Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study.

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.

K-ras gene mutation analysis to diagnosis pancreatic adenocarcinoma from endoscopic ultrasound-guided tissue acquisition; a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high sensitivity for the pathological diagnosis of pancreatic masses, but also a high false-negative rate. K-ras gene mutations occur in over 75 % of pancreatic ductal adenocarcinomas (PDAC), and this meta-analysis evaluated the utility of detecting K-ras gene mutations from EUS-TA specimens for the diagnosis of PDAC. METHODS: Relevant studies in PubMed, the Cochrane Library, and Web of Science were systematically searched. Meta-analysis was performed on data from the selected studies using a bivariate model to provide pooled values of sensitivity, specificity, and their 95 % confidence intervals (CIs). RESULTS: This meta-analysis included 1521 patients (from 10 eligible studies) who underwent EUS-TA with K-ras gene mutation analysis for diagnosis of pancreatic solid masses. The pooled estimates of sensitivity and specificity were 76.6 % (95 % CI, 70.9-81.5 %) and 97.0 % (95 % CI, 94.0-98.5 %), respectively, for pathological diagnosis, 75.9 % (95 % CI 69.5-81.4 %) and 95.3 % (95 % CI, 92.3-97.2 %) for K-ras gene mutation analysis, and 88.7 % (95 % CI 87.1-91.7 %) and 94.9 % (95 % CI, 91.5-97.0 %) for pathological diagnosis in combination with K-ras gene mutation analysis. The sensitivity for diagnosis of PDAC was significantly higher for pathological diagnosis in combination with K-ras gene mutation analysis than for pathological diagnosis or K-ras gene mutation analysis alone (both, p < 0.001). There was no difference in specificity between pathological diagnosis in combination with K-ras gene mutation analysis and both either (p = 0.234, 0.945, respectively). CONCLUSIONS: K-ras gene mutation analysis in combination with to pathological diagnosis of EUS-TA increases the accuracy of differential diagnosis of PDAC.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Is milbemycin a game changer against antifungal drug-resistant mycoses?

Milbemycin oximes are macrocyclic lactones that have a broad spectrum of activity against nematode infection in animals. They are known to block drug efflux, which increases the susceptibility of fungi to azoles. We investigated the effects of milbemycin on the azole susceptibility of fungi (Aspergillus fumigatus, Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum). To screen for changes in azole susceptibility, fungal growth was tested on a culture medium containing 1 µg/ml milbemycin. The results showed that milbemycin increased the azole susceptibility of azole-resistant strains of C. albicans, C. auris, C. neoformans, and T. rubrum. Thus, milbemycin might be useful against antifungal drug-resistant strains.

Milbemycin blocks drug efflux and increases the azole susceptibility of azole-resistant strains of Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum. This drug is expected to be a game changer against antifungal drug-resistant infections.

BMI and Cardiometabolic Traits in Japanese: A Mendelian Randomization Study.

BACKGROUND: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated. METHODS: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The ß-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses. RESULTS: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions. CONCLUSION: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

Safety of skipping the tract dilation step for EUS-guided biliary drainage in patients with unresectable malignant biliary obstruction (with video).

BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.

Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study.

OBJECTIVE: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. DESIGN: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated FFQ. The hazard ratio (HR) and 95 % confidence interval (CI) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. SETTING: The Japan Multi-Institutional Collaborative Cohort Study. PARTICIPANTS: A total of 80 802 participants (34 555 males and 46 247 females), aged 35-69 years. RESULTS: During a mean follow-up of 9·0 years, we identified 2482 deaths including 1495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HR (95 % CI) in females for all-cause mortality according to the intake were 0·68 (0·55, 0·85) for intakes 1-3 times/month, 0·72 (0·57, 0·90) for 1-2 times/week and 0·69 (0·54, 0·88) for ≥ 3 times/week, compared with the rare intake. The corresponding HR (95 % CI) in females for cancer mortality were 0·72 (0·54, 0·96), 0·71 (0·53, 0·96) and 0·64 (0·46, 0·89), respectively. No statistically significant association was observed in males. CONCLUSIONS: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

Endoscopic ultrasound-guided hepaticogastrostomy vs. antegrade metal stent placement keeping an access route in patients with malignant biliary obstruction.

BACKGROUND: Few studies have compared endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) with EUS-guided antegrade metal stent placement (AGMS). The purpose of this study was to compare times to recurrent biliary obstruction (TRBO) in patients who underwent HGS using metal stents (MS) and those who underwent AGMS keeping access routes with plastic stents (AGMS-AR). METHODS: This study retrospectively evaluated consecutive patients who underwent HGS or AGMS between September 2016 and December 2022. TRBO, overall survival (OS), and adverse event (AE) rates were compared in the two groups. The risk factors for RBO were determined using a multivariable Cox proportional hazards model. RESULTS: This study included 32 patients in the HGS group and 30 in the AGMS-AR group. Technical success rate was significantly higher in the HGS than in the AGMS-AR group (100 vs. 80%; P = 0.009). The technical success rate without tract dilation was significantly higher in the AGMS-AR than in the HGS group (83 vs. 38%; P < 0.001). RBO rates were significantly higher in the HGS than in the AGMS-AR group (53 vs. 17%; P = 0.024), whereas AE rates did not differ significantly. TRBO differed significantly in the HGS and AGMS-AR groups (159 days vs. not reached, P = 0.011), whereas OS did not differ significantly. Multivariable analysis revealed that HGS was an independent risk factor for RBO (hazard ratio, 6.48, P = 0.014). CONCLUSION: TRBO was significantly longer in patients who underwent AGMS with PS than HGS. AGMS with PS may be effective after the failure of ERCP in patients with malignant biliary obstruction.

Impact of sarcopenia on recurrent biliary obstruction after EUS-guided biliary drainage in patients with malignant biliary obstruction.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). METHODS: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. RESULTS: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. CONCLUSION: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Wire ThRoUgh Snare Twice (Wire TRUST) technique: A novel method to grasp a lead with inaccessible ends as a supportive femoral approach for transvenous lead extraction.

INTRODUCTION: Transvenous lead extraction (TLE) is a crucial procedure for managing cardiac implantable electronic devices. The use of a combined superior and femoral approach has been found to enhance the success rate of TLE. This report introduces a novel technique, named "Wire ThRoUgh Snare Twice" (Wire TRUST), for effectively grasping a lead without a free end during TLE. METHOD: The Wire TRUST technique was applied in a case involving a 49-year-old male patient requiring TLE due to electrical artifact on the right ventricular (RV) lead, replacement of the RV lead, and pacemaker generator exchange. The Wire TRUST technique involved the insertion of a 4-Fr pigtail catheter and a 6-Fr snare catheter through the 14-Fr sheath inserted from the right common femoral vein. The 4-Fr pigtail catheter was hooked to the RV lead under multidirectional fluoroscopic guidance in the right atrium. The 0.014-in. guidewire was advanced through the pigtail catheter, crossing the RV lead until reaching the inferior vena cava. Subsequently, the distal end of the 0.014-in. guidewire was captured using a snare and pulled, facilitating externalization of the guidewire. After externalization, both ends of the 0.014-in. guidewire were passed through the snare outside the body and reinserted into the 14-Fr sheath. By simultaneously advancing and closing the snare while applying tension to the 0.014-in. guidewire, a secure grip on the lead without free ends was achieved. RESULTS: The Wire TRUST technique enabled successful lead extraction and replacement without any complications. The technique facilitated the co-axial alignment of the powered sheath with the RV lead, ensuring safe and efficient extraction. CONCLUSION: The Wire TRUST technique presents a novel and effective approach for grasping leads with inaccessible ends during TLE.

Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality. OBJECTIVES: We examined long-term associations of carbohydrate and fat intakes with mortality. METHODS: In this cohort study, 34,893 men and 46,440 women aged 35-69 y (mean body mass index of 23.7 and 22.2 kg/m2, respectively) were followed up from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat. RESULTS: During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively). CONCLUSIONS: An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for prediction of pathological response after neoadjuvant chemotherapy in patients with pancreatic cancer.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) plays an important role in the diagnosis of pancreatic lesions. The aim of this study was to evaluate whether CH-EUS is useful for predicting the treatment efficacy of neoadjuvant chemotherapy (NAC) determined by pathological response. METHODS: Patients who underwent CH-EUS before chemotherapy and surgical resection were divided into two groups according to poor (group-P) or rich tumor vascularity (group-R) determined by enhancement pattern on early- and late-phase CH-EUS. The pathological response to chemotherapy was categorized according to Evans' classification. Pathological analysis showing tumor cell destruction (>50 %) defined a good response. RESULTS: Early-phase CH-EUS classified 44 patients into group-R and 50 into group-P, whereas late-phase CH-EUS classified 10 into group-R and 84 into group-P. Early-phase CH-EUS classification resulted in significantly higher numbers of patients with a good response in the rich group (n = 19) than in the poor group (n = 4; P = 0.0015). Multivariate analysis showed that assignment to the rich group was the strongest independent factor associated with chemosensitivity (P = 0.006, hazard ratio = 5.66, 95 % confidence interval: 1.17-19.27). In resectable patients, the enhancement pattern was the only independent factor associated with chemosensitivity (group-P vs. group-R, P = 0.003; HR [95 % CI], 14.59 [1.38-154.38]). Late-phase CH-EUS did not reveal a significant difference between group-P and group-R. CONCLUSIONS: Evaluation of vascular pattern on CH-EUS could be useful for predicting the efficacy of NAC in patients with pancreatic cancer. The enhancement pattern on CH-EUS could be a one of the useful features for determining NAC indications in resectable pancreatic cancer patients.

Moderate-to-vigorous Physical Activity and Sedentary Behavior Are Independently Associated With Renal Function: A Cross-sectional Study.

BACKGROUND: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. METHODS: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR <60 mL/min/1.73 m2. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied. RESULTS: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (P for trend MVPA <0.0001) and lower eGFR (P for trend SB <0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA ≥20 MET·h/day, 0.76; 95% confidence interval [CI], 0.68-0.85 compared to MVPA <5 MET·h/day) and a higher OR of CKD (adjusted OR of SB ≥16 h/day, 1.81; 95% CI, 1.52-2.15 compared to SB <7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD. CONCLUSION: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-cholesterol Levels in J-MICC Study Participants.

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, of which seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex, and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSION: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Sex-specific Relationship Between Stress Coping Strategies and All-cause Mortality: Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults. METHODS: A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy ("sometimes," and "often/very often" use versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated. RESULTS: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs for "sometimes" were 0.81 (95% confidence interval [CI], 0.67-0.97) for emotional expression, 0.79 (95% CI, 0.66-0.95) for emotional support-seeking, and 0.80 (95% CI, 0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (P for interaction = 0.03). CONCLUSION: In a large Japanese sample, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.

GWAS of folate metabolism with gene-environment interaction analysis revealed the possible role of lifestyles in the control of blood folate metabolites in Japanese - the J-MICC Study.

BACKGROUND: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese. METHODS: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. RESULTS: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (ß = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (ß = 0.033, P = 0.048). CONCLUSIONS: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.

Association between awareness of limiting food intake and all-cause mortality: A cohort study in Japan.

BACKGROUND: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. METHODS: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. RESULTS: The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. CONCLUSION: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

Uncovered versus covered expandable metal stents for malignant gastric outlet obstruction caused by intrinsic and extrinsic tumors: meta-analysis and meta-regression analysis.

BACKGROUND AND AIMS: Malignant gastric outlet obstruction (GOO) can be palliated by endoscopic placement of self-expandable metal stents (SEMSs). Studies comparing uncovered (USEMSs) and covered (CSEMSs) SEMSs have yielded inconclusive results. This meta-analysis compared USEMSs with CSEMSs in patients with GOO caused by intrinsic and extrinsic tumors. METHODS: Potentially relevant articles were identified by searching PubMed, the Cochrane Library, and Medline. The primary outcome was stent dysfunction. Relationships between characteristics of tumors causing GOO and the stent dysfunction rate following USEMSs and CSEMS placement were assessed. RESULTS: Overall, six randomized controlled trials and 12 observational studies, including 2431 patients, were identified. Rate of stent dysfunction did not differ significantly between USEMSs and CSEMSs (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.73-1.25, I2 = 44%), but there was heterogeneity. Meta-regression analysis showed that heterogeneity of stent dysfunction was caused by a difference in the ratio of intrinsic-to-extrinsic tumors causing GOO between studies (coefficient, 0.944; 95% CI, 0.30-1.58). Studies were divided into intrinsic and extrinsic tumor groups. Subgroup analysis showed that the stent dysfunction rate did not differ between USEMSs and CSEMSs in the intrinsic tumor group (OR, 1.10; 95% CI, 0.85-1.41; I2 = 32%). In the extrinsic tumor group, USEMS was associated with a lower rate of stent dysfunction than CSEMS (OR, 0.64; 95% CI, 0.47-0.87; I2 = 25%). CONCLUSION: USEMS and CSEMS placement generally showed comparable outcomes among patients with GOO. USEMS was more effective than CSEMS for patients with GOO caused by extrinsic tumors.

Gastrojejunostomy versus endoscopic duodenal stent placement for gastric outlet obstruction in patients with unresectable pancreatic cancer: a propensity score-matched analysis.

BACKGROUND: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC. METHODS: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching. RESULTS: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group. CONCLUSION: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy.

Does endoscopic sphincterotomy contribute to the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis after endoscopic biliary stenting for malignant biliary obstruction? A multicenter prospective cohort study.

BACKGROUND: There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study. METHODS: We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients. RESULTS: Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES. CONCLUSION: Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.