Post-thyroidectomy bleeding: analysis of risk factors from a national registry.

BACKGROUND: Post-thyroidectomy haemorrhage occurs in 1-2 per cent of patients, one-quarter requiring bedside clot evacuation. Owing to the risk of life-threatening haemorrhage, previous British Association of Endocrine and Thyroid Surgeons (BAETS) guidance has been that day-case thyroidectomy could not be endorsed. This study aimed to review the best currently available UK data to evaluate a recent change in this recommendation. METHODS: The UK Registry of Endocrine and Thyroid Surgery was analysed to determine the incidence of and risk factors for post-thyroidectomy haemorrhage from 2004 to 2018. RESULTS: Reoperation for bleeding occurred in 1.2 per cent (449 of 39 014) of all thyroidectomies. In multivariable analysis male sex, increasing age, redo surgery, retrosternal goitre and total thyroidectomy were significantly correlated with an increased risk of reoperation for bleeding, and surgeon monthly thyroidectomy rate correlated with a decreased risk. Estimation of variation in bleeding risk from these predictors gave low pseudo-R2 values, suggesting that bleeding is unpredictable. Reoperation for bleeding occurred in 0.9 per cent (217 of 24 700) of hemithyroidectomies, with male sex, increasing age, decreasing surgeon volume and redo surgery being risk factors. The mortality rate following thyroidectomy was 0.1 per cent (23 of 38 740). In a multivariable model including reoperation for bleeding node dissection and age were significant risk factors for mortality. CONCLUSION: The highest risk for bleeding occurred following total thyroidectomy in men, but overall bleeding was unpredictable. In hemithyroidectomy increasing surgeon thyroidectomy volume reduces bleeding risk. This analysis supports the revised BAETS recommendation to restrict day-case thyroid surgery to hemithyroidectomy performed by high-volume surgeons, with caution in the elderly, men, patients with retrosternal goitres, and those undergoing redo surgery.

Cognitive function, disease burden and the structural connectome in systemic lupus erythematosus.

Objective To investigate brain structural connectivity in relation to cognitive abilities and systemic damage in systemic lupus erythematosus (SLE). Methods Structural and diffusion MRI data were acquired from 47 patients with SLE. Brains were segmented into 85 cortical and subcortical regions and combined with whole brain tractography to generate structural connectomes using graph theory. Global cognitive abilities were assessed using a composite variable g, derived from the first principal component of three common clinical screening tests of neurological function. SLE damage ( LD) was measured using a composite of a validated SLE damage score and disease duration. Relationships between network connectivity metrics, cognitive ability and systemic damage were investigated. Hub nodes were identified. Multiple linear regression, adjusting for covariates, was employed to model the outcomes g and LD as a function of network metrics. Results The network measures of density (standardised ß = 0.266, p = 0.025) and strength (standardised ß = 0.317, p = 0.022) were independently related to cognitive abilities. Strength (standardised ß = -0.330, p = 0.048), mean shortest path length (standardised ß = 0.401, p = 0.020), global efficiency (standardised ß = -0.355, p = 0.041) and clustering coefficient (standardised ß = -0.378, p = 0.030) were independently related to systemic damage. Network metrics were not related to current disease activity. Conclusion Better cognitive abilities and more SLE damage are related to brain topological network properties in this sample of SLE patients, even those without neuropsychiatric involvement and after correcting for important covariates. These data show that connectomics might be useful for understanding and monitoring cognitive function and white matter damage in SLE.

Application of the Target Lipid Model and Passive Samplers to Characterize the Toxicity of Bioavailable Organics in Oil Sands Process-Affected Water.

Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g., naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis.

Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.8 ± 14.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal reference range ( p < 0.0001) and associated with lower MD ( ß = -0.61, p = 0.02), depression ( ß = 0.17, p = 0.001), anxiety ( ß = 0.13, p = 0.006) and higher body mass index ( ß = 0.10, p = 0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration ( p = 0.003) and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( ß = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.

Cancer incidence among HIV-positive women in British Columbia, Canada: Heightened risk of virus-related malignancies.

OBJECTIVES: We used population-based data to identify incident cancer cases and correlates of cancer among women living with HIV/AIDS in British Columbia (BC), Canada between 1994 and 2008. METHODS: Data were obtained from a retrospective population-based cohort created from linkage of two province-wide databases: (1) the database of the BC Cancer Agency, a province-wide population-based cancer registry, and (2) a database managed by the BC Centre for Excellence in HIV/AIDS, which contains data on all persons treated with antiretroviral therapy in BC. This analysis included women (≥ 19 years old) living with HIV in BC, Canada. Incident cancer diagnoses that occurred after highly active antiretroviral therapy (HAART) initiation were included. We obtained a general population comparison of cancer incidence among women from the BC Cancer Agency. Bivariate analysis (Pearson χ(2) , Fisher's exact or Wilcoxon rank-sum test) compared women with and without incident cancer across relevant clinical and sociodemographic variables. Standardized incidence ratios (SIRs) were calculated for selected cancers compared with the general population sample. RESULTS: We identified 2211 women with 12 529 person-years (PY) of follow-up who were at risk of developing cancer after HAART initiation. A total of 77 incident cancers (615/100 000 PY) were identified between 1994 and 2008. HIV-positive women with cancer, in comparison to the general population sample, were more likely to be diagnosed with invasive cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma and Kaposi's sarcoma and less likely to be diagnosed with cancers of the digestive system. CONCLUSIONS: This study observed elevated rates of cancer among HIV-positive women compared to a general population sample. HIV-positive women may have an increased risk for cancers of viral-related pathogenesis.

Hydrated silicate minerals on Mars observed by the Mars Reconnaissance Orbiter CRISM instrument.

Phyllosilicates, a class of hydrous mineral first definitively identified on Mars by the OMEGA (Observatoire pour la Mineralogie, L'Eau, les Glaces et l'Activitié) instrument, preserve a record of the interaction of water with rocks on Mars. Global mapping showed that phyllosilicates are widespread but are apparently restricted to ancient terrains and a relatively narrow range of mineralogy (Fe/Mg and Al smectite clays). This was interpreted to indicate that phyllosilicate formation occurred during the Noachian (the earliest geological era of Mars), and that the conditions necessary for phyllosilicate formation (moderate to high pH and high water activity) were specific to surface environments during the earliest era of Mars's history. Here we report results from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) of phyllosilicate-rich regions. We expand the diversity of phyllosilicate mineralogy with the identification of kaolinite, chlorite and illite or muscovite, and a new class of hydrated silicate (hydrated silica). We observe diverse Fe/Mg-OH phyllosilicates and find that smectites such as nontronite and saponite are the most common, but chlorites are also present in some locations. Stratigraphic relationships in the Nili Fossae region show olivine-rich materials overlying phyllosilicate-bearing units, indicating the cessation of aqueous alteration before emplacement of the olivine-bearing unit. Hundreds of detections of Fe/Mg phyllosilicate in rims, ejecta and central peaks of craters in the southern highland Noachian cratered terrain indicate excavation of altered crust from depth. We also find phyllosilicate in sedimentary deposits clearly laid by water. These results point to a rich diversity of Noachian environments conducive to habitability.

Exposure to individual polycyclic aromatic compounds impairs the cardiac performance of American lobster (Homarus americanus) larvae.

The potential for oil spills poses a threat to marine organisms, the toxicity of which has been attributed primarily to polycyclic aromatic compounds (PACs). Predictive tools such as the target lipid model (TLM) have been developed to forecast and assess these risks. The aim of the present study was to characterize the cardiotoxicity of 10 structurally diverse PACs in American lobster (Homarus americanus) larvae by assessing heart rate following a 48 h exposure in a passive dosing system, and subsequently use the TLM framework to calculate a critical target lipid body burden (CTLBB) for bradycardia. Exposure to 8 of the 10 PACs resulted in concentration-dependent bradycardia, with phenanthrene causing the greatest effect. The TLM was able to effectively characterize bradycardia in American lobsters, and the cardiotoxic CTLBB value determined in this study is among the most sensitive endpoints included in the CTLBB database. This study is one of the first to apply the TLM to a cardiac endpoint and will improve predictive models for assessing sublethal impacts of oil spills on American lobster populations.

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

BACKGROUND/OBJECTIVES: Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. SUBJECTS/METHODS: Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. RESULTS: The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. CONCLUSIONS: Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Effectiveness of ozonation treatment in eliminating toxicity of oil sands process-affected water to Chironomus dilutus.

Water soluble organic compounds (OCs), including naphthenic acids (NAs), are potentially toxic constituents of oil sands process-affected water (OSPW) that is generated during extraction of bitumen from Alberta oil sands. Ozonation can decrease concentrations of OCs in OSPW. However, effects of ozonated-OSPW on multicellular organisms are unknown. A 10-day and a chronic exposure of Chironomus dilutus to OSPW were conducted to assess effects on survival, growth, development, and behavior. Two separate batches of OSPW were treated with 30 or 80 mg ozone (O(3))/L. Wet body masses of larvae exposed to OSPW were 64 to 77% less than their respective controls (p < 0.001). However, both levels of ozonation significantly attenuated effects of OSPW on growth. Similarly, chronic exposure to untreated OSPW resulted in significantly less pupation than in the controls, with 31% and 71% less pupation of larvae exposed to the two batches of OSPW (p < 0.05). Emergence was significantly less for larvae exposed to OSPW, with 13% and 8% of larvae emerging, compared to 81% in controls (p < 0.0001). Both levels of ozonation of OSPW attenuated effects on emergence. These results suggest that OCs degraded by ozonation causes toxicity of OSPW toward C. dilutus, and that ozonation attenuates toxicity of OSPW.

The effect of protease inhibitors derived from potato formulated in a minidrink on appetite, food intake and plasma cholecystokinin levels in humans.

BACKGROUND: Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. OBJECTIVE: To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. DESIGN: Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. RESULTS: PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. CONCLUSIONS: In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.

Health status of fathead minnow (Pimephales promelas) populations in a municipal wastewater effluent-dominated stream in the Canadian prairies, Wascana Creek, Saskatchewan.

Their unique hydrological and climatic conditions render surface water systems in the southern Canadian Prairies at an elevated risk from exposure to contaminants released from municipal wastewater effluents (MWWEs). The aim of this study was to characterize the potential health effects and their underlying molecular mechanisms in populations of fathead minnow (Pimephales promelas; FHM) in Wascana Creek, an effluent dominated stream in Southern Saskatchewan, Canada. Studies were conducted during the spawning season in 2014 and 2015 to assess responses in terms of overall health, reproductive functions, plasma sex steroid hormone levels, and expression of selected genes along the hypothalamus-pituitary-gonadal axis. FHM downstream of the effluent fallout had lower gonadosomatic indices and significantly greater hepatosomatic indices compared to upstream populations. In both male and female FHMs, significantly greater occurrence and severity of gonadal degradation and delayed maturation were observed in downstream fish compared to upstream fish. Downstream males also displayed lower scores of secondary sexual characteristics and a decreasing trend in plasma 11-ketotestosterone levels. Interestingly, no indications of exposure to estrogenic compounds, such as occurrence of testicular oocytes were observed, which was in accordance with the lack of presence of key biomarkers of estrogenic exposure, such as induction of vitellogenin. In general, expression of the majority of transcripts measured in FHMs downstream of the effluent fallout was significantly downregulated, which supports observations of the general deterioration of the health and reproductive status of these fish. Chemical analysis indicated that 10 pharmaceuticals and personal care products (PPCPs) were present at the downstream site, some at sufficiently great concentrations that may present a risk to aquatic organisms. With continuous exposure to a diverse number of stressors including high nutrient and ammonia levels, the presence of a variety of PPCPs and other contaminants, Wascana Creek should be considered as an ecosystem at risk.

Transformation of fibroblasts by allogeneic and xenogeneic transplants of demineralized tooth and bone.

Xenogeneic transplants of powdered, dehydrated, demineralized matrix of bone and tooth were well tolerated in three species of rodents. Differences between the species were found in competence of fibroblasts to be transformed into cartilage and bone in vivo by these preparations. Rat fibroblasts were most susceptible to transformation of this sort; they were transformed by demineralized dentin of guinea pig, mouse, and rat, and to a limited extent, by a specimen of decalcified human bone.

Hemithyroidectomy: the preferred initial surgical approach for management of Hurthle cell neoplasm.

BACKGROUND: The objective of this study was to evaluate the cancer risk of patient clinicopathologic characteristics to determine the optimal approach for the surgical management of individuals with Hurthle cell neoplasm (HN) diagnosed by cytology. METHODS: Patient clinicopathologic characteristics evaluated included age, sex, tumor size, and ipsilateral thyroid lobe nodularity. The association of these characteristics with a pathologic cancer diagnosis was evaluated using Fisher's exact test and Student t test. RESULTS: Of the 422 patients undergoing thyroidectomy, 27 presented with a fine-needle aspiration biopsy diagnosis of HN, and by pathologic assessment 7 HN patients (25.9%) had a cancer diagnosis. Although none of the clinicopathologic characteristics evaluated were able to reliably differentiate benign from malignant tumors, large tumor size and male sex were significantly associated with a pathologic diagnosis of Hurthle cell carcinoma (P < .05). CONCLUSIONS: Hemithyroidectomy represents the preferred initial surgical approach for the management of individuals presenting with nodular thyroid disease and a cytologic diagnosis of HN.

Prevention and control of healthcare-associated infection.

Current policy and initiatives to reduce healthcare-associated infections (HCAIs) are outlined and discussed. Approaches to the effective control and prevention of HCAIs include surveillance, evidence-based infection control practice and responsible antibiotic prescribing.

Pilot study of a screening test for peripheral arterial disease in middle aged men: fibrinogen as a possible risk factor.

A simple one minute exercise test was used as a screening test for asymptomatic peripheral arterial disease in a sample of 100 men in their sixth decade with no previous referrals for cardiovascular disease. Other investigations included resting ECG, non-invasive carotid artery assessment, and plasma biochemical analysis. Of these 100 men (mean age 56), 10 had evidence of peripheral disease on exercise testing, four had ischaemic changes on resting ECG, and one showed evidence of carotid artery stenosis. A total therefore of 15 out of 100 (15%) had asymptomatic arterial disease. These 15 men had increased concentrations of plasma fibrinogen (4.3(0.7) g.litre-1) compared with men with no evidence of arterial disease (3.5(0.7) g.litre-1; p less than 0.01). The one minute exercise test is a useful screening test for peripheral arterial disease, and this pilot study suggests that raised plasma fibrinogen concentrations may be an important risk factor.

Bioaccumulation and molecular effects of sediment-bound metals in zebrafish embryos.

Predicting the bioavailability and effects of metals in sediments is of major concern in context with sediment risk assessment. This study aimed to investigate the bioavailability and molecular effects of metals spiked into riverine sediments to zebrafish (Danio rerio) embryos. Embryos were exposed to a natural and an artificial sediment spiked with cadmium (Cd), copper (Cu), nickel (Ni) and zinc (Zn) individually or as a mixture at concentrations ranging from 150 to 3000 mg/kg dry weight (dw) over 48 h, and uptake of metals was determined. Furthermore, transcript abundances of the metallothioneins MT1 and MT2, the metal-responsive element-binding transcription factor (MTF) and the genes sod1, hsp70 and hsp90α1 were measured as indicators of metal-induced or general cellular stress. D. rerio embryos accumulated metals from sediments at concentrations up to 100 times greater than those spiked to the sediment with the greatest bioaccumulation factor (BAF) for Cu from artificial sediment (275.4 ± 41.9 (SD)). Embryos accumulated greater concentrations of all metals from artificial than from natural sediment, and accumulation was greater when embryos were exposed to individual metals than when they were exposed to the mixture. Exposure of embryos to Zn or the mixture exhibited up to 30-fold greater transcript abundances of MT1, MT2 and hsp70 compared to controls which is related to significant uptake of Zn from the sediment. Further changes in transcript abundances could not be related to a significant uptake of metals from sediments. These studies reveal that metals from spiked sediments are bioavailable to D. rerio embryos directly exposed to sediments and that the induction of specific genes can be used as biomarkers for the exposure of early life stages of zebrafish to metal-contaminated sediments.

The magnitude of the hypercholesterolemia of hypothyroidism is associated with variation in the low density lipoprotein receptor gene.

To assess whether the variable extent to which patients with hypothyroidism become hypercholesterolemic was associated with variation in the genes for the low density lipoprotein (LDL) receptor or apolipoprotein-B, we investigated prospectively 52 patients with primary hypothyroidism treated with L-T4. There was significant reduction in cholesterol, high density lipoprotein cholesterol, LDL cholesterol, and apolipoprotein-A1 and -B after thyroid hormone replacement. The reduction in cholesterol was associated significantly with the magnitude in the reduction of serum TSH levels (P < 0.001) and the variable AvaII restriction site in exon 13 of the LDL receptor gene. For a given reduction in TSH, patients of genotype -/- (no restriction site) demonstrated a reduction in serum LDL cholesterol that was 4-fold greater than that of patients homozygous for the AvaII restriction site (genotype +/+), with heterozygous (+/-) patients showing an intermediate response. The hypocholesterolemic response was significantly greater in patients of the -/- genotype than in patients carrying the +allele (genotypes +/- and +/+; for LDL cholesterol, P < 0.01; for cholesterol, P < 0.05). No such relationship was observed with a variation at any other polymorphic site studied (four in the LDL receptor gene and two in the apolipoprotein-B gene). The magnitude of the decrease in high density lipoprotein cholesterol and apolipoprotein-A1 and -B was independent of the AvaII genotype, the effect of which was specific to LDL cholesterol. Variation within the LDL receptor gene appears to influence the magnitude of both the hypercholesterolemia of hypothyroidism and, consequently, the reduction of serum LDL cholesterol in response to L-T4. Thus, it may be possible to predict which hypothyroid patients are at greatest risk for coronary artery disease.

Comparison of the effects of dietary vitamin E on in vivo and in vitro parameters of lipid peroxidation in the rabbit.

This study has investigated the effect of dietary vitamin E on markers of antioxidant status. Four groups of rabbits received diets containing 30 energy percent (en%) total fat (7.8 en% contributed by linoleic acid) for 12 weeks. D,1-alpha tocopheryl acetate was added to the diets to obtain a range of vitamin E concentrations (49, 114, 179, or 775 tocopherol equivalents per kg diet). Increased vitamin E concentrations were demonstrated in plasma lipoproteins and erythrocyte membranes following supplementation, and dietary effects on lipid peroxidation were investigated by (i) monitoring a fluorescent parinaric acid probe incorporated into erythrocyte membranes in vivo, (ii) determination of malondialdehyde and oxysterols in plasma, and (iii) investigation of the susceptibility of low density lipoprotein (LDL) to copper-induced conjugated diene formation in vitro. No effects of vitamin E were observed on parinaric acid oxidation in vivo or on the accumulation of lipid peroxidation products in plasma, but the resistance of LDL to oxidation in vitro increased significantly as vitamin E was supplemented to the diets. Our results demonstrate that under these dietary conditions (7.8 en% linoleic acid) increasing the vitamin E content of plasma and erythrocytes approximately two-fold does not reduce the level of lipid peroxidation in vivo, indicating sufficient antioxidant capacity on the lowest vitamin E diet. In contrast, LDL became more resistant to an extreme oxidative stress applied in vitro. The relevance of these assays to currently proposed mechanisms of atherosclerosis is discussed.