The expression of PD-L1 on tumor-derived exosomes enhances infiltration and anti-tumor activity of αCD3 × αPD-L1 bispecific antibody-armed T cells.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Verification of a nationwide population-based myopia growth chart in a large longitudinal cohort of 1155 Korean children.

OBJECTIVE: To evaluate predictive value of the myopia growth chart based on population-based health survey data using longitudinal cohorts. METHODS: Patients aged from 5 to 18 years and underwent two or more cycloplegic refraction (CR) exams with at least one year of interval were included. Percentile deviation was calculated by subtracting percentile at final exam from the percentile at initial exam based on the chart. Spherical equivalent (SE) deviation was calculated by SE at final CR subtracted from predicted SE based on initial CR using the chart. RESULTS: 2310 eyes from 1155 subjects were included. There were 1344 eyes (58.2%) categorized as inliers, where both initial and final CR were within the 2nd to 99th percentile. Mean percentile and SE deviations were + 11.0 ± 22.9 percentiles and -0.60 ± 1.33 diopters, each. Outliers, those except the inliers, were 966 eyes (41.8%). Most outliers (709 eyes, 73.4%) were outside the chart for both initial and final exam. The rest of the outliers (257 eyes, 26.2%) were within the 2 to 99 percentile range on the chart at least once, either at initial or final exams; most of those (202 eyes, 78.6%) progressed toward myopia more than predicted. CONCLUSIONS: In our large cohorts, both inliers and outliers tended to progress toward more myopia than predicted from the chart. This suggests the chart predicts childhood myopia rather conservatively. The myopia growth chart may be useful as a screening tool in detecting children at high risk of developing high myopia.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Impact of new-onset arrhythmia on cardiac reverse remodeling following transcatheter aortic valve replacement: computed tomography-derived left ventricular and atrial strains.

OBJECTIVE: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. METHODS: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. RESULTS: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (- 6.7 ± 2.4 vs. - 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, - 15.5 ± 4.0 to - 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). CONCLUSIONS: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. CLINICAL RELEVANCE STATEMENT: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. KEY POINTS: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve.

Different Clinical Features between Definite and Possible Takotsubo Syndrome in a Tertiary Referral Hospital.

BACKGROUND: Although imaging examination to exclude coronary artery disease (CAD) is an indispensable step for a definite diagnosis of takotsubo syndrome (TTS), this step may be overlooked in a substantial proportion of patients with secondary TTS admitted to a tertiary hospital. However, the clinical profiles and outcomes of these patients with "possible TTS" have rarely been investigated. METHODS: Among 420 consecutive TTS patients with characteristic transient ventricular ballooning on repeated echocardiography, 244 patients (58.1%) who underwent an imaging study for CAD were diagnosed with "definite TTS," whereas the remaining 176 were designated with "possible TTS." RESULTS: Overall, hypoxia (67.6%) and dyspnea (55.5%) were predominant presentations. The possible group was characterized by higher prevalence of male gender (46.6% vs. 35.2%, p = 0.019), secondary TTS (97.2% vs. 86.5%, p < 0.001), cancer (43.2% vs. 29.1%, p = 0.003), sepsis (46.0% vs. 32.0%, p = 0.003), and nonapical ballooning pattern (30.7% vs. 21.3%, p = 0.001) with less common ST-segment elevation on electrocardiogram (18.8% vs. 34.0%, p = 0.001). The possible group showed higher frequency of mechanical ventilation (56.2% vs. 40.2%, p = 0.001), pulmonary edema (72.2% vs. 61.5%, p = 0.023), and shock management (70.5% vs. 54.1%, p = 0.001) with similar in-hospital mortality (17.2% vs. 17.0%, p = 0.964). CONCLUSIONS: In real-world clinical practice, coronary evaluation for strict diagnosis of TTS is not frequently feasible. Addition of the possible group without coronary evaluation to the clinical spectrum of TTS would be helpful for fair estimation of clinical implication of TTS.

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.

Lightwand-Guided Insertion of Flexible Reinforced Laryngeal Mask Airway: Comparison with Standard Digital Manipulation Insertion.

BACKGROUND The flexibility of the long flexometallic tube makes insertion of the flexible reinforced laryngeal mask airway (f-LMA) difficult. We compared the usefulness of rigid lightwand-guided f-LMA insertion with standard digital manipulation. MATERIAL AND METHODS Fifty-four patients (aged 19-70 years) were randomly divided into a control group (digital manipulation technique) or the lightwand group (lightwand-guided insertion technique). The insertion profiles, oropharyngeal leak pressure (OLP), peak inspiratory pressure (PIP), expiratory tidal volume, and ventilatory score were measured in patients with neutral, extension, rotation, flexion, and re-neutral head-neck positions in turn. RESULTS The success rate and ease of insertion did not differ between groups, but the insertion time was longer in the lightwand group. The fiberoptic laryngeal view was significantly better in the lightwand group than in the control group. However, the OLP, PIP, expiratory tidal volume, and ventilatory scores were not significantly different between groups according to head-neck positions. The extension posture was associated with a significant negative effect on ventilation, but ventilation returned to initial levels with the other postures. CONCLUSIONS Lightwand-guided f-LMA insertion showed a better fiberoptic laryngeal view than standard digital manipulation, but no improvement in the ventilatory state was observed due to position. Therefore, lightwand-guided insertion could facilitate correct placement of the f-LMA, but it has limited clinical usefulness.

Efficacy of blood urea nitrogen and the neutrophil-to-lymphocyte ratio as predictors of mortality among elderly patients with genitourinary tract infections: A retrospective multicentre study.

OBJECTIVES: To investigate whether initial blood urea nitrogen (BUN) and the neutrophil-to-lymphocyte ratio (NLR) in the emergency department (ED) are associated with mortality in elderly patients with genitourinary tract infections. METHODS: A total of 541 patients with genitourinary tract infections in 5 EDs between November 2016 and February 2017 were included and retrospectively reviewed. We assessed age, sex, comorbidities, vital signs, and initial laboratory results, including BUN, NLR and the SOFA criteria. The primary outcome was all-cause in-hospital mortality. RESULTS: The nonsurvivor group included 32 (5.9%) elderly patients, and the mean arterial pressure (MAP), NLR and BUN were significantly higher in this group than in the survivor group (p < 0.001, p = 0.003, p < 0.001). In multivariate analysis, MAP <70 mmHg, NLR ≥23.8 and BUN >28 mg/dl were shown to be independent risk factors for in-hospital mortality (OR 3.62, OR 2.51, OR 2.76: p = 0.002, p = 0.033, p = 0.038, respectively). Additionally, NLR ≥23.8 and BUN >28 were shown to be independent risk factors for mortality in admitted elderly with complicated UTI (p = 0.030, p = 0.035). When BUN and NLR were combined with MAP, the area under the ROC curve (AUROC) value was 0.807 (0.771-0.839) for the prediction of mortality, the sensitivity was 87.5% (95% CI 71.0-96.5), and the specificity was 61.3% (95% CI 56.9-65.5%). CONCLUSION: The initial BUN and NLR values with the MAP were good predictors associated with all-cause in-hospital mortality among elderly genitourinary tract infections visiting the ED.

The qSOFA score combined with the initial red cell distribution width as a useful predictor of 30 day mortality among older adults with infection in an emergency department.

PURPOSE: This study aimed to investigate whether the qSOFA and initial red cell distribution width (RDW) in the emergency department (ED) are associated with mortality in older adults with infections who visited the ED. METHODS: This was a retrospective study conducted in 5 EDs between November 2016 and February 2017. We recorded age, sex, comorbidities, body temperature, clinical findings, and initial laboratory results, including the RDW. The initial RDW values and the qSOFA criteria were obtained at the time of the ED visit. The primary outcome was 30 day mortality. RESULTS: A total of 1,446 patients were finally included in this study, of which 134 (9.3%) died within 30 days and the median (IQR) age was 77 (72, 82) years. In the multivariable analysis, the RDW (14.0-15.4%) and highest RDW (> 15.4%) quartile were shown to be independent risk factors for 30 day mortality (OR 2.12; 95% CI 1.12-4.02; p = 0.021) (OR 3.35; 95% CI 1.83-6.13; p < 0.001). The patients with qSOFA 2 and 3 were shown to have the high odds ratios of 30-day mortality (OR 3.50; 95% CI 2.09-5.84; p < 0.001) (OR 11.30; 95% CI 5.06-25.23; p < 0.001). The qSOFA combined with the RDW quartile for the prediction of 30 day mortality showed an AUROC value of 0.710 (0.686-0.734). CONCLUSION: The qSOFA combined with the initial RDW value was associated with 30-day mortality among older adults with infections in the ED. The initial RDW may help emergency physicians predict mortality in older adults with infections visiting the ED.

Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Blood pressure levels and cardiovascular risk according to age in patients with diabetes mellitus: a nationwide population-based cohort study.

BACKGROUND: Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. METHODS: Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. RESULTS: Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages. CONCLUSIONS: In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of ≥ 70.

The neutrophil-to-lymphocyte ratio is associated with bacteremia in older adults visiting the emergency department with urinary tract infections.

PURPOSE: We evaluated the clinical features of older adults visiting the emergency department (ED) with urinary tract infections (UTIs), and the diagnostic utility of the neutrophil-to-lymphocyte ratio (NLR) in terms of identifying bacteremia. METHODS: In total, 479 older adults admitted with UTIs via the ED between January 2010 and December 2015 were retrospectively reviewed. We recorded age, sex, comorbidities, body temperature, clinical findings, and initial laboratory results, including the NLR. RESULTS: A UTI with bacteremia was identified in 186 (38.8%) older adults. Bacteremia was associated with a longer hospital stay (median 10 vs. 8 days, p < 0.001). NLRs and C-reactive protein, blood urea nitrogen and creatinine levels were significantly higher in the bacteremia group than in the non-bacteremia group (p < 0.001, p = 0.016, p = 0.008, and p = 0.011, respectively). The area under the curve for the NLR was 0.624 (95% CI = 0.579-0.668, p < 0.001), and the cutoff was 9.0 (sensitivity 74.2, specificity 49.2%). Independent risk factors for bacteremia were an NLR ≥ 9 and fever ≥ 39 °C (OR 2.43, OR 2.75: p < 0.001, p < 0.001, respectively). CONCLUSION: Bacteremia was associated with a longer hospital stay in older adults with UTIs, in whom the initial NLR and high fever reliably predicted bacteremia. The NLR may help emergency physicians to predict bacteremia in older adults with UTIs visiting the ED.

Differential clinical features and long-term prognosis of acute aortic syndrome according to disease entity.

AIMS: To evaluate the acute and long-term prognosis of acute aortic syndrome (AAS) according to the disease entity [intramural haematoma (IMH) vs. aortic dissection (AD)] and the anatomical location (type A vs. B). METHODS AND RESULTS: A total of 1012 patients [672 with AD and 340 with IMH (33.6%)] were enrolled between 1993 and 2015. Compared with AD patients, IMH patients were older and had higher frequency of female sex and distal aorta involvement. The overall crude in-hospital mortality of AAS was 8.6%; type A AD [15.0%; adjusted hazard ratio (aHR) 30.4; 95% confidence interval (CI) 8.62-107.3; P < 0.001], type A IMH (8.0%; aHR 4.85; 95% CI 1.29-18.2; P = 0.019), type B AD (5.0%; aHR 3.51; 95% CI 1.00-12.4; P = 0.051), and type B IMH [1.5%; aHR 1.00 (reference)]. During a median follow-up duration of 8.5 years (interquartile range: 4.0-13.5 years), AD (aHR 2.78; 95% CI 1.87-4.14; P < 0.001) and type A (aHR 2.28; 95% CI 1.45-3.58; P < 0.001) was associated with a higher risk of aortic death. After 90 days, a risk of aortic death was no longer associated with anatomical location (aHR 0.74; 95% CI 0.40-1.36; P = 0.33), but remained associated with disease entity (aHR 1.83; 95% CI 1.10-3.04; P = 0.02). CONCLUSION: The clinical features, response to treatment strategy, and outcomes of IMH patients were distinct from those of AD patients. Both early and late survival was better for IMH than for AD. In addition to the anatomical location of AAS, the disease entity is an independent factor associated with both acute and long-term mortality in patients with AAS. Further investigation is necessary to confirm the prognostic implication of disease entity in different patient populations.

Beryllium-Ion-Selective PEDOT Solid Contact Electrode Based on 9,10-Dinitrobenzo-9-Crown-3-Ether.

A beryllium(II)-ion-selective poly(ethylenedioxythiophene) (PEDOT) solid contact electrode comprising 9,10-dinitrobenzo-9-crown-3-ether was successfully developed. The all-solid-state contact electrode, with an oxygen-containing cation-sensing membrane combined with an electropolymerized PEDOT layer, exhibited the best response characteristics. The performance of the constructed electrode was evaluated and optimized using potentiometry, conductance measurements, constant-current chronopotentiometry, and electrochemical impedance spectroscopy (EIS). Under optimized conditions, which were found for an ion-selective membrane (ISM) composition of 3% ionophore, 30% polyvinylchloride (PVC), 64% o-nitro phenyl octyl ether (o-NPOE), and 3% sodium tetraphenylborate (NaTPB), the fabricated electrode exhibited a good performance over a wide concentration range (10-2.5-10-7.0 M) and a wide pH range of 2.0-9.0, with a Nernstian slope of 29.5 mV/D for the beryllium (II) ion and a detection limit as low as 10-7.0 M. The developed electrode shows good selectivity for the beryllium(II) ion over alkali, alkaline earth, transition, and heavy metal ions.

Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells.

Mucin1 (MUC1) is aberrantly glycosylated and overexpressed in various cancers, and it plays a crucial role in cancerogenesis. MUC1 is a type I membranous protein composed of α and ß subunits. MUC1-α can be cleaved in cancers, exposing MUC1-ß (MUC1-C). MUC1-C is involved with multiple cancer cellular functions, which makes it an attractive target for cancer treatment. However, its multifunctional mechanisms have not been fully elucidated and there has not been a successful therapeutic development against MUC1-C. Through a phage display process, we isolated the specific antibodies for the extracellular domain of MUC1-C. The relevant full IgG antibodies were produced successfully from mammalian cells and validated for their MUC1-C specificities through ELISA, dual FACS analysis, BLI assay, and confocal image analysis. In the comparison with reference antibody, elected antibodies showed characteristic bindings on target antigens. In the functionality assessment of high-ranking antibodies, SKM1-02, -13, and -20 antibodies highly inhibited invasion by triple-negative breast cancer (TNBC) cells and the SKM1-02 showed strong growth inhibition of cancer cells. Our results showed that these MUC1-C specific antibodies will be important tools for the understanding of MUC1 oncogenesis and are also highly effective therapeutic candidates against human breast cancers, especially TNBC cells.

Elderly patients visiting the emergency department for deliberate self-poisoning: do they present a more severe poisoning severity score than the nonelderly patients in the initial 24 h?

PURPOSE: Many elderly patients arrive at the emergency department (ED) complaining of deliberate self-poisoning (DSP). This study determined the poisoning severity of elderly patients who committed DSP. METHODS: A study was performed with 1329 patients (> 15 years of age) who were treated for DSP at two EDs between January 2010 and December 2016. We classified these patients into two groups based on age (an elderly group ≥ 65 years of age and a nonelderly group). Information was collected on age, sex, cause, ingestion time, drug type, suicide attempt history, initial poisoning severity score (PSS), final PSS, outcome, etc. RESULTS: In total, 242 (18.2%) patients were included in the elderly group, of whom 211 (86.9%) were treated for a first suicide attempt. Admission to the intensive-care unit (ICU) (43.8% vs. 25.5%) and endotracheal intubation (16.1% vs. 4.9%) occurred more frequently in the elderly group than in the nonelderly group (p < 0.001). The frequencies of initial severe PSSs (3 and 4) in the elderly group were 9.1% (N = 22) and 1.2% (N = 3), respectively. Multivariate logistic regression analysis showed that the ICU admission of DSP patients was significantly associated with being elderly (OR of 1.47, 95% CI 1.04-2.09, p = 0.029) and with having a GCS of < 13 (OR of 2.67, 95% CI 1.99-3.57, p < 0.001) and an initial PSS of (3,4) (OR of 3.66, 95% CI 2.14-6.26, p < 0.001). In addition, the presence of underlying diseases (coronary heart disease and cerebrovascular disease) yielded high ORs [(OR of 13.13, 95% CI 2.80-61.57, p = 0.001), (OR of 7.34, 95% CI 1.38-39.09, p = 0.020)]. CONCLUSION: Elderly patients who visited the ED for DSP exhibited overall more severe PSSs and poorer in-hospital prognosis than did nonelderly DSP patients.

Distribution of internal thoracic artery perforators: A clincal anatomy study.

There are various modifications of the transverse rectus abdominis musculocutaneous flap and deep inferior epigastric perforator flap to reduce the morbidity of the donor site or to augment the vascularity of the flap. For microanastomosis of multiple pedicles, multiple recipient vessels or an intervening vein graft should be provided. In addition, alternative perforator-based flaps used in breast reconstruction have small caliber pedicles. Therefore, small recipient vessels such as internal thoracic artery perforators are more suitable for appropriate microanastomosis. Therefore, it is important to acquaint the distribution and anatomical characteristics of internal thoracic artery perforators. We researched the perforators running in the intercostal spaces under the pectoralis major muscle to provide an overview of the anatomical distribution and characteristics of the perforators in patients who underwent immediate subpectoral implant-based breast reconstructions. In our study, the major perforators (diameter > 1.5 mm) were easily found 2-7 cm medially between the third and fourth intercostal space and were sparse in the lateral area from the midline of the breast (usually 8-9 cm lateral to the midsternal line) and above the third rib. In each side of the breast, the average number of perforators greater than 1.5 mm was 1.6, and the average number of perforators between 1 mm and 1.5 mm in diameter was 3.2. Our results provide information about perforators in the anterior chest wall related to the breast area. Clin. Anat. 32:471-475, 2019. © 2018 Wiley Periodicals, Inc.

Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells.

BACKGROUND: Calcification of the aortic valve leads to increased leaflet stiffness and consequently to the development of calcific aortic valve disease. However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes calcific aortic valve disease progression. METHODS: We obtained the aortic valve tissues from humans and murine models (wild-type and endothelial nitric oxide synthase-deficient-mice) and cultured the valvular interstitial cells (VICs) and valvular endothelial cells from the cusps. We induced osteogenic differentiation in the primary cultured VICs and examined the effects of the DPP-4 inhibitor on the osteogenic changes in vitro and aortic valve calcification in endothelial nitric oxide synthase-deficient-mice. We also induced calcific aortic stenosis in male New Zealand rabbits (weight, 2.5-3.0 kg) by a cholesterol-enriched diet+vitamin D2 (25 000 IU, daily). Echocardiography was performed to assess the aortic valve area and the maximal and mean transaortic pressure gradients at baseline and 3-week intervals thereafter. After 12 weeks, we harvested the heart and evaluated the aortic valve tissue using immunohistochemistry. RESULTS: We found that nitric oxide depletion in human valvular endothelial cells activates NF-κB in human VICs. Consequently, the NF-κB promotes DPP-4 expression, which then induces the osteogenic differentiation of VICs by limiting autocrine insulin-like growth factor-1 signaling. The inhibition of DPP-4 enzymatic activity blocked the osteogenic changes in VICs in vitro and reduced the aortic valve calcification in vivo in a mouse model. Sitagliptin administration in a rabbit calcific aortic valve disease model led to significant improvements in the rate of change in aortic valve area, transaortic peak velocity, and maximal and mean pressure gradients over 12 weeks. Immunohistochemistry staining confirmed the therapeutic effect of Sitagliptin in terms of reducing the calcium deposits in the rabbit aortic valve cusps. In rabbits receiving Sitagliptin, the plasma insulin-like growth factor-1 levels were significantly increased, in line with DPP-4 inhibition. CONCLUSIONS: DPP-4-dependent insulin-like growth factor-1 inhibition in VICs contributes to aortic valve calcification, suggesting that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression.