Alcohol synthesis based on the SN2 reactions of alkyl halides with the squarate dianion.

A convenient method has been developed for transforming alkyl halides into the corresponding alcohols via an SN2 reaction. Treatment of an alkyl halide with the squarate dianion at high temperature produces mono-alkyl squarate, and a one-pot basic hydrolysis of the intermediate affords the alcohol in good yield.

The outcomes of a standardized protocol for extracorporeal mechanical circulatory support selection-left ventricular challenge protocol.

There are no criteria for surgical mechanical circulatory system (MCS) selection for acute heart failure. Since 2021, we have utilized cardiopulmonary bypass system to assess patients' heart and lung condition to inform surgical MCS selection. we aimed to retrospectively analyze the outcomes of treatments administered using our protocol. We analyzed the data of 19 patients who underwent surgical MCS implantation. We compared patients' characteristics across the biventricular-assist device (BiVAD), central Y-Y extracorporeal membrane oxygenation (ECMO), central ECMO, and left VAD (LVAD) systems. Patients' diagnoses included fulminant myocarditis (47.4%), dilated cardiomyopathy (21.1%), acute myocardial infarction (15.8%), infarction from aortic dissection (5.3%), doxorubicin-related cardiomyopathy (5.3%), and tachycardia-induced myocarditis (5.3%). Eight patients (42.1%) underwent LVAD implantation, 1 (5.2%) underwent central ECMO, 4 (21.1%) underwent BiVAD implantation, and 6 (31.6%) underwent central Y-Y ECMO. 48 h after surgery, both the pulmonary arterial and right atrial pressures were effectively controlled, with median values being 19.0 mmHg and 9.0 mmHg, respectively. No patients transitioned from LVAD to BiVAD in the delayed period. Cerebrovascular events occurred in 21.1%. Successful weaning was achieved in 11 patients (57.9%), and 5 patients (26.3%) were converted to durable LVAD. Two-year cumulative survival was 84.2%. Our protocol showed good results for device selection in patients with heart failure, and device selection according to this protocol enabled good control of the pulmonary and systemic circulations.

Discovery of a potent, orally available tricyclic derivative as a novel BRD4 inhibitor for melanoma.

The epigenetic regulation of the protein bromodomain-containing protein 4 (BRD4) has emerged as a compelling target for cancer treatment. In this study, we outline the discovery of a novel BRD4 inhibitor for melanoma therapy. Our initial finding was that benzimidazole derivative 1, sourced from our library, was a powerful BRD4 inhibitor. However, it exhibited a poor pharmacokinetic (PK) profile. To address this, we conducted a scaffold-hopping procedure with derivative 1, which resulted in the creation of benzimidazolinone derivative 5. This new derivative displayed an improved PK profile. To further enhance the BRD4 inhibitory activity, we attempted to introduce hydrogen bond acceptors. This indeed improved the activity, but at the cost of decreased membrane permeability. Our search for a potent inhibitor with desirable permeability led to the development of tricyclic 18. This compound demonstrated powerful inhibitory activity and a favorable PK profile. More significantly, tricyclic 18 showed antitumor efficacy in a mouse melanoma xenograft model, suggesting that it holds potential as a therapeutic agent for melanoma treatment.

Transthyretin derived amyloid deposits in the atrium and the aortic valve: insights from multimodality evaluations and mid-term follow up.

BACKGROUND: Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. CASE PRESENTATION: We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. CONCLUSIONS: While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures.

Novel application to evaluate endometrial blood flow using transvaginal superb microvascular imaging: A preliminary study describing physiological changes from ovulation to mid-luteal phase.

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.

Prognostic impact of lung computed tomography density in cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation.

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.

A unique cuff-sewing method to implant heartmate3 LVAD for arrhythmogenic right ventricular cardiomyopathy, facilitated by 3D-printing heart model.

Implantation of left ventricular assist device (LVAD) for arrhythmogenic right ventricular (RV) cardiomyopathy is challenging associated with small LV cavity, laterally dislocated LV apex, thin and fragile RV free wall. A 43-year-old male with more than 10 years of medical treatment developed congestive heart failure related to biventricular failure. Durable LVAD was indicated to prevent further deterioration of the RV function, which would be exacerbated by progression of LV dysfunction. To simulate surgery, we printed-out a 3D heart model based on enhanced CT scanning study to identify the optimal coring position in the LV apex, by which the inflow directs the mitral valve. We then found that the mini-cuff of the HeartMate3 should be fixed in the paper-thin RV free wall by the usual cuff-sewing method. In the surgery, after the coring as planned, 5 pairs of interrupted sutures on the medial side were passed from the luminal side of the LV and then to the mini-cuff, and the lateral side of the mini-cuff was fixed with a continuous sutures, not to sew into the RV wall. The surgery was completed without complications with a good hemodynamics. The 3D heart model facilitated this unique method, indicating a usefulness of printed-out heart model for cases with unusual cardiac anatomy, which needs implantation of durable LVAD.

Use of cardiopulmonary bypass is associated with chronic postsurgical pain among patients undergoing coronary artery bypass graft surgery: follow-up of a randomized, clinical trial.

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.

[Asymptomatic Ball Thrombus in Right Atrium Under Anticoagulant Therapy:Report of a Case].

A rare case of isolated right atrial thrombus under anticoagulant therapy for atrial fibrillation is reported herein. The patient was an 81-year-old man undergoing anticoagulant therapy with oral warfarin for atrial fibrillation. During preoperative screening for eye surgery, echocardiography revealed a mobile mass in the right atrium, and emergency hospital admission was indicated. Excision of the right atrial thrombus was performed, and no residual thrombus was detected on postoperative imaging studies. This case was considered a good indication for surgical resection because of potential risk of fatal embolism.

Early Atrial Tachyarrhythmia Recurrence Predicts Late Atrial Tachyarrhythmia Recurrence After the Cryo-Maze Procedure　- An Observational Study.

BACKGROUND: It is unknown whether early atrial tachyarrhythmia (ATA) recurrence occurring within 3 months after the Maze procedure predicts late ATA recurrence.Methods and Results: This study involved 610 patients who underwent the modified Cryo-Maze procedure in conjunction with other cardiac surgery. The primary outcomes were late ATA recurrence, defined as occurring ≥3 months after surgery. The effects of early ATA recurrence on late ATA recurrence were analyzed using a Cox proportional hazards model. The following 11 covariates were considered explanatory variables: early ATA recurrence, age, sex, body surface area, preoperative duration of atrial fibrillation, preoperative left atrial diameter, and concomitant surgery (mitral valve replacement, mitral valve repair, aortic valve replacement, tricuspid annuloplasty, and left atrial appendage closure). Statistical analyses were performed with a 2-sided 5% significance level. Early ATA recurrence occurred in 174 patients (28.5%). Late ATA recurrence occurred in 167 patients (27.5%), with 595 events identified in these patients. The Cox proportional hazards model showed that early ATA recurrence was an independent predictor of late ATA recurrence (hazard ratio, 4.14; 95% confidence interval, 3.00-5.70; P<0.001)Conclusions: Early ATA recurrence was an independent predictor of late ATA recurrence among patients undergoing the modified Cryo-Maze procedure. The blanking period might not be applied to patients undergoing the modified Cryo-Maze procedure.

Early Outcomes of Intuity Rapid Deployment Aortic Valve Replacement Compared With Conventional Biological Valves in Japanese Patients.

BACKGROUND: This study aimed to elucidate the short-term surgical outcomes and hemodynamics of the Intuity valve compared to the standard bioprosthesis in Japanese patients.Methods and Results: Among the 307 consecutive patients who underwent aortic valve replacement (AVR) between February 2019 and March 2021, the Intuity valve was implanted in 95 patients (Intuity group) and a conventional stented bioprosthesis was implanted in 193 patients (conventional group). After propensity score matching, there was no significant difference in in-hospital mortality between the Intuity (n=2, 3%) and conventional groups (n=0, P=0.490). Operation, cardiopulmonary bypass, and aortic cross-clamping times were significantly shorter in the Intuity group. Although the effective orifice area index, trans-prosthetic mean pressure gradient, and peak velocity were similar between the 2 groups at 1 week postoperatively, the Intuity group showed a better mean pressure gradient and peak velocity at 1 year postoperatively. Complete atrioventricular block requiring permanent pacemaker implantation developed in 2 patients (3%) in the Intuity group and none in the conventional group (P=0.476). Mild or greater paravalvular leakage was present in 8 patients (13%) in the Intuity group and 2 patients (3%) in the conventional group (P=0.095). CONCLUSIONS: AVR using the Intuity valve in Japanese patients is satisfactory, with a better valve performance and a low incidence of complete atrioventricular block at 1 year postoperatively.

Transaortic Transcatheter Aortic Valve Replacement in Patients From a Single Institution　- Feasibility, Safety, and Midterm Outcomes.

BACKGROUND: Transaortic transcatheter aortic valve replacement (TAo-TAVR) is an alternative to peripheral or transapical TAVR. The procedural feasibility, safety, and midterm outcomes of TAo-TAVR were investigated in this study.Methods and Results:Eighty-four consecutive patients underwent TAo-TAVR from 2011 to 2021. Their median age was 83 years (interquartile range, 80-87 years). The Edwards SAPIEN and Medtronic CoreValve devices were used in 45 (53.6%) and 38 (45.2%) patients, respectively. The surgical approach was a right mini-thoracotomy in 43 patients (51.2%) and partial sternotomy in 4 patients (4.8%). The remaining 37 patients (44.0%) underwent full sternotomy because of concomitant off-pump coronary artery bypass grafting. VARC-3 device success was achieved in 77 patients (91.7%). Valve migration occurred in 3 patients (3.6%) using a first-generation CoreValve device, necessitating implantation of a second valve. No aortic annulus rupture, aortic dissection, or coronary orifice occlusion occurred. Conversion to surgery was required for 1 patient because of uncontrollable bleeding. Only 1 in-hospital death occurred. New pacemaker implantation was required in 6 patients (7.1%). Echocardiography at discharge showed no or trivial paravalvular leak (PVL) in 58 patients (69.0%), mild PVL in 23 (27.4%), and mild to moderate PVL in 2 (2.4%) patients. The 1- and 3-year incidence of cardiovascular death was 1.6% and 4.8%, respectively, with no structural valve deterioration. CONCLUSIONS: TAo-TAVR is feasible and safe with satisfactory midterm outcomes using both currently available devices.

Short-Term Outcomes of Magnetically Levitated Left Ventricular Assist Device in Advanced Heart Failure　- The Japanese Cohort.

BACKGROUND: The superiority of a fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) in terms of overall survival, stroke events and pump thrombosis has been demonstrated in previous international analyses, so we evaluated a Japanese cohort for the same.Methods and Results: This retrospective observational study was conducted at Osaka University Medical Hospital and the National Cerebral and Cardiovascular Center in Japan. A total of 75 consecutive patients who underwent HeartMate3 (HM3) implantation were included. The primary endpoint was on-device survival, and the secondary endpoint was the incidence of LVAD-related complications at 2 years. All parameters were compared with those of the previously performed HeartMate II (HMII) implantation in 197 cases. The on-device survival rates were 94.7% and 92.3% in the HM3 and HMII groups, respectively, at the 2-year follow-up (P=0.62). The rehospitalization-free rate after implantation was 61.8% in the HM3 group, which was significantly higher than that in the HMII group (relative risk, 0.35; 95% confidence interval [CI], 0.23-0.55; P<0.0001). Event-free survival rates from cerebral cerebrovascular events and pump thrombosis in the HM3 group were significantly higher than those in the HMII group, at 97.2% and 100%, respectively (relative risk, 0.14; 95% CI 0.03-0.58); P=0.0015 and relative risk, not calculated; P=0.049, respectively). CONCLUSIONS: Satisfactory short-term outcomes were observed after HM3 implantation in a Japanese cohort.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves　- Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

BACKGROUND: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Comparison of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and an Aortic Bioprosthetic Valve.

BACKGROUND: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited data comparing DOACs and warfarin in AF patients with an aortic BPV.Methods and Results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51-1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577). CONCLUSIONS: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.

Impact of sleep-disordered breathing on ventricular tachyarrhythmias after left ventricular assist device implantation.

Sleep-disordered breathing (SDB) is associated with an increased risk of adverse events in patients with heart failure (HF); however, its impact in patients implanted with a left ventricular assist device (LVAD) remains unclear. We aimed to investigate the prevalence of SDB in patients with LVAD and its impact on their clinical outcomes. Fifty consecutive patients with LVAD who underwent portable sleep monitoring between September 2017 and April 2018 were prospectively enrolled, and they were followed up for 170 ± 36 days. According to their respiratory disturbance indexes (RDIs), they were categorized into the SDB group (RDI ≥ 15, n = 12) and the non-SDB group (RDI < 15, n = 38). The incidence of adverse events during the follow-up period was investigated after enrollment. Multivariate logistic regression analysis revealed significant differences in SDB in LVAD-implanted patients in terms of the logarithmic transformation brain natriuretic peptide (BNP) values (p = 0.005). The optimal BNP cut-off value for SDB prediction in LVAD-implanted patients was 300 pg/mL (sensitivity: 58.3%, specificity: 94.7%). During follow-up, ventricular tachyarrhythmias (VTas) occurred significantly more frequently in the SDB group (4 [33%] vs. 2 [5%] patients, p = 0.02); Atrial tachyarrhythmia (ATa) also tended to occur more frequently in the SDB group (2 [25%] vs. 2 [2%] patients, p = 0.07). SBD was prevalent in 24% of the LVAD-implanted patients with advanced HF. Furthermore, SDB was significantly associated with high BNP levels and was also potentially associated with subsequent incidence of VTa in patients with LVAD.

Bridge from central extracorporeal life support is a risk factor of cerebrovascular accidents after durable left ventricular assist device implantation.

A bridging strategy from extracorporeal life support (ECLS) is effective in salvage and a bridge to recovery or to a durable left ventricular assist device (LVAD) for acute refractory heart failure. However, the correlation of this strategy with adverse events after durable LVAD implantation has not been fully investigated. This study enrolled 158 consecutive patients who had either the HeartMate II or HeartMate 3 and were implanted for bridge-to-transplantation. These devices were implanted as the primary mechanical support device in 115 patients, whereas the remaining 43 underwent LVAD implantation as the bridge from central ECLS. The primary study endpoint was all-cause mortality and cerebrovascular accidents (CVAs) after durable LVAD implantation, and the secondary endpoints were adverse events. Overall survival was not significantly different between the two groups. In contrast, the probability of CVAs was significantly greater in the bridge group than in the primary group (probability of CVAs, P = 0.002; log-rank test). In Cox multivariate logistic regression analysis, a bridge from central ECLS was an independent predictive factor of CVAs (hazard ratio 4.27, 95% confidence interval 1.43-12.8; P = 0.0095). Patients who are bridged from central ECLS are more frequently complicated by CVAs compared with those who undergo primary implantation of a durable LVAD, but survival is not significantly different between the two groups. A bridge from central ECLS is an independent predictive factor of CVAs post-implantation of an LVAD.

Efficacy of Off-Pump Coronary Artery Bypass Grafting With Concomitant Transcatheter Aortic Valve Replacement.

AIM: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

[Beneficial Effects of the Modified Bicaval Anastomosis Technique for Orthotopic Heart Transplantation from a Size-Mismatched Donor:20-year Single Center Experience].

BACKGROUND: Size-mismatched heart transplantation( HTx) is associated with a risk of stenosis of the caval anastomosis site or low cardiac output syndrome. We developed a modified bicaval anastomosis technique( mBCAT) that achieved an adjustable caval anastomosis to compensate for the size mismatch. This study clarified clinical outcomes of HTx with mBCAT technique according to the degree of the size mismatch. METHODS AND RESULTS: This study consisted of 130 adult patients who underwent HTx with the mBCAT during a 22-year period and were followed up for at least 1 year. The cohort was divided into three groups according to the donor-to-recipient body weight ratio:<0.8, undersized group (n=19);0.8 ~1.3, size-matched group( n=89);and >1.3, oversized group( n=22). The undersized, size-matched, and oversized groups showed no significant differences in the rate of mild or worse tricuspid regurgitation on echocardiography at 1 month [ 1( 5.3%), 8( 9.0%), and 1( 4.6%), respectively;p=0.683] or the survival rate at 10 years( 100%, 96%, and 95%, respectively;p=0.452). The right heart catheter study revealed no pressure gradient across the orifices of both cavae in any patient. Additionally, the cardiac index immediately post-HTx was low in the undersized group, but improved over time in all groups, achieving the comparable value at 6 and 12 months post-HTx. CONCLUSIONS: The mBCAT prevented caval anastomosis-related complications in size-mismatched HTx and achieved excellent hemodynamics regardless of donor size.

Estrogen promotes increased breast cancer cell proliferation and migration through downregulation of CPEB1 expression.

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.