The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Effect of Lactobacillus Rhamnosus GG for Regulation of Inflammatory Response in Radiation-Induced Enteritis.

The purpose of this study was to investigate the role of Lactobacillus rhamnosus GG (LGG) probiotics in radiation enteritis using in vivo mice. A total of 40 mice were randomly assigned to four groups: control, probiotics, radiotherapy (RT), and RT + probiotics. For the group of probiotics, 0.2 mL of solution that contained 1.0 × 108 colony-forming units (CFU) of LGG was used and orally administered daily until sacrifice. For RT, a single dose of 14 Gy was administered using a 6 mega-voltage photon beam to the abdominopelvic area. Mice were sacrifice at day 4 (S1) and day 7 (S2) after RT. Their jejunum, colon, and stool were collected. A multiplex cytokine assay and 16 s ribosomal RNA amplicon sequencing were then performed. Regarding cytokine concentrations in tissues, pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1, showed significantly decreased protein levels in colon tissues of the RT + probiotics group than in the RT alone group (all p < 0.05). As for comparing microbial abundance through alpha-diversity and beta-diversity, no significant differences were observed between the RT + probiotics and RT alone groups, except for an increase in alpha-diversity in the stool of the RT + probiotics group. Upon analysis of differential microbes based on treatment, the dominance of anti-inflammatory-related microbes, such as Porphyromonadaceae, Bacteroides acidifaciens, and Ruminococcus, was observed in the jejunum, colon, and stool of the RT + probiotics group. With regard to predicted metabolic pathway abundances, the pathways associated with anti-inflammatory processes, such as biosynthesis of pyrimidine nucleotides, peptidoglycans, tryptophan, adenosylcobalamin, and propionate, were differentially identified in the RT + probiotics group compared to the RT alone group. Protective effects of probiotics on radiation enteritis were potentially derived from dominant anti-inflammation-related microbes and metabolites.

Fulminant Eosinophilic Myocarditis Without Peripheral Eosinophilia.

Eosinophilic myocarditis is a rare form of myocarditis characterized by eosinophilic infiltration and usually associated with peripheral hypereosinophilia. The clinical spectrum of eosinophilic myocarditis ranges widely, from mildly symptomatic to fulminant disease. When patients have fulminant eosinophilic myocarditis, high-dose corticosteroids can lead to dramatic improvement and peripheral eosinophil counts are used as an indicator of response to treatment. However, in some patients, peripheral eosinophilia is absent at initial presentation; reaching a diagnosis and determining treatment response can be challenging in this situation. This report describes a patient with fulminant eosinophilic myocarditis who initially presented with a normal peripheral eosinophil count, was diagnosed through an early endomyocardial biopsy, and was successfully treated with corticosteroids. Endomyocardial biopsy should be performed to confirm the presence of myocardial eosinophilic infiltration, especially for patients who present with fulminant myocarditis, even when peripheral eosinophilia is absent.

Validation of deep learning-based fully automated coronary artery calcium scoring using non-ECG-gated chest CT in patients with cancer.

This study aimed to demonstrate clinical feasibility of deep learning (DL)-based fully automated coronary artery calcium (CAC) scoring software using non-electrocardiogram (ECG)-gated chest computed tomography (CT) from patients with cancer. Overall, 913 patients with colorectal or gastric cancer who underwent non-contrast-enhanced chest CT between 2013 and 2015 were included. Agatston scores obtained by manual segmentation of CAC on chest CT were used as reference. Reliability of automated CAC score acquisition was evaluated using intraclass correlation coefficients (ICCs). The agreement for cardiovascular disease (CVD) risk stratification was assessed with linearly weighted k statistics. ICCs between the manual and automated CAC scores were 0.992 (95% CI, 0.991 and 0.993, p<0.001) for total Agatston scores, 0.863 (95% CI, 0.844 and 0.880, p<0.001) for the left main, 0.964 (95% CI, 0.959 and 0.968, p<0.001) for the left anterior descending, 0.962 (95% CI, 0.956 and 0.966, p<0.001) for the left circumflex, and 0.980 (95% CI, 0.978 and 0.983, p<0.001) for the right coronary arteries. The agreement for cardiovascular risk was excellent (k=0.946, p<0.001). Current DL-based automated CAC software showed excellent reliability for Agatston score and CVD risk stratification using non-ECG gated CT scans and might allow the identification of high-risk cancer patients for CVD.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Physician adherence and patient-reported outcomes in heart failure with reduced ejection fraction in the era of angiotensin receptor-neprilysin inhibitor therapy.

This Korean nationwide, multicenter, noninterventional, prospective cohort study aimed to analyze physician adherence to guideline-recommended therapy for heart failure (HF) with reduced ejection fraction (HFrEF) and its effect on patient-reported outcomes (PROs). Patients diagnosed with or hospitalized for HFrEF within the previous year were enrolled. Treatment adherence was considered optimal when all 3 categories of guideline-recommended medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors; beta-blockers; and mineralocorticoid receptor antagonists) were prescribed and suboptimal when ≤ 2 categories were prescribed. The 36-Item Short Form Survey (SF-36) scores were compared at baseline and 6 months between the 2 groups. Overall, 854 patients from 30 hospitals were included. At baseline, the optimal adherence group comprised 527 patients (61.7%), whereas during follow-up, the optimal and suboptimal adherence groups comprised 462 (54.1%) and 281 (32.9%) patients, respectively. Patients in the suboptimal adherence group were older, with a lower body mass index, and increased comorbidities, including renal dysfunction. SF-36 scores were significantly higher in the optimal adherence group for most domains (P < 0.05). This study showed satisfactory physician adherence to contemporary treatment for HFrEF. Optimal adherence to HF medication significantly correlated with better PROs.

Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer.

PURPOSE: The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer. MATERIALS AND METHODS: Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed. RESULTS: At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee. CONCLUSION: Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

Coinfections with Respiratory Pathogens among COVID-19 Patients in Korea.

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in upper and lower respiratory specimens and coinfection with other respiratory pathogens in patients with coronavirus disease 2019 (COVID-19) was investigated. Study subjects (N = 342) were retrospectively enrolled after being confirmed as SARS-CoV-2 positive, and their nasopharyngeal swab (NPS), oropharyngeal swab (OPS), and sputum specimens were restored for SARS-CoV-2 retesting and respiratory pathogen detection. The majority of the subjects (96.5%, N = 330) were confirmed as SARS-CoV-2 positive using NPS/OPS specimens. Among the COVID-19 patients (N = 342), 7.9% (N = 27) and 0.9% (N = 3) were coinfected with respiratory viruses and Mycoplasma pneumoniae, respectively, yielding an 8.8% (N = 30) overall respiratory pathogen coinfection rate. Of the respiratory virus coinfection cases (N = 27), 92.6% (N = 25) were coinfected with a single respiratory virus and 7.4% (N = 2) with two viruses (metapneumovirus/adenovirus and rhinovirus/bocavirus). No triple coinfections of other respiratory viruses or bacteria with SARS-CoV-2 were detected. Respiratory viruses coinfected in the patients with COVID-19 were as follows: rhinovirus (N = 7, 2.1%), respiratory syncytial virus A and B (N = 6, 1.8%), non-SARS-CoV-2 coronaviruses (229E, NL63, and OC43, N = 5, 1.5%), metapneumovirus (N = 4, 1.2%), influenza A (N = 3, 0.9%), adenovirus (N = 3, 0.9%), and bocavirus (N = 1, 0.3%). In conclusion, the diagnostic value of utilizing NPS/OPS specimens is excellent, and, as the first report in Korea, coinfection with respiratory pathogens was detected at a rate of 8.8% in patients with COVID-19.

Comparison of Clinical and Echocardiographic Characteristics between Cardiac Myxomas and Masses Mimicking Myxoma.

BACKGROUND AND OBJECTIVES: Cardiac myxoma is the most frequent benign cardiac tumor that can result in cardiac and systemic symptoms. We investigated clinical and echocardiographic characteristics of patients with cardiac masses suggesting myxoma. METHODS: We investigated 265 consecutive patients with an echocardiographic diagnosis of cardiac myxomas in 4 teaching hospitals in Korea. RESULTS: The mean age was 61±16 years and 169 patients (63.8%) were female. The most frequent referral reason for echocardiography was an evaluation of cardiac symptoms (43.4%). Tumors were incidentally detected in 82 patients (30.9%). Left atrium (LA) was the most frequently involved site (84.5%) and 19 patients (7.2%) had non-atrial tumors. The mean tumor size was 38.7×26.0 mm (range, 4-96 mm). Of 186 patients (70.2%) who had pathological diagnosis, 174 (93.5%) were confirmed with myxoma, 8 (4.3%) with other tumors and 4 (2.2%) with thrombi. Compared to myxoma, smaller size (20.4×12.6 mm vs. 41.4×27.6 mm, p<0.01) and non-LA location (87.5% vs. 10.5%, p<0.001) were associated with non-myxoma tumors, and more frequent atrial fibrillation (AF, 75.0% vs. 7.0%, p<0.001) and larger LA diameter (55.0±14.6 mm vs. 41.3±7.7 mm, p=0.001) were related to thrombi. CONCLUSIONS: Of 265 patients with an echocardiographic diagnosis with cardiac myxomas, 174 (65.7%) were surgically confirmed with myxomas. Compared with cardiac myxoma, other tumors were smaller and more frequently found in non-atrial sites. Thrombi were associated with AF and larger LA diameter.

Novel multifunctional 18F-labelled PET tracer with prostate-specific membrane antigen-targeting and hypoxia-sensitive moieties.

Prostate cancer is one of the most frequently found cancers in men worldwide. Prostate-specific membrane antigen (PSMA) is typically highly expressed in prostate cancer, and the Glu-Urea-Lys (GUL) structure has recently received considerable attention as a key unit of PSMA-targeting agents. Additionally, one of the common characteristics of many solid tumors, such as prostate cancer, is hypoxia. In this study, novel multifunctional PSMA inhibitors containing a PSMA-targeting moiety either with or without a hypoxia-sensitive moiety (18F-PEG3-ADIBOT-2NI-GUL and 18F-PEG3-ADIBOT-GUL, respectively; ADIBOT: azadibenzocyclooctatriazole, 2NI: 2-nitroimidazole) were designed and synthesized, and their feasibility as PET tracers for prostate cancer imaging studies was examined. The compounds labelled with 18F via the copper-free click reaction were stable in human serum and showed nanomolar binding affinities in in vitro PSMA binding assays. Micro-PET and biodistribution studies indicate that both 18F-labelled inhibitors successfully accumulated in prostate cancer regions, and 18F-PEG3-ADIBOT-2NI-GUL showed a 2-fold higher tumor-to-total non-target organ ratio than that of 18F-PEG3-ADIBOT-GUL, suggesting that the synergistic effects of the PSMA-targeting GUL moiety and the hypoxia-sensitive 2-nitroimidazole moiety can increase tumor uptake of the novel PET tracers in prostate cancer. These findings suggest that this novel multifunctional PET tracer with an 18F-labelled PSMA inhibitor and a 2-nitroimidazole moiety is a potent candidate to provide better diagnosis of prostate cancer via PET imaging studies.

Clinical profiles of patients with surgically resected pheochromocytoma and paraganglioma.

BACKGROUND/AIMS: Pheochromocytoma and paraganglioma (PPGL) are catecholamine-producing tumors that can cause blood pressure (BP) elevation and cardiovascular complications. Clinical presentation of these tumors may be changed through widespread use of imaging studies, which enables detection of PPGLs before onset of symptoms. We investigated clinical profiles of patients with surgically resected PPGLs. METHODS: From 2005 to 2017, 111 consecutive patients with surgically resected PPGLs in two tertiary hospitals in Korea were studied. RESULTS: Mean age was 52 ± 16 years, 57 patients (51.4%) were male and 54 (48.6%) were hypertensive. Twenty-nine PPGLs (26.1%) were extra-adrenal paragangliomas. Sixteen (14.4%) and seven patients (6.3%) (Group 1, n = 23) were diagnosed during work-up of hypertension and transient cardiomyopathy respectively, and the remainder (Group 2, n = 88) were incidentalomas detected during routine abdominal imaging. Patients in the Group 1 were younger and more frequently symptomatic, and had higher BPs, heart rates and levels of urinary catecholamines than those in the Group 2. Paragangliomas were less frequent and secretion of epinephrine and metanephrine was more predominant in the Group 1 than in Group 2. After the surgical resections, 18.2% of patients still needed antihypertensive medications. CONCLUSION: Out of 111 patients with surgically resected PPGLs, 88 (79.3%) were diagnosed as incidentalomas. Seven patients presented with transient cardiomyopathy and 16 with hypertension. Tumor location and secretion of catecholamine may vary depending on the presence of symptoms.

Ankle ultrasound for detecting anterior talofibular ligament tear using operative finding as reference standard: a systematic review and meta-analysis.

PURPOSE: To evaluate the diagnostic accuracy of ankle ultrasound for detection of anterior talofibular ligament (ATFL) tear with a reference standard of operative finding. METHODS: A computerized search of PubMed and EMBASE databases was performed to identify relevant original articles on ankle ultrasound for ATFL tear. The pooled proportions of the diagnostic accuracy estimates were assessed using random-effects modeling. We also assessed pooled proportions of the diagnostic accuracy according to injury stage (acute or chronic) and severity of injury (complete or partial). Heterogeneity among studies was determined using the inconsistency index (I2). Meta-regression analyses were performed to evaluate the potential sources of heterogeneity. RESULTS: Ten studies were included. The pooled proportion of the diagnostic accuracy of ankle ultrasound for ATFL was 0.95 (95% confidence interval [CI] 0.88-0.98). In subgroup analysis, the pooled proportion of the diagnostic accuracy of ankle ultrasound for acute ATFL tear was 0.92 (95% CI 0.85-0.95). The pooled proportion of the diagnostic accuracy of ankle ultrasound for chronic ATFL tear was 0.96 (95% CI 0.84-0.99). The pooled proportions of the diagnostic accuracy for complete and partial ATFL tear were 0.82 (95% CI 0.72-0.89) and 0.88 (95% CI 0.70-0.96), respectively. In the meta-regression analyses, the inclusion of pediatric patients was only significantly different (p = 0.007). CONCLUSIONS: Ankle ultrasound may be a useful diagnostic modality in the detection of ATFL tear in adults and children, regardless of injury stage and severity. For correct diagnosis of ATFL tear, a high-frequency ultrasound probe and sufficient experience of the examiner are mandatory.

Optic nerve sheath diameter on facial CT: a tool to predict traumatic brain injury.

PURPOSE: To evaluate and compare the optic nerve sheath diameters (ONSDs) of facial trauma patients as observed on facial CT and brain CT, and to evaluate the predictive performance of ONSD as seen on facial CT for traumatic brain injury (TBI). METHODS: We retrospectively enrolled 262 patients with facial trauma who underwent both facial CT and brain CT. Two reviewers independently measured ONSD at 3 mm (ONSD3) and 10 mm behind the globe (ONSD10) for each patient on both CT scans. Final CT reports with clinical progress notes were used as the reference standard. Statistically, multivariate logistic regression analysis, receiver operating characteristic (ROC) curves, and intraclass correlation coefficients (ICCs) were used. RESULTS: Eighty-seven (33.2%) patients were diagnosed with facial fracture, and 21 (8.0%) were diagnosed with intracranial haemorrhage. Neither reviewer observed significant differences (p = 0.15-0.61) between facial CT and brain CT when comparing ONSD3 and ONSD10. ONSD3 on facial CT was a significantly independent factor for distinguishing TBI from negative brain CT scan (p = 0.001); as ONSD3 increased, the risk of TBI increased 8.1-fold. ONSD3 ≥ 4.13 mm exhibited the highest area under the ROC curve (AUC) for predicting TBI (AUC, 0.968; sensitivity, 90.5%; specificity, 98.8%). There were good or excellent interobserver agreements for all measurements (ICC, 0.750-0.875). CONCLUSION: ONSD3 as determined by facial CT is a feasible predictive marker of TBI in facial trauma patients. It can assist emergency physicians in deciding whether immediate further brain imaging is warranted.

Diagnostic Performance of Magnetic Resonance Imaging for Detecting Meniscal Ramp Lesions in Patients With Anterior Cruciate Ligament Tears: A Systematic Review and Meta-analysis.

BACKGROUND: The clinical importance of meniscal ramp lesions in patients with anterior cruciate ligament (ACL) tear has emerged as a major issue. However, the diagnostic accuracy of magnetic resonance imaging (MRI) for detecting ramp lesions has a wide range. PURPOSE: To perform a systematic review and meta-analysis of the diagnostic performance of MRI for diagnosing ramp lesion in patients with ACL tear. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search of PubMed, EMBASE, and the Cochrane Library was performed based on the revised guidelines for the PRISMA DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Accuracy Studies) statement. Diagnostic performance studies using MRI as the index test and arthroscopy as the reference standard for ramp lesion were included. Bivariate and hierarchical summary receiver operating characteristic modeling was used to evaluate the diagnostic performance. Meta-regression analyses were performed to identify potential sources of heterogeneity. RESULTS: The review and meta-analysis included 9 studies from 8 articles (883 patients with ACL tear and reconstruction). The summary sensitivity, summary specificity, and area under the hierarchical summary receiver operating characteristic for ramp lesion were 0.71 (95% CI, 0.59-0.81), 0.94 (95% CI, 0.88-0.97), and 0.90 (95% CI, 0.87-0.92), respectively. Among the potential covariates, magnet strength (P < .01), patient knee position (P = .04), and MRI interpreter (P = .04) were associated with heterogeneity in terms of sensitivity, whereas magnet strength (P = .03) was associated with heterogeneity in terms of specificity. CONCLUSION: MRI demonstrated moderate sensitivity and excellent specificity for diagnosing ramp lesion. Routine arthroscopic assessment is recommended for the presence of ramp lesion, regardless of whether it is suspected on MRI. Further clinicoradiological studies of diagnostic algorithms are needed for identifying ramp lesion, including high-resolution MRI with appropriate knee position.

A Bcr-Abl Inhibitor GNF-2 Attenuates Inflammatory Activation of Glia and Chronic Pain.

GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson's disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our results show that GNF-2 reduced lipopolysaccharide (LPS)-induced nitric oxide and pro-inflammatory cytokine production in cultured glial cells in a c-Abl-dependent manner. The small interfering ribonucleic acid (siRNA)-mediated knockdown of c-Abl attenuated LPS-induced nuclear factor kappa light chain enhancer of activated B cell (NF-κB) activation and the production of pro-inflammatory mediators in glial cell cultures. Moreover, GNF-2 administration significantly attenuated mechanical and thermal hypersensitivities in experimental models of diabetic and inflammatory pain. Together, our findings suggest the involvement of c-Abl in neuroinflammation and pain pathogenesis and that GNF-2 can be used for the management of chronic pain.

Anti-Neuroinflammatory Effect of Jaeumganghwa-Tang in an Animal Model of Amyotrophic Lateral Sclerosis.

Neuroinflammation is considered a critical factor in the pathologic mechanisms of amyotrophic lateral sclerosis (ALS). This study examined the levels of neuroinflammatory proteins in the spinal cord of JGT-treated hSOD1 G93A transgenic mice to determine the effect of Jaeumganghwa-Tang (JGT) on neuroinflammation. Twelve 8-week-old male experimental mice were randomly allocated to three groups: a non-transgenic group, a hSOD1G93A transgenic group, and a hSOD1G93A transgenic group that received JGT 1 mg/g orally once daily for 6 weeks. After 6 weeks, the spinal cord tissues were analyzed for inflammatory proteins (Iba-1, toll-like receptor 4, and tumor necrosis factor-α) and oxidative stress-related proteins (transferrin, ferritin, HO1, and NQO1) by Western blot analysis. Administration of JGT significantly delayed motor function impairment and reduced oxidative stress in hSOD1 G93A transgenic mice. JGT effectively ameliorated neuroinflammation mechanisms by downregulating TLR4-related signaling proteins and improving iron homeostasis in the spinal cord of hSOD1 G93A mice. JGT could help to decrease neuroinflammation and protect neuronal cells by strengthening the immune response in the central nervous system. This is the first study to demonstrate the role of JGT in neuroinflammation in an animal model of ALS.

Neutrophil-to-lymphocyte ratio as a feasible prognostic marker for pyogenic liver abscess in the emergency department.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is an effective predictor of mortality in patients with for various conditions. To date, there are no previous studies on NLR as a prognostic marker for pyogenic liver abscess (PLA), especially on admission to the emergency department (ED). METHODS: From January 2013 to December 2015, 102 patients diagnosed with PLA in the ED were included. Clinico-radiological and laboratory results, including NLR, were evaluated as variables. NLR was calculated as absolute neutrophil count/absolute lymphocyte count. To evaluate the prognosis of PLA, data on hospital mortality, intensive care unit (ICU) admission, and development of septic shock were obtained. Multivariate logistic regression analyses and receiver-operating characteristic (ROC) curve analysis were performed. RESULTS: Among 102 patients, 10 (9.8%) died, 14 (13.7%) were admitted to the ICU, and 15 (14.7%) developed septic shock during hospitalization. Multivariate logistic regression analysis revealed NLR as an independent factor in predicting death [odds ratio (OR), 1.4; p = 0.020], ICU admission (OR, 1.4; p = 0.021), and development of septic shock (OR, 1.6; p = 0.041). NLR showed an excellent predictive performance for death (areas under the ROC curves [AUC], 0.941; cut-off value, 19.7; p < 0.001), ICU admission (AUC, 0.946; cut-off value, 16.9; p < 0.001), and development of septic shock (AUC, 0.927; cut-off value, 16.9; p < 0.001). CONCLUSION: NLR was positively associated with poor prognosis of PLA; elevated NLR could predictor of high risk of death, ICU admission, and development of septic shock. Emergency physicians should consider NLR for the prognosis of PLA and early aggressive treatment, especially in patients with NLR > 16.9.

Synthesis and Evaluation of Multifunctional Fluorescent Inhibitors with Synergistic Interaction of Prostate-Specific Membrane Antigen and Hypoxia for Prostate Cancer.

Prostate cancer is one of the most common cancers in the world. It is widely known that prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, and hypoxia is a common characteristic of many solid tumors, including prostate cancer. In this study, we designed multifunctional fluorescent inhibitors to target PSMA and tumor hypoxia in order to increase the tumor uptake of inhibitors. Novel PSMA inhibitors were prepared using lysine as the backbone to connect three different functional groups: the glutamate-urea-lysine (GUL) structure for inhibiting PSMA, 2-nitroimidazole for the hypoxia-sensitive moiety, and a near-infrared fluorophore (sulfo-Cyanine 5.5). According to the in vitro PSMA binding assay, novel fluorescent inhibitors were demonstrated to have nanomolar binding affinities. Multifunctional inhibitor 2 with one 2-nitroimidazole had a similar inhibitory activity to inhibitor 1 that did not contain the hypoxia targeting moiety, but multifunctional inhibitor 3 with two 2-nitroimidazoles showed lower inhibitory activity than inhibitor 1 due to the bulky structure of the hypoxia-sensitive group. However, in vivo optical imaging and ex vivo biodistribution studies indicated that both multifunctional inhibitors 2 and 3 had higher accumulation in tumors than inhibitor 1 due to a synergistic combination of PSMA and hypoxia targeting moieties. These observations suggest that this novel multifunctional strategy might be a promising approach to improve the diagnosis and therapy of prostate cancer.

Synthesis of Porous Covalent Quinazoline Networks (CQNs) and Their Gas Sorption Properties.

The development of different classes of porous polymers by linking organic molecules using new chemistries still remains a great challenge. Herein, we introduce for the first time the synthesis of covalent quinazoline networks (CQNs) using an ionothermal synthesis protocol. Zinc chloride (ZnCl2 ) was used as the solvent and catalyst for the condensation of aromatic ortho-aminonitriles to produce tricycloquinazoline linkages. The resulting CQNs show a high porosity with a surface area up to 1870 m2 g-1 . Varying the temperature and the amount of catalyst enables us to control the surface area as well as the pore size distribution of the CQNs. Furthermore, their high nitrogen content and significant microporosity make them a promising CO2 adsorbent with a CO2 uptake capacity of 7.16 mmol g-1 (31.5 wt %) at 273 K and 1 bar. Because of their exceptional CO2 sorption properties, they are promising candidates as an adsorbent for the selective capture of CO2 from flue gas.