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To clarify the efficacy and safety of traditional Chinese medicine (TCM) bath in the treatment of psoriasis vulgaris, meta-analysis and systematic evaluation were adopted to comprehensively evaluate the published articles.Combing the terms "traditional Chinese medicine bath" and "psoriasis vulgaris", the articles were searched for in the databases of China Knowledge Network (CNKI), Baidu scholar, Wanfang, Chinese Biomedical Literature Database (CBM), Weipu Database, Medline, Embase, Chinese Medical Citation Index (CMCI), and PubMed. The quality of articles was evaluated using the RevMan 5.3 software provided by the Cochrane system.A total of 13 articles were included. From the funnel chart drawn, it could be seen that the circles and the midline of most articles were not symmetrical, and the publication was biased, so the conclusions obtained were relatively credible. The heterogeneity analysis of TCM bath in treatment of psoriasis vulgaris showed that 13 articles reporting the total effective rate (TER) and the TERs of the two groups displayed obvious differences [P0.05, 95% confidence interval (CI): 2.9 to 4.77]; there were 8 articles reporting the incidence of adverse reactions, and the incidence of adverse reactions between the two groups was greatly different (P0.05, 95% CI: 0.22 to 0.77); and there were 9 articles reporting the psoriasis area and severity index, and the overall efficacy was greatly different between the two groups (P0.05, 95% CI: -5.38 to -1.88).The TER of the meta-analysis of treatment in this study was higher in the experimental group; the incidence of adverse reactions was lower in the experimental group; and the area and severity of psoriasis were lower in the experimental group, so it was concluded that the TCM bath had a significant effect on the treatment of psoriasis vulgaris.

Sudden cardiac arrest from anomalous coronary artery from the opposite sinus of Valsalva is rarely observed in children under 10 years of age. We report a 7-week-old infant with a brief resolved unexplained event from left anomalous aortic origin of a coronary artery who underwent unroofing and again developed syncope at 8 years of age. Ischemia was detected by stress echocardiography both times. (Level of Difficulty: Advanced.), Central Illustration

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BACKGROUND The gut microbiome is an important determinant of health and disease in preterm infants. OBJECTIVES The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. METHODS This prospective, longitudinal study planned to recruit 160 preterm infants born

BACKGROUND Defining workup beyond usual clinical practice that may improve treatment outcomes in men with a prostate-specific antigen (PSA) level of ≤4 ng/mL (vs >4 ng/mL) and Gleason score (GS) 9 to 10 prostate cancer (PC) remains to be determined. METHODS Between February 25, 1992, and February 25, 2016, 17,632 men with clinical T1-4 PC with a biopsy GS of 6 to 10 underwent radical prostatectomy at a single academic center. Multivariable Fine and Gray regressions were used to evaluate the risk of prostate cancer-specific mortality (PCSM) with an interaction model evaluating the prognostic significance of PSA ≤ 4 ng/mL versus PSA > 4 ng/mL among men with PC with a biopsy GS of 9 to 10 versus ≤8, with adjustments made for the time-dependent use of adjuvant and/or salvage radiation therapy and androgen deprivation therapy (ADT) in addition to known PC prognostic factors. RESULTS There was a significant interaction in men with a biopsy GS of 9 to 10 versus ≤8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (adjusted hazard ratio [AHR], 2.87; 95% confidence interval [CI], 1.02-8.08; P = .046). Specifically, among men with a biopsy GS of 9 to 10 and a PSA level of ≤4 ng/mL versus >4 ng/mL, there was a significantly higher rate of PCSM (AHR, 2.59; 95% CI, 1.19-5.67; P = .017); however, there was no significant difference in the risk of PCSM in men with a biopsy GS ≤ 8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (AHR, 0.90; 95% CI, 0.46-1.78; P = .771). Moreover, the time-dependent use of postoperative ADT was also associated with an increased risk of PCSM (AHR, 10.76; 95% CI, 6.88-16.81; P < .0001). CONCLUSIONS Some men with PSA ≤ 4 ng/mL and a biopsy GS of 9 to 10 may have pathologic or genetic variants that make them less amenable to a cure with current standards of care. Additional workup assessing for small cell, neuroendocrine, and genetic variants should be considered.

We investigated relationships between psychometric measures of memory, executive functions (EFs), and task-based measures of Judgments of Learning (JOLs) in individuals with and without Traumatic Brain Injury (TBI), to study functional reorganization after TBI. We hypothesized that, in controls, accuracy of immediate JOLs would be associated with short-term memory and EFs (but not long-term memory, LTM), while accuracy of delayed JOLs would be associated primarily with LTM. We hypothesized that those with good recovery from TBI would demonstrate functional reorganization of the relationships between memory, EFs, and JOLs. Eighteen individuals with TBI and 18 matched controls completed eight neuropsychological tests of memory and EFs. They studied word-pairs, made immediate and delayed JOLs, and took a cued-recall test for the studied word-pairs. Stepwise regression and Lasso analyses generated a predictive model of JOL accuracy for each group. Accuracy of immediate JOLs in controls was predicted by short-term memory, inhibition, switching, and cognitive fluency, while accuracy of delayed JOLs was predicted by verbal recall. In individuals with TBI, inhibition predicted immediate JOL accuracy and switching predicted delayed JOL accuracy. Cognitive reorganization in those with good long-term recovery from TBI may account for the ability to make JOLs with accuracy similar to controls.

This study explored the association of back pain and heart failure (HF) with health outcomes among community-dwelling older adults. Older adults who completed a follow-up in the 11th year (2007–2008) of the Health, Aging, and Body Composition (Health ABC) study were included. The mean age was 83.4 ± 2.78 years. Back pain and heart failure were reported by 55.40% (n = 657) and 8.09 % (n = 96) of the total subjects (N = 1186), respectively. Regression analysis indicated that older adults with back pain reported worse depressive symptoms, fatigue, and physical performance and function compared with those without back pain (p < 0.05), and HF presence increased fatigue levels and decreased physical function (p < 0.05) among older adults with back pain. The high incidence and negative impact of back pain highlight the need to develop strategies for pain management among older adults with and without HF.

Objective To assess whether the time to prostate-specific antigen (PSA) nadir (TTN) has differential prognostic value in men who reach an undetectable vs detectable PSA nadir. Methods Two hundred and four men from a prospective randomized controlled trial involving radiation therapy with or without 6 months of androgen deprivation therapy in unfavorable risk Prostate cancer (CaP) at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality calculated using Fine and Gray competing risk regression. Results After a median follow-up of 18.17years, 160 men died; 30 (18.75%) of CaP. Among men with a PSA nadir ≥ 0.2ng/ml, a TTN Conclusion Men with both a short TTN and detectable PSA nadir could be considered for entry on randomized controlled trials at a novel entry point prior to PSA failure at the time of PSA nadir to completeplanned conventional androgen deprivation therapy vs that plus agent(s) shown to improve outcomes in men with or at high risk of having castrate-resistant CaP.

Gastrointestinal probiotics play an important role in maintaining intestinal bacteria homeostasis. They might benefit people with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which remains a global health challenge. However, there is a controversy regarding the efficacy of probiotics for the treatment of AIDS. This study systematically reviewed the evidence of the effects of existing probiotic interventions on AIDS and sought to provide information on the role of probiotics in the treatment of HIV/AIDS patients. A meta-analysis of studies identified by screening multiple databases was performed using a fixed-effects model in Review Manager 5.2 software. The meta-analysis showed that probiotics could reduce the incidence of AIDS-related diarrhea (RR = 0.60 (95% CI: 0.44–0.82), p = 0.001). The short-term use of probiotics (supplementation duration shorter than 30 days) did not reduce the incidence of diarrhea (RR = 0.76 (95% CI: 0.51–1.14), p = 0.19), while the long-term use of probiotics (supplementation duration longer than 30 days) reduced diarrhea (RR = 0.47 (95% CI: 0.29–0.76), p = 0.002). Probiotics had no effect on CD4 cell counts in HIV/AIDS patients (MD = 21.24 (95% CI: −12.95–55.39), p = 0.22). Our data support that probiotics were associated with an obvious reduction in AIDS-related diarrhea, which indicates the need for additional research on this potential preventive strategy for AIDS.

PURPOSE Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.

We evaluated whether intermediate-risk factors, in addition to age, were associated with risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer.We conducted a prospective cohort study of 1,920 men with Gleason 3+4 adenocarcinoma of the prostate who received brachytherapy (BT) or BT and a median of 4 months of androgen deprivation therapy (ADT). Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether percentage of positive biopsies (PPB), cT2b-T2c stage, prostate-specific antigen (PSA) of 10.1-20.0 ng/ml, and age70 years (median) were associated with risk of PCSM after adjustment for comorbidity.After median follow-up of 7.8 years, 284 men (14.8%) had died (31 from prostate cancer). For BT alone, increasing PPB, PSA of 10.1-20.0 vs. 4.0-10.0 ng/mL, and age70 vs. ≤70 were significantly associated with increased risk of PCSM (adjusted hazard ratio 1.015, 95% confidence interval 1.000-1.031, P = 0.048; 5.55, 2.01-15.29, P0.001; and 3.66, 1.16-11.56, P = 0.03, respectively). The respective results for BT and ADT were 1.009, 0.987-1.031, P = 0.44; 4.17, 1.29-13.50, P = 0.02; and 3.74, 0.87-16.05, P = 0.08.Among men with Gleason score 3+4 prostate cancer treated with BT, the risk of PCSM was elevated in those with PSA of 10.1-20.0 ng/mL and possibly age70 years, despite the addition of ADT. Should these findings be validated in future studies, then advanced imaging and targeted biopsy of suspicious areas should be investigated in an effort to personalize treatment and minimize the risk of PCSM in these men.

Background There are concerns that fruit juice and milk contribute to childhood obesity. Objective Determine the relationship between fruit juice and milk intakes and body mass index (BMI) change among preadolescents/adolescents. Methods Participants aged 9 to 16 years old from the Growing Up Today Study II completed surveys including validated food frequency questionnaires in 2004, 2006 and 2008. The contributions of one serving of juice or milk to total energy intake and 2-year change in BMI were evaluated using multiple linear regression. Additional analyses were conducted with subgroups of juice (orange juice and other fruit juice) and milk (low fat and high fat). Missing values for BMI were imputed using a multiple imputation approach, after which data from 8173 participants and 13 717 2-year interval observations were analysed. Results Baseline fruit juice consumption was inversely associated with BMI change in girls (β = -.102 kg/m2 , SE = 0.038, P value = .008) but not boys after controlling for race, age, baseline BMI, and baseline and 2-year changes in total energy intake and physical activity. Orange juice was inversely associated with BMI change among girls (β = -.137 kg/m2 , SE = 0.053, P value = .010) while other fruit juice, low fat and high fat milk were not associated with BMI change. Conclusion Orange juice was inversely associated with 2-year BMI change among preadolescent/adolescent girls but not boys and there were no significant associations with other juices or milk among either gender.

BACKGROUND Although both PSA nadir (PSAn) and testosterone levels at PSA failure are known prognostic factors in men undergoing radiation therapy (RT) and androgen deprivation therapy (ADT) for unfavorable-risk prostate cancer (PC), it is unclear whether their prognostic significance is independent or overlapping. METHODS Seventy-five men treated with RT with or without 6 months of ADT for unfavorable-risk nonmetastatic PC enrolled in 2 prospective clinical trials between 1986 and 2001 formed the study cohort. Competing risks and Cox multivariable regression were used to assess whether low versus normal serum testosterone at the time of PSA failure and higher PSAn after initial therapy were independently associated with the risk of PC-specific (PCSM) and all-cause mortality (ACM) adjusting for PC prognostic factors. RESULTS After a median follow-up of 15.34 years (interquartile range, 6.66-16.88 years), there were 53 deaths (73.3%): 30 (56.6%) were from PC. Low testosterone at PSA failure was significantly associated with an increased risk of PCSM (adjusted HR [AHR], 7.77; 95% CI, 1.14-52.99; P = .04) and ACM (AHR, 3.01; 95% CI, 1.01-8.96; P = .05), as was higher PSAn (PCSM AHR, 1.03; 95% CI, 1.01-1.05; P

We conducted a study to determine whether patients born with Trisomy 21 and left-to-right shunts who develop pulmonary vein stenosis (PVS) have a longer exposure to shunt physiology compared to those who do not develop PVS. We included patients seen at Boston Children&rsquo, s Hospital between 15 August 2006 and 31 August 2017 born with Trisomy 21 and left-to-right shunts who developed PVS within 24 months of age. We conducted a retrospective 3:1 matched case&ndash, control study. The primary predictor was length of exposure to shunt as defined as date of birth to the first echocardiogram showing mild or no shunt. Case patients with PVS were more likely to have a longer exposure to shunt than patients in the control group (6 vs. 3 months, p-value 0.002). Additionally, PVS patients were also more likely to have their initial repair &ge, 4 months of age (81% vs. 42%, p-value 0.003) and have a gestational age &le, 35 weeks (48% vs. 13%, p-value 0.003). Time exposed to shunts may be an important modifiable risk factor for PVS in patients with Trisomy 21.

Pulmonary vein stenosis (PVS) is a rare, frequently lethal disease with heterogeneous phenotypes and an unclear etiology. Limited studies have reported associations between PVS and congenital heart disease (CHD), chronic lung disease (CLD), and/or prematurity, however, to date, there have been no studies that report detailed clinical syndromic phenotypes and the potential role of genetics in PVS. An existing registry of multivessel PVS patients seen at Boston Children’s Hospital (BCH) was queried between August 2006 and January 2017 for all existing genetic testing data on these patients. PVS was defined as an intraluminal pulmonary venous obstruction in ≥2 vessels with mean pressure gradients &gt, 4 mmHg. One-hundred-and-fifty-seven patients (46% female, with a median age at PVS diagnosis of 3 months) formed the cohort. Seventy-one (45%) patients had available genetic testing information. Of the 71 patients, a likely genetic diagnosis was found in 23 (32%) patients: 13 (57%) were diagnosed with Trisomy 21 (T21), five (22%) with Smith–Lemli–Opitz Syndrome, five (22%) had other pathologic genetic disease, and 24 (33%) had variants of unknown significance. The majority of 13 patients with T21 and PVS had common atrioventricular canal (CAVC) (10, 77%) and all had severe pulmonary hypertension (PHTN), which led to their PVS diagnosis. In our study, PVS was associated with T21, the majority of whom also had CAVC and PHTN. Therefore, complete assessment of the pulmonary veins should be considered for all T21 patients, especially those with CAVC presenting with PHTN. Furthermore, prospective standardized genetic testing with detailed clinical phenotyping may prove informative about potential genetic etiologies of PVS.

Introduction: The American Heart Association (AHA) guidelines recommend testing for inducible myocardial ischemia in all patients with a history of coronary artery aneurysm (CAA) after Kawasaki disease (KD). Because the prevalence of clinical coronary complications is exceedingly low in patients whose worst-ever CAA dimension was Methods: Retrospective study including patients Results: A total of 588 stress tests were performed in 208 patients at median age of 12.4 [IQR 8.8, 16.8] years, 8.3 [IQR 5.0, 12.9] years after diagnosis (Table). Tests were performed using either exercise stress (545 [93%] tests) or pharmacologic stress with dobutamine (43 [7%] tests). Echocardiography was the most frequently used modality (n=481, 82%), followed by nuclear imaging (n=133, 23%) and cardiac MRI (n=53, 9%). Inducible ischemia was found on 11 (2%) tests in 6 (3%) patients. All patients with inducible ischemia had a history of giant CAA with persistent CAA at time of testing (moderate CAA in 2 (18%) tests, giant CAA in 9 (82%) tests). After finding inducible ischemia on stress test, coronary artery bypass grafting was performed in 3 cases, cardiac catheterization in 4, stress testing using a different imaging modality in 1, and careful clinical monitoring without intervention in 3. Conclusions: Inducible ischemia was found in 2% of test after KD, and only in patients with a history of giant CAA. Recommendations in the 2017 AHA guidelines for KD for testing for myocardial ischemia in patients with non-giant CAA should be reconsidered in light of these findings.

This research is motivated from the data from a large Selenium and Vitamin E Cancer Prevention Trial (SELECT). The prostate specific antigens (PSAs) were collected longitudinally, and the survival endpoint was the time to low-grade cancer or the time to high-grade cancer (competing risks). In this article, the goal is to model the longitudinal PSA data and the time-to-prostate cancer (PC) due to low- or high-grade. We consider the low-grade and high-grade as two competing causes of developing PC. A joint model for simultaneously analysing longitudinal and time-to-event data in the presence of multiple causes of failure (or competing risk) is proposed within the Bayesian framework. The proposed model allows for handling the missing causes of failure in the SELECT data and implementing an efficient Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via a novel reparameterization technique. Bayesian criteria, [Formula: see text]DIC[Formula: see text], and [Formula: see text]WAIC[Formula: see text], are introduced to quantify the gain in fit in the survival sub-model due to the inclusion of longitudinal data. A simulation study is conducted to examine the empirical performance of the posterior estimates as well as [Formula: see text]DIC[Formula: see text] and [Formula: see text]WAIC[Formula: see text] and a detailed analysis of the SELECT data is also carried out to further demonstrate the proposed methodology.

BACKGROUND Herein, the authors evaluated how the time to testosterone rebound (TTR) after radiotherapy (RT) and 6 months of androgen deprivation therapy (ADT) impacted the risk of prostate cancer-specific mortality (PCSM) and cardiovascular-specific mortality (CVM) among men with varying comorbidity extent. METHODS Between 1995 and 2001, a total of 206 men who were randomized to receive RT either alone or with 6 months of ADT for unfavorable-risk PC and who had a comorbidity score assigned using the Adult Comorbidity Evaluation 27 metric comprised the study cohort. Multivariable competing risk regression was used to evaluate the impact of and possible interaction between comorbidity and TTR on PCSM and CVM. RESULTS After a median follow-up of 18.19 years, 30 men (18.6%), 39 men (24.2%), and 92 men (57.1%), respectively, had died of PC, CV disease, or other causes. As TTR increased, PCSM significantly decreased in men with no or minimal (adjusted hazard ratio [AHR], 0.53, 95% confidence interval [95% CI], 0.34-0.84 [P =.007]) and moderate to severe (AHR, 0.37; 95% CI, 0.14-0.99 [P = .048]) comorbidity. However, increasing TTR significantly increased the risk of CVM among men with moderate to severe comorbidity (AHR, 1.87; 95% CI, 1.40-2.49 [P

The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA) mutations are not known. Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF FLNA mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range: 0-71 years), with 75 FLNA mutations observed in 80 families. Most (64.9%) subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2% of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (n = 21), and were associated with other structural cardiac malformations in 57.1% of patients, most commonly patent ductus arteriosus (PDA) and valvular abnormalities. TAA most frequently involved the aortic root and ascending aorta, and sinus of Valsalva aneurysms were present in one third of TAA patients. Six TAA patients (28.5%) required surgery (median age 37 yrs, range 13-41 yrs). TAA with its associated complications was also the only recorded cause of premature, non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M, median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller than current recommendations for surgery for other aortopathies. Data from this largest series of LOF FLNA mutation patients underscore the importance of serial follow-up to identify and manage these potentially devastating cardiovascular complications.

17 Background: On July 19, 2012, the Prostate Cancer Intervention versus Observation Trial (PIVOT) was published and reported that after a median follow up of 10 years, radical prostatectomy neither improved overall survival nor reduced prostate cancer (PC)-specific mortality in men with low-risk PC compared to watchful waiting. However, the trial’s applicability may be somewhat limited by the participants’ poorer-than-average overall health. This study aimed to evaluate the impact of the PIVOT by assessing practice patterns before and after its publication. Methods: Between October 1997 and May 2013, 6,818 men with low-risk (n = 5,081, 74.5%) or favorable intermediate-risk (N = 1,737, 25.5%) PC were treated with curative intent at the Chicago PC Foundation. We compared the proportions of these men with ≥2, 1, or 0 comorbid conditions, restricted to myocardial infarction, congestive heart failure, diabetes mellitus, and coronary artery disease. We assessed for a trend in these proportions by time tertile prior to the PIVOT’s publication and compared them one month following PIVOT to the final pre-publication time tertile. Results: Of 6,818 men treated with curative intent, 5,208 (76.5%), 1,307 (19.2%), and 293 (4.3%) had 0, 1, and ≥2 comorbidities, respectively. Prior to PIVOT, the proportion of men with the greatest comorbidity (≥2) increased by time tertile (3.5% vs. 4.2% vs. 5.4%; p = 0.002), while 1 month following publication, there was a decline in the proportion of men with the highest degree of comorbidity (5.4% vs. 2.9%; p = 0.05). In addition to the drop in men with greatest comorbidity, men treated following the publication of the PIVOT were also younger (median age 65.7 vs. 66.8 years; p = 0.04), more likely to be black or Hispanic (24.7% vs. 17.4%; p = 0.003), and more likely to have favorable intermediate than low-risk PC (36.1% vs. 28.4%; p = 0.007). Conclusions: Following the publication of the PIVOT, men with low or favorable intermediate-risk PC whose health was poorer than the national average were less likely to undergo curative treatment, whereas men at higher risk for harboring occult high grade PC despite favorable-risk indices were more likely to undergo curative treatment.

Background Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. Methods Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. Results After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. Conclusions Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society.

Evidence regarding the dose-related impact of doxorubicin on subsequent cardiovascular diseases (CVDs) in Asian patients with diffuse large B-cell lymphoma (DLBCL) without preexisting CVDs is lacking. From a territory-wide electronic database in Hong Kong, we identified adults who were diagnosed with DLBCL and treated with chemotherapy between 2000 and 2018. We evaluated the patients for incident CVDs (including ischemic heart disease, heart failure, and cardiomyopathy). We evaluated the cause-specific cumulative incidence (csCI) of CVD with levels of doxorubicin exposure by using flexible parametric competing risk analysis and adjusting for demographics, comorbidities, therapeutic exposure, cardiovascular risk factors, and lifestyle factors. Controls were age- and sexmatched to DLBCL patients. We analyzed 2600 patients and 13 000 controls. The adjusted cause-specific hazard ratio (HR) for CVD in patients treated with .500 mg doxorubicin compared with non-doxorubicin regimens was 2.65 (95% confidence interval [CI], 1.23-5.74; P 5 .013). The 5-, 10-, and 15-year csCIs were 8.2%, 11.3%, and 12.8% in patients vs 3.1%, 4.4%, and 5.2% in controls, respectively. Hypertension (HR, 6.20; 95% CI, 0.79-48.44; P 5 .082) and use of aspirin/angiotensin-converting enzyme inhibitor/beta-blocker at baseline (HR, 2.13-4.63; P , .001 to .002) might confer a higher risk of subsequent CVDs. In this Hong Kong population-based study, doxorubicin exposure (absolute dose .500 mg), together with hypertension or baseline use of medication for cardiovascular risk factors, was found to be associated with an increase in csCIs of CVDs. Tailoring therapeutic strategies to underlying CVD risk factors and risk-adapted monitoring and follow-up of susceptible DLBCL patients are advisable., United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Harvard Catalyst, Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences) UL1TR002541, HarvardUniversity andits affiliated academic health care centers, Spanish National Health Institute Carlos III Miguel Servet-I Investigator grant/award CP17/00206, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) R01 CA196854

Concerns about orange juice&rsquo, s sugar content have spurred discussions regarding its potential contributions to childhood obesity. The objective of this study was to evaluate the association between 100% orange juice (OJ) consumption and dietary, lifestyle and anthropometric characteristics in children and adolescents. Baseline anthropometric, dietary and lifestyle data from the Growing Up Today Study I (GUTS I) and GUTS II were collected via self-reported questionnaires from 26,554 participants. The mean values of these variables were then computed for children grouped by categories of OJ consumption, and linear trend testing was used to determine whether OJ consumption was linearly related to these variables. Multivariate adjustment modeling was used to calculate odds ratios of being obese or overweight/obese by OJ consumption. Among both boys and girls, OJ intake was positively associated with height, height-for-age z-score (HAZ), intakes of total energy, total energy excluding OJ, fruits and non-starchy vegetables and physical activity. BMI, BMI z-score and BMI-for-age percentile did not differ by OJ consumption. After adjustment for cohort, age, race, total energy intake without OJ, physical activity and screen time, prevalence of overweight/obesity significantly decreased by OJ intake in boys compared to non-consumers (odds ratio (OR) and 95% confidence interval (CI)): 1.17 (1.02, 1.33) for 1&ndash, 3 glasses per month, 1.11 (0.98, 1.26) for 1&ndash, 6 glasses per week, 1.00 (0.85, 1.18) for 1 glass per day, 0.91 (0.73, 1.13) for &ge, 1 glass per day, p-trend = 0.0403). Prevalence of obesity similarly decreased by OJ intake in boys. Prevalence of overweight/obesity and obesity did not significantly differ by OJ intake in girls. The results indicate that children consuming more OJ tended to practice healthier dietary and lifestyle habits without increased prevalence or odds of obesity or overweight.

ObjectiveTo enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors.Study designA 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC.ResultsSixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%,p n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%).ConclusionsThe survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.

Glioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real-time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan-Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit-8 (CCK-8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK-8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR-1304 and circ_0074026 or ERBB4 3'-untranslated region (3'-UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual-luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients' tumor size, WHO grade, disease-free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual-luciferase reporter assay demonstrated that miR-1304 interacted with circ_0074026 and ERBB4 3'-UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR-1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.

OBJECTIVES: Concerns about orange juice's (OJ) high sugar content have contributed to reduced consumption in the U.S. The objective of this study is to evaluate the association between 100% OJ consumption and anthropometric indicators and health-related behaviors in adolescents. METHODS: Data from the Growing Up Today Study (GUTS), an ongoing prospective cohort study of adolescents from across the U.S. which began its first cohort (GUTS I) in 1996 and its second cohort (GUTS II) in 2004, were analyzed. RESULTS: In a cross-sectional examination of baseline data (n = 26,503), there was a significant trend toward lower prevalence of overweight and obesity among children who reported consuming more OJ among boys of GUTS I and girls and boys of GUTS II. Across each cohort and gender, OJ intake was positively associated with height, height-for-age z-score, total energy intake, consumption of fruits and non-starchy vegetables, consumption of foods of low nutritional quality, and physical activity, while screen time was negatively associated with OJ consumption. In boys across both cohorts, the adjusted odds ratios (OR & 95% CI) of being classified as overweight or obese were 0.90 (0.76, 1.08) for 1–3 glasses of OJ per month, 0.94 (0.80, 1.11) for 1–6 glasses per week, 1.01 (0.82, 1.24) for 1 glass per day, and 1.13 (0.87, 1.48) for >1 glass per day (P-trend = 0.3251), using non-consumers as a reference. In girls, the ORs were 0.87 (0.74, 1.30) for 1–3 glasses per month, 0.97 (0.83, 1.14) for 1–6 glasses per week, 1.04 (0.84, 1.28) for 1 glass per day, and 0.68 (0.52, 0.89) for >1 glass per day (P-trend = 0.4345). CONCLUSIONS: The results indicate that children consuming more OJ tended to practice healthier dietary and lifestyle habits than OJ non-consumers. Additionally, a lower prevalence of overweight and obesity was observed among children who consumed more OJ. In adjusted analyses controlling for other obesity risk factors, OJ consumption was not associated with higher odds of being overweight or obese. FUNDING SOURCES: The Florida Department of Citrus, an executive agency of the state of Florida, provided funding for this project.

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

Importance Increased prostate-specific antigen (PSA) levels after treatment (PSA failure) may have different associations with outcomes for men with locally advanced vs localized prostate cancer. Objective To evaluate whether the association between PSA failure and death may be different in locally advanced vs localized prostate cancer. Design, Setting, and Participants This multicenter cohort study included patients from 2 randomized clinical trials. The Dana-Farber Cancer Institute (DFCI) 95-096 trial randomized 206 men with localized prostate cancer from December 1, 1995, to April 15, 2001, whereas the European Organisation for Research and Treatment of Cancer (EORTC) 22961 trial randomized 970 men with locally advanced prostate cancer from October 30, 1997, to May 1, 2002. Data were analyzed from January 1, 2020, to October 31, 2020. Interventions The DFCI 95-096 trial randomized men to 0 vs 6 months of androgen deprivation therapy (ADT) with external beam radiotherapy; the EORTC 22961 trial randomized men to 6 vs 36 months of ADT with external beam radiotherapy. Main Outcomes and Measures For each trial, the PSA doubling time (time to doubling of PSA levels) associated with PSA failure was evaluated. The risk of all-cause mortality associated with PSA failure (nadir plus 2 definition) was evaluated after adjustment of baseline covariates and treatment. Results This analysis included a total of 1173 men (206 from DFCI 95-096 and 967 with available tumor stage from EORTC 22961; median age, 70.0 [interquartile range (IQR), 65.0-74.0 years). For DFCI 95-096, 161 men died (30 [18.6%] due to prostate cancer) at a median follow-up of 18.2 (IQR, 17.3-18.8) years. Among the 108 men with PSA failure, the median PSA doubling time was 13.0 (IQR, 7.4-31.1) months. For EORTC 22961, 230 men died (75 [32.6%] due to prostate cancer) at a median follow-up of 6.4 (IQR, 6.3-6.6) years. Among 290 men who experienced PSA failure, the median PSA doubling time was 5.0 (IQR, 2.9-8.9) months. Compared with DFCI 95-096, PSA failure was associated with a higher risk of all-cause mortality in EORTC 22961 (adjusted hazard ratios, 3.98 [95% CI, 2.92-5.44]; P

Purpose The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P =.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P =.30). Conclusions Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

Purpose Physicians sometimes make management recommendations on the basis of early results from randomized controlled trials (RCTs) relating to reduced prostate-specific antigen (PSA) failure, yet whether this early end point is associated with all-cause mortality (ACM), particularly in men with competing risks, is unknown. Using a validated metric in men treated within the context of an RCT, we aimed to determine whether PSA failure is associated with the risk of ACM stratified by comorbidity score. Patients and Methods Between 1995 and 2001, 206 men with localized (T1b to 2b) intermediate- and high-risk prostate cancer (PC) were randomly assigned to receive radiation therapy or radiation therapy and 6 months of ADT. Cox regression analyses were performed to evaluate whether PSA failure modeled as a time-dependent covariate was associated with an increased risk of ACM among men with Adult Comorbidity Evaluation-27–defined no or minimal versus moderate-to-severe comorbidity adjusting for age, PC prognostic factors, and treatment. Results After a median follow-up of 16.62 years, 156 men (76%) died, 29 of whom (19%) died as a result of PC. PSA failure was associated with an increased ACM risk among men with no or minimal (adjusted hazard ratio, 1.59; 95% CI, 1.03 to 2.46; P = .04), but not moderate or severe comorbidity (adjusted hazard ratio, 1.75; 95% CI, 0.76 to 3.99; P = .19). Conclusion Recommending treatment on the basis of reduced PSA failure observed from early results of RCTs is unlikely to prolong survival in men with moderate-to-severe comorbidity but may prolong survival in men with no or minimal comorbidity, providing evidence to support discussing the early results with these men.

BACKGROUND African American (AA) men are more likely than non-AA men to have a comorbid illness that could interact with androgen-deprivation therapy (ADT) and shorten survival. This study assessed the impact that race had on the risk of all-cause mortality (ACM) and other-cause mortality (OCM) among men definitively treated for favorable-risk prostate cancer (PC). METHODS Between 1997 and 2013, 7252 men with low-risk or favorable intermediate-risk PC were treated with brachytherapy with neoadjuvant ADT (n = 1501) or without neoadjuvant ADT (n = 5751) for a 4-month median duration. Cox and Fine-Gray multivariate regressions were used to analyze whether the risk of ACM and OCM increased among AA men versus non-AA men receiving ADT; adjustments were made for the age at brachytherapy, year of brachytherapy, cardiometabolic comorbidity status, risk group, and ADT treatment propensity score. RESULTS After a median follow-up of 8.04 years, 869 men (12.0%) died: 48 (5.52%) of PC and 821 (94.48%) of other causes. There was a significant association between AA race and an increased risk of both ACM (adjusted hazard ratio [AHR], 1.77; 95% confidence interval [CI], 1.06-2.94; P = .028) and OCM (AHR, 1.86; 95% CI, 1.08-3.19; P = .024) among AA men versus non-AA men who received ADT but not among those who did not receive ADT (AHR for ACM, 1.33; 95% CI, 0.93-1.91; P = .12; AHR for OCM, 1.39; 95% CI, 0.96-2.02; P = .08). CONCLUSIONS ADT use may shorten survival in AA men with favorable-risk PC; therefore, its reservation for the treatment of higher risk PC, for which level 1 evidence supports its use, should be considered. Cancer 2016;122:3608-14. © 2016 American Cancer Society.

Purpose To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity. Methods and Materials This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable–intermediate/high-risk versus favorable–intermediate/low-risk PC were at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score. Results After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P =.001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P =.007) were significantly increased in men with unfavorable–intermediate/high-risk PC versus favorable–intermediate/low-risk PC, with no difference in OCM ( P =.07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P =.029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P =.84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P =.24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P =.20) was increased in men with 2 comorbidities. Conclusions To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorable–intermediate- and high-risk PC.

We evaluated whether a differential impact of adding 6 months of androgen deprivation (ADT) to radiation therapy (RT) on all-cause (ACM), prostate cancer-specific (PCSM), and other-cause mortality (OCM) in men with unfavorable-risk prostate cancer (PC) exists within Gleason score (GS) subgroups. Individual patient data from 743 men with unfavorable-risk PC from two randomized ADT trials were utilized. Competing risks and Cox regression were used to determine whether adding 6 months of ADT to RT significantly impacted PCSM, OCM, and ACM within GS subgroups. Men with GS 9/10 versus ≤8 were significantly more likely to be over 75 (23.3 versus 12.7 %; p = 0.03). At a median follow-up of 11.93 and 11.81 years in the 683 and 60 patients with GS ≤8 and GS 9/10, 315 (46.1 %) and 44 (73.1 %) died, respectively. ADT in men with GS ≤8 was associated with significantly decreased ACM (adjusted hazard ratio (AHR) 0.66; 95 % confidence interval: 0.52–0.82; p

This study aims to demonstrate the possible relationship between the insulin-like growth factor (IGF) system and early miscarriage in polycystic ovarian syndrome (PCOS) patients with euploid embryos. 40 pregnant women included. 9 had PCOS and miscarried; 20 had PCOS and a successful ongoing pregnancy; the remaining 11 women did not have PCOS and miscarried. An ultrasound scan was performed to prove clinical pregnancy and a blood sample was taken on day 55 ± 4 of gestation. Serum samples of IGF-1, insulin-like growth factor binding protein-1 (IGFBP-1), total testosterone, serum hormone binding protein (SHBG), leptin and soluble leptin receptor (sOb-R) were obtained. In miscarriages, samples of decidua were obtained during vaccum curettage. Embryonic chromosomes in all miscarriages were proven to be normal. The expression of IGF-1, IGFBP-1, leptin, long-form leptin receptor and androge sOb-R n receptor (AR) were examined in the decidua. We found that miscarried PCOS patients showed significantly increased free androgen index and free IGF index, as well as decreased SHBG and IGFBP-1 than other two groups in peripheral blood. In the decidua, miscarried PCOS patients showed significantly increased expression of IGF-1 and decreased IGFBP-1 when compared with non-PCOS. AR was not expressed in the decidua of either group. Our results suggest that early miscarriage is associated with increased IGF-1 and decreased IGFBP-1 in PCOS patients.

Summary Aims To explore the expression, methylation pattern, the prognostic value, and the biological consequences of CAMKK2 in gliomas. Methods The expression and methylation pattern of CAMKK2 was inferred and validated from mRNA expression profile (N = 866) and methylation profile (N = 426) of glioma tissue samples, and independent samples were used for further validation by IHC and pyrosequencing. To explore the function of CAMKK2 in gliomas, in vitro studies, colony formation assays and migration and invasion assays were performed. Results We found the upregulation of CAMKK2 in high-grade glioma samples was associated with promoter hypomethylation. An elevated expression of CAMKK2 was associated with worse prognosis. By in vitro assays, we demonstrated that CAMKK2 could promote cell migration, invasion, and proliferation. Conclusions The expression level of CAMKK2 could be regulated by promoter methylation. CAMKK2 serves as a prognostic marker in gliomas and could be a potential therapeutic target in gliomas.

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (1500 vs.500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend0.01], 0.28 (95% CI: 0.08, 0.96; P-trend0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.

ObjectiveTo compare the blood pressure (BP) effects of exercise alone (EXalone), medication alone (MEDSalone) and combined (EX+MEDScombined) among adults with hypertension.Data sourcesPubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus and the Cochrane Library.Eligibility criteriaRandomised controlled trails (RCTs) or meta-analyses (MAs) of controlled trials that: (1) involved healthy adults>18 year with hypertension; (2) investigated exercise and BP; (3) reported preintervention and postintervention BP and (4) were published in English. RCTs had an EX+MEDScombined arm; and an EXalone arm and/or an MEDSalone arm; and MAs performed moderator analyses.DesignA systematic network MA and meta-review with the evidence graded using the Physical Activity Guidelines for Americans Advisory Committee system.OutcomeThe BP response for EXalone, MEDSalone and EX+MEDScombined and compared with each other.ResultsTwelve RCTs qualified with 342 subjects (60% women) who were mostly physically inactive, middle-aged to older adults. There were 13 qualifying MAs with 28 468 participants (~50% women) who were mostly Caucasian or Asian. Most RCTs were aerobic (83.3%), while the MAs involved traditional (46%) and alternative (54%) exercise types. Strong evidence demonstrates EXalone, MEDSalone and EX+MEDScombined reduce BP and EX+MEDScombined elicit BP reductions less than the sum of their parts. Strong evidence indicates EX+MEDScombined potentiate the BP effects of MEDSalone. Although the evidence is stronger for alternative than traditional types of exercise, EXaloneelicits greater BP reductions than MEDSalone.ConclusionsThe combined BP effects of exercise and medications are not additive or synergistic, but when combined they bolster the antihypertensive effects of MEDSalone.PROSPERO registration numberThe protocol is registered at PROSPERO CRD42020181754.

Both back pain and heart failure (HF) have negative influence on all aspects of life. Little is known about the impact of back pain on older adults with HF. We include 1295 older adults who had data collected in the 11th year (2007-2008) of the Health, Aging and Body Composition (Health ABC) study to evaluate the effect of back pain on health status among older adults with and without HF. The participants aged 79-91, 54.8% were female and 34.8% were African American. Among 94 participants with HF, 63 (67.0%) had back pain; among 1201 participants without HF, 649 (54.0%) had back pain. Females reporting back pain had 4.76 (95% CI: 1.83, 12.37) times the odds of having HF compared to those without back pain. Male with back pain, compared to those without back pain, had 1.14 times (95% CI: 0.65, 2.02) the odds of having HF. Depressive symptoms were measured by the Center for Epidemiological Studies-Depression (CES-D) scale. Performance and functions were measured by the Established Populations for Epidemiologic Studies in the Elderly (EPESE) performance score, the Health ABC performance battery score and self-reported difficulty with functional tasks. These symptom and performance measures were significantly associated with both back pain and HF, but not the interaction terms of back pain and HF after adjusting demographic variables including gender, race, smoking status and BMI category. The high incidence and negative impact of back pain highlighted the needs of developing strategies in pain management among older adults with and without HF.

BACKGROUND: Melanoma is a malignant skin cancer that has a poor prognosis in advanced patients. The aim of the present study was to investigate the antitumor role of neferine in melanoma. METHODS: A375 and C32 cells were selected as research vectors in vitro. Cell counting Kit-8, 5-ethynyl-2’-deoxyuridine staining, transwell, and flow cytometry assay were used to examined cell malignant phenotypes. Mitochondrial dysfunction was detected by 5,50,6,60-tetrachloro-1,10,3,30-tetraethyl-imidacarbocyanine iodide staining and enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) generation was measured using oxidation sensitive fluorescent probe. The phosphorylation activity of p38 and Jun-N-terminal kinase (JNK) 1/2 were examined by Western blot. A xenograft model was established via the subcutaneous injection of A375 cells into the right flank of BALB/c mice in vivo. RESULTS: Neferine (2.5, 5, or 10 µM) treatment inhibited proliferation, invasion, and enhanced apoptotic rate of A375 and C32 cells. Neferine treatment induced abnormal changes in mitochondrial membrane potential. Further studies showed that neferine could significantly increase the production of reactive oxygen species (ROS) and 3,4-methylenedioxyamphetamine (MDA) content, decreased the superoxide dismutase (SOD) level. Neferine (5, 10, or 20 mg/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells in vivo, and the expression of Ki67(+) and survivin(+) decreased. Notably, neferine also activated the phosphorylation of p38 and JNK1/2. CONCLUSIONS: Neferine inhibits the proliferative and invasion ability of melanoma cells and promotes their apoptosis, ameliorating the malignant progression of melanoma, likely achieved by upregulating the phosphorylation levels of p38 mitogen-activated protein kinase and JNK1/2.

Exercise stress echocardiography (ESE) is a valuable diagnostic and prognostic tool in adults with hypertrophic cardiomyopathy (HCM). Inducible and resting left ventricular outflow tract gradients are important predictors of heart failure. However, there are minimal data on the utility of this modality in children.Retrospective review of all pediatric HCM patients who underwent ESE at Boston Children's Hospital (January 2007-June 2018) was carried out. Patients were assigned to one of three categories based on left ventricular outflow tract gradients: group 1:30 mm Hg at rest and exercise; group 2:30 mm Hg at rest and ≥30 mm Hg with exercise; and group 3: ≥ 30 mm Hg at rest and exercise. Records were reviewed for earliest occurrence of composite endpoint of any one of the following: cardiac syncope, chest pain, nonsustained and sustained ventricular tachycardia, aborted cardiac arrest, heart failure class ≥ II, or HCM-related death/transplantation.A total of 91 children (67% males) with median age 12 years (6-24 years) at first ESE and median left ventricle wall thickness of 20 mm formed the cohort. Median follow-up duration was 3 years. During ESE, only one child experienced an event and was resuscitated. Of the 91 children, 25 were classified as group 1, 40 as group 2, and 26 as group 3. Twenty-six patients met the composite endpoint, including two heart transplant, one aborted cardiac arrest, and one sudden cardiac death. Group 3 patients had a 5 times higher risk of developing symptoms and/or serious clinical outcome at any age (hazard ratio = 5.18; 95% CI, [1.39-19.2]; P = .014). During our short follow-up time, group 2 patients had a higher risk of outcome, but this did not achieve statistical significance (hazard ratio = 1.95; 95% CI, [0.5-7.6]; P = .33).In this large series of pediatric patients with HCM, ESE can be performed safely and served as an effective tool to identify the lowest risk patients for cardiac outcome.

OBJECTIVES: Given the conflicting evidence regarding fruit juice consumption and childhood obesity, we sought to evaluate associations between 100% orange juice (OJ) consumption and changes in anthropometric parameters in a large prospective cohort of US children and adolescents. METHODS: Participants from the Growing Up Today Study II (n = 7301) completed a baseline questionnaire in 2004 and follow-up questionnaires in 2006 and 2008. Data from these questionnaires were then used to assess mean 2-year changes in anthropometric characteristics in relation to OJ consumption. Changes in body mass index (BMI) percentile and height-for-age z-score (HAZ) were computed across OJ consumption categories using mixed linear regression modeling. RESULTS: Girls’ 2-year mean (SD) change in BMI percentile was not associated with OJ consumption after full adjustment: −0.44 (0.36) for OJ non-consumers, 0.20 (0.41) for 1–3 glasses/month, −0.04 (0.34) for 1–6 glasses/week, and −0.77 (0.62) for ≥1 glass/day (P-trend = 0.49). Meanwhile, girls’ 2-year mean (SD) change in HAZ was positively associated with OJ consumption: 0.03 (0.01) for non-consumers, 0.03 (0.02) for 1–3 glasses/month, 0.06 (0.01) for 1–6 glasses/week, and 0.09 (0.02) for ≥1 glass/day after full adjustment (P-trend = 0.02). There were no significant associations in boys. CONCLUSIONS: These results indicate that OJ consumption was not associated with BMI percentile but was positively associated with HAZ change in girls, suggesting that OJ consumption is unlikely to contribute towards obesity. FUNDING SOURCES: This study was supported by the Florida Department of Citrus, an executive agency of the state of Florida.

4 Background: Whether the time to PSA nadir (TTN) has differential prognostic value in men who reach an undetectable versus detectable PSA nadir remains unknown. Methods: Two-hundred and four men from a prospective randomized controlled trial (RCT) involving radiation therapy with or without 6 months of androgen deprivation therapy (ADT) in unfavorable risk CaP at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality (PCSM) calculated using Fine and Gray competing risk regression. Results: After a median follow-up of 18.17 years, 160 men died; 30 (18.75%) of CaP. Amongst men with a PSA nadir ≥ 0.2 ng/ml, a TTN < median (12 months) was significantly associated with an increased PCSM-risk versus the median or more (AHR 5.07, 95% CI 2.10-12.23, p

Exercise stress echocardiography (ESE) is a versatile diagnostic tool that has been integrated into the standard clinical assessment of adult patients with coronary artery disease, hypertrophic cardiomyopathy (HCM), and pulmonary hypertension. Experience with ESE in children with these disorders is more limited. Given the potential value of this technology is significant, its role in the clinical diagnosis and management of pediatric patients continues to evolve. Since 2006, Boston Children’s Hospital has been performing stress echocardiography in children for both ischemia and assessment of hemodynamics of exercise.

This cohort study examines the association of older age with risk of adverse pathological findings at radical prostatectomy in men with biopsy-confirmed Gleason score 6 prostate cancer.

Cardiac allograft vasculopathy is a leading cause of long-term morbidity & mortality in pediatric heart transplant (Ped HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in identifying ischemia. However, the value of ESE in predicting subsequent CV outcomes is

330 Background: We evaluated whether the intermediate-risk factors of percentage of positive biopsies (PPB), clinical tumor category, and prostate-specific antigen (PSA) level, in addition to age, were associated with the risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer treated with brachytherapy (BT) alone or BT and a short course of androgen deprivation therapy (ADT). Methods: We conducted a prospective cohort study of 1920 consecutively treated men with Gleason 3+4 adenocarcinoma of the prostate who received BT or BT and a median of 4 months of ADT between 10/14/1997 and 5/28/2013. Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether PPB, cT2b-T2c, and PSA of 10.1-20.0 ng/ml, in addition to age greater than the median of 70 years, were associated with the risk of PCSM after adjustment for comorbidity. Results: After a median follow-up of 7.8 years (interquartile range 5.2-10.4 years), 284 men (14.8%) had died, including 31 (10.9% of deaths) from PC of which 18 (58.1%) and 13 (41.9%) occurred in men treated with BT or BT and ADT, respectively. For men treated with BT alone, increasing PPB, PSA of 10.1-20.0 vs 4.0-10.0 ng/mL, and age >70 vs ≤70 years were significantly associated with an increased risk of PCSM (adjusted hazard ratio [AHR] 1.015 95% confidence interval [CI] 1.000-1.031, P=0.048; AHR 5.55, 95% CI 2.01-15.29, P70 years and PSA of 10.1-20.0 ng/ml were significantly associated with an increased risk of PCSM following BT, and adding 4 months of ADT may not be sufficient to mitigate this risk. Advanced imaging and targeted biopsy of suspicious areas should be considered to personalize treatment in order to minimize the risk of PCSM in these men.

289 Background: We evaluated the impact of age > 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age > 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age > 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p < 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- < 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age > 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age > 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.