Comparison of baseline covariate adjustment methods for restricted mean survival time.

The restricted mean survival time provides a straightforward clinical measure that dispenses with the need for proportional hazards assumptions. We focus on two strategies to directly model the survival time and adjust covariates. Firstly, pseudo-survival time is calculated for each subject using a leave-one-out approach, followed by a model analysis that adjusts for covariates using all pseudo-values. This method is used to reflect information of censored subjects in the model analysis. The second approach adjusts for covariates for those subjects with observed time-to-event while incorporating censored subjects using inverse probability of censoring weighting (IPCW). This paper evaluates these methods' power to detect group differences through computer simulations. We find the interpretation of pseudo-values challenging with the pseudo-survival time method and confirm that pseudo-survival times deviate from actual data in a primary biliary cholangitis clinical trial, mainly due to extensive censoring. Simulations reveal that the IPCW method is more robust, unaffected by the balance of censors, whereas pseudo-survival time is influenced by this balance. The IPCW method retains a nominal significance level for the type-1 error rate, even amidst group differences concerning censor incidence rates and covariates. Our study concludes that IPCW and pseudo-survival time methods differ significantly in handling censored data, impacting parameter estimations. Our findings suggest that the IPCW method provides more robust results than pseudo-survival time and is recommended, even when censor probabilities vary between treatment groups. However, pseudo-survival time remains a suitable choice when censoring probabilities are balanced.

Application of sample size re-estimation in clinical trials: A systematic review.

Background: Sample size re-estimation (SSR) is a method used to recalculate sample size during clinical trial conduct to address a lack of adequate information and can have a significant impact on study size, duration, resources, and cost. Few studies to date have summarized the conditions and circumstances under which SSR is applied. We therefore performed a systematic review of the literature related to SSR to better understand its application in clinical trial settings. Methods: PubMed was used as the primary search source, supplemented with information from ClinicalTrials.gov where necessary details were lacking from PubMed. A systematic review was performed according to a pre-specified search strategy to identify clinical trials using SSR. Features of SSR, such as study phase and study start year, were summarized. Results: In total, 253 publications met the pre-specified search criteria and 27 clinical trials were subsequently determined as relevant in SSR usage. Among trials where the study phase was provided, 2 (7.4%) trials were Phase I, 5 (18.5%) trials were Phase II, 11 (40.7%) trials were Phase III, and 2 (7.4%) trials were Phase IV. Conclusion: Our results showed that SSR is also used in Phase I and II, which involve earlier decision making. We expect that SSR will continue to be used in early-phase trials where sufficient prior information may not be available. Furthermore, no major trends were observed in relation to therapy area or type of SSR, meaning that SSR may become a feasible and widely applied method in the future.

Importance of the Multimodality Evaluation of a Double-chambered Right Ventricle for Surgical Indications on Admission for Acute Myocardial Infarction.

We treated a female patient known to have a double-chambered right ventricle (DCRV) who presented with symptoms of an acute myocardial infarction (AMI). Emergent coronary artery catheterization revealed acute right coronary artery (RCA) occlusion and proximal left anterior descending (LAD) stenosis. We performed percutaneous coronary intervention (PCI) for the RCA occlusion. Right heart catheterization revealed a pressure gradient across the mid-RV of 58 mmHg. Computed tomography and magnetic resonance imaging revealed no other congenital cardiac abnormalities. She underwent surgical repair of the RV stenosis and coronary artery bypass surgery for LAD stenosis.

Preloading Coil in Plug Method (p-CIP) with the AVP 2 for large Portosystemic Shunt Embolization.

Hepatic encephalopathy caused by a large portosystemic shunt (PSS) can be treated by endovascular embolization of the shunt. The PSS diameter can be >20 mm; it occasionally poses technical difficulties. Here, a 72-year-old woman with liver cirrhosis, hyperammonemia, and large spleno-renal shunt underwent shunt embolization using an Amplatzer vascular plug 2 (AVP2) and metallic coils. The preloading coil in plug method (p-CIP), which facilitated embolization inside the AVP2 without cannulation from outside, was employed to overcome technical difficulties. We propose the use of p-CIP with an AVP2 as a tool for treatment of hepatic encephalopathy with PSS.

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol.

INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS: Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION: As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.

Spinal Cord Infarction after Transcatheter Embolization of Pelvic Arteriovenous Malformation.

An 80-year-old woman presented with abdominal and right lower limb pain. Radiological examination revealed pelvic arteriovenous malformations (pAVMs). Although transarterial embolization was repeated, dilation of the common iliac vein worsened. Four sessions of embolization were performed for the internal iliac vein. Paraplegia gradually occurred a day after the final procedure. Magnetic resonance imaging revealed thoracic spinal cord edema and paraspinal vasodilatation, suggesting spinal cord infarction. Additional angiography revealed a radiculomedullary vein draining into the spinal canal from the pAVM; hence, surgical interruption was performed. Incomplete venous embolization of the pAVM caused spinal cord congestion and infarction.

Neuroinflammation, Oxidative Stress, and Neurogenesis in a Mouse Model of Chronic Fatigue Syndrome, and the Treatment with Kampo Medicine.

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine. A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1ß, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays. The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1ß, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1ß, IL-6, and IFN-γ in the hippocampus but not in the cortex. The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

Acupuncture on ST36, CV4 and KI1 Suppresses the Progression of Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms underlying its action are still largely unknown. In this study, we established a mouse model of NAFLD by administering a methionine- and choline-deficient (MCD) diet and selected three acupoints (ST36, CV4, and KI1) or nonacupoints (sham) for needling. We then investigated the effects of acupuncture treatment on the progression of NAFLD and the underlying mechanisms. After two weeks of acupuncture treatment, the liver in the needling-nonapcupoint group (NG) mice appeared pale and yellowish in color, while that in the needling-acupoint group (AG) showed a bright red color. Histologically, fewer lipid droplets and inflammatory foci were observed in the AG liver than in the NG liver. Furthermore, the expression of proinflammatory signaling factors was significantly downregulated in the AG liver. A lipid analysis showed that the levels of triglyceride (TG) and free fatty acid (FFA) were lower in the AG liver than in the NG liver, with an altered expression of lipid metabolism-related factors as well. Moreover, the numbers of 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic thiobarbituric acid reactive substances (TBARS) were significantly lower in AG mice than in NG mice. In line with these results, a higher expressions of antioxidant factors was found in the AG liver than in the NG liver. Our results indicate that acupuncture repressed the progression of NAFLD by inhibiting inflammatory reactions, reducing oxidative stress, and promoting lipid metabolism of hepatocytes, suggesting that this approach might be an important complementary treatment for NAFLD.

Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma.

Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator's choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95%CI: 4-23%) and 0% (95%CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95%CI: 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95%CI: 0.337-0.983). The most frequent treatment-related adverse (grade ≥3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator's choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.

Critical roles of inflammation in atherosclerosis.

There is accumulating evidence that vascular inflammation plays critical roles in pathophysiology of atherosclerosis. It is widely accepted that both innate and adaptive immune responses are important for initiation and progression of atherosclerosis, which mainly consist of monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes. Moreover, inflammatory biomarkers such as high-sensitivity C-reactive protein and interleukin-6 are known to predict future cardiovascular events, as well as conventional low-density or high-density lipoprotein cholesterol. Thus, current understanding of the inflammatory mechanisms of atherosclerosis have led us to explore novel therapeutic approaches that reducing vascular inflammation itself could lower the rates of critical cardiovascular events. To address the inflammatory hypothesis of atherosclerosis, results of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial have been recently reported that anti-inflammatory therapy using canakinumab, a monoclonal antibody targeting interleukin-1ß, significantly reduced recurrent cardiovascular events for secondary prevention of myocardial infarction at high inflammatory risk. In this review, we will first outline the mechanisms of atherosclerosis, especially focusing on their inflammatory aspects. Then we will introduce several critical inflammatory biomarkers that contribute to risk stratification of clinical cardiovascular events. Lastly, we will discuss potentiality and future perspectives of reducing inflammation as a novel therapeutic target for atherosclerotic cardiovascular diseases.

Brain structural connectivity and neuroticism in healthy adults.

Understanding the neural correlates of the neurotic brain is important because neuroticism is a risk factor for the development of psychopathology. We examined the correlation between brain structural networks and neuroticism based on NEO Five-Factor Inventory (NEO-FFI) scores. Fifty-one healthy participants (female, n = 18; male, n = 33; mean age, 38.5 ± 11.7 years) underwent the NEO-FFI test and magnetic resonance imaging (MRI), including diffusion tensor imaging and 3D T1WI. Using MRI data, for each participant, we constructed whole-brain interregional connectivity matrices by deterministic tractography and calculated the graph theoretical network measures, including the characteristic path length, global clustering coefficient, small-worldness, and betweenness centrality (BET) in 83 brain regions from the Desikan-Killiany atlas with subcortical segmentation using FreeSurfer. In relation to the BET, neuroticism score had a negative correlation in the left isthmus cingulate cortex, left superior parietal, left superior temporal, right caudal middle frontal, and right entorhinal cortices, and a positive correlation in the bilateral frontal pole, left caudal anterior cingulate cortex, and left fusiform gyrus. No other measurements showed significant correlations. Our results imply that the brain regions related to neuroticism exist in various regions, and that the neuroticism trait is likely formed as a result of interactions among these regions. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan.

Intraplaque Microvascular Flow Signal in Superb Microvascular Imaging and Magnetic Resonance Imaging Carotid Plaque Imaging in Patients with Atheromatous Carotid Artery Stenosis.

Carotid artery atherosclerosis is one of the major risk factors for ischemic stroke. Intraplaque neovascularization (IPN) is one of the steps toward the development of vulnerable plaque. Superb microvascular imaging (SMI) is a new ultrasonographic technique for visualizing low-velocity and microvascular flow by clutter suppression to extract flow signals from large to small vessels and enables visualization of intraplaque microvascular flow (IMVF) without echo contrast media. We aimed to investigate the association between IMVF signal in SMI and MRI plaque imaging among patients with atherosclerotic carotid stenosis. We prospectively enrolled patients (>18 years old) with mild to severe carotid stenosis (more than 50% in cross-sectional area) diagnosed by carotid ultrasonography between August 2017 and April 2018, irrespective of sex and history of stroke. A total of 40 patients (31 men, 9 women; mean age, 75.1 ± 10.0 years) were enrolled. SMI revealed IPN findings in 21 patients. SMI clearly visualized the direction of pulsatile flow movement in microvessels and IPN was easily classified into the two types of Type V (n=2) and Type E (n=19). Multivariate logistic regression analysis presented that microvascular flow signal in carotid plaque on SMI was identified as a significant predictor of intraplaque hemorrhage as evaluated by MRI (OR, 8.46; 95%CI, 1.44-49.9; p=0.018). This study demonstrated a significant association between the presence of IMVF signal in SMI and intraplaque hemorrhage characterized by high-intensity lesions on MRI T1-FFE images.

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS: In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS: Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING: Kyowa Kirin.

Evaluation of Peritumoral Brain Parenchyma Using Contrast-Enhanced 3D Fast Imaging Employing Steady-State Acquisition at 3T for Differentiating Metastatic Brain Tumors and Glioblastomas.

BACKGROUND: Metastatic brain tumors and glioblastomas are the 2 of the most common brain neoplasms in adults. However, distinguishing solitary metastatic brain tumors from glioblastomas on conventional magnetic resonance imaging remains particularly challenging. Thus, we aimed to retrospectively assess the role of contrast-enhanced fast imaging employing steady-state acquisition (CE-FIESTA) imaging in distinguishing between metastatic brain tumors and glioblastomas. MATERIALS AND METHODS: Forty-three patients with metastatic brain tumors and 14 patients with glioblastomas underwent conventional magnetic resonance imaging and CE-FIESTA before surgery. First, 1 neuroradiologist and 1 neurosurgeon classified the CE-FIESTA findings for the peritumoral brain parenchyma by consensus. Next, the 2 neuroradiologists performed an observer performance study comparing tumor shape classification (smooth or irregular margins), a classic imaging finding, with the CE-FIESTA classification of the peritumoral brain parenchyma. RESULTS: The CE-FIESTA findings for the peritumoral brain parenchyma were classified as follows: type A, no hyperintense rim; type B, partial hyperintense rim; and type C, extended hyperintense rim. With regard to the diagnosis of metastatic brain tumors, the observer performance study demonstrated that the mean sensitivity, specificity, and accuracy of an extended hyperintense rim classification (type C) on CE-FIESTA images were 95.3%, 85.7%, and 93.0%, respectively. The accuracy of the CE-FIESTA classification was significantly higher than that of the tumor shape classification. CONCLUSIONS: CE-FIESTA images may provide useful information for distinguishing metastatic brain tumors from glioblastomas, especially when focusing on differences in the peritumoral brain parenchyma.

Intracranial vessel wall lesions in patients with systematic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is related to vasculitis, which causes brain infarctions; however, the pathology of large cerebral vessels has not been fully established. PURPOSE: To demonstrate the prevalence of vessel wall lesions (VWLs) in SLE patients using 3D vessel wall imaging and to assess the relationship between VWLs and brain infarctions. STUDY TYPE: Retrospective. SUBJECTS: Sixty SLE patients and 50 healthy subjects (HS). FIELD STRENGTH/SEQUENCE: Each subject underwent 3T MRI, which included 3D FSE PDWI (CUBE). ASSESSMENT: For each of the 33 segments of the intracranial artery (internal carotid artery ∼ M3 segment of middle cerebral artery [MCA]), the VWLs were scored as either positive or negative, and the VWL score was calculated as the sum of the segments with VWLs. We also evaluated brain lesions on conventional MRI. STATISTICAL TESTS: We used logistic regression analyses to determine the clinical (serological test and cardiovascular risk factors) and imaging characteristics associated with infarctions in SLE patients. RESULTS: For the peripheral vessels such as MCA, VWLs were more common for SLE patients than for HS (43.3% versus 16.7% in M1 segment, 60.4% versus 16.7% in M2 segment, both P < 0.01). There were 21 infarctions in 13 patients (21.7%), and the median VWL score was larger in the patients with infarctions than in those without (13 versus 6, P < 0.01). Multivariate logistic regression analyses revealed a high VWL score ( ≥ 9) to be the only factor independently associated with the presence of infarctions (odds ratio: 10.1, 95% confidence interval: 1.01-101; P < 0.049). DATA CONCLUSION: We demonstrated a substantially high prevalence of VWLs among SLE patients, which were associated with brain infarctions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1237-1246.

Angiogenesis, Cancer, and Vascular Aging.

Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD) among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

Enlarged perivascular spaces are associated with the disease activity in systemic lupus erythematosus.

To determine whether any brain MR abnormalities, including enlarged perivascular spaces (EPVS), were associated with disease activity in systemic lupus erythematosus (SLE) as an inflammatory activity. One hundred and thirty SLE patients with normal MR findings were assessed. With regard to MRI abnormalities, patients with brain atrophy and mild white matter hyperintensity (WMH) on T2WI were not excluded. The disease activity was assessed using the SLEDAI and the BILAG scores. The imaging characteristics included centrum semiovale EPVS (CS- EPVS) and basal ganglia EPVS on T2WI, WMH, and brain atrophy. We used univariate and multivariate logistic regression analyses to determine the clinical (vascular risk factors and blood examinations) and imaging characteristics that were associated with the disease activity of SLE. High CS-EPVS to be the only factor that was independently associated with the severity of the SLEDAI and BILAG scores (odds ratio [OR] 5.77; 95% confidence interval [CI] 2.21-15.00; p < 0.001 for the SLEDAI, and OR 2.64; 95% CI 1.03-6.74; p = 0.042 for the BILAG score). The CS-EPVS in the SLE patients are associated with the systemic disease activity, suggesting that CS- EPVS may be indicative of the reactive changes of the white matter due to the inflammatory activity.

Identification of Heschl's gyrus on phase difference enhanced imaging.

Background The white matter in the Heschl's gyrus (HG-WM) may appear differently to the other gyri on phase difference enhanced imaging (PADRE), which can enhance the myelin density. Purpose To evaluate the signal intensity (SI) of HG-WM using the PADRE technique and to compare the images with susceptibility-weighted imaging (SWI)-like images. Material and Methods The participants included 19 normal controls (38 HGs; mean age, 60.1 years; age range, 28-80 years). Coronal PADRE and SWI-like images were acquired using a 3T magnetic resonance (MR) system. The SI of the HG-WM was classified into three grades based on a comparison with the SI of the superior temporal gyrus: Grade 1, isointense; Grade 2, slightly hypointense, and Grade 3, markedly hypointense. Results In the assessment of the SI of the HG-WM, the HG-WM appeared hypointense in all 38 sites of the 19 participants; the hypointensity corresponded to Grade 2 in 13 (34%) images and Grade 3 in 25 (66%) images. On the other hand, the HG-WM was classified as Grade 1 (isointense) in all of the SWI-like images. Conclusion The HG-WM appears hypointense on PADRE, which probably reflects the higher myelin content. PADRE may be useful for identifying the HG through the assessment of the SI of the HG-WM.

Internal Structures of the Globus Pallidus in Patients with Parkinson's Disease: Evaluation with Phase Difference-enhanced Imaging.

PURPOSE: The medial medullary lamina (MML) separates the medial globus pallidus (GPm) from the lateral. The aim of this study was to assess the changes in appearance of MML related to age using the phase difference-enhanced (PADRE) imaging and to determine whether PADRE can depict the MML in the patients with Parkinson's disease (PD). MATERIALS AND METHODS: We enrolled 20 patients with PD and 50 normal control subjects (NC). First, for the visualization of the MML in the NC, we compared the PADRE, susceptibility-weighted imaging (SWI)-like images and T2 weighted imaging (WI) by using multiple comparison. The grading methods are as follows: grade 1; MML was not delineated, grade 2; less than half of MML was delineated, grade 3; more than half of MML was delineated and grade 4; whole MML was clearly delineated. We determined grade 3 and 4 as good depiction, delineating the GPm. Then, we evaluated patients with PD using the same method. RESULTS: In NC, the delineation of MML was good in 84% of cases on PADRE, but only 34% of cases showed a good depiction on SWI-like images (average grading score 3.31 vs 2.11, P < 0.05). No MML was delineated in all cases on T2 WI. Although younger subjects tended to show whole MML clearly, a part of MML tends to be obscured with age on PADRE. In patients with PD the depiction of MML on PADRE was also good in 90% of cases. CONCLUSION: The PADRE technique facilitates the depiction of the MML within globus pallidus (GP) on a broad range of age NC and patients with PD and it is superior to SWI-like images and T2 WI.

Sex Differences in Associations Among Obesity, Metabolic Abnormalities, and Chronic Kidney Disease in Japanese Men and Women.

AIMS: The present study aimed to investigate relationships among abdominal obesity, metabolic abnormalities, and the prevalence of chronic kidney disease (CKD) in relatively lean Japanese men and women. PARTICIPANTS AND METHODS: The participants included 8133 men and 15 934 women between 40 and 75 years of age recruited from the government health check-up center in Kanazawa City, Japan. The prevalence of abdominal obesity, high blood pressure, dyslipidemia, and high fasting plasma glucose levels were assessed according to the Japanese criteria for metabolic syndrome. The estimated glomerular filtration rate (eGFR) was calculated using the modified Modification of Diet in Renal Disease equation for the Japanese population, and participants with an eGFR <60 mL/min/1.73 m(2) and/or proteinuria were diagnosed with CKD. RESULTS: Overall, 23% of males and 14% of females met criteria for CKD. Having more numerous complicated metabolic abnormalities was significantly associated with a higher odds ratio (OR) of CKD for men and women, irrespective of abdominal obesity. However, there was a sex difference in the OR of CKD for obese participants without metabolic abnormalities, such that abdominal obesity without metabolic abnormalities was significantly associated with a higher OR for men (multivariate-adjusted OR 1.63; 95% confidence interval [CI], 1.16-2.28) but not for women (OR 1.01; 95% CI, 0.71-1.44). CONCLUSIONS: The present findings demonstrated that obesity without metabolic abnormalities was associated with a higher risk of CKD in men but not women in a relatively lean Japanese population.