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Breast cancer (BC) is the most common cancer and second leading cause of death in women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of BC, while the treatment option is limited and has long been considered as a major unmet need. Meta-analysis indicated the anti-tumor potential of anti-depressants, especially selective serotonin-reuptake inhibitors (SSRIs). The SSRI fluoxetine has been shown to suppress BC and ovarian cancer cell growth; however, whether it suppresses tumor progression in vivo is unclear.We established an 4T1 bearing animal model, an orthotopic TNBC model, to identify the mechanism and therapeutic efficacy of fluoxetine.Tumor growth evaluated by caliper and computed tomography scan demonstrated the inhibition effect by fluoxetine treatment. Immunohistochemistry showed that the expression of STAT3-mediated epithelial-to-mesenchymal transition (EMT) proteins and apoptosis-related proteins was decreased.Fluoxetine may induce an anti-TNBC effect via inactivating STAT3 signaling transduction and triggering the caspase-mediated apoptotic pathway.

BACKGROUND Studies investigating the modulators of mortality benefit conferred by peri-angioplasty glycoprotein IIb/IIIa inhibitors in ST-elevation myocardial infarction (STEMI) are still lacking.Methods and Results:A prospective database (n=1,025) of consecutive cases undergoing primary percutaneous coronary intervention for STEMI was retrospectively analyzed. For patients in Killip class I, II or III, IV, the multivariate-adjusted hazard ratios of 30-day all-cause mortality associated with adjunctive tirofiban were 3.873 (95% CI 0.504-29.745; P=0.193), 0.550 (95% CI 0.188-1.609; P=0.275), and 0.264 (95% CI 0.099-0.704; P=0.008), respectively. The P value for a linear trend was 0.032. Patients who had a body mass index (BMI) within 22.9-25.0 kg/m2had a significant benefit from tirofiban (adjusted HR 0.344; 95% CI 0.145-0.814; P=0.015) compared to other BMI groups. The P value for a quadratic trend was 0.012. A novel Killip-BMI score (KBS = 2.5 × Killip category - | BMI - 24 |) was calculated to select the beneficial population. A KBS ≥2 was associated with significant mortality benefit, whereas a KBS

Objective This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort.Study Design This retrospective cohort study used data from the children's database (2000–2012) of the National Health Insurance Research Database (1996–2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged Results A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI]: 1.05–1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41–7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI: 1.00–2.13).Conclusion We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.

The mortality of patients with ST-segment elevation myocardial infarction (STEMI) and refractory cardiogenic shock (RCS) is high. Extracorporeal membrane oxygenation (ECMO) before percutaneous coronary intervention (PCI) has shown some favorable results, but this may delay door-to-balloon (D2B) time. Whether the benefit surpasses the risk of longer D2B time remains controversial.From January 2005 to December 2014, there were 46 patients with STEMI RCS who received ECMO and PCI. Comparison was made between patients whose ECMO were setup before (n = 12) and after (n = 34) the coronary angiography.There were no significant differences on the baseline characteristics. The ECMO before PCI group had significantly better six-month survival (58.3% vs. 14.7%, p = 0.006), and the benefit persisted to the end of two-year follow-up (41.7% vs. 11.8%, p = 0.045). The rates of neurological, vascular, or bleeding complications were not different between the groups. ECMO before PCI was associated with a nonsignificant increase of median D2B time (30 min) and decrease of patients achieving D2B time 90 min (9.1% vs. 32.0%). After adjusting for GRACE score, gender, D2B time, complete revascularization, ECMO before PCI and shock index 0.8 before PCI were significantly associated with six-month survival.In STEMI RCS patients, ECMO before PCI improves both short- and long-term outcomes, even if it nonsignificantly increases the D2B time. Our data suggests that ECMO before PCI is a reasonable and safe strategy in this particularly-ill population.

Background This study aims to observe the effectiveness and safety of idarucizumab in dabigatran-treated patients with severe bleeding or requiring surgery in Taiwan. Methods and Results In Taiwan, 11 dabigatran-treated patients developed severe bleeding, fracture that needed surgery, and acute ischemic stroke requiring thrombolysis. These patients were treated with idarucizumab and obtained adequate hemostasis. Our experiences reconfirmed the efficacy and safety of idarucizumab in Asian patients. Conclusions Idarucizumab improves safety in dabigatran-treated patients. Continued education about the availability and appropriate use of idarucizumab is necessary in Asia.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

The reaction of methyl anthranilates with N-arylcyanamides in the presence of p-TsOH in t-BuOH under reflux afforded predominantly 3-arylquinazolin-4-ones. In contrast, the reaction of the same reactants with TMSCl in t-BuOH at 60 °C followed by the Dimroth rearrangement in aqueous ethanolic sodium hydroxide gave exclusively the regioisomers, 2-(N-arylamino)quinazolin-4-ones. The regioselective synthesis of N-aryl-substituted 2-aminoquinazolin-4-ones can be further applied to the synthesis of benzimidazo[2,1-b]quinazolin-12-ones.

Background Increased myocardial triglyceride (TG) content has been recognized as a risk factor for cardiovascular disease. However, its relation with cardiac function in patients on recovery from acute heart failure (HF) remains unclear. In this cross-sectional study, we sought to investigate the association between myocardial TG content measured on magnetic resonance spectroscopy (1H-MRS) and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. Methods A total of 50 patients who were discharged after hospitalization for acute HF and 21 age- and sex-matched controls were included in the study. Myocardial TG content and LV parameters (function and mass) were measured on a 3.0 T MR scanner. Fatty acid (FA) and unsaturated fatty acid (UFA) content was normalized against water (W) using the LC-Model algorithm. The patient population was dichotomized according to the left ventricular ejection fraction (LVEF

A 19-year-old boy with shortness of breath and chest pain after strenuous exercise presented to emergency department . On physical examination, the neck and shoulders appeared to be swollen. There was crepitus on skin palpation. Chest X-ray disclosed diffuse subcutaneous emphysema and pneumomediastinum. CT showed additional finding of air in epidural space. The patient was discharged after 2 days of hospitalisation with conservative treatment uneventfully. Pneumorrhachis is usually caused by abrupt increase in intrathoracic pressure in instance of forceful vomiting, cough or asthma attack in an otherwise healthy young adult. It is usually accompanied with pneumomediastinum. The management of epidural pneumatosis should be tailored according to its primary cause. For most patients with pneumorrhachis associated to a spontaneous pneumomediastinum without neurological symptoms, this condition is generally self-limited. For epidural free air of large volume that causes neurological deficits, surgical laminectomy may be indicated.

A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

OBJECTIVE: The aim of this article was to assess the usefulness of procalcitonin (PCT) as a marker for predicting dilating (grades III-V) vesicoureteral reflux (VUR) in young children with a first febrile urinary tract infection. METHODS: Children ≤2 years of age with a first febrile urinary tract infection were prospectively evaluated. Serum samples were tested for PCT at the time of admission to a tertiary hospital. All children underwent renal ultrasonography (US), Tc-dimercaptosuccinic acid renal scan, and voiding cystourethrography. The diagnostic characteristics of PCT test for acute pyelonephritis and dilating VUR were calculated. RESULTS: Of 272 children analyzed (168 boys and 104 girls; median age, 5 months), 169 (62.1%) had acute pyelonephritis. There was VUR demonstrated in 97 (35.7%), including 70 (25.7%) with dilating VUR. The median PCT value was significantly higher in children with VUR than in those without (P < 0.001). Using a PCT cutoff value of ≥1.0 ng/mL, the sensitivity and negative predictive value for predicting dilating VUR were 94.3% and 95.4%, respectively, for PCT, and 97.1% and 97.8%, respectively, for the combined PCT and US studies, whereas the positive and negative likelihood ratios were 2.03 and 0.107, respectively, for PCT, and 1.72 and 0.067, respectively, for the combined studies. By multivariate analysis, high PCT values and abnormalities on US were independent predictors of dilating VUR. CONCLUSIONS: PCT is useful for diagnosing acute pyelonephritis and predicting dilating VUR in young children with a first febrile urinary tract infection. A voiding cystourethrography is indicated only in children with high PCT values (≥1.0 ng/mL) and/or abnormalities found on a US.

Objectives: This before–after study investigated the association between an audit program and door-to-balloon times in patients with acute ST-elevation myocardial infarction (STEMI) and explored other factors associated with the door-to-balloon time. Methods: An audit program that collected time data for essential time intervals in acute STEMI was developed with data feedback to both the Department of Emergency Medicine and the Department of Cardiology. The door-to-balloon times for 76 consecutive acute STEMI patients were collected from February 16, 2007, through October 31, 2007, after the implementation of the audit program, as the intervention group. The control group was defined by 104 consecutive acute STEMI patients presenting from April 1, 2006, through February 15, 2007, before the audit was applied. A multivariate linear regression model was used for analysis of factors associated with the door-to-balloon time. Results: The geometric mean 95% CI of the door-to-balloon time decreased from 164.9 (150.3, 180.9) minutes to 141.9 (127.4, 158.2) minutes (p = 0.039) in the intervention phase. The median door-to-balloon time was 147.5 minutes in the control group and 136.0 minutes in the intervention group (p = 0.09). In the multivariate regression model, the audit program was associated with a shortening of the door-to-balloon time by 35.5 minutes (160.4 minutes vs. 195.9 minutes, p = 0.004); female gender was associated with a mean delay of 58.4 minutes (208.9 minutes vs. 150.5 minutes; p = 0.001); posterolateral wall infarction was associated with a mean delay of 70.5 minutes compared to anterior wall infarction (215.4 minutes vs. 144.9 minutes; p = 0.037) and a mean delay of 69.5 minutes compared to inferior wall infarction (215.4 minutes vs. 145.9 minutes; p = 0.044). The use of a glycoprotein IIb/IIIa inhibitor was associated with a 46.1 minutes mean shortening of door-to-balloon time (155.7 minutes vs. 201.8 minutes; p

Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study.Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant (P.0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure.Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosismetabolic acidosisrespiratory acidosismixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.

Human herpesvirus 8 (HHV8) has been consistently linked to Kaposi’s sarcoma and many hematological diseases such as pleural effusion lymphoma, multicentric Castleman’s disease, some lymphoproliferative diseases and posttransplantation bone marrow failure. However, whether patients with hematological disorders are at a higher risk of HHV8 infection has not been determined. In this study, indirect immunofluorescence was used to detect antibodies against lytic antigens of HHV8 in 265 patients with hematological disorders. Our data showed that 24.5% of patients (65/265) were seropositive for HHV8 IgG antibody, which was significantly higher than in our general population (p < 0.001). A significantly higher seropositive rate can be found in patients with lymphoma, leukemia, autoimmune cytopenias and myeloproliferative disorders, but not in patients with myeloma or aplastic anemia. No difference in the seropositive rate is associated with gender or age. We conclude that some patients with hematological disorders are at a higher risk of HHV8 infection.