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Gadoxetic Acid-enhanced Liver MRI: Everything You Need to Know
Since its introduction in the worldwide medical market, gadoxetic acid has attracted considerable interest. The year 2023 marks the 15th anniversary of the introduction of gadoxetic acid in Japan. Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) is the predominantly performed contrast MRI examination for the liver. Its most essential characteristic, namely the hepatobiliary phase, revolutionized the clinical management of liver disease. GA-MRI is currently the most efficient method for focal liver lesion detection and analysis. Meta-analyses demonstrated its excellent effectiveness for the diagnosis of hepatocellular carcinoma and liver metastases. Owing to the extensive usage of gadoxetic acid, a hepatobiliary phase hypointense nodule without arterial phase hyperenhancement is well documented. The existence of such nodules may be a sign of hypervascular hepatocellular carcinoma in nodules and other areas in the liver. Apart from its role in tumor identification and characterization, GA-MRI can help assess response to therapy and liver fibrosis. Therefore, it is proposed to use gadoxetic acid as the first option for MRI of the liver in the majority of patients. The efficacy of gadoxetic acid surpasses its disadvantages, rendering this contrast agent the preferred choice for routine MRI of the liver. The clinical use of GA-MRI is discussed in this review article.journal articl
Impact of high-dose vasopressor during endotoxic shock on the cerebral, lingual, hepatic, and renal microcirculation evaluated by near-infrared spectroscopy in swine
Background: High-dose vasopressors maintain blood pressure during septic shock but may adversely reduce microcirculation in vital organs. We assessed the effect of high-dose norepinephrine and vasopressin on the microcirculation of the brain, tongue, liver, and kidney during endotoxic shock using near-infrared spectroscopy (NIRS).
Methods: Thirteen pigs (24.5 ± 1.8 kg) were anesthetized, and an NIRS probe was attached directly to each organ. Approximately 0.2, 0.5, 1, and 2 μg/kg/min of norepinephrine were administered in a stepwise manner, followed by 0.5, 1, 2, and 5μg/kg/min of sodium nitroprusside in normal condition. Moreover, 1 μg/kg/h of lipopolysaccharide was administered continuously after 100 μg bolus to create endotoxic shock, and after 1000mL of crystalloid infusion, high-dose norepinephrine (2, 5, 10, and 20 μg/kg/min) and vasopressin (0.6, 1.5, 3, and 6 U/min) were administered in a stepwise manner. The relationship between the mean arterial pressure (MAP) and each tissue oxygenation index (TOI) during vasopressor infusion was evaluated.
Results: Three pigs died after receiving lipopolysaccharides, and 10 were analyzed. An increase of >20% from the baseline MAP induced by high-dose norepinephrine during endotoxic shock reduced the TOI in all organs except the liver. The elevation of MAP to baseline with vasopressin alone increased the kidney and liver TOIs and decreased the tongue TOI.
Conclusions: Forced blood pressure elevation with high-dose norepinephrine during endotoxic shock decreased the microcirculation of vital organs, especially the kidney. Cerebral TOI may be useful for identifying the upper limit of blood pressure, at which norepinephrine impairs microcirculation.journal articl
Rate-dependent elevation of the capture threshold after implantation of a leadless pacemaker
The procedural success in the implantation of cardiac electric devices depends on both the implanted position and the electric performance. The capture threshold and the pacing output affect the estimated battery longevity. In a case with a high capture threshold, recapture and reimplantation of a leadless pacemaker are commonly recommended. We experienced a case with the rate-dependent elevation of the capture threshold following the implantation of a leadless pacemaker. The recognition of the rate-dependency of the capture threshold and the acceptable programming could avoid the unnecessary recapture and reimplantation of that, avoiding the increase of procedural risks.journal articl
An effectiveness of oral ω3 fatty acid containing supplement for intestinal failure-associated liver disease in term neonate
症例は日齢11の男児.胆汁性嘔吐,血便の精査を行ったところ腸管壊死が疑われ,緊急手術を施行した.広範囲の小腸切除により残存小腸は空腸50cm,回腸10cm(回盲弁あり)となり,短腸症候群を来した.長期にわたる中心静脈栄養と経腸栄養の不足により,徐々に直接ビリルビン,AST・ALTの上昇を認め,小腸機能不全関連肝障害と診断した.本疾患の治療には静注用ω3系脂肪酸製剤の投与が有効であることが報告されているが,その代表薬であるOmegaven®は我が国では承認されていない薬剤である.
本症例では経口にてω3系油脂高含有製剤であるEPA1100の投与を行い,肝機能障害の改善を認めた.それに加え不足していた脂肪酸もEPA1100の摂取により上昇した.ω3系脂肪酸の経口投与により短腸症候群の児の肝機能が改善するだけでなく,栄養状態の改善にも効果がある可能性が示唆された.Intestinal failure-associated liver dysfunction (IFALD) is seen in patient with short bowel syndrome (SBS), and often become cause of death. Fish oil containing lipid emulsions such as Omegaven® is used to treat IFALD and good prognosis is reported in past studies. But in our country, Omegaven® is an unapproved drug and requires ethics committee approve for use. Here, we report a case of male neonate who underwent on resection of small intestine at 11th day of life because of small intestine necrosis. His small intestine was only 60 cm long after surgery, resulting in SBS. He developed IFALD at day 32. Blood checkup showed increases in direct bilirubin, AST, and ALT. Since we cannot use Omegaven® in our hospital, EPA1100, omega-3 fatty acid containing supplement, was administered orally to this patient. Liver dysfunction improved in two months after EPA1100 administration. In addition, blood concentration of eicosapentaenoic acid and docosahexaenoic acid increased, and arachidonic acid, fatty acid causing inflammation, decreased by fatty acid examination. There was no adverse effect seen in this patient. Oral administration of ω3 fatty acid containing supplement may improve liver function in patient with short bowel syndrome, and may be an alternative drug to intravenous fish oil emulsions.journal articl
Multimorbidity patterns and the relation to self-rated health among older Japanese people: a nationwide cross-sectional study
浜松医科大学博士(医学)doctoral医学系研究科thesi
Changes in the characteristics and outcomes of COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study
浜松医科大学Hamamatsu University School of Medicine博士(医学)doctoral医学系研究科The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed because of virus mutations, vaccine dissemination, treatment development and policies, among other factors. These factors have a dynamic and complex effect on the characteristics and outcomes of patients. Therefore, there is an urgent need to understand those changes and update the evidence. We used a large-scale real-world data set of 937,758 patients with COVID-19 from a nationwide claims database that included outpatients and inpatients in Japan to investigate the changes in their characteristics, outcomes and risk factors for severity/mortality from the early pandemic to the delta variantpredominant waves. The severity of COVID-19 was defined according to the modified World Health Organization clinical-progression ordinal scale. With changing waves, mean patient age decreased, and proportion of patients with comorbidities decreased. The incidences of “severe COVID-19 or death (i.e. ≥severe COVID-19)” and “death” markedly declined (5.0% and 2.9%, wild-type-predominant; 4.6% and 2.2%, alpha variant-predominant and 1.4% and 0.4%, delta variant-predominant waves, respectively). Across the wave shift, risk factors for ≥ severe COVID-19 and death, including older age, male, malignancy, congestive heart failure and chronic obstructive pulmonary disease, were largely consistent. The significance of some factors, such as liver disease, varied as per the wave. This study, one of the largest population-based studies on COVID-19, showed that patient characteristics and outcomes changed during the waves. Risk factors for severity/mortality were similar across all waves, but some factors were inconsistent. These data suggest that the clinical status of COVID-19 will change further with the coming epidemic wave.doctoral thesi
Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study
浜松医科大学Hamamatsu University School of Medicine博士(医学)doctoral医学系研究科Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P= .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.doctoral thesi
Involvement of ribosomal protein L17 and Y-Box binding protein 1 in assembly of hepatitis C virus potentially via their interaction with the 3’ untranslated region of the viral genome
浜松医科大学Hamamatsu University School of Medicine博士(医学)The 3′ untranslated region (3′UTR) of the hepatitis C virus (HCV) RNA genome, which contains a highly conserved 3′ region named the 3′X-tail, plays an essential role in RNA replication and promotes viral IRES-dependent translation. Although our previous work has found a cis-acting element for genome encapsidation within 3′X, there is limited information on the involvement of the 3′UTR in particle formation. In this study, proteomic analyses identified host cell proteins that bind to the 3′UTR containing the 3′X region but not to the sequence lacking the 3′X. Further characterization showed that RNA-binding proteins, ribosomal protein L17 (RPL17), and Y-box binding protein 1 (YBX1) facilitate the efficient production of infectious HCV particles in the virus infection cells. Using small interfering RNA (siRNA)-mediated gene silencing in four assays that distinguish between the various stages of the HCV life cycle, RPL17 and YBX1 were found to be most important for particle assembly in the trans-packaging assay with replication-defective subgenomic RNA. In vitro assays showed that RPL17 and YBX1 bind to the 3′UTR RNA and deletion of the 3′X region attenuates their interaction. Knockdown of RPL17 or YBX1 resulted in reducing the amount of HCV RNA co-precipitating with the viral Core protein by RNA immunoprecipitation and increasing the relative distance in space between Core and double-stranded RNA by confocal imaging, suggesting that RPL17 and YBX1 potentially affect HCV RNA-Core interaction, leading to efficient nucleocapsid assembly. These host factors provide new clues to understanding the molecular mechanisms that regulate HCV particle formation