Background: Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. Methods: The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged ≥20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Results: Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher CHA2DS2-VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). Conclusions: This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

Reassessing the continuing need for and choice of antibiotics by using an antibiotic “time out’’ program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012–2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major “time out’’ intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates.

The prostate-specific membrane antigen (PSMA) is a great target for prostate cancer in the current. The MH-PC-AB-56, a molecule with PSMA-targeted activity and with an albumin-binding motif, was radiolabeled with indium as a diagnostic agent and with lutetium with a therapeutic agent, respectively. We evaluated the molecule's theranostic application with 111In and 177Lu in NanoSPECT/CT imaging. Methods: The radiolabeled peptide, 111In/177Lu-MH-PC-AB-56, was performed with sodium acetate buffer and heating with 15 min or 30 min at 95℃. The radiochemical purity was analyzed by TLC and HPLC. The PSMA-expressed tumor cell LNCaP was implanted right front leg at BALB/c nude mice. NanoSPECT/CT image was performed at 1 h, 4 h, 24 h, 48 h, 72 h, and 96 h after injection of 111In-MH-PC-AB-56 or 177Lu-MH-PC-AB-56. Results: The radiochemical purity of 111In-MH-PC-AB-56 or 177Lu-MH-PC-AB-56 was 99.09 ± 0.38

Background: Atrial fibrillation (AF) prevalence and its risk of stroke rise with ageing. We aimed to investigate the outcomes of NOAC and warfarin in AF patients aged >= 85 years. Methods: This is a retrospective study using Taiwan National Health Insurance Research Database. A total of 15,361 patients aged >= 85 years with AF on oral anticoagulants were identified. The end points included ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite adverse events (ICH or major bleeding or all-cause mortality). Clinical outcomes were compared between each NOAC and warfarin after propensity matching. Results: Before propensity matching, patients taking warfarin were older, more female with more comorbidities than NOACs users. After propensity matching, baseline characteristics did not differ significantly between matched subjects receiving warfarin and each NOAC. Compared to warfarin, dabigatran was associated with a lower risk of ICH (hazard ratio [HR] 0.496), mortality (HR 0.558) and adverse events (HR 0.628), while rivaroxaban was associated with a lower risk of ischaemic stroke (HR 0.781), ICH (HR 0.453), mortality (HR 0.558) and adverse events (HR 0.636). Apixaban was associated with a lower risk of mortality (HR 0.488) and adverse events (HR 0.557) compared to warfarin. (all P < .05). Conclusion: For the efficacy, NOACs were associated with a comparable or lower risk of ischaemic stroke compared to warfarin. For adverse events, NOACs were associated with a lower risk of all-cause mortality and composite adverse events. In the elderly AF population, NOACs could be a more favourable choice for stroke prevention.

Background: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. Methods: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. Results: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission. Conclusion: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal corona viruses. Copyright (c) 2021, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

The Arg–Gly–Asp (RGD) peptide shows a high affinity for αvβ3 integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(111In) radiolabeled DOTA-EB-cRGDfK in αvβ3 integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that 111In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC50 = 71.7 nM). NanoSPECT/CT imaging showed 111In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (111In-DOTA-cRGDfK and 111In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the 111In-DOTA-EB-cRGDfK peptide has a long-term half-life (T1/2λz = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.

Background: Since December 2019, a number of cases and deaths due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been reported worldwide. In spite of clinical manifestations similar to the SARS-CoV epidemic in 2003, affected organs and severity are yet to be defined. Moreover, viral load alterations and viral shielding among different specimens remained scarce. Therefore, clarifying clinical presentations and correlations among viral loads, disease severity, and viral shielding of SARS-CoV-2 infection is crucial in the disease prevention. Methods: The clinical courses of SARS-CoV-2 cases were presented through Gantt charts. Laboratory examinations and reverse-transcriptase quantitative polymerase chain reactions (RT-qPCR) among different specimens were tested periodically. Cycle thresholds (C-T) were recorded and presented as viral loads. Results: From March 2020 to April 2020, 4 SARS-CoV-2 cases were presented, of which, cases 1 and 2 manifested the symptoms severer than cases 3 and 4, along with higher serum lactate dehydrogenase levels and graded for lymphocytopenia. Case 4 initially exhibited anosmia but recovered within a short period. Curves of the C-T of all the cases, except case 2, concaved upward after prescribing hydroxychloroquine (HCQ) and azithromycin. Except for case 4, the C-T in most stool specimens remained undetectable; however, none of the cases presented gastrointestinal symptoms. Surprisingly, the C-T values of the saliva specimens were inconsistent with those of the nasopharyngeal swabs and sputum. Conclusion: SARS-CoV-2 manifests various symptoms. Sudden onset of central nervous system symptoms should be considered. The timing of HCQ and azithromycin administration might be a key factor in the viral load reduction. Positive prediction values of RT-qPCR of different specimens should be tested carefully to prevent false-negative results.

Human papillomavirus (HPV) infection contributes to most anal cancers and premalignant intraepithelial lesions. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM). Sociodemographic characteristics and sexual behaviors were collected by using a structured questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV Genotyping test. Logistic regression was used to estimate risk factors and their associations with high-risk HPV infection and cytological abnormalities. Among 163 MSM, 101 were seropositive for human immunodeficiency virus (HIV) and 62 were seronegative for HIV. The overall prevalence of HPV was 66.2%. A total of 61.9% and 48.2% of participants had never acquired any of either the quadrivalent or nonavalent vaccine HPV types, respectively. Cytological findings showed 15.3% atypical squamous cells of undetermined significance, 16.6% low-grade squamous intraepithelial lesion, 4.9% atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion and 17% high-grade squamous intraepithelial lesion. The number of high-risk HPV types was the predominant risk factor for abnormal anal cytology (OR 2.02, 95% CI 1.27–3.24). Infection with high-risk HPV was a significant predictor for cytological abnormality. MSM should be encouraged to obtain the HPV vaccine.

3097 Introduction: Prostate-specific membrane antigen (PSMA) is a well-known targeting for prostate cancer. PSMA-617 is prostate radionuclide ligand therapy (PRLT) classic idol of NAAG inhibitor-modified. We design a precursor MH-PC-AB-9 that has a spacer link urea-based NAAG inhibitor and albumin binder to change the pharmacokinetics of NAAG inhibitor for PSMA. We use lysine, tyrosine, tyrosine, and glutamic acid (from N-terminal to C-terminal) as a spacer. And 4-(p-Tolyl) butyric acid link the lysine9s side chain as an albumin binder. The chelator is DOTA and the one carboxylic acid of DOTA is conjugating with lysine’ N-terminal. Methods: 20 μg of the precursor was diluted with sodium acetate buffer pH6.0 and added to 0.1 GBq of [In-111] InCl3 in 0.01N HCl. The solution heated to 95 ℃ for 15 min with 500 rpm agitation. Radiochemical purity was established by thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). The TLC chamber was loaded with 10 % methanol in water. The Xselect HSS T3 column (4.6 mm x 250 mm) was used and eluted with a linear gradient from 20 to 60% acetonitrile in water (0.1% TFA) over 10 min at a flow rate of 0.8 mL/min. The detector was used gamma radiated detector and UV detector was adjusted for 220 nm. The bioactivity to recognized PSMA of [In-111] In-MH-PC-AB-9 was performed by LNCaP tumor-bearing mice. Results: The chemical purity of [In-111] In-MH-PC-AB-9 was over 95% determined by TLC and HPLC. The retardation factor of free [In-111] In is 0.27 and [In-111] In-MH-PC-AB-9 is 0.95 in TLC. The retention time of free [In-111] In is 3.26 min and [In-111] In-MH-PC-AB-9 is 11.052 min in HPLC. The distribution of [In-111] In-MH-PC-AB-9 in tumor-bearing mice was imaging with nano-SPECT/CT at 1, 24, 72 hours. There still has radioactive accumulated until post-injection 72 hours at the tumor site. Conclusions: The precursor MH-PC-AB-9 has long circulating time was provided by labeling with [In-111] InCl3 and injected into tumor-bearing mice. And the radioactive was increasing with post-injected time. Hence, MH-PC-AB-9 has improved the blood half-life of the NAAG inhibitor more than PSMA-617. Supporting data Figure1. Thin layer chromatography to analyze the radiochemical purity of [In-111] In-MH-PC-AB-9. A is free [In-111] InCl3; B is [In-111] In-MH-PC-AB-9. Figure2. The radiochemical purity of [In-111] In-MH-PC-AB-9 is analyzed by HPLC. The A and B is radio detector; C is UV detector. Figure3. The biodistribution of [In-111] In-MH-PC-AB-9 is imaging with nano-SPECT/CT at post-injected 1, 24 and 72 hours.

Liposomes are drug nano-carriers that are capable of targeting therapeutics to tumor sites because of enhanced permeability retention (EPR). In several preclinical studies with various tumor-bearing mice models, 188Re-liposome that has been developed by the Institute of Nuclear Energy Research (INER) demonstrates favorable in vivo tumor targeting, biodistribution, pharmacokinetics, and dosimetry. It inhibits the growth of tumors, increased survival, demonstrates good synergistic combination, and was safe to use. This study conducts a phase 0 low-radioactivity clinical trial of nano-targeted radiotherapeutics 188Re-liposome to evaluate the effectiveness with which it targets tumors and the pharmacokinetics, biodistribution, dosimetry, and its safety in use. Twelve patients with metastatic cancers are studied in this trial. Serial whole-body scans and SPECT/CT are taken at 1, 4, 8, 24, 48, and 72 h after intravenous injection of 111 MBq of 188Re-liposome. The effectiveness with which tumors are targeted, the pharmacokinetics, biodistribution, dosimetry, and safety are evaluated using the VelocityAI and OLINDA/EXM software. Blood samples are collected at different time points for a pharmacokinetics study and a safety evaluation that involves monitoring changes in liver, renal, and hematological functions. The T½z for 188Re-liposome in blood and plasma are 36.73 ± 14.00 h and 52.02 ± 45.21 h, respectively. The doses of radiation that are absorbed to vital organs such as the liver, spleen, lung, kidney, and bone marrow are 0.92 ± 0.35, 1.38 ± 1.81, 0.58 ± 0.28, 0.32 ± 0.09, and 0.06 ± 0.01 mGy/MBq, respectively, which is far less than the reference maximum tolerance dose after injection of 188Re-liposome. 188Re-liposome is absorbed by metastatic tumor lesions and the normal reticuloendothelial (RES) system. Certain patients exhibit a therapeutic response. This phase 0 exploratory IND study shows that nanocarrier 188Re-liposome achieves favorable tumor accumulation and tumor to normal organ uptake ratios for a subset of cancer patients. The clinical pharmacokinetic, biodistribution, and dosimetry results justify a further dose-escalating phase 1 clinical trial. Taiwan FDA MA1101G0 (Jan 31, 2012).

BACKGROUND/PURPOSE:Methicillin-resistant Staphylococcus aureus (MRSA) can encode proteins which directly bind bacteria to many tissues and medical devices or catheters to trigger pathogenesis. However, the relationship between genetic backgrounds and virulent factors in MRSA isolates remained incompletely understood yet.METHODS:MRSA isolates were collected from blood cultures of patients with infective endocarditis, bone/joint infection, skin/soft tissue infection, or catheter-related bacteremia in hemodialysis at a tertiary medical center between 2005 and 2011. MRSA isolates were characterized by the methods of spa, multilocus sequence, and staphylococcal cassette chromosome mec (SCCmec) typing. Identification of virulence gene expression was measured by Power SYBR Green PCR Master Mix.RESULTS:Overall collected were 136 MRSA bacteremic isolates, including those from the cases of infective endocarditis (n = 23), bone/joint infection (n = 49), skin/soft tissue infection (n = 20), or catheter-related bacteremia in patients with acute kidney injury or end-stage renal stage receiving hemodialysis (n = 54). CC8-ST239-MRSA-SCCmec type III-spa type t037 was the most prevalent type observed in all of 136 MRSA bacteremic isolates. The prevalent genes in the group of infective endocarditis were clfA, clfB, fnbA, ebpS, eap, emp, sae, and eno; bone/joint infections clfA, emp, sae, and eno; skin/soft tissue infection eno; hemodialysis catheter-related bacteremia clfA and sae. The distribution of each gene was not statically different among four groups.CONCLUSIONS:A major MRSA lineage, CC8-ST239-MRSA-SCCmec type III-spa type t037, is noted among bacteremic MRSA isolates. No disease-specific virulent genes can be identified.

2019 Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is a widely known molecular targeted therapy. PRRT is performed by using a small peptide which is combined with therapeutic radionuclides. We tried to develop a multimodality compound for both PRRT and Boron Neutron capture therapy (BNCT), and also both the binding affinity and the ratio of tumor to normal tissue (T/N) of boron drug will be high than traditional BNCT drugs. We selected peptide-NPY derivative, modified with BSH analogue, as a multimodality drug for BNCT. Neuropeptide Y (NPY) is a 36-amino acid peptide and regulates in various physiological functions through its four receptors. Its receptors are a family of G protein-coupled receptors and can be divided into five subtypes.The aims of this study was to synthesize a long-circulated NPY derivative and evaluate tumor image of the MCF-7 and 4T1 animal model as a candidate for breast cancer therapy. Methods: We synthesized DOTA-Boron-ENPY, which is a 16-amino acid NPY derivative. In our research strategy, we used the recombination of EB(Albumin affinity compound), DOTA, BSH and breast cancer targeted NPY-peptide as the pharmacophore for BNCT, once label with In-111 for PRRT. 30-60μg DOTA-Boron-ENPY peptide reacted with 6mCi indium-111 chloride (from INER) at 95℃ within 15min. The radiochemical purity was detected by Radio-HPLC. In animal study, tumor xenografts were performed in 6-wk-old female BALB/c mice by subcutaneous injection of2[asterisk]106 4T1 cells, and nanoSPECT/CT imaging was performed at 0.5 h to 96h after injecting of the 111In-DOTA-Boron-ENPY.Results: The radiochemical purity of 111In-DOTA-Boron-ENPY was greater than 90%. In vivo study, MCF-7 animal tumors uptake was greater than 7% ID/g in 72 hours post-injection for111In-DOTA-Boron-ENPY. In the 4T1 animal model, tumors uptake was greater than 30% ID/g in 48 hours post-injection for111In-DOTA-Boron-ENPY. It also has a high tumor to muscle ratio (T/M) greater than 4. Conclusions: From the in vivo study, we consider the DOTA-Boron-ENPY as a long circulation radiopharmaceutical candidate for companion diagnostics (CDx). It can be a potential candidate drug in breast tumor for BNCT.

BACKGROUND:Cytomegalovirus (CMV) causes life-threatening infections in immunocompromised host. The clinical significance of asymptomatic CMV viruria in patients receiving hematopoietic stem cell transplantation (HSCT) remains unclear. This study aims to clarify whether antiviral therapy is associated with a favorable clinical outcome.METHODS:HSCT recipients whose urine was culture-positive for CMV were retrospectively reviewed and followed. Viruria episodes were divided according to whether or not antiviral therapy was used. Mortality and the estimated glomerular filtration rate (eGFR) in 2 years following CMV viruria were compared between patients with and without antiviral therapy.RESULTS:Sixty-two episodes of culture-proven asymptomatic CMV viruria were identified in 28 HSCT recipients. Antiviral therapy was used in 35 (56.5%) and spared in 27 (43.5%) viruric episodes. Compared with the baselines, there were no significant difference in the decrements of eGFR between the two groups at the end the 1st year (4.78 vs 5.02 mL/min/1.73 m2, p = 0.968) and the 2nd year (1.13 vs 7.66 mL/min/1.73 m2, p = 0.276). Antiviral therapy for asymptomatic CMV viruria was also not associated with a favorable survival (p = 0.288). On the other hand, presence of CMV viremia correlated with a poorer survival (2-year mortality rate 60% vs 13.33%, p < 0.001).CONCLUSION:Antiviral therapy for asymptomatic CMV viruria is not associated with a clear clinical benefit in HSCT recipients. Further studies may be needed to identify if specific patient populations may benefit from antiviral therapy in CMV viruria.

BACKGROUND/AIM:The biodistribution, pharmacokinetics and therapeutic evaluation of 188Re-human serum albumin microspheres (188Re-HSAM) by labeling with 188Re(I)-tricarbonyl ion (188Re(OH2)3(CO)3)+) were investigated in a GP7TB orthotopic hepatoma rat model.MATERIALS AND METHODS:Male F344 rats received intrahepatic inoculations with GP7TB 1 mm3 cubes. The efficacy of 188Re-HSAM was examined following a single-dose treatment via the intraarterial route. Rats were monitored for survival until death.RESULTS:The labeling efficiency of the 188Re-HSAM was about 80%. After intraarterial administration of 188Re-HSAM, radioactivity in tumors accumulated from 18.41±3.48 %ID/g at 1 h to 12.43±4.70 %ID/g at 24 h. The tumor/liver ratios ranged from 3.03 at 1 h to 1.89 at 72 h. The major uptake organs of 188Re-HSAM were liver (73.35%ID to 48.92%ID), tumor (10.54%ID to 3.51%ID) and kidney (7.48 %ID to 0.14%ID). The T1/2λz of 188Re-HSAM was 259.34 h after intraarterial injection. The AUC(0→96 h) of 188Re-HSAM was 0.69 h*% ID/g. In the efficacy study, the median survival time for the rat (n=6), that received normal saline was 80 d. The median survival times for the mice treated with 10 mCi (n=4), 5.2 mCi (n=6) and 2.9 mCi (n=3) of 188Re-HSAM were 130 d (p=0.003), 106 d (p=0.002) and 83.5 d (p=0.617), respectively. The increase in life span of 10 mCi, 5.2 mCi and 2.9 mCi of 188Re-HSAM were 62.5%, 32.5% and 4.4%, respectively.CONCLUSION:Administration of 188Re-HSAM demonstrated better survival time and therapeutic efficacy at the higher dose in the GP7TB hepatoma model. These results suggested that intraarterial administration of 188Re-HSAM could provide a benefit and promising strategy for delivery of radiotherapeutics in oncology applications.

Sudden cardiac death (SCD), the most devastating manifestation of ventricular arrhythmias (VAs), is the leading cause of mortality in patients with atrial fibrillation (AF). We hypothesized that the CHA2DS2-VASc score, consisting of age and several clinical risk factors, could be used to estimate the individual risk of SCD/VAs for AF patients. From year 2000 to 2011, 288,181 newly-diagnosed AF patients without antecedent SCD/VAs were identified from "Taiwan National Health Insurance Research Database." During the follow-up of 1,065,751 person-years, 11,166 patients experienced SCD/VAs with an annual risk of 1.05% which increased from 0.34% for patients with a CHA2DS2-VASc score of 0% to 2.63% for those with a score of 9. The CHA2DS2-VASc score was a significant predictor of SCD/VAs with an adjusted hazard ratio of 1.21 (95% confidence interval 1.20 to 1.22) per 1 point increment of the score. As the CHA2DS2-VASc score increased from 1 to 9, the hazard ratio of SCD/VAs continuously increased from 1.28 to 4.17 compared with patients with a CHA2DS2-VASc score of 0. In conclusion, CHA2DS2-VASc score was a convenient scoring system which could be used to predict the risk of SCD/VAs in AF patients in addition to its ability for stroke risk stratification.

Neuropeptide Y (NPY) is a 36-amino acid peptide and regulates in various physiological functions through its four receptors.Recently, NPY receptor-Y1R has been found to be overexpressed in breast carcinomas.Although the truncated NPY analog has high affinity with Y1R, it is rapidly metabolized, resulting in low tumor uptake.The aims of this study were to synthesize a long-circulated NPY analog and evaluate tumor image of the 4T1 animal model as a candidate for breast cancer therapy.

Purpose: Liver cancer is the second most common cause of death worldwide. This study was to investigate the SPECT/CT, ultrasound, biodistribution and therapeutic evaluation of Re-188-human serum albumin microspheres (Re-188-HSAM) in the GP7TB orthotopic hepatoma rat model.Materials and methods: HSAM was labeled with Re-188 by using a home-made kit and microwave system. The Re-188-HSAM was administered via intraarterial route. The in vivo distribution of Re-188-HSAM was determined by biodistribution analysis and nanoSPECT/CT system. In efficacy, tumor volumes were tracked longitudinally by three-dimensional ultrasound.Results: The biodistribution and nanoSPECT/CT imaging showed that Re-188-HSAM could accumulate in liver and tumor. The correlation coefficient of tumor volumes done by three-dimensional ultrasound and at autopsy was 0.997. In efficacy, tumor volume in the normal saline-treated group was 1803.2mm(3) at 54 days after tumor inoculation. Tumor volumes in the 103.6 MBq and 240.5 MBq of Re-188-HSAM treated groups were 381 and 267.4mm(3) (p=0.001 and 0.004), respectively.Conclusions: These results show that three-dimensional ultrasound with a high spatial resolution and contrast in soft tissue can become imaging modality in assessing tumor burden and tumor progression in an orthotopic rat model. The longitudinally therapeutic evaluation of Re-188-HSAM demonstrated dose-dependent tumor growth inhibition with increased dose in the GP7TB orthotopic hepatoma rat model.