the compliance of the disks, markedly greater than those of EGCG (1.0 mM).