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• FET in an HRC has the highest risk for PAS in ART. • A history of ≥2 uterine surgeries are a risk factor for PAS in FET in an HRC. • The transfer of blastocysts is a risk factor for PAS in FET in an HRC. • Thin endometrium before ET is a risk factor for PAS in FET in an HRC. Assisted reproductive technology (ART), especially frozen–thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. We performed a case–control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case–control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60–7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15–7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10–24.44). Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies. [ABSTRACT FROM AUTHOR]

• Abdominal trachelectomy affects the pregnancy rate per embryo transfer. • A thin endometrium is seen in patients with a history of abdominal trachelectomy. • A history of abdominal trachelectomy can cause infertility. Abdominal trachelectomy (AT) is a fertility-preservation surgery for patients with early-stage cervical cancer. Few studies have reported the outcomes of assisted reproductive technology (ART) in patients after AT. The aim of this study was to evaluate the outcomes of ART after AT. In this retrospective study, we compared the ART outcomes of 13 patients who underwent AT at another hospital prior to undergoing ART at our clinic (T group) and 52 control patients (non-T group) who did not undergo AT prior to ART, selected on the basis of age, time of treatment onset, and serum anti-Müllerian hormone concentrations, matched 1:4, respectively. Cumulative live birth rates were 62% (8/13) and 65% (34/52) in the T and non-T groups, respectively (p = 0.795). The total number of oocyte retrieval cycles was 34 in the T group and 95 in the non-T group. In all oocyte retrieval cycles, no significant differences were noted in the number of oocyte retrievals, rate of fertilization, and presence of good-quality blastocysts (Gardner classification ≥ BB). The total number of embryo transfer (ET) cycles was 55 in the T group and 109 in the non-T group. The pregnancy and live birth rates per ET were lower in the T group than those in the non-T group (pregnancy rate, 20% vs. 39%, p = 0.017; live birth rate, 15% vs. 30%, p = 0.028; respectively). Endometrial thickness before ET was lower in the T group vs. the non-T group: median (range): 7.4 (3.5–14.3) mm vs. 9.0 (5.5–14.9) mm, respectively; p < 0.0001. Multivariate logistic regression models showed that age at oocyte retrieval (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.66–0.87), use of good-quality blastocysts (adjusted OR, 3.23; 95% CI, 1.20–8.67), and history of AT (adjusted OR, 0.28; 95% CI, 0.11–0.72) were associated with the pregnancy rate per ET. The pregnancy rate per ET was lower in patients with vs. without a history of AT. Clinicians should be aware of the longer time to pregnancy in patients who undergo ART after AT. [ABSTRACT FROM AUTHOR]

OBJECTIVES This study was performed to analyse the impacts of functional mitral stenosis (MS) following mitral valve (MV) repair on late cardiac function and new onset of atrial fibrillation or survival. METHODS We retrospectively reviewed 602 patients with mitral regurgitation who underwent MV repair for Type II dysfunction from 2001. Functional MS was diagnosed when the mean transmitral pressure gradient (MTPG) was ≥5 mmHg on postoperative echocardiography. We analysed preoperative and surgical risk factors for functional MS (MS group). We then compared long-term outcomes and late cardiac function over time between patients in the MS and no-MS groups using a mixed-effects model with repeated measures. RESULTS On postoperative echocardiography, 51 patients had an MTPG of ≥5 mmHg (MS group) and 551 had an MTPG of <5 mmHg (no-MS group). Only the ring size was an independent predictor of MS (28.8 ± 2.1 mm in the no-MS group vs 28.0 ± 1.9 mm in the MS group, P  = 0.004). During follow-up, increases in the tricuspid regurgitation (TR) pressure gradient (P RV-RA) and TR severity over time were significantly greater in the MS group than in the no-MS group (P RV-RA: 0.72 ± 0.16 vs 0.35 ± 0.17 mmHg per year, respectively, P  = 0.03; TR severity: 0.072 ± 0.014 vs 0.034 ± 0.015 per year, respectively, P  = 0.0113). Moreover, the 10-year rate of new onset of atrial fibrillation was significantly lower in the MS group than in the no-MS group (37.5% vs 16.9%, respectively; log-rank P  = 0.003). CONCLUSIONS Annuloplasty using a small-sized ring in MV repair caused a postoperative high MTPG, which induced an elevation in the pulmonary artery pressure and residual TR grade and causing new onset of atrial fibrillation despite a competent MV. [ABSTRACT FROM AUTHOR]

Objectives: We retrospectively evaluated graft patency in patients who underwent no-touch aortic arterial off-pump coronary artery bypass grafting to determine the optimal selection of target vessels for improved graft patency of composite and sequential radial artery I-grafts.Methods: The radial artery was anastomosed to the end of an in situ internal thoracic artery and was sequentially anastomosed to non-left anterior descending arteries. This composite graft was defined as an "I-graft." We evaluated 145 I-grafts with 2, 3, or 4 sequential anastomoses (437 graft segments). A graft segment with the final distal anastomosis of every I-graft was defined as the last graft segment (LGS). When a sequential anastomosis was initiated from the left coronary branch, the I-graft assumed a clockwise course (69.0%). When a sequential anastomosis was initiated from the right coronary branch, the I-graft assumed a counterclockwise course (31.0%).Results: On multivariable analysis, right coronary branch (P < 0.001), moderately stenotic (50-75%) target vessel (P = 0.004), and LGS with moderately stenotic target vessel (P = 0.005) were predictors of mid-term graft occlusion. In situations where the LGS was anastomosed to a severely stenotic target vessel (>75%) with a clockwise course, when the number of moderately stenotic target vessels among sequential graft segments was 0, 1, or ≥2, the mid-term graft patency rates of I-grafts were 94.0%, 86.0%, and 81.4%, respectively.Conclusions: The selection of target vessels for severely stenotic lesions among sequential graft segments and the clockwise course enhance the mid-term graft patency of sequential radial I-grafts. [ABSTRACT FROM AUTHOR]

Donor and recipient characteristics, as well as donor-recipient matching, affect clinical outcomes after heart transplantation (HTx). This study aimed to clarify how donor and recipient characteristics affect the clinical course after HTx. The medical records of all the patients who underwent HTx at the National Cerebral and Cardiovascular Center from 1999 to 2014 were retrospectively reviewed. Sixty-one patients (48 males) underwent HTx. Six recipients (9.8 %) developed primary graft dysfunction (PGD) determined by criteria recently established at a consensus conference. Development of PGD was associated with high-dose inotropic support for the donor heart and a history of stroke in the recipient ( p = 0.04 and p = 0.002, respectively). Recipients with PGD had higher right atrial pressure (RAP) and lower cardiac output (CO) compared with those without PGD at 6 months after HTx (RAP, 6.8 ± 3.6 vs. 2.8 ± 2.2 mmHg, p < 0.001; CO, 4.6 ± 0.8 l vs. 5.8 ± 1.2 l/min, p = 0.02). With respect to survival, patients with PGD had a 5-year survival rate equivalent to those without PGD (83.3 vs. 93.3 %, p = 0.23). High-dose inotropic support for the donor heart and a history of stroke in the recipient are significant predictive factors for the development of PGD. However, recipients with PGD demonstrate mid-term survival comparable to those without PGD. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe physiological changes in endometrial blood flow (minute arterioles running through the endometrium) from ovulation to the mid‐luteal phase using superb microvascular imaging. Material and methods: The study involved 17 women (median age, 32.5 years; first to third interquartile range, 29.8–40.0 years) with regular menstrual cycles who were managed in our institute from 2020 to 2021. The uterus was delineated at the sagittal section using transvaginal ultrasonography incorporated with superb microvascular imaging. For each participant, a total of 28 cycles were observed; 17 cycles observed within one day of ovulation and the implantation period, 5–7 days (D5–7) after ovulation in the same cycle, and nine cycles in which only ovulation was observed, and two cycles in which only D5–7 was observed. Therefore, 26 and 19 images at ovulation and D5–7, respectively, were acquired. Endometrial blood flow was evaluated by depth of the vascular signal in the endometrium and categorized as follows: signals only in the basal layer of the endometrium (grade 1), reaching up to half the endometrium (grade 2), and covering the whole endometrium (grade 3). Changes in the grade of endometrial blood flow from ovulation to D5–7 after ovulation, and the relationship between the grade of endometrial blood flow and the endometrial thickness on ovulation and D5–7 after ovulation, were analyzed. Statistical significance was set at p < 0.05. Results: The endometrial blood flow from ovulation to D5–7 after ovulation during the same menstrual period showed a downgrade in 14 of 17 cycles (82.3%) and no change in the remaining three cycles (17.6%), indicating a decrease in the endometrial blood flow from ovulation to D5–7 after ovulation (p = 0.001). There were differences between the grade of endometrial blood flow and median endometrial thickness on ovulation (grade 1: 5.9 mm, grade 2: 9.1 mm, and grade 3: 11.2 mm); however, no differences in the endometrial thickness were found between the grades on D5–7 after ovulation. Conclusions: In the normal menstrual cycle, endometrial blood flow decreased from ovulation to the mid‐luteal phase, and the endometrial thickness in the ovulatory phase was related to the endometrial perfusion. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the feasibility of off-pump minimally invasive direct coronary artery bypass (MIDCAB) in combination with robotic harvesting of the left internal mammary artery (LIMA). Methods: Since 2004, 33 patients [average age, 64 years; 27 males (82 %)] have undergone MIDCAB with robotic LIMA harvesting performed through the fourth or fifth intercostal space with guidance by enhanced computed tomography (CT). Results: No deaths or major adverse cardiac events occurred. Robotic LIMA harvesting was completed in 30 cases (91 %), while three cases (9 %) required conversion to a median sternotomy due to bleeding. The risk of LIMA injury significantly increased with age ( p = 0.0012). For the 30 successful cases, the average harvest time was 68 min, and the average intraoperative blood loss was 306 ml, with only three patients (9 %) requiring a transfusion. The graft flow was measurable in all cases (average, 34 ml/minute). All grafts were shown to be patent in postoperative evaluations, although CT revealed that the LIMA in one patient was anastomosed to an untargeted artery. Conclusions: Off-pump MIDCAB in combination with robotic harvesting of the LIMA is a reasonable and less invasive procedure than the standard procedures. Potential problems include difficulty controlling bleeding from the graft, especially in elderly patients, and proper identification of the target artery. [ABSTRACT FROM AUTHOR]

OBJECTIVES Although right heart failure (RVF) is an important issue in the management of patients with left ventricular assist devices (LVADs), the benefits of performing tricuspid valve repair in conjunction with LVAD implantation have not been demonstrated. METHODS We retrospectively reviewed the records of 141 patients who received LVAD implantation as a bridge to transplant from May 1999 to January 2013. We assessed short- and long-term right heart function in 69 of these patients who underwent tricuspid valve repair because of moderate-to-severe tricuspid regurgitation (TR) or severe dilatation of the tricuspid annulus. RVF was defined as the need for a right ventricular assist device or >30 days of intravenous inotropic support. TR was graded from 0 to 4, while fibrosis in myocardial biopsy samples was graded pathologically from 0 to 3. RESULTS The average duration of LVAD support was 595 days. Twenty-seven patients developed RVF and their survival rate was significantly worse than that of patients who did not develop RVF (65 vs 91% at 1 year). RVF was significantly related to high preoperative ratio of central venous pressure (CVP) to pulmonary capillary wedge pressure, high total bilirubin, high fibrosis score and high TR grade. In patients who underwent tricuspid valve repair, the TR grade was significantly reduced from 2.6 to 1.0, and this decrease was maintained for 2 years. Although patients who underwent tricuspid valve repair had significantly higher TR grades, ratios of CVP to pulmonary capillary wedge pressure and fibrosis scores preoperatively, no survival impairment was seen. CONCLUSIONS Tricuspid valve repair is a useful and durable adjuvant procedure for restoring deteriorated right ventricular function in patients requiring LVAD implantation. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of mortality after transplantation. We treated a 44-year-old female with off-pump coronary artery bypass grafting (OPCAB) 4 years after heart transplantation. Annual examinations, including coronary angiography and intravenous ultrasound (IVUS), revealed a severe lesion in the left main trunk. The left internal mammary artery was successfully anastomosed to the left anterior descending artery in an off-pump manner. To ensure that patients have a good long-term outcome after heart transplantation, routine examinations, including IVUS, are crucial, because of the nature of CAV. OPCAB is a good option for a left main trunk lesion due to CAV. [ABSTRACT FROM AUTHOR]

OBJECTIVES Aortic insufficiency (AI) often develops during left ventricular assist device (LVAD) support and is related to a poor prognosis. As LVAD implantation and the support duration increase, the risk of acquired aortic valve lesions may increase. We investigated the pathological changes in the aortic valve and its function after long-term LVAD support. METHODS Thirty-five hearts removed at heart transplantation were investigated. Thirty-one patients were supported by extracorporeal pulsatile devices, and 4 were supported by implantable devices. We compared the histological changes in the aortic valve with the echocardiogram results. RESULTS The mean duration of LVAD support was 961 days. Before device implantation, all patients had a normal aortic valve opening, and only 5 had trivial AI. After LVAD support, trivial AI was observed in 18 patients, mild AI in 4 and mild-to-moderate AI in 2. Pathological examination revealed that the aortic valve had become thinner in all patients, ranging from 120 to 1400 µm. The aortic wall had also become thinner in most patients, ranging from 830 to 2220 µm. Left ventricular wall thickness was ranging from 4 to 13 mm, and aortic annular diameter was ranging from 17 to 27 mm. Partial aortic valve fusion was seen in 17 (48.6%) recipients, and curling with leaflet shortening was detected in 22 (62.9%) patients. Dense collagen accumulation in the spongiosa layer was also present. All aortic valves of the patients with mild and mild-to-moderate AI showed a scarce or no opening before explantation. Conversely, the AI grade of patients whose aortic valve frequently opened remained none or trivial. There was no close correlation between these pathological findings and the development of AI independently. CONCLUSIONS Degenerative aortic valve changes were recognized after long-term LVAD support. There was also an increasing prevalence of mild and mild-to-moderate AI, which may have been associated with continuous aortic valve closure. An optimal strategy to prevent AI development should be determined, and careful periodic echocardiographic follow-up is essential. [ABSTRACT FROM AUTHOR]

OBJECTIVES Due to a serious heart donor shortage, the criteria for acceptance for transplantation have been expanded. This study assesses donor-related factors associated with postoperative low output syndrome (LOS) and long-term survival of recipients. METHODS From 1999 to February 2011, 36 heart transplantations were performed at our institute, of which 28 donor hearts (78%) were considered to be marginal due to high inotropic requirement (n = 11), recent episode of cardiac arrest (n = 11), female to male transplantation (n = 11), reduced left ventricular contraction (n = 6), old age (n = 6), small donor heart (n = 5), donor–recipient size mismatch (n = 2), ventricular hypertrophy (n = 2) or prolonged ischaemic time (n = 1). St Thomas solution (n = 6) and Celsior (n = 30) were used for preservation. Ischaemic damage in post-transplant cardiac patients was graded by perioperative ischaemic myocardial injury (PIMI) score (scores 0–3). RESULTS The donor age was 39 ± 11 years old, which was not significantly different to that of the recipients. 50% of the donors were female. Thirty-three donors (92%) required catecholamine at an average of 8.0 ± 5.2 µg/hg/min and echocardiogram findings showed that left ventricular ejection fraction was 65 ± 10%. All recipients survived during the perioperative period (one patient died from sepsis at 4 years after transplantation) for a 10-year survival rate of 95%. Severe primary graft dysfunction was observed in two patients who required intra-aortic balloon pumping or veno-arterial extra-corporeal membrane oxygenation, and five other patients showed postoperative LOS (cardiac index < 2.2 l/min/m2). Left ventricular diastolic diameter smaller than 36 mm (P = 0.0002), high inotropic requirement (P = 0.0089) and left ventricular ejection fraction less than 55% (P = 0.0383) were related to post-transplant LOS. All patients recovered cardiac function and were discharged from the intensive care unit after an average of 6 days. Although preservation with Celsior was not related to LOS, it had relationships with lower CKMB level (P = 0.0013) and lower PIMI score (P = 0.0054). CONCLUSIONS Cautious donor selection is essential when the donor heart has a small ventricular diameter or requires a high level of inotropic support. However, long-term survival in recipients with marginal donor hearts can be anticipated with adequate treatment. [ABSTRACT FROM AUTHOR]

Purpose: Simultaneous injection of autologous bone marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device (LVAD) implantation. Methods: Four patients (age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium. Results: No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7 × 10 to 3.0 × 10, and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by HO positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients. Conclusions: Combined cell transplantation is feasible for patients with severe ischemic cardiomyopathy, and functional recovery is anticipated in selected patients. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate the nutritional advantages of quinoa seeds (Chenopodium quinoa Willd.) cultivated in Japan, antioxidative properties and flavonoid composition were determined and compared to corresponding data for conventionally-used cereals and pseudo-cereals, including quinoa seeds from South America. The antioxidant activities of these grains against DPPH radicals were strongly associated with the total phenolic content of the tested samples. The crude extracts of quinoa seeds cultivated in Japan exhibited higher antioxidative effects than those from South America and other cereals, excluding buckwheat. Four flavonol glycosides were isolated and identified from the Japanese quinoa seeds, and the chemical composition of the flavonoids – quercetin and kaempferol 3-O-(2″,6″-di-O-α-rhamnopyranosyl)-β-galactopyranosides (1 and 4), quercetin 3-O-(2″,6″-di-O-α-rhamnopyranosyl)-β-glucopyranoside (2), and quercetin 3-O-(2″-O-β-apiofuranosyl-6″-O-α-rhamnopyranosyl)-β-galactopyranoside (3) – was evaluated through quantitative determination. Trioside 2 was isolated for the first time from quinoa seeds. These glycosides were not detected in extracts from any of the tested grains except quinoa. The aglycone quercetin content of the Japanese quinoa seeds is higher than in the seeds from South America and buckwheat. The amounts of quercetin and kaempferol formed via acidic hydrolysis in quinoa are much higher than those of conventionally-used edible plants. The quinoa seeds cultivated in Japan are the most effective functional foodstuff – in terms of being a source of antioxidative and bioactive flavonoids – among cereals and pseudo-cereals. [Copyright &y& Elsevier]

Photolyses of thianthrene sulfilimine derivatives in the presence of several olefins were studied and found to afford the corresponding aziridines in good yields, particularly, in case of 2,8-dibromo-[5-(N-tosyl)imino]thianthrene. This reaction was considered to proceed via generation of nitrene by photolytic S-N bond cleavage of thianthrene sulfilimines. Further, photo-aziridination of olefins by thianthrene sulfilimine derivatives was intensively studied to make clear the ability as nitrene precursors. [ABSTRACT FROM AUTHOR]

Background Neuroblastomas are characterized by hemizygous 1p deletions, suggesting that a tumor suppressor gene resides in this region. We previously mapped the smallest region of consistent deletion to a 2-Mb region of 1p36.31 that encodes 23 genes. Based on mutation analysis, expression pattern, and putative function, we identified CHD5 as the best tumor suppressor gene candidate. Methods We determined the methylation status of the CHD5 gene promoter in NLF and IMR5 (with 1p deletion) and SK-N-SH and SK-N-FI neuroblastoma cell lines using methylation-specific sequencing and measured CHD5 mRNA expression by reverse transcription polymerase chain reaction in cells treated with or without 5-aza-2-deoxycytidine, an inhibitor of DNA methylation. We transfected the cells with CHD5 and anti-sense (AS) CHD5 DNA to assess the effect of CHD5 overexpression and suppression, respectively, on colony formation in soft agar and growth of xenograft tumors in athymic mice. We also analyzed the association of CDH5 expression with outcomes of 99 neuroblastoma patients. Statistical tests were two-sided. Results CHD5 expression was very low or absent in neuroblastoma cell lines. The CHD5 promoter was highly methylated in NLF and IMR5 lines, and CHD5 expression increased after treatment with 5-aza-2- deoxycytidine. Clonogenicity and tumor growth were abrogated in NLF and IMR5 cells overexpressing CHD5 compared with antisense CHD5 (clonogenicity: mean no. of colonies per plate, NLF-CHD5, 43 colonies, 95% confidence interval [Cl] = 35 to 51 colonies, vs NLF-CHD5-AS, 74 colonies, 95% Cl = 62 to 86 colonies, P <.001; IMR5-CHD5, 11 colonies, 95% Cl = 2 to 20 colonies, vs IMR5-CHD5-AS, 39 colonies, 95% Cl = 17 to 60 colonies, P = .01; tumor growth, n = 10 mice per group: mean tumor size at 5 weeks, NLF-CHD5, 0.36 cm³, 95% Cl = 0.17 to 0.44 cm³, vs NLF-CHD5-AS, 1.65 cm³, 95% Cl = 0.83 to 2.46 cm³, P = .002; IMR5-CHD5, 0.28 cm³, 95% Cl = 0.18 to 0.38 cm³, vs IMR5-CHD5-AS, 1.15 cm³, 95% Cl = 0.43 to 1.87 cm³ P = .01). High CHD5 expression was strongly associated with favorable event-free and overall survival (P< .001), even after correction for MYCN amplification and 1p deletion (P = .027). Conclusions CHD5 is the strongest candidate tumor suppressor gene that is deleted from 1p36.31 in neuroblastomas, and inactivation of the second allele may occur by an epigenetic mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Several 1- and 2-substituted thianthrene sulfilimine derivatives were prepared and the selectivity toward oxidation and N-tosylimination under several conditions was studied. In the photolysis of trans-5-(N-p-tosyl)iminothianthrene 10-oxide (trans-10), photo isomerization to cis-10 was observed. Further, photoimino-transfer reaction of sulfilimines and their 10-mono- and -dioxide derivatives to sulfides was intensively studied to make clear the ability as nitrene precursors. [Copyright &y& Elsevier]

Carbon monoxide (CO), an endogenous cytoprotective product of heme oxygenase type-1 regulates target thrombotic and inflammatory genes in ischemic stress. Regulation of the gene encoding early growth response 1 (Egr-1), a potent transcriptional activator of deleterious thrombotic and inflammatory cascades, may govern CO-mediated ischemic lung protection. The exact signaling mechanisms underlying CO-mediated cytoprotection are not well understood. In this study we tested the hypothesis that inhibition of mitogen-activated protein kinase-dependent Egr-1 expression may be pivotal in CO-mediated ischemic protection. In an in vivo isogeneic rat lung ischemic injury model, inhaled CO not only diminished fibrin accumulation and leukostasis and improved gas exchange and survival but also suppressed extracellular signal-regulated kinase (ERK) activation, Egr-1 expression, and Erg DNA- binding activity in lung tissue. Additionally, CO-mediated inhibition of Egr-1 reduced expression of target genes, such as tissue factor, serpine-1, interleukin-1, and TNF-α. However, CO failed to inhibit serpine-1 expression after unilateral lung ischemia in mice null for the Egr-1 gene. In RAW macrophages in vitro, hypoxia- induced Egr-1 mRNA expression was ERK-dependent, and CO- mediated suppression of ERK activation resulted in Egr-1 inhibition. Furthermore, CO suppression of ERK phosphorylation was reversed by the guanylate cyclase inhibitor 1H-[i,2,4joxadia- zolo[4,3-a)quinoxalin-1-one but was insensitive to cAMP-dependent protein kinase A inhibition with H89 and NO synthase inhibition with L-nitroarginine methyl ester. This finding indicates that CO suppresses ERK in a cGMP-dependent but cAMP/protein kinase A- and NO-independent manner. Together, these data identify a unifying molecular mechanism by which CO interrupts proinflammatory and prothrombotic mediators of ischemic injury. [ABSTRACT FROM AUTHOR]

The palladium-catalyzed alternating copolymerization of fluoroalkenes, represented as CH2= CH-CH2-Cn-CnF2n+1 with CO was performed using (R,S)-BINAPHOS (2e) as a ligand. The CH2-CnF2n+1 group is the most electronegative substituent ever reported for the copolymerization (Taft's σ* value of 0.90 for CH2CF3). The copolymer obtained from CH2=CH-CH2-C8F17 (1a) existed as a mixture of polyspiroketal and polyketone, while that from CH2=CH-CH2-C4F9 (1b) was a pure polyspiroketal, as was revealed by infrared and 13C-CP/MAS NMR spectroscopies. The terminal structure of the polymer from lb was confirmed by MALDI-TOF MS spectrometry. Detailed NMR studies suggested that the much higher reactivity with (R,S)-BINAPHOS (2e) than that with the conventional ligand DPPP (2a) can be attributed to the unique 1 2-insertion of the fluoroalkene into acylpalladium species. The existence of an electronegative substituent on the a-carbon of the palladium center is successfully avoided in the 1,2- insertion mechanism. [ABSTRACT FROM AUTHOR]

Penicillium chrysogenum exo-arabinanase (Abnx), which releases arabinobiose from the nonreducing terminus of α-1,5-l-arabinan, was found to possess trans-arabinobiosylation activity on various acceptors, such as aliphatic alcohols, sugars, and sugar alcohols. Abnx was found to prefer primary hydroxyl groups in polyhydric alcohols as acceptors over primary hydroxyl groups in monohydric alcohols. Among the 21 different compounds tested, glycerol was the best acceptor for the enzyme. The transfer product of glycerol was identified as O-α-l-arabinosyl-(1→5)-O-α-l-arabinosyl-(1→1)-glycerol on the basis of the spectral data, fast atom bombardment-mass and 1H- and 13C-NMR. Unlike endo-arabinanases, Abnx catalyzed the hydrolysis of linear arabinan without inverting the anomeric configuration. [Copyright &y& Elsevier]

Details the isolation of three brasiliamide congeners, brasiliamides C, D and E, from okara fermented with Penicillium brasilianum Batista JV-379. Evidence that both brasiliamides C and D showed convulsive activity against silkworms with an ED[sub 50] value of 400/mug/g of diet, whereas brasiliamide E showed less activity than the others; Fermentation , extraction and preliminary separation; Structural determination of brasiliamide C.

Approximately 20% of familial amyotrophic lateral sclerosis (FALS) arises from germ-line mutations in the superoxide dismutase-1 (SOD1) gene. However, the molecular mechanisms underlying the process have been elusive. Here, we show that a neuronal homologous to E6AP carboxyl terminus (HECT)-type ubiquitin-protein isopeptide ligase (NEDL1) physically binds translocon-associated protein-δ and also binds and ubiquitinates mutant (but not wild-type) SOD1 proportionately to the disease severity caused by that particular mutant. Immunohistochemically, NEDL1 is present in the central region of the Lewy body-like hyaline inclusions in the spinal cord ventral horn motor neurons of both FALS patients and mutant SOD1 transgenic mice. Two-hybrid screening for the physiological targets of NEDL1 has identified Dishevelled-1, one of the key transducers in the Wnt signaling pathway. Mutant SOD1 also interacted with Dishevelled-1 in the presence of NEDL1 and caused its dysfunction. Thus, our results suggest that an adverse interaction among misfolded SOD1, NEDL1, translocon-associated protein-δ, and Dishevelled-1 forms a ubiquitinated protein complex that is included in potentially cytotoxic protein aggregates and that mutually affects their functions, leading to motor neuron death in FALS. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic stress. Ho-1?deficient (Hmox1-/-) mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled CO. CO drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes, which reduced accrual of microvascular fibrin. CO-mediated ischemic protection observed in wild-type mice was lost in mice null for the gene encoding PAI-1 (Serpine1). These data establish a fundamental link between CO and prevention of ischemic injury based on the ability of CO to derepress the fibrinolytic axis. These data also point to a potential therapeutic use for inhaled CO. [ABSTRACT FROM AUTHOR]

Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion receptor, procoagulant and permeability-related genes are coordinately upregulated by rapid ischemia-mediated activation of Egr-1. Deletion of the gene encoding Egr-1 strikingly diminished expression of these mediators of vascular injury in a murine model of lung ischemia/reperfusion, and enhanced animal survival and organ function. Rapid activation of Egr-1 in response to oxygen deprivation primes the vasculature for dysfunction manifest during reperfusion. These studies define a central and unifying role for Egr-1 activation in the pathogenesis of ischemic tissue damage. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p < 0.001; HOMA-R: β = − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-β < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17−4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HR-QOL) assessment is considered an important aspect of outcome in diabetes treatment. Objective: We investigated the association between QOL and clinical characteristics of patients with diabetes. Methods: Among 571 patients with type 2 diabetes and 958 healthy control subjects, the target subjects who were matched by age and sex were divided into two groups (504 in the diabetic group and 504 in the nondiabetic group). The 36-Item Short Form Health Survey questionnaire (SF-36) was used to evaluate HR-QOL. Unpaired Student's tests and Pearson's chi-square test were used for statistical analyses. Results: (1) Scores of physical functioning, role physical (physical and mental), general health, and social functioning were significantly lower in the diabetic group than in the nondiabetic group (P<0.01). (2) The physical component summary score (PCS) was significantly lower in the diabetic group (P<0.01). There was no significant difference in the mental component summary score (MCS) between the two groups. (3) The PCS score was significantly decreased (P<0.01) with age in both groups. Reduction in the PCS score was faster in the diabetic group than the nondiabetic group, with an approximate difference of 11 years. (4) In the diabetic group, patients with retinopathy, nephropathy, or neuropathy demonstrated a significant reduction in the PCS score (P<0.01); however, no difference was observed in the MCS score. (5) Regarding the association of complications, such as retinopathy, nephropathy, or neuropathy, more were the complications, significantly lower was the PCS score (P<0.01). Conclusions: QOL was significantly decreased in patients with type 2 diabetes compared with that in healthy subjects. QOL of patients with diabetic complications was significantly decreased; thus, such conditions should be taken into account when providing treatment to patients with diabetes. Disclosure: H. Murakami: None. T. Fujita: None. M. Murabayashi: None. S. Mizushiri: None. S. Osonoi: None. Y. Matsuhashi: None. M. Daimon: None. [ABSTRACT FROM AUTHOR]

Objective: Although increase in type 2 diabetes (DM) along with aging is well documented, change in insulin secretion along with aging and factors related to its change in general, nondiabetic, population has not been well examined so far. Therefore, we evaluated the relationships between insulin secretion and age, or aging, in a general population. Methods: 1. cross sectional study: Among participants of the population-based Iwaki study of Japanese people held in 2014-2017, those without diabetes were enrolled (gender (M/F): 536/882; age: 53.0±16.0) 2. longitudinal study: Among participants described above, those attended the study consecutively in 2014 and 2017 were enrolled (gender (M/F): 257/401; age: 53.7±14.1). Insulin secretion was evaluated using homeostasis model assessment (HOMA-β). Results: 1: Univariate regression analyses revealed that the relationship between HOMA-β and age appeared to be non-linear but L-shaped, with an inflection point at about 55 and 50 years for men and women, respectively. Under the ages, HOMA-β are correlated with age (β= -0.32, p<0.01, and β=-0.16, p<0.01, for men and women, respectively), while above the age, such correlation was not observed (p=0.06 and 0.42, respectively).2: Analyses to evaluate factors associated with such decreases in HOMA-β in the 3-year duration showed no significant factor for men but HDL-c (β= -0.30, p<0.01), FIB-4 index representing degree of fibrotic change of liver (β=0.25, p=0.01) and for women after adjustment for multiple factors such as BMI, serum lipid parameters, and, so on. Conclusions: Insulin secretion seems to decrease along with aging till middle age, but after the age, it dose not decrease or stays similar throughout in a general Japanese population, indicating that aging per se may not be a major determinant for impaired insulin secretion in a general, or physiological condition. Further, factors related to abnormal liver function can be markers to predict decrease in insulin secretion, at least, in women. Disclosure: T. Fujita: None. M. Daimon: None. H. Murakami: None. Y. Nishiya: None. M. Murabayashi: None. S. Mizushiri: None. Y. Matsuhashi: None. [ABSTRACT FROM AUTHOR]

Focuses on the isolation and identification of the aldose reductase inhibitor 8-hydroxydaidzein from a methanolic extract of okara fermented with the fungal strain Aspergillus species HK-388. Inhibition of human recombinant aldose reductase; Increase in polyol pathway flux under the condition of hyperglycemia; Conduct of aldose reductase assay.

Objective: Aging is one of the risks for abnormal glucose tolerance or diabetes. Although association between age and, insulin secretion and resistance has been reported in various cross sectional studies, few studies evaluated changes of insulin resistance and secretion along with aging. Research Design and Methods: Among participants of the population-based Iwaki study of Japanese, those participated consecutively from 2014 to 2017 and were nondiabetic were included in this study (Men/Women: 200/294; Age: 21-90 (54.2 ± 13.5)). The effects of aging on homeostasis model assessment indices for insulin resistance (HOMA-R) and β-cell function (HOMA-β) were examined. Results: During the 3-year periods, HOMA-R significantly increased (p<0.0001), while HOMA-β significantly decreased (p<0.0001). Repeatedly measures ANOVA with adjustments for possible confounding and/or intermediating factors showed that the increase in HOMA-R became insignificant after adjustment with factors related to adiposity such as BMI and leptin (p=0.564), while the decrease in HOMA-β stayed significant even after such adjustments (p=0.046). Despite the facts, stepwise multiple regression analysis showed significant association of leptin not only with increases in HOMA-R (p=0.022) but also with decreases in HOMA-β (p =0.003). Conclusion: Insulin resistance increases along with aging probably due to a simultaneous adiposity, while insulin secretion decreases along with aging at least in part independently of such adiposity. However, the association between leptin and decreases in HOMA-β may suggest that adiposity of β-cells may be in part blamed for the decreases. Further, leptin may be a marker to predict those at risk of decreasing insulin secretion. We are now examining such association in details in consideration with blood metabolites and amino acids levels. Disclosure: T. Fujita: None. M. Daimon: None. H. Murakami: None. S. Mizushiri: None. Y. Matsuhashi: None. S. Osonoi: None. M. Murabayashi: None. K. Takahashi: None. Y. Nishiya: None. [ABSTRACT FROM AUTHOR]

Background: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. Case presentation: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m− 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. Conclusions: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management. [ABSTRACT FROM AUTHOR]

Background: Pulmonary complications often occur in patients receiving veno‐arterial extracorporeal membrane oxygenation (VA ECMO). However, the prognostic impact of lung damage has not been fully elucidated. Methods: This single‐center retrospective observational study targeted patients with cardiogenic shock who received VA ECMO between 2012 and 2021. This study included 65 patients who underwent chest computed tomography (CT) on VA ECMO, followed by escalation to central mechanical circulatory support (MCS) with left ventricular venting. The average density of lung CT images was measured using region‐of‐interest methods, and the primary endpoint was 180‐day all‐cause death after escalation to the central MCS. Results: Twenty‐two patients (34%) developed 180‐day all‐cause death. According to the Cox regression analysis, age (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03–1.14; p = 0.001), ischemic etiology (HR, 5.53; 95% CI, 2.09–14.62; p < 0.001), duration of VA ECMO support (HR, 1.19; 95% CI, 1.00–1.40; p = 0.045), and lung CT density (≥ −481 Hounsfield unit [HU]) (HR, 6.33; 95% CI, 2.26–17.72; p < 0.001) were independently associated with all‐cause death. Receiver operating characteristic curve analysis determined that lung CT density ≥ −481 HU is an optimal cutoff value for predicting all‐cause death (area under the curve [AUC], 0.72). The 180‐day overall survival rate for patients with high lung CT density (≥ −481 HU) was significantly lower than that for those with low lung CT density (< −481 HU) (44.4% vs. 81.6%, respectively, p = 0.002). Conclusions: Higher lung CT density could be a useful predictor of death in patients with VA ECMO requiring central MCS escalation. [ABSTRACT FROM AUTHOR]

Background: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. Case presentation: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m− 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. Conclusions: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management. [ABSTRACT FROM AUTHOR]

Driveline infection (DLI) is treated by local irrigation via driveline exit site (DLES) and surgical debridement is considered in patients with deep DLI. We describe three cases of deeply progressed superficial DLI that were considered to require surgical debridement but could be treated with a unique catheter cleaning method using intravenous indwelling catheter, a cotton swab with 10% silver nitrate solution and a monofilament nylon thread. Case 1 was a 60-y-old man with ischemic cardiomyopathy with left ventricular assist device implantation 2 y before. Daily bedside debridement with 10% silver nitrate solution was performed via the DLES. Case 2 was a 43-y-old man with ischemic cardiomyopathy who had recurrent DLI with methicillin-resistant Staphylococcus aureus , and case 3 was a 49-y-old woman with hypertrophic cardiomyopathy, who also showed improvement in their DLI with Pseudomonas aeruginosa. These cleaning methods may be useful for the deeply progressed superficial DLI. [ABSTRACT FROM AUTHOR]

Background: Chronic postsurgical pain (CPSP) worsens patients' mortality, morbidity, and quality of life. Cardiopulmonary bypass is mandatory for cardiac surgery, but it induces intense inflammation. The presence of inflammation is a crucial part of pain sensitization. An extreme inflammatory response due to cardiopulmonary bypass might cause a high prevalence of CPSP after cardiac surgery. We hypothesized that the prevalence and severity of CPSP are higher in patients after on-pump coronary artery bypass graft (CABG) surgery than in those after off-pump CABG surgery. Methods: This prospective, observational study was performed on a cohort from a randomized trial (on-pump CABG: 81 patients, off-pump CABG: 86 patients). A questionnaire about the severity of surgical wound pain that evaluated pain with the numerical rating scale (NRS) was filled out by the patients. NRS responses for current pain, peak pain in the last 4 weeks, and average pain in the last 4 weeks were evaluated. The main outcomes were the severity of CPSP as evaluated using the NRS and the prevalence of CPSP. CPSP was defined as pain with an NRS score > 0. Differences in severity between groups were analyzed using multivariate ordinal logistic regression models adjusted for age and sex, and differences in prevalence between groups were analyzed using multivariate logistic regression models adjusted for age and sex. Results: The questionnaire return rate was 77.0%. During a median follow-up of 17 years, 26 patients complained of CPSP (on-pump CABG: 20 patients, off-pump CABG: 6 patients). Ordinal logistic regression showed that the NRS response for current pain (odds ratio [OR] 2.34; 95% CI 1.12–4.92; P = 0.024) and the NRS response for peak pain in the last 4 weeks (OR 2.71; 95% CI 1.35–5.42; P = 0.005) were significantly higher in patients who underwent on-pump CABG surgery than in those who underwent off-pump CABG. Logistic regression showed that on-pump CABG surgery was an independent predictor of CPSP (OR 2.59; 95% CI 1.06–6.31; P = 0.036). Conclusions: The prevalence and severity of CPSP are higher in patients with on-pump CABG surgery than in those with off-pump CABG surgery. [ABSTRACT FROM AUTHOR]

Excessive uric acid production, which causes gout and hyperuricemia, can be blocked by inhibiting xanthine oxidase (XO). However, some agents to block on XO often cause side effects, thereby necessitating the identification of new inhibitors. During the screening of XO inhibitors from various mushroom extracts, we found that a methanolic extract of the fruiting bodies of Tyromyces fissilis, an inedible and non-toxic fungus, showed inhibitory activity. Both n-hexane and ethyl acetate layers, obtained by partitioning this extract exhibited XO inhibitory activity. Subsequently, using an activity-guided separation method, eight active compounds (1–8) were isolated. The structures of five of the new compounds, 2–4, 6, and 7, were elucidated by spectral analysis and chemical derivatization. All compounds had a salicylic acid moiety with an aliphatic group at the C-6 position. Notably, 2-hydroxy-6-pentadecylbenzoic acid (1) showed the highest level of XO noncompetitive inhibition (58.9 ± 2.2% at 25 µM). Compounds 2–4, 6, and 7 newly isolated from the fruiting bodies of Tyromyces fissilis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 73-year-old woman whose transthoracic echocardiography revealed a tumor-like mass located in the mitral annulus.

This study aimed to evaluate the early and intermediate-term outcomes of patients who underwent concomitant off-pump coronary artery bypass grafting (CABG) and transcatheter aortic valve replacement (TAVR). Between January 2014 and June 2021, 49 patients underwent concomitant off-pump CABG and TAVR via median sternotomy (TAVRCAB group) and 143 underwent concomitant on-pump CABG and surgical aortic replacement. Of the 143 patients who underwent on-pump surgery, 80 (SAVRCAB group) were eligible for comparison. The composite event included all-cause death, heart failure rehospitalisation, repeat revascularisation, brain infarction, and repeat aortic valve replacement. The Society of Thoracic Surgeons' predicted risk for mortality and age were higher in the TAVRCAB group than in the SAVRCAB group (7.1% vs 3.1% [p<0.001]; 81 yrs vs 75 years [p<0.001], respectively), while the surgical time was shorter (289 min vs 352 min; p<0.001). There was no conversion to on-pump surgery in the TAVRCAB group. The postoperative maximum creatinine kinase-MB value was lower in the TAVRCAB group. There was no deep sternal wound infection or repeat revascularisation in either group. Hospital death and brain infarction developed in one patient (1.3%) each in the SAVRCAB group, but in no patients in the TAVRCAB group. The rates of freedom from the composite event were similar between the two groups during the follow-up period. Concomitant off-pump CABG and TAVR would be a less-invasive alternative procedure for treating intermediate or high surgical risk patients with aortic stenosis and coronary artery disease unsuitable for percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

• Acute calcineurin inhibitor (CNI) nephrotoxicity is a common but hard to accurately diagnose complication related to CNI. • Acute CNI nephrotoxicity is caused by the vasoconstriction of the afferent glomerular arterioles. • In current case, kidney Doppler ultrasonography clearly visualized the vasoconstriction of the renal arterioles in a heart transplant recipient. • Kidney Doppler ultrasonography should be aggressively and rapidly performed in heart transplant recipients with acute kidney injury. Acute calcineurin inhibitor (CNI) nephrotoxicity is a common complication associated with CNI exposure. However, it can be difficult to diagnose. Herein, we report a case of acute CNI nephrotoxicity after heart transplant that was visualized using kidney Doppler ultrasonography. A 38-year-old female patient underwent heart transplant 5 years after the use of left ventricular assist device support because of advanced heart failure due to ischemic cardiomyopathy. Corticosteroids, tacrolimus, and mycophenolate mofetil were administered as immunosuppressive regimens postoperatively. The patient gradually developed kidney dysfunction despite a favorable perioperative clinical course and hemodynamics. Serum creatinine increased to 1.89 mg/dL on postoperative day (POD) 9, and the kidney Doppler ultrasonography examination showed severely reduced blood flow in the renal and renal segmental arteries, indicating acute CNI nephrotoxicity due to vasoconstriction of the renal arterioles. After the cessation of tacrolimus, kidney function returned to baseline levels within 2 days, and the kidney Doppler ultrasonography examination on POD 19 revealed a significant increase in blood flow in the renal and renal segmental arteries. Basiliximab followed by everolimus were administered as alternative immunosuppressants. No organic stenosis of the renal artery was detected on the kidney magnetic resonance angiography, and the patient was discharged on POD 51, without any other adverse events, including rejection. Although CNIs are widely used after heart transplant, acute nephrotoxicity should always be considered. After heart transplant, a kidney Doppler ultrasonography should be performed routinely and promptly if there are any clinical manifestations related to kidney function. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Fulminant myocarditis with cardiogenic shock requires extracorporeal life support (ECLS) and has poor outcomes. To improve outcomes, we have converted patients with severely impaired cardiac and multiorgan function from peripheral to central ECLS. In this study, we reviewed these patients' clinical outcomes and investigated associated factors. METHODS We retrospectively studied 70 consecutive patients with fulminant myocarditis under peripheral support from 2006 to 2020. Forty-eight patients underwent surgical conversion to central support, and the remaining patients continued peripheral support. The end point was survival and ventricular assist device-free survival. RESULTS More severe pulmonary congestion and multiorgan failure were present in patients with central than peripheral support. Weaning from ECLS was achieved in 95% and 62% of patients with peripheral and central support, respectively. Five-year survival was not significantly different between patients with central and peripheral support (71.2% vs 87.5%, respectively; P  = 0.15). However, the ventricular assist device-free survival rate was significantly higher in patients with central than peripheral support (82.2% vs 52.0%, respectively; P  = 0.017). A peak creatine kinase-MB level of >180 IU/l, rhythm disturbance and aortic valve closure were detrimental to functional recovery in patients with central support. CONCLUSIONS Conversion to central ECLS is feasible and safe in patients with fulminant myocarditis. Patients with severe myocardial injury as shown by a high creatine kinase-MB level, rhythm disturbance and aortic valve closure should be converted to a durable left ventricular assist device. [ABSTRACT FROM AUTHOR]

A novel tris(4-carboxyphenyl)cyclotriguaiacylene 2 was synthesized by hydrolysis of a novel tris[(4-(methoxycarbonyl)phenyl]cyclotriguaiacylene. The structure was determined by H NMR, C NMR and mass spectroscopic techniques. The crystal structure of 2 was shown by X-ray crystallography to have a face-to-face structure of a pair of molecules of 2. The structure was constructed from 3D hydrogen-bonded network structure. Graphical Abstract: [Figure not available: see fulltext.][Figure not available: see fulltext.]. [ABSTRACT FROM AUTHOR]

Abstract: Commercially available enzyme preparations were screened for enzymes that have a high ability to catalyze direct ester-synthesis of ferulic acid with glycerol. Only a preparation, Pectinase PL “Amano” produced by Aspergillus niger, feruloylated glycerol under the experimental conditions. The enzyme responsible for the esterification was purified and characterized. This enzyme, called FAE-PL, was found to be quite similar to an A. niger ferulic acid esterase (FAE-III) in terms of molecular mass, pH and temperature optima, substrate specificity on synthetic substrates, and the N-terminal amino acid sequence. FAE-PL highly catalyzed direct esterification of ferulic acid and sinapinic acid with glycerol. FAE-PL could feruloylate monomeric sugars including arabinose, fructose, galactose, glucose, and xylose. We determined the suitable conditions for direct esterification of ferulic acid with glycerol to be as follows: 1% ferulic acid in the presence of 85% glycerol and 5% dimethyl sulfoxide at pH 4.0 and 50 °C. Under these conditions, 81% of ferulic acid could be converted to 1-glyceryl ferulate, which was identified by 1H-NMR. The ability of 1-glyceryl ferulate to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was higher than that of the anti-oxidant butyl hydroxytoluene. [Copyright &y& Elsevier]

Reports on the discovery of a novel monoterpene glucoside by researchers from Osaka, Japan. Isolation of the monoterpene glucoside from a methanol extract of the dried aerial parts of thyme; Use of thyme both as food additive and a folk medicine to treat various illnesses; Elucidation on the structure of the novel monoterpene glucosides.

Purpose: A coronary artery aneurysm (CAA) can result in critical cardiac events such as thromboembolic complications or rupture. A saccular CAA located in the left main trunk (LMT) is the most critical form of this pathology and its surgical repair is challenging. We conducted this single-center study to review the surgical outcomes of patients with a saccular CAA in the LMT. Methods: Between May, 2012 and June, 2020, five patients with a saccular CAA in the LMT underwent surgery at our center. The median age at operation was 66.5 (59.7–69) years and the median diameter of the CAA was 13.0 mm (IQR 11–14 mm). Results: The CAA was fully excluded by patch closure of the LMT orifice and direct closure of the distal LMT, supplemented by coronary artery bypass grafting with the exclusive use of arterial conduits. There was no in-hospital mortality, although one patient suffered graft spasm-related myocardial infarction with complete recovery. Post-operative angiography showed a fully excluded LMT in all patients. There was no mortality or adverse cardiac events during follow-up. Conclusions: Our surgical policy for CAA in the LMT is feasible and safe; however, coronary blood flow is dependent on reliable bypasses. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide A predictive model for atrial fibrillation recurrence and the rate of freedom from atrial fibrillation recurrence by each score Open in new tab Download slide A predictive model for atrial fibrillation recurrence and the rate of freedom from atrial fibrillation recurrence by each score OBJECTIVES This study aimed to develop a novel risk score model for quantitative prediction of the rate of atrial fibrillation (AF) recurrence after the Cryo-Maze procedure in patients with persistent AF. METHODS We enrolled 450 consecutive patients who underwent the Cryo-Maze procedure for persistent AF concomitant with other cardiac procedures in our institute between 2001 and 2019. We randomly divided the cohort into two groups. We derived a model in a 'development cohort' (270 patients; 60%) and validated it in a 'test cohort' (180 patients; 40%) by receiver operating characteristic curve analysis. RESULTS The median follow-up was 5.2 (interquartile range: 2.0–9.9) years. The 1-, 5-, 10- and 15-year rates of freedom from AF recurrence in the entire cohort were 91.4%, 83.5%, 76.2% and 57.1%, respectively. Risk factors for AF recurrence examined by logistic regression analysis included F-wave voltage in V1 < 0.2 mV, preoperative AF duration >5 years and left atrial volume index >100 ml/m2. Points were assigned to each risk factor according to its odds ratio. A novel risk score model was developed using these three variables and age, with a range up to 10 points. High score (>7) predicted high rates of AF recurrence after the Cryo-Maze procedure. The area under the receiver operating characteristic curve of the novel risk model score was 0.78 (95% confidence interval: 0.65–0.91) in the test cohort. CONCLUSIONS Use of the Cryo-Maze procedure should be carefully considered in patients with a higher model score because of a higher risk of AF recurrence. [ABSTRACT FROM AUTHOR]

Atrial tachycardia (AT) and atrial fibrillation (AF) commonly occur after cardiac surgeries (CSs). This study investigated the mechanisms and long-term outcomes of AT and AF ablation after various Maze procedures, particularly whether atrial tachyarrhythmias after the Maze procedure occur due to gaps in the Maze lines. We analyzed 37 consecutive cases with atrial tachyarrhythmias after the Maze procedures and concomitant CSs between 2007 and 2019. Fifty-nine atrial tachyarrhythmias were induced in 37 consecutive cases, and 49 of those atrial tachyarrhythmias were mappable ATs. Forty ATs were related to the Maze procedures in the 49 mappable ATs (81.6%). All 37 consecutive cases had residual electrical conductions (gaps) in the Maze lines (88 gaps; 2.4 ± 1.2 gaps/patient). Forty of 88 gaps (45.5%) were associated with gap-related ATs. The common ATs in this study were 1. peri-mitral atrial flutter due to gaps at pulmonary vein isolation (PVI) line to mitral valve annulus (MVA) (20 cases), and 2. peri-tricuspid atrial flutter due to gaps at right atrial incision to the tricuspid valve annulus (TVA) (10 cases). Forty-seven of 49 ATs (95.9%) were successfully ablated at the first session, and there were no complications. The mean follow-up period after ablation was 3.6 ± 3.2 (median, 2.1; interquartile range, 0.89–6.84) years. The Kaplan–Meier analysis of freedom from recurrent atrial tachyarrhythmias after Maze procedure was 82.7% at 1-year follow-up and 75.5% at 4-year follow-up after a single procedure. Reentry was the main mechanism of ATs after Maze procedures and concomitant CSs, and ATs were largely related to the gaps on the Maze lines between the PVI line and the MVA or those on the lines between right atrial incision to the TVA. Long-term follow-up data suggest that catheter ablation of atrial tachyarrhythmias after various Maze procedures is effective and safe. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES We aimed to analyse the pathology of paravalvular leak (PVL), and determine the long-term outcomes of redo mitral valve replacement and risk factors of all-cause mortality. METHODS Seventy-nine patients (mean age 70 ± 9 years; 54 female, 68%) who underwent redo mitral valve replacement for mitral PVL between January 2000 and May 2019 were retrospectively reviewed. Indications for PVL intervention were haemolytic anaemia (57/79, 72%), New York Heart Association class III/IV congestive heart failure (56/79, 71%) and prosthetic valve endocarditis with PVL (2/79, 3%). RESULTS PVL most commonly occurred at lateral sectors (42/79, 55%). Early mortality occurred in 2 patients (3%) due to low cardiac output syndrome. Two patients (3%) had residual PVL at discharge. Sixteen patients (23%) developed late PVL (mean follow-up, 3.4 ± 2.9 years), among whom 11 (69%) developed PVL at same area as that preoperatively. Additionally, 9 patients (56%) developed PVL at lateral sectors in late follow-up. At 1, 5 and 10 years, the survival rate was 93%, 72% and 45%; rate of freedom from cardiac death was 96%, 92% and 78%; and rate of freedom from PVL recurrence was 94%, 82% and 54%, respectively. Chronic kidney disease was the only risk factor in the multivariate analysis for mortality [ P  = 0.013; hazard ratio 4.0 (1.4–11.0)]. CONCLUSIONS Surgery for mitral PVL confers reasonable early and long-term outcomes. Greater attention to the anterolateral annulus may help prevent PVL. [ABSTRACT FROM AUTHOR]

The polyadenylation element binding protein 1 (CPEB1) plays an important role in the regulation of poly(A) tail length at the 3′UTR of mRNA during transcription. Downregulation of CPEB1 expression, which is associated with the loss of mammary epithelial polarity, has been reported in breast cancer. CPEB1 downregulation leads to an increase in tumor aggressiveness of breast cancer. Breast cancer is also known to be responsive to the treatment with steroid hormones, which promotes cancer development and progression; however, the nature of these associations remains unclear. This study aimed to investigate whether estrogen and progesterone impacted CPEB1 expression in breast cancer in order to regulate cell proliferation and migration. MCF7 cell proliferation was increased in response to estrogen treatment, and estrogen application suppressed the expression of CPEB1 mRNA. Cells treated with estrogen or those depleted for CPEB1 by shRNA showed increased wound healing capacity compared with that of control cells in migration assay. Moreover, we found that CPEB1 level of expression in human breast cancer tissue was low compared with that in the healthy tissue. CPEB1 expression was downregulated in response to estrogen activity and in turn, that caused a significantly induced cell migration in breast cancer cells. This suggests that CPEB1 is one of the estrogen responsive genes, which stimulates breast cancer progression. Increasing and/or maintaining CPEB1 expression level has the potential to control breast cancer behavior. • CPEB1 is a key protein on mammary epithelial cell polarity. • Estrogen treatment suppresses the expression of CPEB1 in MCF7 cell. • Estrogen treatment and shRNA for CPEB1 enhances MCF7 cell proliferation and migration. • CPEB1 expression is down regulated in human breast cancer tissue. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) failure is significantly associated with morbidity and mortality after left ventricular assist device (LVAD) implantation. However, it remains unclear whether LVAD implantation could worsen RV function. Therefore, we aimed to investigate the effect of LVAD implantation on RV function by comparing RV energetics derived from the RV pressure–volume curve between before and after LVAD implantation. This exploratory observational study was performed between September 2016 and January 2018 at a national center in Japan. Twenty‐two patients who underwent LVAD implantation were included in the analysis. We measured RV energetics parameters: RV stroke work index (RVSWI), which was calculated by integrating the area within the RV pressure–volume curve; RV minute work index (RVMWI), which was calculated as RVSWI × heart rate; and right ventriculo–arterial coupling, which was estimated as RV stroke volume/RV end‐systolic volume. We compared RV energetics between before and after LVAD implantation. Although RVSWI was similar [424.4 mm Hg · mL/m2 (269.5‐510.3) vs. 379.9 mm Hg · mL/m2 (313.1‐608.8), P = 0.485], RVMWI was significantly higher after LVAD implantation [29 834.1 mm Hg · mL/m2/min (18 272.2‐36 357.1) vs. 38 544.8 mm Hg · mL/m2/min (29 016.0‐57 282.8), P = 0.001], corresponding to a significantly higher cardiac index [2.0 L/min/m2 (1.4‐2.2) vs. 3.7 L/min/m2 (3.3‐4.1), P < 0.001] to match LVAD flow. Right ventriculo–arterial coupling was significantly higher after LVAD implantation [0.360 (0.224‐0.506) vs. 0.480 (0.343‐0.669), P = 0.025], suggesting that the efficiency of RV performance improved. In conclusion, higher RVMWI with higher cardiac index to match LVAD flow and improved efficiency of RV performance indicate that LVAD implantation might not worsen RV function. [ABSTRACT FROM AUTHOR]