Quality of life after brain injury-overall scale, Japanese version: assessment of reliability and validity.

This study analyzed the linguistic and psychometric validation of the Japanese version of the Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) consisting of six items which cover several TBI-relevant domains. We hypothesized that the Japanese version has good reliability, convergent validity, and divergent validity, compared with its long version, the 37-item QOLIBRI. The QOLIBRI-OS Japanese version was forward and back-translated from the English version. In total, 129 individuals participated in this study after experiencing a traumatic brain injury and attending clinics, rehabilitation centers, and support centers in Japan. The structure of the QOLIBRI-OS was investigated by confirmatory factor analyses and compared with the QOLIBRI. Only one factor was extracted, and a model with one underlying factor had a good fit. The QOLIBRI-OS showed good-to-excellent internal consistency and test-retest reliability. The QOLIBRI-OS was positively correlated with the QOLIBRI, Short Form Health Survey-36 version 2, and Glasgow Outcome Scale Extended, and negatively correlated with the Hospital Anxiety and Depression Scale. The results suggest that the QOLIBRI-OS Japanese version is a reliable and valid tool for assessing disease-specific health-related QOL in individuals after traumatic brain injury in Japan.

[Hypokalemia and potassium replacement therapy in allogeneic hematopoietic stem cell transplantation].

Hypokalemia is common in allogeneic hematopoietic stem cell transplantation (allo-HCT) patients and is associated with non-relapse mortality (NRM). Therefore, it is extremely important to replace potassium adequately. We evaluated the safety and efficacy of potassium replacement therapy by retrospectively analyzing the incidence and severity of hypokalemia in 75 patients who received allo-HCT at our institution. 75% of patients developed hypokalemia during the allo-HSCT, and 44% of patients had grade 3-4 levels of hypokalemia. NRM was significantly higher in patients with grade 3-4 hypokalemia than in patients without severe hypokalemia (one-year NRM: 30% vs 7%, p=0.008). Although 75% of the patients required potassium replacement that exceeded the range of potassium chloride solutions package inserts in Japan, we did not experience any adverse events associated with hyperkalemia. Our current observations suggested that the Japanese package insert for potassium solution injection should be revised for potassium needs.

Long-term prognosis of patients undergoing radiofrequency catheter ablation for atrial fibrillation: comparison between heart failure subtypes based on left ventricular ejection fraction.

AIMS: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). METHODS AND RESULTS: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). CONCLUSION: This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.

Reverse Remodeling and Non-Contrast T1 Hypointense Infarct Core in Patients With Reperfused Acute Myocardial Infarction.

BACKGROUND: Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it.Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month follow-up (hazard ratio: 0.087, 95% confidence interval: 0.017-0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. CONCLUSIONS: ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.

Development of a clinical tool for rating the body function categories of the ICF generic-30/rehabilitation set in Japanese rehabilitation practice and examination of its interrater reliability.

BACKGROUND: The International Classification of Functioning, Disability, and Health (ICF) Generic-30 (Rehabilitation) Set is a tool used to assess the functioning of a clinical population in rehabilitation. The ICF Generic-30 consists of nine ICF categories from the component "body functions" and 21 from the component "activities and participation". This study aimed to develop a rating reference guide for the nine body function categories of the ICF Generic-30 Set using a predefined, structured process and to examine the interrater reliability of the ratings using the rating reference guide. METHODS: The development of the first version of the rating reference guide involved the following steps: (1) a trial of rating patients by several raters; (2) cognitive interviews with each rater to analyze the thought process involved in each rating; (3) the drafting of the rating reference guide by a multidisciplinary panel; and (4) a review by ICF specialists to confirm consistency with the ICF. Subsequently, we conducted a first field test to gain insight into the use of the guide in practice. The reference guide was modified based on the raters' feedback in the field test, and an inter-rater reliability test was conducted thereafter. Interrater agreement was evaluated using weighted kappa statistics with linear weights. RESULTS: The first version of the rating reference guide was successfully developed and tested. The weighted kappa coefficient in the field testing ranged from 0.25 to 0.92. The interrater reliability testing of the rating reference guide modified based on the field test results yielded an improved weighted kappa coefficient ranging from 0.53 to 0.78. Relative improvements in the weighted kappa coefficients were observed in seven out of the nine categories. Consequently, seven out of nine categories were found to have a weighted kappa coefficient of 0.61 or higher. CONCLUSIONS: In this study, we developed and modified a rating reference guide for the body function categories of the ICF Generic-30 Set. The interrater reliability test using the final version of the rating reference guide showed moderate to substantial interrater agreement, which encouraged the use of the ICF in rehabilitation practice.

Functional assessment of intermediate coronary artery stenosis with 4-Fr catheters.

The 4-Fr catheter system is not recommended for invasive functional assessment of coronary artery stenosis, because it tends to distort the aortic waveform. This study aimed to identify the incidence of aortic waveform distortion and a feasible method for correct diagnosis of coronary artery stenosis with a 4-Fr catheter. We retrospectively investigated 178 lesions with intermediate coronary artery stenosis. Non-hyperemic distal coronary artery pressure (Pd) and aortic pressure (Pa) were measured with a 4-Fr diagnostic or 6-Fr guiding catheter before and after saline flush. The mean Pd/mean Pa (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated before and after flushing. We compared the effect of flushing on the changes in Pd/Pa and iFR between the 4-Fr diagnostic and 6-Fr guiding catheters. Using the 4-Fr diagnostic catheter, there was a significant decrease in incidence of aortic waveform distortion from 42.0% (47 lesions) before flushing to 1.8% (2 lesions) after flushing (p < 0.001); the incidence was only 3.0% before saline flush and decreased to 0% after saline flush when using the 6-Fr guiding catheter. The presence of aortic waveform distortion influenced the iFR when the 4-Fr system was used. Functional measurements with the 4-Fr diagnostic catheter require adequate saline flush to remove the influence of aortic waveform distortion.

Diagnostic performance of coronal view in comparison with transverse view of three-dimensional automated breast ultrasound.

BACKGROUND: Automated breast ultrasound (ABUS) is one of the first ultrasound devices which enables the de-coupling of image acquisition and interpretation. Another feature of ABUS is the coronal view, utilizing three-dimensional volume data reconstructed from two-dimensional transverse images acquired automatically. PURPOSE: To assess the diagnostic performance of coronal view interpretation by comparing it with that of the transverse view. MATERIAL AND METHODS: This was a retrospective, multi-case, observer study using a cancer-enriched dataset of ABUS images at a single institution with approval by an Institutional Review Board. The 100 scan datasets selected between October 2014 and January 2017 included 70 non-cancer cases and 30 malignancies. In the present observer study, two experienced physicians provided their confidence levels regarding the malignancy of each of the 100 scan datasets independently. The reading times for interpretation of coronal and transverse views were recorded. RESULTS: Area under the receiver operating characteristic curves for two observers with the transverse view (0.856) was improved by use of the coronal view (0.917, P = 0.036). The average reading times were 140.4 s with the coronal view and 148.5 s with the transverse view per scan dataset (P = 0.246). CONCLUSION: It is conceivable that the accurate use of the coronal view will lead to improvement in diagnostic performance in breast cancer screening, although this needs to be confirmed with a larger prospective study.

Computer-Aided Diagnosis Scheme for Distinguishing Between Benign and Malignant Masses on Breast DCE-MRI Images Using Deep Convolutional Neural Network with Bayesian Optimization.

Although magnetic resonance imaging (MRI) has a higher sensitivity of early breast cancer than mammography, the specificity is lower. The purpose of this study was to develop a computer-aided diagnosis (CAD) scheme for distinguishing between benign and malignant breast masses on dynamic contrast material-enhanced MRI (DCE-MRI) by using a deep convolutional neural network (DCNN) with Bayesian optimization. Our database consisted of 56 DCE-MRI examinations for 56 patients, each of which contained five sequential phase images. It included 26 benign and 30 malignant masses. In this study, we first determined a baseline DCNN model from well-known DCNN models in terms of classification performance. The optimum architecture of the DCNN model was determined by changing the hyperparameters of the baseline DCNN model such as the number of layers, the filter size, and the number of filters using Bayesian optimization. As the input of the proposed DCNN model, rectangular regions of interest which include an entire mass were selected from each of DCE-MRI images by an experienced radiologist. Three-fold cross validation method was used for training and testing of the proposed DCNN model. The classification accuracy, the sensitivity, the specificity, the positive predictive value, and the negative predictive value were 92.9% (52/56), 93.3% (28/30), 92.3% (24/26), 93.3% (28/30), and 92.3% (24/26), respectively. These results were substantially greater than those with the conventional method based on handcrafted features and a classifier. The proposed DCNN model achieved high classification performance and would be useful in differential diagnoses of masses in breast DCE-MRI images as a diagnostic aid.

[Post-transplant lymphoproliferative disorder localized to the colon presented with mild diarrhea after cord blood transplantation].

Post-transplant lymphoproliferative disorder (PTLD) usually develops with systemic symptoms, such as fever, generalized lymphadenopathy, and elevation in the lactate dehydrogenase level. Here, we present the case of a 65-year-old female patient with PTLD localized to the colon; the patient only had mild diarrhea without systemic symptoms. She had myelodysplastic syndrome and was treated with cord blood transplantation (CBT). She had a past medical history of sigmoid colon cancer treated with colonosectomy and adjuvant chemotherapy. After CBT, she achieved complete remission and was discharged after 60 days. Further, 79 days after CBT, she presented with abdominal pain. Computed tomography scan revealed adhesive ileus. The abdominal pain was resolved in 1 day with conservative treatment, however, mild diarrhea persisted. Therefore, we performed colonoscopy and found multiple ulcerative lesions in the upper colon. A pathological examination revealed PTLD. Furthermore, elevation of EBV-DNA in the blood was also confirmed. There was no detectable lesion on positron emission tomography-computed tomography (PET-CT) outside the colon; thus, we diagnosed PTLD localized into the colon that was successfully treated with rituximab. Our present experience suggests that it might be important to perform endoscopy and monitoring of EBV-DNA for early detection of PTLD, especially localized in the gastrointestinal tract.

Visual Hallucinations and Impaired Conscious Visual Perception in Parkinson Disease.

Visual hallucinations (VHs) are common in patients with Parkinson disease (PD), especially those with dementia, whereas auditory hallucinations are quite rare. Recent studies have revealed the involvement of several regions along the visual information-processing system that contribute to the pathophysiological mechanism of VHs: the eyes and retina, retinofugal projection, lateral geniculate nucleus, striate cortex, ventral pathways in the temporal cortices, and frontal and parietal cortices. In addition, the concurrent involvement of other systems in the brainstem and basal forebrain further modify VHs in PD. In this review, we discuss the pathophysiological association between the regional involvement of these areas and VHs.

[Development of skin squamous cell carcinoma on the scalp in a hydroxycarbamide-treated polycythemia vera patient].

Hydroxycarbamide is a widely used cytoreductive agent for treating polycythemia vera and essential thrombocythemia. Although hydroxycarbamide is usually well tolerated by most patients for long periods, some patients experience mucosal or cutaneous adverse events. Furthermore, a series of case report have indicated an association of hydroxycarbamide use with the development of non-melanoma skin cancer, especially in western countries. Here, we present the case of an elderly Japanese polycythemia vera patient who developed squamous cell carcinoma of the skin on the scalp after 10 years of exposure to hydroxyurea.

[Angioimmunoblastic T-cell lymphoma complicated with various autoimmune abnormalities and myelofibrosis].

Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with immunological abnormalities, such as hypergammaglobulinemia, autoimmune cytopenia, and the presence of various autoantibodies. Few reports on AITL have also described the development of myelofibrosis resulting from the invasion of lymphoma cells that produced various cytokines, including TGF-ß. Interestingly, recent studies demonstrated that autoimmunity can directly cause autoimmune myelofibrosis (AIMF). Usually, bone marrow fibrosis associated with AIMF is rapidly improved by treatment. Here, we describe our experience with a case of AITL complicated with the presence of numerous autoimmune abnormalities, including positive Coombs, anti-nuclear antibody, anti-ds-DNA antibody, anti-phospholipid antibody, and cold agglutinin tests. The patient presented with severe bone marrow fibrosis (MF-3) at the initial diagnosis. After two courses of the CHASE therapy, myelofibrosis rapidly disappeared, and the autoimmune abnormalities were ameliorated. These findings suggest that the bone marrow fibrosis observed in this case was partly attributable to an AIMF-like mechanism.

Guillain-Barré syndrome in a patient with renal cell carcinoma following the first course of pazopanib therapy.

Pazopanib, one of the antiangiogenic drugs, has recently become a first-line treatment for metastatic renal cell carcinoma. The most common adverse effects of pazopanib include diarrhea, fatigue, and nausea, but neuropathic complication has not been documented. Here, we report the first case of a patient with metastatic renal cell carcinoma who developed acute neuropathy mimicking Guillain-Barré syndrome following the first course of pazopanib therapy. A 75-year-old man with a metastatic renal cell carcinoma was admitted for rapidly progressive weakness and numbness in the extremities after the first course of pazopanib therapy. Neurological examination revealed symmetrical distal limb weakness, sensory disturbance, and areflexia. Based on the clinical pictures, conduction slowing on the nerve conduction studies of the extremities and albuminocytologic dissociation on the cerebrospinal fluid examination, a diagnosis of Guillain-Barré syndrome was made. After discontinuation of pazopanib and a subsequent high-dose intravenous immunoglobulin therapy, symptoms rapidly resolved and the patient became ambulatory with a cane. Serological and neuroradiological examinations failed to reveal any possible causes for the neuropathy other than pazopanib. While the benefits of pazopanib for metastatic renal cell carcinoma far outweigh this neurotoxic effect, physicians prescribing this drug should be aware of this rare complication of neuropathy.

Characteristics of Changes in Caregiver Burden during Follow-up at a Memory Clinic: A Retrospective Cohort Study.

Background: Because dementia is a long-term condition, the appropriate involvement of health-care professionals is considered important. However, little is known about the factors associated with changes in family caregiver burden. Objective: To clarify changes in family caregiver burden and associated factors during follow-up at a memory clinic. Methods: A retrospective cohort study was conducted, enrolling 495 pairs of patients with dementia or mild cognitive impairment and their family caregivers. A total of 120 pairs completed the second evaluation. The caregiver burden was assessed using the Zarit Burden Interview (ZBI). Data at the initial visit and after an average follow-up of about 2 years were compared and analyzed. Results: At initial visit, the patients' mean age, Mini-Mental State Examination (MMSE) and ZBI scores were 78.6±5.6 years, 23.3±3.5, and 22.6±16.7, respectively. At follow-up, MMSE scores decreased (21.4±4.5, p < 0.001), but ZBI scores remained similar (22.5±13.6). When the difference in ZBI scores between the two time points was defined as ΔZBI, and the related factors were analyzed by multiple regression analysis, ZBI scores at the initial visit, start of psychotropic drug, and decrease of neuropsychiatric symptoms were identified as significant factors (p < 0.001, p = 0.003, p < 0.001, respectively). A significant negative correlation was found between ZBI scores at the initial visit and ΔZBI (r = -0.588, p < 0.001). Conclusions: These findings suggest the importance of assessing changes in the burden experienced by family caregivers during the disease follow-up.

Potential Usefulness a Coronal View using an Automated Breast Ultrasound System in Detecting Breast Lesions.

Objective: An automated breast ultrasound system (ABUS) combined with screening mammography has increased cancer detection rates; however, supplemental ABUS use has increased recall rates. In this study, we aimed to identify an accurate and efficient method of ABUS interpretation and evaluate the potential usefulness of its coronal view versus the conventional transverse view. Materials and Methods: This retrospective observer study included comprised 114 ABUS cases (40 normal, 35 benign, 39 malignant). Ten physicians from multiple institutions interpreted the anonymized coronal and transverse views independently. The observers scored their confidence in the lesion detection for each case using a continuous scale and recorded reading times for each coronal and transverse view interpretation. Free-response receiver operating characteristic analysis was employed to compare detection accuracies between views; a paired t-test was used to compare the average reading times. Results: Detection accuracy did not differ significantly between the coronal and transverse views (figure of merit=0.740 and 0.745, respectively; p = 0.72). However, the average reading time for the coronal view was significantly shorter than that for the transverse view (149.7 vs. 200.3 seconds per case, p = 0.003). Conclusion: The coronal view obtained with the ABUS was useful for interpretation and associated with significantly shorter reading times compared with the conventional transverse view while maintaining breast lesion detection accuracy.

The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells.

To investigate the biological significance of Rho-associated coiled-coil-containing protein kinase (ROCK) 2 in the human trabecular meshwork (HTM), changes in both metabolic phenotype and gene expression patterns against a specific ROCK2 inhibitor KD025 were assessed in planar-cultured HTM cells. A seahorse real-time ATP rate assay revealed that administration of KD025 significantly suppressed glycolytic ATP production rate and increased mitochondrial ATP production rate in HTM cells. RNA sequencing analysis revealed that 380 down-regulated and 602 up-regulated differentially expressed genes (DEGs) were identified in HTM cells treated with KD025 compared with those that were untreated. Gene ontology analysis revealed that DEGs were more frequently related to the plasma membrane, extracellular components and integral cellular components among cellular components, and related to signaling receptor binding and activity and protein heterodimerization activity among molecular functions. Ingenuity Pathway Analysis (IPA) revealed that the detected DEGs were associated with basic cellular biological and physiological properties, including cellular movement, development, growth, proliferation, signaling and interaction, all of which are associated with cellular metabolism. Furthermore, the upstream regulator analysis and causal network analysis estimated IL-6, STAT3, CSTA and S1PR3 as possible regulators. Current findings herein indicate that ROCK2 mediates the IL-6/STAT3-, CSTA- and S1PR3-linked signaling related to basic biological activities such as glycolysis in HTM cells.

Prediction of early falls using adherence and balance assessments in a convalescent rehabilitation ward.

Objectives: To predict falls by adding an adherence assessment to a static balance ability assessment, and to evaluate fall prediction accuracy. Methods: This study included 416 patients who were admitted to a 45-bed convalescent rehabilitation ward over a 2-year period. The patients were assessed at the time of admission using the Standing Test for Imbalance and Disequilibrium (SIDE) and three additional, newly developed adherence items. Patients were divided into two groups: a group that experienced falls (fall group) and a group that did not experience falls (non-fall group) within 14 days of admission. The sensitivity and specificity of the assessment items for predicting falls were calculated. Results: Sensitivity was 0.86 and specificity was 0.42 when the cutoff was between SIDE levels 0-2a and 2b-4. Combining balance assessment using the SIDE with the memory and instruction adherence items improved fall prediction accuracy such that the sensitivity was 0.75 and the specificity was 0.64. Conclusions: Our analysis suggested that adherence assessment can improve fall risk prediction accuracy.

Examination of the lifestyle of head injury patients using the Frenchay Activities Index.

Objectives: The purpose of this study was to capture the lifestyle characteristics of traumatic brain injury (TBI) patients by administering the Frenchay Activities Index (FAI), a self-assessment questionnaire used for assessing life-related activities, among TBI patients. Methods: This study was conducted using the revised FAI Self-Assessment Form, administering an interview-based questionnaire survey to TBI patients and healthy participants. The target group comprised 60 traumatic brain injury patients who had progressed from at least 1 year since the injury, with a comparison group of 788 healthy participants. Results: A comparison of FAI scores between TBI patients and healthy participants by questionnaire revealed that TBI patients exhibited significantly higher FAI scores than healthy participants for outdoor walking and transportation use (Mann-Whitney U test, P<0.01). A comparison by occupation revealed that TBI patients were significantly less among the unemployed and other categories (Mann-Whitney U test, P<0.01). For office workers, government employees, high school students, and college students, scores were higher among TBI patients compared with healthy participants, although the differences were not significant. Conclusions: Although TBI patients were less active than healthy participants in life-related activities, their scores for cleaning up after meals and cleaning and putting things in order were close to those of healthy participants, indicating that TBI patients cannot be considered to be inactive. The findings also revealed differences in TBI patients' engagement in life-related activities and frequency of activities depending on their social position.

The chaperone protein GRP78 released from MPN cells increases the expression of lysyl oxidase in a human stromal cell line.

Impaired function of the endoplasmic stress (ER) response causes numerous pathological conditions, including tissue fibrosis. In the present study, we aimed to determine the pathological role of ER stress response systems in myeloproliferative neoplasms (MPNs). We found increased expression of the chaperone protein glucose-regulated protein (GRP) 78, a central regulator of ER stress, in megakaryocytes from primary myelofibrosis or postessential thrombocythemia myelofibrosis patients. GRP78 was overexpressed in JAK2V617F-harboring cell lines; however, inhibitors of ER stress did not affect the expression levels of GRP78. In contrast, ruxolitinib, a well-known inhibitor of JAK2V617F, clearly blocked GRP78 expression in these cells through downregulation of transcription factor 4 (ATF4). Interestingly, GRP78 was secreted from HEL and SET-2 cells into culture media. Coculture of these cells with HS-5 cells, a human bone marrow stroma-derived cell line, induced enhanced expression of lysyl oxidase (LOX), which mediates cross-linking of collagen fibers and induces tissue fibrosis, in HS-5 cells. An anti-GRP78 neutralizing antibody abrogated LOX elevation; in contrast, recombinant GRP78 protein induced LOX protein expression in HS-5 cells. Our observations suggest that the oncogenic protein JAK2V617F induces overexpression and release of GRP78, which may induce a fibrotic phenotype in surrounding bone marrow stromal cells.