Glycemic Variability as a Predictor of Graft Failure Following Infrainguinal Bypass for Peripheral Arterial Disease: A Retrospective Cohort Study.

BACKGROUND: Glycemic variability (GV), measured as the change in visit-to-visit glycated hemoglobin (HbA1c), increases the risk of multiple adverse outcomes. However, the impact of GV on graft patency following infrainguinal bypass (IIB) is unknown. A retrospective cohort study was undertaken to assess the impact of GV on graft patency. METHODS: A 3-year single-center retrospective case notes analysis of all people undergoing IIB between 2017 and 2019. Rutherford stage, graft conduit, level of bypass, procedure details, baseline demographics, comorbidities, and GV were assessed. Time to reintervention, ipsilateral amputation, or death was recorded to determine primary patency (PP). RESULTS: One hundred six IIB outcomes were analyzed: mean (± standard deviation) age 68.0 (9.2) years; 69 (65.1%) male, 37 (33.9%), 75 (70.8%) had diabetes mellitus; and 46 (43.4%) underwent elective procedures. GV > 9.1% was associated with significantly lower median PP than GV < 9.1%, 198 (97-753.5) vs. 713 (166.5-1,044.5) days (P = 0.045). On univariate analysis, GV > 9.1% vs. < 9.1% was significantly associated with PP (hazard ratio [HR] 1.85 [confidence interval {CI} 1.091-3.136], P = 0.022). Bypass level was also a univariate predictor, with below knee bypasses (HR 2.31 [CI 1.164-4.564], P = 0.017), and tibial (HR 2.00 [CI 1.022-3.090], P < 0.043) having lower PP than above knee bypasses. On multivariate adjustment, GV > 9.1% and level of bypass remained independent predictors of PP, HR 1.96 (95% CI: 1.12-3.42, P = 0.018) and HR 2.54 (95% CI: 1.24-5.22, P = 0.011), respectively. CONCLUSIONS: GV is an independent predictor of PP following infrainguinal bypass, thus optimizing GV should be a therapeutic target.

Axillary necklace graft salvage of a locally infected Haemodialysis with Reliable Outflow (HeRO®) graft.

BACKGROUND: A 48-year-old patient presented 4 months after insertion of a right sided Haemodialysis with Reliable Outflow (HeRO®, Merit Medical) graft with a discharging abscess at the site of the brachial artery anastomosis. There was localised involvement of the arterial Gore® Acuseal inflow graft that necessitated its removal. The venous outflow component was thought salvageable as infection was well localised to the region of the antecubital fossa. OBJECTIVES: Alternative access options were limited so we sought to preserve the venous outflow portion of the patient's original graft - minimising tissue damage and avoiding the need for a dialysis line. METHODS: The infected arterial graft was excised, leaving behind the original SuperHero® connector and venous graft. A left sided tunnelled axillary necklace technique was utilised to restore arterial inflow. RESULTS: After a four-day recovery, the patient went on to successfully resume their usual haemodialysis regimen without any complications. Convalescent imaging, repeat blood cultures, and monitoring of inflammatory markers showed no signs of residual infection at 6 weeks. CONCLUSIONS: The originality of this case was the way in which an axillary necklace inflow graft was connected to the pre-existing venous outflow portion of the HeRO® haemodialysis graft system, allowing the excision of the infected inflow graft at the brachial anastomosis. This technique could be viewed as an effective salvage procedure as it allowed the venous outflow portion of the original graft to remain in situ, minimised tissue damage and enabled the patient to swiftly resume haemodialysis without the need for a line.

Effect of permeable biofilm on micro- and macro-scale flow and transport in bioclogged pores.

Simulations of coupled flow around and inside biofilms in pores were conducted to study the effect of porous biofilm on micro- and macro-scale flow and transport. The simulations solved the Navier-Stokes equations coupled with the Brinkman equation representing flow in the pore space and biofilm, respectively, and the advection-diffusion equation. Biofilm structure and distribution were obtained from confocal microscope images. The bulk permeability (k) of bioclogged porous media depends on biofilm permeability (kbr) following a sigmoidal curve on a log-log scale. The upper and lower limits of the curve are the k of biofilm-free media and of bioclogged media with impermeable biofilms, respectively. On the basis of this, a model is developed that predicts k based solely on kbr and biofilm volume ratio. The simulations show that kbr has a significant impact on the shear stress distribution, and thus potentially affects biofilm erosion and detachment. The sensitivity of flow fields to kbr directly translated to effects on the transport fields by affecting the relative distribution of where advection and diffusion dominated. Both kbr and biofilm volume ratio affect the shape of breakthrough curves.

Validation of the Edinburgh Claudication Questionnaire in 1st generation Black African-Caribbean and South Asian UK migrants: a sub-study to the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study.

BACKGROUND: We determined the diagnostic accuracy of the Edinburgh Claudication Questionnaire (ECQ) in 1st generation Black African-Caribbean UK migrants as previous diagnostic questionnaires have been found to be less accurate in this population. We also determined the diagnostic accuracy of translated versions of the ECQ in 1st generation South Asian UK migrants, as this has not been investigated before. METHODS: Subjects were recruited from the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study, a community based screening survey for heart failure in minority ethnic groups. Translated versions of the ECQ were prepared following a recognised protocol. All participants attending screening between October 2007 and February 2009 were asked to complete the ECQ in the language of their choice (English, Punjabi, Bengali, Urdu, Hindi or Gujarati). Subjects answering positively to experiencing leg pain or discomfort on walking were asked to return to have Ankle Brachial Pressure Index (ABPI) measured. RESULTS: 154 out of 2831 subjects participating in E-ECHOES (5.4%) were eligible to participate in this sub-study, for which 74.3% returned for ABPI assessment. Non-responders were younger than participants (59[9] vs. 65[11] years; p=0.015). Punjabi, English and Bengali questionnaires identified participants with Intermittent Claudication, so these questionnaires were assessed. The sensitivities (SN), specificities (SP), positive (PPV) and negative (NPV) predictive values were calculated. English: SN: 50%; SP: 68%; PPV: 43%; NPV: 74%. Punjabi: SN: 50%; SP: 87%; PPV: 43%; NPV: 90%. Bengali: SN: 33%; SP: 50%; PPV: 13%; NPV: 73%. There were significant differences in diagnostic accuracy between the 3 versions (Punjabi: 83.8%; Bengali: 45%; English: 62.2%; p<0.0001). No significant differences were found in sensitivity and specificity between illiterate and literate participants in any of the questionnaires and there was no significant different difference between those under and over 60 years of age. CONCLUSIONS: Our findings suggest that the ECQ is not as sensitive or specific a diagnostic tool in 1st generation Black African-Caribbean and South Asian UK migrants than in the Edinburgh Artery Study, reflecting the findings of other diagnostic questionnaires in these minority ethnic groups. However this study is limited by sample size so conclusions should be interpreted with caution.

Outcomes of post-operative duplex ultrasound following arteriovenous fistula formation: A pragmatic single-centre experience.

BACKGROUND: Duplex ultrasound surveillance with pre-emptive treatment of an identified stenosis is increasingly being utilised to help maintain arteriovenous fistula patency. This study aims to determine whether post-operative duplex ultrasound surveillance can improve fistula patency at 12 months and improve the proportion of 'pre-haemodialysis' patients commencing haemodialysis via a usable fistula. METHODS: All arteriovenous fistulae formed between 1st January 2015 and 31st August 2017 in a single, tertiary vascular centre were included. Primary and secondary patency at 12 months, along with the proportion of pre-haemodialysis patients commencing haemodialysis via a usable arteriovenous fistula, were compared between the fistulae undergoing duplex ultrasound surveillance and 'standard practice'. RESULTS: Two hundred forty-one arteriovenous fistulae were created in 216 patients. A higher proportion of brachiobasilic transposition arteriovenous fistula and patients undergoing arteriovenous fistula creation following a previously failed access were identified in the duplex ultrasound surveillance group. Primary patency at 12 months (hazard ratio = 0.43, 95% confidence interval = 0.30-0.61, p < .001) was significantly lower in the duplex ultrasound surveillance group compared with the 'standard practice' group. Despite this, no difference was identified in secondary patency at 12 months (hazard ratio = 1.82, 95% confidence interval = 0.87-3.80, p = .112). No difference was also identified in the proportion of pre-haemodialysis patients starting haemodialysis with a usable arteriovenous fistula (duplex ultrasound surveillance = 65.0% vs standard practice = 77.8%; odds ratio = 0.53, 95% confidence interval 0.58-1.19, p = .279). CONCLUSION: Post-operative duplex ultrasound surveillance following arteriovenous fistula formation is associated with higher rates of post-operative intervention; however, this does not translate into improved secondary patency or the proportion of pre-haemodialysis patients commencing HD via their fistula.

Peripheral arterial disease and Virchow's triad.

Peripheral arterial disease (PAD) is an important global healthcare problem associated with considerable morbidity and mortality. This disease is an important manifestation of atherosclerosis and the pathophysiological processes involved in its development, progression and complications are atherothrombosis and thromboembolism. Over 150 years ago, Virchow described a triad of abnormalities (abnormal blood flow, abnormal vessel wall and abnormal blood constituents) associated with thrombus formation (thrombogenesis). An improvement in biochemical techniques has allowed quantification of various components of Virchow's triad, and as a consequence, there has been increasing interest in the measurement of such biomarkers in understanding the development and progression of PAD, as well as its symptomatic complications. This review discusses quantifiable components of Virchow's triad that have been associated with PAD and their clinical utility as risk factors for PAD.

Real-time determination of chloride anion concentration in aqueous-DMSO using a pyrrole-strapped calixpyrrole anion receptor.

The use of a pyrrole-strapped calix[4]pyrrole () permits the determination of chloride anion concentrations in mixed aqueous DMSO-d(6)-H(2)O environments via proton NMR spectroscopy.

Vital exhaustion and cardiovascular disease: are circulating fibrinogen and D-dimer levels a plausible link?

Vital exhaustion has been implicated in the development and progression of cardiovascular disease. In addition, elevated levels of fibrinogen and D-dimer have been associated with an increased risk of cardiovascular disease. Some studies have suggested that fibrinogen and D-dimer are associated with acute, chronic, and perceived stress. In this issue, Kudielka et al examine the relationship between circulating fibrinogen and D-dimer levels and vital exhaustion in a cross-sectional study of middle-aged teachers in Germany, to examine the plausible link between chronic stress and the development of cardiovascular disease. This commentary discusses the limited available evidence of the mechanisms responsible for the association between vital exhaustion and the development of cardiovascular disease and highlights the limitations of previous research and discusses future directions.

Mineral Ecology: Surface Specific Colonization and Geochemical Drivers of Biofilm Accumulation, Composition, and Phylogeny.

This study tests the hypothesis that surface composition influences microbial community structure and growth of biofilms. We used laboratory biofilm reactors (inoculated with a diverse subsurface community) to explore the phylogenetic and taxonomic variability in microbial communities as a function of surface type (carbonate, silicate, aluminosilicate), media pH, and carbon and phosphate availability. Using high-throughput pyrosequencing, we found that surface type significantly controlled ~70-90% of the variance in phylogenetic diversity regardless of environmental pressures. Consistent patterns also emerged in the taxonomy of specific guilds (sulfur-oxidizers/reducers, Gram-positives, acidophiles) due to variations in media chemistry. Media phosphate availability was a key property associated with variation in phylogeny and taxonomy of whole reactors and was negatively correlated with biofilm accumulation and α-diversity (species richness and evenness). However, mineral-bound phosphate limitations were correlated with less biofilm. Carbon added to the media was correlated with a significant increase in biofilm accumulation and overall α-diversity. Additionally, planktonic communities were phylogenetically distant from those in biofilms. All treatments harbored structurally (taxonomically and phylogenetically) distinct microbial communities. Selective advantages within each treatment encouraged growth and revealed the presence of hundreds of additional operational taxonomix units (OTU), representing distinct consortiums of microorganisms. Ultimately, these results provide evidence that mineral/rock composition significantly influences microbial community structure, diversity, membership, phylogenetic variability, and biofilm growth in subsurface communities.

Characterization of Microbial Mat Microbiomes in the Modern Thrombolite Ecosystem of Lake Clifton, Western Australia Using Shotgun Metagenomics.

Microbialite-forming communities interact with the environment and influence the precipitation of calcium carbonate through their metabolic activity. The functional genes associated with these metabolic processes and their environmental interactions are therefore critical to microbialite formation. The microbiomes associated with microbialite-forming ecosystems are just now being elucidated and the extent of shared pathways and taxa across different environments is not fully known. In this study, we profiled the microbiome of microbial communities associated with lacustrine thrombolites located in Lake Clifton, Western Australia using metagenomic sequencing and compared it to the non-lithifying mats associated with surrounding sediments to determine whether differences in the mat microbiomes, particularly with respect to metabolic pathways and environmental interactions, may potentially contribute to thrombolite formation. Additionally, we used stable isotope biosignatures to delineate the dominant metabolism associated with calcium carbonate precipitation in the thrombolite build-ups. Results indicated that the microbial community associated with the Lake Clifton thrombolites was predominantly bacterial (98.4%) with Proteobacteria, Cyanobacteria, Bacteroidetes, and Actinobacteria comprising the majority of annotated reads. Thrombolite-associated mats were enriched in photoautotrophic taxa and functional genes associated with photosynthesis. Observed δ(13)C values of thrombolite CaCO3 were enriched by at least 3.5‰ compared to theoretical values in equilibrium with lake water DIC, which is consistent with the occurrence of photoautotrophic activity in thrombolite-associated microbial mats. In contrast, the microbiomes of microbial communities found on the sandy non-lithifying sediments of Lake Clifton represented distinct microbial communities that varied in taxa and functional capability and were enriched in heterotrophic taxa compared to the thrombolite-associated mats. This study provides new insight into the taxa and functional capabilities that differentiate potentially lithifying mats from other non-lithifying types and suggests that thrombolites are actively accreting and growing in limited areas of Lake Clifton.

Bacterial diversity and ecosystem function of filamentous microbial mats from aphotic (cave) sulfidic springs dominated by chemolithoautotrophic "Epsilonproteobacteria".

Filamentous microbial mats from three aphotic sulfidic springs in Lower Kane Cave, Wyoming, were assessed with regard to bacterial diversity, community structure, and ecosystem function using a 16S rDNA-based phylogenetic approach combined with elemental content and stable carbon isotope ratio analyses. The most prevalent mat morphotype consisted of white filament bundles, with low C:N ratios (3.5-5.4) and high sulfur content (16.1-51.2%). White filament bundles and two other mat morphotypes had organic carbon isotope values (mean delta13C=-34.7 per thousand, 1sigma=3.6) consistent with chemolithoautotrophic carbon fixation from a dissolved inorganic carbon reservoir (cave water, mean delta13C=-7.4 per thousand for two springs, n=8). Bacterial diversity was low overall in the clone libraries, and the most abundant taxonomic group was affiliated with the "Epsilonproteobacteria" (68%), with other bacterial sequences affiliated with Gammaproteobacteria (12.2%), Betaproteobacteria (11.7%), Deltaproteobacteria (0.8%), and the Acidobacterium (5.6%) and Bacteriodetes/Chlorobi (1.7%) divisions. Six distinct epsilonproteobacterial taxonomic groups were identified from the microbial mats. Epsilonproteobacterial and bacterial group abundances and community structure shifted from the spring orifices downstream, corresponding to changes in dissolved sulfide and oxygen concentrations and metabolic requirements of certain bacterial groups. Most of the clone sequences for epsilonproteobacterial groups were retrieved from areas with high sulfide and low oxygen concentrations, whereas Thiothrix spp. and Thiobacillus spp. had higher retrieved clone abundances where conditions of low sulfide and high oxygen concentrations were measured. Genetic and metabolic diversity among the "Epsilonproteobacteria" maximizes overall cave ecosystem function, and these organisms play a significant role in providing chemolithoautotrophic energy to the otherwise nutrient-poor cave habitat. Our results demonstrate that sulfur cycling supports subsurface ecosystems through chemolithoautotrophy and expand the evolutionary and ecological views of "Epsilonproteobacteria" in terrestrial habitats.

Experimental determination of sorption in fractured flow systems.

Fracture "skins" are alteration zones on fracture surfaces created by a variety of biological, chemical, and physical processes. Skins increase surface area, where sorption occurs, compared to the unaltered rock matrix. This study examines the sorption of organic solutes on altered fracture surfaces in an experimental fracture-flow apparatus. Fracture skins containing abundant metal oxides, clays, and organic material from the Breathitt Formation (Kentucky, USA) were collected in a manner such that skin surface integrity was maintained. The samples were reassembled in the lab in a flow-through apparatus that simulated approximately 2.7 m of a linear fracture "conduit." A dual-tracer injection scheme was utilized with the sorbing or reactive tracer compared to a non-reactive tracer (chloride) injected simultaneously. Sorption was assessed from the ratio of the first temporal moments of the breakthrough curves and from the loss of reactive tracer mass and evaluated as a function of flow velocity and solute type. The breakthrough curves suggest dual-flow regimes in the fracture with both sorbing and non-sorbing flow fields. Significant sorption occurs for the reactive components, and sorption increased with decreasing flow rate and decreasing compound solubility. Based on moment analysis, however, there was little retardation of the center of solute mass. These data suggest that non-equilibrium sorption processes dominate and that slow desorption and boundary layer diffusion cause extensive tailing in the breakthrough curves.

A mass balance approach to investigating geochemical controls on secondary water quality impacts at a crude oil spill site near Bemidji, MN.

Secondary water quality impacts can result from a broad range of coupled reactions triggered by primary groundwater contaminants. Data from a crude-oil spill research site near Bemidji, MN provide an ideal test case for investigating the complex interactions controlling secondary impacts, including depleted dissolved oxygen and elevated organic carbon, inorganic carbon, CH4, Mn, Fe, and other dissolved ions. To better understand these secondary impacts, this study began with an extensive data compilation of various data types, comprising aqueous, sediment, gas, and oil phases, covering a 260m cross-sectional domain over 30years. Mass balance calculations are used to quantify pathways that control secondary components, by using the data to constrain the sources and sinks for the important redox processes. The results show that oil constituents other than BTEX (benzene, toluene, ethylbenzene, o-, m- and p-xylenes), including n-alkanes and other aromatic compounds, play significant roles in plume evolution and secondary water quality impacts. The analysis underscores previous results on the importance of non-aqueous phases. Over 99.9% of the Fe(2+) plume is attenuated by immobilization on sediments as Fe(II) and 85-95% of the carbon biodegradation products are outgassed. Gaps identified in carbon and Fe mass balances and in pH buffering mechanisms are used to formulate a new conceptual model. This new model includes direct out-gassing of CH4 and CO2 from organic carbon biodegradation, dissolution of directly produced CO2, and sorption with H(+) exchange to improve pH buffering. The identification of these mechanisms extends understanding of natural attenuation of potential secondary impacts at enhanced reductive dechlorination sites, particularly for reduced Fe plumes, produced CH4, and pH perturbations.

Ethnic/racial differences in circulating markers of angiogenesis and their association with cardiovascular risk factors and cardiovascular disease.

OBJECTIVE: To determine (a) whether ethnic/racial differences exist in circulating markers of angiogenesis (Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), soluble Tie-2 receptor (sTie-2) and Angiogenin) between South Asian (SA; from India, Pakistan and Bangladesh); Black African-Caribbean and White (W) ethnic groups, and (b) associations between these markers in stable cardiovascular disease (CVD) and its risk factors. PATIENTS AND METHODS: We recruited 243 subjects (82 SA, 84 Black and 77 W) with symptomatic and clinically confirmed CVD (n=108), risk factor controls (with ≥ 1 cardiovascular risk factor, e.g. smoking, diabetes mellitus, dyslipidaemia, hypertension) and with ankle brachial pressure index >1) (n=64) and healthy controls free of CVD and risk factors (n=56). Angiogenic markers were measured by enzyme linked immunoassay. RESULTS: In healthy controls, angiogenin was higher in SA and Black subjects, compared to Whites (p<0.05). sTie-2 correlated inversely with angiogenin (p=0.001), was higher in women (p=0.029) and was lower in smokers (p=0.007). Overall, age (p=0.001) was the only independent factor associated with angiopoietin-1. Angiogenin (p=0.01) and SBP (p=0.014) were both independently higher in the Black group compared to the White group. CONCLUSIONS: Ethnic, racial, and demographic differences are evident in certain circulating markers of angiogenesis. With the exception of an effect of smoking on sTie-2, these differences are not influenced by the presence of other risk factors, nor the presence of stable cardiovascular disease.

In situ detection of novel Acidobacteria in microbial mats from a chemolithoautotrophically based cave ecosystem (Lower Kane Cave, WY, USA).

Lower Kane Cave, Wyoming (USA), has hydrogen sulfide-bearing springs that discharge into the cave passage. The springs and cave stream harbour white filamentous microbial mats dominated by Epsilonproteobacteria. Recently, novel 16S rRNA gene sequences from the phylum Acidobacteria, subgroup 7, were found in these cave mats. Although Acidobacteria are ubiquitously distributed in many terrestrial and marine habitats, little is known about their ecophysiology. To investigate this group in Lower Kane Cave in more detail, a full-cycle rRNA approach was applied based on 16S and 23S rRNA gene clone libraries and the application of novel probes for fluorescence in situ hybridization. The 16S and 23S rRNA gene clone libraries yielded seven and six novel acidobacterial operational taxonomic units (OTUs) respectively. The majority of the OTUs were affiliated with subgroups 7 and 8. One OTU was affiliated with subgroup 6, and one OTU could not be assigned to any of the present acidobacterial subgroups. Fluorescence in situ hybridization distinguished two morphologically distinct, rod-shaped cells of the acidobacterial subgroups 7 and 8. Although the ecophysiology of Acidobacteria from Lower Kane Cave will not be fully resolved until cultures are obtained, acidobacterial cells were always associated with the potentially chemolithoautotrophic epsilon- or gammaproteobacterial filaments, suggesting perhaps a lifestyle based on heterotrophy or chemoorganotrophy.

Filamentous "Epsilonproteobacteria" dominate microbial mats from sulfidic cave springs.

Hydrogen sulfide-rich groundwater discharges from springs into Lower Kane Cave, Wyoming, where microbial mats dominated by filamentous morphotypes are found. The full-cycle rRNA approach, including 16S rRNA gene retrieval and fluorescence in situ hybridization (FISH), was used to identify these filaments. The majority of the obtained 16S rRNA gene clones from the mats were affiliated with the "Epsilonproteobacteria" and formed two distinct clusters, designated LKC group I and LKC group II, within this class. Group I was closely related to uncultured environmental clones from petroleum-contaminated groundwater, sulfidic springs, and sulfidic caves (97 to 99% sequence similarity), while group II formed a novel clade moderately related to deep-sea hydrothermal vent symbionts (90 to 94% sequence similarity). FISH with newly designed probes for both groups specifically stained filamentous bacteria within the mats. FISH-based quantification of the two filament groups in six different microbial mat samples from Lower Kane Cave showed that LKC group II dominated five of the six mat communities. This study further expands our perceptions of the diversity and geographic distribution of "Epsilonproteobacteria" in extreme environments and demonstrates their biogeochemical importance in subterranean ecosystems.