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3.
Neurosci Lett ; 755: 135907, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33887382

RESUMO

Corticospinal excitability in humans can be facilitated during imagination and/or observation of upper-limb motor tasks. However, it remains unclear to what extent facilitation levels may differ from those elicited during execution of the same tasks. Twelve able-bodied individuals were recruited in this study. Motor evoked potentials (MEPs) in extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles were elicited through transcranial magnetic stimulation of the primary motor cortex during: (i) rest; (ii) wrist extension; and (iii) wrist flexion. Responses were compared between: (1) motor imagery combined with virtual action observation (MI + AO; first-person virtual wrist movements shown on a computer display, while participants remained at rest and imagined these movements); and (2) motor execution (ME; participants extended or flexed their wrist). During MI + AO, ECR MEPs were facilitated during the extension phase but not the flexion phase, while FCR MEPs were facilitated during the flexion phase but not extension phase, compared to rest. During the ME condition, same, but greater, modulations were shown as those during MI + AO, while background muscle activities were similar in the rest phase as during extension and flexion phase in the MI + AO condition. Our results demonstrated that kinesthetic MI that included imagination and observation of virtual hands can elicit phase-dependent muscles-specific corticospinal facilitation of wrist muscles, consistent to those during actual hand extension and flexion. Moreover, we showed that MI + AO can contribute considerably to the overall corticospinal facilitation (∼20 % of ME) even without muscle contractions. These findings support utility of computer graphics-based motor imagery, which may have implications for rehabilitation and development of brain-computer interfaces.

4.
BMC Gastroenterol ; 21(1): 189, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892649

RESUMO

BACKGROUND: Hepatitis C virus is the leading cause of liver cirrhosis and hepatocellular carcinoma in Japan. We aimed to examine the long-term (> 20 years) mortality and hepatocellular carcinoma rates and associated risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis (Child-Pugh B or C). METHODS: Cumulative survival and hepatocellular carcinoma rates were determined using Kaplan-Meier analysis. Independent risk factors were identified by multivariate analysis. A two-tailed P-value of < 0.05 was considered significant. RESULTS: The patients were followed up for a median of 2 years (range 0.5-24.2 years). In total, 62.3%, 41.7%, 4.7%, and 68.3% of the patients had a history of hepatocellular carcinoma, ascites, hepatic encephalopathy, and esophageal varices, respectively. The 1-, 5-, 10-, and 20-year cumulative overall survival rates in the total cohort was 74.9%, 29.0%, 9.1%, and 1.4%, respectively. The 1-, 3-, 5-, and 10-year cumulative survival rates for patients without hepatocellular carcinoma were 93.1%, 54.4%, 18.2%, and 4.0%, respectively, and the corresponding cumulative post-decompensation hepatocellular carcinoma rates were 14.0%, 31.6%, 46.1%, and 66.2%, respectively. The independent risk factors for mortality were older age, Child-Pugh C cirrhosis, the presence of hepatocellular carcinoma, low estimated glomerular filtration rate, low serum sodium level, low platelet count, and high γ-glutamyl transferase and α-fetoprotein levels for all patients and older age, Child-Pugh C cirrhosis, and low estimated glomerular filtration rate for patients without hepatocellular carcinoma. Overall, 1035 patients (73.3%) died; the causes of death were liver failure with/without hepatocellular carcinoma, pneumonia, sepsis, cardiovascular disease, and non-hepatocellular carcinoma malignancies. The corresponding morality rates per person-year were 133.4, 59.9, 10.9, 10.6, 9.0, and 5.2, respectively. CONCLUSIONS: Among Japanese patients with decompensated hepatitis C virus-related cirrhosis, hepatocellular carcinoma is associated with poor prognosis. Our results highlight the importance of managing liver-related events, including hepatocellular carcinoma, in these patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Estudos de Coortes , Hepacivirus , Humanos , Japão/epidemiologia , Cirrose Hepática , Estudos Retrospectivos , Fatores de Risco
5.
Ann Surg Oncol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33904001

RESUMO

BACKGROUND: With the introduction of new molecular-targeted agents, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are benefiting from salvage interventions; however, the actual rate of conversion surgery and its prognostic advantages remain unclear. METHODS: The clinical outcomes of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were reviewed and the efficacy of additional therapy, including surgery, was investigated. RESULTS: Of the 107 patients who were initially unsuitable for curative-intent therapy or transarterial chemoembolization (TACE), 54 (50.5%) received further therapy after lenvatinib treatment (surgery [n = 16] and TACE or other treatments [n = 38]). Of the 16 patients who received surgical intervention, R0 resection was achieved in 9 (8.4%) patients. Survival analysis confirmed that successful conversion to R0 resection was associated with a longer time to treatment failure (hazard ratio [HR] 0.04, 95% confidence interval [CI] 0.01-0.29; p = 0.002) and better disease-specific survival (HR 0.04, 95% CI 0.01-0.30; p = 0.002) compared with no additional treatment, while additional treatment other than surgery or R2 resection was associated with only a marginal or no prognostic advantage. Multivariate analysis confirmed that a decrease in plasma des-gamma-carboxyprothrombin levels compared with baseline levels (odds ratio 22.22, 95% CI 3.42-144.29; p = 0.001) was significantly correlated with successful R0 resection after lenvatinib treatment, irrespective of the tumor response as assessed by imaging analysis. CONCLUSIONS: In selected patients with advanced HCC, conversion surgery after lenvatinib treatment may offer significant survival benefit as long as R0 resection is achieved.

6.
Sci Rep ; 11(1): 7929, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846449

RESUMO

The emergence of drug-resistant bacteria has become a major problem worldwide. Bacterial dipeptidyl peptidases 7 and 11 (DPP7s and DPP11s), belonging to the family-S46 peptidases, are important enzymes for bacterial growth and are not present in mammals. Therefore, specific inhibitors for these peptidases are promising as potential antibiotics. While the molecular mechanisms underlining strict specificity at the S1 subsite of S46 peptidases have been well studied, those of relatively broad preference at the S2 subsite of these peptidases are unknown. In this study, we performed structural and biochemical analyses on DPP7 from Stenotrophomonas maltophilia (SmDPP7). SmDPP7 showed preference for the accommodation of hydrophobic amino acids at the S2 subsite in general, but as an exception, also for asparagine, a hydrophilic amino acid. Structural analyses of SmDPP7 revealed that this exceptional preference to asparagine is caused by a hydrogen bonding network at the bottom of the S2 subsite. The residues in the S2 subsite are well conserved among S46 peptidases as compared with those in the S1 subsite. We expect that our findings will contribute toward the development of a universal inhibitor of S46 peptidases.

7.
Clin J Gastroenterol ; 14(2): 555-559, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33428067

RESUMO

We report a rare case of amebiasis associated with an intraabdominal abscess without colitis, an intestinal perforation, or other extraintestinal amebiasis. A patient was admitted with cirrhosis and a history of spontaneous bacterial peritonitis (SBP) and was found to have a high C-reactive protein (CRP) level. Dynamic CT and ultrasound echo findings showed an intraabdominal abscess. No intestinal lesions or extraintestinal lesions other than the intraabdominal abscess were observed. Blood cultures and puncture fluid cultures were negative for bacteria. However, microscopic examination of the puncture fluid showed a cystic form of amoeba, leading to a diagnosis of an amoeba abscess. The abscess disappeared after 10 days of oral treatment with metronidazole. When an abdominal abscess is seen in an immunocompromised patient such as a cirrhotic patient, amoeba infection should be considered as a possible diagnosis.

8.
Hepatol Res ; 51(4): 503-508, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33462964

RESUMO

Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients worldwide. We previously reported a patient with CHB and cirrhosis in whom viral breakthrough occurred during combination therapy with TDF and entecavir (ETV) against ETV-resistant virus. A recent Korean report showed that two patients with viral breakthrough during treatment with TDF-containing regimens were found to carry five reverse transcriptase (rt) mutations ([rt]S106C[C], rtH126Y[Y], rtD134E[E], rtM204I/V, and rtL269I [I]), with the C, Y, E, and I mutations being associated with tenofovir resistance. We report the clinical course up to September 2019 in our patient, and compare the HBV mutations to those of the two Korean patients. Four mutations (rtS106C, rtD134N/S[N/S], rtM204V, and rtL269I) plus ETV resistance (rtL180M and rtS202G) existed when she developed viral breakthrough during ETV and TDF combination therapy in April 2013. Moreover, three mutations (rtS106C, rtD134N, and rtL269I) existed at baseline. Our patient's father is Korean. Considering these factors, patients with these three or four mutations (CYEI or CN/SI) at baseline could experience tenofovir resistance in addition to lamivudine (LAM) or ETV resistance. In addition, HBV DNA levels fluctuated during tenofovir alafenamide (TAF) and LAM therapy in our patient, although treatment was switched from LAM, TDF, and ETV to LAM and TAF combination therapy in April 2018. In conclusion, three mutations (CN/SI) plus ETV resistance (rtL180M, rtM204V, and rtS202G) can cause tenofovir resistance. Long-term therapy with tenofovir against ETV-resistant virus has the potential to induce viral breakthrough and resistance, necessitating careful follow-up.

9.
Brain Dev ; 43(1): 45-54, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32736903

RESUMO

In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant enzyme protein with abnormal steric structure that is expressed by gene mutation. Chaperone therapy is a new molecular therapeutic approach primarily for lysosomal diseases. The misfolded mutant enzyme is digested rapidly or aggregated to induce endoplasmic reticulum stress. As a result, the catalytic activity is lost. The following sequence of events results in chaperone therapy to achieve correction of molecular pathology. An orally administered low molecular competitive inhibitor (chaperone) is absorbed into the bloodstream and reaches the target cells and tissues. The mutant enzyme is stabilized by the chaperone and subjected to normal enzyme proteinfolding (proteostasis). The first chaperone drug was developed for Fabry disease and is currently available in medical practice. At present three types of chaperones are available: competitive chaperone with enzyme inhibitory bioactivity (exogenous), non-competitive (or allosteric) chaperone without inhibitory bioactivity (exogenous), and molecular chaperone (heat shock protein; endogenous). The third endogenous chaperone would be directed to overexpression or activated by an exogenous low-molecular inducer. This new molecular therapeutic approach, utilizing the three types of chaperone, is expected to apply to a variety of diseases, genetic or non-genetic, and neurological or non-neurological, in addition to lysosomal diseases.

10.
Hepatol Res ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270344

RESUMO

AIMS: Hepatitis B surface antigen (HBsAg) seroclearance indicates a "functional cure" in chronic hepatitis B virus (HBV) infection (CHB). However, several cases of hepatocellular carcinoma (HCC) development have been reported after HBsAg seroclearance. We evaluated the potential of HBsAg and hepatitis B core-related antigen (HBcrAg), measured by the ultra-highly sensitive assays, in cases with HCC development after HBsAg seroclearance. METHODS: We enrolled 17 patients with CHB who achieved HBsAg seroclearance, defined by the conventional assay using Architect HBsAg QT kit (5 HCC patients and 12 non-HCC patients). HBsAg and HBcrAg were measured in their stored serum samples using ultra-highly sensitive assays featuring "immunoassay for total antigen including complex via pretreatment (iTACT)" technology. RESULTS: All 5 patients who developed HCC were positive for HBsAg or HBcrAg by iTACT-HBsAg or iTACT-HBcrAg at all follow-up points. HBcrAg levels in the HCC group, using iTACT-HBcrAg, were significantly higher than those in the non-HCC group at HBsAg seroclearance (3.6 LogU/mL (2.8-4.2) vs. 2.6 (<2.1-3.8), p=0.020). The best cutoff value of iTACT-HBcrAg for predicting HCC development was 2.7 LogU/mL by receiver operating characteristic curve analysis. The prevalence of HBcrAg ≥2.7 in the HCC group was significantly higher than that in non-HCC group (100% (5/5) vs. 33% (4/12), p=0.029). CONCLUSIONS: Residual low viral antigen might predict HCC development even if HBsAg seroclearance was achieved according to a conventional assay. The results suggest that iTACT assays of HBsAg and HBcrAg would be useful for monitoring CHB patients. (239 words).

11.
Oncology ; : 1-8, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207358

RESUMO

BACKGROUND: The sensitivity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in hepatocellular carcinoma (HCC) is low; however, clinical evidence demonstrating its prognostic value in patients with HCC has recently been reported. This study aimed to assess the value of 18F-FDG-PET/CT as a tool for evaluating the response of HCC to lenvatinib treatment. METHODS: We evaluated 11 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT from April 2018 to December 2019. The tumor-to-normal liver ratio (TLR) of the target tumor was measured before and during the course of lenvatinib treatment with 18F-FDG-PET/CT (pre and post analysis, respectively), with a TLR ≥2 classified as PET-positive HCC. At the time of each evaluation, we also used the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the modified RECIST (mRECIST), and the tumor marker alfa-fetoprotein (AFP). RESULTS: Of 11 patients, 3 (27%) and 8 (73%) had an objective response to lenvatinib treatment at the time of post-analysis by RECIST 1.1 and mRECIST, respectively. There were 3 (27%) and 7 (64%) patients with PET-positive HCC at the time of pre- and post-analysis, respectively. There was a significant correlation between the rates of change in AFP and TLR during lenvatinib treatment (r = 0.69, p = 0.019). Based on these results, we were able to perform liver resection on 4 patients with PET-positive HCC as conversion therapy. Three samples from these patients showed poorly differentiated tumors. CONCLUSION: 18F-FDG-PET/CT has potential as an evaluation tool for describing biological tumor behavior and reflecting disease progression, location, and treatment response. This modality may provide useful information for considering prognosis and subsequent therapy.

12.
BMC Gastroenterol ; 20(1): 368, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148171

RESUMO

BACKGROUND: The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m2) are unknown. METHODS: In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3-4) and mortality in lean NAFLD patients. RESULTS: Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan-Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ - 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ - 1.455 were predictors of overall survival. CONCLUSIONS: Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ - 1.455 or history of liver cancer should be monitored carefully during follow-up.

13.
Proc Natl Acad Sci U S A ; 117(47): 29959-29967, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33177239

RESUMO

Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. LY3502970 is a partial agonist, biased toward G protein activation over ß-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective against other class B G protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration. A high-resolution structure of LY3502970 in complex with active-state GLP-1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain (ECD), extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY3502970 and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetes mellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands.

14.
Medicine (Baltimore) ; 99(43): e22764, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120784

RESUMO

Health-related quality of life (HRQOL) is lower in individuals with autoimmune hepatitis (AIH) than in the general population. However, previous evaluations of HRQOL for AIH have included a broad range of disease activities. The aim of this study was to clarify HRQOL among patients with AIH in remission.We assessed HRQOL in patients with AIH in remission, patients with chronic hepatitis C (CHC) with eradicated hepatitis C virus (HCV) and patients with primary biliary cholangitis (PBC) using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ).Participants comprised 62 patients with AIH in remission, 39 patients with CHC with eradicated HCV and 66 patients with PBC. Median ages of patients were 63, 69, and 64 years, respectively. Overall score (5.6 vs 5.9, P = .02) and fatigue (5.2 vs 5.6, P = .01) and worry (5.6 vs 6.0, P = .01) domain scores of the CLDQ were significantly lower in patients with AIH in remission than in CHC with eradicated HCV, and similar to scores except for the systemic symptoms domain in patients with PBC. Disease duration was associated with lower scores on systemic symptoms and activity domains of the CLDQ in patients with AIH in remission.Patients with AIH in remission show impaired HRQOL associated with disease duration.


Assuntos
Hepatite Autoimune , Qualidade de Vida , Idoso , Feminino , Hepatite C Crônica , Hepatite Autoimune/terapia , Humanos , Cirrose Hepática Biliar , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Autorrelato
15.
Gynecol Oncol ; 159(2): 546-553, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951893

RESUMO

OBJECTIVE: To elucidate tumor mutation profiles associated with outcomes of uterine cervical cancer (UCC) patients treated with definitive radiotherapy. METHODS: Ninety-eight patients with newly diagnosed and pathologically confirmed UCC (82 squamous cell carcinomas, 12 adenocarcinomas, and four adenosquamous carcinomas) who were treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Genetic mutations were identified and analyzed for correlations with clinical outcome. RESULTS: Recurrent mutations were observed in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes (i.e., FGFR1-4) was almost as high (24.5%) as that in PIK3CA and ARID1A, both of which are well-studied drivers of UCC. Fifty-five percent (21 of 38) of the identified FGFR mutations were located in the FGFR protein tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%, respectively; P = 0.010). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS (P = 0.005), independent of clinicopathological variables. CONCLUSIONS: FGFR mutations are associated with worse PFS in UCC patients treated with definitive radiotherapy. These results warrant further validation in prospective studies.

16.
Oncology ; : 1-10, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998139

RESUMO

INTRODUCTION: It remains unclear whether TERT promoter mutation (TERT C228T) in serum cell-free DNA (cfDNA) is useful for the diagnosis of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: In this retrospective study, we analyzed the relationships between TERT C228T in serum cfDNA and levels of AFP and PIVKAII in 57 Japanese patients with histopathologically confirmed NAFLD background, consisting of 36 patients with HCC and 21 without HCC. We also examined the liver-related survival rate and HCC recurrence rate after the initial treatment for HCC. TERT C228T was detected using a highly sensitive method based on wild-type blocking PCR (detection limit in excess of 0.7% mutant-type DNA). RESULTS: In all of the 57 patients, multivariate analysis identified TERT C228T positive as significant determinant of primary HCC. In the 36 patients with HCC, the percentage of patients positive for TERT C228T was 63.9%. The percentage of patients positive for TERT C228T with normal AFP and PIVKAII was 35.3%. The positive predictive value and specificity for prediction of BCLC stage 0 or A were both high. In 6 patients, TERT C228T was repeatedly negative during follow-up but became positive at the time of HCC diagnosis. Four patients who underwent HCC surgical resection had well-differentiated solitary HCC measuring <30 mm, and all were TERT C228T positive with normal AFP and PIVKAII. TERT C228T status had no influence on the cumulative liver-related survival rate and HCC recurrence rate. CONCLUSIONS: Our results highlight the superiority of TERT C228T in serum cfDNA compared with AFP and PIVKAII in the early diagnosis of primary HCC in NAFLD patients.

17.
Hepatol Res ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939922

RESUMO

AIM: The number of patients with fatty liver disease (FLD) is increasing globally. Ethanol consumption in FLD is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the effects of alcohol consumption on the occurrence of multiple HCCs remain unclear. We explored the relationship between the daily ethanol intake and the HCC number. METHODS: This single-center retrospective study enrolled 114 patients without viral or immune hepatitis undergoing first-line HCC treatment who had been diagnosed with FLD by abdominal ultrasonography or a liver biopsy at the same time as or before HCC detection. We categorized patients into four groups according to the daily alcohol consumption (<20 g: non-alcoholic fatty liver disease, n = 45; 20-39 g: low-intermediate ethanol intake with FLD, n = 13; 40-69 g: high-intermediate ethanol intake with FLD, n = 31; ≥70 g: alcoholic fatty liver disease, n = 25). The relationship between the daily ethanol consumption and the number of HCCs (single or multiple) was examined. RESULTS: The risk of multiple HCCs was significantly higher in the high-intermediate ethanol intake with FLD (HR 2.89, 95% CI 1.04-8.02, P = 0.042) and alcoholic fatty liver disease (HR 3.14, 95% CI 1.07-9.22, P = 0.037) groups than in the others. A multivariate analysis showed that a daily ethanol intake ≥40 g was associated with a significantly increased risk of multiple HCCs (HR 2.82, 95% CI 1.16-6.88, P = 0.023). CONCLUSIONS: Our findings suggest that a high daily ethanol intake might lead to multiple hepatocarcinogenesis in patients with FLD.

18.
Intern Med ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32963154

RESUMO

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥ 400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients or Materials We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.

19.
Meta Gene ; 26: 100785, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32835005

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and caused a pandemic. To monitor the global transmission pattern of SARS-CoV-2, it is required to constantly update the phylogenetic tree of genomic sequences with 29.9 kb, which may be time consuming. Phylogenetic analysis of SARS-CoV-2 may be accelerated by making a multiple alignment of nucleotide sequences using the CPA (combining pairwise alignments) method, in which a pairwise alignment is made for a reference and each of other sequences, and the pairwise alignments are combined into a multiple alignment. Here it is shown from the analysis of 3729 genomic sequences for SARS-CoV-2 and outgroup strains that the CPA method can produce a multiple alignment with an elevated or a reduced number of variable sites depending on the reference compared to the OMA (ordinary multiple alignment) method, which was considered to be the most reliable. In particular, the topology of the phylogenetic tree constructed from the multiple alignment made using the CPA method adopting the outgroup sequence as the reference was considerably different from that using the OMA method, suggesting that the outgroup sequence may not be suitable as the reference in the CPA method.

20.
Sci Rep ; 10(1): 14250, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859968

RESUMO

The Japanese diagnostic guidelines for autoimmune hepatitis (AIH) were proposed in 2014. This study aimed to determine the trends and characteristics of AIH based on a Japanese nationwide survey. Data for 796 patients who were newly diagnosed with AIH from 2014 to 2017 were collected from January to March, 2019 from 54 hospitals throughout Japan. Clinical characteristics, including treatment, were compared with those reported in a prior 2015 survey. The population had a median age of 63 years at diagnosis, and the male to female ratio was 1:5.3. The numbers of women was significantly lower in this survey than in the 2015 survey. Moreover, the incidence of AIH with histological acute hepatitis increased significantly from 11.0 to 21.7%. The changes in the laboratory findings, such as in transaminase and immunoglobulin G levels and antinuclear antibody titers, as well as in prednisolone treatment, reflected an increasing incidence of acute AIH. The clinical characteristics of AIH changed rapidly, in parallel with the increasing incidence of acute AIH. The elucidation and diagnosis of AIH with acute hepatitis are important in the management of AIH.

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