STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Cooper Pair Density of Bi2Sr2CaCu2O8+ x in Atomic scale at 4.2 K.

In pursuit of the elusive mechanism of high- T C superconductors (HTSC), spectroscopic imaging scanning tunneling microscopy (SI-STM) is an indispensable tool for surveying local properties of HTSC. Since a conventional STM utilizes metal tips, which allow the examination of only quasiparticles and not superconducting (SC) pairs, Josephson tunneling using STM has been demonstrated by many authors in the past. An atomically resolved scanning Josephson tunneling microscopy (SJTM), however, was realized only recently on Bi2Sr2CaCu2O8+ x (Bi-2212) below 50 mK and on the Pb(110) surface at 20 mK. Here we report the atomically resolved SJTM on Bi2Sr2CaCu2O8+ x at 4.2 K using Bi-2212 tips created in situ. The I- V characteristics show clear zero bias conductance peaks following Ambegaokar-Baratoff (AB) theory. A gap map was produced for the first time using an atomically resolved Josephson critical current map I C( r) and AB theory. Surprisingly, we found that this new gap map is anticorrelated to the gap map produced by a conventional method relying on the coherence peaks. Quasiparticle resonance due to a single isolated zinc atom impurity was also observed by SJTM, indicating that atomically resolved SJTM was achieved at 4.2 K. Our result provides a starting point for realizing SJTM at even higher temperatures, rendering possible investigation of the existence of SC pairs in HTSC above the T C.

Associations of various blood pressure parameters with functional outcomes after endovascular thrombectomy in acute ischaemic stroke.

BACKGROUND AND PURPOSE: High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0-2), were analysed. RESULTS: Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP [each 10 mmHg increase, odds ratio 0.82 (0.69-0.97)] and higher systolic successive variation (SV) [each 10% increase, odds ratio 0.37 (0.18-0.76)] were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint  = 0.05). CONCLUSION: The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.

Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy.

Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma-shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a-dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma-shock that p47phox knock-out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end-organ injury and activated protein C-mediated coagulopathy. In summary, we demonstrate that trauma-shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a-dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.

Effects of clarithromycin on the pharmacokinetics of evogliptin in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVE: Evogliptin (DA-1229), a novel dipeptidyl peptidase (DPP)-4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome (CYP) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. METHODS: An open-label, two-phase, crossover study was conducted with 12 healthy subjects. On day 1, a single dose of evogliptin 5 mg was administered alone to assess the reference PK profile of evogliptin. On day 10, after a 2-day pretreatment with clarithromycin, evogliptin 5 mg was administered again to evaluate the effect of CYP inhibition on the PK profile of evogliptin. Administration of clarithromycin continued until day 14. Blood sampling in the reference and test phases was performed until 96 and 168 hours after dosing, respectively for PK assays. RESULTS: Eleven of the 12 subjects completed the study, and their data were analysed. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the geometric mean peak plasma concentration (Cmax ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞ ) of evogliptin increased by 116.5% and 89.6%, respectively. WHAT IS NEW AND CONCLUSION: Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.

Association between recovery from Bell's palsy and body mass index.

BACKGROUND: Although many factors have been found to be involved in recovery from Bell's palsy, no study has investigated the association between recovery from Bell's palsy and obesity. This study therefore evaluated the association between recovery from Bell's palsy and body mass index (BMI). METHODS: Subjects were classified into five groups based on BMI (kg/m2 ). Demographic and clinical characteristics were compared among these groups. Assessed factors included sex, age, time from paralysis to visiting a hospital, the presence of comorbidities such as diabetes mellitus and hypertension, degree of initial facial nerve paralysis by House-Brackmann (H-B) grade and neurophysiological testing, and final recovery rate. RESULTS: Based on BMI, 37 subjects were classified as underweight, 169 as normal weight, 140 as overweight, 155 as obese and 42 as severely obese. Classification of the degree of initial facial nerve paralysis as moderate or severe, according to H-B grade and electroneurography, showed no difference in severity of initial facial paralysis among the five groups (P > 0.05). However, the final recovery rate was significantly higher in the normal weight than in the underweight or obese group (P < 0.05). CONCLUSIONS: Obesity or underweight had no effect on the severity of initial facial paralysis, but the final recovery rate was lower in the obese and underweight groups than in the normal group.

Is there a Relationship between Bone Morphology and Injured Ligament on Imaging Studies and Laxity on Ankle Stress Radiographs?

This study aimed to investigate the relationship between bone morphology and injured ligaments on imaging studies and laxity on ankle stress radiographs in patients with lateral ankle instability. In total, 115 patients who had undergone ankle MRI, ankle radiography, and stress radiography were included. Distal tibial articular surface angle, bimalleolar tilt, medial and lateral malleolar relative length, medial malleolar slip angle, anterior inclination of the tibia, and fibular position were measured on ankle radiographs. Tibiotalar tilt angle and anterior translation of the talus were measured on ankle stress radiographs. Degree of ligament injury was evaluated on ankle MRIs. Multiple regression analysis was performed using the following independent variables: age, sex, and factors significantly associated with ankle stress view on univariate linear regression analysis. Age (p=0.041), sex (p=0.014), degree of anterior talofibular ligament injury (p<0.001), and bimalleolar tilt (p=0.016) were correlated with tibiotalar tilt angle. Fibular position and degree of posterior talofibular ligament injury were factors significantly related to anterior translation of the talus. Differences in patient characteristics might predispose ankle stress radiograph results. Comparison of both ankles on stress radiographs is superior to applying fixed numerical values to the injured side in order to reduce the influence of patient factors.

The preventive effects of lifestyle intervention on the occurrence of diabetes mellitus and acute myocardial infarction in metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. STUDY DESIGN: Observational study on disease occurrence after lifestyle intervention. METHODS: The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. RESULTS: In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644-0.879) and 0.499 (95% CI: 0.251-0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. CONCLUSIONS: Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail.

Steroid plus antiviral treatment for Bell's palsy.

OBJECTIVES: The effectiveness of antiviral agents for the treatment of Bell's palsy is uncertain. We evaluated whether a steroid with an antiviral agent (S + A group) provided better recovery outcomes than a steroid alone (S group) in patients with Bell's palsy. SUBJECTS AND DESIGN: A total of 1342 patients diagnosed with Bell's palsy who visited the Kyung Hee Medical Center in Seoul, Korea, from 2002 to 2012 were included in this study. Patients in the S + A group were treated with prednisolone and antiviral agents (n = 569) and those in the S group with prednisolone alone (n = 773). Outcomes were measured using the House-Brackmann (HB) scale according to age, initial disease severity, electroneurography (ENoG) findings and underlying comorbidities. RESULTS: The rate of recovery (HB grades I and II) with initially severe Bell's palsy (HB grades V and VI) was higher in the S + A than in the S group (P = 0.001). However, the rates of recovery were similar with initially moderate palsy (HB grades II-IV) (P = 0.502). In patients classified according to age and ENoG-determined severity of palsy, the overall recovery rate was higher in the S + A than in the S group, but the differences were not statistically significant (P > 0.05 for both). The recovery rate without diabetes mellitus (DM) and hypertension (HTN) was higher in the S + A group than in the S group (P = 0.031). But in the patients with HTN and DM, the difference in recovery rates between the S + A and S groups was not statistically significant (P = 0.805). CONCLUSIONS: Treatment with a steroid plus antiviral agent resulted in significantly higher recovery rates than steroid therapy alone in patients with initially severe Bell's palsy and without either HTN or DM, and a nonsignificant trend towards higher recovery rates in all patients with Bell's palsy in this study. Antiviral agents may therefore help in the treatment of Bell's palsy.

Changes of knee joint and ankle joint orientations after high tibial osteotomy.

OBJECTIVE: We sought to determine (1) whether change in the tibial plateau inclination (TPI) after high tibial osteotomy (HTO) is different from change in the knee joint line orientation (KJLO) relative to the ground; (2) whether, in varus knee OA patients before and after HTO, these radiographic measures are different from those in normal control; and (3) whether the postoperative values of the TPI and KJLO relative to the ground are associated with short term clinical outcome scores after HTO. DESIGN: Fifty patients who underwent HTO and 75 normal controls were assessed with four radiographic measures. We compared the measures before HTO with those after HTO and with those of the normal controls, then examined associations between the postoperative radiographic measures and clinical outcome scores 1-year after HTO. RESULTS: After HTO, TPI increased 9.0°, whereas KJLO relative to the ground only increased 4.1°, with a compensatory change of the ankle joint line orientation. However, the postoperative KJLO relative to the ground in the HTO group was significantly different from that of the normal controls (mean difference, 4.9°; P < 0.001). In the multiple regression analyses, the postoperative radiographic measures were not associated with outcome clinical scores 1 year after HTO. CONCLUSION: After HTO the relative KJLO changed significantly less than did the anatomical geometry of the proximal tibia. Although the KJLO after the HTO was still significantly different from that of normal knees, its value did not adversely affect clinical outcome scores 1 year after HTO.

The cortical contrast accumulation from brain computed tomography after endovascular treatment predicts symptomatic hemorrhage.

BACKGROUND AND PURPOSE: The prognostic value of contrast accumulation from non-contrast brain computed tomography taken immediately after endovascular reperfusion treatment in acute ischaemic stroke patients to predict symptomatic hemorrhage was studied. METHODS: Between July 2007 and August 2014, acute anterior circulation ischaemic stroke patients who were treated by intra-arterial thrombolysis or thrombectomy were included. Contrast accumulation was defined as a high attenuation area from non-contrast brain computed tomography immediately taken after endovascular reperfusion treatment, and patients were categorized into three groups according to the presence and location of contrast: (i) negative, (ii) cortical involvement and (iii) non-cortical involvement. The rates of symptomatic hemorrhage after 24 h and functional outcome at discharge were compared between patients with and without cortical involvement. RESULTS: Of 64 patients who were treated by endovascular intervention, contrast accumulation was detected in 56, including 33 patients with cortical involvement and 23 patients without cortical involvement. The cortical involvement pattern was more frequently associated with symptomatic hemorrhage (13 vs. 1 patient, P = 0.003) and with grave outcome at discharge with modified Rankin Scale 5 or 6 (14 vs. 4, P = 0.048) than the non-cortical involvement group. Multivariate logistic regression analysis including initial collateral status and occlusion site disclosed that cortical involvement pattern independently predicted symptomatic hemorrhage after endovascular treatment (odds ratio 19.0, confidence interval 1.6-227.6, P = 0.020). CONCLUSION: Our study provides evidence that the cortical involvement of contrast accumulation is associated with symptomatic hemorrhage after endovascular reperfusion treatment.

Comparison of steroid administration methods in patients with idiopathic sudden sensorineural hearing loss: a retrospective observational study.

OBJECTIVES: To compare the recovery rates of patients with idiopathic sudden sensorineural hearing loss (ISSHL) treated with oral systemic steroids (PO) or intratympanic steroid injection (IT) or both. DESIGN: A retrospective observational study. SETTING: Tertiary referral centre. PARTICIPANTS: Eight hundred and forty-four patients diagnosed with ISSHL within 14 days of the onset of symptoms. The patients were divided into three groups by treatment modality. MAIN OUTCOME MEASURES: Threshold of pure-tone tests, age, accompanying symptoms and underlying diseases were compared. The level of final hearing recovery was evaluated by the application of the results of the pure-tone test that was performed at least 3 months after the completion of each treatment. RESULTS: Final hearing recovery rate differed significantly by the type of treatment (P = 0.031). Recovery rates in the PO and combined groups were significantly higher in patients with mild (85.1% and 88.6%, respectively) than with profound (52.8% and 69.0%, respectively) hearing loss (P < 0.05). In contrast, severity and recovery rate were not significantly correlated in the IT group (P > 0.05). Combined treatment yielded significantly higher recovery rates than other treatment modalities in patients without hypertension (HTN) and diabetes mellitus (DM) (P = 0.021). CONCLUSION: In the group treated with combined therapy, better hearing improvement was obtained than in the groups treated with systemic steroid only or with intratympanic steroid injection only without complications. These findings suggest that the combination of systemic administration and intratympanic injection may improve patient prognosis.

Association between genetic variants in the IRGM gene and tuberculosis in a Korean population.

PURPOSE: To investigate immunity-related guanosine triphosphatase family M (IRGM) genetic variants associated with susceptibility to tuberculosis (TB) in a Korean population. METHODS: We conducted a prospective case-control study including 193 patients with active TB in Severance Hospital and 230 age- and sex-matched unrelated controls registered in Yonsei Cardiovascular Genome Center. Based on associations with other chronic inflammatory conditions, we analyzed the allele and genotype frequencies of rs72553867, rs10065172, and rs12654043 among patients with TB and healthy controls. RESULTS: The T allele of rs10065172 was significantly associated with protection against developing TB based on allele frequency [P = 0.042; odds ratio (OR) 0.75] and genotype distribution in the codominant model (P = 0.036; OR 0.73). CONCLUSIONS: This is the first study to identify a significant association between the IRGM single-nucleotide polymorphism (SNP) rs10065172 and susceptibility to active TB disease in an Asian population. The results suggest that IRGM genetic variants could be associated with susceptibility to active TB disease in the Korean population.

Phase stability of Li-Mn-O oxides as cathode materials for Li-ion batteries: insights from ab initio calculations.

In this work, we present a density-functional theory (DFT) investigation of the phase stability, electrochemical stability and phase transformation mechanisms of the layered and over-lithiated Mn oxides. This study includes the thermodynamic stability of Li and oxygen vacancies, to examine the electrochemical activation mechanisms of these cathode materials. The DFT calculations provide phase diagrams of the Li-Mn-O system in both physical and chemical potential spaces, including the crystals containing vacancies as independent phases. The results show the ranges of electrochemical activity for both layered LiMnO2 and over-lithiated Li2MnO3. By using a thermodynamic model analysis, we found that the required temperature for oxygen evolution and Li vacancy formation is too high to be compatible with any practical synthesis temperature. Using solid-state transition calculations, we have identified the key steps in the phase transition mechanism of the layered LiMnO2 into the spinel phase. The calculated effects of pH on the Li-Mn-O phase stability elucidated the mechanism of Mn(2+) formation from the spinel phase under acidic conditions.

Ankle fractures have features of an osteoporotic fracture.

UNLABELLED: We report the bone attenuation of ankle joint measured on computed tomography (CT) and the cause of injury in patients with ankle fractures. The results showed age- and gender-dependent low bone attenuation and low-energy trauma in elderly females, which suggest the osteoporotic features of ankle fractures. INTRODUCTION: This study was performed to investigate the osteoporotic features of ankle fracture in terms of bone attenuation and cause of injury. METHODS: One hundred ninety-four patients (mean age 51.0 years, standard deviation 15.8 years; 98 males and 96 females) with ankle fracture were included. All patients underwent CT examination, and causes of injury (high/low-energy trauma) were recorded. Mean bone attenuations of the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis were measured on CT images. Patients were divided into younger age (<50 years) and older age (≥50 years) groups, and mean bone attenuation and causes of injury were compared between the two groups in each gender. RESULTS: Proportion of low-energy trauma was higher in the older age group than in the younger age group, but the difference was only significant in female gender (p = 0.011). The older age group showed significantly lower bone attenuation in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis than the younger age group in both genders. The older age group showed more complex pattern of fractures than the younger age group. With increasing age, bone attenuations tended to decrease and the difference of bone attenuation between the genders tended to increase in the talus, medial malleolus, lateral malleolus, and distal tibial metaphysis. CONCLUSIONS: Ankle fracture had features of osteoporotic fracture that is characterized by age- and gender-dependent low bone attenuation. Ankle fracture should not be excluded from the clinical and research interest as well as from the benefit of osteoporosis management.

Prediction of hemorrhagic transformation in acute ischaemic stroke by micro- and macroalbuminuria after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis (IVT). This study was conducted to assess whether micro- and macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin-to-creatinine ratios would correlate with the degree of HT. METHODS: This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro- and macroalbuminuria might be independent predictors of HT. RESULTS: One-hundred and fifty-four patients were included in the study. Fifty-one patients had HT. The presence of micro- or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106-5.841; P = 0.028). There were significant relationships between the presence of micro- and macroalbuminuria and types of HT. CONCLUSION: In conclusion, the results of this study suggest that the presence of micro- and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke.

Conversion rates of an interferon-γ release assay and the tuberculin skin test in the serial monitoring of healthcare workers.

PURPOSE: Regular monitoring of latent tuberculosis (TB) infection in healthcare workers (HCWs) is recommended, but the view about the effective method and performance of serial monitoring is controversial. The aim of this study was to determine differences in conversion rates according to TB exposure risk using the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT), and to evaluate the reproducibility and within-subject variability of the QFT-GIT in South Korea. METHODS: Fifty-three HCWs were grouped according to their risk for TB exposure: group 1, high risk (n = 21); group 2, low risk (n = 32). Baseline and follow-up TSTs and QFT-GITs were performed from June 2009 to July 2011. Enzyme-linked immunosorbent assays (ELISAs) were repeated for the second QFT-GIT and a third QFT-GIT was performed after 8 weeks when discordant results of the second TST and QFT-GIT or a conversion or reversion were observed. RESULTS: No difference in the QFT-GIT conversion rate was evident between the two groups (15.4 vs. 6.5 %, p = 0.57), and no TST conversion was observed. The rate of QFT-GIT positivity was higher in the high-risk group (first QFT-GIT: 38.1 vs. 3.1 %, p = 0.002; second QFT-GIT: 33.3 vs. 9.4 %, p = 0.039). The re-test reproducibility of QFT-GIT results was high (100 %), and the within-subject results of repetitive QFT-GITs were variable. CONCLUSIONS: Stricter prevention strategies remain necessary in HCWs at high risk of TB exposure, and serial interferon-γ release assays (IGRAs) should be interpreted with caution in HCWs.

Epidemiological analysis of critically ill adult patients with pandemic influenza A(H1N1) in South Korea.

A total of 245 patients with confirmed 2009 H1N1 influenza were admitted to the intensive-care units of 28 hospitals (South Korea). Their mean age was 55.3 years with 68.6% aged >50 years, and 54.7% male. Nine were obese and three were pregnant. One or more comorbidities were present in 83.7%, and nosocomial acquisition occurred in 14.3%. In total, 107 (43.7%) patients received corticosteroids and 66.1% required mechanical ventilation. Eighty (32.7%) patients died within 30 days after onset of symptoms and 99 (40.4%) within 90 days. Multivariate logistic regression analysis showed that the clinician's decision to prescribe corticosteroids, older age, Sequential Organ Failure Assessment score and nosocomial bacterial pneumonia were independent risk factors for 90-day mortality. In contrast with Western countries, critical illness in Korea in relation to 2009 H1N1 was most common in older patients with chronic comorbidities; nosocomial acquisition occurred occasionally but disease in obese or pregnant patients was uncommon.