Background and Objectives: De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-STsegment elevation ACS (NSTE-ACS). Methods: This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year. Results: Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48– 0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48–2.26; p=0.915; p for interaction=0.271). Conclusions Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs. MATERIALS AND METHODS: The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared. RESULTS: Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS. CONCLUSION: NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.
Humans ; Korea ; Multivariate Analysis ; Neoplasm Metastasis ; Neurilemmoma* ; Neurofibromatoses* ; Neurofibromatosis 1* ; Pathology ; Sarcoma ; Seoul

BACKGROUND: The purpose of this study was to investigate plasma levels of endostatin and vascular endothelial growth factor (VEGF) in normal subjects and in patients with pituitary adenoma and to evaluate change in these levels following stereotactic radiosurgery (SRS) for pituitary adenoma. METHODS: Peripheral venous blood was collected from five patients with pituitary adenoma before SRS using Gamma Knife and at the 1 week and 1 month follow-up visits. Plasma endostatin and VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. RESULTS: Mean baseline plasma endostatin level (105.3 ng/mL, range, 97.0-120.2 ng/mL) in patients with pituitary adenoma was higher than that of the healthy controls (86.6 ng/mL, range, 71.3-98.2 ng/mL) (p=0.001). Mean plasma VEGF level was 89.5 pg/mL (range, 24.1-171.8 pg/mL) in patients with pituitary adenoma at baseline and 29.3 pg/mL (range, 9.2-64.3 pg/mL) in the control group (p=0.050). Plasma endostatin level changed to 106.6 ng/mL 1 week after SRS and decreased to 95.9 ng/mL after 1 month. Plasma VEGF level following SRS decreased to 74.1 pg/mL after 1 week and 79.0 pg/mL after 1 month. There was a trend toward decreased plasma endostatin and VEGF concentrations 1 month after SRS compared to baseline levels (p=0.195, p=0.812, respectively). CONCLUSION: Plasma endostatin and VEGF levels in patients with pituitary adenoma were significantly elevated over controls at baseline, which decreased from baseline to 1 month after SRS for pituitary adenomas.
Endostatins* ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Pituitary Neoplasms* ; Plasma ; Radiosurgery* ; Vascular Endothelial Growth Factor A*

OBJECTIVE: The purpose of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to assess the therapeutic response of brain abscess. METHODS: A study was conducted on 10 consecutive patients with brain abscess. Magnetic resonance imaging (MRI) with diffuse-weighted imaging (DWI) was performed at 3 and 6 weeks after surgical treatment and intravenous antibiotics therapy and FDG-PET at 6 weeks after treatment. The extent of the abscess, signal changes on MRI, and FDG-PET standardized uptake values were analyzed and correlated with the response to therapy. RESULTS: Aspiration or craniotomy with excision of the abscess followed by intravenous antibiotics for 6-8 weeks resulted in good recovery with no recurrence. In 10 patients, two had low signal intensity on the DWI; one had no uptake on FDG-PET imaging after 6 weeks antibiotics and discontinued intravenous treatment, but the other patient had diffuse, increased uptake on FDG-PET imaging after 6 weeks antibiotics and underwent an additional 2 weeks of intravenous antibiotics. The remaining eight patients had high signals on the DWI. Four had no uptake on FDG-PET imaging and the treatment period varied from 6 to 8 weeks (mean, 6.75 weeks). Among the other four patients, FDG was accumulated in a diffuse or local area corresponding to a high signal area within the DWI and 2 weeks of intravenous antibiotics was added. CONCLUSION: MRI plus FDG-PET improved the accuracy of assessing therapeutic responses to antibiotics treatment of brain abscess and aided in optimizing therapy.
Abscess ; Anti-Bacterial Agents ; Brain ; Brain Abscess ; Craniotomy ; Electrons ; Humans ; Magnetic Resonance Imaging ; Positron-Emission Tomography ; Recurrence

OBJECTIVE: The tethered cord syndrome results in progressive neurological deficits. Although it may remain controversial, many physicians recommend definitive surgery to untether the cord as soon as this condition is identified. We retrospectively evaluate the pre-operative and post-operative course of 38 tethered cord patients with spinal dysraphism in an attempt to learn the natural history of the disease and to determine the effectiveness of the surgical treatment. METHODS: The medical records, operation notes and radiographs were evaluated. The follow up period ranged from 4 months to 12 years with a mean follow-up of 28.6 months. Twenty-seven patients were younger than 15 years of age. RESULTS: At presentation, 26 of the patients were asymptomatic. In three of 11 adult symptomatic patients, their neurological deficits worsened after trauma or exercise. Improvement of motor strength was documented in two out of 5 patients. Five of nine patients with bladder symptoms improved, however, none had a complete return of their bladder function. CONCLUSION: Childhood patients were less symptomatic than the adult patients. Adult patients showed progression of their symptoms that were not improved even after the operation in most of the cases. Asymptomatic tethered spinal cord can be symptomatic as time passes by and even at an old age. Future research should be focused on the operative methods to prevent the delayed deterioration after surgery, rather than on the usefulness of preventive surgery in asymptomatic patients.
Adult ; Follow-Up Studies ; Humans ; Medical Records ; Natural History ; Neural Tube Defects ; Retrospective Studies ; Spinal Cord* ; Spinal Dysraphism ; Urinary Bladder

BACKGROUND: Neuronal death in acute-phase cerebral ischemic injury is caused by necrosis. However, neuronal injury after reperfusion can be associated with apoptosis. METHODS: We used Sprague-Dawley rats whose brains were reperfused after middle cerebral artery occlusion for either 30 min or 2 h. We examined a relationship between apoptosis and the expression of inducible nitric oxide synthase (iNOS) in the brain tissue from 3 h to 14 days after reperfusion in both groups. RESULTS: TUNEL and iNOS positivity were closely related in both groups. The 2-h ischemia group exhibited increases in the amount of TUNEL and iNOS-positive cells for up to 3 days after reperfusion, at which the TUNEL and iNOS-positive cells decreased. The 30-min ischemia group exhibited peak positivity 24 h after reperfusion, followed by a similar decrease. iNOS mRNA expression peaked 3 h after reperfusion in the 30-min ischemia group, at which time it decreased. In the 2-h ischemia group, iNOS mRNA increased 3 h after reperfusion, peaked 24 h after reperfusion, and then decreased. CONCLUSION: These results indicated the occurrence of delayed apoptosis in transient cerebral ischemia. Increased expression of iNOS is closely associated with this apoptosis, and oxygen free radical-producing materials, such as nitric oxide, may play an important role in the induction of this apoptosis.
Apoptosis* ; Brain ; Brain Ischemia* ; In Situ Nick-End Labeling ; Infarction, Middle Cerebral Artery ; Ischemia ; Ischemic Attack, Transient ; Necrosis ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase Type II* ; Oxygen ; Rats, Sprague-Dawley ; Reperfusion ; RNA, Messenger

OBJECTIVE: Central nervous system has unique inflammatory responses to the exposure to the endotoxin and immature brain may have a different response with that of the mature. The authors conduct this experiment to elucidate the characteristics of inflammatory response in immature brain. METHODS: Lipopolysaccharide(LPS) was injected in the right caudate nucleus in 7-day-old and adult Sprague-Dawley rats. The doses were 1 microliter of 0.1, 0.5, and 2.0mg/ml of LPS and the same amount of saline for controls. The rats were sacrificed 24hours after injections. Light microscopic examination was performed to evaluate the leukocyte recruitment, and reverse transcriptase-polymerase chain reaction(RT-PCR) to measure the expression of interleukin-1beta(IL-1beta) and tumor necrosis factor-alpha(TNF-alpha) mRNA. RESULTS: Light microscopic examination revealed more pronounced leukocyte infiltration in neonatal brain than in adult, even though lower than in peripheral tissue. RT-PCR revealed dose dependent expression of IL-1beta and TNF-alpha mRNA in both neonatal and adult brain as in peripheral tissue. CONCLUSION: These results support that the immature brain is more vulnerable to the LPS induced inflammation in terms of leukocyte infiltration and possibly resultant brain damage. However, the mechanism of inflammatory response in immature brain should be studied further in association with the research of the activity of microglia, astrocyte, blood brain barrier, chemokine, and adhesion molecule in immature brain.
Adult ; Animals ; Astrocytes ; Blood-Brain Barrier ; Brain* ; Caudate Nucleus ; Central Nervous System ; Humans ; Inflammation ; Interleukin-1beta ; Leukocytes ; Microglia ; Necrosis ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Tumor Necrosis Factor-alpha

OBJECTIVE: To compare observer performance using liquid-crystal display (LCD) and cathode-ray tube (CRT) monitors in the interpretation of soft-copy chest radiographs for the detection of small solitary pulmonary nodules. MATERIALS AND METHODS: By reviewing our Medical Center's radiologic information system, the eight radiologists participating in this study (three board-certified and five resident) retrospectively collected 40 chest radiographs showing a solitary noncalcified pulmonary nodule approximately 1 cm in diameter, and 40 normal chest radiographs. All were obtained using a storage-phosphor system, and CT scans of the same patients served as the gold standard for the presence of a pulmonary nodule. Digital images were displayed on both high-resolution LCD and CRT monitors. The readers were requested to rank each image using a five point scale (1 = definitely negative, 3 = equivocal or indeterminate, 5 = definitely positive), and the data were interpreted using receiver operating characteristic (ROC) analysis. RESULTS: The mean area under the ROC curve was 0.8901+/-0.0259 for the LCD session, and 0.8716+/-0.0266 for the CRT session (p > 0.05). The reading time for the LCD session was not significantly different from that for the CRT session (37.12 and 41.46 minutes, respectively; p = 0.889). CONCLUSION: For detecting small solitary pulmonary nodules, an LCD monitor and a CRT monitor are comparable.

Although the survival rate in childhood cancer is increased with current improvements of diagnostic and therapeutic methods, the incidence of second malignancy is now increasing. Therefore close follow-up with high index of suspicion for second malignancies are important for cancer survivng patients. We report our experiences of 3 second malignancies which were glioblastoma multiforme after treatment of acute lymphoblastic lymphoma, Philadelphia positive leukemia after treatment of osteosarcoma and acute myelogenous leukemia occuring in the course of chemotherapy for acute lymphoblastic leukemia. It is imperative that survivors of childhood cancer be closely followed for the detection of not only the relapse of original disease but also the occurrence of second malignancy.
Drug Therapy ; Follow-Up Studies ; Glioblastoma ; Humans ; Incidence ; Leukemia ; Leukemia, Myeloid, Acute ; Neoplasms, Second Primary* ; Osteosarcoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Radiotherapy ; Recurrence ; Survival Rate ; Survivors