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Study Design A retrospective cohort study. Purpose To investigate the outcomes of balloon kyphoplasty (BKP) for vertebral compression fractures (VCFs) at the distal end or adjacent vertebra of the fused segments in patients with diffuse idiopathic skeletal hyperostosis (DISH). Overview of Literature Vertebral fractures in the midportion of the fused segments in patients with DISH are generally unstable; thus, immobilization is recommended. However, VCFs classified as type A in the AO classification are observed at the distal end and adjacent vertebra of the fused segments, and treatment strategies for VCFs associated with DISH remain controversial. Methods The outcomes of 72 patients who underwent BKP for VCFs between 2015 and 2021 were retrospectively investigated. Patients with DISH were assigned to group D (n=21), whereas those without DISH were assigned to group ND (n=51). Back pain, incidence of subsequent adjacent fractures, reoperation rates, and local kyphosis were statistically analyzed. Results VCFs in group D occurred at the distal end or adjacent vertebra of the fused segments, and no fractures occurred in the midportion of the fused segment. Back pain improved in both groups, with no significant differences between them. Subsequent adjacent fractures were observed in three of the 21 patients in group D and 11 of the 51 patients in group ND, with no significant difference between them. Reoperation was performed in one patient each in groups D and ND, with no significant difference between the groups. Postoperatively, local kyphosis progressed significantly in group D. Conclusions Although local kyphosis is more advanced in patients with DISH, BKP is effective for VCFs at the distal end or adjacent vertebra of the fused segments and may be useful in older patients with high complication rates.

Background: Percutaneous left atrial appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF). However, since the left atrial appendage (LAA) contributes to left atrial volume and serves as a buffer for increasing left atrial pressure, this procedure may impair left atrium (LA) compliance, enlarge LA, and deteriorate diastolic function. In this study, we sought to investigate the change in left atrial volume index (LAVI) following LAAC and its effect on prognosis. Methods and Results: We analyzed 225 patients from the OCEAN-LAAC registry, an ongoing, multicenter Japanese study. Comparing LAVI measurements at baseline and 6 months after LAAC, no significant increase was observed (55.0 [44.0, 70.0] ml/m2 vs. 55.0 [42.0, 75.6] ml/m2; P = 0.31). However, some patients underwent LAVI increase. Particularly, a smaller LAVI (odds ratio [OR]: 0.98 [95 % confidence interval (CI): 0.97–0.996]) and elevated tricuspid regurgitation pressure (TRPG) at baseline (OR: 1.04 [95 % CI: 1.00 – 1.08]) were significantly related to the increase in LAVI at 6-month follow-up. In addition, a 5 ml/m2 increase in LAVI was significantly associated with subsequent heart failure hospitalization (HFH) (hazard ratio: 3.37 [95 % CI: 1.18–9.65]). This association, however, was not observed in patients with lower baseline LAVI (≤55 ml/m2) but was only seen in those with a baseline LAVI over 55 ml/m2. Conclusion: Our study demonstrated an increase in LAVI after LAAC was related to smaller LAVI or elevated TRPG at baseline. The LAVI increase was significantly associated with subsequent HFH.

Study Design This study adopted a retrospective cohort study design. Purpose This study aimed to clarify the influence of diffuse idiopathic skeletal hyperostosis (DISH) on bone fusion after transforaminal lumbar interbody fusion (TLIF). Overview of Literature The negative effects of DISH on lumbar degenerative diseases have been reported, and DISH may be involved in the onset and severity of lumbar spinal canal stenosis. Patients with DISH have significantly more reoperations after posterior lumbar fusion, including TLIF. However, the effects of DISH on bone fusion after TLIF have not been reported. Methods The medical records of patients with intervertebral TLIF from 2012 to 2018 were retrospectively examined. The patients were divided into those with fusion and those with pseudoarthrosis, and the following data were compared: age, sex, DISH, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation. Statistical analyses were performed using regression models. Results In this study, 180 patients (78.6%) had fusion and 49 patients (21.4%) had pseudoarthrosis. The number of patients with DISH was significantly higher in the pseudoarthrosis group than in the fusion group (36.7% and 21.7%, respectively; univariate p=0.031, multivariate p=0.019). No significant differences in age, sex, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation were observed between the two groups. The risk factors for bone fusion were statistically analyzed in 57 patients with DISH. DISH with a caudal end below Th11 was an independent risk factor for pseudoarthrosis (univariate p=0.011, multivariate p=0.033). Conclusions DISH is an independent risk factor for pseudoarthrosis after one intervertebral TLIF, and DISH with a caudal end below Th11 is associated with a higher risk of pseudoarthrosis than DISH without a caudal end below Th11.

Abstract Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p

Biologics targeting the molecules associated with type 2 inflammation have significantly improved the outcomes of patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Chronic eosinophilic airway/lung diseases including chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic bronchitis, and eosinophilic granulomatosis with polyangiitis share clinical features with eosinophilic asthma and CRPwNP, which are mostly adult-onset and may develop simultaneously or consecutively. These eosinophilic airway/lung diseases respond well to initial treatment with systemic corticosteroids, but often recur when the corticosteroids are tapered. The management of these “refractory” cases is an unmet need for clinicians. We first reviewed the standard treatments for these chronic eosinophilic airway/lung diseases, followed by the definition and prevalence of refractory diseases and the role of biologics in their management. The available evidence varies from case reports and case series to randomized control trials, depending on the type of disease; however, these studies provide not only a direction for clinical practice, but also insights into the pathophysiology of each disease. Physicians should discuss the efficacy and costs of biologics in patients with refractory eosinophilic airway/lung diseases to minimize not only the current symptoms, but future risks as well.

IntroductionCerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, “total SVD score” – which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia– and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke.Methods and designThis prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0–4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan–Meier method.ResultsConsecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0–83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33–64.23; HR 2.81, 95% CI 1.08–7.30; HR 2.90, 95% CI 1.22–6.88, respectively).ConclusionThe accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Background: Measurement of allergen-specific IgE antibodies to inhaled allergens is important for the diagnosis and risk evaluation of allergic diseases such as asthma and allergic rhinitis. This study aimed to elucidate the prevalence of allergen sensitization among the healthy population in Japan using serum samples stocked in the Japanese Red Cross for blood donation. Methods: Age- and gender-stratified serum samples (n = 800) from residents in Tokyo aged 20–59 years were randomly selected from the stocked serum obtained for blood donation in 2005. Total and specific IgE antibodies to 17 inhaled allergens were measured by the ImmunoCAP method. Individuals with positive (≥0.35 UA/mL) specific IgE antibodies to at least one inhaled allergen were defined as atopic. Stocked serums from donors aged 20–29 years in Sapporo, Osaka, Fukuoka, and Okinawa (n = 200 each) were also obtained for the measurement of IgE to six common inhaled allergens, to evaluate regional differences in the rate of positivity. Results: Among residents in Tokyo, the prevalence of atopy was 78.0% and highest in men aged 20–29 years (94.0%), which decreased with age. The prevalence of specific IgE antibodies was highest for Japanese cedar pollen (66.8%), followed by cypress pollen (46.8%), Dermatophagoides pteronyssinus (38.3%), and moths (30.1%). Examination of IgE to Japanese cedar pollen, D. pteronyssinus, and moths identified 97.6% of atopic subjects in Tokyo. There were substantial regional differences in the prevalence of pollen IgE positivity. Conclusions: This study demonstrated an extremely high prevalence of positivity in inhaled allergen-specific IgE antibodies among healthy adults in Japan.

There are a few reports on the treatment of nonunited tibial anterior cruciate ligament (ACL) avulsion fractures. To our knowledge, this is the first report of a case of nonunited tibial ACL avulsion fracture 30 years after injury. A 36-year-old woman injured her knee during a road traffic accident 30 years ago. Since then, she had persistent knee instability that was left untreated. She presented to our clinic because of knee pain she had been experiencing for a week. Radiography and computed tomography revealed tibial ACL avulsion fracture nonunions. Screw fixation with arthroscopy was performed, and bone fusion was obtained. The knee injury and osteoarthritis outcome score improved from 24 points preoperatively to 83 points postoperatively. The nonunion of intercondylar eminence fractures of the tibia, even up to 30 years after the initial injury, can be treated by osteosynthesis with arthroscopy.

Objectives To analyse the clinical characteristics and prognosis of acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema.Design A multicentre retrospective cohort studySetting Two university hospitals in JapanParticipants Patients admitted to hospitals due to AE of IPF diagnosed based on a multidisciplinary discussion.Interventions NonePrimary and secondary outcome measures 90-day mortality rateMethods We retrospectively analysed consecutive patients with AE of IPF, with or without pulmonary emphysema, admitted to two university hospitals between 2007 and 2018.Results Among 62 patients (median age, 75 years; 48 men) admitted for AE of IPF, 29 patients (46%) presented with concomitant pulmonary emphysema. There was no significant difference in the arterial partial oxygen pressure/fraction of inhaled oxygen (P/F) ratio or other laboratory and radiographic data between patients with and without emphysema. The 90-day mortality rate was significantly lower in patients with emphysema than in those with IPF alone (23% vs 52%, p=0.03). The median survival time was significantly longer in patients with emphysema than in those with IPF alone (405 vs 242 days, p=0.02).Conclusion Patients with IPF and emphysema had better short-term survival after AE than those with non-emphysematous IPF.

Abstract Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia–reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia–reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography–mass spectrometry to identify ischemia–reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia–reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia–reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia–reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia–reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia–reperfusion injury.

Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0–4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m2), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11–2.39) at category G4 (eGFR 15–

Objective: To describe the detailed clinical course of patients with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Methods: We conducted a case series of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan, between January 29 and May 28, 2020. We describe the patient characteristics and clinical course from onset. Additionally, we fitted logistic regression models to investigate the associations between patient characteristics and the 30-day mortality rate. Results: A total of 125 patients who received invasive mechanical ventilation (median age [interquartile range], 68 [57–73] years; male, 77.6%) were enrolled. Overall, the 30-day mortality was 24.0%, and the median (interquartile range) length of ICU stay and length of invasive mechanical ventilation use were 16 (12–29) days and 13 (9–26) days, respectively. From clinical onset, 121 patients (96.8%) were intubated within 14 days. In multivariable logistic regression analysis, age of 65 years or older (odds ratio, 3.56; 95% confidence interval, 1.21–10.49; P = 0.02) and male sex (odds ratio, 3.75; 95% confidence interval, 1.00–11.24, P = 0.04) were significantly associated with a higher 30-day mortality rate. Conclusions: In this case series of patients with COVID-19 who received invasive mechanical ventilation in Japan, the 30-day mortality rate was 24.0%, and age 65 years or older and male sex were associated with higher 30-day mortality rate.

Abstract Background Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. Methods From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. Results There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. Conclusions Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate determining step for NAD+ synthesis and is of interest as a drug target. Here the authors identify and characterize a small molecule NAMPT activator SBI-797812, elucidate its mode of action and show that it increases intracellular NMN and NAD+ levels in cultured cells and elevates liver NAD+ in mice.

Background: The extracellular volume (ECV) calculated by T1 mapping, and tissue-tracking strain using cardiac magnetic resonance (CMR) are useful for assessing the left ventricular (LV) function. However, those parameters are controversial for assessing left atrial (LA) function. This study aimed to investigate the usefulness of CMR to evaluate the LA function using those parameters. Furthermore, those LA function parameters were compared in each LV function. Methods: A total of 65 consecutive patients who underwent contrast CMR were prospectively enrolled (age 55.7 ± 14. 6 years, males 67.7%). Among the 65 patients, there were 15 without hypertension, diabetes, or atrial fibrillation (Healthy group). The remaining 50 patients were divided into two groups according to a left ventricular ejection fraction (LVEF) of 50%. We assessed the correlations between the LV- and LA-CMR parameters among the three groups (LVEF

Abstract Background Although frailty and cognitive impairment are critical risk factors for disability and mortality in the general population of older inhabitants, the prevalence and incidence of these factors in individuals treated in the specialty outpatient clinics are unknown. Methods We recently established a frailty clinic for comprehensive assessments of conditions such as frailty, sarcopenia, and cognition, and planned 3-year prospective observational study to identify the risk factors for progression of these aging-related statuses. To date, we recruited 323 patients who revealed symptoms suggestive of frailty mainly from a specialty outpatient clinic of cardiology and diabetes. Frailty status was diagnosed by the modified Cardiovascular Health Study (mCHS) criteria and some other scales. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Japanese version of the Montreal Cognitive Assessment (MoCA-J), and some other modalities. Sarcopenia was defined by the criteria of the Asian Working Group for Sarcopenia (AWGS). In this report, we outlined our frailty clinic and analyzed the background characteristics of the subjects. Results Most patients reported hypertension (78%), diabetes mellitus (57%), or dyslipidemia (63%), and cardiovascular disease and probable heart failure also had a higher prevalence. The prevalence of frailty diagnosed according to the mCHS criteria, cognitive impairment defined by MMSE (≤27) and MoCA-J (≤25), and of AWGS-defined sarcopenia were 24, 41, and 84, and 31%, respectively. The prevalence of frailty and cognitive impairment increased with aging, whereas the increase in sarcopenia prevalence plateaued after the age of 80 years. No significant differences were observed in the prevalence of frailty, cognitive impairment, and sarcopenia between the groups with and without diabetes mellitus, hypertension, or dyslipidemia with a few exceptions, presumably due to the high-risk subjects who had multiple cardiovascular comorbidities. A majority of the frail and sarcopenic patients revealed cognitive impairment, whereas the frequency of suspected dementia among these patients were both approximately 20%. Conclusions We found a high prevalence of frailty, cognitive impairment, and sarcopenia in patients with cardiometabolic disease in our frailty clinic. Comprehensive assessment of the high-risk patients could be useful to identify the risk factors for progression of frailty and cognitive decline.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. Methods: In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. Results: Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44–68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (

Abstracts: Background: Several serological tests for specific precipitin or IgG are available to demonstrate type III hypersensitivity reactions to Aspergillus species and are essential for infectious fungal disease diagnosis. These assays are also important for allergic bronchopulmonary aspergillosis (ABPA) diagnosis; however, their concordance in ABPA was not well studied. Methods: Fifty-two ABPA patients diagnosed based on ISHAM criteria were enrolled. Precipitins and IgG specific to Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, or Aspergillus terreus were measured using Ouchterlony double immunodiffusion tests and ImmunoCAP method, respectively. A. fumigatus-specific IgG was also determined using complement-fixation (CF) method. Results: Forty-eight percent of cases were double-positive for A. fumigatus-specific precipitin and IgG (ImmunoCAP), whereas 3 (6%) and 14 (28%) cases were positive for precipitin or IgG alone, respectively. Kappa coefficient between these measurements was 0.32, suggesting poor concordance. Double-positive cases were more likely to present: Aspergillus sp. in sputum culture, lower pulmonary functions, peripheral blood eosinophilia, higher total IgE and A. fumigatus-specific IgG titer than precipitin-negative cases. A. fumigatus-specific IgG (CF) was positive only in 8 (15%) cases. The presence of A. fumigatus-specific precipitin or IgG was associated with antibodies specific for other Aspergillus spp., suggesting cross-reactivity. Conclusions: Positive rate of A. fumigatus-specific precipitin or IgG (ImmunoCAP) was superior to IgG (CF), but relatively poor concordance was noted between precipitin and IgG (ImmunoCAP). Positive precipitin for A. fumigatus suggests more active diseases. Cross-reactivity may exist between antibodies to different Aspergillus spp. Therefore, the type III hypersensitivity results in ABPA diagnosis should be carefully evaluated. Keywords: ABPA, Aspergillus fumigatus, concordance, IgG, precipitin

The pharmacological effects of rivoglitazone, a novel thiazolidinedione-derivative peroxisome proliferator–activated receptor (PPAR)-γ agonist, were characterized in vitro and in vivo. Rivoglitazone activated human PPARγ more potently compared with rosiglitazone and pioglitazone and had little effect on PPARα and PPARδ activity in luciferase reporter assays. In Zucker diabetic fatty (ZDF) rats, 14-day administration of rivoglitazone decreased the plasma glucose and triglyceride (TG) levels in a dose-dependent manner. The glucose-lowering effect of rivoglitazone was much more potent than those of pioglitazone (ED50: 0.19 vs. 34 mg/kg) and rosiglitazone (ED50: 0.20 vs. 28 mg/kg). In addition, rivoglitazone showed potent antidiabetic effects in diabetic db/db mice. In Zucker fatty rats, rivoglitazone at a dose of 0.1 mg/kg clearly ameliorated insulin resistance and lowered plasma TG levels by accelerating the clearance of plasma TG. Gene expression analysis in the liver and heart of ZDF rats treated with rivoglitazone for 14 days suggested that rivoglitazone may reduce hepatic glucose production and modulate the balance of the cardiac glucose/fatty acid metabolism in diabetic animals. In summary, we showed that rivoglitazone is a potent and selective PPARγ agonist and has a potent glucose-lowering effect via improvement of the insulin resistance in diabetic animal models. Keywords:: thiazolidinedione, peroxisome proliferator–activated receptor (PPAR)-γ, diabetes mellitus, insulin resistance, gene expression