Search

Background: No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer.Method: This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI95%).Results: Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI95%: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI95%: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI95%: 0.54-1.32, p = 0.5), compared to HIC.Conclusion: Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer.

Travis, SK, Pritchard, HJ, Mujika, I, Gentles, JA, Stone, MH, and Bazyler, CD. Characterizing the tapering practices of United States and Canadian raw powerlifters. J Strength Cond Res 35(12S): S26-S35, 2021-The purpose of this study was to characterize the tapering practices used by North American powerlifters. A total of 364 powerlifters completed a 41-item survey encompassing demographics, general training, general tapering, and specific tapering practices. Nonparametric statistics were used to assess sex (male and female), competition level (regional/provincial, national, and international), and competition lift (squat, bench press, and deadlift). The highest training volume most frequently took place 5-8 weeks before competition, whereas the highest training intensity was completed 2 weeks before competition. A step taper was primarily used over 7-10 days while decreasing the training volume by 41-50% with varied intensity. The final heavy (>85% 1 repetition maximum [1RM]) back squat and deadlift sessions were completed 7-10 days before competition, whereas the final heavy bench press session was completed

Background DriveSafe DriveAware (DSDA) has been validated as an off-road screening tool for predicting on-road driving performance in clinical populations, but its utility in people with Huntington's disease (HD) is unknown. Objective Our aim was to evaluate the utility of DSDA in people with HD by demonstrating sensitivity of DSDA scores to HD progression and exploring associations between DSDA performance and cognitive functions that are essential to driving and impaired in people with HD. Methods We administered the iPad application version of DSDA to 26 pre-symptomatic and symptomatic participants with HD. Disease progression was assessed via measures of motor impairment, disease burden and functional capacity. Standardised neuropsychological tests were used to assess cognitive function across several domains including attention, processing speed, planning, and visuoperception. Results Results underscore the sensitivity of DSDA to HD progression and cognitive impairment; that is, poorer DSDA performance was associated with greater HD severity and poorer cognitive ability across the domains of attention, processing speed, and planning. Nevertheless, we identified a proportion of participants with HD who were predicted to pass on-road testing based on DSDA, but scored in the impaired range on multiple cognitive tests. These participants tended to score closer to the cut-off score used by DSDA to categorise pass/fail outcomes. Conclusions Our findings demonstrate potential for use of DSDA in the HD population, however, significant variability in cognitive performance among those predicted to 'pass' on-road driving assessment suggests the screening tool requires further development for use with HD drivers.

Background: Breast cancer, is increasing in prevalence amongst South East (SE) Asian women, highlighting the need for high quality, early diagnoses. This study investigated radiologists’ detection efficacy in a developing (DC) and developed (DDC) SE Asian country, as compared to Australian radiologists. Methods: Using a test-set of 60 mammographic cases, 20 containing cancer, JAFROC figures of merit (FOM) and ROC area under the curves (AUC) were calculated as well as location sensitivity, sensitivity and specificity. The test set was examined by 35, 15, and 53 radiologists from DC, a DDC and Australia, respectively. Results: DC radiologists, compared to both groups of counterparts, demonstrated significantly lower JAFROC FOM, ROC AUC and specificity scores. DC radiologists had a significantly lower location sensitivity than Australian radiologists. DC radiologists also demonstrated significantly lower values for age, hours of reading per week, and years of mammography experience when compared with other radiologists. Conclusion: Significant differences in breast cancer detection parameters can be attributed to the experience of DC radiologists. The development of inexpensive, innovative, interactive training programs are discussed. This nonuniform level of breast cancer detection between countries must be addressed to achieve the World Health Organisation goal of health equity.

There is significant debate over Iran’s nuclear program and their potential for weaponization. One camp of scholars and policy makers argue that a nuclear Iran would bring stability to the region while others argue that the regime will become a more aggressive threat. To better analyze the situation we must understand Iran’s intentions. To investigate Iran’s intentions I use a multimethod approach, employing operational code and image theory, to examine the worldview of Ali Khamenei, Iran’s Supreme Leader, in regards to how he perceives the international system broadly, and the United States specifically. Understanding Khamenei’s perceptions and motivations provides a foundation on which to analyze the issue of a nuclear Iran. The results suggest that Khamenei is moderate and seeks to compromise and work with other actors, provided the other actors negotiate without making threats, consistent with prior research positing that nuclear weapons are sought to increase influence on the world stage.

Pritchard, HJ, Barnes, MJ, Stewart, RJC, Keogh, JWL, and McGuigan, MR. Short-term training cessation as a method of tapering to improve maximal strength. J Strength Cond Res 32(2): 458-465, 2018-The aim of this study was to determine the effects of 2 different durations of training cessation on upper- and lower-body maximal strength performance and to investigate the mechanisms underlying performance changes following short-term training cessation. Eight resistance trained males (23.8 ± 5.4 years, 79.6 ± 10.2 kg, 1.80 ± 0.06 m, relative deadlift 1 repetition maximum of 1.90 ± 0.30 times bodyweight [BW]) each completed two 4-week strength training periods followed by either 3.5 days (3.68 ± 0.12 days) or 5.5 days (5.71 ± 0.13 days) of training cessation. Testing occurred pretraining (T1), on the final day of training (T2), and after each respective period of training cessation (T3). Participants were tested for salivary testosterone and cortisol, plasma creatine kinase, psychological profiles, and performance tests (countermovement jump [CMJ], isometric midthigh pull, and isometric bench press [IBP]) on a force plate. Participants' BW increased significantly over time (p = 0.022). The CMJ height and IBP peak force showed significant increases over time (p = 0.013, 0.048, and 0.004, respectively). Post hoc testing showed a significant increase between T1 and T3 for both CMJ height and IBP peak force (p = 0.022 and 0.008 with effect sizes of 0.30 and 0.21, respectively). No other significant differences were seen for any other measures. These results suggest that a short period of strength training cessation can have positive effects on maximal strength expression, perhaps because of decreases in neuromuscular fatigue.

IntroductionFollowing the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post-treatment surveillance. Systemic recurrence is most often detected in the lungs. The most appropriate surveillance frequency and modality remain unknown and, as such, clinical practice is highly varied. We plan to assess the feasibility of conducting a multi-centre randomised controlled trial (RCT) that will evaluate the effect on overall 5-year survival of two different surveillance frequencies and imaging modalities in patients with STS who undergo surgical excision with curative intent.Methods and analysisThe Surveillance After Extremity Tumor Surgery trial will be a multi-centre 2×2 factorial RCT. Patients with non-metastatic primary Grade II or III STS treated with excision will be allocated to one of four treatment arms1: chest radiograph (CXR) every 3 months for 2 years2; CXR every 6 months for 2 years3; chest CT every 3 months for 2 years or4 chest CT every 6 months for 2 years. The primary outcome of the pilot study is the feasibility of a definitive RCT based on a combination of feasibility endpoints. Secondary outcomes for the pilot study include the primary outcome of the definitive trial (overall survival), patient-reported outcomes on anxiety, satisfaction and quality of life, local recurrence-free survival, metastasis-free survival, treatment-related complications and net healthcare costs related to surveillance.Ethics and disseminationThis trial received provisional ethics approval from the McMaster/Hamilton Health Sciences Research Ethics Board on 7 August 2019 (Project number 7562). Final ethics approval will be obtained prior to commencing patient recruitment. Once feasibility has been established and the definitive protocol is finalised, the study will transition to the definitive study.Trial registrationNCT03944798; Pre-results.

Background Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. Methods The By‐Band study was designed in the UK in 2009–2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux‐en‐Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. Results The pilot phase recruited over 13 months in 2013–2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. Conclusion Adaptation of a two‐group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/)., Something to consider

Anticholinergic use is common in the elderly, and among patients with overactive bladder (OAB). We conducted a historical cohort study examining the relationship between anticholinergic exposure and intensity on the risk of falls and fractures based on administrative claims data for Medicare Advantage members with OAB. Patients newly diagnosed or treated for OAB were identified and followed until disenrollment or end of the study period. Primary outcome was a combined endpoint consisting of falls or fractures. The Anticholinergic Cognitive Burden (ACB) scale was used to define and quantify daily anticholinergic exposure (unexposed, current and past); exposure intensity (low, moderate or high) was determined accounting for daily dose and anticholinergic potency. Cox proportional hazards models were used to determine association between anticholinergic exposure and falls/fractures controlling for potential confounders. There were 113,311 patients with mean age of 74.8 (±6.2) years included in the study. Current anticholinergic exposure was associated with a 1.28-fold increased hazard of a fall/fracture (95% confidence interval [CI]: 1.23–1.32, P

Objectives: Nerve block administration in concert with general anesthesia can help manage post-operative pain and provide favorable muscle relaxation of the operative leg in hip surgery. However, the optimal nerve blockade_if any_for arthroscopic surgery of the hip remains undefined. Considerations specific to hip arthroscopy include control of intra-operative pain, adequate muscle relaxation to allow for distraction for work in the central compartment, and post-operative pain control. Dold et al. recently reported in AJSM that a pre-operative femoral nerve block administered in concert with general anesthesia led to decreased patient-reported pain scores at the 60 minute mark post-operatively. Given this demonstrated benefit of the pre-operative femoral nerve block, we hypothesized that a regional block that anesthetized the femoral nerve and the lateral femoral cutaneous nerve (as the fascia iliaca block does), or one that anesthetized the obturator nerve in addition to the femoral and lateral femoral cutaneous nerves (i.e. the lumbar plexus block), would provide additional benefit. The purpose of this study is to examine the effects of pre-operative fascia iliaca and lumbar plexus nerve blocks on post-operative pain and secondary post-operative variables following arthroscopic surgery of the hip. Methods: A retrospective chart analysis was conducted on 145 patients undergoing arthroscopic surgery of the hip in 3 groups. Group 1 (n=55) received general anesthesia only, Group 2 (n=30) received general anesthesia and a fascia iliaca nerve block, and Group 3 (n=60) received general anesthesia and a lumbar plexus nerve block. Post-operative measures were recorded, examined and compared. The primary outcome measure was patient reported pain scores (0-10) at 0, 30, 60, 90 and 120 minutes in the post-anesthesia care unit (PACU). Secondary variables examined included time spent in the PACU, morphine equivalent administered, and presence of nausea requiring anti-emetic medication. Results: Mid-term analysis revealed no benefit to the fascia iliaca block; this regional anesthesia technique showed no significant effect on any of the measured post-operative variables when compared to general anesthesia alone. We therefore abandoned this block in favor of the lumbar plexus block. Patients receiving a lumbar plexus block exhibited significantly decreased pain at each time point when compared to the fascia iliaca group, and at all but one time point when compared to the general anesthesia group (P

Pritchard, HJ, Tod, DA, Barnes, MJ, Keogh, JW, and McGuigan, MR. Tapering practices of New Zealand's elite raw powerlifters. J Strength Cond Res 30(7): 1796-1804, 2016-The major aim of this study was to determine tapering strategies of elite powerlifters. Eleven New Zealand powerlifters (28.4 ± 7.0 years, best Wilks score of 431.9 ± 43.9 points) classified as elite were interviewed, using semistructured interviews, about their tapering strategies. Interviews were transcribed verbatim and content analyzed. Total training volume peaked 5.2 ± 1.7 weeks from competition while average training intensity (of 1 repetition maximum) peaked 1.9 ± 0.8 weeks from competition. During tapering, volume was reduced by 58.9 ± 8.4% while intensity was maintained (or slightly reduced) and the final weight training session was performed 3.7 ± 1.6 days out from competition. Participants generally stated that tapering was performed to achieve full recovery; that accessory work was removed around 2 weeks out from competition; and deadlifting takes longer to recover from than other lifts. Typically participants stated that trial and error, and changes based on "feel" were the sources of tapering strategies; equipment used and movements performed during tapering are the same as in competition; nutrition was manipulated during the taper (for weight cutting or performance aims); and poor tapering occurred when too long (1 week or more) was taken off training. These results suggest that athletes may benefit from continuing to strength train before important events with reduced volume and maintained intensity. Only exercises that directly assist sports performance should remain in the strength program during tapering, to assist with reductions in fatigue while maintaining/improving strength expression and performance.

Winwood, PW, Dudson, MK, Wilson, D, Mclaren-Harrison, JKH, Redjkins, V, Pritchard, HJ, and Keogh, JWL. Tapering practices of strongman athletes. J Strength Cond Res 32(5): 1181-1196, 2018-This study provides the first empirical evidence of how strongman athletes taper for strongman competitions. Strongman athletes (n = 454) (mean ± SD: 33.2 ± 8.0 years, 178.1 ± 10.6 cm, 108.6 ± 27.9 kg, 12.6 ± 8.9 years general resistance training, 5.3 ± 5.0 years strongman implement training) completed a self-reported 4-page internet survey on tapering practices. Analysis by sex (male and female), age (≤30 and >30 years), body mass (≤105 and >105 kg), and competitive standard (local/regional amateur, national amateur and professional) was conducted. Eighty-seven percent (n = 396) of strongman athletes reported that they used a taper. Athletes stated that their typical taper length was 8.6 ± 5.0 days, with the step taper the most commonly performed taper (52%). Training volume decreased during the taper by 45.5 ± 12.9%, and all training ceased 3.9 ± 1.8 days out from competition. Typically, athletes reported that training frequency and training duration stayed the same or decreased and training intensity decreased to around 50% in the last week. Athletes generally stated that tapering was performed to achieve recovery, rest, and peak performance; the deadlift, yoke walk, and stone lifts/work took longer to recover from than other lifts; assistance exercises were reduced or removed in the taper; massage, foam rolling, nutritional changes, and static stretching were strategies used in the taper; and, poor tapering occurred when athletes trained too heavy/hard or had too short a taper. These data will assist strongman athletes and coaches in the optimization of tapering variables leading to more peak performances. Future research could investigate the priming and preactivation strategies strongman athletes use on competition day.

Recent developments in the Internet of Things (IoT), social media, and the data sciences have resulted in larger volumes of data than ever before, offering more opportunity for observing and understanding behaviors. Advances in data analytic and machine learning techniques have also enabled assessments to be more multi-faceted, incorporating data from more sources. Machine learning algorithms such as Decision Trees and Random Forests, K-nearest neighbors, and Artificial Neural Networks have been used to uncover hidden patterns in data and derive predictions and recommendations from a wide range of data types and sources. However, these do not necessarily yield insights into behaviors in complex systems/domains. Methods from mathematics such as Set Theory, Graph Theory, and Network Science may be useful in shedding light on the interactions and relationships within and across domains. This paper provides a description of the applications, strengths, and limitations of some of these techniques and methods.

Healthcare-associated infections (HAIs) represent serious complications for patients within pediatric cardiac intensive care units (CICU). HAIs are associated with increased morbidity, mortality and resource utilization. There are few studies describing the epidemiology of HAIs across the entire spectrum of patients (surgical and nonsurgical) receiving care in dedicated pediatric CICUs.Retrospective analyses of 22,839 CICU encounters from October 2013 to September 2016 across 22 North American CICUs contributing data to the Pediatric Cardiac Critical Care Consortium clinical registry.HAIs occurred in 2.4% of CICU encounters at a rate of 3.3 HAIs/1000 CICU days, with 73% of HAIs occurring in children1 year. Eighty encounters (14%) had ≥2 HAIs. Aggregate rates for the 4 primary HAIs are as follows: central line-associated blood stream infection, 1.1/1000 line days; catheter-associated urinary tract infections, 1.5/1000 catheter days; ventilator-associated pneumonia, 1.9/1000 ventilator days; surgical site infections, 0.81/100 operations. Surgical and nonsurgical patients had similar HAIs rates/1000 CICU days. Incidence was twice as high in surgical encounters and increased with surgical complexity; postoperative infection occurred in 2.8% of encounters. Prematurity, younger age, presence of congenital anomaly, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT) 4-5 surgery, admission with an active medical condition, open sternum and extracorporeal membrane oxygenation were independently associated with HAIs. In univariable analysis, HAI was associated with longer hospital length of stay and durations of urinary catheter, central venous catheter and ventilation. Mortality was 24.4% in patients with HAIs versus 3.4% in those without, P0.0001.We provide comprehensive multicenter benchmark data regarding rates of HAIs within dedicated pediatric CICUs. We confirm that although rare, HAIs of all types are associated with significant resource utilization and mortality.

Objective Chylothorax complicates the postoperative course of patients after congenital heart surgery. Innominate vein thrombosis and stenosis have been associated with postoperative chylothorax. Revascularization and angioplasty can be accomplished using transcatheter techniques. We report our experience with this procedure for the management of postoperative chylothorax. Design This is a retrospective case series of patients who underwent catheter revascularization and/or angioplasty of the innominate vein following cardiac surgery at our institution from January 1, 2008 through April 9, 2014. Setting The cardiovascular intensive care unit and cardiac catheterization laboratory at the University of Alabama at Birmingham and Benjamin Russell Hospital for Children in Birmingham, Alabama were used as settings for the study. Patients Out of 112 patients with postoperative chylothorax, 7 (6.3%) underwent transcatheter dilation of the innominate vein for occlusion/stenosis. The median age of the cohort was 1 month (15 days–6 years); median weight was 3 kg (2.7–22.2). Diagnosis was made a median 8 days (2–20) and persisted for a median of 24 days (9–44). Most patients failed medical management (low fat diet, nothing by mouth, and/or octreotide). Results Cardiac catheterization occurred at a median 9 days (2–29) after chylothorax diagnosis. Median chest tube output on the day prior to procedure was 63 (12–149) cc/kg/day and decreased to 23 (0–64) cc/kg/day 2 days postprocedure (P = .01). Effusions resolved in a median of 5 days (1–16). There were no clinical complications postcatheterization. All patients who have undergone repeat angiography have maintained patency of the innominate vein. There was no mortality. Complications from chylothorax included prolong hospitalization, hyponatremia, hypoproteinemia, coagulopathy, lymphopenia, and infection. Conclusions Innominate vein occlusion and stenosis associated with chylous effusion are amenable to transcatheter revascularization and/or angioplasty, consistently leading to improvement, if not full resolution of chylothorax.

The closer a line extends toward a surrounding frame, the longer it appears. This is known as a framing effect. Over 70 years ago, Teodor Kunnapas demonstrated that the shape of the visual field itself can act as a frame to influence the perceived length of lines in the vertical-horizontal illusion. This illusion is typically created by having a vertical line rise from the center of a horizontal line of the same length creating an inverted T figure. We aimed to determine if the degree to which one fixates on a spatial location where the two lines bisect could influence the strength of the illusion, assuming that the framing effect would be stronger when the retinal image is more stable. We performed two experiments: the visual-field and vertical-horizontal illusion experiments. The visual-field experiment demonstrated that the participants could discriminate a target more easily when it was presented along the horizontal versus vertical meridian, confirming a framing influence on visual perception. The vertical-horizontal illusion experiment determined the effects of orientation, size, and eye gaze on the strength of the illusion. As predicted, the illusion was strongest when the stimulus was presented in either its standard inverted T orientation or when it is rotated 180° compared to other orientations, and in conditions in which the retinal image was more stable, as indexed by eye tracking. Taken together, we conclude that the results provide support for Teodor Kunnapas’ explanation of the vertical-horizontal illusion.

We describe surgical repair of symptomatic tricuspid valve regurgitation in the early posttransplant period in a small child. The tricuspid valve regurgitation was due to injury to the valve and chordal apparatus during surveillance endomyocardial biopsy. The described surgical technique produced durable improvement in valve function.

Objective: To explore individuals’ experiences of receiving either standard care or comprehensive cardiac rehabilitation post minor stroke or transient ischaemic attack. Design: A qualitative study using semi-structured interviews, alongside a randomized controlled trial, exploring the effectiveness of comprehensive cardiac rehabilitation compared with standard care. Interviews were transcribed verbatim and subjected to thematic analysis. Setting: Individuals’ homes. Subjects: People who have experienced a minor stroke or transient ischaemic attack and who were partaking in a secondary prevention randomized controlled trial (6–7 months post the event, 17 males, five females; mean age 67 years). Interventions: Not relevant. Main measures: Not relevant. Results: Four themes were identified: information delivery, comparing oneself with others, psychological impact, attitudes and actions regarding risk factor reduction. Participants indicated a need for improved information delivery, specific to their own risk factors and lifestyle changes. Many experienced psychological impact as a result of their minor stroke. Participants were found to make two types of social comparison; the comparison of self to another affected by stroke, and the comparison of self to cardiac patients. Conclusion: Comprehensive cardiac rehabilitation was reported to have positive effects on people’s motivation to exercise. Following a minor stroke, many individuals do not recall information given or risk factors specific to them. Downward comparison with individuals who have had a cardiovascular event led to some underplaying the significance of their minor stroke.

The Fontan operation has low mortality, but is associated with significant postoperative morbidity, including prolonged chest tube output (PCTO), which is associated with prolonged hospital length of stay (PLOS). We sought to identify variables present early in the clinical course that could predict patients at high risk for PCTO and PLOS. Retrospective data were collected on 84 Fontan (extracardiac conduit) operations from 1/2008 to 12/2013 at a single institution. PCTO was defined as ≥8 days (75th percentile); PLOS was defined as ≥12 days postoperatively (75th percentile). Multivariate regression was used to determine covariates associated with PCTO and PLOS. Median age was 3.5 years (IQR 3-5); weight was 14.5 kg (IQR 13-17). There was no mortality. LOS was 9 days (IQR 3-11), and duration of chest tube drainage 6 days (IQR 5-8) at 15 ml/kg/day (IQR 9-20). In univariate analysis, only systemic right ventricle, 24-h 5 % albumin administration, 24-h fluid balance, and 12-h inotrope score were associated with PCTO. In multivariate analysis, only 5 % albumin administration in first 24 h (p 0.001) and PCTO were independently associated with PLOS. ROC curve analysis showed patients receiving25 ml/kg of 5 % albumin in first 24-h predicted PLOS (94 % specificity, 93 % sensitivity, AUC = 0.95, p 0.001). Increased colloid in the first 24-h post-CPB strongly predicts PCTO and PLOS after Fontan operation, potentially providing an early identification of a cohort with unfavorable Fontan physiology. A better understanding of the role of colloid resuscitation after Fontan is necessary, and efforts to reduce perioperative colloid administration could decrease hospital morbidity.

Norrin signaling is protumorigenic in GBM progression A-Introduction: Norrin, a secreted factor encoded by the Norrie Disease Protein gene (NDP), is an atypical WNT ligand that specifically binds the FZD4 receptor and activates the canonical WNT signaling pathway in endothelial cells to regulate vascular development and barrier function in the brain. Recently, our group identified a novel tumor inhibitory function of NDP/FZD4 signaling in the endothelium in mouse models of medulloblastoma. Here we investigated the function of the NDP/FZD4 signaling axis in glioblastoma (GBM) progression. B-Experimental approaches GBM patients' survival data was obtained from TCGA and analyzed using the cBioportal server. Low passage mitogen expanded GBM cancer stem cell lines were established from primary tumors using standard conditions. NDP expression in experimental cell lines was modulated using lentiviral delivery of short hairpins or full length cDNA. Cell number was assessed by trypan blue cell counting, and sphere forming cell frequency was tested using extreme limited dilution assay (ELDA). For in vivo assessment of tumorigenesis, experimental and control cell lines were xenografted intracranially in NOD/SCID/Gamma (NSG) mice and symptomatic animals were euthanized and brains collected for histological analysis. C-Results Analysis of GBM data from TCGA showed that survival and NDP expression are negatively GBM. Gene expression analysis indicated variable expression levels of NDP/FZD4 signaling pathway components in a panel of 10 primary GBM stem cell lines. In vitro gain and loss of function studies showed that NDP promotes proliferation and sphere formation in GBM. Moreover, the effects of are recapitulated in xenografts. NDP appears to control GBM differentiation, as it affects the proportion of cycling (Ki67+) cells and the level of stemness (Sox2 levels). Finally, NDP function is independent of FZD4 and canonical Wnt signaling, indicating that it functions through an alternative pathway. D-Conclusions Our in vitro and in vivo results indicate that Norrin might have an oncogeneic role in GBM. In addition, the effect of Norrin is FZD4- and WNT-independent. Our results indicate that targeting Norrin GBM might be a potential therapeutic approach. Citation Format: Ahmed A. Elsehemy, Hayden Selvadurai, Katherine Rowland, Peter Dirks, Valerie Wallace. Norrin signaling is protumorigenic in glioblastoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1117.

Ammonia is used as a stimulant in strength based sports to increase arousal and offset fatigue however little is known about its physiological and performance effects. The purpose of this study was twofold (1) establish the physiological response to acute ammonia inhalation (2) determine whether the timing of the physiological response corresponds with a performance enhancement, if any.Fifteen healthy males completed two trials. Trial one investigated the beat-to-beat middle cerebral artery blood flow velocity (MCAv), heart rate (HR) and mean arterial pressure (MAP) response to ammonia inhalation. During trial two, participants performed a maximal single mid-thigh pull (MTP) at various time points following ammonia inhalation in a randomised order: MTPs were conducted immediately, 15, 30 and 60 s following ammonia inhalation. A MTP with no ammonia inhalation served as the control. During this trial maximal MTP force, rate of force development (RFD) and electromyography (EMG) activity were recorded.MCAvmean increased and peaked on average by 6 cm s(-1) (P 0.001), 9.4 ± 5.5 s following ammonia inhalation. Similarly, HR was increased by 6 ± 11 beats per minute 15 s following ammonia inhalation (P 0.001). MAP remained unchanged following inhalation (P = 0.51). The use and timing of ammonia inhalation had no effect on maximal force, RFD or EMG (all P 0.2) compared to control.MCAv was elevated despite no increase in MAP occurring; this is indicative of a cerebrovascular vasodilation. Despite the marked cerebrovascular and cardiovascular response to ammonia inhalation no ergogenic effect was observed during the MTP, irrespective of the timing of administration.

Aim To identify the incidence and risk of suicide and self harm, among patients prescribed antidepressant drugs. Methods A retrospective cohort study, with nested case control, of patients identified from a nonrandom sample of general practices in New Zealand from 1996 to 2001. A total of 57 361 patients who received a prescription for a single antidepressant were identified from the RNZCGP Research Unit Database. Suicides within 120 days of a prescription were identified from the New Zealand National Mortality Database and self-harm events within 120 days of a prescription were identified from the New Zealand Hospital discharge database. Results 26 suicides and 330 episodes of self-harm were identified within 120 days of an antidepressant prescription. On univariate analysis the association, expressed as OR (95% CI), between selective serotonin reuptake inhibitors (SSRIs) and self harm and suicide were 2.26 (1.27–4.76) and 1.92 (0.77–4.83), respectively. When corrected for the confounding effects of age, gender and depression/suicidal ideation there was an association between SSRIs and self harm, OR 1.66 (95% CI 1.23–2.23), but not for suicide, 1.28 (0.38–4.35). Paroxetine was a significant risk factor for suicide on univariate analysis, 4.23 (1.19–14.95), but not when corrected for age, gender and depression/suicidal ideation, 2.76 (0.30–24.87). Conclusions Age, gender and pre-existing depression/suicidal ideation are important confounders in observational studies of the association between antidepressants and suicide or self harm.

Objective Hemolysis, occurring during cardiopulmonary bypass, is associated with lipid peroxidation and postoperative acute kidney injury. Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury. This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass. Design Single-center prospective randomized double-blinded study. Setting University-affiliated pediatric hospital. Patients Thirty children undergoing elective surgical correction of a congenital heart defect. Interventions Patients were randomized to acetaminophen (OFIRMEV [acetaminophen] injection; Cadence Pharmaceuticals, San Diego, CA) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass. Measurement and main results Markers of hemolysis, lipid peroxidation (isofurans and F2-isoprostanes), and acute kidney injury were measured throughout the perioperative period. Cardiopulmonary bypass was associated with a significant increase in free hemoglobin (from a prebypass level of 9.8 ± 6.2 mg/dL to a peak of 201.5 ± 42.6 mg/dL postbypass). Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery. The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes. Acetaminophen attenuated the increase in plasma isofurans compared with placebo (p = 0.02 for effect of study drug). There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation. Acetaminophen did not affect postoperative creatinine, urinary neutrophil gelatinase-associated lipocalin, or prevalence of acute kidney injury. Conclusion Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation. Acetaminophen attenuated the increase in plasma isofuran concentrations. Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass.

To compare clinical profiles of Shang Ring versus conventional circumcisions.Parallel group open-label randomized controlled trial with one-to-one allocations in 2 sites.We enrolled HIV-negative men aged 18-54 years in Homa Bay, Kenya, and Lusaka, Zambia and followed them at 2, 7, 14, 21, 28, 42, and 60 days after Shang Ring versus conventional circumcision. We compared the duration of surgery, postoperative pain using a visual analog scale, adverse events rates, time to complete wound healing by clinical assessment, participant acceptability, and provider preferences between circumcision groups.We randomized 200 men to each group; 197 and 201 contributed to the Shang Ring and conventional surgery analyses, respectively. Adverse event rates were similar between groups. Pain scores at most time points were similar, however, the Shang Ring group reported higher scores for worst pain during erections (3.5 ± 1.9 vs. 2.3 ± 1.7; P0.001). Significantly more men were satisfied with the cosmetic appearance following Shang Ring male circumcision (MC), 95.7% versus 85.9% (P = 0.02) in Kenya, and 96.8% versus 71.3% (P0.01) in Zambia. Although median time to complete wound healing was 43 days in both groups, conventional circumcisions healed on average 5.2 days sooner (P0.001). Shang Ring procedures took one-third the time of conventional MC, 7 versus 20 minutes. All circumcision providers preferred the Shang Ring.Safety profiles of the 2 techniques were similar, all MC providers preferred the Shang Ring technique, and study participants preferred the Shang Ring's cosmetic results. The Shang Ring should be considered for adult MC as programs scale-up.

Ventricular assist devices (VADs) are used in children with severe heart failure as a bridge to heart transplantation or recovery. Severe pulmonary dysfunction may preclude their use, leaving extracorporeal membrane oxygenation (ECMO) as the most frequently used option for combined cardiac and respiratory failure. There are few case reports describing the use of an oxygenator in combination with VAD support, but none that describes long-term utilization. We report the successful use of a low-resistance oxygenator placed into the right-sided VAD (RVAD) circuit of an infant with life-threatening respiratory failure. The oxygenator enabled immediate reversal of hypoxaemia and hypercarbia and recovery of the RVAD function. The oxygenator remained within the VAD circuit for 15 days, facilitating complete lung recovery. An oxygenator used in conjunction with a VAD may be a life-saving therapy, allowing adequate oxygenation and ventilation in severe respiratory and cardiac failure. Extended use may facilitate the prevention of ventilator-associated lung injury and organ dysfunction. This therapy may be an attractive intermediate step in the transition from, or alternative to ECMO, in patients requiring VAD placement with associated acute lung injury.

BACKGROUND AND PURPOSE Excess morbidity/mortality in rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease. In this ‘proof-of-concept’ study, vascular function was characterized in the murine collagen-induced arthritis (mCIA) model, the benchmark choice for evaluation of the pathological processes and assessment of new therapies. EXPERIMENTAL APPROACH Mice in the very early stages of arthritis development [and appropriate naive (non-immunized) age-matched controls] were used in the study. Blood pressure was measured using tail cuff plethysmography. Vascular function in rings of isolated aorta was studied with isometric tension myography. Levels of NO metabolites (NOx), MMP-9 protein and IL-1β in plasma and MMP-9 protein in aortic homogenates were quantified. KEY RESULTS Impaired vascular contractile responses in arthritis were unaffected by ex vivo inhibition of NOS (endothelial/neuronal and inducible) or COX activities. Endothelium-dependent and -independent relaxation, plasma NOx and blood pressure were unaffected by arthritis. Plasma and aortic homogenate MMP-9 protein levels were increased significantly in arthritis. Incubation of aortic tissues from naive control animals with exogenous MMP-9 impaired subsequent contractile responses, mirroring that observed in arthritis. A role for IL-1β in perpetuating contractile dysfunction and increasing aortic MMP-9 was excluded. CONCLUSIONS AND IMPLICATIONS These data identify for the first time a relationship between early arthritis and contractile dysfunction and a possible role for MMP-9 therein, in the absence of overt endothelial dysfunction or increased NO production. As such, MMP-9 may constitute a significant target for early intervention in RA patients with a view to decreasing risk of cardiovascular disease.

Background Although individuals with diabetes mellitus frequently have dyslipidaemias and high blood pressure, much of the increased risk for coronary heart disease is not explained by these and other classical risk factors. Thus, other less widely recognized risk factors, including increased susceptibility of low-density lipoprotein (LDL) to oxidation, might enhance vascular dysfunction and atherogenesis in diabetes. Aims We compared both the rate and extent of LDL oxidation ex vivo between 78 poorly controlled individuals with type 1 diabetes and 78 age- and sex-matched non-diabetic controls. We then initiated intensive insulin therapy for 3 months to determine the impact of improved glucose control on LDL composition and oxidation. Results Diabetic and non-diabetic individuals did not have significantly different body weights, dietary intake, blood pressure, renal function or plasma lipid levels. LDL composition was also similar in both groups. In contrast, vitamin E content in LDL was significantly lower in diabetic patients. Measures of LDL lipid oxidation, including conjugated diene, lipid peroxide and thiobarbituric acid reactive substances formation, as well as measures of LDL protein modification, were significantly greater in diabetic patients. Levels of hyperglycaemia correlated strongly with each measure of LDL lipid oxidation (r ranges from 0·60–0·81, P