Background
Most studies on lower limb lymphedema have been conducted in gynecologic cancer patients who underwent surgery for gynecologic malignancy. This study aimed to evaluate the risk factors for ...lower limb lymphedema development in gynecologic cancer patients who underwent initial treatment.
Methods
A retrospective cohort design was used to follow 903 gynecologic cancer patients who underwent treatment at Kurume University Hospital between January 1, 2013 and December 31, 2015. Data analyses were performed in 356 patients, and the patients were followed up until December 31, 2017. The model comprised two components to facilitate statistical model construction. Specifically, a discrete survival time model was constructed, and a complementary log–log link model was fitted to estimate the hazard ratio. Associations between risk factors were estimated using generalized structural models.
Results
The median follow-up period was 1083 (range 3–1819) days, and 54 patients (15.2%) developed lower limb lymphedema, with a median onset period of 240 (range 3–1415) days. Furthermore, 38.9% of these 54 patients developed lower limb lymphedema within 6 months and 85.2% within 2 years. International Federation of Gynecology and Obstetrics stage, radiotherapy, and number of lymph node dissections (≥ 28) were significant risk factors.
Conclusion
Simultaneous examination of the relationship between lower limb lymphedema and risk factors, and analysis among the risk factors using generalized structural models, enabled us to construct a clinical model of lower limb lymphedema for use in clinical settings to alleviate this condition and improve quality of life.
Patients with Parkinson's disease are often frail and likely to be malnourished. Several studies have reported the adverse effects of malnutrition on functional outcomes; however, the association ...between nutritional status and activities of daily living is unclear among patients with Parkinson's disease. This study aimed to investigate the relationship between nutritional status and activities of daily living in patients with Parkinson's disease. We conducted a retrospective cohort study with the data of 124 patients who were consecutively admitted to a rehabilitation hospital in Japan, among whom the data of 61 patients were included in the analyses. The Controlling Nutritional Status score was used to measure the nutritional status of the participants, and the motor subdomain of the Functional Independence Measure was used to assess the activities of daily living. Piecewise linear mixed-effects models were fitted to the data after adjusting for confounding factors. A poor nutritional status (i.e., Controlling Nutritional Status score >3) was significantly associated with a poor Functional Independence Measure gain, which was defined as difference in the score values of the Functional Independence Measures between discharge and admission. Our findings could aid in developing nutritional intervention programs for patients with Parkinson's disease by employing the Controlling Nutritional Status score to improve their activities of daily living.
Objective
The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, ...which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF‐15) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF‐15 is a more useful biomarker for MDs than several conventional biomarkers.
Methods
We measured the serum levels of GDF‐15 and fibroblast growth factor 21 (FGF‐21), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF‐15 and FGF‐21 concentrations were measured by enzyme‐linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate‐to‐pyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS).
Results
Mean GDF‐15 concentration was 6‐fold higher in MD patients compared to healthy controls (2,711 ± 2,459 pg/ml vs 462.5 ± 141.0 pg/mL; p < 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF‐15 than FGF‐21 and other conventional biomarkers. Our date suggest that GDF‐15 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity.
Interpretation
Our results suggest that measurement of GDF‐15 is the most useful first‐line test to indicate the patients who have the mitochondrial respiratory chain deficiency. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696
CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate‐cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species ...(ROS). This mechanism confers ROS resistance to CSC and CD44v9‐expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS‐mediated apoptosis. Twenty non‐pretreated HCC tissues and 7 HCC tissues administered HAIC therapy with CDDP before surgical resection were subjected to immunohistochemistry analysis of CD44v9 and xCT expression. Human HCC cell lines HAK‐1A and HAK‐1B were used in this study; the latter was also used for xenograft experiments in nude mice to assess in vivo efficacy of combination treatment. CD44v9 positivity was significantly higher in HAIC‐treated tissues (5/7) than in non‐pretreated tissues (2/30), suggesting the involvement of CD44v9 in the resistance to HAIC. xCT was significantly expressed in poorly differentiated HCC tissues. Combination treatment effectively killed the CD44v9‐harboring HAK‐1B cells through ROS‐mediated apoptosis and significantly decreased xenografted tumor growth. In conclusion, the xCT inhibitor SASP augmented ROS‐mediated apoptosis in CDDP‐treated HCC cells, in which the CD44v9‐xCT system functioned. As CD44v9 is typically expressed in HAIC‐resistant HCC cells, combination treatment with SASP with CDDP may overcome such drug resistance.
This study is the first to show high expression of CD44v9, a cancer stem cell marker, in chemoresistant hepatocellular carcinoma cells, which were previously exposed to chemotherapeutic agents through hepatic arterial infusion chemoembolization.
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (OMIM 540000) is the most dominant subtype of mitochondrial myopathy. The aim of this study was to determine ...the prevalence, natural course, and severity of MELAS.
A prospective cohort study of 96 Japanese patients with MELAS was followed between June 2003 and April 2008. Patients with MELAS were identified and enrolled based on questionnaires administered to neurologists in Japan. MELAS was defined using the Japanese diagnostic criteria for MELAS. Two follow-up questionnaires were administered to neurologists managing MELAS patients at an interval of 5years.
A prevalence of at least 0.58 (95% confidential interval (CI), 0.54–0.62)/100,000 was calculated for mitochondrial myopathy, whereas the prevalence of MELAS was 0.18 (95%CI, 0.02–0.34)/100,000 in the total population. MELAS patients were divided into two sub-groups: juvenile form and adult form. Stroke-like episodes, seizure and headache were the most frequent symptoms seen in both forms of MELAS. Short stature was significantly more frequent in the juvenile form, whereas hearing loss, cortical blindness and diabetes mellitus were significantly more frequent in the adult form. According to the Japanese mitochondrial disease rating scale, MELAS patients showed rapidly increasing scores (mean±standard deviation, 12.8±8.7) within 5years from onset of the disease. According to a Kaplan–Meier analysis, the juvenile form was associated with a higher risk of death than the adult form (hazard ratio, 3.29; 95%CI, 1.32–8.20; p=0.0105).
We confirmed that MELAS shows a rapid degenerative progression within a 5-year interval and that this occurs in both the juvenile and the adult forms of MELAS and follows different natural courses. This article is part of a Special Issue entitled: Biochemistry of Mitochondria.
►The disease-based prevalence of MELAS is 0.18/100,000 in Japanese cohort study. ►MELAS has two subtypes, juvenile and adult, characterized by severity of disease. ►MELAS is a very severe disorder among mitochondrial myopathies. ►JMDRS is useful for evaluation of the disease progression in MELAS. ►Stroke-like episodes, headache and convulsion are the common symptoms in MELAS.
Abstract The Strengths and Difficulties Questionnaire (SDQ) is a short screening instrument which addresses the positive and negative behavioral attributes of infants, children and adolescents. The ...SDQ is widely used to evaluate child developmental disabilities, psychological and psychiatric conditions or disorders in Japan. However, we did not have normative data for the Japanese version until now. To establish the community-based data and properties for the Japanese version, we collected and evaluated parent ratings of a total of 2899 Japanese children aged 4–12 years, including 1463 boys and 1436 girls. Statistical evaluation of psychometric properties included a factor analysis verifying the proposed scale structure, an assessment of scale homogeneities, and the determination of age, gender and relationship of each difficulties scale, or prosocial scale. The total difficulties score in boys (8.70 ± 5.03) was higher than in girls (7.86 ± 4.88). Based on the distributions of SDQ scores observed in the Japanese community sample, recommended bandings identifying normal, borderline, and abnormal (clinical ranges) were defined for each scale, and some gender difference was found in some difficulties and prosocial SDQ scores. After evaluating parent ratings obtained in a community-based sample, the Japanese SDQ was shown to possess favorable psychometric properties. Thus, the Japanese translation of this popular and versatile instrument seems to be approximately as reliable and useful as the original English questionnaire.
Background
Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to ...patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients.
Aims
To stratify the risk of PEP for CBD stones based on CBD-related diseases.
Methods
A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm’s method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A.
Results
The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted
p
values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%;
p
< 0.001).
Conclusions
The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.
To prevent unpleasant symptoms in medical students during systematic anatomy practice, we aimed to develop and validate a model that predicts the likelihood of these symptoms occurring during ...practice based on risk factors prior to the start of practice. A total of 452 medical students enrolled from 2014 to 2018 were surveyed before and during practice, with questions regarding their sex, psychological status, subjective symptoms, and allergies. The sum of the scores concerning three subjective symptoms related to the eyes and three subjective symptoms related to the nose and fatigue were defined as the “eye-score” and “mask-score,” respectively, and a total score of 7 or more was considered symptomatic. A prediction model was developed based on a generalized linear mixed model; the outcome variable in the model was symptoms during practice, and the explanatory variables were indoor formaldehyde concentration during practice, sex, and pre-practice status, such as the students’ psychological state, eye-score, mask-score, and the presence of allergies. Five-fold cross-validation was used to assess internal validity and the prediction model was applied to 110 medical students enrolled in 2021 to assess external validity. The sensitivity and specificity by five-fold cross-validation were 0.843 and 0.314 for eye symptoms and 0.847 and 0.432 for mask symptoms. In the external validity assessment, the sensitivity and specificity were 0.889 and 0.207 for eye symptoms and 0.879 and 0.532 for mask symptoms. The prediction model developed in this study can be used in future measures aimed at preventing symptoms in students.
Programmed death ligand 1 (PD-L1) has been reported to be expressed in various malignancies and is considered to be a prognostic factor and an immunotherapeutic target. The aim of this study was to ...characterize PD-L1 expression in thymoma and determine statistical associations between this expression and clinical features.
We reviewed formalin-fixed, paraffin-embedded tissue specimens from 82 thymoma cases accumulated at Kurume University, the majority of which achieved surgical complete resection. Expression of PD-L1 was evaluated by immunohistochemistry. Statistical associations between PD-L1 expression and clinicopathologic features were evaluated by using χ(2) test and Fisher's exact test. Disease-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test. Predictive factors for disease-free survival after complete resection were analyzed by using a Cox proportional hazards model in univariate and multivariate analysis.
Overall, 44 thymoma cases (54%) revealed high PD-L1 expression. High PD-L1 expression was statistically associated with Masaoka stage III/IV disease (p = 0.043) and World Health Organization type B2 or B3 thymoma (p = 0.044). Disease-free survival after complete resection in high PD-L1 expression was significantly worse than that in low PD-L1 expression (p = 0.021), although there was no significant difference in overall survival (p = 0.957). Multivariate analysis also revealed high PD-L1 expression as an independent risk factor for recurrence (p = 0.008).
Characterization of PD-L1 expression in thymoma should enable more effective clinical approaches, including prognostic stratification of patients and potential use of anti-PD-L1 antibody immunotherapy.
This study aimed to validate the Japanese version of the Child’s Sleep Habits Questionnaire (CSHQ-J) and identify which factors affect the CHSQ-J total score.
The participants were 3158 children ...(aged 4–12 years) and their parent/guardian, as community samples from large, medium-sized, and small cities. Each parent/guardian filled in the questionnaire set (CSHQ-J, Pittsburgh Sleep Quality Index, demographic data: family structure, sleep environment, participants’ present illness, and economic information); we also collected 51 clinical samples from our facility to calculate the cutoff score. According to the age of the participants in the original CSHQ (4–10 years), validation was assessed statistically via exploratory and confirmatory factor analyses and internal consistency (verified by Cronbach’s α). Multivariate analysis was conducted to identify factors affecting the CSHQ-J total score.
We received responses from 2687 participants (response rate: 85%) and analyzed 1688 participants who were the age of the original CSHQ participants. The alpha coefficients of each subscale of the CSHQ-J ranged from 0.43 to 0.68. The cutoff score was 48 (sensitivity: 0.69, specificity: 0.79). The confirmatory and exploratory factor analyses did not converge. Multivariate analysis showed that the factors that significantly influenced the CSHQ-J total score were co-sleeping, supplemental sleep, and child’s age. Present illness, especially adenoids, also significantly influenced CSHQ total score.
The CSHQ-J has adequate internal consistency and is useful for screening for pediatric sleep disorders. Supplemental sleep, habit of co-sleeping, and child’s age should be considered when using the CSHQ-J as a screening tool for sleep problems in children.
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