Computed tomography findings for predicting the future occurrence of pancreatic cancer: value of pancreatic volumetry.

BACKGROUND: The features of pancreatic parenchyma that tend to progress towards pancreatic cancer (PC) are unknown. We performed volumetry of the pancreas in PC patients using computed tomography (CT) scans acquired before detection of PC, and investigated whether CT findings of pancreatic parenchyma could predict the future occurrence of PC. METHODS: Between April 2009 and March 2017, a total of 3769 patients underwent abdominal contrast-enhanced CT, the scans of which were archived as digital images. Among them, 15 PC patients underwent abdominal CT 6-120 months before diagnosis of PC. This retrospective study compared the 15 PC patients (PC group) with 15 propensity score-matched subjects without PC (non-PC group). Pancreatic volumetry and radiological findings were compared between the two groups. RESULTS: There were significant differences between the PC and non-PC groups in the volume of the main pancreatic duct (MPD) plus any cystic lesion (P = 0.007), volume of the MPD plus any cystic lesion/body surface area (BSA; P = 0.009), MPD diameter (P = 0.011), and MPD diameter/BSA (P = 0.013). Univariate analysis revealed volume of MPD plus any cystic lesion/BSA ≥ 0.53 mL/m2 (odds ratio [OR] 38.50, P = 0.002), volume of pancreatic parenchyma/BSA < 27.0 mL/m2 (OR 12.25, P = 0.030), and MPD diameter/BSA ≥ 1.0 mm/m2 (OR 13.00, P = 0.006) as significant risk factors for PC. CONCLUSIONS: Quantification of the volume of MPD plus any cystic lesion/BSA, volume of pancreatic parenchyma/BSA, and MPD diameter/BSA on pre-diagnosis CT were useful for predicting the future occurrence of PC.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Diffusion-weighted MRI predicts the histologic response for neoadjuvant therapy in patients with pancreatic cancer: a prospective study (DIFFERENT trial).

PURPOSE: Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS: We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS: Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P < 0.001/< 0.0001). The post-treatment cutoff value of ADC at the site of vascular contact for discriminating histological response of tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.42 × 10-3 mm2/s. It predicts R0 with 88% sensitivity, 50% specificity, and 61% accuracy. For histological response, the post-treatment whole-tumor ADC cutoff value for discriminating between tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS: Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.

A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer.

OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. RESULTS: Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5-59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). CONCLUSIONS: This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.

Hemodynamic vascular biomarkers for initiation of paraclinoid internal carotid artery aneurysms using patient-specific computational fluid dynamic simulation based on magnetic resonance imaging.

PURPOSE: We performed computational fluid dynamics (CFD) for patients with and without paraclinoid internal carotid artery (ICA) aneurysms to evaluate the distribution of vascular biomarkers at the aneurysm initiation sites of the paraclinoid ICA. METHODS: This study included 35 patients who were followed up for aneurysms using 3D time of flight (TOF) magnetic resonance angiography (MRA) and 3D cine phase-contrast MR imaging. Fifteen affected ICAs were included in group A with the 15 unaffected contralateral ICAs in group B. Thirty-three out of 40 paraclinoid ICAs free of aneurysms and arteriosclerotic lesions were included in group C. We deleted the aneurysms in group A based on the 3D TOF MRA dataset. We performed CFD based on MR data set and obtained wall shear stress (WSS), its derivatives, and streamlines. We qualitatively evaluated their distributions at and near the intracranial aneurysm initiation site among three groups. We also calculated and compared the normalized highest (nh-) WSS and nh-spatial WSS gradient (SWSSG) around the paraclinoid ICA among three groups. RESULTS: High WSS and SWSSG distribution were observed at and near the aneurysm initiation site in group A. High WSS and SWSSG were also observed at similar locations in group B and group C. However, nh-WSS and nh-SWSSG were significantly higher in group A than in group C, and nh-SWSSG was significantly higher in group A than in group B. CONCLUSION: Our findings indicated that nh-WSS and nh-SWSSG were good biomarkers for aneurysm initiation in the paraclinoid ICA.

[Examination about the Direction for Uses of the Radiation Exposure Reduction Mechanism (Organ Effective Modulation) in Consideration of Organ Sensitivity].

Automatic exposure control technology can reduce the radiation dose during CT. The purpose of this study is to reveal the important points regarding the usage of organ effective modulation (OEM), by evaluating the characteristics of OEM, an automatic exposure control technology. An analysis of the dosage profiles revealed that OEM may not work with the first rotation of the X-ray tube in the helical method and wide volume method. This phenomenon can be avoided by using the orbital synchronism helical method. This was also demonstrated upon measurement of the integrated absorption dose at the imaging start position. An analysis of standard deviation measurement revealed that with the combined use of OEM and x-y modulation, the reduction in dose may significantly vary depending on the presence or absence of the gantry tilt. Based on the above results, when using OEM to reduce the dose at the imaging start position, the combined use of x-y modulation should be avoided and the orbital synchronism helical method should be used.

A phase II study of carboplatin plus weekly paclitaxel with bevacizumab for elderly patients with non-squamous non-small-cell lung cancer (NEJ016).

Background The efficacy and safety of bevacizumab in elderly patients with non-small cell lung cancer remain controversial. This study focused on both selecting fit elderly patients and overcoming interpatient variability with respect to pharmacodynamics. Methods Elderly (age: ≥70 years) patients with advanced non-squamous non-small cell lung cancer were enrolled. Patients with uncontrolled congestive heart failure and uncontrolled diabetes were excluded. The treatment regimen comprised carboplatin at an area under the curve of 5 mg/ml/min on day 1, paclitaxel at 90 mg/m2 on days 1 and 8, and bevacizumab at 15 mg/kg on day 1 every 21 days for up to 4 cycles, followed by maintenance bevacizumab. Dose reduction due to side effects was performed, with a wide range of doses of paclitaxel from 23 mg/m2/week to 60 mg/m2/week. Results Of the 36 patients entered, 38.9% required a dose reduction or cancellation of paclitaxel administration on day 8, and 75% patients were able to complete 4 cycles of triplet therapy. The response rate, primary endpoint, was 69.4% (95% confidence interval [CI]: 51.9-83.7). The median progression free survival and overall survival were 8.4 months and 29.2 months, respectively. The most common adverse events included neutropenia, hypertension, anemia, and infection. Although Grade ≥ 3 adverse events were observed in 24 patients (66.7%), there were no deaths due to toxicity. Conclusion Carboplatin plus weekly paclitaxel with bevacizumab is a feasible, effective first-line regimen for elderly non-small cell lung cancer patients. (UMIN00006622).

Hypointense hepatocellular carcinomas on apparent diffusion coefficient mapping: Pathological features and metastatic recurrence after hepatectomy.

AIM: The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy. METHODS: In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion-weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non-hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences. RESULTS: The 52 HCC were evaluated as 26 hypointense and 26 non-hypointense tumors. No significant differences between the hypointense and non-hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non-hypointense group. The cumulative 3-year metastatic recurrence rates of the hypointense and non-hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence. CONCLUSION: Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.

Signal intensity of small hepatocellular carcinoma on apparent diffusion coefficient mapping and outcome after radiofrequency ablation.

AIM: It has been reported that the apparent diffusion coefficient (ADC) value of hepatocellular carcinomas (HCC) on diffusion-weighted magnetic resonance imaging (MRI) is associated with their histological grade. The present study aimed to evaluate whether the signal intensity of small hypervascular HCC on the ADC map is related to the treatment outcome of radiofrequency ablation (RFA). METHODS: Between February 2008 and August 2012, 136 consecutive patients with initial small hypervascular HCC (≤3 tumors and ≤3 cm in diameter) were examined by diffusion-weighted MRI before RFA. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense and non-hypointense. Critical recurrence was defined as more than three intrahepatic recurrences, recurrence with vascular invasion, seeding, dissemination and/or extrahepatic metastasis. RESULTS: The median follow up was 619 days. The cumulative 2-year recurrence rates of the hypointense and non-hypointense on the ADC map groups were 79% and 50% (P < 0.001), respectively, with cumulative 2-year local recurrence rates of 18% and 7% (P = 0.014) and cumulative 2-year critical recurrence rates of 38% and 13% (P = 0.005), respectively. The cumulative 3-year survival rates were 60% and 82% (P = 0.007), respectively. On multivariate analysis, hypointensity on the ADC map was the strongest independent factor related to recurrence and survival after RFA. CONCLUSION: The signal intensity of HCC on the ADC map was strongly associated with outcome after RFA. These results suggest that treatment strategy should be determined carefully even for small HCC when they appear hypointense on the ADC map.

Improved accuracy of diagnosis of lumbar intra and/or extra-foraminal stenosis by use of three-dimensional MR imaging: comparison with conventional MR imaging.

BACKGROUND: The purposes of this study were to assess the reliability of 3-dimensional magnetic resonance (MR) imaging (3D MRI) and conventional MRI (CMRI) for detection of lumbar intra and/or extra-foraminal stenosis (LIEFS) and to compare the diagnostic accuracy of the 2 imaging modalities. METHODS: A total of 60 sets of 3D MR and CMR images from 20 healthy volunteers and 40 LIEFS patients were qualitatively rated according to defined criteria by 3 independent, blinded readers. Kappa statistics were used to characterize intra and inter-reader reliability for qualitative rating of data. Multireader, multicase analysis was used to compare lumbar foraminal stenosis detection between the 2 modalities. RESULTS: Intra-reader agreement for 3D MRI was excellent, with kappa = 0.90; that for CMRI was good, with kappa = 0.78. Average inter-reader agreement for 3D MRI was good, with kappa = 0.79, whereas that for CMRI was moderate, with kappa = 0.41. Average area under the ROC curve values (1st reading/2nd reading) for detection of lumbar foraminal stenosis using 3D MRI and CMRI were 0.99/0.99 and 0.94/0.92, respectively. Detection of LIEFS with 3D MRI was significantly better than with CMRI (P = 0.0408/0.0294). CONCLUSIONS: These results suggest that CMRI was of limited use for detection of the presence of LIEFS. Isolated imaging with CMRI may risk overlooking the presence of LIEFS. In contrast, reliability of 3D MRI for detection of LIEFS was good. Furthermore, readers' performance in the diagnosis of LIEFS can be improved by use of 3D MRI. Therefore, 3D MRI is recommended when using imaging for diagnosis of LIEFS.

Contrast enrichment of spinal cord MR imaging using a ratio of T1-weighted and T2-weighted signals.

PURPOSE: We aimed to assess if the T1-weighted (T1w)/T2-weighted (T2w) signal ratio could be used to improve image contrast in MR spinal cord imaging. MATERIALS AND METHODS: T1w and T2w cervical spinal cord MR images were acquired from 23 normal subjects using 3 Tesla (T) MR scanner. In addition, a multiple sclerosis patient, and a cervical spondylotic myelopathy patient were evaluated. White matter (WM) and gray matter (GM) signal intensities were measured for each image (T1w, T2w, and T1w/T2w) for seven cervical segments in each subject to calculate the contrast. Age-related changes in signal intensity were assessed at each location (lateral column, anterior column, dorsal column, and GM) for each image. Additionally, the imaging results of two subjects with spinal diseases and the controls were numerically compared. RESULTS: The contrast between the WM and GM in the T1w/T2w ratio image was approximately twice as much as that in the T1w and T2w images (mean ± SD = 1.8 ± 0.4). The signal intensity ratio was related to age. For both clinical patients, the signal intensities were significantly lower in the lesion areas in the ratio images. CONCLUSION: The T1w/T2w ratio images demonstrated increased image contrast compared with T1w and T2w images alone and, reduced inter-individual signal intensity differences.

Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

[Study of scan parameters using three-dimensional cine phase contrast imaging for pulmonary artery velocity measurement].

Pulmonary artery flow velocity, flow volume and their derived biomarkers, such as acceleration time (AT), acceleration volume (AV) and peak velocity (PV), vary depending on the severity and type of pulmonary disease. Therefore, accurate measurements of pulmonary artery velocity are very important for assessing the severity of pulmonary disease. The purpose of this study was to optimize the imaging parameters for pulmonary artery flow velocity using 3D cine PC MR, and to evaluate AT, AV, and PV for pulmonary hypertension. We changed the flip angle (FA) and view per segment (VPS). FA influenced the signal intensity, which was calculated from the magnitude images. Smaller VPS improved the accuracy of PV. Consequently, optimal setting of FA and VPS was important for hemodynamic analysis. We established the optimal FA and VPS for use in the hemodynamic analysis. AV and PV at the right pulmonary artery differed significantly between healthy volunteers and patients with pulmonary hypertension. Hemodynamic analysis of 3D cine PC MR imaging was considered promising for the evaluation of pulmonary disease.

Ecklonia cava polyphenol protects the liver against ethanol-induced injury in rats.

BACKGROUND: The development of alcoholic liver disease is a complex process that involves both the parenchymal and non-parenchymal cells of the liver. We examined the effect of an Ecklonia cava extract on ethanol-induced liver injury. METHODS: Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or 0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl4) (0.1 ml/kg of body weight). RESULTS: In the cultured hepatocytes, the ECP treatment suppressed the ethanol-induced increase in cell death by maintaining intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the ethanol-induced increases in type I collagen and α-smooth muscle actin expression by maintaining intracellular levels of reactive oxygen species and GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the progression of liver fibrosis in rats treated with ethanol and CCl4. ECP treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4-treated rats. ECP treatment fully protected the rats against ethanol- and CCl4-induced liver injury. GENERAL SIGNIFICANCE: ECP may be a candidate for preventing ethanol-induced liver injury.

Is visceral fat really a coronary risk factor? A multi-detector computed tomography study.

Metabolic syndrome (MS) is currently considered to be a risk factor for arteriosclerotic disease. The accumulation of visceral fat leads to arteriosclerotic disease after other risk factors have developed and either direct or mutual effects occur. The aim of this study was to verify whether visceral fat serves as an independent coronary risk factor. A total of 3157 patients who had undergone multi-detector computed tomography (MDCT) were analyzed via computed tomographic angiography and the measurement of their visceral fat area. Coronary arteries with > 70% stenosis were considered to be significant. The visceral fat area was measured at the umbilical level, and an area of 100 cm2 or more was defined as visceral obesity. Coronary risk factors (ie, hypertension, dyslipidemia, diabetes mellitus, family history, and smoking) were obtained from the patient medical records. The patients were divided into two groups: a visceral obesity group, 1130 patients (137.0 ± 31.1 cm2) and a nonvisceral obesity group, 2027 patients (57.3 ± 25.8 cm2). A significant difference in the incidence of coronary stenosis between the two groups was observed. According to multivariable analysis, the factors affecting coronary stenosis were age, gender, dyslipidemia, diabetes mellitus, and the ratio of visceral to subcutaneous fat. Visceral obesity was not found to be an independent coronary risk factor. Visceral obesity demonstrated the predominant presence of coronary risk factors.

Technical Background for 4D Flow MR Imaging.

Recently, the hemodynamic assessments with 3D cine phase-contrast (PC) MRI (4D flow MRI) have attracted considerable attention from clinicians. Unlike 2D cine PC MRI, the technique allows for cardiac phase-resolved data acquisitions of flow velocity vectors within the entire FOV during a clinically viable period. Thus, the method has enabled retrospective flowmetry in the spatial and temporal axes, which are essential to derive hemodynamic parameters related to vascular homeostasis and those to the progression of the pathologies. Accelerations in imaging are critical for this technology to be clinically viable; however, a high SNR or velocity-to-noise ratio (VNR) is also vital for accurate flow measurements. In this chapter, the technologies enabling this difficult balance are discussed.

A single-arm open-label pilot study of brief mindfulness meditation to control impulsivity in Parkinson's disease.

BACKGROUND: Impulse control disorders are detrimental neuropsychiatric symptoms of Parkinson's disease. Increased impulsivity is a predisposing factor for impulse control disorders and should therefore be controlled. Recently, mindfulness meditation as a non-drug therapy has been reported to be useful in improving neuropsychiatric symptoms, such as impulsivity. METHODS: We performed a prospective single-arm, open-label pilot trial to investigate the effectiveness of mindfulness meditation to control impulsivity in patients with Parkinson's disease (UMIN clinical trials registry: UMIN000037779). RESULTS: Twenty patients with Parkinson's disease were enrolled in an 8-week mindfulness meditation program. As a primary outcome, we investigated whether the score of the Barratt Impulsiveness Scale (BIS-11) was significantly reduced after the intervention. As an exploratory examination, functional connectivity changes were also assessed by resting-state functional magnetic resonance imaging. After the intervention, the BIS-11 score was decreased from 59.5 [55.6, 63.3] (mean [95% confidence interval]) to 55.2 [50.3, 60.1] (ΔBIS-11: -4.2, [-7.5, -0.9]). Functional connectivity was increased in the default mode network (DMN) at a cluster including the precuneus, posterior cingulate gyrus, and left posterior lobe (false discovery rate-adjusted p [FDR-p] = 0.046) and in the right frontoparietal network (FPN) at the medial frontal lobe (FDR-p = 0.039). CONCLUSIONS: This open-label, single-arm pilot study provided preliminary data for mindfulness meditation to control the impulsivity of patients with PD. A brief mindfulness meditation program may be effective in controlling impulsivity in PD and may change the functional connectivity of the DMN and right FPN.

Cognitive functions relating to aberrant interactions between task-positive and task-negative networks: Resting fMRI study of patients with schizophrenia.

Brain functional connectivity in the resting-state represents intrinsic functional states and correlates with cognitive performance. In patients with schizophrenia, reports on the relationships between forms of functional disconnectivity in local areas and cognitive disability have used resting-state functional magnetic resonance imaging data. Meanwhile, cognitive deficits in relation to inter-network forms of functional connectivity on a large scale are not well understood. This study examines cognitive functions in relation to the number of resting-state inter-network forms of functional connectivity focusing on task-positive networks (fronto-parietal network [FPN] and cingulo-opercular network [CON]) and task-negative network (default mode network [DMN]). We compare patients with schizophrenia (SCH group) and healthy controls (HC group). We conducted a functional network analysis by applying graph theory and evaluated cognitive functions using the Brief Assessment of Cognition in Schizophrenia. The number of forms of functional connectivity between FPN and DMN and between CON and DMN were significantly higher in SCH group than in HC group, and those in SCH group were also weakly correlated with their attention scores. It is suggested that fewer than typical functional segregations between task-positive and task-negative networks in SCH group relate to inefficient distribution of cognitive resources and low attentional abilities.

Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.

RATIONALE: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. OBJECTIVES: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. METHODS: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O(2)) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 microg Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 microg Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk). MEASUREMENTS AND MAIN RESULTS: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. CONCLUSIONS: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013).

Inhibitory effects of Ecklonia cava extract on high glucose-induced hepatic stellate cell activation.

Nonalcoholic steatohepatitis (NASH) is a disease closely associated with obesity and diabetes. A prevalence of type 2 diabetes and a high body mass index in cryptogenic cirrhosis may imply that obesity leads to cirrhosis. Here, we examined the effects of an extract of Ecklonia cava, a brown algae, on the activation of high glucose-induced hepatic stellate cells (HSCs), key players in hepatic fibrosis. Isolated HSCs were incubated with or without a high glucose concentration. Ecklonia cava extract (ECE) was added to the culture simultaneously with the high glucose. Treatment with high glucose stimulated expression of type I collagen and α-smooth muscle actin, which are markers of activation in HSCs, in a dose-dependent manner. The activation of high glucose-treated HSCs was suppressed by the ECE. An increase in the formation of intracellular reactive oxygen species (ROS) and a decrease in intracellular glutathione levels were observed soon after treatment with high glucose, and these changes were suppressed by the simultaneous addition of ECE. High glucose levels stimulated the secretion of bioactive transforming growth factor-ß (TGF-ß) from the cells, and the stimulation was also suppressed by treating the HSCs with ECE. These results suggest that the suppression of high glucose-induced HSC activation by ECE is mediated through the inhibition of ROS and/or GSH and the downregulation of TGF-ß secretion. ECE is useful for preventing the development of diabetic liver fibrosis.