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The prognostic value of classifying the degree of metastatic lymph node regression grade after neoadjuvant chemoradiotherapy remains unclear. The aim was to assess the prognostic value of lymph node regression grade in patients with rectal cancer treated with chemoradiotherapy. We reviewed a total of 421 patients with rectal cancer who underwent neoadjuvant long-course chemoradiotherapy. All lymph nodes were examined retrospectively for evidence of response to chemoradiotherapy, and lymph node regression grade was scored as lymph node regression grade 0 (normal lymph node), lymph node regression grade 1 (100% fibrosis), lymph node regression grade 2 (< 25% cancer cells), lymph node regression grade 3 (25%–50% cancer cells), lymph node regression grade 4 (50%–75% cancer cells), and lymph node regression grade 5 (> 75% cancer cells). The prognostic importance of lymph node regression grade was evaluated. Among 301 ypN0 patients, 27 patients were scored as lymph node regression grade 1. The 5-year recurrence-free survival and local recurrence rates in lymph node regression grade 1 patients were similar to those in lymph node regression grade 0 patients (96.3% versus 88.1% in recurrence-free survival and 0% versus 2.7% in local recurrence); however, among 120 ypN+ (lymph node regression grade 2-5) patients, the 5-year recurrence-free survival and local recurrence rates were poor regardless of the lymph node regression grade score (38.1%–61.1% in recurrence-free survival and 8.4%–14.0% in local recurrence). In the multivariate analysis, an intensified regimen using systemic chemotherapy was independently associated with more lymph node regression grade 1 (P <.001; odds ratio, 6.06; 95% confidence interval, 2.33–16.20) among patients with lymph node regressions grade 1 through 5. Furthermore, in the multivariate analysis, ypT3-4 (hazard ratio, 7.82; 95% confidence interval, 2.80–27.32; P <.001), lymph node regression grade 1 (hazard ratio, 0.048; 95% confidence interval, 0.002–0.27; P <.001), the number of retrieved lymph nodes < 12 (hazard ratio, 5.48; 95% confidence interval, 1.48–16.38; P =.014), and no perioperative chemotherapy (hazard ratio, 3.01; 95% confidence interval, 1.53–5.68; P =.002) were independent predictors of recurrence-free survival. Complete lymph node regression after chemoradiotherapy is a strong prognostic factor in rectal cancer. [ABSTRACT FROM AUTHOR]

Background Brain-derived neurotropic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We investigated whether serum BDNF level was associated with prognosis in patients with heart failure (HF). Methods and Results We measured the serum BDNF level in 58 patients with HF (59.2 ± 13.7 years old, New York Heart Association functional class I–III) at baseline, and adverse events, including all cardiac deaths and HF rehospitalizations, were recorded during the median follow-up of 20.3 months. In a univariate analysis, serum BDNF levels were significantly associated with peak oxygen capacity (β = 0.547; P = .003), anaerobic threshold (β = 0.929; P = .004), and log minute ventilation/carbon dioxide production slope (β = −10.15; P = .005), but not Patient Health Questionnaire scores (β = −0.099; P = .586). A multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 0.41, 95% confidence interval 0.20–0.84; P = .003). The receiver operating characteristic curve demonstrated that low levels of BDNF (<17.4 ng/mL) were associated with higher rates of adverse events compared with high levels of BDNF (≥17.4 ng/mL; log rank test: P < .001). Conclusions Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that these levels can be a useful prognostic biomarker. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to reveal the personality traits of individuals with major and other depressive episodes among the young adult population. Furthermore, character traits of individuals with ideas of suicide or self-harm were also investigated in this study. Methods: The subjects of this study were 1421 university students who completed the Patient Health Questionnaire (PHQ-9) and the Temperament and Character Inventory (TCI). The subjects were divided into three separate groups: the major depressive episode group (N = 41), the other depressive episode group (N = 97), and the non-depressive controls (N = 1283). This separation was achieved using the PHQ-9 algorithm diagnosis. We compared the TCI scores using an analysis of variance. Moreover, the Cochran-Armitage trend test was used to determine the diagnosis, ideas of suicide or self-harm, and analysis of character profiles. Results: The major depressive episode group had significantly higher HA (P < 0.001), lower RD (P < 0.001), lower SD (P < 0.001), and lower C (P < 0.001) scores than non-depressive controls. The other depressive episode group had significantly higher HA scores (P < 0.001) and lower SD scores (P < 0.001) than non-depressive controls. The Cochran-Armitage trend test revealed that the prevalence of depressive episodes decreased as the character profiles matured (χ²trend = 57.2, P < 0.0001). The same tendency was observed in individuals who had ideas of suicide or self-harm (χ²trend = 49.3, P < 0.0001). Conclusion: High HA and low SD scores were common personality traits among young adults with major depressive episodes. Furthermore, the immaturity of character profiles was clearly associated with depressive episodes and ideas of suicide or self-harm. [ABSTRACT FROM AUTHOR]

Abstract: Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the effects of the angiotensin II receptor blocker (ARB) candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of cardiovascular (CV) events in Japanese high-risk hypertensive patients. After 3.2years follow-up, CV events rate was 17.6–17.7 per 1000 person-years in each group, which was much lower than we expected. Since it has not been known whether the same efficacy of two drugs is sustained beyond the current trial, a longer follow-up period will be needed. The Steering Committee of CASE-J trial decided to extend the trial for 3years as an observational study (CASE-J Ex). In CASE-J Ex, the primary end point is a composite of CV events and the secondary endpoints are all-cause death and new-onset diabetes. After Committee''s decision, 245 doctors agreed to participate in CASE-J Ex and 2236 patients (1141 with candesartan-based regimens and 1095 with amlodipine-based regimens) were re-enrolled. The baseline characteristics of CASE-J Ex participants were similar to CASE-J participants and still balanced well between candesartan and amlodipine. Recently, the interest of antihypertensive treatment has focused to differentiation of the effects of antihypertensive agents on the incidence of CV events as well as blood pressure lowering effect. CASE-J Ex will clarify the long-term effects of ARB and CCB on CV mortality and morbidity. Additionally, because the number of diabetic patients is increased, the evidences from CASE-J Ex will be valuable. [Copyright &y& Elsevier]

The net treatment effect (∆) is a new method to assess the treatment benefit that combines multiple time-to-event, binary and continuous endpoints according to a pre-specified sequence. It represents the net probability for a random patient treated in the experimental arm to have a better overall outcome than a random patient from the control arm does. We aimed at characterizing the impact of follow-up on ∆ estimated from both time-to-event and binary toxicity endpoints, in randomized controlled trials (RCTs) of irinotecan-based regimen in advanced/metastatic gastric cancer (AGC). Three RCTs are reanalysed. The net treatment effect using from one to three outcomes (i.e. overall survival, time to progression and toxicity in this order) and the hazard ratio (HR) were estimated after various cut-off dates and compared to the values obtained after complete follow-up were reported. In all three RCTs (897 patients), the irinotecan-based regimen was superior to the non-irinotecan containing regimen in terms of HR and ∆. This superiority was lower when the net treatment effect also accounted for toxicity. The HR was slightly less influenced by an incomplete follow-up than ∆ was, but correction proposed by Péron to account for censored observations showed quite robust results. The net treatment effect using Péron's correction can be used in case of interim analyses or high censoring rates. In addition to relative measures such as the hazard ratio, it provides a simple mean to evaluate the net treatment effect with and without toxicity outcomes. • In advanced gastric cancer, we studied the net effect of irinotecan-based regimen accounting for overall survival, time to progression and toxicity using the generalized pairwise comparisons (GPC) approach. • The net benefit gives an insight of the relative influence of various outcomes as hierarchized by the researcher or the patient. • Incomplete follow-up has slightly stronger influence on GPC analysis than it has on hazard ratio. • In the presence of incomplete follow-up, bias-corrected estimator proposed by Péron et al. provides the most stable results. [ABSTRACT FROM AUTHOR]

Patients with Crohn's disease (CD) can require multiple intestinal surgeries. We examined time trends and risk factors for reoperation in patients with CD who underwent intestinal surgery, focusing on the effects of postoperative medical treatments. We performed a retrospective analysis of 1871 patients with CD who underwent initial intestinal resection at 10 tertiary care institutions in Japan, with an initial surgical date after May 1982. We collected data on the background characteristics of all patients, including Montreal Classification, smoking status, and medical therapy after surgery (tumor necrosis factor antagonists [anti-TNF] agents or immunomodulators). The primary outcome was requirement for first reoperation. Rate of reoperation was estimated using the Kaplan–Meier method, and risk factors for reoperation were identified using the Cox regression model. The overall cumulative 5- and 10-year reoperation rates were 23.4% and 48.0%, respectively. Multivariable analysis showed that patients who underwent the initial surgery after May 2002 had a significantly lower rate of reoperation than patients who underwent surgery before April 2002 (hazard ratio [HR], 0.72; 95% CI, 0.61–0.86). Preoperative smoking (HR, 1.40; 95% CI, 1.18–1.68), perianal disease (HR, 1.50; 95% CI, 1.27–1.77), and ileocolic type of CD (HR, 1.42; 95% CI, 1.20–1.69) were significant risk factors for reoperation. Postoperative use of immunomodulators (HR, 0.60; 95% CI, 0.44–0.81) and anti-TNF therapy (HR, 0.71; 95% CI, 0.57–0.88) significantly reduced the risk. Anti-TNF was effective in the bionaive subgroup. The rate of reoperation in patients with CD significantly decreased after May 2002. Postoperative use of anti-TNF agents might reduce the reoperation rate for bionaive patients with CD. [ABSTRACT FROM AUTHOR]

Background EUS-guided FNA (EUS-FNA) has become the most efficacious way to obtain specimens from a solid lesion adjacent to the GI tract. Previous reports regarding the use of a stylet during EUS-FNA were all based on cytological diagnosis and have showed no significant superiority in terms of diagnostic yield. Objective To clarify the noninferiority of EUS-FNA without a stylet (S−) compared with EUS-FNA with a stylet (S+) on histological assessment. Design A prospective, single-blind, randomized, controlled crossover study. Setting Five tertiary referral centers in Japan. Patients Patients referred for EUS-FNA of a solid lesion. Intervention EUS-FNA S+ and S− in a total of 4 alternate passes with randomization to S+ first or S− first. Main Outcome Measurements The primary endpoint was the acquisition rate of an appropriate and sufficient specimen for histological assessment. The secondary endpoints were cellularity, contamination, bloodiness, diagnostic ability, and diagnostic accuracy. Results We enrolled 107 patients (110 lesions) and analyzed 220 specimens each in the S+ and S− groups. The acquisition rate of appropriate and sufficient specimens in the S+ group was 121 of 220 (55.0%) and 122 of 220 (55.5%) in the S− group. The difference in the acquisition rate of the specimen (S− minus S+) based on the generalized estimating equation was 0.42% (95% confidence interval, −6.72% to 7.56%), which was less than 10% of the prespecified noninferiority margin of this study. With regard to cellularity, contamination, bloodiness score, diagnostic ability, and diagnostic accuracy, there were no significant differences between both groups. There were no dropouts in the study. Limitations A variety of target lesions, multiple pathologists, lack of an assessment of intraobserver and interobserver variability, and a single-blind study for the pathologists. Conclusion EUS-FNA S− is noninferior to EUS-FNA S+ on histological assessment. (Clinical trial registration number: UMIN000008695.) [ABSTRACT FROM AUTHOR]

Abstract Background It is necessary to determine whether there are adverse health effects of prenatal exposure to long-term, low levels of mercury and selenium. However, there are limited that reports on the association between mercury levels by selenium levels and birth size. Therefore, we examined whether maternal mercury levels during pregnancy had any effect on infant birth size, and size, and whether selenium levels influenced this relationship. Objectives To examine the association between mercury and selenium levels during pregnancy with infant birth size. Methods The Japan Environment and Children's Study is a prospective birth cohort conducted between 2011 and 2014. Total mercury levels and total selenium levels in maternal blood during the second and third trimesters were measured using Inductively Coupled Plasma-Mass Spectrometry. Birth weight and small-for-gestational-age were confirmed by medical records. Small-for-gestational-age was defined as birth weight below the 10th percentile according to standard percentile for gender, parity, and gestational age. Multiple linear and logistic regression analyses were used to examine the association between maternal mercury exposure and birth weight or small-for-gestational-age adjusted for confounders (including maternal age and body mass index pregnancy). Results Overall, 15,444 pregnant women were included in this study. Median (inter-quartile range) of blood mercury and selenium levels were 3.66 (2.59–5.18) ng/g and 170.0 (158.0–183.0) ng/g, respectively. Compared to infants of mothers with the highest blood selenium level, those of mothers with the lowest blood selenium level had neither a significant birth weight increase (9 g, 95% confidence interval: −6, 25) nor a significant odds ratio for small-for-gestational-age (0.903, 95% confidence interval: 0.748, 1.089). Compared to infants of mothers with the lowest blood mercury level, those of mothers with the highest blood mercury level had neither a significant birth weight reduction (−12 g, 95% confidence interval: −27, 4) nor a significant odds ratio for small-for-gestational-age (0.951, 95% confidence interval: 0.786, 1.150). Compared to infants of mothers with the lowest quartile of maternal blood mercury level, all infants of mothers with the highest quartile of maternal blood mercury level had a reduced birth head circumference of 0.073 cm (95% confidence interval: −0.134, −0.011). Conclusions There was no association between maternal blood mercury levels and small-for-gestational-age and birth weight among 15,444 pregnant women. In a Japanese population, which has a relatively higher blood mercury level than reported in Western population, reduced birth size was not found to be associated with blood mercury levels, with the exception of birth head circumference. Highlights • We examined association between maternal mercury and selenium with birth outcomes. • 15,444 pregnant Japanese women were included in the prospective birth cohort study. • An association between blood mercury and birth head circumference was found. • No association between blood selenium and birth size was found. • Increased small-for-gestational-age from blood mercury levels was not observed. [ABSTRACT FROM AUTHOR]

The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014–2015 to 2016–2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p < 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients ( p < 0.001). The number of biphasic fever episodes in influenza A- or B-infected patients aged 0–4 years was 2.89-times greater than that in patients aged 10–18 years ( p = 0.010), and the number of episodes in influenza A- or B-infected patients aged 5–9 years was 2.13-times greater than that in patients aged 10–18 years ( p = 0.012). [ABSTRACT FROM AUTHOR]

Background The synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer. Methods Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT. PD-L1 expression on the tumour cells (tPD-L1) and on the stromal immune cells (iPD-L1) was evaluated before and after CRT. CD8+ cell density in tumour area (tCD8+) before CRT and in the stromal area (sCD8+) before and after CRT was also evaluated. Results High tPD-L1 expression was observed in only three patients (1.0%). High iPD-L1 expression significantly increased from 31.7% before CRT to 49.2% after CRT (P < 0.0001). The increase in high iPD-L1 expression after CRT was only observed in patients with tumour regression grades 1 and 2. High iPD-L1 expression was associated with high tCD8+ cell density before CRT (P < 0.0001) and sCD8+ cell density after CRT (P < 0.0001). High tCD8+ cell density before CRT was associated with better disease-free survival (DFS) (P = 0.0331), but its improved effect on DFS could be observed in patients with high iPD-L1 expression (P = 0.0081), not in patients with low iPD-L1 expression (P = 0.516). Conclusion The present study demonstrated the significant correlations between iPD-L1 expression and CD8+ cell density both before and after CRT. [ABSTRACT FROM AUTHOR]

Background It has been reported that skeletal muscle mass and strength are decreased in patients with heart failure (HF), and HF is associated with both reduced exercise capacity and adverse clinical outcomes. Myostatin has been known as a negative regulator of muscle growth, follistatin as the myostatin antagonist, maintaining tissue homeostasis. We thus determined serum myostatin levels in HF patients and whether they are associated with skeletal muscle wasting. Methods and results Forty one consecutive HF patients (58 ± 15 years old, New York Heart Association class I–III) and 30 age-matched healthy subjects as controls (53 ± 8 years old) were studied. Serum myostatin levels were significantly lower in HF patients than controls (18.7 ± 7.4 vs. 23.6 ± 5.2 ng/mL, P < 0.001). Circumference of the thickest part of the right thigh was significantly small (468 ± 72 vs. 559 ± 37 mm, P = 0.001) and lower extremity muscular strength was lower in patients with HF (129 ± 55 vs. 219 ± 52 N × m, P < 0.001). Fourteen HF patients (34%) had muscle wasting. By univariate analysis, higher age, higher serum follistatin, and lower serum myostatin were significantly associated with the presence of muscle wasting. By multivariate analysis, serum myostatin levels were independently associated with muscle wasting (OR = 0.77, 95% CI [0.58, 0.93], P = 0.02). Conclusion Serum myostatin levels were significantly decreased in HF patients and associated with lower extremity muscle wasting, suggesting that myostatin may be an important factor for maintaining skeletal muscle mass and strength in HF. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We investigated the prognosis of Japanese patients with metastatic renal cell carcinoma (RCC), and analyzed the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification. Materials and methods: The endpoint of the present study was overall survival. Relationships between overall survival and potential prognostic factors were assessed using the Cox proportional hazard model with a step-wise procedure. Prognostic assessment was also performed according to the MSKCC risk classification. The predictive accuracy of the MSKCC risk classification was measured employing the concordance index. Results: The median survival for all patients was 22 months (95% CI, 19–28 months). The eight factors were identified as independent prognostic factor; time from initial diagnosis to metastasis, low hemoglobin (Hb), lactate dehydrogenase (LDH), corrected serum calcium (cCa), C-reactive protein (CRP), and the presence or absence of liver metastasis, bone metastasis, and lymph node metastasis. When the MSKCC risk classification was applied to patients, the median overall survival was not reached and 26 and 10 months in the patients classified as favorable, intermediate, and poor risk, respectively. The c-index was 0.73. Conclusions: The prognosis of Japanese metastatic renal cell carcinoma patients may be better than that of previous studies from North America or Europe. Although there are some differences in the rate of patients in the risk groups and survival time by risk group between these patients, the MSKCC risk classification may be applicable for Japanese patients with metastatic renal cell carcinoma. [Copyright &y& Elsevier]

Background: Lateral pelvic lymph node dissection for rectal cancer is a difficult technique due to the complex pelvic anatomy involved. Three-dimensional (3D) organ models have been introduced as education tools to study anatomy in some fields. In this study, we educated the participants about pelvic anatomy using a 3D model, and evaluated learning efficiency, comparing the outcomes with those using a traditional textbook.Study Design: This study was a randomized, controlled, single-center trial conducted between July 2018 and July 2019. A total of 102 participants (34 medical students, 34 residents, and 34 surgeons) were enrolled. Participants were randomly assigned to the 3D model group or the textbook group. First, they completed a short test to confirm their basic knowledge before further education. After collocated education, they completed the same short test again and another long test to evaluate their learning outcomes.Results: Before education, there was no significant difference in the short test scores between the 3D model group and the textbook group. After education, the short and long test scores of the 3D model group were significantly higher than those of the textbook group for students (short test; p = 0.05, long test; p = 0.03), residents (short test; p = 0.05, long test; p = 0.002), and surgeons (short test; p = 0.009, long test; p < 0.001).Conclusions: Using a 3D pelvic model is superior to using a textbook when learning pelvic anatomy required for lateral pelvic lymph node dissection. [ABSTRACT FROM AUTHOR]