BACKGROUND AND PURPOSE: Few studies have investigated the relationship between the specific functional factors potentially associated with functional level and stroke recurrence. We conducted a study of patients with noncardioembolic ischemic stroke (NCIS) to determine the functional factors affecting recurrence within the first year. METHODS: In total, 568 first-ever NCIS patients (age=65.1±17.4 years, mean±SD) were analyzed in a multicenter, prospective cohort study registered from August 2012. Demographic characteristics, past medical history, comorbidities, laboratory data, stroke features in neuroimaging, acute treatments, and medications at discharge were assessed. Functional factors reflecting gross functional impairment, ambulatory function, motor function, activities of daily living, cognition, language ability, swallowing function, mood, and quality of life were comprehensively evaluated in face-to-face assessments using standardized tools at the time of discharge. RESULTS: The cumulative incidence of stroke recurrence in NCIS was 6.0% (n=34) at 1 year. The period from admission to discharge was 34.4±7.0 days. The independent predictors of stroke recurrence within 1 year in multivariate Cox proportional-hazards regression analyses were 1) age [per-year hazard ratio (HR)=1.04, 95% confidence interval (CI)=0.97–1.06, p=0.048], 2) Charlson Comorbidity Index higher than 2 (HR=1.72, 95% CI=1.26–2.22, p=0.016), 3) modified Rankin Scale score of 3 or more at discharge (HR=1.56, 95% CI=1.22–1.94, p=0.032), and 4) Functional Ambulation Category of 3 or less at discharge (HR=2.56, 95% CI=1.84–3.31, p=0.008). CONCLUSIONS: In addition to patient age, moderate-to-severe functional impairment requiring the help of others (especially for ambulation) at the time of discharge and the severity of comorbidity were independent predictors of stroke recurrence within 1 year of the first NCIS.
Activities of Daily Living ; Cognition ; Cohort Studies* ; Comorbidity ; Deglutition ; Disability Evaluation ; Humans ; Incidence ; Language ; Neuroimaging ; Prospective Studies ; Quality of Life ; Recurrence* ; Rehabilitation* ; Stroke* ; Walking

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Although current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation. METHODS: A total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24–48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24–48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years. RESULTS: During follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66–0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67–0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24–48 hours) in model 3. CONCLUSIONS: Early statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682
Bias (Epidemiology) ; Consensus ; Death ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention

OBJECTIVES: Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-β signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. METHODS: The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. RESULTS: Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. CONCLUSION: Losartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity.
Animals ; Axons ; Blotting, Western ; Brain Stem ; Cochlea ; Cochlear Nucleus ; Evoked Potentials, Auditory, Brain Stem ; GAP-43 Protein ; Hearing Loss ; Hearing ; Losartan ; Plastics ; Rats ; Tinnitus ; Transforming Growth Factors ; Vesicular Glutamate Transport Protein 1 ; Vesicular Glutamate Transport Protein 2

PURPOSE: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of parainfluenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to examine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. METHODS: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medical records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical information were cross-sectionally reviewed and analyzed. RESULTS: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11–31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hospitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). CONCLUSION: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most common cause of childhood croup; however, croup epidemics could be attributed to other viruses.
Child ; Coronavirus ; Croup ; Demography ; Electronic Health Records ; Hospitalization ; Humans ; Korea ; Male ; Mycoplasma ; Paramyxoviridae Infections ; Polymerase Chain Reaction ; Respiratory Syncytial Viruses ; Retrospective Studies ; Reverse Transcription ; Rhinovirus ; Seasons

BACKGROUND: Lung cancer is a leading cause of morbidity and mortality worldwide, and the incidence continues to rise. Although many prognostic factors have been identified, the clinical characteristics and outcomes in Korean lung cancer patients are not well defined. METHODS: Of the 23,254 new lung cancer cases registered at the Korea Central Cancer Registry in 2013, total 489 patients from 19 hospitals were abstracted by the Korean Central Cancer Registry. The clinical data retrospectively analyzed, patients were followed up until December 2015. RESULTS: The median age was 69 years (interquartile range, 60–74 years); 65.4% were male and 62.1% were ever-smokers. Cough was the most common initial symptom (33.5%); 13.1% of patients were asymptomatic. While squamous cell carcinoma was the most common subtype in male patients (37.2%), adenocarcinoma was the most frequent histological type in all patients (48.7%) and females (76.3%). The majority of patients received treatment (76.5%), which included surgery, radiation therapy, and chemotherapy. Older age (hazard ratio [HR], 1.037), lower body mass index (HR, 0.904), ever-smoker (HR, 2.003), small cell lung cancer (HR, 1.627), and distant metastasis (HR, 3.990) were independent predictors of mortality. Patients without symptoms (HR, 0.387) and without treatment (HR, 0.364) were associated with a favorable outcome in multivariate Cox analysis. CONCLUSION: Lung cancer in Korea occurs predominantly in elderly patients, with adenocarcinoma being the most frequent subtype. The prognosis was poorer in ever-smokers and older, malnourished, and untreated patients with advanced lung cancer.
Adenocarcinoma ; Aged ; Body Mass Index ; Carcinoma, Squamous Cell ; Cough ; Drug Therapy ; Epidemiology ; Female ; Humans ; Incidence ; Korea ; Lung Neoplasms ; Lung ; Male ; Mortality ; Neoplasm Metastasis ; Pilot Projects ; Prognosis ; Retrospective Studies ; Small Cell Lung Carcinoma

PURPOSE: The use of immediate breast reconstruction (IBR) has been debated because it may be a causative factor in adjuvant treatment delay and may subsequently increase the probability of recurrence. We investigated whether IBR was related to adjuvant treatment delay and survival outcomes. METHODS: We retrospectively analyzed the duration from operation to adjuvant treatment administration and survival outcomes according to IBR status among patients with breast cancer who underwent mastectomy followed by adjuvant chemotherapy from January 2005 to December 2014. Propensity score matching was performed to balance the clinicopathologic baseline characteristics between patients who did and did not undergo IBR. RESULTS: Of 646 patients, 107 (16.6%) underwent IBR, and the median follow-up was 72 months. The median duration from surgery to adjuvant chemotherapy was significantly longer in patients who underwent IBR than in those who did not (14 vs. 12 days, respectively, p = 0.008). Based on propensity score matching, patients who underwent IBR received adjuvant therapy 3 days later than those who did not (14 vs. 11 days, respectively, p = 0.044). The duration from surgery to post-mastectomy radiation therapy (PMRT) did not significantly differ between the 2 groups. Local recurrence-free survival, regional recurrence-free survival, systemic recurrence-free survival, and overall survival were also not significantly different between the 2 groups (p = 0.427, p = 0.445, p = 0.269, and p = 0.250, respectively). In the case-matched cohort, survival outcomes did not change. CONCLUSION: IBR was associated with a modest increase in the duration from surgery to chemotherapy that was statistically but not clinically significant. Moreover, IBR had no influence on PMRT delay or survival outcomes, suggesting that it is an acceptable option for patients with non-metastatic breast cancer undergoing mastectomy.
Breast Implants ; Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Cohort Studies ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Mammaplasty ; Mastectomy ; Propensity Score ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

PURPOSE: We investigate biases in the assessments of left ventricular function (LVF), by compressed sensing (CS)-cine magnetic resonance imaging (MRI). MATERIALS AND METHODS: Cardiovascular cine images with short axis view, were obtained for 8 volunteers without CS. LVFs were assessed with subsampled data, with compression factors (CF) of 2, 3, 4, and 8. A semi-automatic segmentation program was used, for the assessment. The assessments by 3 CS methods (ITSC, FOCUSS, and view sharing (VS)), were compared to those without CS. Bland-Altman analysis and paired t-test were used, for comparison. In addition, real-time CS-cine imaging was also performed, with CF of 2, 3, 4, and 8 for the same volunteers. Assessments of LVF were similarly made, for CS data. A fixed compensation technique is suggested, to reduce the bias. RESULTS: The assessment of LVF by CS-cine, includes bias and random noise. Bias appeared much larger than random noise. Median of end-diastolic volume (EDV) with CS-cine (ITSC or FOCUSS) appeared −1.4% to −7.1% smaller, compared to that of standard cine, depending on CF from (2 to 8). End-systolic volume (ESV) appeared +1.6% to +14.3% larger, stroke volume (SV), −2.4% to −16.4% smaller, and ejection fraction (EF), −1.1% to −9.2% smaller, with P < 0.05. Bias was reduced from −5.6% to −1.8% for EF, by compensation applied to real-time CS-cine (CF = 8). CONCLUSION: Loss of temporal resolution by adopting missing data from nearby cardiac frames, causes an underestimation for EDV, and an overestimation for ESV, resulting in underestimations for SV and EF. The bias is not random. Thus it should be removed or reduced for better diagnosis. A fixed compensation is suggested, to reduce bias in the assessment of LVF.
Bias (Epidemiology) ; Compensation and Redress ; Diagnosis ; Magnetic Resonance Imaging ; Magnetic Resonance Imaging, Cine ; Noise ; Stroke Volume ; Ventricular Function, Left ; Volunteers