Comparison of Novel Telemonitoring System Using the Single-lead Electrocardiogram Patch With Conventional Telemetry System.

BACKGROUND AND OBJECTIVES: Although a single-lead electrocardiogram (ECG) patch may provide advantages for detecting arrhythmias in outpatient settings owing to user convenience, its comparative effectiveness for real-time telemonitoring in inpatient settings remains unclear. We aimed to compare a novel telemonitoring system using a single-lead ECG patch with a conventional telemonitoring system in an inpatient setting. METHODS: This was a single-center, prospective cohort study. Patients admitted to the cardiology unit for arrhythmia treatment who required a wireless ECG telemonitoring system were enrolled. A single-lead ECG patch and conventional telemetry were applied simultaneously in hospitalized patients for over 24 hours for real-time telemonitoring. The basic ECG parameters, arrhythmia episodes, and signal loss or noise were compared between the 2 systems. RESULTS: Eighty participants (mean age 62±10 years, 76.3% male) were enrolled. The three most common indications for ECG telemonitoring were atrial fibrillation (66.3%), sick sinus syndrome (12.5%), and atrioventricular block (10.0%). The intra-class correlation coefficients for detecting the number of total beats, atrial and ventricular premature complexes, maximal, average, and minimal heart rates, and pauses were all over 0.9 with p values for reliability <0.001. Compared to a conventional system, a novel system demonstrated significantly lower signal noise (median 0.3% [0.1-1.6%] vs. 2.4% [1.4-3.7%], p<0.001) and fewer episodes of signal loss (median 22 [2-53] vs. 64 [22-112] episodes, p=0.002). CONCLUSIONS: The novel telemonitoring system using a single-lead ECG patch offers performance comparable to that of a conventional system while significantly reducing signal loss and noise. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0008176.

Clinical Outcomes of Intracardiac Echocardiography-Guided Contrast Agent-Free Cryoballoon Ablation in Atrial Fibrillation Patients With Renal Insufficiency.

BACKGROUND AND OBJECTIVES: Previous studies have reported an association between impaired renal function and poor outcomes after radiofrequency catheter ablation in patients with atrial fibrillation (AF). However, outcomes of cryoballoon ablation (CBA) in patients with renal insufficiency are not fully elucidated. This study aimed to compare outcomes of CBA in AF patients with chronic kidney disease (CKD) versus those without CKD and to assess changes in renal function over 12 months following CBA. METHODS: A total of 839 patients (65.1% with non-paroxysmal AF [PAF]) who underwent de novo CBA were prospectively enrolled. We divided patients into two groups based on creatinine clearance rate (CCr) and performed intracardiac echocardiography (ICE)-guided contrast agent-free CBA. RESULTS: In comparison with patients without CKD (CCr >50, n=722), those with CKD (CCr ≤50, n=117) were older and predominantly female, had a lower body mass index, and showed a higher prevalence of heart failure and hypertension. Mean CHA2DS2-VAS score was significantly higher in CKD group than in non-CKD group. Procedure-related complications were not significantly different between two groups. During a mean follow-up period of 25.4±11.9 months, clinical recurrence occurred in 182 patients (21.7%) and not significantly different between two groups. In multivariate analysis, non-PAF and left atrial size were independent predictors of AF recurrence. CCr levels significantly improved over 12 months after CBA in CKD group. CONCLUSIONS: ICE-guided contrast-agent-free CBA showed comparable long-term clinical outcomes without increasing procedure-related complications and improvement of renal function over 12 months following CBA in AF patients with CKD.

Effects of Escitalopram on the Functional Neural Circuits in an Animal Model of Adolescent Depression.

PURPOSE: Although escitalopram is known to be an effective drug for adult depression, its disease-modifying efficacy on adolescents remains controversial. The present study aimed to evaluate the therapeutic effect of escitalopram on behavioral aspects as well as functional neural circuits by means of positron emission tomography. PROCEDURES: To generate the animal models of depression, restraint stress was used during the peri-adolescent period (RS group). Thereafter, escitalopram was administered after the end of stress exposure (Tx group). We performed NeuroPET studies of glutamate, glutamate, GABA, and serotonin systems. RESULTS: The Tx group showed no body weight change compared to the RS group. In the behavioral tests, the Tx group also displayed the similar time spent in open arms and immobility time to those for RS. In the PET studies, brain uptake values for the Tx group revealed no significant differences in terms of glucose, GABAA, and 5-HT1A receptor densities, but lower mGluR5 PET uptake compared to the RS group. In the immunohistochemistry, the Tx group showed the significant loss of neuronal cells in the hippocampus compared to the RS group. CONCLUSION: The administration of escitalopram had no therapeutic effect on the adolescent depression.

Safety and efficacy of intracardiac echocardiography-guided zero-fluoroscopic cryoballoon ablation for atrial fibrillation: a prospective randomized controlled trial.

AIMS: The development of intracardiac echocardiography (ICE) has enabled fluoroless atrial fibrillation (AF) ablation using three-dimensional electroanatomical mapping systems. However, fluoroless cryoballoon ablation (CBA) remains challenging, mainly because of the lack of a visual mapping system. Hence, this study aimed to investigate the safety and efficacy of fluoroless CBA for AF under ICE guidance. METHODS AND RESULTS: Patients (n = 100) who underwent CBA for paroxysmal AF were randomly assigned to zero-fluoroscopic (Zero-X) and conventional groups. Intracardiac echocardiography was used to guide the transseptal puncture and catheter and balloon manipulation in all enrolled patients. The patients were prospectively followed for 12 months after CBA. The mean age was 60.4 years, and the left atrial (LA) size was 39.4 mm. Pulmonary vein isolation (PVI) was achieved in all patients. In the Zero-X group, fluoroscopy was used in only one patient because of unstable phrenic nerve capture during right-sided PVI. The procedure time and LA indwelling time in the Zero-X group were not statistically different compared with that in the conventional group. Fluoroscopic time (9.0 vs. 0.008 min) and radiation exposure (29.4 vs. 0.02 mGy) were significantly shorter in the Zero-X group than in the conventional group (P < 0.001). The complication rate did not differ between the two groups. During a mean follow-up of 663.3 ± 172.3 days, the recurrence rate was similar (16.0 vs. 18.0%; P = 0.841) between the groups. Multivariate analysis revealed that LA size was the only independent predictor of clinical recurrence. CONCLUSION: Intracardiac echocardiography-guided fluoroless CBA for AF was a feasible strategy without compromising acute and long-term success or complication rates.

Safety of a single bolus administration of heparin without the measurement of activated clotting time during cryoballoon ablation: a prospective randomized controlled trial.

BACKGROUND: Single-shot ablation has emerged as an effective technique for index atrial fibrillation (AF) ablation, with an advantage of short procedure time. Although recent guidelines recommend peri-procedural uninterrupted oral anticoagulants (OACs), the intra-procedural anticoagulation strategy remains uncertain under non-vitamin K OACs (NOACs). We investigated procedural safety of a single bolus administration of heparin without activated clotting time (ACT) measurement during cryoballoon ablation (CBA). METHODS: Two hundred patients (64.2 ± 10.0 years, 70% with non-paroxysmal AF) who underwent CBA with uninterrupted NOACs were randomly assigned to No-ACT group and ACT group. A bolus of heparin (100 U/kg) was routinely administered immediately after transseptal puncture. In the ACT group, an additional injection of heparin (30 U/kg) was administered if ACT at 30 min after the initial bolus was < 300 s. RESULTS: There were no differences in baseline characteristics including CHA2DS2-VASc score between the two groups. The left atrium indwelling and procedure times were 60.4 ± 13.1 min and 78.9 ± 13.9 min, respectively, and not significantly different between the two groups. The mean ACT was 335.2 ± 59.9 s in the ACT group. Any bleeding rate was 3.2% in all patients and there was no statistically significant difference in bleeding complications between the two groups. In the ACT group, groin hematoma, laryngopharyngeal bleeding, and hemoptysis occurred in 3, 1, and 1 patient, respectively. Cardiac tamponade occurred in 1 patient in the No-ACT group. No thromboembolic events occurred during the 30-day follow-up after CBA. CONCLUSIONS: Single bolus administration of heparin without ACT measurement is a feasible anticoagulation strategy for CBA in patients with uninterrupted NOAC intake.

A Multi-Center, Prospective Observational Study to Investigate the Safety, Compliance, and Efficacy of Omethyl QTlet Soft Capsule.

Omega-3 fatty acids have been shown to be effective in lowering triglyceride (TG) levels; however, tolerability issues arise due to the large size of the pills. The purpose of this study was to examine the safety, compliance, and efficacy of Omethyl QTlet soft capsules (OQCs). This multi-center, prospective, observational study evaluated the safety, compliance, and efficacy of OQCs. Patients with hypertriglyceridemia with a history of omega-3 fatty acid intake were enrolled in this study and were prescribed OQCs (2 g−4 g/day) for eight weeks. All adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) were recorded for safety evaluation. Adherence to treatment was assessed using questionnaires, and efficacy was assessed by changes in lipid and lipoprotein levels after eight weeks from baseline. The convenience of taking medication was analyzed for 580 patients, and the efficacy test was performed for 563 patients. The AE and ADR rates were 8.2% and 5.7%, respectively. There were only two SAEs. Of the patients, 55.8% responded that the OQC improved medication convenience, and mean changes in TG, total cholesterol, LDL-C, and non-HDL-C from baseline to eight weeks were −37.88 mg/dL, −11.56 mg/dL, −5.55 mg/dL, and −10.87 mg/dL, respectively (p-values < 0.001). In patients who had previously taken omega-3 fatty acids, OQCs showed safety and efficacy in lowering TG, and it was confirmed that compliance with medicine also improved compared to omega-3 fatty acids.

Corrigendum: Amyloid pathology induces dysfunction of systemic neurotransmission in aged APPswe/PS2 mice.

[This corrects the article DOI: 10.3389/fnins.2022.930613.].

Amyloid pathology induces dysfunction of systemic neurotransmission in aged APPswe/PS2 mice.

This study aimed to investigate how amyloid pathology affects the functional aspects of neurotransmitter systems in Alzheimer's disease. APPswe/PS2 mice (21 months of age) and wild-type (WT) mice underwent positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). First, we obtained 18F-FDG and 18F-florbetaben PET scans to evaluate neuronal integrity and amyloid pathology. Second, 18F-FPEB and 18F-FMZ PET data were acquired to assess the excitatory-inhibitory neurotransmission. Third, to monitor the dopamine system, 18F-fallypride PET was performed. Amyloid PET imaging revealed that radioactivity was higher in the AD group than that in the WT group, which was validated by immunohistochemistry. In the cortical and limbic areas, the AD group showed a 25-27% decrease and 14-35% increase in the glutamatergic and GABAergic systems, respectively. The dopaminergic system in the AD group exhibited a 29% decrease in brain uptake compared with that in the WT group. A reduction in glutamate, N-acetylaspartate, and taurine levels was observed in the AD group using MRS. Our results suggest that dysfunction of the neurotransmitter system is associated with AD pathology. Among the systems, the GABAergic system was prominent, implying that the inhibitory neurotransmission system may be the most vulnerable to AD pathology.

Does isolation of the left atrial posterior wall using cryoballoon ablation improve clinical outcomes in patients with persistent atrial fibrillation? A prospective randomized controlled trial.

AIMS: Posterior wall isolation (PWI) of the left atrium (LA) adjunct to pulmonary vein isolation (PVI) by radiofrequency catheter ablation has shown favourable outcomes in patients with persistent atrial fibrillation (PeAF). This study was sought to investigate the efficacy and safety of additional PWI by cryoballoon ablation (CBA) alone in patients with PeAF. METHODS AND RESULTS: Patients who underwent de novo CBA for PeAF (n = 100) were randomly assigned (1 : 1) to the PVI only group and PVI combined with PWI (PVI+PWI) group. Procedural and clinical outcomes were prospectively compared over a 12-month follow-up.Baseline characteristics, including mean AF duration (56.2 ± 43.2 months) and LA size (48.2 ± 7.7 mm), were well-balanced between the groups. Successful PVI was achieved in all patients. In the PVI+PWI group, complete PWI by CBA was achieved in 31 (62%) patients. The LA indwelling and procedure times were significantly longer in the PVI+PWI group. The complication rates were not different between groups. During a mean follow-up of 457.9 ± 61.8 days, the recurrence rate of atrial tachyarrhythmia was significantly lower in the PVI+PWI group than in the PVI only group (24% vs. 46%; P = 0.035). The recurrence-free survival rate was significantly higher in the PVI+PWI group compared with the PVI only group, irrespective of complete PWI (log-rank P = 0.013). Multivariate analysis showed that adjunctive PWI [hazard ratio (HR) 0.255; P = 0.003] and LA size (HR 1.079; P = 0.014) were independent predictors of clinical recurrence. CONCLUSION: Compared with PVI only, adjunctive PWI achieved exclusively by CBA resulted in better clinical outcomes without increasing complications in patients with PeAF.

Improving Theranostic Gallium-68/Lutetium-177-Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer.

We developed a novel therapeutic radioligand, [177Lu]1h, with an albumin binding motif and evaluated it in a prostate-specific membrane antigen (PSMA)-expressing tumor xenograft mouse model. Fourteen PSMA target candidates were synthesized, and binding affinity was evaluated with an in vitro competitive binding assay. First, four compound candidates were selected depending on binding affinity results. Next, we selected four compounds ([68Ga]1e, [68Ga]1g, [68Ga]1h, and [68Ga]1k) were screened for tumor targeting efficiency by micro-positron emission tomography/computed tomography (micro-PET/CT) imaging. Finally, [177Lu]1h compound was evaluated the tumor targeting efficiency and therapeutic efficiency by micro-single-photon emission computed tomography/computed tomography (micro-SPECT/CT), biodistribution, and radiotherapy studies. Estimated human effective dose was calculated by biodistribution data. Compound 1h showed a high binding affinity (Ki value = 4.08 ± 0.08 nmol/L), and [177Lu]1h showed extended blood circulation (1 hour = 10.32 ± 0.31, 6 hours = 2.68 ± 1.07%ID/g) compared to [177Lu]PSMA-617 (1 h = 0.17 ± 0.10%ID/g). [177Lu]1h was excreted via the renal pathway and showed high tumor uptake (24.43 ± 3.36%ID/g) after 1 hour, which increased over 72 hours (72 hours = 51.39 ± 9.26%ID/g). Mice treated with 4 and 6 MBq of [177Lu]1h showed a median survival rate of >61 days. In particular, all mice treated with 6 MBq of [177Lu]1h survived for the entire monitoring period. The estimated human effective dose of [177Lu]1h was 0.07 ± 0.01 and 0.03 ± 0.00 mSv/MBq in total body and kidney, respectively. The current study indicates that [177Lu]1h has the potential for further investigation of metastatic castration-resistant prostate cancer (mCRPC) therapy in clinical trials.

Does merged three-dimensional mapping improve contact force and long-term procedure outcome in atrial fibrillation ablation? (MICRO-AF study): a prospective randomized controlled study.

Integration of electroanatomical map (EAM) with preacquired three-dimensional (3D) cardiac images provides detailed appreciation of the complex anatomy of the left atrium (LA) and pulmonary vein (PV). High-density (HD) multi-electrode mapping catheters have enabled creating more accurate EAM reflecting real-time volume-rendered LA-PV geometry during atrial fibrillation (AF) ablation. However, no study has compared the outcomes of AF ablation using HD-EAM versus 3D-merged map. We aimed to investigate the procedural and clinical outcomes of AF ablation with HD-EAM (HD-EAM group) versus 3D-merged map (Merge group). One hundred patients (59.5 ± 11.5 years, 53% with paroxysmal AF [PAF]) were randomly assigned (1:1) to HD-EAM or Merged group. HD multi-electrode mapping and contact force (CF)-sensing catheters were used to create virtual LA-PV chamber and to perform wide antral circumferential ablation (WACA), respectively. The two groups showed no significant differences in baseline characteristics and procedural data including ablation time, fluoroscopy time, LA voltage, and CF. PV isolation with a single WACA line was achieved in 21 (42%) and 27 (54%) patients in the Merge and HD-EAM groups, respectively (P = NS). CF was significantly lower in lesions with gap than lesions without gap after a single WACA (7.3 ± 7.3 g vs. 16.0 ± 8.3, respectively, P < 0.001). During the 12-month follow-up, no significant difference in AF recurrence was observed between two groups, irrespective of AF type. In multivariate analysis, non-PAF was an independent risk factor for AF recurrence. Integration of 3D cardiac imaging did not improve procedural and clinical outcomes. HD-EAM provides an accurate real-time LA geometry.

Bosworth-type fibular entrapment fracture of the ankle without dislocation: a rare case report and a review of the literature.

Bosworth fracture-dislocation of ankle is a rare and irreducible type of ankle injury, with a high incidence of complication. This type of fracture was defined originally as entrapment of the proximal fragment of the fibula behind the posterior tubercle of the distal tibia. Recently, many variants of this type of fracture dislocation have been reported, but all of those reports included the syndesmosis ligament injury of ankle. Here, we report a case of a particularly rare variant of Bosworth fracture-dislocation without syndesmosis ligament injury of ankle. A 48-year-old male presented with a Bosworth fracture dislocation with entrapment of proximal fragment behind the tibia. After temporary treatment in emergency department was applied, emergency open reduction and internal fixation with a plate and screws was performed due to irreducibility of the fracture fragment. The fractured lateral malleolus was entrapped behind the tibia and rupture of the interosseous ligament was found intraoperatively. The anterior inferior tibiofibular ligament, a part of syndesmosis ligament of ankle, was grossly intact and no abnormal findings was seen by fluoroscopy with external rotational stress. Moreover, the deltoid ligament was found to be normal in ultrasonography. There were no complications after surgery and the patient showed full functional recovery at 2 years follow up. These fractures will frequently be irreducible and should be considered for open reduction and internal fixation with the careful evaluation of injury mechanisms with syndesmotic stability.

A systematic review comparing the results of early vs delayed ligament surgeries in single anterior cruciate ligament and multiligament knee injuries.

PURPOSE: The purpose of this study was to compare clinical outcomes and incidence of concomitant injuries in patients undergoing early vs delayed surgical treatment of single anterior cruciate ligament (ACL) injury and multiligament knee injury (MLKI). METHODS: A literature search using PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health, and Scopus from their inception to April 30, 2020 was conducted. Studies with levels I to IV evidence reporting the incidence of meniscus or cartilage injury according to early vs delayed surgery in single ACL injuries and MLKIs were included. In the meta-analysis, data based on the number of meniscus and cartilage injuries were extracted and pooled. Lysholm and Tegner scores were analyzed using two-sample Z-tests to calculate the non-weighted mean difference (NMD). A meta-regression analysis was also performed to determine the effect of single ACL injury and MLKI/study design. RESULTS: Sixteen studies on single ACL injury and 14 studies on MLKI were included in this analysis. In the analysis, there were significant decreases in Lysholm score (NMD - 5.3 [95% confidence interval (CI) - 7.37 to - 3.23]) and Tegner score (NMD - 0.25 [95% CI - 0.45 to - 0.05]) and increases in risk of meniscus tear (odds ratio [OR] 1.73 [95% CI 1.1-2.73], p = 0.01) and cartilage injury (OR 2.48 [95% CI 1.46-4.2], p = 0.0007) in the delayed surgery group regardless of single ACL injury or MLKI. The result of the meta-regression analysis indicated that single ACL injury and MLKI/study design were not significant moderators of overall heterogeneity (p > 0.05). CONCLUSIONS: Our study suggests that delayed ACL surgery significantly resulted in a higher risk of meniscus tear and cartilage injury and decreased Lysholm and Tegner scores compared to early ACL surgery. The Lysholm scores in the delayed MLKI surgery group were significantly decreased, but the risks of meniscus tear and cartilage injury in the delayed MLKI surgery group remained unclear. LEVEL OF EVIDENCE: Level III, meta-analysis.

Evaluation of the neuroprotective effect of taurine in Alzheimer's disease using functional molecular imaging.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31-40% higher than that in the AD group (cortex: 40%, p < 0.05; striatum: 32%, p < 0.01; hippocampus: 36%, p < 0.01; thalamus: 31%, p > 0.05) and 3-14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aß pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.

Efficacy of high-power and short-duration ablation in patients with atrial fibrillation: a prospective randomized controlled trial.

AIMS: The formation of radiofrequency lesions depends on the power and duration of ablation, and the contact force (CF). Although high power (HP) creates continuous and transmural lesions, most centres still use 25-30 W for 30-40 s for safety reasons. We evaluated the clinical efficacy and safety of a HP and short-duration (HPSD) strategy for atrial fibrillation (AF) ablation. METHODS AND RESULTS: One hundred and fifty patients [58.2 ± 10.0 years, 48% with paroxysmal AF (PAF)] scheduled for index AF ablation using a CF-sensing catheter were randomly assigned to three groups [30 W, 40 W, and 50 W at ablation sites of anterior, roof, and inferior segments of pulmonary vein (PV) antra and roof line between each upper PV]. In 25-30 W for ≤20 s was applied at posterior wall ablation site in all subjects. Compared with the 30 W and 40 W groups, procedure (P < 0.001) and ablation times (P < 0.001) were shorter and ablation number for PV isolation (P < 0.001) was smaller in the 50 W group. There were no significant differences in the CF and ablation index (AI) among the three groups. There were no significant differences in the procedure-related complication rates. During the 12-month follow-up, AF recurred in 24 (16%) patients with no significant difference among the groups (P = 0.769). In the multivariate analysis, non-PAF [hazard ratio (HR) 2.836, P = 0.045] and AI (HR 0.983, P = 0.001) were independent risk factors for AF recurrence. CONCLUSION: Radiofrequency ablation with HPSD is a safe and effective strategy with reduced ablation number and shortened procedure time compared to conventional ablation.

Predictors of survival following veno-arterial extracorporeal membrane oxygenation in patients with acute myocardial infarction-related refractory cardiogenic shock: clinical and coronary angiographic factors.

BACKGROUND: This study aimed to identify the determinant factors of survival in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock (RCS) who underwent veno-arterial extracorporeal membrane oxygenation (ECMO). METHODS: Sixty-nine consecutive patients with AMI-related RCS were enrolled in the study. They were treated with ECMO and primary percutaneous coronary intervention (PCI). The clinical scores and coronary angiography (CAG) factors related to 100-day survival were evaluated. RESULTS: Thirty patients (43.5%) survived for more than 100 days. The CAG showed that 19 (27.5%) patients had left main disease (LMD). There were 17 (24.6%), 27 (39.1%), and 25 (36.3%) patients with one-vessel, two-vessel, and three-vessel disease, respectively. There were significant differences between the survivors and non-survivors in the simplified acute physiology score II (SAPSII) (65.4±17.2 vs. 83.1±13.0, P<0.001), sepsis-related organ failure assessment score (SOFA) (10.4±2.7 vs. 12.3±2.5, P=0.004), survival after veno-arterial extracorporeal membrane oxygenation score (SAVE) (-4.4±4.3 vs. -8.4±3.1, P<0.001), CPR time (15.8±16.6 vs. 30.0±29.5, P=0.048), LMD [4 (13.3%) vs. 15 (38.5%), P=0.029], and number of coronary artery disease (NCAD) (P<0.001). Multivariate logistic regression analysis showed that NCAD (OR 3.788, P=0.008) was one of the independent predictors of mortality. The ROC analysis showed that SAPSII (AUC 0.786, P<0.001), SOFA (AUC 0.715, P=0.002), and SAVE (AUC 0.766, P<0.001) equally predict mortality. The combined NCAD parameters more accurately predicted mortality and differences in the AUC values (d-AUC) between SAPSII plus NCAD vs. SAPSII (d-AUC 0.073, z=2.256, P=0.024), SOFA plus NCAD vs. SOFA (d-AUC 0.058, z=2.773, P=0.006), and SAVE plus NCAD vs. SAVE (d-AUC 0.036, z=2.332, P=0.020). CONCLUSIONS: The SAPSII, SOFA, and SAVE scores predict the prognosis of ECMO-treated AMI patients with RCS. The CAG findings reinforce the predictive power of each score.

Brain natriuretic peptide levels predict 6-month mortality in patients with cardiogenic shock who were weaned off extracorporeal membrane oxygenation.

There are limited data regarding the association between brain natriuretic peptide (BNP) levels obtained after weaning from extracorporeal membrane oxygenation (ECMO) and the outcomes of patients with acute coronary syndrome (ACS)-associated cardiogenic shock.We prospectively obtained data regarding patients (aged ≥ 19 years) with ACS-associated cardiogenic shock who received ECMO and were subsequently weaned off the treatment. BNP levels were collected at 5 time points: pre-ECMO implantation, post-ECMO implantation, pre-ECMO weaning, day 1 after ECMO weaning, and day 5 after ECMO weaning.Of 48 patients with ACS-related cardiogenic shock, 33 were included in this analysis. Mean patient age was 59.0 (50.0-66.5) years, and 5 patients (15.2%) were women. Eight patients had asystole/pulseless electrical activity before ECMO and 14 (42.4%) had 3-vessel disease on coronary angiography. During the 6-month follow up, 12 (36.4%) patients died. BNP levels after ECMO weaning were significantly different between 6-month survivors and non-survivors. Cox proportional hazards model revealed that BNP levels (tertiles) on days 1 and 5 after ECMO weaning were significantly associated with 6-month mortality (hazard ratio, 7.872; 95% confidence interval, 1.870-32.756; 8.658 and 1.904-39.365, respectively). According to the Kaplan-Meier curves, the first tertile had significantly longer survival compared to the third tertile for both days 1 and 5 after ECMO weaning.Post-ECMO weaning BNP levels (days 1 and 5) were significantly associated with increased 6-month mortality in patients with ACS complicated by refractory cardiogenic shock who were weaned off ECMO.

Evaluation of the Neuroprotective Effect of Microglial Depletion by CSF-1R Inhibition in a Parkinson's Animal Model.

PURPOSE: Neuroinflammation in Parkinson's disease (PD) is known to play a pivotal role in progression to neuronal degeneration. It has been reported that colony-stimulation factor 1 receptor (CSF-1R) inhibition can effectively deplete microglia. However, its therapeutic efficacy in PD is unclear still now. PROCEDURES: To elucidate this issue, we examined the contribution of microglial depletion to PD by behavioral testing, positron emission tomography (PET) imaging, and immunoassays in sham, PD, and microglial depletion PD model (PLX3397 was administered to PD groups, with n = 6 in each group). RESULTS: The microglial depletion in PD model showed improved sensory motor function and depressive-like behavior. NeuroPET revealed that PLX3397 treatment resulted in partial recovery of striatal neuro-inflammatory functions (binding values of [18F]DPA-174 for PD, 1.47 ± 0.12, p < 0.01 vs. for PLX3397 in PD: 1.33 ± 0.26) and the dopaminergic (binding values of 18F-FP-CIT for PD, 1.32 ± 0.07 vs. for PLX3397 in PD: 1.54 ± 0.10, p < 0.01) and glutamatergic systems (binding values of [18F]FPEB for PD: 9.22 ± 0.54 vs. for PLX3397 Tx in PD: 9.83 ± 0.96, p > 0.05). Western blotting for microglia showed similar changes. CONCLUSION: Microglial depletion has inflammation-related therapeutic effects, which have beneficial effects on motor and nonmotor symptoms of PD.

Identification of Markers Associated With Development of Stroke in "Clinically Low-Risk" Atrial Fibrillation Patients.

Background Stroke and thromboembolic events may still occur in "clinically low-risk" atrial fibrillation (AF) patients as categorized by CHA2DS2-VASc score. Our aim was to assess the proportion of "clinically low-risk" patients using a nongender CHA2DS2-VASc (ie, CHA2DS2-VA) score of 0 to 1 among patients who experienced AF-associated stroke and to identify markers associated with stroke in "clinically low-risk" patients. Methods and Results We retrospectively recruited nonvalvular AF patients who experienced embolic stroke between 2013 and 2016 from 9 institutes in Korea. AF patients with CHA2DS2-VA score of 0 to 1 at the time of stroke were analyzed and compared with "clinically low-risk" AF patients without stroke. A total of 3033 subjects with AF-associated stroke were recruited. Of these, 583 patients (19.2%) had CHA2DS2-VA score of 0 to 1. On multivariate analysis, age (≥60 years), N-terminal pro B-type natriuretic peptide (≥300 pg/mL), creatinine clearance (<50 mL/min), and left atrial dimension (≥45 mm) were independently associated with stroke. With the combined application of these 4 factors (collectively, ABCD score) to the "clinically low-risk" patients, the c-index was 0.858 (95% CI 0.838-0.877; P<0.001). Conclusions The present study suggests a new insight into how additional use of markers can further refine stroke risk differentiation among AF patients initially classified as "clinically low-risk." Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03147911.

Age dependency of mGluR5 availability in 5xFAD mice measured by PET.

The major pathologies of Alzheimer's disease (AD) are amyloid plaques and hyperphosphorylated tau. The deposition of amyloid plaques leads to synaptic dysfunction, neuronal cell death, and cognitive impairment. Among the neurotransmitters, glutamate is the most abundant in the mammalian brain and plays an important role in synaptic plasticity. With respect to synaptic transmission, metabotropic glutamate receptor 5 (mGluR5) is highly affected by amyloid pathology. However, the neuropathologic changes in the protein expression of mGluR5 in AD remain unclear. Therefore, to elucidate the alteration in mGluR5 expression with the progression of AD, we performed serial behavioral tests, longitudinal imaging studies, and histopathological immunoassay for both 5xFAD (n = 14) mice and age-matched wild-type mice (n = 14). The 5xFAD mice started showing severe hyperactivity and memory impairment from 7 months of age. In addition, mGluR5 positron emission tomography revealed that while the binding values in the wild-type mice were similar over time, those in 5xFAD mice fluctuated from 5 months of age. Furthermore, the 5xFAD mice presented a 35% decrease in the binding values of their cortical and subcortical areas at 9 months of age compared with those at 3 months of age. Magnetic resonance spectroscopy and histopathological studies showed similar changes. In conclusion, mGluR5 availability changes with age, and mGluR5 positron emission tomography could successfully detect this synaptic change in the 5xFAD mice.