Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Comparison of survival times of advanced cancer patients with palliative care at home and in hospital.

OBJECTIVES: One primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments. METHOD: We compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay. RESULTS: A total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1-11.8] vs. 9 days [95% CI 8.3-10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9-35.4] vs. 22 days [95% CI 20.3-22.9], p < 0.001), and the Months Prognosis, (65 days [95% CI 58.2-73.2] vs. 32 days [95% CI 28.9-35.4], p < 0.001). CONCLUSION: In this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.

Accumulated unhealthy behaviours and insomnia in Japanese dwellers with and without cardiovascular risk factors: a cross-sectional study.

OBJECTIVES: To date, the association between accumulated unhealthy behaviours and insomnia in individuals stratified according to the presence or absence of major cardiovascular risk factors is unclear. This study aimed to examine the effect of accumulated unhealthy behaviours on insomnia in Japanese dwellers. DESIGN: Cross-sectional study. SETTING: Baseline data between April 2012 and March 2015. PARTICIPANTS: Our study used cross-sectional data among Japanese aged 35-74 years in a rural community (N=9565), the attendees of annual municipal or work site health check-up programmes. MAIN OUTCOME MEASURES: Insomnia was assessed by Athens Insomnia Scale, which was set at 6 points and greater; other scales were given. Participants were categorised into three groups by their number of unhealthy behaviours (no exercise habit, smoking, alcohol drinking, skipping breakfast and obesity): 0-1, 2-3, 4 or more. The association between accumulated unhealthy behaviours and insomnia was estimated by logistic regression analysis. Further analysis was done after stratification of cardiovascular risk factors assessed by anthropometrics and clinical biochemistry measurements. RESULTS: The overall prevalence of insomnia was 13.3% for men and 19.3% for women. Men with unhealthy behaviour factors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy group (trend p=0.013). Women with four or more unhealthy behaviour factors were more likely to have insomnia, compared with the lowest groups (OR 1.175, 95% CI 1.077 to 1.282). Insomnia has an association with the unhealthy behaviours among men without cardiovascular risk factors (lowest groups: OR 1.133, 95% CI 1.037 to 1.238, trend p=0.026). Women without hypertension were more likely to have suspected insomnia, compared with the lowest group (OR 1.215, 95% CI 1.101 to 1.341). CONCLUSION: The results showed accumulated unhealthy behaviours were associated with increased risk of insomnia in Japanese dwellers. For healthy population without cardiovascular risk factors, unhealthy behaviours should be considered as background conditions for insomnia.

Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV1 Decline: A Longitudinal Cohort Study.

BACKGROUND: Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV1) decline. METHODS: Participants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV1 measurement in 2012-2014 and 2018-2019, and a worksite population (n = 722; mean age 49.3 years) without FEV1 data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population. RESULTS: Prevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, -34 to 2 mL/year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers. CONCLUSIONS: HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

Metabolic profiling of charged metabolites in association with menopausal status in Japanese community-dwelling midlife women: Tsuruoka Metabolomic Cohort Study.

BACKGROUND: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. METHODS: The participants were 1193 female residents aged 40-60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. RESULTS: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. CONCLUSION: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims.

BACKGROUND: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. METHODS: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. RESULTS: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93-0.96) and 0.97 (95% CI, 0.96-0.98) for antihypertensive medications, 0.94 (95% CI, 0.91-0.97) and 0.98 (95% CI, 0.98-0.99) for diabetes medications, and 0.84 (95% CI, 0.82-0.87) and 0.98 (95% CI, 0.97-0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. CONCLUSIONS: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

Long-Term Exposure to Particulate Matter and Mortality from Cardiovascular Diseases in Japan: The Ibaraki Prefectural Health Study (IPHS).

AIM: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. METHODS: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40-79 years for 17 years (1993-2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. RESULTS: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014-1.300) for men and 1.097 (0.985-1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991-1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. CONCLUSION: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

Impact of Tobacco Smoking on Outcomes After Posterior Decompression Surgery in Patients With Cervical Spondylotic Myelopathy: A Retrospective Multicenter Study.

STUDY DESIGN: This was a case-control study. OBJECTIVE: The objective of this study was to clarify the surgical outcomes after cervical posterior decompression in patients who smoked. SUMMARY OF BACKGROUND DATA: Smoking is associated with poor outcomes in the field of spinal surgery. However, the impact of tobacco smoking on the outcomes after posterior decompression surgery has not been fully evaluated in patients with cervical spondylotic myelopathy. MATERIALS AND METHODS: In this retrospective multicenter study, 587 patients with cervical spondylotic myelopathy were enrolled at 17 institutions in Japan. Patients underwent cervical laminoplasty or laminectomy and were followed up for at least 1 year after surgery. Outcome measures were: preoperative smoking status, perioperative complications, the Japanese Orthopedic Association scale, and the Visual Analog Scale for neck pain. After adjusting for age and sex by exact matching, smoking and nonsmoking groups were compared using an unpaired t test for continuous variables or a χ test for categorical variables. RESULTS: There were 182 (31%) current smokers and 405 (69%) nonsmokers including previous smokers. After matching, 158 patients were extracted from each group. Demographic data and surgical information were almost the same between the groups. Regarding postoperative complications, there was no significant difference in the rate of surgical site infection, cerebrospinal fluid leakage, hematoma, segmental motor paralysis, or neurological deficit. However, smokers showed a significantly higher risk for delirium (3.8% vs. 0.0%, P=0.039). Smokers and nonsmokers showed comparable changes in functional recovery according to Japanese Orthopedic Association scores (3.2±2.1 vs. 3.0±2.1, P=0.425) and in neck pain reduction using the Visual Analog Scale (-1.7±3.1 vs. -1.4±2.8, P=0.417) at the final follow-up. CONCLUSIONS: Smokers exhibited functional restoration and neck pain reduction after cervical posterior decompression. Attention is required, however, for the postoperative complication of delirium, which could be caused by the acute cessation of tobacco smoking after admission. LEVEL OF EVIDENCE: Level III.

Association of blood cadmium levels in pregnant women with infant birth size and small for gestational age infants: The Japan Environment and Children's study.

BACKGROUND: There is growing evidence of an association between cadmium (Cd) and unfavorable birth outcomes. The effect of Cd exposure on anthropometric measures at birth or small for gestational age (SGA) infants in a large, nationwide Japanese cohort remains to be clarified. OBJECTIVES: To analyze the association between maternal blood Cd levels at different sampling times and sex-dependent infant birth size, weight, body length, chest, and head circumferences, in addition to SGA. METHODS: Data of 17,584 pregnant women in the Japan Environment and Children's Study were analyzed for anthropometric measurements. For SGA determination, 13,969 cases of vaginal delivery were analyzed after excluding infants born by cesarean section. Maternal blood Cd levels were categorized into quartiles (Q1-Q4), and the Q1 was used as a reference. Multiple linear regression analysis was performed for anthropometric measurements, and multiple logistic regression analysis was used to investigate the association of maternal blood Cd levels with the risk of SGA. RESULTS: Birth weight tended to decrease according to the increase in quartiles of blood Cd levels (15.63 g decrease [95% confidence level (CI): -33.26, 2.01] for Q4). The overall analysis revealed no decreases in body length and head and chest circumference, but subgroup analysis revealed that chest circumference tended to decrease according to the increase in quartiles in the female sex/third-trimester stratification (0.16 cm decrease [95% CI: -0.32, 0.00] for Q4). SGA risk was also higher and paralleled the increase in blood Cd levels associated with the female sex/third-trimester group (Odds Ratio 1.90 [95% CI: 1.23, 2.94] for Q4). CONCLUSION: Our results provide further evidence of sex-specific health risks associated with Cd exposure in early life in a large Japanese pregnancy cohort.

Pre-hepatectomy type IV collagen 7S predicts post-hepatectomy liver failure and recovery.

BACKGROUND: Liver resection is an effective treatment for benign and malignant liver tumors. However, a method for preoperative evaluation of hepatic reserve has not yet been established. Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve. When determining eligibility for hepatectomy, the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy. AIM: To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery. METHODS: This study was a retrospective cohort study. We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016. Early post-hepatectomy liver failure (PHLF) was defined using the International Study Group of Liver Surgery's definition of PHLF. Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of < 2 mg/dL and > 2.8 g/dL, respectively, and the time taken for Child-Pugh score to return to Child-Pugh class A. RESULTS: Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function. Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S ≤ 6 ng/mL than in those with type IV collagen 7S > 6 ng/mL. In additional analyses, similar results were observed in patients without chronic viral hepatitis associated with fibrosis. CONCLUSION: Preoperative type IV collagen 7S is a preoperative predictor of PHLF and long-term postoperative liver function recovery. It can also be used in patients without chronic hepatitis virus.

Predictive factors for liver volume and function recovery after resection using three-dimensional analysis.

BACKGROUND: Clinical and biological factors that predict liver volume recovery rate (LVRR) after liver resection of different resected volume (RV) have not been studied extensively. Moreover, it remains uncertain whether remnant liver volume influences the liver function recovery rate (LFRR). This study examined the predictive factors for LVRR after liver resections of different RV and investigated LFRR by focusing on LVRR improvements after hepatectomy. METHODS: Patients who underwent hepatectomy between January 2013 and August 2015 were reviewed retrospectively. LVRR and LFRR were assessed at postoperative months (POMs) 3, 6, and 12. LVRR was evaluated on the basis of RV (0%-15%, 15%-30%, 30%-45%, and >45%). LFRR was evaluated using total bilirubin, prothrombin time, and platelet count. RESULTS: LVRR was lower with more extensive liver resections. Significant independent predictors of LVRR were type IV collagen 7s domain levels and resection magnitude. Platelet count correlated positively with LVRR at all POMs. CONCLUSIONS: Resected livers regenerated after surgery but did not reach preoperative volumes. Preserving the liver as much as possible during resection can result in greater LFRR after hepatectomy. Therefore, decisions regarding liver resection volume should be made very carefully, particularly in patients with higher type IV collagen 7s domain levels.

Clinical outcomes and prognostic factors for cavernous hemangiomas of the spinal cord: a retrospective cohort study

OBJECTIVE: Intramedullary cavernous hemangioma (CH) is a rare vascular lesion that is mainly characterized by the sudden onset of hemorrhage in young, asymptomatic patients, who then experience serious neurological deterioration. Despite the severity of this condition, the therapeutic approach and timing of intervention for CH remain matters of debate. The aim of this study was to evaluate the clinical characteristics of CH patients before and after surgery and to identify prognostic indicators that affect neurological function in these patients. METHODS: This single-center retrospective study included 66 patients who were treated for intramedullary CH. Among them, 57 underwent surgery and 9 patients received conservative treatment. The authors collected demographic, symptomology, imaging, neurological, and surgical data. Univariate and multivariate logistic regression analyses were performed to identify the prognostic indicators for neurological function. RESULTS: When comparing patients with stable and unstable gait prior to surgery, patients with unstable gait had a higher frequency of hemorrhagic episodes (52.4% vs 19.4%, p = 0.010), as assessed by the modified McCormick Scale. The lesion was significantly smaller in patients who underwent conservative treatment compared with surgery (2.5 ± 1.5 mm vs 5.9 ± 4.1 mm, respectively; p = 0.024). Overall, the patients experienced significant neurological recovery after surgery, but a worse preoperative neurological status was identified as an indicator affecting surgical outcomes by multivariate analysis (OR 10.77, 95% CI 2.88­40.36, p < 0.001). In addition, a larger lesion size was significantly associated with poor functional recovery in patients who had an unstable gait prior to surgery (8.6 ± 4.5 mm vs 3.5 ± 1.6 mm, p = 0.011). CONCLUSIONS: Once a hemorrhage occurs, surgical intervention should be considered to avoid recurrence of the bleeding and further neurological injury. In contrast, if the patients with larger lesion presented with worse preoperative functional status, surgical intervention could have a risk for aggravating the functional deficiencies by damaging the thinning cord parenchyma. Conservative treatment may be selected if the lesion is small, but regular neurological examination by MRI is needed for assessment of a change in lesion size and for detection of functional deterioration. ABBREVIATIONS: AIS = ASIA Impairment Scale; ASIA = American Spinal Injury Association; CH = cavernous hemangioma; EBL = estimated blood loss; JOA = Japanese Orthopaedic Association; mMS = modified McCormick Scale.

Blood mercury, lead, cadmium, manganese and selenium levels in pregnant women and their determinants: the Japan Environment and Children's Study (JECS).

The Japan Environment and Children's Study (JECS) is a birth-cohort study of 100,000 mother-child dyads that aims to investigate the effect of the environment on child health and development. Mercury (Hg), lead (Pb), cadmium (Cd), manganese (Mn) and selenium (Se) are considered to be important co-exposures when examining the effect of other chemical substances on child development. The levels of these elements in the blood of 20,000 randomly selected mid/late-term pregnant women from the whole JECS cohort were analysed using inductively coupled plasma-mass spectrometry. The median concentrations (interquartile ranges) for Pb, Hg, Cd, Mn and Se were 0.63 (0.51-0.78) µg dl-1, 3.83 (2.70-5.43) µg l-1, 0.70 (0.52-0.95) µg l-1, 16.1 (13.2-19.6) µg l-1 and 178 (165-192) µg l-1, respectively. Hg and Se correlated positively with each other (Spearman's ρ = 0.287), as did Pb and Cd (ρ = 0.239) and Cd and Mn (ρ = 0.267). The blood Pb levels decreased by 5-10-fold over the past 25 years. The main predictors of the blood levels of each element were fish consumption for Hg, maternal age and non-alcoholic beverage consumption for Pb, maternal age and smoking for Cd, gestational age at sampling for Mn and serum protein levels for Se. These results revealed the historical trends and current predictors of the blood levels of these elements in pregnant Japanese women.

Does Posterior Cervical Decompression Conducted by Junior Surgeons Affect Clinical Outcomes in the Treatment of Cervical Spondylotic Myelopathy? Results From a Multicenter Study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To evaluate the outcomes of posterior cervical decompression for cervical spondylotic myelopathy (CSM) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. METHODS: We reviewed outcomes for 675 patients who underwent surgery for CSM, were followed at least 1 year after surgery, and were assessed preoperatively and at final follow-up by Japanese Orthopaedic Association (JOA) scores and by the visual analog scale (VAS) for the neck. Cervical alignment was assessed on radiographs by C2-C7 angles, and range of motion (ROM) by extension minus flexion C2-C7 angles. We compared outcomes for BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and for NBCS surgeons. RESULTS: BCS surgeons performed 432 of 675 laminoplasties. NBCS surgeons were primary in 243 surgeries, of which 187 were directly supervised by a BCS surgeon. BCS surgeons required significantly less time in surgery (98.0 ± 39.5 vs 108.1 ± 49.7 min; P < .01). BCS and NBCS surgeons had comparable perioperative complications rates, and preoperative-to-postoperative changes in JOA scores (2.9 ± 2.1 vs 3.1 ± 2.3; P = .40) and VAS (-1.5 ± 2.9 vs -1.4 ± 2.5; P = .96). Lordotic cervical alignment and ROM were maintained after operations by both groups. CONCLUSIONS: Surgical outcomes such as functional recovery, complication rates, and cervical dynamics were comparable between the BCS and NBCS groups. Thus, posterior cervical decompression for CSM is safe and effective when performed by junior surgeons who have been trained and supervised by experienced spine surgeons.

Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site.

PURPOSE: Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS: Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS: One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. CONCLUSION: Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

Prevalence of Metabolic Syndrome and Lifestyle Characteristics by Business Type among Japanese Workers in Small- and Medium-sized Enterprises.

This cross-sectional study investigated the associations of business type with the prevalence of metabolic syndrome (MetS) and lifestyle characteristics among workers in small- and medium-sized enterprises. In total, data from 167,736 workers (114,746 men and 52,990 women) who participated in health checkups in 2013 were analyzed using multilevel logistic regression models. The odds ratios (ORs) of having MetS, defined based on the criteria of the joint interim statement, were significantly higher in employees of transportation businesses (reference OR =1) than in other business types among men (OR: 0.67-0.85) and similar result was observed among women (OR: 0.70-0.88). The prevalence of a smoking habit was significantly higher in transportation workers than in employees of other businesses for both men and women. Furthermore, male transportation workers were more likely to skip breakfast, engage in <1 h/day of walking, walk at a slower speed, and eat dinner just before going to bed. Female transportation workers were more likely to have gained 10 kg since the age of 20 years. In conclusion, the prevalence of MetS was higher in transportation workers than in workers from other businesses; the associated risk factors may also vary by sex. To effectively promote public health, the labor environment, such as the business type, should be considered.

A combination of routine laboratory findings and vital signs can predict survival of advanced cancer patients without physician evaluation: a fractional polynomial model.

INTRODUCTION: There have been no reports about predicting survival of patients with advanced cancer constructed entirely with objective variables. We aimed to develop a prognostic model based on laboratory findings and vital signs using a fractional polynomial (FP) model. METHODS: A multicentre prospective cohort study was conducted at 58 specialist palliative care services in Japan from September 2012 to April 2014. Eligible patients were older than 20 years and had advanced cancer. We developed models for predicting 7-day, 14-day, 30-day, 56-day and 90-day survival by using the FP modelling method. RESULTS: Data from 1039 patients were analysed to develop each prognostic model (Objective Prognostic Index for advanced cancer [OPI-AC]). All models included the heart rate, urea and albumin, while some models included the respiratory rate, creatinine, C-reactive protein, lymphocyte count, neutrophil count, total bilirubin, lactate dehydrogenase and platelet/lymphocyte ratio. The area under the curve was 0.77, 0.81, 0.90, 0.90 and 0.92 for the 7-day, 14-day, 30-day, 56-day and 90-day model, respectively. The accuracy of the OPI-AC predicting 30-day, 56-day and 90-day survival was significantly higher than that of the Palliative Prognostic Score or the Prognosis in Palliative Care Study model, which are based on a combination of symptoms and physician estimation. CONCLUSION: We developed highly accurate prognostic indexes for predicting the survival of patients with advanced cancer from objective variables alone, which may be useful for end-of-life management. The FP modelling method could be promising for developing other prognostic models in future research.

Evaluation of Pancreatic Fibrosis With Acoustic Radiation Force Impulse Imaging and Automated Quantification of Pancreatic Tissue Components.

OBJECTIVES: The aim of this study was to determine whether computer-assisted digital analysis and acoustic radiation force impulse (ARFI) imaging were useful for assessing pancreatic fibrosis, and if ARFI imaging predicted postoperative pancreatic fistula (POPF). METHODS: Seventy-eight patients scheduled to undergo pancreatic resection were enrolled. Shear wave velocity (SWV) at the pancreatic neck was measured preoperatively using ARFI imaging. Pancreatic tissue components on a whole slide image were quantified using an automatic image processing software. The relationship between SWV, fibrotic tissue content, and POPF incidence and clinical severity was analyzed. RESULTS: The median collagen fiber, fatty tissue, and acinar cell contents were 11.6%, 8.5%, and 61.3%, respectively. Unlike fatty tissue, collagen fiber content and acinar cells were correlated with SWV (ρ = 0.440, P < 0.001 and ρ = -0.428, P < 0.001, respectively). Although collagen fiber content and SWV were associated with the overall incidence of POPF (P = 0.004 and 0.001, respectively), collagen fiber content and SWV had no statistical correlation with clinically relevant POPF (P = 0.268 and 0.052, respectively). CONCLUSIONS: We objectively quantified the pancreatic tissue components using an automatic image processing software. Shear wave velocity was significantly related to collagen fiber content and suggests that ARFI imaging can be useful for evaluating pancreatic fibrosis.

Prevalence and Distribution of Diffuse Idiopathic Skeletal Hyperostosis on Whole-spine Computed Tomography in Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Multicenter Study.

STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To clarify the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: DISH and cervical OPLL frequently coexist, and can cause ankylosing spinal fractures due to biomechanical changes and fragility of the affected vertebrae. The epidemiology and pathophysiology of DISH occurring with cervical OPLL are unclear. MATERIALS AND METHODS: We used whole-spine computed tomography to determine the prevalence of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical radiographs. We established a novel system for grading the progression of DISH based on a cluster analysis of the DISH distribution along the spine. We calculated the correlation coefficient between this grading system and patient age. RESULTS: The prevalence of DISH in patients with cervical OPLL was 48.7%. Patients with DISH were significantly older than those who did not have DISH (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2, and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for grading DISH progression based on the number of regions involved, from grade 0 to 6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a weak but significant correlation between the DISH grade and patient age. CONCLUSIONS: DISH was present in nearly half of the patients with cervical OPLL. DISH was more common in older patients. DISH developed at the thoracic level and progressed into the cervical and/or lumbar spine with age. LEVEL OF EVIDENCE: Level III.