The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland–Altman plot described no bias between the mean values (mean differences: − 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.

BackgroundClinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma.MethodsThe clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed.ResultsOf 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P = 0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P = 0.0018), an absence of intrapancreatic nerve invasion (P = 0.028), and undergoing an R0 resection (P = 0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P = 0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P = 0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P = 0.0316).ConclusionsWe conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

Objective Accumulating evidence suggests that the use of proton pump inhibitors (PPIs) is associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients, although the results are inconsistent. We aimed to examine whether PPI use is associated with SBP in Japan, where the administration of PPIs is strictly regulated. Methods In this single-center retrospective study, we reviewed 65 patients with liver cirrhosis who were admitted between January 2008 and January 2013 due to ascites. The administration of any PPI for at least one week prior to admission was regarded as PPI use. Results Eighteen cirrhotic patients with SBP and 47 without SBP were identified. Both the serum bilirubin levels and international normalized ratio (INR) values were significantly elevated in the patients with SBP (p=0.007, 0.002). The model for end-stage liver disease scores (mean±SD) were 16.1±9.9 and 12.5±9.3 in those with and without SBP (p=0.009), respectively. PPIs were used in 16 out 18 in patients with SBP and 27 of 47 patients without SBP (p=0.002). A multivariate analysis identified INR (odds ratio (OR)=15.3, 95% CI 2.96-76.9, p=0.001) and PPI use (OR=6.41, 95% CI=1. 16-35.7, p=0.033) to be independent risk factors for SBP. Conclusion The use of PPIs in cirrhotic patients with ascites is independently associated with SBP in the Japanese clinical setting.

Aim: Patients with chronic liver diseases (CLD) suffer from a variety of subjective symptoms, and the assessment of healthrelated quality of life (HRQOL) is crucial. The Chronic Liver Disease Questionnaire (CLDQ) is the first liver disease-specific instrument for this purpose. In this study we aimed to develop the Japanese version of CLDQ and to assess its validity and reliability in Japanese patients with chronic viral hepatitis.Methods: The participants included 135 Japanese patients chronically infected with hepatitis B or C virus. The Japanese version of the CLDQ was developed according to the standard "back-translation" method. In addition to the Japanese version of the CLDQ, we asked the patients to fill out two other selfreport questionnaires: the Japanese versions of the 36-Item Short Form Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS). Then, the internal consistency, convergent and discriminant validity of the Japanese version of CLDQ were statistically examined.Results: Cronbach's alpha of the Japanese version of the CLDQ was acceptable. The mean score was lower in emotional domains of the CLDQ, compared with those in somatic domains. Pearson correlations between Japanese CLDQ and SF-36 and HADS were significant. The mean of the CLDQ scores decreased in all domains in patients with liver cirrhosis compared with those in patients with chronic hepatitis. Conclusion:The Japanese version of the CLDQ is a reliable and valid instrument for assessment of the HRQOL of Japanese patients with chronic viral hepatitis. The results also suggest that the HRQOL of Japanese patients is mainly impaired by emotional factors rather than somatic symptoms, and significantly worsened by progression of the disease.

Aims Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate CO, biliverdin, and iron. Since these products have antiatherogenic properties, HO-1 may play a protective role against the progression of atherosclerosis. However, plasma HO-1 levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), have not been clarified yet. Methods We investigated plasma HO-1 levels by ELISA in 410 consecutive patients undergoing elective coronary angiography who also had an ankle-brachial index (ABI) test for PAD screening. Results Of the 410 study patients, CAD was present in 225 patients (55%) (1-vessel (1-VD), n = 91; 2-vessel (2-VD), n = 66; 3-vessel disease (3-VD), n = 68). PAD (ABI < 0.9) was found in 36 (9%) patients. Plasma HO-1 levels did not differ between 225 patients with CAD and 185 without CAD (median 0.44 versus 0.35 ng/mL), but they were significantly lower in 36 patients with PAD than in 374 without PAD (0.27 versus 0.41 ng/mL, P < 0.02). After excluding the 36 patients with PAD, HO-1 levels were significantly higher in 192 patients with CAD than in 182 without CAD (0.45 versus 0.35 ng/mL, P < 0.05). HO-1 levels in 4 groups of CAD(−), 1-VD, 2-VD, and 3-VD were 0.35, 0.49, 0.44, and 0.44 ng/mL, respectively, and were highest in 1-VD (P < 0.05). In the multivariate analysis, HO-1 levels were inversely associated with PAD, whereas they were also associated with CAD. The odds ratios for PAD and CAD were 2.12 (95% CI = 1.03–4.37) and 0.65 (95% CI = 0.42–0.99) for the HO-1 level of <0.35 ng/mL, respectively. Conclusions Plasma HO-1 levels were found to be low in patients with PAD, in contrast to high levels in patients with CAD.

AIMTo elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC).METHODSTumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker.RESULTSIn total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors.CONCLUSIONDCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

Regular aerobic physical activity is of utmost importance in maintaining a good health status and preventing cardiovascular diseases (CVDs). Although cardiopulmonary exercise testing (CPX) is an essential examination for noninvasive estimation of ventilatory threshold (VT), defined as the clinically equivalent to aerobic exercise, its evaluation requires an expensive respiratory gas analyzer and expertize. To address these inconveniences, this study investigated the feasibility of a deep learning (DL) algorithm with single-lead electrocardiography (ECG) for estimating the aerobic exercise threshold. Two hundred sixty consecutive patients with CVDs who underwent CPX were analyzed. Single-lead ECG data were stored as time-series voltage data with a sampling rate of 1000 Hz. The data of preprocessed ECG and time point at VT calculated by respiratory gas analyzer were used to train a neural network. The trained model was applied on an independent test cohort, and the DL threshold (DLT; a time of VT estimated through the DL algorithm) was calculated. We compared the correlation between oxygen uptake of the VT (VT–VO2) and the DLT (DLT–VO2). Our DL model showed that the DLT–VO2 was confirmed to be significantly correlated with the VT–VO2 (r = 0.875; P < 0.001), and the mean difference was nonsignificant (−0.05 ml/kg/min, P > 0.05), which displayed strong agreements between the VT and the DLT. The DL algorithm using single-lead ECG data enabled accurate estimation of VT in patients with CVDs. The DL algorithm may be a novel way for estimating aerobic exercise threshold.

Aim: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated.Methods: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening.Results: CAD was found in 224 patients (1-vessel [1-VD], n = 92; 2-vessel [2-VD], n = 65; 3-vessel disease [3-VD], n = 67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(−), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P < 0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P < 0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI= 1.01–4.49) for a low FGF-21 level (< 15.6 pg/mL).Conclusion: No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.