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1.
Lab Med ; 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38619047

Lipids interfere with absorbance measurements conducted using colorimetric methods. To monitor lipemia, some systems measure absorbance using an analyzer. This report describes a novel case of interference with the lipemia index without lipemia. A 64-year-old woman with giant basal cell carcinoma underwent resection and sentinel lymph node biopsy. The patient had been subcutaneously injected with patent blue during sentinel lymph node resection. After surgery, her serum and urine were yellow-green, and the lipemia index, calculated by measuring absorbance at 658 nm (main wavelength) and 694 nm (secondary wavelength) using a JCA-BM8040 chemistry analyzer, was high. The absorbance spectrum of the patient's serum and patent blue solution were compared to determine the cause of the high lipemia index. The patient's serum and the patent blue solution showed absorption at wavelengths between 540 and 698 nm. Moreover, the absorbance was concentration-dependent for patent blue. These results thus indicated that the patient's serum contained patent blue. Here, we report a case wherein patent blue affected the lipemia index. Thus, it must be noted that patent blue injection may yield inaccurate results when evaluating lipemia index.

2.
Langmuir ; 40(12): 6229-6243, 2024 Mar 26.
Article En | MEDLINE | ID: mdl-38483280

The adsorption behavior of poly(methyl acrylate) (PMA)-based polymer additives and their mechanical response under fluid lubrication in narrow gaps were investigated by using neutron reflectometry, microchannel devices, and the narrow gap viscometer. The surface adsorption layer formed by the polymer additive in a stationary field that was investigated by neutron reflectometry was only about 3 nm thick. On the other hand, when the sample oil containing the polymer additive was flowed into the microchannel device with channels about 500 nm deep, the adsorption layer grew over a long period of time and eventually formed a layer that appeared to be more than 100 nm thick. The mechanical response was measured during one-directional rotation with a constant gap length by using the narrow gap viscometer. The results showed that the effective viscosity increased in the low shear rate range. The same behavior was also observed in the reciprocating rotational tests, where the mechanical response showed a distinctive distortion only when the shear rate was low near 0 rpm. The results of the neutron reflectometer, incorporating the narrow gap viscometer, showed no effect of the rotational speed with regard to the structure of the homogeneous layer over a large area. However, the discrepancy between the reflectivity profile and the fitting curve became progressively more pronounced with time, confirming the formation of inhomogeneous structures with time. It is finally suggested that the inhomogeneous structure is due to the formation of local aggregates by PMA molecules, and it acts as flow resistance only in the low shear rate, resulting in an increase in effective viscosity.

3.
Reproduction ; 167(2)2024 Feb 01.
Article En | MEDLINE | ID: mdl-38271797

After fertilization, the human sperm tail lost its fibrous sheath at the pronuclear stage to become coiled and then attached to one of the first mitotic spindle poles. The tip of the sperm tail was branched and its degree did not change from the pronuclear stage to the second mitosis.


Fertilization , Sperm Tail , Humans , Male , Semen , Spermatozoa , Mitosis
4.
Soft Matter ; 19(46): 9074-9081, 2023 Nov 29.
Article En | MEDLINE | ID: mdl-37987102

Organic-inorganic materials have been widely utilized in various fields as multifunctional materials. Poly(dimethyl siloxane) (PDMS), a typical inorganic polymer, has industrially appealing functions, such as transparency, biocompatibility, and gas permeability; however, it has poor mechanical properties. We incorporated organic-inorganic hybrid elastomers (PDMS-γCD-AAl⊃P(EA-HEMA) (x)) with movable crosslinks, and we utilized hydrogen bonds as reversible crosslinks. The organic polymer poly ethyl acrylate-r-hydroxy ethyl methacrylate (P(EA-HEMA)) penetrated the cavity of triacetylated γ-cyclodextrin (γCD), which was introduced into the side chains of PDMS, and it compounded with PDMS at the nanoscale. Structural studies involving visual and X-ray scattering measurements revealed that movable crosslinks improved the compatibility levels of PDMS and acrylate copolymers. However, macroscopic phase separation occurred when the number of reversible crosslinks increased. Furthermore, studies on the mobility levels of acrylate copolymers and movable crosslinks indicated that the relaxation behaviour of PDMS-γCD-AAl⊃P(EA-HEMA) (x) changed with changing numbers of reversible crosslinks. Introducing reversible crosslinks improved the Young's modulus and toughness values. The movable and reversible crosslinks between the organic and inorganic polymers contributed to the high elongation properties. The design of PDMS-γCD-AAl⊃P(EA-HEMA) (x) incorporated cooperatively movable and reversible crosslinks to achieve high compatibility of immiscible polymers and to control the mechanical properties.

5.
Sci Rep ; 13(1): 18268, 2023 Oct 25.
Article En | MEDLINE | ID: mdl-37880304

An operando analysis method has been established for evaluating the interfacial structure of an adsorbed layer formed by an additive on a metal surface under fluid lubricated conditions. A parallel-face narrow gap viscometer installed in an energy-resolved neutron reflectometer is used to evaluate the change in the interfacial structure under high shear. The viscometer was designed to operate at a high shear rate while maintaining a µm-order constant gap between two parallel surfaces. When an additive-free base oil was sandwiched in the gap, the neutron reflectivity profiles without and with upper surface rotation were the same. This demonstrates that the reflectivity profiles can be accurately measured regardless of whether the upper surface is rotated. When a base oil containing a polymethacrylate-based additive was sandwiched in the gap, both the thickness and density of the adsorbed additive layer in the rotation (shear field) condition were lower than those in the non-rotation (static) condition. This demonstrates that the proposed method can be used to analyse the structural changes in the adsorbed layer formed by an oil additive on a surface. This combination of a neutron reflectometer and narrow gap viscometer is a promising approach to near-future tribological studies.

6.
PLoS One ; 17(12): e0278663, 2022.
Article En | MEDLINE | ID: mdl-36455208

Selection of high-quality embryos is important to achieve successful pregnancy in assisted reproductive technology (ART). Recently, it has been debated whether RNA-sequencing (RNA-Seq) should be applied to ART to predict embryo quality. However, information on genes that can serve as markers for pregnant expectancy is limited. Furthermore, there is no information on which transcriptome of trophectoderm (TE) or inner cell mass (ICM) is more highly correlated with pregnant expectancy. Here, we performed RNA-Seq analysis of TE and ICM of human blastocysts, the pregnancy expectation of which was retrospectively determined using the clinical outcomes of 1,890 cases of frozen-thawed blastocyst transfer. We identified genes that were correlated with the expected pregnancy rate in ICM and TE, respectively, with a larger number of genes identified in TE than in ICM. Downregulated genes in the TE of blastocysts that were estimated to have lower expectation of pregnancy included tight junction-related genes such as CXADR and ATP1B1, which have been implicated in peri-implantation development. Moreover, we identified dozens of differentially expressed genes by regrouping the blastocysts based on the maternal age and the Gardner score. Additionally, we showed that aneuploidy estimation using RNA-Seq datasets does not correlate with pregnancy expectation. Thus, our study provides an expanded list of candidate genes for the prediction of pregnancy in human blastocyst embryos.


Blastocyst , Transcriptome , Female , Pregnancy , Humans , Maternal Age , Retrospective Studies , Sequence Analysis, RNA
7.
Intern Med ; 61(21): 3157-3164, 2022.
Article En | MEDLINE | ID: mdl-36328582

Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP) >400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. Results The median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Sorafenib/therapeutic use , alpha-Fetoproteins , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Prognosis , Bilirubin , Retrospective Studies , Ramucirumab
8.
Medicine (Baltimore) ; 101(40): e30871, 2022 Oct 07.
Article En | MEDLINE | ID: mdl-36221372

To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.


Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Bevacizumab/adverse effects , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Molecular Targeted Therapy , Phenylurea Compounds , Quinolines , Sorafenib/therapeutic use
9.
Aliment Pharmacol Ther ; 56(4): 713-722, 2022 08.
Article En | MEDLINE | ID: mdl-35735794

BACKGROUND: Tenofovir alafenamide (TAF) may be preferable to other nucleos(t)ide analogues (NA) regarding outcomes against chronic hepatitis B virus (HBV) infection. AIMS: To evaluate the longer term virological/biochemical effectiveness of TAF and the renal safety of sequential therapy to TAF in real-world settings METHODS: This multi-centre, retrospective cohort study included consecutive adult patients who were switched from other NAs to TAF. We assessed the virological and biochemical responses up to 144 weeks. We performed sensitivity analyses for a subgroup with chronic kidney disease (CKD) at baseline. RESULTS: We analysed the data of 391 patients with chronic hepatitis B previously treated with entecavir (ETV) (n = 174), tenofovir disoproxil fumarate (TDF) (n = 116) or an NA combination (n = 101) for ≥ 24 months. HBV DNA <10 IU/ml at week 144 was found for 99% of patients, regardless of prior NA regimen or HBV DNA level at baseline. For patients who switched from TDF to TAF, total, low-density lipoprotein, high-density lipoprotein cholesterol and triglycerides were significantly increased after the switch. Patients who switched from a nucleotide analogue to TAF had an improved estimated glomerular filtration rate, although the rate of hypophosphataemia (<2.5 mg/dl) remained 9.7% at week 144. The virological and biochemical responses of patients with CKD were similar to the overall results. CONCLUSIONS: Switching to TAF remained effective and safe for up to 3 years. Given the increasing comorbidities related to ageing, it will be important to carefully follow the change in the lipid levels of patients with a prior TDF-based regimen.


Hepatitis B, Chronic , Renal Insufficiency, Chronic , Adenine/adverse effects , Adult , Alanine/therapeutic use , Antiviral Agents/adverse effects , DNA, Viral , Hepatitis B, Chronic/drug therapy , Humans , Renal Insufficiency, Chronic/drug therapy , Retrospective Studies , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Treatment Outcome
10.
Sci Rep ; 12(1): 1473, 2022 01 27.
Article En | MEDLINE | ID: mdl-35087112

Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells because of their capacity for self-renewal. Aldehyde dehydrogenase1A1 (ALDH1A1) and CD133 are promising candidate of CSC markers in non-small cell lung cancer (NSCLC). Furthermore, TP53 is frequently mutated in lung cancer, and the loss of its function is associated with malignant characteristics. However, the relationship between CSCs and mutant p53 in lung adenocarcinoma is not well-established. We examined the expression of ALDH1A1, CD133, and mutant p53 in lung adenocarcinoma patients and conducted a clinicopathological study. Triple-negative cases without ALDH1A1, CD133, and mutant p53 expression in lung adenocarcinoma were shown to have a much better prognosis than others. Our present results suggest that detection of CSC markers and mutant p53 by immunohistochemical staining may be effective in therapeutic strategies for lung adenocarcinoma.


Adenocarcinoma of Lung/mortality , Biomarkers, Tumor/analysis , Lung Neoplasms/mortality , Lung/pathology , AC133 Antigen/analysis , AC133 Antigen/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Aged , Aldehyde Dehydrogenase 1 Family/analysis , Aldehyde Dehydrogenase 1 Family/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lung/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Mutation , Pneumonectomy , Prognosis , Retinal Dehydrogenase/analysis , Retinal Dehydrogenase/metabolism , Retrospective Studies , Risk Assessment/methods , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
11.
Hepatol Int ; 16(2): 282-293, 2022 Apr.
Article En | MEDLINE | ID: mdl-35075593

BACKGROUND AND AIMS: Outcome data of sequential hepatitis B virus treatment with tenofovir alafenamide (TAF) are limited. We aimed to assess the effectiveness and renal safety of TAF in chronic hepatitis B (CHB) patients who were previously treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or a nucleos(t)ide analogue (NA) combination. METHODS: This multicenter, retrospective, cohort study included 458 consecutive CHB patients who switched to TAF monotherapy after at least 2 years of treatment with another NA. The longitudinal virological/laboratory responses were evaluated up to 96 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. RESULTS: The proportions of complete viral suppression (CVS) (HBV DNA < 20 IU/mL) at week 96 were 99.0%, 98.5%, and 98.4% in the prior ETV (n = 198), TDF (n = 137), and NA combination (n = 123) groups, respectively. Almost all patients with HBV DNA of 20-2000 IU/mL at baseline achieved CVS at week 96. On multivariable generalized estimated equation analysis, a low quantitative hepatitis surface antigen (qHBsAg) level at baseline was associated with a lower follow-up qHBsAg level (coefficient 0.81, p < 0.001). The eGFR showed greater improvement in patients with CKD compared to those without (coefficient 21.7, p < 0.001). However, the increase of eGFR reached a peak between weeks 24 and 48. CONCLUSIONS: Based on this longitudinal data analysis up to 96 weeks, sequential NA therapy with a switch to TAF is a good option to achieve high viral suppression and renal safety.


Hepatitis B, Chronic , Renal Insufficiency, Chronic , Adenine , Alanine , Antiviral Agents/therapeutic use , Cohort Studies , DNA, Viral , Female , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Male , Retrospective Studies , Tenofovir/analogs & derivatives , Treatment Outcome
12.
J Gastroenterol Hepatol ; 37(2): 371-377, 2022 Feb.
Article En | MEDLINE | ID: mdl-34618379

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long-term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. METHODS: This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon-free DAA treatment before September 2016. The impact of treatment on long-term hepatic function was followed for at least 4 years after the end of treatment, and the progression to decompensation was evaluated. RESULTS: The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin-bilirubin (ALBI) grade 2b. During a short-term follow-up 1 year after the end of treatment, FIB-4 index and ALBI score significantly improved. The achievement rates of FIB-4 < 3.25 (40%) and ALBI grade 1 (70%) reached their plateau in the first year; however, there were significant further improvements in platelet count and α-fetoprotein level after the first year. The annual incidence of decompensation was 1.30 (95% confidence interval 0.83-2.02) per 100 person-years. In multivariable analysis, male sex and modified ALBI grade 2b at baseline were associated with decompensation. CONCLUSIONS: In a large real-world cohort of patients with compensated cirrhosis treated with a DAA, remarkable improvement in hepatic function was seen after HCV cure, especially during the first year after the end of treatment. Treatment in the early stage of cirrhosis would be of great benefit for preventing liver deterioration to decompensation.


Antiviral Agents , Hepatitis C , Liver Cirrhosis , Aged , Antiviral Agents/therapeutic use , Cohort Studies , Female , Hepatitis C/drug therapy , Humans , Liver Cirrhosis/drug therapy , Liver Cirrhosis/physiopathology , Male , Treatment Outcome
13.
J Gastroenterol Hepatol ; 37(1): 190-199, 2022 Jan.
Article En | MEDLINE | ID: mdl-34374128

BACKGROUND AND AIM: Early hepatocellular carcinoma (HCC) recurrence is common, even after achieving hepatitis C virus (HCV) cure. This study was carried out to assess the long-term trends and predictors of recurrence after HCV cure by direct-acting antivirals (DAAs). METHODS: This retrospective, multicenter cohort study enrolled 365 consecutive patients with chronic hepatitis C who required HCC treatment following sustained viral response (SVR) by DAA administration. Patients with HCC recurrence before SVR were excluded. Late HCC recurrence and its predictors beyond the post-treatment early phase (24 weeks after SVR) were evaluated. RESULTS: The data of 326 patients were available for the final analysis. The median follow-up duration from SVR determination was 2.7 years. Median age was 74, and 220 (67.5%) were 70 or over. The corresponding 5-year cumulative HCC recurrence rates of previous curative and palliative treatment groups were 45.4% and 65.7%, respectively (log-rank test: P < 0.001). Cox regression multivariable analysis revealed that cirrhosis (hazard ratio [HR] 1.85, P = 0.021), the number of HCC nodules (≥ 2) (HR 1.52, P = 0.031), and previous palliative HCC treatment (HR 1.71, P = 0.012) were independent predictors of late recurrence, in addition to the predictors of early recurrence; AFP > 7 ng/mL at 12 weeks after DAA administration, time from HCC complete response (CR) to DAA initiation (< 1 year), and the number of HCC treatments necessary to achieve CR (≥ 2). CONCLUSIONS: The evaluation of fibrosis and characteristics of the previous HCC would allow for better HCC recurrence stratification, which would be helpful for developing long-term surveillance strategies.


Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Liver Neoplasms/pathology , Liver Neoplasms/virology , Recurrence , Retrospective Studies , Sustained Virologic Response , Treatment Outcome
14.
Infect Dis Rep ; 13(3): 742-747, 2021 Aug 24.
Article En | MEDLINE | ID: mdl-34449650

The rapid detection of SARS-CoV-2 is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) can yield results more quickly than PCR. We evaluated the performance of ICA and CLEIA using 34 frozen PCR-positive (17 saliva samples and 17 nasopharyngeal swabs [NPS]) and 309 PCR-negative samples. ICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity rates of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with a positivity of 82% in saliva and 100% in NPS. These results suggest that the use of ICA should be limited to an earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.

15.
Reprod Med Biol ; 20(3): 260-266, 2021 Jul.
Article En | MEDLINE | ID: mdl-34262393

PURPOSE: Although giant oocytes (GOs) having about twice cytoplasmic volume compared with general oocytes in mammals including the human are rarely recovered, it is thought that GOs have potentially chromosomal abnormalities. The aim of the present study was to assess chromosome numbers in chromosome-spindle complexes (CSCs) and polar bodies of human GOs by using micromanipulation for sampling and next-generation sequencing (NGS) for analyses of the chromosome numbers. METHODS: When recovered oocytes whose cytoplasm has lager than 140 µm or above, the oocytes were defined as GOs, and recovered GOs were vitrified. After warming, the CSCs, polar bodies, and enucleated cytoplasm were collected by micromanipulation from 3 GOs. The collected samples were analyzed by NGS. RESULTS: Chromosomal aneuploidy in the GOs was confirmed in all the three GOs. Comparing the CSCs with the chromosomes from polar bodies, the deletion and overlapping chromosome numbers were complementary in each GO. CONCLUSIONS: The authors could collect the CSCs and the polar bodies from human GOs by micromanipulation, and then could analyze the chromosome numbers of the GOs by NGS method. As our data suggest that human GOs have chromosomal abnormalities, GOs should be excluded from clinical purpose as gamete sources for embryo transfer in the human.

16.
Reproduction ; 161(5): V19-V22, 2021 05.
Article En | MEDLINE | ID: mdl-33843613

Unlike in mice, multinucleated blastomeres appear at a high frequency in the two-cell-stage embryos in humans. In this Point of View article, we demonstrate that the first mitotic spindle formation led by sperm centrosome-dependent microtubule organizing centers may cause a high incidence of zygotic division errors using human tripronuclear zygotes.


Centrosome/physiology , Microtubule-Organizing Center/physiology , Spermatozoa/physiology , Spindle Apparatus/physiology , Zygote/physiology , Humans , Male
17.
J Surg Case Rep ; 2021(4): rjab156, 2021 Apr.
Article En | MEDLINE | ID: mdl-33927880

Paraneoplastic limbic encephalitis (PLE) is one of paraneoplastic neurological syndrome (PNS). We herein report a case of PLE due to lung squamous cell carcinoma. A 80-year-old woman visited because of several neurological symptoms. Brain magnetic resonance imaging revealed hyperintense signals at the splenium of the corpus callosum, suggesting limbic encephalitis. Chest X-ray and computed tomography showed a 17 × 14 mm tumor in the left lung field, suggesting lung cancer. Surgical examination revealed T1bN0M0 lung squamous cell carcinoma. She died 50 days after surgery due to the rapid progression of encephalitis. PLE is an extremely rare disorder, and even a case in the early stage of cancer shows poor prognosis. We should doubt a possibility of PLE, and detailed brain examination should be performed in case of consciousness disorder with rapid progression in the cancer patient.

18.
Anticancer Res ; 41(2): 905-910, 2021 Feb.
Article En | MEDLINE | ID: mdl-33517296

BACKGROUND/AIM: CD133 is a promising candidate marker for cancer stem cells. However, clinical studies on CD133 expression in human lung adenocarcinoma have not yet been conducted. We hypothesized that CD133 expression in lung adenocarcinoma is a poor prognostic factor. PATIENTS AND METHODS: CD133 expression in lung adenocarcinoma was examined clinicopathologically. Then, clinicopathological parameters and patient prognosis were investigated. Moreover, CD133 expression was examined via immunohistochemical staining, and the relationship between CD133 expression and clinicopathological parameters was explored. RESULTS: Approximately 48.0% (49/102) of patients had CD133-positive cells. Based on a subgroup analysis, the CD133-positive group with pStage I+II disease had a significantly worse disease-free interval than the CD133-negative group (p<0.05). CONCLUSION: CD133 expression may be a poor prognostic factor in lung adenocarcinoma.


AC133 Antigen/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/metabolism , Lung Neoplasms/pathology , Up-Regulation , Adenocarcinoma of Lung/metabolism , Adult , Aged , Aged, 80 and over , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/metabolism , Male , Middle Aged , Neoplasm Staging , Neoplastic Stem Cells/metabolism , Prognosis , Survival Analysis
19.
JGH Open ; 5(1): 34-40, 2021 Jan.
Article En | MEDLINE | ID: mdl-33490611

BACKGROUND AND AIM: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. METHODS: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. RESULTS: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. CONCLUSIONS: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV.

20.
Infect Dis Ther ; 9(4): 851-866, 2020 Dec.
Article En | MEDLINE | ID: mdl-32897520

INTRODUCTION: Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. RESULTS: The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child-Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5-13). The albumin-bilirubin (ALBI) score ranged from - 3.01 to - 0.45 (median - 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child-Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child-Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10-4 and 2.42 × 10-4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. CONCLUSION: Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. TRIAL REGISTRATION: UMIN registration no, 000038587.

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