Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Restrictive annuloplasty or replacement on reverse remodeling for nonischemic dilated cardiomyopathy.

BACKGROUND: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. METHODS: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). RESULTS: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14-32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). CONCLUSIONS: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM.

Feasibility of an animal model for long-term mechanical circulatory support with Impella 5.5 implanted through carotid artery access in sheep.

Impella is a mechanical circulatory support device of a catheter-based intravascular microaxial pump for left ventricular support and unloading. However, nonclinical studies assessing the effects of the extended duration of left ventricular unloading on cardiac recovery are lacking. An animal model using Impella implanted with a less invasive procedure to enable long-term support is required. This study aimed to evaluate the feasibility of an animal model for long-term support with Impella 5.5 implanted through carotid artery access in sheep.Impella 5.5 was implanted in four sheep through the proximal region of the left carotid artery without a thoracotomy, and myocardial injuries were induced by coronary microembolization. Support by Impella 5.5 was maintained for 4 weeks, and the animals were observed. The position of Impella 5.5 and cardiac function was evaluated using cardiac computer tomography at 2 and 4 weeks after implantation.All four animals completed the 4-week study without major complications. The discrepancy in the Impella 5.5 flow rate between the conscious and anesthetized states was observed depending on the device's position. Animals in whom the inflow was above the left ventricular papillary muscle had a relatively high flow rate under the maximum performance level without a suction alarm during the conscious state. Pathological changes in the aortic valve were observed. Cardiac function under the minimum performance level was observed with no remarkable deterioration.The animal model with myocardial injuries supported for 4 weeks by Impella 5.5 implanted through carotid artery access in sheep was feasible.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Radiation Therapy for Sister Mary Joseph's Nodule: A Review.

Purpose: Umbilical metastasis, known as Sister Mary Joseph's nodule (SMJN), is a manifestation of advanced malignant disease. Patients with SMJN usually require supportive care or palliative systemic chemotherapy. However, with the increasing number of older and infirm patients, radiation therapy for SMJN is needed more frequently. Therefore, we conducted this review to provide insights into radiation treatment for this rare condition. Methods and Materials: We searched PubMed on October 16, 2022, and obtained 275 articles that described SMJN or metastatic tumors within or near the umbilicus, as well as 255 case reports or case series (298 patients) and 20 reviews, original articles, or other study types, 1 of which also described a case. Results: The prognosis of patients with SMJN is extremely poor. However, some patients can survive for more than 2 years. The primary organs of the umbilical metastasis are mainly in the gastrointestinal tract, including the stomach, colon, and pancreas. In addition to these organs, the ovaries, uterine corpus, and breasts are the major organs affected in women. Metastasis may be divided into 4 types according to the tumor location and mechanism of the extension: within the umbilicus, not within although existing near or adjacent to the umbilicus, in the umbilical or paraumbilical hernia sac, and iatrogenic disease. Only 7 reports described patients who received radiation therapy in detail. The patients were divided into 2 groups: a relatively long course and high total dose (approximately 45 Gy) group, and a short course and low total dose group. Conclusions: Umbilical metastasis, known as SMJN, is a rare disease and is divided into 4 types based on the location of the disease and extent mechanism. Although the prognosis of the disease is poor, some patients survive for more than 2 years. Only 7 case reports precisely described radiation therapy. Half of the patients were treated with a short course, whereas the other half were treated with relatively high doses of up to 45 Gy.

Mitral valve repair for degenerative mitral regurgitation with Carpentier's functional classification type II in elderly patients: a single center experience.

OBJECTIVE: Mitral valve (MV) repair for Carpentier functional classification Type II (C-II) mitral regurgitation (MR) is widely accepted because of its efficacy. It is unclear whether MV repair has the same benefits in elderly patients as in younger patients because of their lower life expectancy. Herein, we examined the midterm results of MV repair for C-II mitral regurgitation, especially in patients aged ≧70 years. METHOD: A retrospective review was performed on 176 patients who underwent MV repair for C-II mitral regurgitation with a median age of 65 years; 55 (31%) patients were ≧70 years, and 124 were male (71%). Lesions of the mitral valve were isolated from the anterior leaflet (48 patients), posterior leaflet (113 patients), and both leaflets (15 patients), and included seven patients with Barlow's disease. We compared the outcomes between patients aged ≧70 years (≧70 years; median age, 76 years) and those aged < 70 years (median age, 60 years). RESULTS: In terms of the durability of MV repair in elderly patients, there were no significant differences in the rates of freedom from reoperation or MR recurrence at 5 years between patients aged < 70 years and those aged ≧70 years (reoperation:98% in < 70 years versus 89% in ≧70 years; P = 0.4053; MR recurrence:95% in < 70 years versus 81% in ≧70 years; P = 0.095). The mitral valve complexity was divided into two grades: Simple (isolated posterior mitral lesion) and Complex (isolated anterior lesion or both lesions). In patients aged < 70 years, there was no significant difference in the rate of freedom from MR recurrence at 5 years between the Simple and Complex groups (96% vs. 91%; P = 0.1029). In contrast, in patients aged ≧70 years, the MR recurrence rate at 3 years in Complex was significantly higher in the Complex group than in the Simple (100% vs. 80%; P = 0.0265). CONCLUSIONS: We studied the outcomes of MV repair for C-II in MR. In elderly patients, MR recurrence was higher in complex lesions than in simple lesions. MV replacement may be considered for elderly patients with complex mitral valve lesions, if appropriately selected.

Low Atmospheric Oxygen Attenuates Alpha Oscillations in the Primary Motor Cortex of Awake Rats.

Oxygen is pivotal for survival of animals. Their cellular activity and cognitive behavior are impaired when atmospheric oxygen is insufficient, called hypoxia. However, concurrent effects of hypoxia on physiological signals are poorly understood. To address this question, we simultaneously recorded local field potentials in the primary motor cortex, primary somatosensory, and anterior cingulate cortex, electrocardiograms, electroolfactograms, and electromyograms of rats under acute hypoxic conditions (i.e., 5.0% O2). Exposure to acute hypoxia significantly attenuated alpha oscillations alone in the primary motor cortex, while we failed to find any effects of acute hypoxia on the oscillatory power in the somatosensory cortex or anterior cingulate cortex. These area- and frequency-specific effects by hypoxia may be accounted for by neural innervation from the brainstem to each cortical area via thalamic relay nuclei. Moreover, we found that heart rate and respiratory rate were increased during acute hypoxia and high heart rate was maintained even after the oxygen level returned to the baseline. Altogether, our study characterizes a systemic effect of atmospheric hypoxia on neural and peripheral signals from physiological viewpoints, leading to bridging a gap between cellular and behavioral levels.

Paradigm shift in myocarditis treatment.

Although most cases of myocarditis are self-limiting with a gradual improvement in cardiac function, the involvement of myocarditis in sudden cardiac death among children and young adults remains substantial, with rates of 3-17 % and 8.6-12 %, respectively. Moreover, the risk of developing chronic dilated cardiomyopathy ranges from 21 % to 30 % in all cases confirmed by biopsy. Current therapeutic strategies for myocarditis and its complications range from standard supportive care for heart failure and arrhythmias to etiologically oriented, case-based therapeutic options. For example, immunosuppression is indicated only in certain forms of acute myocarditis with clinical or endomyocardial biopsy evidence of immune checkpoint inhibitor-induced myocarditis and autoimmune diseases, including giant cell myocarditis, eosinophilic myocarditis, vasculitis, or cardiac sarcoidosis. However, our views on myocarditis treatment have changed considerably over the past two decades, thanks to the emergence of regenerative cells/tissues as well as drug and gene delivery systems. Cell-based therapies are now growing in popularity in any field of medicine. Studies evaluating the therapeutic efficacy of different stem cells in the treatment of acute myocarditis and its chronic complications have shown that although the experimental characteristics varied from study to study, in general, these strategies reduced inflammation and myocardial fibrosis while preventing myocarditis-induced systolic dysfunction and adverse remodeling in animal models.

The usefulness of chest drain and epicardial pacing wire culture for diagnosing mediastinitis after open-heart surgery.

PURPOSE: Culture of extracted drains or epicardial pacing wires is an easy and noninvasive method for detecting mediastinitis after open-heart surgery, although studies on its sensitivity and specificity are limited. We, therefore, investigated the usefulness of this approach for diagnosing mediastinitis. METHODS: We retrospectively studied the culture results of drains and epicardial pacing wires extracted from 3308 patients. Prediction models of mediastinitis with and without culture results added to clinical risk factors identified by a logistic regression analysis were compared. RESULTS: The incidence of mediastinitis requiring surgery was 1.89% (n = 64). Staphylococcus was the causative bacterium in 64.0% of cases. The sensitivity, specificity, and positive and negative predictive values of positive culture results were 50.8%, 91.8%, 10.7%, and 99.0%, respectively. Methicillin-resistant Staphylococcus aureus had the highest positive predictive value (61.5%). A multivariate analysis identified preoperative hemodialysis (OR 5.40 [2.54-11.5], p < 0.01), long operative duration (p < 0.01), postoperative hemodialysis (OR 2.25 [1.01-4.98], p < 0.05), and positive culture result (OR 10.2 [5.88-17.7], p < 0.01) as independent risk factors. The addition of culture results to pre- and postoperative hemodialysis and a lengthy operative time improved the prediction of mediastinitis. CONCLUSIONS: A culture survey using extracted drains and epicardial pacing wires may provide useful information for diagnosing mediastinitis.

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports.

Introduction: With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies. Study design: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response. Results: In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation. Conclusions: Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.

Risk factor analysis for aortic dissection after aortic valve replacement in patients with tricuspid aortic valve.

OBJECTIVE: Aortic dilatation concurrent with aortic valve disease is a common condition. However, the incidence of aortic dissection after aortic valve replacement for tricuspid aortic valve has not been fully investigated. Therefore, we performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. METHODS: We retrospectively reviewed 599 patients who underwent aortic valve replacement at our hospital between January 2000 and December 2020. We performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. RESULTS: Seven patients developed late aortic dissections during the follow-up period. All patients with aortic dissection underwent aortic valve replacement for aortic regurgitation. Multivariable analysis revealed that aortic regurgitation was an independent predictor of aortic dissection (p < 0.0001). The mean ascending aortic diameter at aortic valve replacement for aortic regurgitation was significantly greater in patients with aortic dissection than in those without aortic dissection (46 [43.5-46] mm vs. 39 [36-42] mm, p < 0.001). The predictive cutoff value of ascending aortic diameter was indicated using receiver operating characteristic curve analysis; 46.0 mm (area under the curve: 0.8987). Freedom rates from aortic dissection in patients with aortic regurgitation and an ascending aortic diameter ≥ 46 mm were significantly lower than those in patients with an ascending aortic diameter < 46 mm (66.7% vs. 100% at 5 years, p < 0.0001). CONCLUSION: Aortic regurgitation combined with ascending aortic dilatation at aortic valve replacement could be a significant risk factor for late aortic dissection.

Acute severe aortic insufficiency during cardiopulmonary bypass in a bicuspid aortic valve with unrecognized annular displacement and fibrous strands: a case report.

Background: Bicuspid aortic valve (BAV) with displacement of the attachment of the conjoined aortic leaflet and fibrous strands is a rare cardiac malformation. We report a case of BAV that presented as acute massive aortic regurgitation during cardiopulmonary bypass for a planned non-valve-related procedure and was successfully treated by emergency aortic valve replacement. Case summary: A 70-year-old man with triple vessel coronary disease and severe left ventricular systolic dysfunction underwent coronary bypass grafting and graft replacement of the ascending aorta. Acute aortic regurgitation occurred during ventricular fibrillation and after de-clamping of the aortic graft. Intra-operative findings included a fused BAV (right-left cusp fusion), very asymmetrical leaflet (commissure angle of the non-fused leaflet 135°), three aortic sinuses, and conjoined leaflets originating from the myocardium in the inter-ventricular septum. The aortic leaflets were resected and replaced with a prosthetic aortic valve at the attachment site of the conjoined leaflets. Post-operatively, no peri-valvular leaks were observed, and left ventricular function was improved. Discussion: Intra-operative acute massive aortic regurgitation may be caused by a morphologically abnormal aortic leaflet and root complex in patients with a BAV. The dilated aortic root, asymmetrical leaflet, and abnormal aortic leaflet insertion, with thick septal myocardium of the coronary aortic sinus, might have caused unstable leaflet co-aptation, leading to deformation of the aortic leaflets influenced by the change in myocardial tone and intra-operative change in the sinotubular junction. Familiarity with the classification of congenital BAV, and the anatomy of the normal and abnormal aortic root complex, is important.

Clinical Outcomes of Left Ventricular Assist Device Pump Infection.

Few studies have focused on the clinical outcomes and risk factors of left ventricular assist device (LVAD) pump infection, and no standard treatment for LVAD pump infection has been established. Therefore, we used a therapeutic flowchart to manage LVAD pump infections. We retrospectively evaluated 220 patients who underwent continuous-flow LVAD implantation between January 2005 and March 2021 at Osaka University, Japan. First, we performed wound debridement, negative-pressure wound therapy, antibiotic treatment, and omental flap transposition. Subsequently, we administered conservative treatment, scheduled implantable LVAD exchange, or emergent removal of the implantable LVAD and exchange for extracorporeal LVAD or percutaneous LVAD (IMPELLA). Pump infections occurred in 32 patients. The survival rates of patients with pump infections during LVAD support were 93%, 74%, and 61% at 180 days, 1 year, and 2 years after LVAD pump infection, respectively. Fifteen patients underwent successful heart transplantation. Bridge-to-bridge surgery, preoperative use of venoarterial extracorporeal membrane oxygenation or percutaneous LVAD, high lactate dehydrogenase levels, and driveline infection were significantly associated with pump infection. Our study reveals that poor preoperative condition and driveline infection were significant risk factors for LVAD pump infection.

Successful surgical repair of adult anomalous origin of the left main coronary artery from the pulmonary artery syndrome complicated by severe mitral regurgitation: a case report.

Background: The number of diagnosed cases of anomalous origin of the left main coronary artery from the pulmonary artery (ALCAPA) in adults has increased substantially because of modern advances in non-invasive cardiac imaging. Here, we report successful surgical repair in an adult patient with ALCAPA complicated by severe mitral regurgitation (MR) and persistent atrial fibrillation. Case summary: ALCAPA syndrome was detected in a 65-year-old Asian woman with persistent atrial fibrillation by coronary computed tomographic angiography. An echocardiogram revealed severe MR caused by annular dilation, atrial enlargement, and posterior mitral leaflet tethering. In addition to ALCAPA repair, mitral valve repair and Cox-Maze IV cryoablation were performed. Mitral valve repair was performed using augmentation with an autologous pericardial patch in the posterior leaflet and ring annuloplasty. Discussion: Because the mechanism of MR with ALCAPA in an adult varies by comorbidity, mitral valve repair should be performed according to the valvular and subvalvular morphologies. It is essential to develop strategies that provide adequate myocardial protection during the surgical treatment of ALCAPA considering coronary steal and non-coronary collateral blood flow.

Staged left ventricular assist device reimplantation via the left anterior wall approach for a patient with severe pump pocket infection.

Pump pocket infection (PPI) is a refractory condition that can cause lethal complications in patients with a left ventricular assist device (LVAD). We report a case of PPI after LVAD implantation for ischemic cardiomyopathy that was successfully treated with staged pump reimplantation into the left ventricular anterior wall with the pedicled omental transfer. Major modification of the pump implantation site might be a useful strategy for local infection control of severe PPI.

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

Blue light imaging and linked color imaging as a screening mode for esophageal squamous cell carcinoma in high-risk patients: Multicenter randomized trial.

OBJECTIVES: Blue light imaging (BLI) and linked color imaging (LCI) are superior to conventional white light imaging for detecting esophageal squamous cell carcinoma (ESCC). Hence, we compared their diagnostic performances in ESCC screening. METHODS: This open-labeled, randomized controlled trial was performed at seven hospitals. Patients with a high risk of ESCC were randomly assigned to the BLI group (BLI followed by LCI) and LCI group (LCI followed by BLI). The primary end-point was the detection rate of ESCC in the primary mode. The main secondary end-point was its miss rate in the primary mode. RESULTS: In total, 699 patients were enrolled. The detection rate of ESCC did not significantly differ between the BLI and LCI groups (4.0% [14/351] vs. 4.9% [17/348]; P = 0.565); however, the number of patients with ESCC tended to be smaller in the BLI group (19 vs. 30). Notably, the miss rate of ESCC was lower in the BLI group (26.3% [5/19] vs. 63.3% [19/30]; P = 0.012) and LCI detected no ESCCs missed by BLI. The sensitivity was higher in BLI (75.0% vs. 47.6%; P = 0.042); on the other hand, the positive predictive value in BLI tended to be lower (28.8% vs. 45.5%; P = 0.092). CONCLUSIONS: The detection rates of ESCC did not significantly differ between BLI and LCI. Although BLI may have the potential to be advantageous over LCI for the diagnosis of ESCC, it is still unclear whether BLI is superior to LCI, and a further large-scale study is needed. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT1022190018-1).

Enhanced myocardial blood flow in ischemic cardiomyopathy by a slow-release synthetic prostacyclin agonist combined with coronary artery bypass grafting: The first human study in a Phase I/IIa clinical trial.

Background: YS-1402, which is a polymerized form of the synthetic prostacyclin agonist ONO-1301, has been proven in several preclinical studies to induce therapeutic effects for patients with ischemic cardiomyopathy (ICM). In this human study, we assessed the safety, tolerability, and efficacy of YS-1402, combined with coronary artery bypass grafting (CABG), for ICM. Methods: Twenty-four patients with ICM whose left ventricular ejection fraction was <40% with an indication for CABG were double-blindly assigned to four groups: placebo, 10-mg YS-1402, 30-mg YS-1402, and 100-mg YS-1402. YS-1402 or placebo medications were administered on the surface of the left ventricle at the time of the CABG. Pre- and postoperative cardiac function and myocardial blood flow were assessed for 6 months postoperatively, along with a safety assessment. Results: No severe adverse events were related to YS-1402. The maximum blood concentration of ONO-1301 was less than that of the no observable adverse effect level. Significantly increased myocardial blood flow (MBF) and cardiac function were observed in the YS-1402 group 26 weeks postoperatively, although no improvement in MBF occurred in the placebo group. Conclusion: This Phase I/IIa parallel group-controlled, dose-escalation study of YS-1402 combined with CABG for ICM demonstrated the safety, tolerability, and potential efficacy of YS-1402.

Less Invasive Left Ventricular Unloading With Impella May Improve the Clinical Outcomes of Fulminant Myocarditis.

Fulminant myocarditis (FM) requiring temporary mechanical circulatory support (t-MCS) has a high mortality rate. Peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) are sometimes insufficient to induce cardiac recovery. For patients with FM refractory to VA-ECMO with IABP, we have applied a biventricular assist device (BIVAD) or Impella to unload the left ventricle and to fully support the systemic circulation. In the last 10 years, 37 refractory FM patients histologically diagnosed with myocarditis and who did not recover with VA-ECMO were treated with BIVAD (n = 19) or Impella (n = 18). No significant difference was found between the Impella and BIVAD groups in preoperative findings other than serum creatinine level. Seventeen of 18 patients in the Impella group were successfully weaned from t-MCS in 9 (6-12) days. Conversely, the temporary BIVAD was removed in 21 (11-38) days in 10 of 19 patients. Six patients died while on temporary BIVAD because of multiple organ failure and cerebral bleeding, and three patients required conversion to implantable VAD. Compared with BIVAD, left ventricular unloading with Impella could be less invasive and could promote cardiac recovery in refractory FM patients. The Impella has the potential to provide effective temporary MCS for FM patients.