Interleukin-5 alleviates cardiac remodelling via the STAT3 pathway in angiotensin II-infused mice.

Interleukin-5 (IL-5) has been reported to be involved in cardiovascular diseases, such as atherosclerosis and cardiac injury. This study aimed to investigate the effects of IL-5 on cardiac remodelling. Mice were infused with angiotensin II (Ang II), and the expression and source of cardiac IL-5 were analysed. The results showed that cardiac IL-5 expression was time- and dose-dependently decreased after Ang II infusion, and was mainly derived from cardiac macrophages. Additionally, IL-5-knockout (IL-5-/-) mice were used to observe the effects of IL-5 knockout on Ang II-induced cardiac remodelling. We found knockout of IL-5 significantly increased the expression of cardiac hypertrophy markers, elevated myocardial cell cross-sectional areas and worsened cardiac dysfunction in Ang II-infused mice. IL-5 deletion also promoted M2 macrophage differentiation and exacerbated cardiac fibrosis. Furthermore, the effects of IL-5 deletion on cardiac remodelling was detected after the STAT3 pathway was inhibited by S31-201. The effects of IL-5 on cardiac remodelling and M2 macrophage differentiation were reversed by S31-201. Finally, the effects of IL-5 on macrophage differentiation and macrophage-related cardiac hypertrophy and fibrosis were analysed in vitro. IL-5 knockout significantly increased the Ang II-induced mRNA expression of cardiac hypertrophy markers in myocardial cells that were co-cultured with macrophages, and this effect was reversed by S31-201. Similar trends in the mRNA levels of fibrosis markers were observed when cardiac fibroblasts and macrophages were co-cultured. In conclusions, IL-5 deficiency promote the differentiation of M2 macrophages by activating the STAT3 pathway, thereby exacerbating cardiac remodelling in Ang II-infused mice. IL-5 may be a potential target for the clinical prevention of cardiac remodelling.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Pain perception, aqueous humour cytokines, and miosis response following first and second eye femtosecond laser-assisted cataract surgery: A randomised, prospective, intraindividual study.

BACKGROUND: To compare pain perception, pupil behaviours, and cytokine levels during first-eye and second-eye femtosecond laser-assisted cataract surgery (FLACS) and determine which is better regarding a short or long interval for bilateral FLACS. METHODS: Notably, 96 eyes of 48 patients with bilateral cataracts underwent the first surgeries in the left or right eye, according to a random sequence. They were further randomised into 2- and 6-week subgroups based on surgery intervals. Pupil size was measured from captured images, and pain perception was assessed using a visual analog scale (VAS). Aqueous humour prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 levels were also quantitatively analysed. All patients were followed for 1 week to evaluate changes in endothelial cell density (ECD), central corneal thickness (CCT), and macular central subfield thickness (CST). RESULTS: Ocular pain was significantly higher in patients who underwent second-eye FLACS. First tear break-up time was negatively correlated with VAS score. MCP-1 levels were significantly higher in patients who underwent second-eye FLACS, and VAS scores were positively correlated with MCP-1 levels across all patients. There were no differences between sequential FLACS in miosis, PGE2, IL-6, IL-8 levels and changes in postoperative ECD, CCT, and CST. Patients who underwent second-eye FLACS after 6 weeks showed more CCT, CST, and MCP-1 changes than baseline. CONCLUSION: Second-eye FLACS causes more pain and upregulated MCP-1. There was no difference between sequential FLACS in PGE2 levels, miosis, and postoperative inflammation. Furthermore, first-eye FLACS triggered a sympathetic irritation, particularly after a 6-week interval.

Impact of left atrial appendage orifice diameter on the safety and efficacy of left atrial appendage closure using the LAmbre device.

BACKGROUND: The diameter and shape of the left atrial appendage (LAA) orifices may influence occluder selection and the outcomes of left atrial appendage closure (LAAC) procedure. This study aimed to evaluate the impact of LAA orifice diameter on the safety and efficacy of LAAC using the LAmbre device. METHODS: A total of 133 patients with nonvalvular atrial fibrillation (AF) who underwent LAAC with the LAmbre device between June 2018 and June 2020 were included in this study. The patients were categorized into two groups based on the maximal diameter of the LAA orifice: the large LAA group (n = 45) with a maximal orifice diameter of ≥31 mm, and the normal LAA group (n = 88) with a maximal orifice diameter of <31 mm. The study assessed periprocedural characteristics and long-term clinical follow-up. RESULTS: Successful implantation of the LAmbre device was observed in all patients. The incidence of periprocedural peridevice leakage (PDL) was significantly higher in the large LAA group (P < 0.001), while the incidence of acute pericardial effusion (PE) during the procedure was comparable between the two groups (P = 1.000). After a mean follow-up period of 4.8 ± 1.7 years, three patients in the large LAA group developed delayed PE, while no patients in the normal LAA group did (P = 0.037). Additionally, a larger LAA maximal orifice diameter was associated with a higher prevalence of PDL (P = 0.001) and PE (including both acute and delayed PE) (P = 0.027). The optimal cutoff value of the LAA maximal orifice diameter for predicting PDL and PE after LAAC with the LAmbre device was determined to be 30 mm. CONCLUSION: The findings suggest that the LAmbre device is a safe and feasible option for occluding the LAA, regardless of its orifice diameter. However, it is important to note that a larger LAA orifice diameter may increase the risk of PDL and delayed PE.

Thioredoxin-1 regulates the autophagy induced by oxidative stress through LC3-II in human lens epithelial cells.

Oxidative stress plays a major role in age-related cataract development. The cellular antioxidant protein thioredoxin-1 (Trx-1) and its negative regulator, thioredoxin binding protein-2 (TBP-2), are pivotal in the cellular redox balance during oxidative stress. The aim of this study is to investigate the effect of Trx-1 and TBP-2 on LC3 I/LC3 II in oxidative stress-induced autophagy in human lens epithelial cells (LECs). In our study, LECs were treated with 50 µM H2 O2 for different durations, and the expression of Trx-1 and TBP-2 were measured by RT-PCR and Western blot. Trx-1 activity was evaluated by the thioredoxin activity fluorescent assay. The subcellular localization of Trx-1 and TBP-2 was evaluated by cellular immunofluorescence. The interaction between Trx-1 and TBP-2 was examined by co-immunoprecipitation. The cell viability was detected using CCK-8, and the expression of LC3-II/LC3-I was detected to evaluate the autophagy. The results showed that the mRNA levels of the Trx-1 and TBP-2 were kinetically changed after treatment with H2 O2 for different durations. Exposure to H2 O2 increased the expression of TBP-2 but not Trx-1, while the exposure inhibited Trx-1 activity. TBP-2 was co-localized with Trx-1, and exposure to H2 O2 increased the interaction between TBP-2 and Trx-1. Trx-1 overexpression enhanced the autophagic response under normal circumstances and it might regulate autophagy in the initial phase. This study demonstrates the differential role of Trx-1 in cellular oxidative stress response, oxidative stress increased Trx-1 interaction with TBP-2, and Trx-1/TBP-2 regulated the autophagic response in the initial phase through LC3-II.

Non-typical persistent hyperplastic primary vitreous: a rare case report and review of the literature.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature (PFV), is a clinical entity that traditionally presents with leukocoria, microphthalmia, retinal dysplasia, or eyeball shrinkage which is associated with poor vision. However, there is a dearth of literature on cases of PHPV in adulthood or with asymptomatic occurrence. This report presents the clinical and pathological findings of a non-typical PHPV case and discuss the current knowledge for this condition. CASE PRESENTATION: A 68-year-old healthy male was referred to our outpatient department for evaluation of age-related cataract without other visual symptoms. Preoperative fundus examination occasionally detected an isolated stalk-like band extending to the posterior pole of the eye with normal central vitreous and retina. Other ocular examinations including b-mode ultrasonography, optical coherence tomography did not unveil any abnormalities, which caused diagnostic uncertainty. We referred to cataract surgery along with histopathological study, that revealed characteristics of PHPV including fibrous connective tissues mainly composed of fibrocyte proliferation and a very few capillary vessels. Thereafter, a definitive diagnosis of non-typical PHPV was established. CONCLUSION: Our case is unique due to it was not discovered until adulthood, presence with only age-related cataract, and accompanied with normal central vitreous and retina. Histopathological explorations lead to an accurate diagnosis of the condition. Those results broaden the phenotype spectrums of PHPV and further provide clinical clues for the cognition of the disease.

Correlation between Serum Myosin Light Chain 4 Levels and Recurrence after Radiofrequency Ablation in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia that is harmful to human health. This study aims to explore the relationship between myosin light chain 4 (MYL4) and AF recurrence after radiofrequency ablation (RFA). Patients with AF (n = 85) were enrolled, and healthy subjects (n = 90) with normal sinus rhythm and no previous history of AF were selected as controls. The serum levels of MYL4, transforming growth factor (TGF) -ß1, and procollagen type-I C-terminal propeptide (PICP) were determined. The correlation between MYL4 and atrial fibrosis remodeling indicators (TGF-ß1/PICP) and left atrial diameter (LAD) was analyzed. The influence of MYL4 on AF recurrence after RFA was evaluated, and the independent correlation between them was assessed. Patients with AF and the controls showed no significant differences in age, gender, body mass index, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, white blood cell count, neutrophil/lymphocyte ratio, brain natriuretic peptide, and history of smoking, drinking, hypertension, and diabetes (P > 0.05), but with increased LAD in patients with AF (P < 0.01). Serum MYL4 level was reduced in patients with AF (0.6 ± 0.2) compared with that of controls (0.1 ± 0.6) (P < 0.01), and it was negatively correlated with TGF-ß1, PICP, and LAD (r = -0.2389, P < 0.05; r = -0.5174, P < 0.01; r = -0.3191; P < 0.01). Low levels of MYL4 increased the risk of AF recurrence after RFA (χ2 = 16.64; P < 0.0001). A low MYL4 level in patients with AF showed a poorer prognosis. Serum MYL4 level and AF type were independent risk factors affecting AF recurrence after RFA.

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids.

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem-stamp strategy for the construction of the key isoprene unit, which consists of two steps: one-carbon extension of aldehydes to the alkenyl boronates by the boron-Wittig reaction and the rhodium-catalyzed reaction of alkenyl boronates with 2,3-allenols to yield enals. This chem-stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, ß-carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3-allenols, creation of new non-natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

Noncoding RNAs in cataract formation: Star molecules emerge in an endless stream.

For decades, research on the pathological mechanism of cataracts has usually focused on the abnormal protein changes caused by a series of risk factors. However, an entire class of molecules, termed non-coding RNA (ncRNA), was discovered in recent years and proven to be heavily involved in cataract formation. Recent studies have recognized the key regulatory roles of ncRNAs in cataracts by shaping cellular activities such as proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT). This review summarizes our current insight into the biogenesis, properties and functions of ncRNAs and then discusses the development of research on ncRNAs in cataracts. Considering the significant role of ncRNA in cataract formation, research on novel associated regulatory mechanisms is urgently needed, and the development of therapeutic alternatives for the treatment of cataracts seems promising.

Safety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device.

BACKGROUND/PURPOSE: Anticoagulant therapy is suggested within 45 days after Watchman device implantation for stroke prevention in patients with atrial fibrillation (AF). A previous study demonstrated that non-vitamin K antagonist oral anticoagulants (NOACs) were a feasible peri- and postprocedural alternative to warfarin. The present study aimed to compare the safety and efficacy of using different anticoagulants (low-dose NOACs vs. warfarin) within 45 days after Watchman device implantation in a Chinese population. METHODS: Patients with successful Watchman device implantation from October 2014 to June 2020 were included. All patients received anticoagulants within 45 days after the procedure, and those patients were divided into three groups according to the type of postprocedural anticoagulants. Transesophageal echocardiography follow-up was performed 45 days post procedure to assess residual flow and the occurrence of device-related thrombus (DRT). RESULTS: A total of 368 patients were enrolled in the study. The study population was divided into three groups: the warfarin group (n = 77), the dabigatran group (n = 165) and the rivaroxaban group (n = 126). Periprocedural major bleeding was higher in the warfarin group (2.6% vs. 0% vs. 0%, P = 0.043), while minor bleeding was comparable among the groups (3.9% vs. 1.2% vs. 0.8%, P = 0.230). No periprocedural transient ischemic attack/stroke occurred. At follow-up, the incidence of DRT was higher in the warfarin group than in the other groups (4.2% vs. 0.6% vs. 0.8%; P = 0.116), but the difference was not statistically significant. The rates of thromboembolic and bleeding events were similar in the three groups. CONCLUSION: The safety and efficacy of low-dose dabigatran and rivaroxaban were comparable to those of warfarin within 45 days after Watchman device implantation in a Chinese population.

A novel co-catalyzed system between persulfate and chlorite by sonolysis for removing triphenylmethane derivative.

Triphenylmethane (tpm) derivatives (e.g. tpmCV) have threatened the safety of the aquatic environment due to the potential toxicity and carcinogenicity. In this study, the novel ultrasonic/persulfate/chlorite (US/S2O82-/ClO2-) oxidation process was developed for the effective removal of tpmCV in wastewater. The apparent non-integer kinetics (n around 1.20) of tpmCV degradation under different factors (R2Adj > 0.990) were investigated, respectively. Inhibiting effects of anions were greater than those of cations (except Fe(II/III)). The adding of micromolecule organic acids could regulate degradation towards positive direction. The double response surface methodology (RSM) was designed to optimize tpmCV removal process, and the acoustic-piezoelectric interaction was simulated to determine the propagation process of acoustic wave in the reactor. The possible degradation pathway was explored to mainly include carbonylation, carboxylation, and demethylation. The estimated effective-mean temperature at the bubble-water interface was calculated from 721 to 566 K after introducing the ClO2-, however, the adsorption or partitioning capacity of tpmCV in the reactive zone was widened from 0.0218 to 0.0982. The proposed co-catalysis of US/S2O82-/ClO2- was based on the determined active species mainly including ClO2, SO4⋅-, and ⋅OH. Compared with other US-based processes, the operating cost (3.97 $/m3) of US/S2O82-/ClO2- with the EE/O value (16.8 kWh/m3) was relatively reduced.

LPS induces cardiomyocyte necroptosis through the Ripk3/Pgam5 signaling pathway.

Necroptosis is a new type of cell death. However, the role of necroptosis in LPS-related cardiomyocyte damage has not been fully understood. The aim of our study is to explore the molecular mechanism underlying inflammation-mediated cardiomyocyte necroptosis. H9C2 cardiomyocyte cell line was treated with LPS. Then, cell viability and necroptosis were measured through qPCR and ELISA. Pathway analysis was performed to verify whether Ripk3/Pgam5 signaling pathway is implicated into the regulation of cardiomyocyte necroptosis. The results demonstrated that LPS reduced cardiomyocyte viability and activated necroptosis. At the molecular levels, oxidative stress and inflammation were triggered by LPS and these alterations may contribute to the activation of necroptosis. Finally, we found that Ripk3/Pgam5 signaling pathway was activated by LPS in cardiomyocyte and this signaling pathway may explain the regulatory mechanism underlying LPS-mediated necroptosis. Altogether, our results demonstrated that septic cardiomyopathy is associated with an activation of necroptosis through the Ripk3/Pgam5 signaling pathway.

Percutaneous Left Atrial Appendage Closure Confirmed by Intra-Procedural Transesophageal Echocardiography under Local Anesthesia: Safety and Clinical Efficacy.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) is usually performed under general anesthesia (GA) guided by transesophageal echocardiography (TEE), or under local anesthesia (LA) guided by intracardiac echocardiography (ICE). GA is known to carry some disadvantages. It is sometimes technically challenging to obtain adequate imaging of the left atrial appendage (LAA) with LAAC guided by ICE. This study aimed to assess the safety and clinical efficacy of LAAC guided by TEE under LA in patients with non-valvular atrial fibrillation (AF). METHODS: A total of 159 patients (70.5 ± 8.2 years; 66% male) with AF who had a high risk of stroke and bleeding or who had contraindications for oral anticoagulation underwent LAAC under LA. TEE or computed tomography (CT) follow-up was scheduled approximately 6 weeks after the procedure. Patients were followed to assess ischemic stroke and major bleeding events. RESULTS: The LAA was successfully occluded in 152 patients (95.6%). There were 2 (1.3%) periprocedural major adverse events. A total of 142 patients (93.4%) finished TEE or CT follow-up. Thrombus formation as seen on the device was documented in 2 patients. All of the LAAs were completely sealed with the absence of flow or with minimal flow. The median follow-up period was 522 days, resulting in a total of 216 patient-years. Ischemic stroke occurred in 4 patients. The annual ischemic stroke rate was 1.9/100 person-years. Major bleeding occurred in 2 patients. The annual major bleeding rate was 1.9/100 person-years. CONCLUSIONS: In this study, percutaneous LAAC using TEE under LA was safe and showed encouraging results for stroke prevention and major bleeding reduction.

Femtosecond laser assisted cataract surgery in a cataract patient with a "0 vaulted" ICL: a case report.

BACKGROUND: Femtosecond laser assisted cataract surgery (FLACS) combined with implantable collamer lenses (ICLs) extraction has been shown to be a feasible method for patients developing cataracts after the ICL implantation. All reported cases had shallow vaults, ranging from 47 µm (µm) to 100 µm. We report for the first time, a case in which the FLACS was performed on the "0" vault eye. CASE PRESENTATION: A 38-year-old man with anterior subcapsular cataracts underwent the FLACS combined with ICLs extraction 6 years after ICLs implantation in both eyes. In his left eye, the ICL touched the anterior capsule, existing "0" vault. During the capsulotomy, cavitation bubbles were trapped in the shallow space beneath the ICL, developing from small bubbles into big ones, which resulted in the incomplete capsulotomy. Comparatively, in the right eye, the ICL vault was measured 72 µm, and the capsulotomy was complete and no big cavitation bubbles formed. In both eyes, capsulotomy zones were manually assigned to the anterior capsule surface in the process of laser identification. However, the nuclear pre-fragmentations were unsuccessful in both eyes. Other steps of surgeries were performed uneventfully. Depending on the design of monovision, the uncorrected distance visual acuity (UDVA) was 20/32, and the near uncorrected visual acuity (UCVA) was 20/25 in both eyes postoperatively. CONCLUSIONS: This case suggested that the surgeon should pay attention to the incomplete laser capsulotomy when using a femtosecond laser in cataractous cases with "0" vaulted ICLs, and manual adjustment was required in the process of laser identification.

Effects of lens extraction versus laser peripheral iridotomy on anterior segment morphology in primary angle closure suspect.

PURPOSE: To compare the anatomical effects on anterior segment by lens extraction (LE, phacoemulsification with posterior chamber intraocular lens implantation) and laser peripheral iridotomy (LPI) in primary angle closure suspect (PACS) eyes. METHODS: This prospective comparative cohort trial included a total of 122 consecutive patients identified as PACS aged 52 to 80 years. LE or LPI was performed based on each patient's choice. The anterior segment optical coherence tomography (ASOCT) and gonioscopy were conducted at baseline and 4 weeks post-operation. Outcome measures include percentage of residual angle closure, mean angle width (modified Shaffer grade), angle opening distance (AOD), trabecular iris angle (TIA), trabecular iris space area (TISA), anterior chamber depth (ACD), iris curvature (I-Curve), lens vault (LV), intraocular pressure (IOP), and best-corrected visual acuity (BCVA). RESULTS: All anterior angle parameters (AOD, TIA, and TISA) were significantly greater after LE than LPI (P < 0.001 for all). ACD (P < 0.001) increased, LV (P < 0.001) decreased, IOP (P < 0.001) decreased, and BCVA (P < 0.001) increased after LE. However, no significant changes were found in ACD (P = 0.782), LV (P = 0.616), IOP (P = 0.112), and BCVA (P = 0.131) after LPI. In both groups, I-Curve decreased after the operation, but the iris was flatter after LE than LPI (P < 0.001). Gonioscopically, the LE group achieved a larger post-operative angle width (modified Shaffer grade) than LPI (P < 0.001) and all anterior chamber angles were open (defined as posterior pigmented trabecular meshwork (PTM) visible with static gonioscopy) after operation. Nevertheless, after LPI, 12 eyes (20.0%) still had two or more quadrants and 32 eyes (53.3%) still had at least one quadrant in which the posterior PTM could not be observed. CONCLUSIONS: Compared with LPI, LE resulted in a wider anterior chamber angle, a deeper anterior chamber, and a lower IOP in PACS eyes. Moreover, no residual angle closure was observed after LE, which could morphologically prevent the progress of angle closure. TRIAL REGISTRATION: ChiCTR1800016511.

Combination of left atrial appendage closure and catheter ablation in a single procedure for patients with atrial fibrillation: Multicenter experience.

BACKGROUND/PURPOSE: Experience in procedures combining left atrial appendage (LAA) closure (LAAC) and catheter ablation (CA) was scarce in Chinese nonvalvular atrial fibrillation (AF) patients with high risks for stroke and bleeding. We aimed to investigate the efficacy and safety of the combination therapy with LAAC and AF CA in a single procedure based on the multicenter data and medium-term follow-up results. METHODS: A total of 122 AF patients with a mean CHA2DS2-VASc score of 4.3 ± 1.4 and HAS-BLED score of 3.3 ± 1.0 were enrolled. The Watchman (n = 83) devices were implanted either before or after AF ablations in the same procedure, while the Amplatzer Cardiac Plug (ACP, n = 39) devices were implanted immediately after CA. AF recurrence and transesophageal echocardiography results were evaluated. RESULTS: All devices were successfully implanted and acute complete LAA occlusions were achieved in 115 (94.3%) of patients. Neither acute nor chronic peri-device leaks greater than 5 mm were detected. Oral anticoagulation was held in all patients but two with asymptomatic device-related thrombi, which were resolved after prolonged anticoagulation. AF-free success rate without antiarrhythmic drugs was 76.2% after a mean follow-up of 11.5 ± 6.8 months. No serious complications were observed during the follow-up. CONCLUSION: The combination therapy with LAAC and AF ablation in a single procedure was efficacious and safe in the Chinese symptomatic AF population with high risk for stroke and bleeding.

Association of Left Atrial Appendage Voltage with Ischemic Stroke in Patients with Atrial Fibrillation.

BACKGROUND: Low atrial voltage is associated with an increased risk of stroke. The relationship between left atrial appendage voltage (LAAV) and ischemic stroke remains unknown. Low LAAV may predict the prevalence of ischemic stroke in patients with atrial fibrillation (AF). METHODS: A total of 1108 patients with AF referred for catheter ablation were consecutively included from January 2015 to May 2018. The patients were divided into stroke and control groups based on previous ischemic stroke by neuroimaging criteria. LAAV was measured with a circular mapping catheter in sinus rhythm after ablation. Variables were compared, and logistic regression was performed to assess the relationship between LAAV and stroke. RESULTS: A total of 120 patients (10.8%) had a history of ischemic stroke. The patients in the stroke group were older and had higher percentages of hypertension, diabetes mellitus and coronary/vascular disease. The CHA2DS2-VASc score was higher and left atrial diameter was larger in the patients with stroke. More left atrial appendage thrombi and spontaneous echo contrast were detected in the stroke group. LAAV was significantly lower in the stroke group compared with the controls (5.3 ± 1.8 mV vs. 6.5 ± 1.8 mV; p < 0.001). Multivariate logistic regression revealed that a lower LAAV was associated with increased stroke prevalence [odds ratio = 0.75; 95% confidence interval (CI) 0.65-0.87; p < 0.001]. LAAV had a predictive value, with an area under the curve of 0.83 (95% CI 0.79-0.87; p < 0.001). With an optimal cut-off value of 5.2 mV for LAAV, the sensitivity and specificity were 75% and 74%, respectively. CONCLUSIONS: Lower LAAV in AF patients was associated with increased ischemic stroke prevalence. Whether LAAV is related to incident stroke requires further studies.

Optimal combination strategy of left atrial appendage closure plus catheter ablation in a single procedure in patients with nonvalvular atrial fibrillation.

BACKGROUND: The efficacy and safety of combining left atrial appendage closure (LAAC) plus atrial fibrillation (AF) catheter ablation (CA) in a single procedure has been established, but the optimal combination strategy has not been thoroughly elucidated to date. OBJECTIVE: We aimed to investigate the impact of different combination strategies on clinical outcomes. METHODS: Eighty-two consecutive patients with symptomatic AF (mean CHA2 DS2 -VASc score 4.4 ± 1.4, mean HAS-BLED score 3.5 ± 1.0) were enrolled. LAAC with the Watchman device was performed either before (occlusion-first group, N  =  52) or after (ablation-first group, N  =  30) CA. Procedural and clinical data were retrospectively analyzed to evaluate the advantages of each strategy. RESULTS: Complete device occlusions were achieved in 92.3% and 90.0% of patients, respectively (P  =  0.719). Neither acute nor chronic peridevice leak greater than 5 mm was detected. Oral anticoagulants were held in all patients, except two (one in each group) with asymptomatic device-related thrombi. AF-free success rates were comparable between groups with a mean follow-up of 11.2 ± 7.3 months (75.0% vs. 70.0%, log-rank P  =  0.311). The new peridevice leak rate was significantly lower in the occlusion-first group (7.7% vs. 26.7%, P  =  0.019). Multivariate logistic regression demonstrated that the combination strategy was independently associated with the new peridevice leak (P  =  0.025, OR 13.3). CONCLUSIONS: Both occlusion-first and ablation-first strategies were efficacious and safe as combined procedures in patients with nonvalvular AF; however, the occlusion-first strategy was associated with lower new peridevice leak rates at follow-up.

Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice.

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than that of the control mice, and the progression of cataracts was also much faster than the age-matched controls. Lenses of KO mice contained lower levels of protein thiols and GSH with a significant accumulation of S-glutathionylated proteins. Actin, αA-crystallin, and ßB2-crystallin were identified by Western blot and mass spectroscopy as the major S-glutathionylated proteins in the lenses of 16-month-old Grx2 KO mice. Compared with the WT control, the lens of Grx2 KO mice had only 50% of the activity in complex I and complex IV and less than 10% of the ATP pool. It was concluded that Grx2 gene deletion altered the function of lens structural proteins through S-glutathionylation and also caused severe disturbance in mitochondrial function. These combined alterations affected lens transparency.

Comparison of Drug Concentrations in Human Aqueous Humor after the Administration of 0.3% Gatifloxacin Ophthalmic Gel, 0.3% Gatifloxacin and 0.5% Levofloxacin Ophthalmic Solutions.

PURPOSE: To investigate the penetration of 0.3% gatifloxacin ophthalmic gel, 0.3% gatifloxacin ophthalmic solution and 0.5% levofloxacin ophthalmic solution into aqueous humor after topical application. MATERIALS AND METHODS: Age-related cataract patients (150 eyes in 150 cases) receiving phacoemulsification were randomly divided into three groups: a 0.3% gatifloxacin gel group (n=50), a 0.3% gatifloxacin solution group (n=50), and a 0.5% levofloxacin solution group (n=50). Each group was administered one drop of gel or solution every 15 minutes for four doses. Aqueous samples were collected at different time points after the last drop. High pressure liquid chromatography (HPLC) was applied to determine the concentrations. The one-way ANOVA analysis was performed. RESULTS: Our data indicated that the concentration of the gatifloxacin gel group was higher than that of the gatifloxacin solution group at all time points (P <0.05); moreover, the gatifloxacin gel group exhibited higher levels than the levofloxacin solution group at 120.0 min and 180.0 min (P<0.05). Furthermore, the gatifloxacin gel produced the highest concentration at 120.0 min, and the gatifloxacin and levofloxacin solutions reached their peak values at 60.0 min. CONCLUSIONS: 0.3% gatifloxacin ophthalmic gel application produced highest aqueous humor drug concentration, maintained the longest time, had the best penetration and bioavailability.