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1.
Article in English | MEDLINE | ID: mdl-38694541

ABSTRACT

Objectives: This study aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis. Methods: The Japanese government declared a state of emergency in April 2020 due to the COVID-19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022. Results: Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0-1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single-stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups. Conclusions: Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID-19 pandemic resulted in an increase in the number of single-stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.

3.
Opt Lett ; 49(14): 3978-3981, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008755

ABSTRACT

We have newly developed, to the best of our knowledge, a detection method for broadband infrared pulses based on sum-frequency generation spectroscopy in reflection geometry, which can avoid a restriction of the detection bandwidth originating from the phase mismatch that is inevitable for the upconversion in transmission geometry. Using a GaAs crystal, we successfully demonstrated the ultra-broadband detection of the infrared pulses generated from a two-color laser-induced air plasma filament in a region from 300 to 3300 cm-1. With the advantage of ultra-short infrared pulses, the present detection method holds promise for application to time-resolved, ultra-broadband vibrational spectroscopy.

4.
J Am Med Inform Assoc ; 31(7): 1561-1568, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38758661

ABSTRACT

OBJECTIVES: Linking information on Japanese pharmaceutical products to global knowledge bases (KBs) would enhance international collaborative research and yield valuable insights. However, public access to mappings of Japanese pharmaceutical products that use international controlled vocabularies remains limited. This study mapped YJ codes to RxNorm ingredient classes, providing new insights by comparing Japanese and international drug-drug interaction (DDI) information using a case study methodology. MATERIALS AND METHODS: Tables linking YJ codes to RxNorm concepts were created using the application programming interfaces of the Kyoto Encyclopedia of Genes and Genomes and the National Library of Medicine. A comparative analysis of Japanese and international DDI information was thus performed by linking to an international DDI KB. RESULTS: There was limited agreement between the Japanese and international DDI severity classifications. Cross-tabulation of Japanese and international DDIs by severity showed that 213 combinations classified as serious DDIs by an international KB were missing from the Japanese DDI information. DISCUSSION: It is desirable that efforts be undertaken to standardize international criteria for DDIs to ensure consistency in the classification of their severity. CONCLUSION: The classification of DDI severity remains highly variable. It is imperative to augment the repository of critical DDI information, which would revalidate the utility of fostering collaborations with global KBs.


Subject(s)
Drug Interactions , Knowledge Bases , RxNorm , Japan , Humans , Vocabulary, Controlled , East Asian People
5.
Target Oncol ; 19(4): 635-644, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38807017

ABSTRACT

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment. OBJECTIVE: We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV. METHODS: We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators. RESULTS: The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV. CONCLUSIONS: The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.


Enfortumab vedotin, an antibody-drug conjugate that targets Nectin-4, is currently used for patients with metastatic urothelial carcinoma who no longer respond to checkpoint inhibitors. In the present report, we investigated which clinical indicators can predict achieving an objective response to enfortumab vedotin at the initiation of treatment. Among the blood-based putative indicators, the C-reactive protein-albumin ratio showed the highest value for predicting the treatment response to enfortumab vedotin. As the C-reactive protein-albumin ratio can be easily assessed from blood tests, physicians can consider evaluating it at the start of the EV treatment.


Subject(s)
Antibodies, Monoclonal , C-Reactive Protein , Humans , Male , Female , Aged , C-Reactive Protein/metabolism , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacology , Middle Aged , Aged, 80 and over , Neoplasm Metastasis , Carcinoma, Transitional Cell/drug therapy , Urologic Neoplasms/drug therapy , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy
6.
Article in English | MEDLINE | ID: mdl-38634347

ABSTRACT

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

7.
Target Oncol ; 19(3): 401-410, 2024 May.
Article in English | MEDLINE | ID: mdl-38546942

ABSTRACT

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. OBJECTIVE: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. PATIENTS AND METHODS: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. RESULTS: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). CONCLUSIONS: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.


Enfortumab vedotin (EV) is an antibody­drug conjugate targeting Nectin-4 and is now utilized for patients with metastatic urothelial carcinoma following treatment with checkpoint inhibitors (CPIs). Until recently, repeating chemotherapy using platinum drugs or continuing CPIs were often the treatments used for these patients. In the present study, we reported real-world treatment outcomes, mainly focusing on EV and repeating chemotherapy. Although the objective responses to the treatments were comparable, the duration of response for patients responding to the treatment was significantly longer in patients treated with EV than in those repeating chemotherapy, resulting in extended survival time with EV treatment.


Subject(s)
Antibodies, Monoclonal , Immune Checkpoint Inhibitors , Humans , Male , Female , Aged , Middle Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Aged, 80 and over , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology , Neoplasm Metastasis , Carcinoma, Transitional Cell/drug therapy , Adult , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Retrospective Studies
8.
Clin J Gastroenterol ; 17(3): 401-411, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38528198

ABSTRACT

BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Neoplasm Recurrence, Local , Radiofrequency Ablation , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Female , Aged , Retrospective Studies , Middle Aged , Chemotherapy, Adjuvant , Risk Factors , Aged, 80 and over
9.
Cells ; 13(6)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38534382

ABSTRACT

BACKGROUND: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. METHODS: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. RESULTS: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. CONCLUSIONS: Our study provides strong support for tofogliflozin in the prevention of liver cirrhosis-related PH.


Subject(s)
Benzhydryl Compounds , Endothelial Cells , Glucosides , Hypertension, Portal , Rats , Male , Animals , Endothelial Cells/pathology , Rats, Inbred F344 , Liver Cirrhosis/pathology , Hypertension, Portal/drug therapy
10.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473925

ABSTRACT

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21-3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.


Subject(s)
Venous Thrombosis , von Willebrand Factor , Humans , von Willebrand Factor/metabolism , Portal Vein/metabolism , ADAMTS13 Protein , Prognosis , Japan , Liver Cirrhosis/pathology , Venous Thrombosis/complications , Biomarkers
11.
Hepatol Res ; 54(3): 252-260, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37897705

ABSTRACT

AIM: Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are considered safe nucleoside/nucleotide analogs (NA) for the kidney. This study aimed to investigate the long-term effects of ETV or TAF on renal function in elderly patients with chronic hepatitis B (CHB) in Japan. METHODS: The study included 246 CHB patients treated with ETV (184 patients) or TAF (62 patients) for at least 2 years. These patients were divided into two groups: those <65 years of age (130 patients) and those ≥65 years of age (116 patients). The effects of the NAs on renal functions were examined by comparing the estimated glomerular filtration rates (eGFR) from baseline to 2 years between the two groups. RESULTS: The change in eGFR from baseline to 1 or 2 years after treatment was significantly decreased in both groups. However, the amount of change at 1 and 2 years was significantly greater in the group aged ≥65 years than in the group aged <65 years. The amount of change in eGFR from baseline to 1 and 2 years after treatment was significantly greater in the group aged ≥65 years than in the group aged <65 years, regardless of the type of NA, the prior treatment history, cirrhosis/chronic hepatitis, hypertension, dyslipidemia, and diabetes. Additionally, logistic regression analysis showed that age ≥65 years was independently associated with a decreased eGFR after 2 years of NA treatment. CONCLUSIONS: Long-term administration of NA to CHB patients over 65 years of age should be carefully monitored for renal impairment.

12.
Oncology ; 102(4): 291-298, 2024.
Article in English | MEDLINE | ID: mdl-37820607

ABSTRACT

INTRODUCTION: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. MATERIALS AND METHODS: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence. RESULTS: Logistic multivariate analysis showed platelet count (≤12 × 104/µL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/µL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001). CONCLUSION: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.


Subject(s)
Carcinoma, Hepatocellular , Esophageal and Gastric Varices , Liver Neoplasms , Varicose Veins , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Retrospective Studies , Esophageal and Gastric Varices/diagnostic imaging , Esophageal and Gastric Varices/etiology , Liver Cirrhosis
13.
Biochim Biophys Acta Mol Cell Res ; 1871(2): 119649, 2024 02.
Article in English | MEDLINE | ID: mdl-38097064

ABSTRACT

Sarcopenia is associated with mortality in patients with nonalcoholic steatohepatitis (NASH). Angiotensin II receptor blocker (ARB) has been suggested to prevent sarcopenia, but reports on its effect on NASH-derived skeletal muscle atrophy in conjunction with insulin-like growth factor 1 (IGF-1)-mediated muscle homeostasis are few. Our aim was to examine the combined effect of the ARB losartan and IGF-1 replacement on skeletal muscle atrophy in a methionine-choline deficient (MCD) diet-fed murine steatohepatitis model. The MCD-fed mice developed steatohepatitis and skeletal muscle atrophy, as indicated by the reduction of psoas muscle mass and attenuation of forelimb and hindlimb grip strength. Significantly suppressed steatohepatitis and skeletal muscle atrophy was observed after single treatment with ARB or IGF-1, and these effects were augmented after combination treatment. Treatment with ARB and IGF-1 effectively inhibited ubiquitin proteasome-mediated protein degradation by reducing forkhead box protein O1 (FOXO1) and FOXO3a transcriptional activity in the skeletal muscle. Combined ARB and IGF-1 decreased the intramuscular expression of proinflammatory cytokines (i.e., TNFα, IL6, and IL1ß) and increased the Trolox equivalent antioxidant capacity and antioxidant enzymes (CAT, GPX1, SOD2, and CYTB). This antioxidant effect was based on downregulation of NADPH oxidase (NOX) 2, normalization of mitochondrial biogenesis and dynamics. Moreover, ARB increased the hepatic and plasma IGF-1 levels and improved steatohepatitis, leading to enhanced skeletal muscle protein synthesis mediated by IGF-1/ AKT/ mechanistic target of rapamycin signaling. Collectively, combined ARB and IGF-1 replacement could be a promising new therapeutic target for NASH-derived skeletal muscle wasting.


Subject(s)
Non-alcoholic Fatty Liver Disease , Sarcopenia , Humans , Mice , Animals , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Sarcopenia/drug therapy , Sarcopenia/metabolism , Sarcopenia/pathology , Angiotensin II/metabolism , Angiotensin II/pharmacology , Angiotensin II/therapeutic use , Insulin-Like Peptides , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Angiotensin Receptor Antagonists/metabolism , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Antioxidants/metabolism , Angiotensin-Converting Enzyme Inhibitors/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Muscle, Skeletal/metabolism , Muscular Atrophy/drug therapy , Muscular Atrophy/metabolism , Homeostasis
14.
Nano Lett ; 24(1): 222-228, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38147363

ABSTRACT

Chirality of massless fermions emerging in condensed matter is a key to understand their characteristic behavior as well as to exploit their functionality. However, the chiral nature of massless fermions in Dirac semimetals has remained elusive, due to equivalent occupation of carriers with the opposite chirality in thermal equilibrium. Here, we show that the isospin degree of freedom, which labels the chirality of massless carriers from a crystallographic point of view, can be injected by circularly polarized light. Terahertz Faraday rotation spectroscopy successfully detects the anomalous Hall conductivity by a light-induced isospin polarization in a three-dimensional Dirac semimetal, Cd3As2. Spectral analysis of the Hall conductivity reveals a long scattering time and a long decay time, which are characteristic of the isospin. The long-lived, robust, and reversible character of the isospin promises a potential application of Dirac semimetals in future information technology.

15.
Oncology ; 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37839399

ABSTRACT

BACKGROUND AND PURPOSE: It is well known that patients with objective response to pembrolizumab have a durable duration of response leading to favorable survival outcomes. We investigated the possibility of predicting the objective response with concise indicators obtained from daily clinical practice. Methods In our multi-institutional cohort, 220 platinum-refractory metastatic urothelial carcinomas (mUC) treated with pembrolizumab for at least six weeks with complete information of objective response were investigated. Results The median follow-up was 7.3 months, and 119 patients deceased during the follow-up. A multivariate logistic regression analysis exhibited two independent variables predicting the objective response, including the neutrophil-lymphocyte ratio (NLR) change at six weeks of treatment and liver metastasis. We proposed a risk group using these two indicators. Patients with no predictive indicators / one of those were assigned to favorable (42%) / intermittent (47%) risk groups. Patients with both indicators were assigned to poor risk (11%). Notably, the objective response rate was well delineated in 41%, 25%, and 0% for favorable, intermediate, and poor risk groups, respectively (p<0.001). Distinct overall survival (OS) between the risk groups was also confirmed with the median OS of 14.1, 11.7, and 4.2 months in favorable, intermediate, and poor risk groups, respectively. CONCLUSIONS: At the six weeks of the pembrolizumab treatment, our risk model predicts the objective response rate precisely. Notably, those classified as 'poor risk'-marked by liver metastasis and a heightened NLR-should be considered for alternative therapy with a different mode of action, highlighting a critical decision point in treatment optimization.

16.
Phys Rev Lett ; 131(9): 096901, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37721840

ABSTRACT

We experimentally elucidate the origin of the anomalous Hall conductivity in a three-dimensional Dirac semimetal, Cd_{3}As_{2}, driven by circularly polarized light. Using time-resolved terahertz Faraday rotation spectroscopy, we determine the transient Hall conductivity spectrum with special attention to its sign. Our results clearly show the dominance of direct photocurrent generation assisted by the terahertz electric field. The contribution from the Floquet-Weyl nodes is found to be minor when the driving light is in resonance with interband transitions. We develop a generally applicable classification of microscopic mechanisms of light-induced anomalous Hall conductivity.

17.
Mod Rheumatol Case Rep ; 8(1): 91-94, 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-37606624

ABSTRACT

Autoimmune diseases, including dermatomyositis, can be complicated by an acquired autoimmune coagulation factor XIII deficiency, which sometimes results in fatal bleeding. Here, we report the case of a young woman with anti-NPX-2 antibody-positive dermatomyositis who developed massive haemothorax with acquired factor XIII deficiency during treatment, including plasma exchange therapy. Emergency transcatheter arterial embolisation was performed and coagulation factor XIII concentrates (Fibrogammin P® 240 U/day for 5 days) were supplemented. Subsequently, the patient was discharged and managed with oral prednisolone and tacrolimus. Coagulation system test results were followed up regularly and remained within normal limits and the patient progressed without recurrence of bleeding symptoms. Coagulation factor XIII deficiency cannot be assessed without measuring coagulation factor XIII activity because common coagulation-fibrinolytic system test results are not abnormal. The measurement of factor XIII activity should be performed when autoimmune diseases are complicated by unexplained bleeding.


Subject(s)
Autoimmune Diseases , Dermatomyositis , Factor XIII Deficiency , Female , Humans , Factor XIII Deficiency/complications , Factor XIII Deficiency/diagnosis , Factor XIII Deficiency/therapy , Factor XIII , Hemothorax/complications , Dermatomyositis/complications , Dermatomyositis/diagnosis , Dermatomyositis/therapy , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis
18.
Diagnostics (Basel) ; 13(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37443613

ABSTRACT

Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance.

20.
Phys Rev Lett ; 130(18): 186402, 2023 May 05.
Article in English | MEDLINE | ID: mdl-37204880

ABSTRACT

We study the electronic structure of the ferromagnetic spinel HgCr_{2}Se_{4} by soft-x-ray angle-resolved photoemission spectroscopy (SX-ARPES) and first-principles calculations. While a theoretical study has predicted that this material is a magnetic Weyl semimetal, SX-ARPES measurements give direct evidence for a semiconducting state in the ferromagnetic phase. Band calculations based on the density functional theory with hybrid functionals reproduce the experimentally determined band gap value, and the calculated band dispersion matches well with ARPES experiments. We conclude that the theoretical prediction of a Weyl semimetal state in HgCr_{2}Se_{4} underestimates the band gap, and this material is a ferromagnetic semiconductor.

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