First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Exosomes in ascites from patients with human pancreatic cancer enhance remote metastasis partially through endothelial-mesenchymal transition.

BACKGROUND: Despite advances in multidisciplinary treatment, the prognosis of pancreatic cancer remains poor. Since distant metastasis defines prognosis, elucidation of the mechanism of metastasis is important for improving survival. Exosomes are extracellular secretory vesicles and are responsible for intercellular communication. In this study, we investigated whether exosomes secreted by human pancreatic cancer cells are involved in promoting distant metastasis of cancer and the mechanism that underlies the promotion of metastasis. METHODS: Exosomes were isolated from ascites of a patient with pancreatic cancer and a patient with liver cirrhosis as a control. Three days after the administration of exosomes to nude mice, GFP-labeled human pancreatic cancer cells were injected via the spleen or tail vein, and then the liver and lungs were histologically analyzed. To elucidate the mechanism, vascular permeability was estimated using FITC-dextran in place of pancreatic cancer cells in vivo and human umbilical vascular endothelial cells (HUVECs) were used to analyze vascular permeability and the induction of endothelial-mesenchymal transition (EndMT) in vitro. RESULTS: Distant metastasis and vascular permeability were significantly enhanced in mice treated with exosomes from pancreatic cancer patients in comparison to exosomes from a control patient in vivo. In addition, exosomes from pancreatic cancer patients significantly enhanced vascular permeability and the induction of EndMT in HUVECs in vitro. CONCLUSION: Exosomes derived from pancreatic cancer cells form a pre-metastatic niche and promote the extravasation and colonization of pancreatic cancer cells to remote organs, partially through endothelial-mesenchymal transition.

Comparison of phrenic nerve injury and its effect on the extrapulmonary vein structures with cryoballoon and hot-balloon ablation systems: considering the lesion created on the superior vena cava as a surrogate marker.

Preventing phrenic nerve injury (PNI) during balloon-based ablation is essential. The superior vena cava-right atrial (SVC-RA) junction is located just opposite the balloon position during right superior pulmonary vein (RSPV) ablation, and the phrenic nerve runs nearby on the lateral side. We compared the occurrence of PNI between the two balloon-based ablation systems and also the lesions created at the SVC-RA junction, which were expected to represent the effect on extra-PV structures. Cryoballoon ablation (CBA, n = 110) and hot-balloon ablation (HBA, n = 90) were performed in atrial fibrillation patients. High-density maps of the SVC-RA junction were created in 93 patients (CBA = 53, HBA = 40), and the damaged area (< 1.0 mV) was determined as an "SVC lesion". CBA had a higher occurrence of transient PNI (7.3% vs 1.1%, p = 0.035), but all recovered during the 6-month follow-up. An apparent SVC lesion was documented in 43% of the patients (40/93), and all patients with PNI had this lesion. CBA created a frequent (CBA vs HBA = 55% vs 28%, p = 0.008) and wider (0.8[0.4-1.7] cm2 vs 0.5[0.3-0.7] cm2, p = 0.005) SVC lesion than HBA. A multivariate analysis revealed that the use of a CBA system was a predictive factor of the occurrence of SVC lesions. CBA had a higher occurrence of transient PNI but not a permanent form. Every patient with PNI had lesions on the SVC-RA junction, and CBA revealed more substantial ablation effects at the SVC-RA junction than HBA. This may be caused by the different characteristics of the two balloon-based ablation systems and their balloon positions.

Evaluating the Differences Between Fluorescein Tear Break-up Time and Noninvasive Measurement Techniques.

OBJECTIVES: To compare fluorescein tear break-up time (BUT) and noninvasive BUT measured using interferometry and corneal topography. METHODS: We investigated 34 eyes of 34 patients with dry eye (mean age 39.2±8.3 years) and 16 eyes of 16 non-dry eye subjects (33.5±6.5 years). Tear film stability was measured using fluorescein BUT, noninvasive BUT (NIBUT)-DR1 with an interferometer, and noninvasive keratographic BUT (NIKBUT)-first and average using corneal topography. Correlations between fluorescein BUT and noninvasive BUT parameters were determined statistically. The noninvasive BUTs were compared between the dry eye and non-dry eye groups. The agreement between fluorescein and noninvasive BUTs was described using Bland-Altman analysis. RESULTS: Fluorescein BUT was significantly correlated with NIBUT-DR1, NIKBUT-first, and NIKBUT-average. The Bland-Altman analysis revealed bias and 95% limits of agreement between fluorescein BUT and noninvasive BUTs as follows: NIBUT-DR1: 2.07 s, -5.33 to 9.46 s; NIKBUT-first: 3.39 s, -5.46 to 12.24 s; NIKBUT-average: 6.61 s, -1.58 to 14.79 s. The noninvasive BUTs were significantly different between the two groups. When NIBUT-DR1, NIKBUT-first, and NIKBUT-average with Bland-Altman correction were used as an index for dry eye, the cut-off values were 7.1, 8.4, and 11.6 s, respectively. The sensitivities were 0.735, 0.818, and 0.727 and specificities were 0.500, 0.437, and 0.562, respectively. CONCLUSION: Fluorescein BUT and noninvasive BUTs were significantly correlated, and noninvasive BUTs had higher values than fluorescein BUT. Considering the differences between fluorescein BUT and noninvasive BUTs, noninvasive methods can be used as effective tool for diagnosing dry eye.

Characteristics of laterality in the optic nerve head microcirculation obtained by laser speckle flowgraphy in healthy subjects.

PURPOSE: To determine the characteristics of the laterality of the ocular microcirculation parameters obtained from laser speckle flowgraphy (LSFG) in the optic nerve head (ONH). SUBJECTS AND METHODS: We reanalyzed a total of 240 healthy subjects (169 men, 71 women) who had participated in a medical checkup program. We analyzed the average mean blur rate (MBR), maximum MBR (Max-MBR), minimum MBR (Min-MBR), and area ratio of the blood stream (ARBS). As the pulse waveform parameters, we also calculated the skew, blowout score (BOS), blowout time (BOT), rising rate, falling rate, flow acceleration index (FAI), acceleration time index (ATI), resistivity index (RI), and beat strength over MBR (BOM). All parameters were compared between left and right eyes. RESULTS: MBR-average, MBR-Max, MBR-Min, ARBS, skew, BOT, rising rate, falling rate, FAI, ATI, and ARBS did not differ significantly between the right and left eyes. The BOS in the right eyes was significantly lower than that of the left eyes, and the RI and BS in the right eyes were significantly higher than those of the left eyes. Similarly, for the whole of the ONH, the BOS in the tissue area (Tissue) and in the vessel area (Vessel) of the right eyes were significantly lower than those of the left eyes, and RI-Tissue, RI-Vessel, BOM-Tissue, and BOM-Vessel in the right eyes were significantly higher than those of the left eyes. CONCLUSION: By using LSFG, we observed laterality of the BOS, RI, and BOM, all of which are pulse wave form parameters in the ONH.

Evaluation of the Lubricating Effect of Hyaluronic Acid on Contact Lenses Using a Pendulum-Type Friction Tester Under Mimicking Physiological Conditions.

OBJECTIVE: To evaluate the lubricating effect of hyaluronic acid (HA) on soft contact lenses (SCLs) measured using a pendulum-type friction tester. METHODS: We measured the coefficient of friction (CoF) of narafilcon A, delefilcon A, and etafilcon A with polyvinylpyrrolidone (PVP), daily disposable SCL material, using a modified pendulum-type friction tester. Sample SCLs were set on an acrylic plastic half-ball and placed into the polyethylene terephthalate hemisphere cup filled with 0.4 mL of test lubricants that included saline and 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% (wt/vol) HA (molecular weight, 850 kDa). The viscosities of saline and HA were measured using an Ubbelohde viscometer. RESULTS: The CoF of the SCL under a low concentration (0.05%) of HA was the lowest and significantly lower than saline in narafilcon A and delefilcon A (P<0.05, Steel multiple comparison test). Under higher HA concentrations (0.3%, 0.4%, and 0.5%), the CoF was significantly higher than that of saline (P<0.01, Steel' multiple comparison test) in all three SCLs. There were no significant differences of CoF among three SCLs in saline and all concentrations of HA. The HA viscosities increased exponentially with the concentration (Y=1.2829e9.286X). CONCLUSION: The viscosity of a high concentration of HA may increase the friction of SCLs, which may have a deleterious effect on the ocular surface.

Pancreatic cancer cell-derived exosomes induce epithelial-mesenchymal transition in human pancreatic cancer cells themselves partially via transforming growth factor ß1.

Distant metastasis is a dismal prognostic factor of pancreatic cancer. Metastasis is established in several steps, but the mechanism underlying the very early stages remains unclear. Epithelial-mesenchymal transition (EMT) is involved in these stages. Although signaling molecules have been reported to induce EMT, the mechanism underlying their origin is unclear. In this study, we hypothesized that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves, a notion we entertained because we found EMT in in vitro three-dimensional colonies of cancer cells, with vimentin-positive cells observed in some of the budding pancreatic cancer cells and in single cells outside the colony as well. First, we clarified that pancreatic cancer cell-derived exosomes induce EMT in cancer cells themselves. Next, we examined the involvement of transforming growth factor-ß1 (TGF-ß1), and TGF-ß1 knock-down in pancreatic cancer cells with TGF-ß1 siRNA significantly suppressed TGF-ß1 gene expression in cancer cells, and exosomal TGF-ß1 was significantly reduced in the secretory exosomes. Exosomes from TGF-ß1 knock-down cells suppressed EMT induction in cancer cells themselves and TGF-ß1 protein expression in target cells. Taken together, these findings suggest that TGF-ß1 is involved in EMT induction via exosomes, results that may support the production of effective metastasis inhibitors.

Metagenomic Shotgun Sequencing Analysis of Canalicular Concretions in Lacrimal Canaliculitis Cases.

Lacrimal canaliculitis is a rare infection of the lacrimal canaliculi with canalicular concretions formed by aggregation of organisms. Metagenomic shotgun sequencing analysis using next-generation sequencing has been used to detect pathogens directly from clinical samples. Using this technology, we report cases of successful pathogen detection of canalicular concretions in lacrimal canaliculitis cases. We investigated patients with primary lacrimal canaliculitis examined in the eye clinics of four hospitals from February 2015 to July 2017. Eighteen canalicular concretion specimens collected from 18 eyes of 17 patients were analyzed by shotgun metagenomics sequencing using the MiSeq platform (Illumina). Taxonomic classification was performed using the GenBank NT database. The canalicular concretion diversity was characterized using the Shannon diversity index. This study included 18 eyes (17 patients, 77.1 ± 6.1 years): 82.4% were women with lacrimal canaliculitis; canalicular concretions were obtained from 12 eyes using lacrimal endoscopy and six eyes using canaliculotomy with curettage. Sequencing analysis detected bacteria in all samples (Shannon diversity index, 0.05-1.47). The following genera of anaerobic bacteria (>1% abundance) were identified: Actinomyces spp. in 15 eyes, Propionibacterium spp., Parvimonas spp. in 11 eyes, Prevotella spp. in 9 eyes, Fusobacterium spp. in 6 eyes, Selenomonas spp. in 5 eyes, Aggregatibacter spp. in 3 eyes, facultative and aerobic bacteria such as Streptococcus spp. in 13 eyes, Campylobacter spp. in 6 eyes, and Haemophilus spp. in 3 eyes. The most common combinations were Actinomyces spp. and Streptococcus spp. and Parvinomonas spp. and Streptococcus spp., found in 10 cases. Pathogens were identified successfully using metagenomic shotgun sequencing analysis in patients with canalicular concretions. Canalicular concretions are polymicrobial with anaerobic and facultative, aerobic bacteria.

A novel metric linking stellate ganglion neuronal population dynamics to cardiopulmonary physiology.

Cardiopulmonary sympathetic control is exerted via stellate ganglia (SG); however, little is known about how neuronal firing patterns in the stellate ganglion relate to dynamic physiological function in the heart and lungs. We performed continuous extracellular recordings from SG neurons using multielectrode arrays in chloralose-anesthetized pigs (n = 6) for 8-9 h. Respiratory and left ventricular pressures (RP and LVP, respectively) and the electrocardiogram (ECG) were recorded concomitantly. Linkages between sampled spikes and LVP or RP were determined using a novel metric to evaluate specificity in neural activity for phases of the cardiac and pulmonary cycles during resting conditions and under various cardiopulmonary stressors. Firing frequency (mean 4.6 ± 1.2 Hz) varied spatially across the stellate ganglion, suggesting regional processing. The firing pattern of most neurons was synchronized with both cardiac (LVP) and pulmonary (RP) activity indicative of cardiopulmonary integration. Using the novel metric to determine cardiac phase specificity of neuronal activity, we found that spike density was highest during diastole and near-peak systole. This specificity was independent of the actual LVP or population firing frequency as revealed by perturbations to the LVP. The observed specificity was weaker for RP. Stellate ganglion neuronal populations exhibit cardiopulmonary integration and profound specificity toward the near-peak systolic phase of the cardiac cycle. This novel approach provides practically deployable tools to probe stellate ganglion function and its relationship to cardiopulmonary pathophysiology.NEW & NOTEWORTHY Activity of stellate ganglion neurons is often linking indirectly to cardiac function. Using novel approaches coupled with extended period of recordings in large animals, we link neuronal population dynamics to mechanical events occurring at near-peak systole. This metric can be deployed to probe stellate ganglion neuronal control of cardiopulmonary function in normal and disease states.

The influence of hemorrhagic shock on ocular microcirculation by obtained by laser speckle flowgraphy in a white rabbit model.

PURPOSE: To clarify the continuous changes in the retinal vessels' and choroid's microcirculation during hemorrhagic shock and resuscitation in a rabbit model. METHODS: Hemorrhagic shock by the removal of blood (30 mL) and resuscitation by a blood-return technique was induced in anesthetized male New Zealand White rabbits (n = 10). We evaluated the retinal vessel blood flow (relative flow volume: RFV) and choroidal blood flow (mean blur rate in the choroid area: MBR-CH) by laser speckle flowgraphy (LSFG), with simultaneous measurements of systemic hemodynamics and laboratory parameters. RESULTS: RFV and MBR-CH showed significant decreases immediately after the initiation of blood removal and recovered by blood return. The lactate concentration tended to increase from baseline by the blood-removal operation, and it was significantly higher at the end of observation period. The %RFV and %MBR-CH each showed a significant positive correlation with mean arterial blood pressure, cardiac output, carotid blood flow, and central venous pressure. %RFV showed a significant positive correlation with %central venous oxygen saturation and negatively correlated with %lactate. The %hemoglobin did not show a significant correlation with %RFV or %MBR-CH. CONCLUSION: This rabbit hemorrhagic shock model confirmed that ocular microcirculation measurements by LSFG feasibly reflect variations in systemic hemodynamics during hemorrhagic shock and recovery.

Cryofreezing for slow-pathway modification in patients with slow-fast AVNRT: Efficacy, safety, and electroanatomical relation between sites of transient AV block and sites of successful cryoablation.

INTRODUCTION: Cryoablation has emerged as an alternative to radiofrequency ablation for treating atrioventricular nodal reentrant tachycardia (AVNRT). The aim of this prospective study was to evaluate the efficacy and safety of cryoapplication at sites within the mid/high septal region of Koch's triangle and the relation between sites of transient AV block (AVB) and sites of successful cryoablation. METHODS AND RESULTS: Included were 45 consecutive patients undergoing slow-fast AVNRT cryoablation. Initial delivery of cryoenergy was to the mid-septal to high septal region of Koch's triangle. Transient AVB occurred during cryoenergy delivery in 62% (28/45) of patients. Median distance between sites at which cryofreezing successfully eliminated slow pathway conduction and sites of AVB was 4.0 (3.25-5.0) mm. Sites of successful cryoablation tended to be to the left and inferior to the AVB sites. The atrial/ventricular electrogram ratio was significantly lower at sites of successful cryoablation than at AVB sites (0.25 [0.17-0.56] vs. 0.80 [0.36-1.25], p < .001). Delayed discrete or fractionated atrial electrograms were recorded more frequently at sites of successful cryoablation than at AVB sites (78% vs. 20%, p < .001). No persistent AV conduction disturbance occurred, and 96% (43/45) of patients showed absence of recurrence at a median follow-up time of 25.0 months. CONCLUSION: Cryoablation of slow-fast AVNRT and targeting the mid/high septal region of Koch's triangle was highly successful. AVB frequently emerged near the site at which the slow pathway was eliminated but always resolved by regulating the energy delivery under careful monitoring, and it may be distinguishable by its local electrogram features.

Utility of hot-balloon-based pulmonary vein isolation under balloon surface temperature monitoring: First clinical experience.

INTRODUCTION: A new hot balloon system that registers balloon surface temperature (BST) during energy delivery is now available for clinical use in Japan. This study sought to investigate the utility of BST measurement for achievement of pulmonary vein isolation (PVI) by a single-shot energy delivery strategy during hot balloon ablation (HBA). METHODS: We applied and tested the system in 30 consecutive patients undergoing HBA for paroxysmal or early-persistent atrial fibrillation (AF). We also performed real-time PV potential monitoring using a circular catheter. RESULTS: Acute PVI was achieved with single hot balloon shots in 88% (106/120) of the PVs. Real-time BSTs and PV potentials were recorded in all cases. Mean BST at documentation of PVI was 49.4°C, and acute reconnections were observed in most cases (86%, 12/14) in which the single-shot technique was ineffective. Time-to-isolation (TTI) (23.1 ± 8.7 s vs. 36.3 ± 9.3 s, p < .01) and median BST (59.9 ± 2.6°C vs. 55.7 ± 1.9°C, p < .01) differed significantly between cases in which PVI was achieved (vs. those in which PVI was not achieved). Multivariable analysis revealed strong association between both TTI and median BST and acute PVI. The best median BST cutoff value for achieving PVI with a single shot was >58.7°C (sensitivity 67.0%, specificity 100%). CONCLUSION: Our data suggest that real-time BST monitoring during energy applications is useful for predicting achievement of acute PVI by a single shot during HBA.

Decrease in choroidal blood flow after half and one-third dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: The effect of various reduced doses of verteporfin photodynamic therapy (PDT) on choroidal blood flow in chronic central serous chorioretinopathy (CSC) remains unclear. Therefore, this study aimed to evaluate choroidal blood flow after half-dose PDT (1/2PDT) and one-third dose PDT (1/3PDT) with verteporfin for chronic CSC using laser speckle flowgraphy and spectral-domain optical coherence tomography. METHODS: Twenty-seven eyes of 27 patients with serous retinal detachment (SRD) caused by chronic CSC for more than 6 months were included in this study. Patients were divided into the 1/2PDT (n = 12; January 2018 to July 2019) and 1/3PDT (n = 15; August 2016 to December 2017) groups based on the treatment period. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and mean blur rate in the macular area (m-MBR) and optic nerve head (ONH-MBR) were obtained using laser speckle flowgraphy and evaluated at baseline (pre-treatment), and 2 weeks, 1 month, 3 months, and 6 months after treatment. RESULTS: We found that SRD disappeared after 1 month in 92 and 93% of patients' eyes in the 1/2PDT and 1/3PDT groups, respectively. Recurrence of SRD was observed in one eye at the 6-month follow-up after 1/2PDT and two eyes at the 3-month follow-up after 1/3PDT. No significant improvement was observed in baseline BCVA in the 1/3PDT and 1/2PDT groups. The average m-MBR against baseline significantly decreased at 2 weeks and 1, 3, and 6 months in the 1/2PDT group. The average m-MBR against baseline decreased significantly only at the 2 weeks follow-up in the 1/3PDT group. The average rate of change in the CCT against baseline decreased significantly throughout for up to 6 months in the 1/2PDT group and for up to 3 months in the 1/3PDT group. No significant fluctuation was observed in the ONH-MBR. CONCLUSIONS: Here, PDT significantly affected choroidal blood flow depending on the verteporfin dose in chronic CSC. TRIAL REGISTRATION: This trial was retrospectively registered ( UMIN000026850 ; Approval date 03/04/2017).

Evaluation of In Vitro Wettability of Soft Contact Lenses Using Tear Supplements.

OBJECTIVE: To evaluate the interaction between tear supplements and soft contact lenses (SCLs), we measured the contact angles (CAs) on the SCLs using commercially available tear supplements. METHODS: We used four daily disposable conventional hydrogel lenses (etafilcon A, etafilcon A+ polyvinylpyrrolidone, nelfilcon A, and omafilcon A containing 2-methacryloyloxyethyl phosphorylcholine [MPC]) and four silicone hydrogel lenses (narafilcon A, senofilcon A, delefilcon A, and stenfilcon A). The CAs on the SCLs were measured using a sessile drop technique and four different types of sessile drops, including saline, artificial tears, lubricants containing 2-MPC (MPC solution), and 0.1% hyaluronate acid (HA). RESULTS: The CA values associated with the silicone hydrogel lenses were significantly (P<0.001) lower than those associated with the conventional hydrogel lenses with all four solutions. The mean CA of 0.1% HA was significantly (P<0.01) higher than that of saline. The mean CA of the MPC solution was significantly (P<0.01) lower than that of saline with the conventional hydrogel lenses but significantly (P<0.05) higher than that of saline with the silicone hydrogel lenses. CONCLUSIONS: The CAs associated with the silicone hydrogel SCLs were higher with the use of the MPC solutions and HA in vitro. The measured CAs may depend on ingredient agents, surface treatment of the CLs, and components of the tear supplements.

Hot balloon versus cryoballoon ablation for persistent atrial fibrillation: Lesion area, efficacy, and safety.

INTRODUCTION: The clinical efficacy and safety of hot balloon ablation (HBA) for the treatment of persistent AF (PerAF) remain unclear. We aimed to evaluate the clinical efficacy and safety of HBA versus cryoballoon ablation (CBA) as a treatment for PerAF. METHODS: Of 195 consecutive patients who underwent initial catheter ablation for PerAF (AF lasting for longer than 7 days but shorter than 12 months), 158 propensity score-matched (79 HBA and 79 CBA) patients were included in our retrospective study. All patients who underwent HBA received applications of energy to the upper posterior LA wall with a larger balloon in addition to single shots to each pulmonary vein (PV) ostium, whereas those who underwent CBA received simple single-shot applications. The electrically isolated surface area (ISA), including the PV antrum and part of the posterior LA wall, was assessed by high-resolution mapping. RESULTS: The success of the PV isolation with balloon shots alone did not differ between HBA and CBA (81% vs. 85%; p = .52). The ISA was generally wide in both groups and significantly larger in the HBA group than in the CBA group (61 ± 16% vs. 51 ± 12%; p < .001). The incidence of procedure-related complications did not differ significantly (HBA 4% vs. CBA 1%; p = .62) nor did the arrhythmia recurrence rate (HBA 11% vs. CBA 18% at 18 months; p = .26). CONCLUSION: Despite the difference in protocols, HBA and CBA performed for PerAF appear comparable in terms of wide antral lesion creation, clinical efficacy, and safety. Further prospective studies, based on a unified methodology, are needed.

Bacterial keratoconjunctivitis caused by Staphylococcus argenteus belonging to sequence type 1223 isolated in Japan.

Staphylococcus argenteus, characterized by the formation of non-pigmented (white) colonies, was recently identified as a new lineage separated from Staphylococcus aureus. However, correct identification of this lineage is difficult because of the similar characteristics to S. aureus. Here, we describe the first known case of keratoconjunctivitis due to S. argenteus in a 64-year-old man with diabetes. The symptoms of the patient were not improved by antibiotic therapy using levofloxacin eye drops (15 mg/mL). The conjunctival scraping was cultured, and coagulase-positive staphylococci forming white colonies were detected. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry confirmed the species as S. argenteus with a spectral score of 1.97. After the antibiotic was changed to vancomycin eye drops (10 mg/mL), the patient's symptom clearly improved. Multi-locus sequence typing showed that this isolate belonged to sequence type 1223, which has been predominantly isolated worldwide. Furthermore, this isolate harbored various virulence genes associated with S. aureus, such as staphylococcal enterotoxins and leukocidin. Since only limited information is available for this organism, further studies are needed to establish the epidemiology of S. argenteus.

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas.

BACKGROUND: Malignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis. METHODS: By using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK. RESULTS: The median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P < 0.01), whereas that of pSmad3L was 3.4%, 4.3%, and 42.4%, respectively (P < 0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P < 0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P < 0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P < 0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P < 0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05-0.93), 3.83 (range, 0.85-5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0-36.9) and 82.1 (range, 46.2-97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7-30.8) and 90.9 (range 52.9-98.5), respectively (P = 0.02). CONCLUSIONS: pSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

Characterization of Residual Conduction Gaps After HotBalloon-Based Antral Ablation of Atrial Fibrillation　- Evidence From Ultra-High-Resolution 3-Dimensional Mapping.

BACKGROUND: The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 [interquartile range: 0.06-0.27] mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases. CONCLUSIONS: HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.

Physiological role of nitric oxide for regulation of arterial stiffness in anesthetized rabbits.

We assessed effects of acetylcholine and Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) on the cardio-ankle vascular index (CAVI), an indicator of arterial stiffness from origin of aorta to tibial artery, in halothane-anesthetized rabbits. Acetylcholine decreased the blood pressure, femoral vascular resistance and CAVI, whereas l-NAME did not affect the CAVI at a hypertensive dose. The acetylcholine-induced decrement of CAVI was completely suppressed by l-NAME. These results suggest that the arterial stiffness in rabbits may be independent from homeostatic production of nitric oxide, however, it can be decreased by large amounts of nitric oxide that are intrinsically produced by exogenously administered acetylcholine.

Angiotensin II acutely increases arterial stiffness as monitored by cardio-ankle vascular index (CAVI) in anesthetized rabbits.

The cardio-ankle vascular index (CAVI) has been established as a stiffness indicator from thoracic aorta to tibial arteries. To better understand physiological regulatory factors for the arterial stiffness, we assessed effects of angiotensin II and adrenaline on the CAVI in anesthetized rabbits. A hypertensive dose of angiotensin II (300 ng/kg, i.v.) increased the CAVI as well as the heart-ankle pulse wave velocity (haPWV). On the other hand, although a hypertensive dose of adrenaline (1000 ng/kg, i.v.) increased the haPWV, it did not affect the CAVI. These results suggest that angiotensin II may act as a regulatory factor for arterial stiffness.