Percutaneous transhepatic sclerotherapy for ascending colonic varices due to left-sided portal hypertension.

Left-sided portal hypertension (LSPH) causes varices and splenomegaly due to splenic vein issues. Colonic varices are rare and lack standardized treatment. We report the successful treatment of colonic varices caused by LSPH, by addressing both the afferent and efferent veins. A 70-year-old man with distal cholangiocarcinoma had surgery without splenic vein resection, leading to proximal splenic vein stenosis and varices at multiple locations. Percutaneous transhepatic splenic venography revealed that collateral veins flowed into the ascending colonic varices and returned to the portal vein. Complete thrombosis of the varices was achieved by injecting sclerosants and placing coils in both the afferent and efferent veins. The procedure was safe and effective, with no variceal recurrence. This approach provides a minimally invasive option for treating colonic varices associated with LSPH.

KUS121, a VCP modulator, has an ameliorating effect on acute and chronic heart failure without calcium loading via maintenance of intracellular ATP levels.

AIMS: As heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models. METHODS AND RESULTS: Cultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca2+ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors. CONCLUSIONS: KUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF.

Transparaumbilical Intravariceal Sclerotherapy for Duodenal Varices Using Outflow Embolization.

A 55-year-old patient was admitted for variceal treatment, a complication of chronic portal hypertension and liver cirrhosis. Imaging studies revealed prominent duodenal varices, the pancreaticoduodenal vein as its afferent pathway, a drainer vessel into the inferior vena cava, and a paraumbilical vein. We successfully performed complete obliteration of the varix, including its afferent and efferent vessels, via the paraumbilical vein approach.

Afferent vein embolization via retrograde approach as a potential treatment strategy for bleeding duodenal varices.

The standard treatment for ruptured duodenal varices remains to be established. Emergency balloon-occluded retrograde transvenous obliteration is challenging in patients with bleeding because re-rupture of varices can occur due to increased pressure when using the retrograde approach. Herein, we describe a case in which a catheter was retrogradely advanced to the afferent vein beyond bleeding duodenal varices; however, the varices re-ruptured during coil embolization, and a part of the catheter was deviated into the intestinal tract. The rupture site was embolized by liquid embolic materials from the microcatheter. Embolization via retrograde approach needs to be carefully performed.

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element-binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element-binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism-related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH.

Liquid Enteral Nutrients Alter the Pharmacokinetics of Orally Administered Carbamazepine in Rats.

The interaction between enteral nutrients (ENs) and drugs co-administered through a nasogastric (NG) tube reportedly affects the absorption and resultant plasma concentrations of the respective drugs. However, the gastrointestinal absorption of carbamazepine (CBZ), an antiepileptic drug, co-administered with liquid ENs through an NG tube has not been clarified. In this study, we measured the recovery rate (%) of CBZ (Tegretol® powder) passed through an NG tube when co-administered with distilled water or ENs (F2α®, Racol® NF, Ensure Liquid®, and Renalen® LP) of different compositions, frequently used in Japan. We also measured the plasma CBZ level in 26 rats after oral co-administration of CBZ with liquid ENs. The CBZ recovery rate was close to 100% in rats of all EN groups after passage through the NG tube. Furthermore, CBZ area under the plasma concentration-time curve from time zero to 9 h (AUC0→9h) of the Ensure liquid® group decreased compared with that of control group (P < 0.05) and Renalen® LP group (P < 0.01). However, the AUC0→9h of CBZ remained unchanged when co-administered with Ensure liquid® 2 h after initial CBZ administration. In conclusion, the co-administration of CBZ with Ensure Liquid® caused a reduction in the absorption of CBZ from the gastrointestinal tract, without adsorption on the NG tube. The administration of Ensure Liquid® 2 h after CBZ is a way to prevent a decrease in plasma CBZ concentration. Our findings suggest that carefully monitoring the plasma levels of CBZ is necessary in co-administation with Ensure liquid® to prevent the unintended effects of the interaction between CBZ and liquid EN.

Periprocedural management and clinical outcomes of invasive procedures after venous thromboembolism: from the COMMAND VTE registry.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Quantitative evaluation of COVID-19 pneumonia severity by CT pneumonia analysis algorithm using deep learning technology and blood test results.

PURPOSE: To evaluate whether early chest computed tomography (CT) lesions quantified by an artificial intelligence (AI)-based commercial software and blood test values at the initial presentation can differentiate the severity of COVID-19 pneumonia. MATERIALS AND METHODS: This retrospective study included 100 SARS-CoV-2-positive patients with mild (n = 23), moderate (n = 37) or severe (n = 40) pneumonia classified according to the Japanese guidelines. Univariate Kruskal-Wallis and multivariate ordinal logistic analyses were used to examine whether CT parameters (opacity score, volume of opacity, % opacity, volume of high opacity, % high opacity and mean HU total on CT) as well as blood test parameters [procalcitonin, estimated glomerular filtration rate (eGFR), C-reactive protein, % lymphocyte, ferritin, aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, creatine kinase, hemoglobin A1c, prothrombin time, activated partial prothrombin time (APTT), white blood cell count and creatinine] differed by disease severity. RESULTS: All CT parameters and all blood test parameters except procalcitonin and APPT were significantly different among mild, moderate and severe groups. By multivariate analysis, mean HU total and eGFR were two independent factors associated with severity (p < 0.0001). Cutoff values for mean HU total and eGFR were, respectively, - 801 HU and 77 ml/min/1.73 m2 between mild and moderate pneumonia and - 704 HU and 53 ml/min/1.73 m2 between moderate and severe pneumonia. CONCLUSION: The mean HU total of the whole lung, determined by the AI algorithm, and eGFR reflect the severity of COVID-19 pneumonia.

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity.

Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33-/- mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-ß-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.

Usefulness of coil-assisted retrograde transvenous obliteration II (CARTO-II) for the treatment of ascending colonic varix: a case report.

BACKGROUND: Colonic varices are rare among ectopic varices. A previous report demonstrated that once bleeding from colonic varices occurs, it can be fatal. Several treatments for colonic varices exist, including surgical, endoscopic, and endovascular treatments; however, management of colonic varices has not been standardized. For colonic varices, minimally invasive therapies would be desirable. Balloon-occluded retrograde transvenous obliteration (B-RTO) is one of the treatment options for colonic varices to prevent their rupture. Two cases of successful conventional B-RTO for these varices have already been reported. However, B-RTO using coil-assisted retrograde transvenous obliteration II (CARTO-II) procedure for these varices has not been reported. CASE PRESENTATION: A 71-year-old male patient had liver cirrhosis caused by hepatitis C virus infection. A varix was located at the ascending colon, which was coincidentally found on colonic endoscopy. Contrast-enhanced computed tomography (CT) showed that the feeder vein was the ileocolic vein and that the main draining vein was the right renal vein. Physicians concluded that treatment was required to avoid the risk of death from massive bleeding due to varix rupture. However, endoscopic and surgical treatments were difficult due to the anatomical location of the varix and the high risk of operative compilations, respectively. This ascending colonic varix was treated by balloon-occluded retrograde transvenous obliteration (B-RTO) using coil-assisted retrograde transvenous obliteration II (CARTO-II) procedure via the right renal vein. There were no complications during the procedure and no recurrences for 36 months during long-term follow-up. CONCLUSIONS: CARTO-II can be one of the effective treatment techniques for ascending colonic varices.

Electrochemical Reactions of Iodine Molecules Encapsulated in Single-Walled Carbon Nanotubes.

We prepared iodine molecules encapsulated in single-walled carbon nanotubes (I@SWCNTs) by electro-oxidation of iodide ions with empty SWCNT electrode. Li-ion battery electrode properties of I@SWCNTs were investigated. It was found that the I@SWCNT sample can catch and release Li ions reversibly. We performed Raman measurements to reveal the Li-ion storage mechanism of I@SWCNT. It is plausible that chemical reactions of I2 from/into LiI in SWCNTs occur during Li-ion charging/discharging of I@SWCNT. We also prepared the CsI@SWCNT sample to verify that alkali metal ions can be extracted from alkali metal halide in SWCNTs. The extraction of cesium ions from CsI@SWCNT was confirmed by Raman measurements. It was also found that I@SWCNT can work as a Li-ion battery electrode in solid electrolyte as well.

Rapid Plasma Etching for Fabricating Fused Silica Microchannels.

In order to advance the performances of micro chemical and biochemical systems on a chip, the fabrication of microstructures such as channels and pillars is an essential basic technology. However, conventional fabrication methods based on wet etching have limitations in their applications for device engineering. In this study, we report on a new microchannel fabrication process on a fused silica substrate using photoresist and plasma etching based on C3F8, CHF3, and Ar gases. Deep, rectangular microchannels, having vertical angles close to 90°, 10 µm-scale deep and low surface roughness of less than 1 nm, could be fabricated on a fused silica substrate at high etching rates on the order of 5 - 7 nm s-1. This metal-free fabrication methodology is expected to be a low-cost, easy, and simple technique for a fused silica microstructure applications.

Acute myocardial infarction and 30-year coronary aneurysm follow-up by serial angiography in a young adult with Kawasaki disease.

The number of adult patients with coronary artery disease caused by Kawasaki disease (KD) is gradually increasing, but some patients drop out of clinical follow-up. However, careful, long-term follow-up and establishment of an optimal treatment strategy are needed in these patients, as well as cooperation between pediatric and adult cardiologists. We report a case of acute myocardial infarction in a young adult patient with KD whose serial coronary angiography was followed up for over 30 years. Successful reperfusion therapy was performed with thrombus aspiration, rotational atherectomy, and implantation of a drug-eluting stent.