Hyperlipidemia Prevention and Management Utilizing Lifestyle Changes.

Hyperlipidemia incidence is on the rise and lifestyle behavior change is the first-line therapy. Left untreated, hyperlipidemia can result in cardiovascular disease leading to increased morbidity and mortality in persons worldwide. Evidence has demonstrated behavioral changes such as increased exercise, healthy nutrition, smoking cessation, alcohol abstinence, and other lifestyle modification interventions significantly decrease the incidence and severity of hyperlipidemia. The purpose of this article is to review the evidence of lifestyle interventions in preventing and managing hyperlipidemia and to suggest innovative ways to integrate those techniques into clinical practice. Recommendations on hyperlipidemia specific to pregnancy, polycystic ovary syndrome, and estrogen deficiency are also discussed.

Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma.

BACKGROUND: While neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition. PATIENTS AND METHODS: This is a follow-up study of a previously published phase Ib clinical trial of 30 patients with resectable stage III/IV cutaneous melanoma who received one dose of 200 mg IV neoadjuvant pembrolizumab 3 weeks before surgical resection, followed by 1 year of adjuvant pembrolizumab. The primary outcomes were 5-year overall survival (OS), 5-year recurrence-free survival (RFS), and recurrence patterns. RESULTS: We report updated results at 5 years of follow-up with a median follow-up of 61.9 months. No deaths occurred in patients with a major pathological response (MPR, <10% viable tumor) or complete pathological response (pCR, no viable tumor) (n = 8), compared to a 5-year OS of 72.8% for the remainder of the cohort (P = 0.12). Two of eight patients with a pCR or MPR had a recurrence. Of the patients with >10% viable tumor remaining, 8 of 22 patients (36%) had a recurrence. Additionally, the median time to recurrence was 3.9 years for patients with ≤10% viable tumor and 0.6 years for patients with >10% viable tumor (P = 0.044). CONCLUSIONS: The 5-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date. Response to neoadjuvant therapy continues to be an important prognosticator with regard to OS and RFS. Additionally, recurrences in patients with pCR occur later and are salvageable, with a 5-year OS of 100%. These results demonstrate the long-term efficacy of single-agent neoadjuvant/adjuvant PD-1 blockade in patients with a pCR and the importance of long-term follow-up for these patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02434354.

Major Pelvic Ring Injuries: Fewer Transfusions Without Deaths from Bleeding During the Last Decade.

BACKGROUND: Pelvic fracture-associated bleeding can be difficult to control with historically high mortality rates. The impact of resuscitation advancements for trauma patients with unstable pelvic ring injuries is unknown. We hypothesized that the time elapsed since introduction of our protocol would be associated with decreased blood transfusion requirements. METHODS: A level 1 trauma center's prospective pelvic fracture database was reviewed from 01/01/2009-31/12/2018. All patients with unstable pelvic ring injuries initially presenting to our institution were included. Adjusted regression analysis was performed on the overall cohort and separately for patients in traumatic shock (TS). The primary outcome was 24 h packed red blood cell (PRBC) requirements. Secondary outcomes were 24 h plasma, cryoprecipitate, platelet and intravenous fluid (IVF) requirements, length of stay and mortality. RESULTS: Patients with mechanically unstable pelvic ring injuries (n = 144, median [Q1-Q3] age 44 [28-55] years, 74% male) received a median (Q1-Q3) of 0 (0-4) units PRBC within 24 h, with TS patients (n = 47, 42 [28-60] years, 74% male) receiving 6 (4-9) units PRBC. There was no decrease in 24 h PRBC requirements for the overall cohort (years; IRR = 0.91, 95% CI 0.83-1.01; p = 0.07). TS patients had decreases in 24 h PRBC (years; IRR = 0.90, 95%CI 0.84-0.96; p = 0.002), plasma (IRR = 0.92, 95%CI 0.85-0.99; p = 0.019), cryoprecipitate (IRR = 0.88, 95%CI 0.81-0.95; p = 0.001) and IVF (IRR = 0.94, 95%CI 0.90-0.98; p = 0.004). There were 5 deaths (5/144, 3.5%) with no deaths due to acute hemorrhage. CONCLUSIONS: Over this 10-year period, there was no hemorrhage-related mortality among patients presenting with pelvic fractures. Crystalloid and transfusion requirements decreased for patients presenting with traumatic shock.

Time to definitive fixation of pelvic and acetabular fractures.

BACKGROUND: The timing of definitive surgical stabilization is a controversial topic of pelvic and acetabular fracture (PAF) management. Historically, staged care with delayed definitive fixation was recommended; however, more recently, some centers have shown early definitive fixation to be feasible in most patients. We hypothesized that time to definitive fixation of PAF decreased without adverse outcomes. METHODS: A level 1 trauma center's prospective pelvic fracture database was retrospectively analyzed. A total of 341 of the 1,270 consecutive PAF patients had surgery between January 2009 and December 2018. Demographics, polytrauma status, hemodynamic stability, time to definitive operation, length of intensive care unit stay, hospital length of stay, mortality were recorded. Data is presented as mean ± SD, percentages. Statistical significance was determined at p < 0.05. RESULTS: There were 34 ± 8 per year operatively treated PAF patients during the study period. The demographics (age, 44.1 ± 18 years; 74.5% males) and injury severity (Injury Severity Score, 20; interquartile range, 16-29) did not change. Time to definitive fixation on average was 85 ± 113 hours (range, 0.8-1286 hours). Linear regression analysis demonstrated a decrease in time to definitive fixation considering all patients (ß = -0.186, p = 0.003). pelvic ring fractures with polytrauma (ß = -1.404, p = 0.03). and hemodynamically unstable patients (ß = -1.428, p = 0.037). There was no significant change in mortality, length of stay, or intensive care unit length of stay for the overall cohort or any subgroup. CONCLUSION: Time to definitive fixation in PAF has decreased during the last decade, with the largest decrease in time to fixation occurring in the hemodynamically unstable and pelvic fracture with polytrauma cohorts. The timely definitive internal fixation is achievable without increased length of stay. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Development of human electrophysiological brain networks.

Functional activity in the human brain is intrinsically organized into independently active, connected brain regions. These networks include sensorimotor systems, as well as higher-order cognitive networks such as the default mode network (DMN), which dominates activity when the brain is at rest, and the frontoparietal (FPN) and salience (SN) networks, which are often engaged during demanding tasks. Evidence from functional magnetic resonance imaging (fMRI) suggests that although sensory systems are mature by the end of childhood, the integrity of the FPN and SN develops throughout adolescence. There has been little work to corroborate these findings with electrophysiology. Using magnetoencephalography (MEG) recordings of 48 participants (aged 9-25 yr) at rest, we find that beta-band functional connectivity within the FPN, SN, and DMN continues to increase through adolescence, whereas connectivity in the visual system is mature by late childhood. In contrast to fMRI results, but replicating the MEG findings of Schäfer et al. (Schäfer CB, Morgan BR, Ye AX, Taylor MJ, Doesburg SM. Hum Brain Mapp 35: 5249-5261, 2014), we also see that connectivity between networks increases rather than decreases with age. This suggests that the development of coordinated beta-band oscillations within and between higher-order cognitive networks through adolescence might contribute to the developing abilities of adolescents to focus their attention and coordinate diverse aspects of mental activity. NEW & NOTEWORTHY Using magnetoencephalography to assess beta frequency oscillations, we show that functional connectivity within higher-order cognitive networks increases from childhood, reaching adult values by age 20 yr. In contrast, connectivity within a primary sensory (visual) network reaches adult values by age 14 yr. In contrast to functional MRI findings, connectivity between cognitive networks matures at a rate similar to within-network connectivity, suggesting that coordination of beta oscillations both within and between networks is associated with maturation of cognitive skills.

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity.

Impaired corticomuscular and interhemispheric cortical beta oscillation coupling in amyotrophic lateral sclerosis.

OBJECTIVES: The neural activity of the primary motor cortex is variably synchronised with contralateral peripheral electromyographic signals, which is thought to facilitate long-range communication through the motor system. Such corticomuscular coherence (CMC) is typically observed in the beta-band (15-30 Hz) range during steady force production. We aimed to measure pathological alteration to CMC resulting from ALS. METHODS: CMC was appraised during a forearm grip task in 17 ALS patients contrasted against age-matched healthy controls. An exploratory comparison with a group of asymptomatic ALS gene carriers and neuropathy disease mimics was also undertaken. Neural signals were acquired by whole-head magnetoencephalography and localised via structural MRI to the motor cortices. RESULTS: During light voluntary muscular contraction, beta-band CMC was significantly reduced in ALS patients compared to healthy controls. Propagation of motoric beta rhythms across the cortical hemispheres was also shown to be impaired in ALS patients. CMC was preserved in the asymptomatic gene carrier and did not distinguish ALS patients from neuropathy mimics. CONCLUSION: Functional connectivity metrics reveal an ALS-related decrease in both corticomuscular and interhemispheric communication during bilateral grip force production. SIGNIFICANCE: MEG-derived beta oscillation coupling may be a potential biomarker of motor system dysfunction in ALS, against which to measure future therapeutic efficacy.

Increased cerebral functional connectivity in ALS: A resting-state magnetoencephalography study.

OBJECTIVE: We sought to assess cortical function in amyotrophic lateral sclerosis (ALS) using noninvasive neural signal recording. METHODS: Resting-state magnetoencephalography was used to measure power fluctuations in neuronal oscillations from distributed cortical parcels in 24 patients with ALS and 24 healthy controls. A further 9 patients with primary lateral sclerosis and a group of 15 asymptomatic carriers of genetic mutations associated with ALS were also studied. RESULTS: Increased functional connectivity, particularly from the posterior cingulate cortex, was demonstrated in both patient groups compared to healthy controls. Directionally similar patterns were also evident in the asymptomatic genetic mutation carrier group. CONCLUSION: Increased cortical functional connectivity elevation is a quantitative marker that reflects ALS pathology across its clinical spectrum, and may develop during the presymptomatic period. The amelioration of pathologic magnetoencephalography signals might be a marker sensitive enough to provide proof-of-principle in the development of future neuroprotective therapeutics.

The heritability of multi-modal connectivity in human brain activity.

Patterns of intrinsic human brain activity exhibit a profile of functional connectivity that is associated with behaviour and cognitive performance, and deteriorates with disease. This paper investigates the relative importance of genetic factors and the common environment between twins in determining this functional connectivity profile. Using functional magnetic resonance imaging (fMRI) on 820 subjects from the Human Connectome Project, and magnetoencephalographic (MEG) recordings from a subset, the heritability of connectivity among 39 cortical regions was estimated. On average over all connections, genes account for about 15% of the observed variance in fMRI connectivity (and about 10% in alpha-band and 20% in beta-band oscillatory power synchronisation), which substantially exceeds the contribution from the environment shared between twins. Therefore, insofar as twins share a common upbringing, it appears that genes, rather than the developmental environment, have the dominant role in determining the coupling of neuronal activity.

The effects of ambient temperature and heatwaves on daily Campylobacter cases in Adelaide, Australia, 1990-2012.

Campylobacter spp. is a commonly reported food-borne disease with major consequences for morbidity. In conjunction with predicted increases in temperature, proliferation in the survival of microorganisms in hotter environments is expected. This is likely to lead, in turn, to an increase in contamination of food and water and a rise in numbers of cases of infectious gastroenteritis. This study assessed the relationship of Campylobacter spp. with temperature and heatwaves, in Adelaide, South Australia. We estimated the effect of (i) maximum temperature and (ii) heatwaves on daily Campylobacter cases during the warm seasons (1 October to 31 March) from 1990 to 2012 using Poisson regression models. There was no evidence of a substantive effect of maximum temperature per 1 °C rise (incidence rate ratio (IRR) 0·995, 95% confidence interval (95% CI) 0·993-0·997) nor heatwaves (IRR 0·906, 95% CI 0·800-1·026) on Campylobacter cases. In relation to heatwave intensity, which is the daily maximum temperature during a heatwave, notifications decreased by 19% within a temperature range of 39-40·9 °C (IRR 0·811, 95% CI 0·692-0·952). We found little evidence of an increase in risk and lack of association between Campylobacter cases and temperature or heatwaves in the warm seasons. Heatwave intensity may play a role in that notifications decreased with higher temperatures. Further examination of the role of behavioural and environmental factors in an effort to reduce the risk of increased Campylobacter cases is warranted.

Management of Incidental Adrenal Masses: A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee presents recommendations for managing adrenal masses that are incidentally detected on CT or MRI. These recommendations represent an update to the adrenal component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Adrenal Subcommittee, constituted by abdominal radiologists and an endocrine surgeon, developed this algorithm. The algorithm draws from published evidence coupled with expert subspecialist opinion and was finalized by a process of iterative consensus. Algorithm branches categorize incidental adrenal masses on the basis of patient characteristics and imaging features. For each specified combination, the algorithm concludes with characterization of benignity or indolence (sufficient to discontinue follow-up) and/or a subsequent management recommendation. The algorithm addresses many, but not all, possible pathologies and clinical scenarios. Our goal is to improve the quality of patient care by providing guidance on how to manage incidentally detected adrenal masses.

The influence of motor function on processing speed in preterm and term-born children.

This study investigates the relationship between motor function and processing speed in preterm children. Processing speed was compared in 145 adolescents, born 25-41 weeks gestational age, utilizing tasks including differing motor demands. The influence of motor cortex excitability and functional motor skills on task performance was assessed. For tasks with motoric demands, differences in performance between preterm and term-born children were mediated by the relationship between gestational age, corticomotor excitability, and motor function. There were no differences in non-motor processing speed task performance between preterm and term-born children. Measures of processing speed may be confounded by a timed motor component.

Measurement of dynamic task related functional networks using MEG.

The characterisation of dynamic electrophysiological brain networks, which form and dissolve in order to support ongoing cognitive function, is one of the most important goals in neuroscience. Here, we introduce a method for measuring such networks in the human brain using magnetoencephalography (MEG). Previous network analyses look for brain regions that share a common temporal profile of activity. Here distinctly, we exploit the high spatio-temporal resolution of MEG to measure the temporal evolution of connectivity between pairs of parcellated brain regions. We then use an ICA based procedure to identify networks of connections whose temporal dynamics covary. We validate our method using MEG data recorded during a finger movement task, identifying a transient network of connections linking somatosensory and primary motor regions, which modulates during the task. Next, we use our method to image the networks which support cognition during a Sternberg working memory task. We generate a novel neuroscientific picture of cognitive processing, showing the formation and dissolution of multiple networks which relate to semantic processing, pattern recognition and language as well as vision and movement. Our method tracks the dynamics of functional connectivity in the brain on a timescale commensurate to the task they are undertaking.

Altered cortical beta-band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis.

Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15-30 Hz) power. Cortical beta-band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven "classical" ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS-associated gene mutations were compared with age-similar healthy control groups. Augmented beta desynchronization was observed in both contra- and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237-254, 2017. © 2016 Wiley Periodicals, Inc.

Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study.

OBJECTIVE: To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. DESIGN: Retrospective cohort study in South Australia for the period January 1986 to December 2002. SETTING: A whole of population study. POPULATION: A census of all IVF and ICSI linked to registries for births, pregnancy terminations, and birth defects (diagnosed before a child's fifth birthday). METHODS: Odds ratios (ORs) for birth defects were calculated among IVF, ICSI, and natural conceptions for maternal age, parity, pre-pregnancy BMI, smoking, pre-existing diseases, and conditions in pregnancy, with adjustment for confounding factors. MAIN OUTCOME MEASURES: Birth defects classified by International Classification of Diseases (ninth revision) and British Paediatric Association (ICD9-BPA) codes. RESULTS: There were 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The unadjusted prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. In contrast, for IVF and ICSI combined, relative to natural conceptions, births to women aged ≤29 years had a higher risk (adjusted odds ratio, aOR 1.42; 95% confidence interval, 95% CI 1.04-1.94), births to women aged 35-39 years had no difference in risk (aOR 1.01; 95% CI 0.74-1.37), and births to women aged ≥40 years had a lower risk of defects (aOR 0.45; 95% CI 0.22-0.92). Defects were also elevated for nulliparity, anaemia, and urinary tract infection in births after ICSI, but not after IVF. CONCLUSIONS: The usual age-birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI. TWEETABLE ABSTRACT: Risk of birth defects in women over 40 years is lower after infertility treatment than for natural conceptions.

Nursing Home Registered Nurses' and Licensed Practical Nurses' Knowledge of Causes of Falls.

Reducing falls in nursing homes requires a knowledgeable nursing workforce. To test knowledge, 8 validated vignettes representing multifactorial fall causes were administered to 47 nurses from 3 nursing homes. Although licensed practical nurses scored higher than registered nurses in individual categories of falls, when we computed the average score of all 8 categories between groups of registered nurses and licensed practical nurses, registered nurses scored higher (F = 4.106; P < .05) in identifying 8 causal reasons for older adults to fall.

The effect of temperature on different Salmonella serotypes during warm seasons in a Mediterranean climate city, Adelaide, Australia.

Changing trends in foodborne disease are influenced by many factors, including temperature. Globally and in Australia, warmer ambient temperatures are projected to rise if climate change continues. Salmonella spp. are a temperature-sensitive pathogen and rising temperature can have a substantial effect on disease burden affecting human health. We examined the relationship between temperature and Salmonella spp. and serotype notifications in Adelaide, Australia. Time-series Poisson regression models were fit to estimate the effect of temperature during warmer months on Salmonella spp. and serotype cases notified from 1990 to 2012. Long-term trends, seasonality, autocorrelation and lagged effects were included in the statistical models. Daily Salmonella spp. counts increased by 1·3% [incidence rate ratio (IRR) 1·013, 95% confidence interval (CI) 1·008-1·019] per 1 °C rise in temperature in the warm season with greater increases observed in specific serotype and phage-type cases ranging from 3·4% (IRR 1·034, 95% CI 1·008-1·061) to 4·4% (IRR 1·044, 95% CI 1·024-1·064). We observed increased cases of S. Typhimurium PT9 and S. Typhimurium PT108 notifications above a threshold of 39 °C. This study has identified the impact of warm season temperature on different Salmonella spp. strains and confirms higher temperature has a greater effect on phage-type notifications. The findings will contribute targeted information for public health policy interventions, including food safety programmes during warmer weather.