Clinical characteristics and analysis of prognostic factors in methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis. METHODS: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019. RESULTS: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality). CONCLUSION: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE.

Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Deep learning with convolution neural network detecting mesiodens on panoramic radiographs: comparing four models.

The aim of this study was to develop an optimal, simple, and lightweight deep learning convolutional neural network (CNN) model to detect the presence of mesiodens on panoramic radiographs. A total of 628 panoramic radiographs with and without mesiodens were used as training, validation, and test data. The training, validation, and test dataset were consisted of 218, 51, and 40 images with mesiodens and 203, 55, and 61 without mesiodens, respectively. Unclear panoramic radiographs for which the diagnosis could not be accurately determined and other modalities were required for the final diagnosis were retrospectively identified and employed as the training dataset. Four CNN models provided within software supporting the creation of neural network models for deep learning were modified and developed. The diagnostic performance of the CNNs was evaluated according to accuracy, precision, recall and F1 scores, receiver operating characteristics (ROC) curves, and area under the ROC curve (AUC). In addition, we used SHapley Additive exPlanations (SHAP) to attempt to visualize the image features that were important in the classifications of the model that exhibited the best diagnostic performance. A binary_connect_mnist_LeNet model exhibited the best performance of the four deep learning models. Our results suggest that a simple lightweight model is able to detect mesiodens. It is worth referring to AI-based diagnosis before an additional radiological examination when diagnosis of mesiodens cannot be made on unclear images. However, further revaluation by the specialist would be also necessary for careful consideration because children are more radiosensitive than adults.

Redo laparoscopic colorectal resection: a retrospective analysis with propensity score matching.

PURPOSE: Reports of redo laparoscopic colorectal resection (Re-LCRR) are scarce. In order to evaluate the safety and short-term outcomes of Re-LCRR, we performed a matched case-control analysis of patients who underwent this procedure for colorectal cancer. METHOD: This was a retrospective, monocentric study that included patients who underwent Re-LCRR for colorectal cancer between January 2011 and December 2019 at our institution. The patients were compared to a 2:1 matched sample. Matching was conducted based on age, sex, BMI, surgical procedure, and clinical stage. RESULT: Twenty-nine patients underwent Re-LCRR (RCRR group) and were compared to 58 patients selected by matching who underwent LCRR as primary resection (PCRR group). The median of age of the 29 patients of RCRR group was 75 (IQR 56-81) years and the RCRR group included 14 males. The median operative time of the RCRR group was 167 (IQR 126-232) minutes, and the median intraoperative blood loss was 5 (IQR 2-35) ml. In the RCRR group, there were no cases that required conversion to laparotomy. The short-term outcomes of the two groups did not differ to a statistical extent with respect to operative time (p = 0.415), intraoperative blood loss (p = 0.971), rate of conversion to laparotomy (p = 0.477), comorbidity (p = 0.215), and postoperative hospital stay (p = 0.809). No patients in either group experienced postoperative anastomotic leakage or required re-operation due to postoperative complications, and there was no procedure-related death. However, in terms of oncological factors, although there was no difference in the number of cases with a positive radical margin between the two groups (p = 1.000), the number of harvested lymph nodes in the RCRR group was significantly lower than that in the PCRR group (p = 0.015) and the RCRR group included 10 cases with less than 12 harvested lymph nodes. CONCLUSION: Re-LCRR is associated with good short-term results and can be safely performed; however, the number of harvested lymph nodes is significantly reduced in comparison to primary resection cases, and further studies are needed to evaluate its long-term prognosis.

Clinical evaluation of anterior nasal cavity swab specimens by a rapid antigen test using a GLINE-2019-nCoV Ag Kit to diagnose COVID-19.

The promising diagnostic performance of rapid antigen tests (RATs) using non-invasive anterior nasal (AN) swab specimens to diagnose COVID-19 has been reported. A large number of RATs are commercially available; however, the careful assessment of RATs is essential prior to their implementation in clinical practice. We evaluated the clinical performance of the GLINE-2019-nCoV Ag Kit as a RAT using AN swabs in a prospective, blinded study. Adult patients who visited outpatient departments and received SARS-CoV-2 tests between August 16 and September 8, 2022, were eligible for this study. Patients who were aged under 18 years and patients without appropriate specimens were excluded. Two sets of AN and nasopharyngeal (NP) swabs were collected from all patients. Each set of specimens was tested by the RAT and quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Of the 138 recruited patients, 84 were positive and 54 were negative by RT-qPCR using NP swabs. The positive agreement rate between RT-qPCR using NP swabs and RAT using AN swabs was 78.6% (95% confidence interval [CI], 68.3%-86.8%), the negative agreement rate was 98.1% (95% CI, 90.1%-99.9%), and the overall agreement rate was 86.2% (95% CI, 79.3%-91.5%), with a κ coefficient of 0.73. The positive agreement rate in the early phase (≤3 days from symptom onset) was >80%, but this fell to 50% in the late phase (≥4 days). This study demonstrates that the GLINE-2019-nCoV Ag Kit using AN swabs has good clinical performance and might be a reliable alternative method for diagnosing COVID-19.

A New Method to Detect Variants of SARS-CoV-2 Using Reverse Transcription Loop-Mediated Isothermal Amplification Combined with a Bioluminescent Assay in Real Time (RT-LAMP-BART).

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which there are several variants. The three major variants (Alpha, Delta, and Omicron) carry the N501Y, L452R, and Q493R/Q498R mutations, respectively, in the S gene. Control of COVID-19 requires rapid and reliable detection of not only SARS-CoV-2 but also its variants. We previously developed a reverse transcription loop-mediated isothermal amplification assay combined with a bioluminescent assay in real time (RT-LAMP-BART) to detect the L452R mutation in the SARS-CoV-2 spike protein. In this study, we established LAMP primers and peptide nucleic acid probes to detect N501Y and Q493R/Q498R. The LAMP primer sets and PNA probes were designed for the N501Y and Q493R/Q498R mutations on the S gene of SARS-CoV-2. The specificities of RT-LAMP-BART assays were evaluated using five viral and four bacterial reference strains. The sensitivities of RT-LAMP-BART assays were evaluated using synthetic RNAs that included the target sequences, together with RNA-spiked clinical nasopharyngeal and salivary specimens. The results were compared with those of conventional real-time reverse transcription-polymerase chain reaction (RT-PCR) methods. The method correctly identified N501Y and Q493R/Q498R. Within 30 min, the RT-LAMP-BART assays detected up to 100-200 copies of the target genes; conventional real-time RT-PCR required 130 min and detected up to 500-3000 copies. Surprisingly, the real-time RT-PCR for N501Y did not detect the BA.1 and BA.2 variants (Omicron) that exhibited the N501Y mutation. The novel RT-LAMP-BART assay is highly specific and more sensitive than conventional real-time RT-PCR. The new assay is simple, inexpensive, and rapid; thus, it can be useful in efforts to identify SARS-CoV-2 variants of concern.

Factors related to the skin thickness of cardiovascular implantable electronic device pockets.

INTRODUCTION: The skin overlying cardiovascular implantable electronic devices (CIEDs) sometimes becomes very thin after implantations, which could cause a device erosion. The factors related to the skin thickness of device pockets have not been elucidated. This study aimed to evaluate the skin thickness of CIED pockets and search for the factors associated with the thickness. METHODS: Seventeen skin thickness points around the CIED pocket were measured through ultrasonography in each patient. RESULTS: A total of 101 patients (76 ± 11 years, 26 female) were enrolled. The median duration from the implantation to the examination was 95 months (quartile: 52.5-147.5). The median skin thickness overlying the device was 4.1 mm (3.3-5.9). Patients with heart failure and malignancy had thinner skin overlying the CIED than those without. A significant correlation existed between skin thickness and body mass index (BMI), hemoglobin, serum creatinine, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction. In contrast, age, gender, and device size did not exhibit a significant correlation with skin thickness. A multivariate logistic regression analysis revealed that chronic heart failure and a decrease in the eGFR and BMI were independent predictive factors of "very thin (≦3.3 mm)" skin of the CIED pocket late after an implantation. CONCLUSION: Aside from a low BMI, the comorbidities (low hemoglobin, heart failure, and renal dysfunction) had a stronger impact on the skin thickness overlying the device than the device size. A careful observation of the device pocket should be performed in patients with those risk factors.

Prevalence, molecular characterization, and drug susceptibility of extended-spectrum ß-lactamase-producing Klebsiella pneumoniae, K. quasipneumoniae, and K. variicola in Japan.

Klebsiella pneumoniae is an extended-spectrum ß-lactamase (ESBL)-producing bacterium (ESBL-KP). Recently, K. quasipneumoniae and K. variicola were reclassified from K. pneumoniae based on genome sequencing. However, the molecular characteristics and antimicrobial susceptibility patterns of ESBL-producing K. quasipneumoniae (ESBL-KQ) and ESBL-producing K. variicola (ESBL-KV) remain unclear. Here, we aimed to distinguish ESBL-KQ and ESBL-KV from ESBL-KP in terms of frequency, genomic characteristics, and antimicrobial susceptibility patterns. Of the 74 ESBL-KP isolates, 12 (16.2%) were reclassified as ESBL-KQ and 1 (1.4%) as ESBL-KV. Patients with ESBL-KP and ESBL-KQ infections were of similar age; ESBL-KQ infection was more frequent in men. Infection-associated mortality seemed to be similar in patients with ESBL-KQ and ESBL-KP infections, without a statistically significant difference (p = 0.99). Genetic analysis revealed that 19.1% of ESBL-producing Klebsiella isolates harbored AmpC. The prevalence of AmpC was higher with ESBL-KP (31.1%) than with ESBL-KQ (8.3%), although this difference was not statistically significant (p = 0.52). The frequency of ESBL-KQ with AmpC and quinolone-resistance-associated genes in clinical samples increased annually (p = 0.04). The prevalence of Klebsiella with fluoroquinolone-resistance genes did not differ significantly between species (p > 0.99). The gene profiles of ESBL-KQ and ESBL-KP differed, and the prevalence of antimicrobial resistance via AmpC and fluoroquinolone-resistance genes increased. Further studies are required to distinguish ESBL-KP and ESBL-KQ and determine the mechanism underlying the spread of AmpC and quinolone-resistance genes to prevent further spread of these genes.

Sex Differences in the Regional Analysis of Nonpulmonary Vein Foci and Epicardial Adipose Tissue in Patients With Atrial Fibrillation.

BACKGROUND: The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role.Methods and Results: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). CONCLUSIONS: Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.

Development of a Visualization Deep Learning Model for Classifying Origins of Ventricular Arrhythmias.

BACKGROUND: Several algorithms have been proposed for differentiating the right and left outflow tracts (RVOT/LVOT) arrhythmia origins from 12-lead electrocardiograms (ECGs); however, the procedure is complicated. A deep learning (DL) model, a form of artificial intelligence, can directly use ECGs and depict the importance of the leads and waveforms. This study aimed to create a visualized DL model that could classify arrhythmia origins more accurately.Methods and Results: This study enrolled 80 patients who underwent catheter ablation. A convolutional neural network-based model that could classify arrhythmia origins with 12-lead ECGs and visualize the leads that contributed to the diagnosis using a gradient-weighted class activation mapping method was developed. The average prediction results of the origins by the DL model were 89.4% (88.2-90.6) for accuracy and 95.2% (94.3-96.2) for recall, which were significantly better than when a conventional algorithm is used. The ratio of the contribution to the prediction differed between RVOT and LVOT origins. Although leads V1 to V3 and the limb leads had a focused balance in the LVOT group, the contribution ratio of leads aVR, aVL, and aVF was higher in the RVOT group. CONCLUSIONS: This study diagnosed the arrhythmia origins more accurately than the conventional algorithm, and clarified which part of the 12-lead waveforms contributed to the diagnosis. The visualized DL model was convincing and may play a role in understanding the pathogenesis of arrhythmias.

[A Rare Case of Primary Splenic Malignant Lymphoma Associated with Esophagogastric Junction Neuroendocrine Carcinoma(NEC)].

A 75-year-old man was showed wall thickening just below esophagogastric junction(EGJ)by gastroscopy(GS). Biopsy indicated mucinous carcinoma. He was referred to our hospital. Computed tomography(CT), PET-CT showed EGJ cancer and splenic tumor. EGJ cancer was diagnosed GE, Siewert Type Ⅱ, GrePostAnt, Type 1, cT2, cN0, cM0, cStage Ⅰ. The patient underwent total gastrectomy, lower esophagectomy, D2+ #19, 20, 110, 111, 112 lymph nodes dissection, Rou-en- Y reconstruction, distal pancreatectomy, splenectomy, cholecystectomy, and enterostomy. Postoperative complication was pancreatic fistula(Grade Ⅱ). Pathological diagnosis was esophagogastric junction cancer, neuroendocrine carcinoma(NEC), GE, Siewert Type Ⅱ, GrePostAnt, Type 1, pT2(MP), pN1, pM0, pStage ⅡA. Splenic tumor was diagnosed splenic malignant lymphoma, large B-cell, diffuse(DLBCL), NOS, low-immediate risk. Patient was discharged 15 days after the operation and underwent adjuvant chemotherapy with S-1. In this case, he started taking S-1 because the prognosis of NEC is poorer than PSML. There was no evidence of recurrence after 5 months from gastrectomy. As a result of searching for"neuroendocrine tumor"and"malignant lymphoma"in the JAMAS, there was no report of NEC associated with malignant lymphoma. We experienced the rare case of primary splenic malignant lymphoma associated with EGJ NEC. In the case of gastric cancer with splenic tumor, malignant lymphoma of spleen should be concerned.

[A Case of Laparoscopic Total Gastrectomy for Juvenile Polyposis of Stomach with Synchronous Multiple Intramucosal Carcinomas].

The patient was a 57-year-old woman. She was referred to our hospital because severe anemia. Upper gastrointestinal endoscopy revealed polyposis throughout the stomach and lobulated polyps in cardia, greater curve of middle body of the stomach, and angulus. Colonoscopy and small bowel endoscopy showed no obvious abnormal findings. Based on these findings, a laparoscopic total gastrectomy with D1 lymph node dissection was performed for suspected juvenile polyposis of stomach with severe anemia. The gross examination of the resection specimen revealed diffuse polyposis throughout the stomach, and histopathological examination revealed hyperplasia of the orbital epithelium throughout the stomach and lack of edema in lamina propria of mucous and eosinophil leukocytic infiltration, leading to the diagnosis of juvenile polyposis of stomach. Two well differentiated adenocarcinomas were found in 2 locations, which remained within the mucosa. We report a case of laparoscopic total gastrectomy for juvenile polyposis of the stomach with gastric cancer, with some discussion of the literature.

Antibody response patterns in COVID-19 patients with different levels of disease severity in Japan.

We analyzed antibody response patterns according to the level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan. We analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). Immunoglobulin M (IgM) and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays. The peaks of fitting curves for the optical density (OD) values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cut-off values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases. Our findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases.

Circulating intermediate monocytes and atrial structural remodeling associated with atrial fibrillation recurrence after catheter ablation.

BACKGROUND: Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. METHODS: Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. RESULTS: Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (ß = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. CONCLUSION: Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.

Feasibility of catheter ablation in patients with persistent atrial fibrillation guided by fragmented late-gadolinium enhancement areas.

BACKGROUND: A computer simulation model has demonstrated that atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome. METHODS: A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group. RESULTS: Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in seven, AT conversion in eight patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p = .023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients, but AF did not. CONCLUSIONS: FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response.

Late-gadolinium enhancement properties associated with atrial fibrillation rotors in patients with persistent atrial fibrillation.

BACKGROUND: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. OBJECTIVE: The purpose of this study was to evaluate the LGE properties of AF rotors in patients with persistent AF. METHODS: A total of 287 segments in 15 patients with persistent AF (long-standing persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity and the density which was evaluated by the entropy (LGE-entropy) and the volume ratio of the enhancement voxel (LGE-volume ratio), respectively. RESULTS: NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7% and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments; p = .001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of five patients with AF recurrence, NPAs outside the PV antrum were not ablated in three patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. CONCLUSION: AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas.

Total Synthesis of Cochlearol†B via Intramolecular [2+2] Photocycloaddition.

Herein, we describe the first total synthesis of cochlearol B, a meroterpenoid natural product featuring a 4/5/6/6/6-fused pentacyclic structure. Key steps, oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition, which constructed the pentacyclic structure in highly stereoselective manner, allowed efficient access to cochlearol B with the longest linear sequence of 16 steps, and in 9 % overall yield. Single-crystal X-ray crystallographic analysis clearly confirmed the stereochemistry of cochlearol B.

Different tissue thermodynamics between the 40 W and 20 W radiofrequency power settings under the same ablation index/lesion size index.

INTRODUCTION: The ablation index (AI) and lesion size index (LSI) are novel markers for predicting the ablation lesion quality, however, collateral damage is still a concern. This study aimed to compare the lesion characteristics and tissue temperature profiles between 20 W (20 Ws) and 40 W (40 Ws) ablation settings under the same AI and LSI. METHODS: An ex vivo model consisting of swine myocardium (5-6 mm thickness) in a circulating, warmed saline bath was used. Twenty-one tissue temperature electrodes were used. Radiofrequency applications with different power settings were performed with a 10 to 12 g contact force until the AI and LSI reached 350 and 4.5, respectively. RESULTS: A total of 120 radiofrequency (RF) applications and 2520 tissue temperature profiles were analyzed. The speed of the tissue temperature rise with 40 Ws was significantly faster than that with 20 Ws. However, the maximum tissue temperature did not significantly differ between 20 and 40 Ws with the same AI (44.6°C ± 3.9°C vs 45.1°C ± 6.4°C, P = .73), and was significantly lower for 40 Ws with the same LSI (42.8°C ± 3.4°C vs 40.0°C ± 3.4°C, P = .003). For both the AI and LSI, the number of electrodes exhibiting high temperatures (≥39°C) was significantly larger and the duration of high tissue temperatures was significantly longer with 20 Ws. The thermal latency with 40 Ws was greater. CONCLUSIONS: Although the targeted AI and LSI were the same for both 20 and 40 Ws, the tissue temperature profiles differed greatly depending on the RF power setting. A high power setting based on the AI and LSI may reduce the collateral thermal damage.

Lesion characteristics between cryoballoon ablation and radiofrequency ablation with a contact force-sensing catheter: Late-gadolinium enhancement magnetic resonance imaging assessment.

BACKGROUND: Pulmonary vein isolation (PVI) lesions after cryoballoon ablation (CBA) are characterized as a wider and more continuous than that after conventional radiofrequency catheter ablation (RFCA) without the contact force (CF)-sensing technology. However, the impact on the lesion characteristics of ablation with a CF-sensing catheter has not been well discussed. We sought to assess the lesions using late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) and to compare the differences between the two groups (CB group vs. RF group). METHODS: A total of 30 consecutive patients who underwent PVI were enrolled (CB group, 18; RF group, 12). The RF applications were delivered with a target lesion size index (LSI) of 5. The PVI lesions were assessed by LGE-MRI 3 months after the PVI. The region around the PV was divided into eight segments: roof, anterior-superior, anterior carina, anterior inferior, bottom, posterior inferior, posterior carina, and posterior superior segment. The lesion width and visual gap of each segment were compared between the two groups. The visual gaps were defined as no-enhancement site of >4 mm. RESULTS: The mean LSI was 4.7 ± 0.7. The lesion width was significantly wider but the visual gaps were more frequently documented at the bottom segment of right PV in the CBA group (lesion width: 8.1 ± 2.2 vs. 6.3 ± 2.2 mm; p = .032; visual gap at the bottom segment or right PV: 39% vs. 0%; p = .016). CONCLUSIONS: The PVI lesion was wider after CBA, while the visual gaps were fewer after RFCA with a CF-sensing catheter.

Circulating intermediate monocytes and toll-like receptor 4 correlate with low-voltage zones in atrial fibrillation.

Inflammation has been suggested to play a key role in the pathogenesis of atrial fibrillation (AF). Our hypothesis was that this inflammation, mediated by intermediate monocytes and toll-like receptor 4 (TLR4), causes the formation and expansion of low-voltage zones (LVZs). Prior to ablation, the monocyte subsets of 78 AF patients and TLR4 expression of 66 AF patients were analyzed via a flow cytometric analysis. Based on the CD14/CD16 expression, the monocytes were divided into three subsets: classical, intermediate, and non-classical. At the beginning of the ablation session, voltage mapping was performed. LVZs were defined as all bipolar electrogram amplitudes of < 0.5 mV. Correlations between the flow cytometric analysis results and presence of LVZs, as well as the total area of the LVZ, were examined. Patients with LVZs clearly had a higher proportion of intermediate monocytes (10.0 ± 3.6% vs. 7.2 ± 2.7%, p < 0.001) than those without LVZs. TLR4 was much more frequently expressed in the intermediate monocytes than other two monocyte subsets (p < 0.001). Moreover, the TLR4 expression level in intermediate monocytes correlated positively with the total area of the LVZs (r = 0.267, p = 0.030), especially in patients with paroxysmal AF (r = 0.365, p = 0.015). The intermediate monocytes and TLR4 expression positively correlated with LVZs in AF patients.