Relationship between quantitative physical activity and deterioration of locomotive function: a cross-sectional study using baseline data from a cohort.

BACKGROUND: In aged society, health policies aimed at extending healthy life expectancy are critical. Maintaining physical activity is essential to prevent the deterioration of body functions. Therefore, it is important to understand the physical activity levels of the target age group and to know the content and intensity of the required physical activity quantitatively. Especially we focused the role of non-exercise activity thermogenesis and sedentary time, which are emphasized more than the introduction of exercise in cases of obesity or diabetes. METHODS: A total of 193 patients from 25 institutions were included. Participants underwent a locomotive syndrome risk test (stand-up test, 2-step test, and Geriatric Locomotive Function Scale-25 questionnaire) and were classified into three stages. Physical activity was quantitatively monitored for one week with 3-axial accelerometer. Physical activity was classified into three categories; (1) Sedentary behavior (0 ∼ ≤ 1.5 metabolic equivalents (METs)), (2) Light physical activity (LPA:1.6 ∼ 2.9 METs), and (3) Moderate to vigorous physical activity (MVPA: ≥3 METs). We investigated the relationship between physical activity, including the number of steps, and the stages after gender- and age- adjustment. We also investigated the relationship between social isolation using Lubben's Social Network Scale (LSNS), as social isolation would lead to fewer opportunities to go out and less outdoor walking. RESULTS: Comparison among the three stages showed significant difference for age (p = 0.007) and Body Mass Index (p < 0.001). After gender-and age-adjustment, there was a significant relation with a decrease in the number of steps (p = 0.002) and with MVPA. However, no relation was observed in sedentary time and LPA. LSNS did not show any statistically significant difference. Moderate to high-intensity physical activity and the number of steps is required for musculoskeletal disorders. The walking, not sedentary time, was associated to the locomotive stages, and this finding indicated the importance of lower extremity exercise. CONCLUSIONS: Adjusting for age and gender, the number of steps and moderate to vigorous activity levels were necessary to prevent worsening, and there was no effect of sedentary behavior. Merely reducing sedentary time may be inadequate for locomotive disorders. It is necessary to engage in work or exercise that moves lower extremities more actively.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography.

BACKGROUND: Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension (CTEPH), approximately 20%-29% of patients exhibit a restrictive pattern on pulmonary function testing. AIM: To quantify longitudinal changes in lung volume and cardiac cross-sectional area (CSA) in patients with CTEPH. METHODS: In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019, we evaluated 15 patients with CTEPH who had chest computed tomography (CT) performed at baseline and after at least 6 mo of therapy. We matched the CTEPH cohort with 45 control patients by age, sex, and observation period. CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test. RESULTS: Total, right lung, and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline (total, P = 0.004; right lung, P = 0.003; right lower lobe; P = 0.01). In the CTEPH group, the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group (total, P = 0.01; right lung, P = 0.007; right lower lobe, P = 0.01; CSA, P = 0.0002). There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort. CONCLUSION: After at least 6 mo of treatment, CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

Generalization of a clinical diagnosis support tool for lumbar spinal stenosis: Can the ankle brachial pressure index be replaced by palpation of the posterior tibial artery in the lumbar spinal stenosis diagnostic support tool? (DISTO project).

BACKGROUND: The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. METHODS: This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. RESULTS: The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. CONCLUSION: When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. LEVEL OF EVIDENCE: Level 3.

Association of serum s-adenosylmethionine, s-adenosylhomocysteine, and their ratio with the risk of dementia and death in a community.

We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007-2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

Diagnostic accuracy of the lumbar spinal stenosis-diagnosis support tool and the lumbar spinal stenosis-self-administered, self-reported history questionnaire.

Despite the applicability of the lumbar spinal stenosis (LSS)-diagnosis support tool (DST) and the LSS-self-administered, self-reported history questionnaire (SSHQ), their diagnostic accuracy has never been compared with that of the well-known North American Spine Society (NASS) clinical description of LSS. This study aimed to compare the diagnostic accuracy of the two diagnostic tools with that of the NASS guidelines' clinical description of LSS in a Japanese secondary care hospital setting. This multicenter cross-sectional study used data from the lumbar spinal stenosis diagnostic support tool (DISTO) project, which was conducted from December 1, 2011 to December 31, 2012. Japanese adults with low back pain (LBP) aged ≥20 years were consecutively included. The reference standard was LSS diagnosed by orthopedic physicians. The diagnostic accuracy of the two support tools was compared. Of 3,331 patients, 1,416 (42.5%) patients were diagnosed with LSS. The NASS clinical description of LSS had a sensitivity of 63.9% and specificity of 89.5%. The LSS-DST and LSS-SSHQ had sensitivities of 91.3% and 83.8% and specificities of 76.0% and 57.6%, respectively, with substantial improvements in sensitivity (P < 0.0001). Similar results were obtained when we limited included patients to those aged >60 years. These findings indicated that the LSS-DST and LSS-SSHQ were more sensitive in screening patients with LBP for a diagnosis of LSS than the NASS clinical description of LSS. This study strongly supports prioritizing the use of either of these two diagnostic support tools for screening.

Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis.

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.

Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).

BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

Clinical characteristics of hoarding disorder in Japanese patients.

Previous studies have reported clinical characteristics of hoarding disorder (HD), such as early onset, a chronic course, familiality, high unmarried rate, and high rates of comorbidities. However, clinical research targeting Japanese HD patients has been very limited. As a result, there is a low recognition of HD in Japan, leading to insufficient evaluation and treatment of Japanese HD patients. The aim of the current study was to delineate the clinical characteristics of Japanese HD patients. Thirty HD patients, 20 obsessive-compulsive disorder (OCD) patients, and 21 normal controls (NC) were targeted in this study. The HD group had a tendency toward higher familiality, earlier onset, and longer disease duration compared to the OCD group. In addition, the HD group showed a significantly higher unmarried rate than the NC group. The top two comorbidities in the HD group were major depressive disorder (56.7%) and attention-deficit/hyperactivity disorder (26.7%). The HD group had significantly higher scores on hoarding rating scales and lower scores on the Global Assessment of Functioning Scale than the other two groups. The current study showed a clinical trend in Japanese HD patients similar to previous studies in various countries, suggesting that HD may be a universal disease with consistent clinical symptoms.

Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia.

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.

Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke: A Randomized Clinical Trial and Meta-analysis.

IMPORTANCE: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that a systolic blood pressure (BP) target less than 120 mm Hg was superior to less than 140 mm Hg for preventing vascular events. This trial excluded patients with prior stroke; therefore, the ideal BP target for secondary stroke prevention remains unknown. OBJECTIVE: To assess whether intensive BP control would achieve fewer recurrent strokes vs standard BP control. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial (RCT) of standard vs intensive BP control in an intent-to-treat population of patients who had a history of stroke. Patients were enrolled between October 20, 2010, and December 7, 2016. For an updated meta-analysis, PubMed and the Cochrane Central Library database were searched through September 30, 2018, using the Medical Subject Headings and relevant search terms for cerebrovascular disease and for intensive BP lowering. This was a multicenter trial that included 140 hospitals in Japan; 1514 patients who had a history of stroke within the previous 3 years were approached, but 234 refused to give informed consent. INTERVENTIONS: In total, 1280 patients were randomized 1:1 to BP control to less than 140/90 mm Hg (standard treatment) (n = 640) or to less than 120/80 mm Hg (intensive treatment) (n = 640). However, 17 patients never received intervention; therefore, 1263 patients assigned to standard treatment (n = 630) or intensive treatment (n = 633) were analyzed. MAIN OUTCOMES AND MEASURES: The primary outcome was stroke recurrence. RESULTS: The trial was stopped early. Among 1263 analyzed patients (mean [SD] age, 67.2 [8.8] years; 69.4% male), 1257 of 1263 (99.5%) completed a mean (SD) of 3.9 (1.5) years of follow-up. The mean BP at baseline was 145.4/83.6 mm Hg. Throughout the overall follow-up period, the mean BP was 133.2/77.7 (95% CI, 132.5-133.8/77.1-78.4) mm Hg in the standard group and 126.7/77.4 (95% CI, 125.9-127.2/73.8-75.0) mm Hg in the intensive group. Ninety-one first recurrent strokes occurred. Nonsignificant rate reductions were seen for recurrent stroke in the intensive group compared with the standard group (hazard ratio [HR], 0.73; 95% CI, 0.49-1.11; P = .15). When this finding was pooled in 3 previous relevant RCTs in a meta-analysis, the risk ratio favored intensive BP control (relative risk, 0.78; 95% CI, 0.64-0.96; P = .02; absolute risk difference, -1.5%; 95% CI, -2.6% to -0.4%; number needed to treat, 67; 95% CI, 39-250). CONCLUSIONS AND RELEVANCE: Intensive BP lowering tended to reduce stroke recurrence. The updated meta-analysis supports a target BP less than 130/80 mm Hg in secondary stroke prevention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01198496.

Validation of a novel digital health monitoring system to measure the volume of voided urine.

AIM: To validate a novel digital health monitoring system to measure the volume of voided urine. METHODS: Micturition volume was calculated using our novel digital self-health monitoring system of urine excretion (s-HMSU) in 18 participants (16 women and 2 men; average age, 40.8 years), without a history of voiding symptoms. Participants completed a self-reported questionnaire regarding their medical history and water intake during the period of observation, as well as the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. To assess the reliability of the voided volumes measured using the s-HMSU, the intraclass correlation coefficient (ICC) was calculated between the volume and the change in body weight before and after micturition. RESULTS: The CLSS questionnaire confirmed the absence of urinary system diseases in all participants. The medical history was also negative with the exception of hypertension in one participant. The ICC (1,1) between the measured volume of urine excretion using the s-HMSU and the change in body weight was 0.972 (95% confidence interval, 0.957-0.982). CONCLUSIONS: The s-HMSU system provides a reliable measure of voiding volume and is appropriate for home use. It has the potential to facilitate large-scale clinical research to examine the relationship between medical diseases and voiding dysfunction.

Longitudinal Changes of Physical Activity and Sedentary Time in the Middle-Aged and Older Japanese Population: The Hisayama Study.

BACKGROUND: The purpose of this study was to describe changes in physical activity volumes and sedentary time over 3 years in the middle-aged and older Japanese population. METHODS: Study participants included 1151 Japanese community-dwelling residents aged ≥40 years in 2009 who underwent 2 sets of health examinations (2009 and 2012). Using a triaxial accelerometer, longitudinal changes in sedentary time, light physical activity volume, moderate to vigorous physical activity volume, number of steps, and total physical activity volume were evaluated according to sex, age (40-49, 50-59, 60-69, 70-79, and ≥80 y), and obese (nonobese and obese) categories. RESULTS: Sedentary time significantly increased, and all physical activity volumes significantly decreased among all participants. Although most variables did not change significantly in the 40-49 and 50-59 year age categories, similar changes as all participants were observed across all other categories. In the correlation analyses, changes in sedentary time correlated, at most, only modestly for each change in physical activity volumes, indicating that increased physical activity volume does not always lead to decreased sedentary time, and vice versa. CONCLUSIONS: Strategies to reduce sedentary time and promote physical activity are needed in Japan, particularly for people aged ≥60 years.

Reference values of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire in patients with lumbar spinal stenosis and characteristics of deterioration of QOL: Lumbar Spinal Stenosis Diagnosis Support Tool: DISTO project.

BACKGROUND: The reference values of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in patients with lumbar spinal stenosis (LSS) are still unknown. This multicenter cross-sectional survey was performed to determine the reference values and disease-specific characteristics of deterioration of QOL caused by LSS itself, not by aging, through comparison of patients with and without LSS who had an outpatient visit for low back pain by age and sex groups. METHODS: The present study was performed at 564 medical centers and clinics. The JOABPEQ was measured for 8338 patients aged 20 years or over who came to an outpatient clinic for low back pain (LBP) and were examined for whether they had LSS using the LSS diagnosis support tool (LSS-DST). Scores in the five JOABPEQ domains were compared between the LSS group and the LBP without LSS group (LBP group) for each age and sex group. RESULTS: Scores for Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders were significantly lower in the LSS group than in the LBP group. CONCLUSION: The percentiles of JOABPEQ scores in patients with LSS were clarified and could be used as reference values. Deterioration of QOL caused by LSS itself, not by aging, are characterized by Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders.

Race and nodal disease status are prognostic factors in patients with stage IVB cervical cancer.

BACKGROUND: Patients presenting with stage IVB cervical cancer pose a significant clinical challenge. While previous studies described several poor prognostic factors, they were limited by small sample sizes. The aim of this study was to identify clinicopathological prognostic factors in a large sample of patients with stage IVB cervical cancer at a single institution. METHODS: Patients with primary stage IVB cervical cancer diagnosed between 1992 and 2011 were extracted from a search of the MD Anderson Cancer Center registry. Clinicopathological data retrieved from their medical records included demographics (age and race), tumor characteristics (primary lesion size, grade, and histology), TNM classification, and metastatic site (nodal/organ). Treatment approach (radiation, chemotherapy, or both) and intent (palliation or curative) were recorded. Survival rates were evaluated using the Kaplan-Meier method. Cox proportional hazards regression was used to model the association between key variables and overall survival (OS). RESULTS: Two hundred sixty-six patients with stage IVB cervical cancer were identified. Their median OS was 12.7 months. The hazard ratio for African-Americans vs. patients with other ethnicities was 1.76 (95% confidence interval [CI], 1.18-2.54, P = 0.0063), and that for patients with para-aortic nodes alone vs. more extensive metastases was 0.37 (95% CI, 0.26-0.51, P < 0.0001). Other clinicopathological factors were not significantly associated with survival. CONCLUSIONS: African-American race was an independent adverse prognostic factor in this cohort. On the other hand, nodal disease in the para-aortic chain alone predicted a favorable prognosis.

Establishment of reference scores and interquartile ranges for the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in patients with low back pain.

BACKGROUND: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was developed in 2007, including the five domains of Pain-related disorder, Lumbar spine dysfunction, Gait disturbance, Social life disturbance, and Psychological disorder. It is used by physicians to evaluate treatment efficacy by comparing scores before and after treatment. However, the JOABPEQ does not allow evaluation of the severity of a patient's condition compared to the general population at a single time point. Given the unavailability of a standard measurement of back pain, we sought to establish reference scores and interquartile ranges using data obtained from a multicenter, cross-sectional survey taken in Japanese primary care settings. METHODS: The Lumbar Spinal Stenosis Diagnosis Support Tool project was conducted from 2011 to 2012 in 1657 hospitals in Japan to investigate the establishment of reference scores using JOABPEQ. Patients aged ≥ 20 years undergoing medical examinations by either non-orthopaedic primary care physicians or general orthopedists were considered for enrollment. RESULTS: A total of 10,651 consecutive low back pain patients (5331 men, 5320 women, 18 subjects with missing sex data) who had undergone a medical examination were included. Reference scores and interquartile ranges for each of the five domains of the JOABPEQ according to age and sex were recorded. The median score and interquartile range are the same in the domain of Pain-related disorder in all ages and sexes. The reference scores for Gait disturbance, Social life disturbance and Psychological disorder declined with increasing age in both age- and sex-stratified groups, while there was some different trend in Lumbar spine dysfunction between men and women. CONCLUSION: Reference scores and interquartile ranges for JOABPEQ were generated based on the data from the examination data. These provide a measurement standard to assess patient perceptions of low back pain at any time point during evaluation or therapy.

Prognostic implications of HER2 heterogeneity in gastric cancer.

The prognostic implications of human epidermal growth receptor 2 (HER2) heterogeneity in gastric cancer (GC) are not well established. Therefore, the aim of the present study was to determine to the effect of HER2 status on the prognosis of GC patients. We retrieved data on 248 pathologically-confirmed, consecutive patients with primary adenocarcinoma of the stomach or gastro-esophageal junction who underwent surgical resection at Kurume University Medical Center between July 2000 and December 2012. HER2 status was classified as HER2 positive or negative and HER2 heterogeneity or homogeneity. The endpoint was overall survival (OS), which was compared using the generalized Wilcoxon test. HER2 status was positive in 36 patients (14.5%) and negative in 212 patients (85.5%). Among the 36 HER2 positive patients, 25 patients (69.4%) had HER2 heterogeneity and the remaining 11 patients (30.6%) had HER2 homogeneity. Among the 141 patients with stage III or IV disease, the prognosis of the HER2 homogeneity group was significantly worse than that of the HER2 heterogeneity group (p = 0.019; median OS 193 and 831 days, respectively). The prognosis was not significantly different between the HER2 positive group and the HER2 negative group (p = 0.84; median OS 552 and 556 days, respectively). The present study was conducted with small samples, however, the results of the study suggest that HER2 homogeneity but not HER2 positivity may represent a prognostic indicator in GC.

Augmented Association Between Blood Pressure and Proteinuria in Hyperuricemic Patients With Nonnephrotic Chronic Kidney Disease.

BACKGROUND: Hyperuricemia (HU) may enhance susceptibility to hypertensive renal damage via disrupted autoregulation of glomerular hemodynamics. The effect of HU on the association between blood pressure (BP) and proteinuria remains unknown in patients with chronic kidney disease (CKD). METHODS: In total, 109 patients with nonnephrotic CKD (55 men and 54 females) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. Correlation between BP and urine protein (UP) level was examined based on the presence of HU, which was defined as the use of urate-lowering drugs or serum uric acid levels of ≥7 and ≥5 mg/dl in males and females, respectively, which were associated with increased risks of hyalinosis in our previous study. RESULTS: Median age, BP, estimated glomerular filtration rate, and UP level were 38 years, 124/74 mm Hg, 82 ml/min/1.73 m2, and 0.8 g/gCr, respectively. In patients with HU (n = 59), log-transformed systolic BP (SBP) was significantly correlated with log-transformed UP level (r = 0.49, P < 0.0001); this was not observed in patients without HU (n = 50). Multiple regression analysis (R2 = 0.21, P = 0.0001) revealed that the interaction between HU and log-transformed SBP with respect to proteinuria was significantly correlated with log-transformed UP level (ß = 7.0, P = 0.03), independent of age, sex, and potential confounding factors; however, this statistical significance was completely eliminated after adjustment for the arteriolar hyalinosis index. CONCLUSIONS: HU potentiates susceptibility to hypertensive glomerular damage via disrupted autoregulation in patients with nonnephrotic CKD.

Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan.

AIM: The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan. METHODS: Two hundred and fifty-six patients diagnosed with AIH were enrolled. A person-year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from "The Monitoring of Cancer Incidence in Japan Project" in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined. RESULTS: Twenty-seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34-2.96), and was high among female patients at 2.49 (95% CI, 1.60-3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05-25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45-40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64-52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485). CONCLUSION: The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.

Development and validation of a risk assessment tool for gastric cancer in a general Japanese population.

BACKGROUND: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. METHODS: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the validation cohort. RESULTS: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort. CONCLUSIONS: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual's risk of future gastric cancer.

White-coat and masked hypertension are associated with albuminuria in a general population: the Hisayama Study.

Epidemiological and clinical studies have investigated the influence of hypertension on chronic kidney disease (CKD), but limited data are available for the associations of white-coat hypertension (WCHT), masked hypertension (MHT) and sustained hypertension (SHT) with kidney dysfunction in general populations. We examined the associations of these types of hypertension with CKD (albuminuria and reduction in estimated glomerular filtration rate (eGFR)) in a cross-sectional survey of 2974 community-dwelling Japanese aged ⩾40 years. The types of hypertension were defined based on combined measurements of clinic and home blood pressures. Albuminuria was determined as urinary albumin-creatinine ratio (UACR) levels ⩾30.0 mg g-1. The eGFR was calculated using the Japanese equation. The age- and sex-adjusted geometric mean of the UACR values was significantly higher in the subjects with WCHT (20.2 mg g-1), MHT (19.6 mg g-1) and SHT (31.6 mg g-1) than in those with normotension (NT) (12.5 mg g-1) (all P<0.001). Compared with NT, all types of hypertension were significantly associated with an increased likelihood of albuminuria (the age- and sex-adjusted prevalence of albuminuria; NT 14.1%, WCHT 26.3%, MHT 26.4% and SHT 43.3%; all P<0.001). These associations remained significant even after adjustment for other risk factors. However, the age- and sex-adjusted mean of eGFR and the prevalence of low eGFR (<60 ml min-1 per 1.73 m2) did not differ between NT and the three hypertension types. The associations of the types of hypertension with the likelihood of CKD were similar to those for albuminuria. Our findings suggest that WCHT, MHT and SHT are associated with albuminuria in the general Japanese population.