Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 +/- 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 +/- 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients.
Aged ; Atrial Fibrillation/epidemiology/mortality/*pathology ; Atrial Flutter/*epidemiology/mortality/pathology ; Atrial Premature Complexes/*epidemiology/mortality/pathology ; Disease Progression ; Echocardiography ; Female ; Heart Atria/pathology/ultrasonography ; Humans ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Retrospective Studies ; Tachycardia, Ectopic Atrial/*epidemiology/mortality/pathology ; Tachycardia, Paroxysmal/*epidemiology/mortality/pathology ; Thromboembolism/epidemiology/mortality ; Treatment Outcome

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Platelet Disorders/chemically induced ; Child ; Child, Preschool ; Contrast Media/*adverse effects/diagnostic use ; Databases, Factual ; Female ; Humans ; Infant ; Infant, Newborn ; Iodine Radioisotopes/chemistry ; Male ; Middle Aged ; Neoplasms/radionuclide imaging ; Radiopharmaceuticals/*adverse effects/diagnostic use ; Urologic Diseases/chemically induced ; Young Adult

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter gamma-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABABR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABAB1R protein levels, but decreased protein kinase A-alpha (PKA-alpha), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-alpha. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
Animals ; Baclofen ; Brain ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Carrier Proteins ; Ethanol ; Fetal Alcohol Syndrome ; gamma-Aminobutyric Acid ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Phosphorylation ; Pregnancy ; Protein Kinases ; Rats ; Receptors, Neurotransmitter ; RNA Interference ; RNA, Small Interfering ; Signal Transduction

BACKGROUND: Diagnosing a pulmonary embolism is difficult because its presenting symptoms are nonspecific and there are limitations with all of the objective tests. The D-dimer is known to be a marker of the lysis of intravascular cross-linked fibrin as a result of the activation of the endogenous fibrinolytic pathways, and the D-dimer assay is these an objective method for diagnosing a pulmonary embolism. This study assessed the benefits of the D-dimer test for diagnosing a pulmonary embolism using semiquantitative latex agglutination. METHODS: The latex agglutination results of 185 patients were retrospectively reviewed. The D-dimer test was performed at the time a pulmonary embolism was suspected. Ninety patients(group I) were diagnosis with PE through spiral chest CT or a chest CT angiogram, perfusion/ventilation scans, and/or pulmonary angiogram. Ninety-five patients (group II) were found not to have a pulmonary embolism through the above tests. RESULTS: The male to female ratio and mean age in groups I and II was 37:55, and 57 years old to 50:45 and 52 years old, respectively. When the cut off value for a positive D-dimer assay was set to 500 microgram, the sensitivity, positive predictive value, negative predictive value and specificity was 86.7%, 61.4%, 79.3%, and 48.4%, respectively. CONCLUSION: The semiquantitative latex agglutination method in the D-dimer test has a lower sensitivity and negative predictive value than the well known ELISA test particularly for small emboli. Therefore, this test is not a suitable screening test for excluding a pulmonary embolism.
Agglutination* ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrin ; Humans ; Latex* ; Male ; Mass Screening ; Middle Aged ; Pulmonary Embolism* ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUND: New stent implantation during intracoronary brachytherapy is discouraged due to the high risk of late thrombosis. However, new stent implantation is inevitable in some cases due to the inadequate ballooning or major dissections. Long-term follow-up results of newly implanted stents during brachytherapy are not well-known. We performed this study to evaluate the long-term clinical outcomes of newly implanted stents during intracoronary brachytherapy. METHODS: In the Seoul national university Post-Angioplasty RhEnium irradiation (SPARE) trial, patients were treated with conventional catheter-based technique and then randomized to either beta- radiation (RG) or control group (CG). Radiation was performed with 188 -rhenium-filled conventional balloon catheter system. From 1999 to 2001, new stent implantation was performed in 58 and 56 patients in RG and CG, respectively. Clinical and angiographic follow up data were analyzed. RESULTS: In RG, short-term angiographic restenosis rate was lower than CG (28.6% vs 53%, p=0.03). In RG, late thrombosis was found in 3 patients. However, there was no late thrombosis in CG. Two year major cardiac event rates were not different between the 2 groups (RG: 25.9% vs CG: 28.3%). Independent predictors for major cardiac event in RG were major dissections (>or=type C) after stent implantation (beta=70, p=0.01) and longer administration of dual antiplatelets (aspirin+clopidogrel/ ticlopidine, >6 months, beta=0.07, p=0.04). CONCLUSION: Stenting during intracoronary brachytherapy seems to be ineffective in reducing long-term event rates. When new stent implantation is inevitable during brachytherapy, extreme attention is required not to make a dissection and long-term dual antiplatelet treatment should be followed after stent implantation.
Angioplasty ; Brachytherapy ; Catheters ; Follow-Up Studies ; Humans ; Rhenium ; Seoul ; Stents* ; Thrombosis ; Ticlopidine

Local cutaneous reactions have been reported at injection sites of interferon therapy, but these are usually erythema or rarely induration. Skin necrosis at the injection site is rare. We describe here a patient with multiple sclerosis who presented with cutaneous necrosis at the injection sites of interferon-β. Biopsy of the necrotic lesion showed dermal vessel thrombosis and complete ischemic coagulative necrosis of epidermis and dermis.
Biopsy ; Dermis ; Epidermis ; Erythema ; Humans ; Interferon-beta* ; Interferons ; Multiple Sclerosis ; Necrosis* ; Skin* ; Thrombosis

A 26-year-old man with intermittent lower, abdominal, cramping pain, nausea, vomiting, and diarrhea was found to have intussusception by computed tomography. Whole emergency laparotomy was performed, intus-susception reduced spontaneously. Postoperately, familial adenomatous polyposis (FAP) was diagnosed by colonoscopy and barium enema. Innumerous polyps were found in the entire colon and one of these was presumed to have caused sigmoid invagination. If is believed that FAP is quite a rare cause of colonic intus-susception. This case of a 26-year-old man with an intussusception of the colon due to FAP is herein reported. It is important that surgeons and internists are aware of this rare cause of intussusception due to FAP because of the therapeutic implications.
Adenomatous Polyposis Coli* ; Adult ; Barium ; Colon* ; Colon, Sigmoid ; Colonoscopy ; Diarrhea ; Emergencies ; Enema ; Humans ; Intussusception* ; Laparotomy ; Muscle Cramp ; Nausea ; Polyps ; Vomiting

OBJECTIVES: The early detection of ectopic tubal pregnancy in unruptured state is increased as the transvaginal sonography and sensitive serum hCG test are available. For this unruptured tubal pregnancy, the medical treatment using methotrexate via various routes and dosage is being tried. Our study was to evaluate the efficacy of single systemic injection of methotrexate in the treatment of unruptured tubal pregnancies. Material and METHODS: From the January 1997 to July 1999, of 152 ectopic pregnancy patients, 22 patients who were diagnosed as unruptured tubal pregnancies were treated with single-dose systemic methotrexate injection (50 mg/m2/IM). Exclusion criteria were unstable vital signs with hemoperitoneum, adnexal mass > 5-6 cm. Serum hCG titers were checked before injection and 4, 7 day after injection. If serum hCG titer declined more than 15% on 7 day after injection compared with titer on 4 day, the weekly hCG titer was followed until it was <10 mIU/ml .If the hCG titer did not decline more than 15 %, a second dose was given. If hCG titer was not decreased or vital signs became unstable after 1-2 injections, the treatment was considered failure and surgery was done. RESULTS: 18 cases (82%) of 22 were successfully treated with single-dose methotrexate. The mean size of ectopic mass and initial serum hCG titers were 2.7+/-1.3 cm (range, 1.5-5.4 cm) and 3,298+/-1,007 mIU/ml (range, 132-12,239), respectively. Of 22, 6 cases (28%) needed second dose of methotrexate. The mean time to resolution of serum beta-hCG titer was 27.5+/-13.6 days (range, 8-53 days). Elevation of liver enzyme did not occurred in all cases during treatment. Initial hCG titer was more important prognostic factor than ectopic mass size for successful medical treatment. CONCLUSION: Single-dose methotrexate appears to be an effective medical treatment for the unruptured tubal pregnancy. However, patients selection using strict criteria is needed to increase its success rate.
Female ; Hemoperitoneum ; Humans ; Liver ; Methotrexate* ; Pregnancy ; Pregnancy, Ectopic ; Pregnancy, Tubal* ; Vital Signs

Microinvasive carcinoma of the uterine cervix(Stage Ia) is the earliest stage of squamous carcinoma. The transition from preinvasive to invasive disease is a crucial juncture in the development of cervical cancer. The clinical experience that microinvasive lesions carry a better prognosis justifies a separate diagnostic category. To investigate the clinical and pathological aspects of microinvasive cervical carcinoma, a retrospective study was made on 84 cases, histologically reconfirmed surgical specimens, which had been treated during the period from January, 1985 to December, 1996 at Department of Obstetrics and Gynecology, Kyung-pook National University Hospital. We defined microinvasive carcinoma as stromal invasion not exceeding a depth of Smm from the base of the epithelium presented by FIGO in 1985. The results obtained were as follows; 1. Mean age of 84 patients was 46.9 year old, all were parous women but not 1 patients. 60 cases(71.4%) belonged to stage Ial and 24 cases(28,6%) to stage Ia2. 2. Chief complaints were postcoital spotting and leukorrhea. 3, The corresponding rate of Pap. smear to histologic diagnosis was approximately 29.8%. However correponding rate within one histologic grade was about 33,3%. 4. According to the colposcopic examination, 26.4% of cases revealed suspected abnormal findings suggesting invasive lesion. 5. As to the reports of punch biopsy, 55.1% of cases showed microinvasive and/or invasive lesion. With additional diagnostic conization of cervix, the preoperative diagnosis were correct in 72%. 6. Operation performed were simple hysterectomy, extrafascial hysterectomy or modified radical hysterectomy with both pelvic LN dissection, Simple hysterectomy was most commonly performed. 7. Post-treatment complications were developed in 73.9% of patients who were done with modified radical hysterectomy with both pelvic LN dissection and bladder dysfunction was developed in 50% of the patients.
Biopsy ; Carcinoma, Squamous Cell ; Cervix Uteri* ; Conization ; Diagnosis ; Epithelium ; Female ; Gynecology ; Humans ; Hysterectomy ; Leukorrhea ; Metrorrhagia ; Obstetrics ; Prognosis ; Retrospective Studies ; Urinary Bladder ; Uterine Cervical Neoplasms