Evaluation of point-of-care thumb-size bispectral electroencephalography device to quantify delirium severity and predict mortality.

BACKGROUND: We have developed the bispectral electroencephalography (BSEEG) method for detection of delirium and prediction of poor outcomes. AIMS: To improve the BSEEG method by introducing a new EEG device. METHOD: In a prospective cohort study, EEG data were obtained and BSEEG scores were calculated. BSEEG scores were filtered on the basis of standard deviation (s.d.) values to exclude signals with high noise. Both non-filtered and s.d.-filtered BSEEG scores were analysed. BSEEG scores were compared with the results of three delirium screening scales: the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS) and the Delirium Observation Screening Scale (DOSS). Additionally, the 365-day mortalities and the length of stay (LOS) in the hospital were analysed. RESULTS: We enrolled 279 elderly participants and obtained 620 BSEEG recordings; 142 participants were categorised as BSEEG-positive, reflecting slower EEG activity. BSEEG scores were higher in the CAM-ICU-positive group than in the CAM-ICU-negative group. There were significant correlations between BSEEG scores and scores on the DRS and the DOSS. The mortality rate of the BSEEG-positive group was significantly higher than that of the BSEEG-negative group. The LOS of the BSEEG-positive group was longer compared with that of the BSEEG-negative group. BSEEG scores after s.d. filtering showed stronger correlations with delirium screening scores and more significant prediction of mortality. CONCLUSIONS: We confirmed the usefulness of the BSEEG method for detection of delirium and of delirium severity, and prediction of patient outcomes with a new EEG device.

[Surgical Outcome of Sublobar Resection in High-risk Patients with Non-small Cell Lung Cancer].

OBJECTIVES: Pulmonary lobectomy is the standard surgical procedure for resectable non-small cell lung cancer (NSCLC), while sublobar resection is an important surgical alternative for high-risk patients with comorbidities. We evaluated the treatment outcome and prognostic factors of sublobar resection in high-risk patients with NSCLC. METHODS: Eighty three high-risk patients who underwent compromised sublobar resection for clinical-N0 NSCLC with a solid appearance were retrospectively reviewed. A total of 47 wedge resections and 36 segmentectomies performed. RESULTS: Poor pulmonary function and synchronous or metachronous multiple lung cancer were found in 56.7% and 20.5% of patients respectively, all requiring sublobar resection. There were 21 instances of tumor recurrence and 24 deaths during a mean follow-up of 1,500 days. There was no local recurrence in the segmentectomy group. The 3-year recurrence free survival (RFS) and overall survival (OS) were 72.6% and 73.8% respectively. A multivariate analysis indicated that resection type and lymphatic invasion were independent prognostic factors for RFS. In the wedge resection group, a ratio of surgical margin to clinical tumor size greater than 1 (MT ratio≥1) was an independent prognostic factor for RFS( 87.1%,p=0.001). CONCLUSION: Segmentectomy leads to a favorable prognosis. MT ratio was independently associated with a longer RFS in the wedge resection group.

Association between social functioning and prefrontal cortex function during a verbal fluency task in schizophrenia: A near-infrared spectroscopic study.

AIM: Impaired social functioning is a common characteristic of patients with schizophrenia. Social functioning requires the complex operation of various executive functions. Deficits in the prefrontal cortex (PFC) have been implicated in executive dysfunction. Here we aimed to clarify the relation between subjectively and objectively assessed social functioning, and their associations with PFC function in patients with schizophrenia. METHODS: Twenty-three patients and 22 age- and sex-matched healthy controls (HC) were assessed. In the schizophrenia group, self- and caregiver-rated social functioning were measured using the Specific Level of Functioning Assessment (SLOF). The hemodynamic responses elicited by a verbal fluency task (VFT) in three regions of interest in the frontotemporal area were measured using multi-channel near-infrared spectroscopy (NIRS). We also investigated psychiatric symptoms, neurocognition, and cognitive insight to assess possible confounding factors. RESULTS: Significant positive correlations were found between self- and caregiver-rated SLOF composite scores and three subdomain scores. Self- and caregiver-rated SLOF composite scores were significantly associated with dorsolateral PFC and frontopolar cortex (DLPFC/FPC) activation during the VFT. Psychiatric symptoms, global functioning, neurocognition, and cognitive insight were not associated with NIRS signals. General psychopathology was associated with NIRS signals in the ventrolateral PFC and the anterior temporal cortex. DLPFC and FPC activity may be associated with social functioning in patients with schizophrenia. CONCLUSION: Our results suggest that the two distinct assessments of social functioning were significantly correlated. Moreover, DLPFC and FPC function was strongly associated with social functioning and the ability to carry out daily life in patients with schizophrenia.

Facial expression perception correlates with verbal working memory function in schizophrenia.

AIMS: Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. METHODS: Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. RESULTS: Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. CONCLUSIONS: These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia.

Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in elderly depressed patients.

AIM: This study investigated whether or not and how much milnacipran influences the indexes of I-metaiodobenzylguanidine (I-MIBG) scintigraphy, early heart-to-mediastinum (H/M) ratio, delayed H/M ratio, and wash-out rate. METHODS: Six elderly depressed patients participated in the study. All six patients met the diagnostic criteria for a major depressive disorder. They were taking milnacipran for their depression. They needed differential diagnosis for Lewy body diseases due to their symptomatology. I-MIBG scintigraphy was performed twice for each subject, once under prescription of milnacipran and the other without prescription of milnacipran. RESULTS: Both early and delayed phase H/M ratio were significantly lower when taking milnacipran (early phase H/M ratio, P < 0.01, Cohen's d 1.62; delayed phase H/M ratio, P < 0.005, Cohen's d 1.98) than when not taking the drug. Wash-out rate (%) was significantly higher when taking milnacipran (P < 0.05, Cohen's d 2.31) than when off the drug. CONCLUSION: Taking milnacipran substantially influences the indexes of I-MIBG scintigraphy, indicating that taking the drug possibly causes a false-positive result for Lewy body diseases diagnosis.

New instrument for measuring multiple domains of social cognition: construct validity of the Social Cognition Screening Questionnaire (Japanese version).

AIM: The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ) (Japanese version). METHODS: We first tested whether the subscale scores and the total score of the SCSQ could discriminate patients with schizophrenia from normal controls. Next, we tested the internal consistency. Finally, we investigated the relation between the subscale scores and other measures of social cognition and social functioning that were presumed to correspond to the subscale's scores, including the Hinting Task, the Ambiguous Intentions Hostility Questionnaire (AIHQ), the Beck Cognitive Insight Scale and the Social Functioning Scale. RESULTS: The subscale scores and the total score appeared to show more robust between-group differences than other measures of social cognition, such as the AIHQ and the Hinting Task. The total score distinguished the patients from normal controls with an area under the receiver-operator curve of 0.84, which indicated a high level of discrimination. The Cronbach's alpha for the four subscales was 0.72, which was considered acceptable. In terms of criterion-related validity, theory of mind, metacognition and hostility bias subscale scores showed significant correlations with the Hinting Task, Beck Cognitive Insight Scale and AIHQ, respectively. Moreover, the theory of mind subscale score showed a significant correlation with four domain scores of the Social Functioning Scale. The present results indicated good construct validity and internal consistency of the SCSQ. CONCLUSIONS: Although this is an interim report with a small sample size, the SCSQ holds promise as an efficient measure for social cognition.

[Tumors of the diaphragm, diagnosis and surgical treatment].

Primary tumors of the diaphragm are very rare, and we often have difficulties in preoperative diagnosis and accurate evaluation of invasion. We experienced 3 surgical cases of tumor of diaphragm:primary mucinous adenocarcinoma, metastatic gastrointestinal stromal tumor, and mesothelioma. Besides computed tomography (CT) and conventional magnetic resonance imaging(MRI), respiratory dynamic cine magnetic resonance imaging (cine MRI) was performed. Cine MRI was acquired using steady state free precession (SSFP) sequence, and about 80 consecutive images of the same slice were taken while a patient breathed deeply. In all cases, cine MRI showed lack of tumor movement along the diaphragm during respiration. During surgery, we found that tumor was originated from diaphragm and there was no adhesion to other organs. Securing a sufficient margin, we resected tumor including the diaphragm. Since the defect of diaphragm was from 4 to 5cm in short diameter, we could close the diaphragm by direct suture. Cine MRI could provide useful information concerning discrimination between diaphragmatic and para-diaphragmatic tumor.

Report from the Committee for Improving the Work Environment of Japanese Surgeons: survey on effects of the fee revision for medical services provided by surgeons.

PURPOSE: The aim of this study was to achieve improvements in the work environment of Japanese surgeons and shortage of surgeons. METHODS: Questionnaires were distributed to selected Japanese surgical Society (JSS) members. Retrospective analysis was conducted comparing the current 2011 survey with previous 2007 survey. To examine the influence of 2010 revision of the fee for medical services performed by surgeons, we distributed a second questionnaire to directors of hospitals and administrators of clerks belonging to official institutes in JSS. Collective data were analyzed retrospectively. RESULTS: The main potential causes for the shortage of surgeons in Japan were long hours (72.8 %), excessive emergency surgeries (69.4 %), and high risk of lawsuit (67.7 %). Mean weekly working hours of surgeons in national or public university hospitals and private university hospitals were 96.2 and 85.6, respectively. Approximately 70 % of surgeons were forced to do hardworking tasks, possibly leading to death from overwork. Of note, approximately 25 % of surgeons had over time of more than 100 h a week, coinciding to the number of hours that might lead to death from fatigue, described in the Japanese labor law. Although the total medical service fee in hospitals, especially in large-scale hospitals with more than 500 beds, increased markedly after 2010 revision of the fee for medical services performed by surgeons, few hospitals gave perquisites and/or incentives to surgeons. CONCLUSION: To prevent and avoid collapse of the surgical specialty in Japan, an improvement in the work environment of surgeons by initiation of the JSS would be required as soon as possible.

[Cognitive remediation].

Cognitive deficits are a core symptom of schizophrenia and marked in the sub-domains of cognition. They have been shown to predict whether a patient will be able to meet functional goals. Because of the small effect size of pharmacotherapy on cognitive function, cognitive remediation has gradually been introduced into the psychiatric rehabilitation. This non-pharmacological treatment for improving neurocognition aims to enhance the neurocognitive strategies relevant to their chosen recovery goals through engaging the participants in learning activities in a highly motivated way. Most meta-analytic studies on this new treatment report moderate effect sizes on cognition with the notable differences in their effects possibly due to their distinct practice methods. The impact of this treatment on daily functioning, however, has been found to be smaller than that on neurocognitive skills. It is thus suggested that cognitive remediation should be implemented in concert with other types of programs for psychiatric rehabilitation.

The pilot study of a Neuropsychological Educational Approach to Cognitive Remediation for patients with schizophrenia in Japan.

The main aim of this study is to demonstrate the feasibility and efficacy of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR) in Japan. This multi-site study used a quasi-experimental design. Fifty-one patients with schizophrenia or schizoaffective disorder participated. The NEAR program consisted of two 1-h computer sessions per week and an additional group meeting session lasting 30 to 60 min once a week. The subjects completed 6 months of NEAR sessions before being assessed. Moreover, taking into consideration the possible practice effect, we assessed 21 control patients twice with an interval of 6 months. We assessed cognitive function by using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J). Consequently, the NEAR group showed significant improvement in overall cognitive function, and in comparison with the control group, these findings were generally similar except for motor speed. Although the present study has its limitations, it demonstrates that the NEAR is feasible in Japan as well as it is in Western countries.

[Clinicopathologic analysis of small-sized non-small cell lung cancer].

We reviewed the data on 149 patients who underwent complete resection for small-sized (≤ 2 cm)peripheral non-small cell lung cancer at our institution between January 2002 and July 2010. Patients with small-sized lung cancer underwent a lobectomy in 121, segmentectomy in 13, and wedge resection in 15 cases. The overall and 5-year disease-free survivals were 89% and 82%, respectively. The 5-year disease-free survival of patients with tumors exceeding 1.5 cm was lower than that of patients with tumors 1.5 cm or smaller (p=0.01). The 5-year disease-free survival for patients without pleulal invasion was 87%, whereas it was 45% for those with pleulal invasion (p=0.004). The 5-year disease-free survival according to the serum level of carcinoembrionic antigen( CEA) were 82% for the normal group and 70% for the high group( p=0.007). Although the results were not significantly different, patients with tumors with high maximum standardized uptake value (SUV) on FDG-PET/CT showed a trend toward a lower 5-year disease-free survival rate( p=0.10). There were no recurrences in patients with ground-glass opacity (GGO) or GGO-dominant lesion including those who underwent sublober resection. Multivariate analysis showed that tumor size and pleural invasion were independent prognostic factors. Indication of sublober resection for solid-type small-sized non-small cell lung cancer (NSCLC) should be carefully determined considering tumor size, pleural involvement, serum carcinoembryonic antigen( CEA) level, and maximum SUV.

Clinical implication of HLA class I expression in breast cancer.

BACKGROUND: Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified. METHODS: A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed. RESULTS: The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval. CONCLUSION: The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.

Immediate breast reconstruction using autologous free dermal fat grafts provides better cosmetic results for patients with upper inner cancerous lesions.

PURPOSE: Although breast-conserving therapy (BCT) is the standard form of treatment for early-stage breast cancer, in patients with small breasts cosmetic results can be poor, especially when the lesion is located on the inner upper quadrant area. This study analyzes our use of autologous free dermal fat grafts (FDFGs) for immediate breast reconstruction. METHODS: A total of 23 patients who received a partial mastectomy for an inner upper quadrant lesion from 1992 to 2006 at Kagoshima University Hospital were retrospectively divided into three groups according to the reconstructive procedure that was used for the defect after partial mastectomy: immediate reconstruction using an autologous FDFG from the lower abdomen (group FDFG); patients receiving only rotation and fixation of the parenchymal adipose tissue or gland to repair the defect (group GL); and a third group who underwent immediate reconstruction using a miniflap of the latissimus dorsi (group LD). RESULTS: The total duration of surgery in group FDFG was significantly shorter than in group LD (P < 0.01). The mean volume of blood lost in group FDFG was significantly lower than in group LD (P < 0.01). The breast retraction assessment (BRA) of group FDFG was significantly better than for the patients in groups GL and LD (P < 0.01). The total score using the ABNSW system for cosmetic assessment was significantly better in group FDFG than in group GL (P < 0.01). Similarly, the total score in group FDFG using the assessment by the Japanese Breast Cancer Society was significantly higher than that in group GL (P < 0.01). CONCLUSION: Immediate breast reconstruction for a defect after a partial mastectomy of an upper inner quadrant malignant lesion using FDFG can be especially useful for patients with small breasts.

[Outcome studies of cognitive remediation for schizophrenia].

Cognitive remediation purports to improve the cognitive dysfunction of schizophrenia, and has many forms. Eighty percent of people with schizophrenia suffer from cognitive dysfunction. The impact of cognitive dysfunction on everyday activity is widespread. Cognitive remediation as a non-pharmaceutical, psychosocial treatment modality for cognitive dysfunction has received attention as medical treatment has been able to make only limited gains. The ultimate goal of cognitive remediation is to improve the functional outcome. The increased interest in cognitive remediation resulted in numerous reports of outcome studies and meta-analysis. This paper reports different methods of cognitive remediation, evaluations of outcome studies, and various outcome indices. Cognitive remediation differs according to whether specific cognitions are targeted, and whether a method takes a compensatory or restorative approach. This paper briefly reviews methods of cognitive remediation which demonstrated their effect through RCT: IPT, NEAR, CET, and NET. Cognitive remediation often includes sessions that aim for transfer of the gained learning, such as verbal sessions or vocational skills training. Cognitive remediation is considered most effective when included as part of a comprehensive rehabilitation program. It is important to note that various studies report different outcome indices, control groups, and effect sizes in evaluating the effect of cognitive remediation.

Case Report: GABAergic and Serotoninergic Agents for the Treatment and Prevention of Prolonged Dissociative Stupor.

Dissociative stupor is a common psychiatric disease lacking an established standard treatment. The lack of therapeutic options may be due to the spontaneous and quick complete remission of most patients. However, since some patients experience multiple relapses and prolonged stupor, investigating potential prevention and treatment options is critical. We reported the case of a 61-year-old Japanese woman who presented with intermittent dissociative stupor for several months. Despite her prolonged symptoms, the administration of lorazepam, escitalopram, and aripiprazole, which selectively enhance GABAergic and serotoninergic activity, improved her stupor and prevented relapse. These findings may help with the treatment of persistent dissociative stupor.

New Cutoff Scores for Delirium Screening Tools to Predict Patient Mortality.

BACKGROUND/OBJECTIVES: Detecting delirium is important to identify patients with a high risk of poor outcomes. Although many different kinds of screening instruments for delirium exist, there is no solid consensus about which methods are the most effective. In addition, it is important to find the most useful tools in predicting outcomes such as mortality. DESIGN: Retrospective cohort study. SETTING: University of Iowa Hospitals and Clinics. PARTICIPANTS: A total of 1,125 adult inpatients (mean age = 67.7; median age = 69). MEASUREMENTS: Post hoc analyses were performed based on existing data from the Confusion Assessment Method for Intensive Care Unit (CAM-ICU), Delirium Rating Scale-Revised-98 (DRS), and the Delirium Observation Screening Scale (DOSS). Correlation among these scales and relationships between 365-day mortality and each scale were evaluated. RESULTS: A positive result on the CAM-ICU ("CAM-ICU positive") was associated with higher DRS and DOSS scores. A DRS score = 9/10 was the best cutoff to detect CAM-ICU positive, and DOSS = 2/3 was the best cutoff to detect CAM-ICU positive. CAM-ICU positive was associated with high 365-day mortality. DRS score = 9/10 and DOSS score = 0/1 were found to differentiate mortality risk the most significantly. Higher DRS and DOSS scores significantly coincided with a decrease in a patient's survival rate at 365 days. CONCLUSION: The best DRS and DOSS cutoff scores to differentiate 365-day mortality risk were lower than those commonly used to detect delirium in the literature. New cutoff scores for the DRS and DOSS might be useful in differentiating risk of mortality among hospital patients.

Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model.

AIM: This study aimed to assess the response of endogenous beta-hydroxybutyrate to psychological stress, and its association with nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome, and stress-induced behavior. METHODS: Male C57BL/6J mice were subjected to 1-hour restraint stress to examine changes in the endogenous beta-hydroxybutyrate and active NLRP3 levels in the prefrontal cortex. Subsequently, we created a depression model applying 10-day social defeat stress to the male C57BL/6J mice. RESULTS: One-hour restraint stress rapidly increased beta-hydroxybutyrate levels in the blood. The active NLRP3 levels in the prefrontal cortex also increased significantly. A correlation was found between the increased beta-hydroxybutyrate levels in the blood and the active NLRP3 levels in the prefrontal cortex. The mice exposed to social defeat stress exhibited depression- and anxiety-like behavioral changes in the open field, social interaction, and forced swim tests. There was a correlation between these behavioral changes and endogenous beta-hydroxybutyrate levels. Among the social defeat model mice, those with high beta-hydroxybutyrate levels tended to have more depression- and anxiety-like behavior. CONCLUSIONS: The increased blood beta-hydroxybutyrate levels due to psychological stress correlate with the active NLRP3 levels in the prefrontal cortex, suggesting that the increased beta-hydroxybutyrate levels due to stress may reflect a reaction to brain inflammation. In addition, mice with higher blood beta-hydroxybutyrate levels tend to exhibit increased depression- and anxiety-like behaviors; thus, an increase in blood beta-hydroxybutyrate levels due to stress may indicate stress vulnerability.

Bispectral EEG (BSEEG) quantifying neuro-inflammation in mice induced by systemic inflammation: A potential mouse model of delirium.

Most of the animal studies using inflammation-induced cognitive change have relied on behavioral testing without objective and biologically solid methods to quantify the severity of cognitive disturbances. We have developed a bispectral EEG (BSEEG) method using a novel algorithm in clinical study. This method effectively differentiates between patients with and without delirium, and predict long-term mortality. In the present study, we aimed to apply our bispectral EEG (BSEEG) method, which can detect patients with delirium, to a mouse model of delirium with systemic inflammation induced by lipopolysaccharides (LPS) injection. We recorded EEG after LPS injection using wildtype early adulthood mice (2~3-month-old) and aged mice (18-19-month-old). Animal EEG recordings were converted for power spectral density to calculate BSEEG score using the similar BSEEG algorithm previously developed for our human study. The BSEEG score was relatively stable and slightly high during the day. Alternatively, the BSEEG score was erratic and low in average during the night. LPS injection increased the BSEEG score dose-dependently and diminished the diurnal changes. The mean BSEEG score increased much more in the aged mice group as dosage increased. Our results suggest that BSEEG method can objectively "quantify" level of neuro-Inflammation induced by systemic inflammation (LPS), and that this BSEEG method can be useful as a model of delirium in mice.