Autonomic imbalance as a property of symptomatic Brugada syndrome.

The autonomic properties in 27 patients with the electrocardiographic morphology of Brugada syndrome were investigated using 24-h Holter monitoring: 10 patients had a history of ventricular fibrillation (VF; Br-VF group) and 17 did not (Br-N group); there were 26 healthy subjects enrolled in this study. All subjects underwent normal Holter data monitoring and power spectral analysis. Few extrasystoles were observed in either group, and the mean heart rate (HR), maximum HR, and total heart beats over 24 h were obtained. All of these measurements were significantly lower in the Br-VF group than in the Br-N and healthy subject groups. The RR interval variability was analyzed over 512 beats every 10 min. The high-frequency component (0.15-0.40 Hz; HF), low-frequency component (0.04-0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. The HF was significantly higher and LF/HF ratio lower in the Br-VF group than in the healthy subjects. The HF was also significantly higher than in the Br-N group. During the night (00.00-05.00 h), the HF was significantly higher in the Br-VF group, and the LH/HF lower. During the day (12.00-17.00 h), the HF was significantly higher in the Br-VF group, but there was no difference in the LF/HF. These results indicate that high vagal tone and low sympathetic tone are specific properties of symptomatic Brugada syndrome.     

Recurrent aspiration pneumonia precipitated by obstructive sleep apnea

ObjectiveThe clearance of the pharynx by deglutition and the respiratory phase patterns associated with deglutition are important in protecting airways and lungs against aspiration. The deglutition and respiratory phase patterns during sleep in patients (without swallowing disorders while awake) with obstructive sleep apnea (OSA) precipitating recurrent intractable aspiration pneumonia were investigated.MethodsAfter videoendoscopic and videofluorographic examinations of swallowing showed subjects had no swallowing disorders while awake, two adults with recurrent intractable aspiration pneumonia precipitated by severe OSA were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing and compared with the same patients before and under CPAP therapy.ResultsCPAP therapy cured recurrent intractable aspiration pneumonia. Swallows following and/or followed by inspiration (uncoordinated deglutition with respiration), which were frequently observed before CPAP therapy, were markedly reduced under CPAP therapy. On the other hand, swallows following and/or followed by expiration (coordinated deglutition with respiration) markedly increased under CPAP therapy. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the deglutition frequency. Before and under CPAP therapy, swallowing was infrequent and absent for long periods. However, respiratory phase patterns associated with sleep-related deglutition in patients with OSA under CPAP therapy markedly improved.ConclusionsIn patients (without swallowing disorders while awake) with OSA precipitating recurrent intractable aspiration pneumonia, the high rate of uncoordinated deglutition with respiration (swallows following and/or followed by inspiration) during sleep were markedly reduced and the rate of coordinated deglutition with respiration (swallows following and/or followed by expiration) was markedly increased under CPAP therapy.Sleep-related deglutition and respiratory phase patterns are likely to adversely influence aspiration pneumonia in patients with OSA. CPAP therapy improved not only apnea-hypopnea during sleep and sleep quality but also sleep-related deglutition, especially respiratory phase patterns associated with deglutition in patients with OSA. CPAP therapy may decrease the risk of aspiration and greatly improve aspiration-related diseases such as aspiration pneumonia.     

Elevated total iron-binding capacity as a predictor of response to deferasirox therapy in the setting of chronic iron overload

It is difficult to predict the efficacy of deferasirox (DFX) as its pharmacokinetics varies among patients. The area under the curve (AUC) is reportedly useful for determining adequate DFX dosage; however, serum concentration measurements are often challenging. Effective DFX dosage is thus defined by assessing the efficacy of this agent in clinical practice. To analyze a predictive response marker to DFX therapy for use in adjusting the effective dosage during the early treatment phase, we retrospectively evaluated 39 DFX-treated patients. We defined response as a >40 % decrease in serum ferritin concentration from the pretreatment level. A maximum elevation of the total iron-binding capacity (TIBC) correlated with response in a multivariate analysis of iron metabolic markers (R ² = 0.37, p < 0.001). A receiver operating characteristic curve analysis revealed that TIBC elevation had an AUC of 0.85 (p < 0.001) and the optimal cut-off value of TIBC elevation was 150 µg/dl. TIBC elevation of >150 µg/dl is a favorable predictor of effective ferritin reduction in DFX therapy (hazard ratio 29.6, 95 % confidence interval 4.8–183.6; p < 0.001). DFX therapy with TIBC monitoring may enable the determination of the minimum effective DFX dosage.     

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate–activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.     

Vascular endoscopic and macroscopic observations after crush stenting of coronary artery bifurcations in pigs.

The crush stent technique has recently been proposed to limit the development of restenosis between drug-eluting stents implanted at coronary artery bifurcations. We studied the stent expansion, apposition to the vessel, and aspect of the overlapping stents after in vivo crush stent implantation. Crush stent implantation was performed at coronary bifurcations in anesthetized swines. The treated sites were examined using intravascular ultrasound and a vascular endoscope. The stents removed from the vessel were analyzed macroscopically. After final kissing balloon inflation, an adequate apposition of the stent to the vessel wall was confirmed by vascular endoscopy and visual inspection. However, the side-branch stent was narrowed at the site of stent overlap, and the overlapping stents in the main branch created a metal mass, which could promote the development of thrombosis. The technique of crush stent implantation with additional kissing balloon inflation is feasible and promising. However, it may be limited by thrombosis and restenosis at the carina because of stent overlapping and potential incomplete apposition. Additional studies are needed to confirm the safety and long-term clinical results of this technique.     

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos)

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large‐scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30‐day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30‐day mortality among patients with Grade I or Grade III AC, but significantly lower 30‐day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018

The Tokyo Guidelines 2013 (TG13) include new topics in the biliary drainage section. From these topics, we describe the indications and new techniques of biliary drainage for acute cholangitis with videos. Recently, many novel studies and case series have been published across the world, thus TG13 need to be updated regarding the indications and selection of biliary drainage based on published data. Herein, we describe the latest updated TG13 on biliary drainage in acute cholangitis with meta‐analysis. The present study showed that endoscopic transpapillary biliary drainage regardless of the use of nasobiliary drainage or biliary stenting, should be selected as the first‐line therapy for acute cholangitis. In acute cholangitis, endoscopic sphincterotomy (EST) is not routinely required for biliary drainage alone because of the concern of post‐EST bleeding. In case of concomitant bile duct stones, stone removal following EST at a single session may be considered in patients with mild or moderate acute cholangitis except in patients under anticoagulant therapy or with coagulopathy. We recommend the removal of difficult stones at two sessions after drainage in patients with a large stone or multiple stones. In patients with potential coagulopathy, endoscopic papillary dilation can be a better technique than EST for stone removal. Presently, balloon enteroscopy‐assisted endoscopic retrograde cholangiopancreatography (BE‐ERCP) is used as the first‐line therapy for biliary drainage in patients with surgically altered anatomy where BE‐ERCP expertise is present. However, the technical success rate is not always high. Thus, several studies have revealed that endoscopic ultrasonography‐guided biliary drainage (EUS‐BD) can be one of the second‐line therapies in failed BE‐ERCP as an alternative to percutaneous transhepatic biliary drainage where EUS‐BD expertise is present.