Intractable Ventricular Tachycardia Prior to an Overt Cardiac Tumor Mass of Metastatic Cardiac Rhabdomyosarcoma (Spindle-cell Type).

We herein report a 37-year-old man who experienced recurrence of metastatic cardiac rhabdomyosarcoma along with intractable ventricular tachycardia (VT) 7 years after resection of rhabdomyosarcoma in his right elbow. At 36 years old, he developed VT unresponsive to radiofrequency catheter ablation (RFCA). Initially, the cardiac tumor was not detected, but it gradually grew in size at the RFCA site. A surgical biopsy confirmed the diagnosis of metastatic cardiac rhabdomyosarcoma. Despite radiation therapy, cardiac tumor progression and VT instability could not be prevented. Ultimately, the patient died 27 months after the initial documentation of VT.

Usefulness of cardiac magnetic resonance for early detection of cancer therapeutics-related cardiac dysfunction in breast cancer patients.

BACKGROUND: Prognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful. METHODS: We prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF>10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12­lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated. RESULTS: A total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from -27.9 ± 3.9 to -24.7 ± 3.5%, respectively, both P < 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P < 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P < 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15-4.75, P = 0.02]. CONCLUSIONS: These results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients.

A retrospective investigation to establish new screening approach for the detection of patients at high risk of Fabry disease in male left ventricular hypertrophy patients.

BACKGROUND: The prevalence of Fabry disease (FD) in male patients with left ventricular hypertrophy (LVH) is about 1%. From the perspective of performing more efficient screening with measurement of α-galactosidase (α-Gal) activity, it is important to raise the pretest probability. METHODS: We retrospectively investigated the prevalence of FD in 701 male patients with LVH who already had been screened by measurement of α-Gal activity in eight hospitals. From the viewpoint of enzymatic screening, we validated previously reported clinical features of FD including the electrocardiographic and echocardiographic characteristics with comparing each clinical determinant between patients with FD and non-FD patients. We finally aimed to establish a new screening approach for the detection of patients at high risk of FD. RESULTS: There were five FD patients (0.7%) in the 701 male patients with LVH. Those five patients with FD all had the cardiac variant type and age at detection of LVH was ≥35 years in all patients. In LVH patients with LV ejection fraction (EF) ≥ 50%, Pend-Q interval < 40 msec, SV1 + RV5 > 4.0 mV, and diffuse LVH were important determinants of FD. In LVH patients with LVEF < 50%, asymmetric septal hypertrophy and posterior wall motion abnormality seemed to be associated with FD. CONCLUSIONS: In our retrospective study, the prevalence of FD in male patients with LVH was found to be 0.7%. We established the efficient combinations of clinical determinants using age at detection of LVH, Pend-Q interval, high voltage, and LVH pattern in an echocardiogram.

Immunoglobulin a suppresses B cell receptor-mediated activation of mouse B cells with differential inhibition of signaling molecules.

CONTEXT: We previously reported that monoclonal mouse immunoglobulin (Ig) A, OA-4, attenuates sensitization in mice by suppressing B cell activation. OBJECTIVE: Here, it is demonstrated for the first time that mouse IgA inhibits mouse B cell activation in vitro under natural conditions (i.e. in the absence of chemical, physical, and genetic modifications of IgA and B cells). MATERIALS AND METHODS: Mouse splenocytes were stimulated with anti-B cell receptor (BCR) antibody or lipopolysaccharide (LPS) in the presence or absence of OA-4. Splenic B cell proliferation and the activation of several intracellular signaling molecules were measured. RESULTS: Anti-BCR antibody-induced proliferation was markedly inhibited by OA-4 or the commercially available mouse IgA S107, whereas LPS-induced proliferation was weakly attenuated by a high concentration of OA-4. Moreover, OA-4 markedly decreased the anti-BCR antibody-induced phosphorylation of p44/42 mitogen-activated protein kinase (ERK) and CD22 and decreased phosphorylated phospholipase (PLC) γ2 and intracellular Ca2+ levels moderately, whereas protein kinase B (Akt) phosphorylation was not affected by OA-4. The MAPK/ERK kinase-ERK and phosphoinositide 3-kinase-Akt pathways were found to play a role in the proliferation of splenocytes induced by anti-BCR antibody based on experiments with their inhibitors. In contrast to that in splenic B cells, ERK phosphorylation induced by anti-BCR antibody in A20 cells was not inhibited by OA-4. The modulatory effects of IgA were different among the cell types and signaling pathways. CONCLUSION: IgA is a potential immunoregulatory drug utilizing new mechanisms that affect splenic B cells but not A20 lymphomas.

Perioperative and anesthetic risk factors of surgical site infection in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Surgical site infection is a major perioperative issue. The morbidity of surgical site infection is high in major digestive surgery, such as pancreaticoduodenectomy. The comprehensive risk factors, including anesthetic factors, for surgical site infection in pancreaticoduodenectomy are unknown. The aim of this study was to investigate the perioperative and anesthetic risk factors of surgical site infection in pancreaticoduodenectomy. METHODS: This was a retrospective cohort study conducted in a single tertiary care center. A total of 326 consecutive patients who underwent pancreaticoduodenectomy between January 2009 and March 2018 were evaluated. Patients who underwent resection of other organs were excluded. The primary outcome was the incidence of surgical site infection, based on a Clavien-Dindo classification of grade 2 or higher. Multivariable logistic regression analysis was performed to investigate the association between surgical site infection and perioperative and anesthetic factors. RESULTS: Of the 326 patients, 116 (35.6%) were women. The median age was 70 years (interquartile range; 64-75). The median duration of surgery was 10.9 hours (interquartile range; 9.5-12.4). Surgical site infection occurred in 60 patients (18.4%). The multivariable analysis revealed that the use of desflurane as a maintenance anesthetic was associated with a significantly lower risk of surgical site infection than sevoflurane (odds ratio, 0.503; 95% confidence interval [CI], 0.260-0.973). In contrast, the duration of surgery (odds ratio, 1.162; 95% CI, 1.017-1.328), cerebrovascular disease (odds ratio, 3.544; 95% CI, 1.326-9.469), and ischemic heart disease (odds ratio, 10.839; 95% CI, 1.887-62.249) were identified as significant risk factors of surgical site infection. CONCLUSIONS: Desflurane may be better than sevoflurane in preventing surgical site infection in pancreaticoduodenectomy. Cerebrovascular disease and ischemic heart disease are potential newly-identified risk factors of surgical site infection in pancreaticoduodenectomy.

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice.

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.

Chronically skipping breakfast impairs hippocampal memory-related gene expression and memory function accompanied by reduced wakefulness and body temperature in mice.

Acute or chronic effects of consuming or skipping breakfast on cognitive performance in humans are controversial. To evaluate the effects of chronically skipping breakfast (SB) on hippocampus-dependent long-term memory formation, we examined hippocampal gene expression and applied the novel object recognition test (NORT) after two weeks of repeated fasting for six hours from lights off to mimic SB in mice. We also examined the effects of SB on circadian rhythms of locomotor activity, food intake, core body temperature (CBT) and sleep-wake cycles. Skipping breakfast slightly but significantly decreased total daily food intake without affecting body weight gain. Locomotor activity and CBT significantly decreased during the fasting period under SB. The degree of fasting-dependent CBT reduction gradually increased and then became stabilized after four days of SB. Electroencephalographic data revealed that repeated SB significantly decreased the duration of wakefulness and increased that of rapid eye movement (REM) and of non-REM (NREM) sleep during the period of SB. Furthermore, total daily amounts of wakefulness and NREM sleep were significantly decreased and increased, respectively, under SB, suggesting that SB disrupts sleep homeostasis. Skipping breakfast significantly suppressed mRNA expression of the memory-related genes, Camk2a, Fkbp5, Gadd45b, Gria1, Sirt1 and Tet1 in the hippocampus. Recognition memory assessed by NORT was impaired by SB in accordance with the gene expression profiles. These findings suggested that chronic SB causes dysregulated CBT, sleep-wake cycles and hippocampal gene expression, which results in impaired long-term memory formation.

Non-invasive screening using ventilatory gas analysis to distinguish between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Clinical presentations associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) at rest are highly similar. Differentiating between CTEPH and PAH using non-invasive techniques remains challenging. Thus, we examined whether analysis of ventilatory gas in response to postural changes can be useful as a non-invasive screening method for pulmonary hypertension (PH), and help differentiate CTEPH from PAH. METHODS: We prospectively enrolled 90 patients with suspected PH and performed right heart catheterization, ventilation/perfusion scan and ventilatory gas analysis. Various pulmonary function parameters were examined in the supine and sitting postures, and postural changes were calculated (Δ(supine - sitting)). RESULTS: In total, 25 patients with newly diagnosed PAH, 40 patients with newly diagnosed CTEPH and 25 non-PH patients were included. ΔEnd-tidal CO2 pressure (PET CO2 ) was significantly lower in patients with CTEPH and PAH than in non-PH patients (both P < 0.001). ΔPET CO2 < 0 mm Hg could effectively differentiate PH from non-PH (area under the curve (AUC) = 0.969, sensitivity = 89%, specificity = 100%). Postural change from sitting to supine significantly increased the ratio of ventilation to CO2 production (VE/VCO2 ) in the CTEPH group (P < 0.001). By contrast, VE/VCO2 significantly decreased in the PAH group (P = 0.001). Notably, CTEPH presented with higher ΔVE/VCO2 than PAH, although no differences were observed in haemodynamic and echocardiographic parameters between the two groups (P < 0.001). Furthermore, ΔVE/VCO2 > 0.8 could effectively differentiate CTEPH from PAH (AUC = 0.849, sensitivity = 78%, specificity = 88%). CONCLUSION: Postural changes in ventilatory gas analysis are useful as a non-invasive bedside evaluation to screen for the presence of PH and distinguish between CTEPH and PAH.

Usefulness of ventilatory gas analysis for the non-invasive evaluation of the severity of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organic thrombotic obstructions in the pulmonary arteries with reduced pulmonary vascular reserve. This study aimed to examine whether postural changes in ventilatory gas analysis parameters are useful for assessing pulmonary hemodynamics in patients with CTEPH. METHODS: A total of 44 patients with newly diagnosed CTEPH (CTEPH group), 33 patients with improved CTEPH (mean pulmonary arterial pressure [mPAP] <25 mm Hg), and 25 controls were enrolled. Patients with improved CTEPH referred to patients without residual PH who were previously diagnosed with CTEPH and already received optimal therapies. Various pulmonary function parameters were examined in supine and sitting positions, and postural changes were calculated (Δ[supine - sitting]). In 32 patients with CTEPH, we examined hemodynamic and ventilatory gas analysis parameters before the first balloon pulmonary angioplasty (BPA) and during follow-up. RESULTS: Patients with CTEPH had significantly lower supine end-tidal carbon dioxide pressure (PETCO2) and ΔPETCO2 than controls (both P < 0.001), and these parameters were significantly correlated with mPAP (R2 = 0.507, P < 0.0001 and R2 = 0.470, P < 0.001, respectively). Supine PETCO2 and ΔPETCO2 were significantly lower in patients with improved CTEPH than in controls (both P < 0.001). Hemodynamic and echocardiographic parameters were comparable in both groups. Furthermore, significant correlation between the change in mPAP and change in supine PETCO2 by BPA was noted (R2 = 0.478, P < 0.001). CONCLUSION: These results indicate that postural changes in ventilatory gas analysis parameters are useful and non-invasive method for the evaluation of mPAP, which is one of the hemodynamic parameters of CTEPH severity.

Downregulation of integrin-αvß6 on keratinocytes in the scar of lichen planopilaris and folliculitis decalvans: Relevance for the disappearance of epidermal Langerhans cells.

Primary cicatricial alopecia (PCA) is a group of poorly understood mechanisms in which the destruction of hair follicles leads to permanent hair loss. Lichen planopilaris (LPP) is a type of lymphocytic PCA and it has been known for epidermal Langerhans cells (LC) to disappear in the scar of LPP. We also found that epidermal LC also disappeared in the scar of folliculitis decalvans (FD), a type of neutrophilic PCA. Of note was that epidermal LC did not disappear in the scar of discoid lupus erythematosus, another type of lymphocytic PCA, suggesting that LC disappearance in the scar was not always a common feature of PCA. We found that the expression of integrin (ITG)-αvß6 in scar epidermis was significantly diminished in LPP and FD, but not in other PCA and disorders accompanied with scar formation. We also found that exogenous interleukin-1ß and α-interferon downregulated ITG-αvß6 expression in normal human epidermal keratinocytes. These data suggest that downregulation of ITG-αvß6 may be one of the causes of LC disappearance in the scar of LPP and FD.

Successful Management of Acute Congestive Heart Failure by Emergent Caesarean Section Followed by Adrenalectomy in a Pregnant Woman with Cushing's Syndrome-induced Cardiomyopathy.

Congestive heart failure (CHF) is rare during pregnancy. We herein report a 35-year-old woman who developed CHF with severe left ventricular dysfunction at 35 weeks' gestation. She underwent emergency Caesarean section followed by intensive-care treatment for CHF. The diagnosis of Cushing's syndrome (CS) caused by adrenal adenoma was confirmed by endocrinological examinations and histology after adrenalectomy. She was discharged on heart failure medications and glucocorticoid replacement therapy. Both the symptoms and cardiac function had recovered after 12 months of follow-up. This case highlights the importance of considering CS-induced cardiomyopathy as a cause of CHF in pregnant women.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

Clinical Diversity in Patients with Anderson-fabry Disease with the R301Q Mutation.

Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A (α-GAL A). We herein report 10 cases of AFD in 5 families (3 men and 7 women) that were found to have a specific common mutation in R301Q [G-to-A transition in exon 6 (codon 301) resulting in the replacement of a glutamine with an arginine residue]. We evaluated their clinical characteristics, residual enzymatic activity, and plasma concentrations of globotriaosylsphingosine (Lyso-Gb3). Although all 10 cases had cardiac and renal manifestations in common, their clinical manifestations were markedly divergent despite the same genetic abnormality.

Effects of Hepatitis C Virus Antibody-Positivity on Cardiac Function and Long-Term Prognosis in Patients With Adult Congenital Heart Disease.

It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction <50% was significantly higher in the HCV antibody-positive group compared with the HCV antibody-negative group (17 vs 5.4%, p = 0.014). During a mean follow-up period of 10.1 years (interquartile range 6 to 14 years), the CEP was noted in 51 patients. Kaplan-Meier analysis showed the HCV antibody-positive group had significantly poor event-free survival than the HCV antibody-negative group (log-rank, p = 0.002). In contrast, HCV ribonucleic acid-positivity was not a significant predictor of the CEP in the HCV antibody-positive group (log-rank, p = 0.442). Furthermore, the HCV antibody-positivity was significantly associated with the CEP in both univariable and multivariable Cox regression models (hazard ratio 2.37, 95% confident interval 1.32 to 4.15, p = 0.005 and 1.96, 1.06 to 3.63, p = 0.032, respectively). In conclusion, these results suggest that more attention should be paid to HCV antibody-positivity in the management of ACHD patients.

Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding.

Chrononutrition is the science of nutrition based on chronobiology. Numerous epidemiological studies have shown that fish oil (FO) reduces the risk of cardiovascular events through various actions such as lowering triglycerides. The present study aimed to determine the time of day when the hypertriglyceridemia-decreasing ability of FO is optimal in mice. A high-fructose diet (HFrD) that induces hyperlipidemia in mice was replaced with the same diet containing 4% FO (HFrD-4% FO) at different times of the day for 2 weeks as described below. Mice were fed with HFrD alone (CTRL) or with HFrD containing 4% FO for 12 h around the time of activity onset [breakfast (BF)-FO] or offset [dinner (DN)-FO]. Plasma and liver concentrations of triglycerides and total cholesterol were reduced in BF-FO but not in DN-FO mice compared with CTRL mice. The temporal expression of genes associated with fatty acid synthesis such as Fasn, Acaca, Scd1 and Acly in the liver was significantly suppressed in both BF-FO and DN-FO mice. Expression levels of Scd1 in epididymal adipose tissue were significantly suppressed only in the BF-FO mice. Plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid were far more increased in BF-FO than in DN-FO mice. Significantly more of these n-3 polyunsaturated fatty acids (PUFAs) were excreted in the feces of DN-FO than of BF-FO mice. These findings suggest that dietary FO exerts more hypolipidemic activity at the time of breakfast than dinner because the intestinal absorption of n-3 PUFAs is more effective at that time.

Delayed autonomic neuropathy in a patient with diethylene glycol poisoning: a case report.

Case: A 72-year-old man presented to our hospital after ingesting insecticide containing approximately 2 mL/kg diethylene glycol, which exceeded the lethal dose of 1 mL/kg. The patient recovered from critical symptoms on acute phase until day 3, but received artificial ventilation for muscle weakness secondary to sensorimotor neuropathy on days 11-54. Outcome: Even after marked improvement from sensorimotor neuropathy, the patient continued to complain of orthostatic hypotension. Autonomic neuropathy was identified by positive result of a head-up tilt test, and reduction in coefficient of variation of R-R intervals and cardiac iodine-123-metaiodobenzylguanidine uptake for the assessment of cardiac sympathetic activity. The patient's symptoms fully recovered 2 years after the exposure to diethylene glycol. Conclusion: This case shows the first report of delayed autonomic neuropathy after recovery from severe sensorimotor neuropathy, and suggests the importance of continuous monitoring for late-onset neurological complications.

Comprehensive evaluation of the effectiveness and safety of balloon pulmonary angioplasty for inoperable chronic thrombo-embolic pulmonary hypertension: long-term effects and procedure-related complications.

AIMS: Although balloon pulmonary angioplasty (BPA) improves haemodynamics and short-term prognosis in patients with inoperable chronic thrombo-embolic pulmonary hypertension (CTEPH), the long-term effects of BPA, and procedure-related complications remain to be fully elucidated. METHODS AND RESULTS: From July 2009 to October 2016, we performed a total of 424 BPA sessions in 84 consecutive patients with inoperable CTEPH. We used 3D reconstructed computed tomography to determine target lesions of pulmonary arteries and optical computed tomography to select balloon size, if needed. In 77 patients (92%) who completed the BPA treatment [65 ± 14 (SD) years-old, male/female 14/63], haemodynamics and exercise capacity were examined at 6 months after last BPA and in the chronic phase [>12 months after first BPA, 31 (20, 41) months]. The BPA treatment significantly improved mean pulmonary arterial pressure (38 ± 10 to 25 ± 6 mmHg), pulmonary vascular resistance (7.3 ± 3.2 to 3.8 ± 1.0 Wood units), and 6-minute walk distance (380 ± 138 to 486 ± 112 m) (all P < 0.01), and the improvements persisted throughout the follow-up period (43 ± 27 months) (N = 53). In the 424 sessions, haemoptysis was noted in 60 sessions (14%), and non-invasive positive pressure ventilation (NPPV) was used to treat haemoptysis and/or hypoxemia in 33 sessions (8%). Furthermore, 5-year survival was 98.4% (only one patient died of colon cancer) with no peri-procedural death. CONCLUSION: These results indicate that BPA improves haemodynamics and exercise capacity in inoperable CTEPH patients with acceptable complication rate and that the beneficial haemodynamic effects of BPA persist for years with resultant good long-term prognosis.

Cinnamic acid shortens the period of the circadian clock in mice.

Cinnamic acid (CA) derivatives have recently received focus due to their anticancer, antioxidant, and antidiabetic properties. The present study aimed to determine the effects of cinnamic acid on the circadian clock, which is a cell-autonomous endogenous system that generates circadian rhythms that govern the behavior and physiology of most organisms. Cinnamic acid significantly shortened the circadian period of PER2::LUC expression in neuronal cells that differentiated from neuronal progenitor cells derived from PER2::LUC mouse embryos. Cinnamic acid did not induce the transient mRNA expression of clock genes such as Per1 and Per2 in neuronal cells, but significantly shortened the half-life of PER2::LUC protein in neuronal cells incubated with actinomycin D, suggested that CA post-transcriptionally affects the molecular clock by decreasing Per2 mRNA stability. A continuous infusion of CA into mice via an Alzet osmotic pump under constant darkness significantly shortened the free-running period of wheel-running rhythms. These findings suggest that CA shortens the circadian period of the molecular clock in mammals.

Focal Reduction in Cardiac 123I-Metaiodobenzylguanidine Uptake in Patients With Anderson-Fabry Disease.

BACKGROUND: It remains to be elucidated whether cardiac sympathetic nervous activity is impaired in patients with Anderson-Fabry disease (AFD).Methods and Results:We performed 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and gadolinium-enhanced cardiovascular magnetic resonance (CMR) in 5 AFD patients. MIBG uptake in the inferolateral wall, where wall thinning and delayed enhancement were noted on CMR, was significantly lower compared with the anteroseptal wall. The localized reduction in MIBG uptake was also noted in 2 patients with no obvious abnormal findings on CMR. CONCLUSIONS: Cardiac sympathetic nervous activity is impaired in AFD before development of structural myocardial abnormalities. (Circ J 2016; 80: 2550-2551).

Inhibitory Effects of Vegetable Juices on CYP3A4 Activity in Recombinant CYP3A4 and LS180 Cells.

It is thought that eating habits induces individual variation in intestinal absorption and metabolism of drugs. The objective of this research was to clarify the influence of vegetables juices on CYP3A4 activity, which is an important enzyme in intestine. Five vegetables juices (VJ-o, Kagome Original(®); VJ-g, Kagome 30 kinds of vegetables and fruits(®); VJ-p, Kagome Purple vegetables(®); VJ-r, Kagome Sweet Tomato(®); and VJ-y, Kagome Fruity Salada(®); KAGOME Co., Ltd., Aichi, Japan) were centrifuged (1630×g, 10 min) and filtered using filter paper and 0.45-µm membrane filters. In this study, recombinant CYP3A4 and LS180 cells were used for the evaluation of CYP3A4 activity. The metabolisms to 6ß-hydroxytestosterone by recombinant CYP3A4 were significantly inhibited by VJ-o, VJ-g, and VJ-y in a preincubation time-dependent manner, and CYP3A4 activity in LS180 cells were significantly inhibited by VJ-o and VJ-y. These results show that the difference in ingestion volume of vegetable juices and vegetables might partially induce individual difference in intestinal drug metabolism.