Lung volume measurement using chest CT in COVID-19 patients: a cohort study in Japan.

OBJECTIVE: This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. METHODS: This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. RESULTS: The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. CONCLUSION: Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.

CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome.

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st-4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

Integrated assessment of computed tomography density in pectoralis and erector spinae muscles as a prognostic biomarker for coronavirus disease 2019.

BACKGROUND ＆ AIMS: Muscle quantification using chest computed tomography (CT) is a useful prognostic biomarker for coronavirus disease 2019 (COVID-19). However, no studies have evaluated the clinical course through comprehensive assessment of the pectoralis and erector spinae muscles. Therefore, we compared the impact of the areas and densities of these muscles on COVID-19 infection outcome. METHODS: This multicenter retrospective cohort study was conducted by the COVID-19 Task Force. A total of 1410 patients with COVID-19 were included, and data on the area and density of the pectoralis and erector spinae muscles on chest CT were collected. The impact of each muscle parameter on the clinical outcome of COVID-19 was stratified according to sex. The primary outcome was the percentage of patients with severe disease, including those requiring oxygen supplementation and those who died. Additionally, 167 patients were followed up for changes in muscle parameters at three months and for the clinical characteristics in case of reduced CT density. RESULTS: For both muscles, low density rather than muscle area was associated with COVID-19 severity. Regardless of sex, lower erector spinae muscle density was associated with more severe disease than pectoralis muscle density. The muscles were divided into two groups using the receiver operating characteristic curve of CT density, and the population was classified into four (Group A: high CT density for both muscles, Group B: low CT density for pectoralis and high for erector spinae muscle. Group C: high CT density for pectoralis and low for erector spinae muscle, Group D: low CT density for both muscles). In univariate analysis, Group D patients exhibited worse outcomes than Group A (OR: 2.96, 95% CI: 2.03-4.34 in men; OR: 3.02, 95% CI: 2.66-10.4 in women). Multivariate analysis revealed that men in Group D had a significantly more severe prognosis than those in Group A (OR: 1.82, 95% CI: 1.16-2.87). Moreover, Group D patients tended to have the highest incidence of other complications due to secondary infections and acute kidney injury during the clinical course. Longitudinal analysis of both muscle densities over three months revealed that patients with decreased muscle density over time were more likely to have severe cases than those who did not. CONCLUSIONS: Muscle density, rather than muscle area, predicts the clinical outcomes of COVID-19. Integrated assessment of pectoralis and erector spinae muscle densities demonstrated higher accuracy in predicting the clinical course of COVID-19 than individual assessments.

Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

Epicardial adipose tissue measured from analysis of adipose tissue area using chest CT imaging is the best potential predictor of COVID-19 severity.

BACKGROUND: Computed tomography (CT) imaging is widely used for diagnosing and determining the severity of coronavirus disease 2019 (COVID-19). Chest CT imaging can be used to calculate the epicardial adipose tissue (EAT) and upper abdominal visceral adipose tissue (Abd-VAT) areas. The EAT is the main source of inflammatory cytokines involved in chest inflammatory diseases; thus, the EAT area might be a more useful severity predictor than the Abd-VAT area for COVID-19. However, to the best of our knowledge, there are no large-scale reports that sufficiently consider this issue. In addition, there are no reports on the characteristics of patients with normal body mass index (BMI) and high adipose tissue. AIM: The purpose of this study was to analyze whether the EAT area, among various adipose tissues, was the most associated factor with COVID-19 severity. Using a multicenter COVID-19 patient database, we analyzed the associations of chest subcutaneous, chest visceral, abdominal subcutaneous, and Abd-VAT areas with COVID-19 outcomes. In addition, the clinical significance of central obesity, commonly disregarded by BMI, was examined. METHODS: This retrospective cohort study evaluated patients with COVID-19 aged ≥18 years In Japan. Data including from chest CT images collected between February 2020 and October 2022 in four hospitals of the Japan COVID-19 Task Force were analyzed. Patient characteristics and COVID-19 severity were compared according to the adipose tissue areas (chest and abdominal subcutaneous adipose tissue [Chest-SAT and Abd-SAT], EAT, and Abd-VAT) calculated from chest CT images. RESULTS: We included 1077 patients in the analysis. Patients with risk factors of severe COVID-19 such as old age, male sex, and comorbidities had significantly higher areas of EAT and Abd-VAT. High EAT area but not high Abd-VAT area was significantly associated with COVID-19 severity (adjusted odds ratio (aOR): 2.66, 95 % confidence interval [CI]: 1.19-5.93). There was no strong correlation between BMI and VAT. Patients with high VAT area accounted for 40.7 % of the non-obesity population (BMI < 25 kg/m2). High EAT area was also significantly associated with COVID-19 severity in the non-obesity population (aOR: 2.50, 95 % CI: 1.17-5.34). CONCLUSIONS: Our study indicated that VAT is significantly associated with COVID-19 severity and that EAT is the best potential predictor for risk stratification in COVID-19 among adipose tissue areas. Body composition assessment using EAT is an appropriate marker for identifying obesity patients overlooked by BMI. Considering the next pandemic of the global health crisis, our findings open new avenues for implementing appropriate body composition assessments based on CT imaging.

Clinical utilization of artificial intelligence-based COVID-19 pneumonia quantification using chest computed tomography - a multicenter retrospective cohort study in Japan.

BACKGROUND: Computed tomography (CT) imaging and artificial intelligence (AI)-based analyses have aided in the diagnosis and prediction of the severity of COVID-19. However, the potential of AI-based CT quantification of pneumonia in assessing patients with COVID-19 has not yet been fully explored. This study aimed to investigate the potential of AI-based CT quantification of COVID-19 pneumonia to predict the critical outcomes and clinical characteristics of patients with residual lung lesions. METHODS: This retrospective cohort study included 1,200 hospitalized patients with COVID-19 from four hospitals. The incidence of critical outcomes (requiring the support of high-flow oxygen or invasive mechanical ventilation or death) and complications during hospitalization (bacterial infection, renal failure, heart failure, thromboembolism, and liver dysfunction) was compared between the groups of pneumonia with high/low-percentage lung lesions, based on AI-based CT quantification. Additionally, 198 patients underwent CT scans 3 months after admission to analyze prognostic factors for residual lung lesions. RESULTS: The pneumonia group with a high percentage of lung lesions (N = 400) had a higher incidence of critical outcomes and complications during hospitalization than the low percentage group (N = 800). Multivariable analysis demonstrated that AI-based CT quantification of pneumonia was independently associated with critical outcomes (adjusted odds ratio [aOR] 10.5, 95% confidence interval [CI] 5.59-19.7), as well as with oxygen requirement (aOR 6.35, 95% CI 4.60-8.76), IMV requirement (aOR 7.73, 95% CI 2.52-23.7), and mortality rate (aOR 6.46, 95% CI 1.87-22.3). Among patients with follow-up CT scans (N = 198), the multivariable analysis revealed that the pneumonia group with a high percentage of lung lesions on admission (aOR 4.74, 95% CI 2.36-9.52), older age (aOR 2.53, 95% CI 1.16-5.51), female sex (aOR 2.41, 95% CI 1.13-5.11), and medical history of hypertension (aOR 2.22, 95% CI 1.09-4.50) independently predicted persistent residual lung lesions. CONCLUSIONS: AI-based CT quantification of pneumonia provides valuable information beyond qualitative evaluation by physicians, enabling the prediction of critical outcomes and residual lung lesions in patients with COVID-19.

Successfully treated bronchopulmonary oxalosis caused by Aspergillus tubingensis in a non-neutropenic patient: A case report and review of the literature.

Pulmonary oxalosis can be fatal, and Aspergillus tubingensis is commonly resistant to azoles in Japan. We report a case of bronchopulmonary oxalosis caused by A. tubingensis in a non-neutropenic patient who was successfully treated with voriconazole monotherapy. The susceptibility of the isolates to voriconazole and the effective elimination of contagious necrotic tissue by expectoration seemed to be two major factors contributing to the patient's survival. According to the literature review, pulmonary oxalosis is associated with a high mortality rate over a short term. An exploration of detailed information about the genomic characteristics and drug susceptibility of Aspergillus isolates is important for the development of treatment strategies for this life-threatening disease.

Liganded T3 receptor ß2 inhibits the positive feedback autoregulation of the gene for GATA2, a transcription factor critical for thyrotropin production.

The serum concentration of thyrotropin (thyroid stimulating hormone, TSH) is drastically reduced by small increase in the levels of thyroid hormones (T3 and its prohormone, T4); however, the mechanism underlying this relationship is unknown. TSH consists of the chorionic gonadotropin α (CGA) and the ß chain (TSHß). The expression of both peptides is induced by the transcription factor GATA2, a determinant of the thyrotroph and gonadotroph differentiation in the pituitary. We previously reported that the liganded T3 receptor (TR) inhibits transactivation activity of GATA2 via a tethering mechanism and proposed that this mechanism, but not binding of TR with a negative T3-responsive element, is the basis for the T3-dependent inhibition of the TSHß and CGA genes. Multiple GATA-responsive elements (GATA-REs) also exist within the GATA2 gene itself and mediate the positive feedback autoregulation of this gene. To elucidate the effect of T3 on this non-linear regulation, we fused the GATA-REs at -3.9 kb or +9.5 kb of the GATA2 gene with the chloramphenicol acetyltransferase reporter gene harbored in its 1S-promoter. These constructs were co-transfected with the expression plasmids for GATA2 and the pituitary specific TR, TRß2, into kidney-derived CV1 cells. We found that liganded TRß2 represses the GATA2-induced transactivation of these reporter genes. Multi-dimensional input function theory revealed that liganded TRß2 functions as a classical transcriptional repressor. Then, we investigated the effect of T3 on the endogenous expression of GATA2 protein and mRNA in the gonadotroph-derived LßT2 cells. In this cell line, T3 reduced GATA2 protein independently of the ubiquitin proteasome system. GATA2 mRNA was drastically suppressed by T3, the concentration of which corresponds to moderate hypothyroidism and euthyroidism. These results suggest that liganded TRß2 inhibits the positive feedback autoregulation of the GATA2 gene; moreover this mechanism plays an important role in the potent reduction of TSH production by T3.

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs). OBJECTIVE: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD. METHODS: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control). RESULTS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p < 0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both plasma (p < 0.01) and ELF (p < 0.05), while plasma sVE-cadherin levels were inversely correlated with the extent of emphysema (p < 0.05). MMP-7 levels were correlated with sE-cadherin levels in ELF. CONCLUSIONS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.

Plasma Cathepsin S and Cathepsin S/Cystatin C Ratios Are Potential Biomarkers for COPD.

Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD. Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction ("at risk"; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses. Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001). Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD.

Small Cell Lung Cancer Expressing Glutamate Decarboxylase with Latent Autoimmune Diabetes in Adults.

Small cell lung cancer (SCLC) causes paraneoplastic syndromes, such as diabetes mellitus, by eliciting the expression of various antibodies including anti-glutamate decarboxylase (GAD) antibody. A 62-year-old woman presented to our hospital with a 1-week history of progressive dyspnea and difficulty in walking. Computed tomography showed a tumor obstructing the left bronchus and obstructive lung abscesses with pleural effusions. A biopsy during bronchoscopy revealed SCLC, and the clinical stage was ultimately determined to be IIIB. SCLC was complicated by diabetes mellitus with high titers of serum anti-GAD antibody. An immunohistochemical analysis showed GAD expression in the cancer cells, which is a novel finding.

Plasma cytokine profiles related to smoking-sensitivity and phenotypes of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) develops only in smoking-sensitive smokers and manifests heterogeneous phenotypes, including emphysema and non-emphysema types. We aimed to identify biomarkers related to the smoking-sensitivity and phenotypes of COPD. Among 240 smokers suggestive of COPD, we studied on four groups defined by % forced expiratory volume in one second (FEV1) and computed tomography-based pulmonary emphysema. Plasma concentrations of 33 inflammatory markers were measured in four groups as well as Non-smokers using multiplex protein arrays. IL-5, IL-7 and IL-13 were identified to be associated with smoking sensitivity and IL-6 and IL-10 were candidate biomarkers for airway-lesion dominant COPD.

Analysis of comorbid factors that increase the COPD assessment test scores.

BACKGROUND: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. METHODS: An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients' reports, physicians' records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. RESULTS: The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. CONCLUSIONS: Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized. TRIAL REGISTRATION: Clinical trial registered with UMIN (UMIN000003470).

Anger is a distinctive feature of epilepsy patients with depression.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

The transgenic rat strain S284L-TG harbors the S284L mutant of the neuronal nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4), which is responsible for human autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). S284L-TG rats have epileptic seizure phenotypes during slow-wave sleep, similar to those in NFLE. We previously demonstrated that γ-aminobutyric acid (GABA)ergic action of these rats was suppressed before the onset of ADNFLE seizures, and that glutamate release in the epileptic focus lesion was increased at the onset of epilepsy. Here, mRNA analysis revealed that Cl(-)-accumulating Na-K-2Cl cotransporter 1 (NKCC1) levels were increased and Cl(-)-extruding K-Cl cotransporter 1 and 2 (KCC1 and KCC2) levels were decreased at the onset of ADNFLE seizures in S284L-TG rat frontal cortexes, which perturbed the GABAergic inhibitory system. The reversal potentials (EGABA) of GABAA receptor-mediated currents in cortical layer V pyramidal neurons of S284L-TG rats also changed their polarity from hyperpolarization to depolarization, and S284L-TG miniature excitatory postsynaptic currents (mEPSCs), but not miniature inhibitory postsynaptic currents (mIPSCs), significantly increased in both amplitude and frequency. Administration of 25mg/kg/day furosemide before, but not after, the onset of interictal discharges prevented idiopathic epileptic activity, reversed the depolarizing shift of EGABA and increased mEPSC amplitude to normal levels. These data indicate that early treatment with an agent that normalizes pathogenesis has a prophylactic effect on epilepsy. We propose a strategy for prophylactic medication against idiopathic epilepsy through the suppression of epileptogenesis and/or ictogenesis.

Association between the dopamine D2 receptor (DRD2) polymorphism and the personality traits of healthy Japanese participants.

BACKGROUND: Dopamine neurotransmitter systems have been associated with reward-related and novelty-seeking personality traits. We investigated the possible relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the TaqI A and -141C Ins/Del polymorphisms in the dopamine D2 receptor gene (DRD2). METHODS: The sample consisted of 1084 healthy Japanese medical students and medical staff (age=29.0±9.7 years), each of whom completed the TCI. Their genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between gene polymorphisms and the scores for TCI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting age. Males and females were analyzed separately. Epstatis was assesses using two-way ANCOVA between the DRD2 and ANKK1 genes. RESULTS: Men with the Ins/Del genotype of the -141C Ins/Del polymorphism had significantly higher self-directedness scores than those with the Ins/Ins genotype (p=0.021). None of the TCI scores differed among women with regard to the three genotype groups of the -141C Ins/Del polymorphism. The DRD2/ANKK1 Taq1 A polymorphism did not affect any TCI factor for either men or women. An epistatic analysis did not reveal main effects of the two genes with regard to TCI scores, but an ANKK1×DRD2 interaction significantly predicted TCI scores. CONCLUSION: These findings suggest the possibility that the -141C Ins/Del polymorphism and the DRD2/ANKK1 Taq1 A polymorphism are not strongly linked to personality traits directly, but influences them under the interaction between the DRD2 and ANKK1 genes.

[A case of advanced lung adenocarcinoma with cavity formation shrunken by bevacizumab added on the 3rd course of 6th-line chemotherapy].

A 65-year-old man was pointed out to have an abnormal lung shadow by chest radiograph in a medical examination in 2007. An extensive examination diagnosed him as a case of advanced lung adenocarcinoma. He was treated by chemotherapy up to the 5th-line(cisplatin+docetaxel→CPT-11+S-1→amrubicin→gemcitabine+vinorelbine→pemetrexed), and the evaluation after the 5th-line treatment revealed disease progression. As he still maintained good performance status, the 6th- line treatment with carboplatin(AUC6, day 1)+paclitaxe(l 200mg/m2, day 1)(Q3W)was administered in March, 2010. The tumor size had been increasing slightly after 2 courses of chemotherapy, although it was within the range of stable disease. Therefore, bevacizumab(15mg/kg, day 1)was added after the 3rd course of treatment, and the tumor began shrinking obviously with cavity formation. Although the positioning of bevacizumab has not been established after 2nd-line treatment for advanced non-small cell lung carcinoma, we experienced a case of good tumor response by adding the bevacizumab in the middle of the 6th-line chemotherapy.

Superoxide dismutase 2 Val16Ala polymorphism is a risk factor for the valproic acid-related elevation of serum aminotransferases.

The association between the superoxide dismutase 2 (SOD2) Val16Ala polymorphism and the serum aminotransferase levels was retrospectively investigated in 207 valproic acid-treated patients with epilepsy. The Val/Val genotype tended to show elevated alanine aminotransferase levels (odds ratio=3.5; P=0.056). In addition, an elevated γ-glutamyltransferase level was associated with the Val/Val genotype (odds ratio=3.1; P=0.022). The SOD2 Val/Val genotype may therefore contribute to a valproic acid-induced elevation in the serum aminotransferase levels.

[Personalized medicine for epilepsy based on the pharmacogenomic testing].

Currently a trial-and-error approach is employed to determine the most effective antiepileptic drug (AED) and dosage for a patient, and almost 30% of all patients are resistant to AED therapy. Introduction of personalized medicine for epilepsy based on pharmacogenomic testing is a new avenue for optimizing AED therapy. However, several crucial issues remain to be resolved before this initiative can be fully pursued. This article provides a critical review of the status and perspectives in the development of personalized medicine for epilepsy based on pharmacogenetic variations that may affect efficacy, tolerability, and safety of AEDs, such as variations in the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450), or drug transporters (e.g., MDR1, MRP2).