Importance of the relative epicardial connection locations and right-sided pulmonary vein isolation line for successful pulmonary vein isolation.

INTRODUCTION: The presence of an epicardial connection (EC) decreases the success rate of pulmonary vein isolation (PVI); however, the effect of designing isolation lines has not been evaluated. We sought to clarify the effects of designing an anterior line for right-sided PVI considering the presence and location of the EC. METHODS: Seventy-four consecutive patients who underwent initial catheter ablation for atrial fibrillation were retrospectively included in this study. The presence of the EC was determined by the left atrial (LA) activation map during right atrial pacing, and patients were divided into EC-positive (n = 23, 31%) and EC-negative (n = 51, 69%) groups. EC-positive patients were further subdivided based on the EC location: on-the-line group, (EC on the PVI line, n = 11); inside-line group (EC on the pulmonary vein [PV] side, n = 10); and outside-line group (EC on the LA side, n = 2). The PVI parameters were compared among the three groups. RESULTS: The success rates of the first-pass isolation were comparable between the EC-negative and EC-positive groups (70.6% vs. 60.9%, ns), but the success rate was significantly higher in the on-the-line group than in the inside-line group (91% vs. 20%, p = 0.002). First-pass isolation was successful in both patients in the outside-line group. Additional carina ablation was required only in the inside-line group. CONCLUSIONS: The association between the EC site and the right-sided PV anterior isolation line affected the success rate of first-pass isolation. For successful right-sided PVI, it is important to consider the EC site when designing the PVI line.

Comparison of Cryoballoon and Contact Force-Sensing Radiofrequency Ablation for Persistent Atrial Fibrillation in Clinical Practice.

BACKGROUND: Outcomes of cryoballoon ablation for persistent atrial fibrillation (AF) are unclear, especially in Japanese patients, so the effectiveness and safety of cryoballoon ablation in clinical practice were retrospectively compared with those of contact force-sensing radiofrequency (CFRF) ablation including the high-power protocol.Methods and Results:Consecutive patients with persistent AF were reviewed, and 253 and 265 patients who underwent cryoballoon and CFRF ablation, respectively, were enrolled. The primary endpoint was atrial arrhythmia recurrence. The secondary endpoints were periprocedural complications and repeat ablation. The rate of additional left atrial (LA) ablation after pulmonary vein isolation (PVI) was similar between groups (68.8% cryoballoon vs. 74.0% CFRF, P=0.19). Freedom from atrial arrhythmia recurrence was comparable between groups over a follow-up of 25.5±12.5 months (72.3% cryoballoon vs. 69.8% CFRF; adjusted hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.59-1.21, P=0.36). Outcomes were similar in the subgroups of PVI alone and PVI plus additional LA ablation. LA posterior wall isolation, absence of defragmentation, and low creatine clearance, but not catheter selection, were associated with the primary endpoint. Periprocedural complications (adjusted HR 0.73, 95% CI 0.34-1.54, P=0.41) and repeat ablation (adjusted HR 1.11, 95% CI 0.71-1.74, P=0.64) were similar for both procedures. CONCLUSIONS: Cryoballoon ablation for persistent AF in Japanese clinical practice had acceptable outcomes comparable to those of advanced CFRF ablation.

Mechanism of improvement in atrial functional mitral regurgitation after catheter ablation for atrial fibrillation: Three-dimensional analysis using multislice computed tomography.

BACKGROUND: Several factors associated with atrial functional mitral regurgitation development have been reported; however, geometric changes in the mitral apparatus after catheter ablation for atrial fibrillation have not been sufficiently investigated. This study aimed to clarify what determines improvements in atrial functional mitral regurgitation after sinus rhythm restoration in patients who underwent catheter ablation for atrial fibrillation by using multislice computed tomography. METHODS: We analysed volumetric multislice computed tomography images of 44 atrial fibrillation patients with significant atrial functional mitral regurgitation (moderate or worse) before and after catheter ablation. We measured the three-dimensional geometry of the mitral apparatus including the mitral annular area and interpapillary muscle distance. We calculated the differences before and after catheter ablation (Δmitral annular area, Δinterpapillary muscle distance) and assessed mitral regurgitation severity based on the mitral regurgitant jet area and its changes before and after catheter ablation (Δjet area) using transthoracic echocardiography. RESULTS: After catheter ablation, the jet area was significantly decreased. The left ventricular ejection fraction was significantly increased and the left ventricular volume had a decreasing trend. The Δjet area was significantly correlated with the Δinterpapillary muscle distance (r = .43; p = .004). The Δinterpapillary muscle distance was the strongest determinant of improvements in atrial functional mitral regurgitation severity (p = .026). CONCLUSIONS: Decreased interpapillary muscle distance was strongly associated with improvements in atrial functional mitral regurgitation. Amelioration of left ventricular dysfunction by sinus rhythm restoration might be related to improvements in atrial functional mitral regurgitation after catheter ablation.

[A Case of Malignant Lymphoma of the Ileum and Uterine Cervix with Perforating Peritonitis of Ileum Tumor Detected during Chemotherapy].

A 77-year-old woman was admitted to our hospital because of right lower abdominal pain. CT revealed tumors in the ileum and uterine cervix. After a gynecological biopsy of the uterine tumor, we diagnosed Stage Ⅳ diffuse large B-cell lymphoma. We treated her with R-THPCOP chemotherapy. On day 8 after the first chemotherapy, she developed perforated peritonitis, and an emergency partial ileum resection was performed. Histopathologically, viable cells were not found in the resected intestine. Chemotherapy was resumed on postoperative day 21, and she achieved a complete response 8 months after the surgery. Gastrointestinal malignant lymphoma is sometimes reported in cases requiring emergency surgery. Therefore, information sharing between hematologist and surgeon is recommended.

Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation.

BACKGROUND: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting. METHODS: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. RESULTS: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. CONCLUSIONS: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.

Atrial tachycardia with multiple reconductions across the surgical incision.

Incisional atrial tachycardia (AT) with multiple penetrating points on one surgical incision has not been reported yet. We present a case of incisional AT following mitral valve annuloplasty with a superior transseptal approach, in which two reconduction sites were parts of the reentrant circuit. Radiofrequency ablation at the reconduction site successfully terminated the tachycardia. A total of four penetrating points were found on the incision line, and radiofrequency ablation at these sites was completed. Detailed mapping of possible reconduction sites along the incision line should be performed to avoid further instances of AT following open heart surgery.

Comparison of dragging ablation and point-by-point ablation with a laser balloon on linear lesion formation.

INTRODUCTION: Lesion size and continuity in dragging laser balloon (LB) ablation, which may enable fast and durable pulmonary vein isolation for atrial fibrillation, are unknown. We evaluated the differences in size and continuity of linear lesions formed by dragging ablation and conventional point-by-point ablation using an LB in vitro model. METHODS AND RESULTS: Chicken muscles were cauterized using the first-generation LB in dragging and point-by-point fashion. Dragging ablation was manually performed with different dragging speeds (0.5-2°/s) using an overlap ratio of the beginning and last site during one application at 12 W/20 s and 8.5 W/30 s. Point-by-point ablation was performed with 25% and 50% overlap ratios at six energy settings (5.5 W/30 s to 12 W/20 s). Lesion depth, width, and continuity were compared. Lesion continuity was assessed by the surface and deep visible gap degree categorized from 1 (perfect) to 3 (poor). Twenty lesions were evaluated for each ablation protocol. Lesion depth and width in dragging ablation at high power (12 W) were comparable with most measurements in point-by-point ablation. Lesion depth and width were smaller at faster-dragging speed and lower power (8.5 W) in dragging ablation. The surface visible gap degree was better in dragging ablation at all dragging speeds than a 25% overlapped point-by-point ablation (p < .001). CONCLUSION: Dragging LB ablation at high power provides deep and continuous linear lesion formation comparable with that of point-by-point LB ablation. However, lesion depth and width depending on the dragging speed and power.

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

Acetylcholine spasm provocation test by trans-radial artery and brachial vein approach.

BACKGROUND: Temporary pace maker is necessary because of transient block or bradycardia during the intracoronary acetylcholine spasm provocation tests based on the Japanese Circulation Society guidelines. OBJECTIVES: We examined the feasibility and safety of the acetylcholine spasm provocation test via the radial artery and brachial vein approach. METHODS: We tried to perform the acetylcholine spasm provocation tests in 252 patients via the radial artery and brachial vein approach procedures during 5 years. Acetylcholine was injected in incremental doses of 20/50/80 µg into the right coronary artery (RCA) and 20/50/100/200 µg into the left coronary artery (LCA). Back-up pacing rate was set at 40 beats/min. Positive spasm was defined as transient ≥90% luminal narrowing and ischemic electrocardiographic change or usual chest pain. RESULTS: The procedure success of radial artery and brachial vein access was 94.4% (238/252) and 93.3% (235/252), respectively. We performed 221 patients (87.7%) with acetylcholine tests by radial artery and brachial vein approach. We changed to the brachial approach due to the failures of radial artery access in 14 patients. We also changed to the femoral vein in 11 patients and internal jugular vein in two patients. Back-up pace maker rhythm was observed in 92.1% (232/252) of all study patients, while it was significantly higher in the RCA testing than that in the LCA tests (84.9% (191/225) vs. 52.2% (131/251), P < 0.001). No irreversible complication was found. CONCLUSIONS: We recommend the radial artery and brachial vein approach for safety and convenience when performing the acetylcholine spasm provocation tests.

Differential incidence and morphology of provoked spasm between intracoronary acetylcholine and ergonovine testing: recommendation of supplementary use.

When cardiologists diagnose patients with coronary spastic angina, Japanese Circulation Society (JCS) guidelines recommend the intracoronary injection of acetylcholine (ACh) and ergonovine (ER) as class I. However, the pharmacological difference between ACh and ER is controversial in the clinic. We performed both ACh and ER tests in the same 528 patients during 26 years. We investigated the provoked spasm configuration, spasm site, and clinical characteristics of provoked spasm between ACh and ER, retrospectively. We defined positive spasm as ≥90% luminal narrowing. Provoked positive spasm was observed in 161 right coronary arteries (RCA) including 83 ACh just positive, 35 ER just positive, and 43 both positive. In contrast, positive spasm was documented in 172 left coronary arteries (LCA) including 94 ACh just positive, 28 ER just positive, and 50 both positive. ACh provoked spasm more distally and diffusely, while ER induced spasm more proximally and totally or focally in the RCA. In the LCA, ACh provoked spasm more proximally, whereas ER induced spasm more distally. ER testing after the negative ACh tests of RCA and LCA documented new positive spasms in 10.3% (35/340) and 7.4% (28/376), respectively. Coronary artery trees may each have a sensitive receptor on each segment. We recommend the supplementary use of ACh and ER to document coronary artery spasm in the cardiac catheterization laboratory.

Safety and optimal protocol of provocation test for diagnosis of multivessel coronary spasm.

We examined the safety of acetylcholine (ACh) and ergonovine (ER) tests retrospectively and investigated the optimal protocol of provocation test for diagnosis of multivessel coronary spasm. We performed 1546 ACh tests and 1114 ER tests during 23 years. ACh was injected in incremental doses of 20/50/80 µg into the right coronary artery (RCA) and of 20/50/100/200 µg into the left coronary artery (LCA) over 20 s. ER was administered in total doses of 40 µg into the RCA and of 64 µg into the LCA over 2-4 min. When a coronary spasm was induced and did not resolve spontaneously within 3 min after the completion of ACh/ER injection, or when hemodynamic instability due to coronary spasms occurred, 2.5-5.0 mg of nitrate was administered into the responsible vessel. To relive provoked spasm, it is necessary to administer nitrate in 31 cases by ACh and in 76 cases by ER (2.0 vs. 6.8 %, p < 0.01) before another vessel attempts. Multivessel spasms were often observed in LCA testing than in RCA testing on both agents [ACh: 78.6 % (11/14) vs. 11.8 % (2/17), p < 0.001, ER: 37.8 % (14/37) vs. 20.5 % (8/39), ns]. Even after the administration of nitrates, positive coronary spasm was obtained in 21.1 % by ACh and 52.9 % by ER tests on another coronary artery. No irreversible complications were recognized on both tests. We should firstly perform spasm provocation tests in the LCA and we may be able to diagnose another vessel spasm by performing the complete spasm provocation tests after the administration of nitrates to relieve provoked spasm in the first attempt.

Complete definite positive spasm on acetylcholine spasm provocation tests: comparison of clinical positive spasm.

In the clinical grounds, patients with ≥90 % luminal narrowing during acetylcholine (ACh) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90 % luminal narrowing when performing ACh tests, retrospectively. We performed 763 ACh tests over 13 years (2001-2013). We analyzed chest symptoms and positive ischemic ECG changes during ACh tests. More than 90 % luminal narrowing was found in 441 patients (57.8 %) including 355 patients in the right coronary artery (RCA) and 363 patients in the left coronary artery (LCA). Chest symptom was observed in 386 patients (87.5 %) including 293 patients in the RCA and 304 patients in the LCA. ST elevation was found in 161 patients including 110 in the RCA and 85 patients in the LCA, while ST depression was recognized in 146 patients including 119 patients in the RCA and 117 patients in the LCA. Three quarter of patients with ≥90 % luminal narrowing had significant ischemic ECG changes, whereas two-third of patients with ≥90 % luminal narrowing complained usual chest pain accompanied with significant ischemic ECG changes. Unusual chest symptom was complained in 7.3 % patients with ≥90 % luminal narrowing. Neither chest symptom nor ECG changes were found in 30 patients (6.8 %) with ≥90 % luminal narrowing. A third of these patients had ischemic findings on non-invasive tests before catheterization and six patients had subtotal or total occlusion. We should realize some limitation to define positive coronary spasm based on the ischemic ECG change and chest symptom during ACh tests.

Structure activity relationship study of burkholdine analogues toward simple antifungal agents.

Cyclic and linear lipopeptides, burkholdine analogues, were synthesized by conventional Fmoc-SPPS and cyclisation with DIPC/HOBt in the solution phase. Synthesized peptides were evaluated for antifungal activities with MIC values against Saccharomyces cerevisiae and Aspergillus oryzae. As a result, the stereochemistry of the amino acid residues and sequences of burkholdine analogues exerted a significant influence on antifungal activities. In addition, we found a linear burkholdine analogue with moderate antifungal activities.

Maximal acetylcholine dose of 200 µg into the left coronary artery as a spasm provocation test: comparison with 100 µg of acetylcholine.

As a spasm provocation test of acetylcholine (ACH), incremental dose up (20/50/100 µg) into the left coronary artery (LCA) is recommended in the guidelines established by Japanese Circulation Society. Recently, Ong et al. reported the ACOVA study which maximal ACH dose was 200 µg in the LCA. We compared the angiographic findings between ACH 100 µg and ACH 200 µg in the LCA and also examined the usefulness and safety of ACH 200 µg in Japanese patients without variant angina. As a spasm provocation test, we performed intracoronary injection of ACH 200 µg after ACH 100 µg in 88 patients (55 males, 68.4 ± 11.7 years old) including 59 ischemic heart disease (IHD) patients and 29 non-IHD patients. Positive spasm was defined as >99 % transient stenosis (focal spasm) or 90 % severe diffuse vasoconstriction (diffuse spasm). Positive spasm by ACH 200 µg was significantly higher than that by ACH 100 µg (36 pts: 40.9 % vs. 17 pts: 19.3 %, p < 0.01). Diffuse distal spasm on the left anterior descending artery was more recognized in ACH 200 µg than in ACH 100 µg (30.7 vs. 13.6 %, p < 0.01). In 29 rest angina patients, positive spasm by ACH 200 µg (19 pts) was significantly higher than that by ACH 100 µg (7 pts) (65.5 vs. 24.1 %, p < 0.01). No serious irreversible complications were found during ACH 200 µg. Administration of ACH 200 µg into the LCA was safe and useful. We may reexamine the maximal ACH dose into the LCA.

Age effects on plasma cholesterol and triglyceride profiles and metabolite concentrations in dogs.

BACKGROUND: In dogs, occurrence of lipid metabolism disorders such as obesity and diabetes mellitus has increased markedly in recent years. Hyperlipidemia has been regarded as a common characteristic for obese animals and hyperlipidemic condition may be associated with inflammation, oxidative stress and lipid composition changes. In this study, we investigated the changes in plasma cholesterol and triglyceride (TG) profiles and metabolite concentrations in 24 dogs (young group: 0-7 years old, n = 12, aged group: 8-13 years old, n = 12). RESULTS: Plasma adiponectin (ADN) concentrations were significantly lower in aged dogs than those in young dogs (mean ± SD, 17.2 ± 10.0 µg mL-1 vs 29.3 ± 12.5 µg mL-1, respectively; P <0.05). Although there were no significant differences statistically, aged dogs showed significantly higher plasma alpha1- acid glycoprotein (alpah1-AG) levels compared to those in young dogs. Plasma cholesterol lipoprotein and TG lipoprotein were divided into four fractions by biphasic agarose gel electrophoresis technique. The levels of the third TG-lipoprotein fraction from the positive pole (TG Fraction 3) were significantly higher in aged dogs than in young dogs (mean ± SD, 143.0 ± 109.3 mg dL-1 vs 55.2 ± 31.3 mg dL-1, respectively; P <0.05). On the correlation coefficient analysis by Peason's method, moderate positive correlations were seen between the age and TG (r = 0.446, P = 0.029), TG Fraction 3 (r = 0.516, P = 0.010), malondialdehyde (r = 0.146, P = 0.043), alpha-1 AG (r = 0.448, P = 0.028) levels, respectively. Moderate negative correlations were seen the age and total cholesterol (TC) Fraction 2 (r = -0.446, P = 0.029), glucose (r = -0.637, P = 0.001), ADN (r = -0.408, P = 0.048), respectively. CONCLUSIONS: Present data suggest biochemical characteristics of lipid metabolism disorder may be affected by aging in dogs.

Implementation of multifaceted diagnostic stewardship for Clostridioides difficile infection during the COVID-19 pandemic at a small Japanese hospital.

Objective: Clostridioides difficile infection (CDI) is a common, healthcare-associated infection. However, in Japan, testing for CDI is infrequent, suggesting that its incidence may be underestimated. This study aimed to examine the implementation of a multifaceted, diagnostic stewardship (DS) for CDI in a small Japanese hospital during the coronavirus 2019 pandemic. Design: Before-after study. Setting: A small Japanese community hospital. Participants: Healthcare workers including physicians, nurses, and pharmacists. Interventions: A multifaceted intervention including (1) the addition of CD testing criteria to the hospital guidelines; (2) provision of a tutorial on CD testing to physicians, nurses, and pharmacists; (3) assessment by clinical pharmacists and nurses of the need for CD testing in patients with nosocomial diarrhea and issuance of recommendations for CD testing to physicians; (4) reporting of data on the CD testing rate and CDI incidence in the study center. Results: The CD testing rate increased before the pandemic (+0.16/10,000 patient-days (PD); P = .28), decreased significantly during the pandemic (-0.79/10,000 PD; P = .02), and then increased significantly immediately after the implementation of the intervention (+29.6/10,000 PD; P < .01). Similarly, the CDI incidence increased significantly before the pandemic (+0.26/10,000 PD; P = .02) and decreased significantly during the pandemic (-0.49/10,000 PD; P = .01). Implementation of the intervention resulted in an immediate and significant increase in the CDI incidence (+6.2/10,000 PD; P < .01). Conclusion: Multifaceted DS involving multidisciplinary specialists was effective in improving CD testing, suggesting that appropriate testing can contribute to diagnosing CDI accurately.

Improved seizure liability detection by combining rat hippocampal brain slice electrophysiology with in vivo behavior observation following intracerebroventricular drug administration.

An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good candidates. Firstly, in vitro electrophysiological measurement by a multielectrode array system in rat hippocampal brain slices was employed to confirm an increase in electrically evoked population spike (PS) area, the occurrence of multiple population spikes (MPSs), and thereby the seizure liability of five positive control chemicals: picrotoxin, 4-aminopyridine, pentylenetetrazole, penicillin G, and chlorpromazine. Aspirin, a negative control, did not affect PS area or generate MPSs. Furthermore, baclofen, an anticonvulsant drug, decreased PS area and inhibited the increase in PS area or occurrence of MPSs induced by picrotoxin. A comparative study of seizure liability among carbapenem antibiotics revealed that tienam > carbenin > omegacin and finibax. Despite leading to a strong decrease in PS area, physostigmine, cisplatin, and paroxetine still produced MPSs. Therefore, the increase in PS area or the occurrence of the MPS are considered significant evaluation parameters for seizure liability. In contrast, the in vitro electrophysiological measurement could not detect the seizure liability of diphenhydramine or fluvoxamine. A follow-up study of in vivo mouse behavioral change induced by intracerebroventricular administration of these drugs clearly detected convulsions. The in vitro electrophysiological study using hippocampal brain slices combined with in vivo behavior observation study of drug candidates administered by intracerebroventricular injection can implement to assess the seizure liability of even small amounts, especially in the early stages of drug development.

Evaluation after implementation of chemical bowel preparation for surgical site infections in elective colorectal cancer surgery and role of antimicrobial stewardship pharmacist: Retrospective cohort study.

BACKGROUND: We evaluated the predictive factors for surgical site infections (SSIs) in elective colorectal cancer surgery and the role of antimicrobial stewardship (AS) pharmacists in modifying the clinical pathway. MAIN BODY: Between February 2017 and January 2022, 414 elective colorectal cancer surgeries were performed. The results of multivariate analysis by SSI incidence were adjusted odds ratio (aOR): 0.45; 95% confidence interval (CI): 0.22-0.96 (P = 0.039) for sex (female), aOR: 0.27; 95% CI: 0.13-0.58 (P < 0.001) for laparoscopy, aOR: 0.42; 95% CI: 0.19-0.91 (P = 0.029) for chemical bowel preparation. The median (interquartile range) postoperative length of stay was 12 (10.0-18.5) vs. 10 (9.0-13.0) days before and after the clinical pathway was modified (P < 0.001). CONCLUSION: The role of AS pharmacists was primarily to conduct a literature search to explore whether SSIs could be ameliorated by pharmacotherapy, coordinate the addition of chemical bowel preparation, and epidemiologically confirm their effectiveness.

Association of HFA-PEFF score with clinical outcomes after catheter ablation for atrial fibrillation.

BACKGROUND: The Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing and final aetiology (HFA-PEFF) score has been developed for diagnosing heart failure with preserved ejection fraction (HFpEF), which is frequently associated with atrial fibrillation (AF). We aimed to investigate whether preprocedural HFA-PEFF score could be used to predict clinical outcomes in patients with AF who underwent catheter ablation (CA). METHODS: Overall, 1679 patients with AF who underwent primary CA (71±10 years, 1218 males (72.5%), median follow-up duration 3.3 years) from July 2011 to December 2019 were included in this retrospective study. HFpEF was defined as an HFA-PEFF score ≥5. The primary study outcome was 5-year major adverse cardiovascular and cerebrovascular events (MACCE), which is a composite of all-cause death, hospitalisation for heart failure (HF) and hospitalisation for stroke. RESULTS: The prevalence of HFpEF was 32.3%, but only 7.7% were diagnosed with HF at the time of CHADS2 scoring. Five-year MACCE occurred in 77 patients (4.6%). The cumulative 5-year incidence of MACCE was significantly higher in the HFpEF group than in the non-HFpEF group (11.2% vs 4.8% at 5 years, p<0.001). In the multivariable analysis, HFpEF by the HFA-PEFF score was associated with MACCE (adjusted HR 1.65, 95% CI 1.02 to 2.65, p=0.041). CONCLUSIONS: Early detection of HFpEF using the HFA-PEFF score may have clinical applications in guiding therapeutic decision-making and improving prognosis by preventing HF and stroke in patients with AF undergoing CA.

Characteristics of two different cryoballoon systems for treatment of paroxysmal atrial fibrillation: study protocol for a multicenter randomized controlled trial (CONTRAST-CRYO Trial).

BACKGROUND: Single-shot pulmonary vein isolation (PVI) utilizing cryothermal energy is an effective and safe treatment for atrial fibrillation (AF) patients. A novel cryoballoon system, POLARx™, has been recently introduced. The aim of this study was to compare the efficacy, safety, and biophysical parameters of PVI between the novel cryoballoon system, POLARx™, and the standard cryoballoon system, Arctic Front Advance Pro™ (AFA-Pro), in patients with paroxysmal AF. METHODS: The CONTRAST-CRYO trial is a prospective, multicenter, open-label, randomized controlled study performed at seven large cardiac centers. This study was approved by the central ethics committee or the local ethics committee of each participating hospital and has been registered at UMIN Clinical Trials Registry (UMIN000049948). The trial will assign 200 patients with paroxysmal AF undergoing PVI to POLARx™ and AFA-Pro in a 1:1 randomization. The primary endpoint is the one-shot acute success rate of the right inferior pulmonary vein. Second endpoints include freedom from documented atrial fibrillation, atrial flutter, or atrial tachycardia without antiarrhythmic drugs at 12 months after the procedure, freedom from re-do procedures, the incidence of procedure-related adverse events, freezing duration, and the biophysical parameters during applications for each PV, total procedure and fluoroscopy time, and PVI durability during re-do procedures. CONCLUSION: The CONTRAST-CRYO trial is a prospective, multicenter, randomized study designed to elucidate the difference in the efficacy, safety, and biophysical parameters between POLARx™ and AFA-Pro in paroxysmal AF patients undergoing PVI. The findings from this trial may provide a valuable indication for selecting the optimal cryoballoon system. CLINICAL TRIAL REGISTRATION:  UMIN000049948.