Clinical and radiographic phenotypes of patients with multifocal subcortical versus cortical cerebral infarcts.

BACKGROUND AND PURPOSE: Infarct topology is a key determinant in classification of a stroke as potentially embolic, with cortical and multifocal lesions being presumed embolic. Whether isolated subcortical multifocal infarcts are likely embolic has not been well studied. METHODS: A prospective, single-center cohort study of consecutive patients with acute multifocal strokes confirmed on diffusion-weighting imaging (DWI) was queried, and patients compared according to the presence of isolated subcortical infarct topology versus cortical ± subcortical topology. Descriptive statistics and multivariable logistic regression were used to determine independent predictors of cryptogenic, subcortical infarcts. RESULTS: Of 1739 patients screened, 743 had complete diagnostic testing with DWI evidence of acute infarction, 183 (24.6%) of whom had a multifocal stroke pattern. Isolated subcortical involvement was disproportionate among patients with ESUS (64.9%) when compared to patients with cardioembolic (24.3%) or large vessel disease (10.8%, p<0.01). Following multivariable adjustment, independent predictors of isolated subcortical multifocal infarction were milder strokes (OR 0.94, 95%CI 0.89-0.98) and higher grade Fazekas score (OR 2.32, 95%CI 1.02-5.29), while cardioembolism (OR 0.30, 95%CI 0.08-1.13) and large vessel disease (OR 0.27, 95%CI 0.08-0.91) remained inversely associated (as compared to ESUS). CONCLUSIONS: These data suggest that multifocal subcortical infarctions are less likely to have an associated proximal embolic source than multifocal infarctions with cortical involvement. The strong association with chronic microvascular disease suggests this topology is more consistent with acute-on-chronic microvascular injury rather than an occult embolic source.

Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3.

Mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3 (MAPK6/ERK3) is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary dysfunction and by defects in function, activation, and positive selection of T cells. To study the role of ERK3 in vivo, we generated mice carrying a conditional Erk3 allele with exon 3 flanked by loxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-cre and a clear reduction of the protein kinase MK5 is detected, providing the first evidence for the existence of the ERK3/MK5 signaling complex in vivo In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile and do not display pulmonary hypoplasia, acute respiratory failure, abnormal T-cell development, reduction of thymocyte numbers, or altered T-cell selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality and lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin resistance cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal, suggesting redundant functions of both protein kinases.

ATP Content and Cell Viability as Indicators for Cryostress Across the Diversity of Life.

In many natural environments, organisms get exposed to low temperature and/or to strong temperature shifts. Also, standard preservation protocols for live cells or tissues involve ultradeep freezing in or above liquid nitrogen (-196°C or -150°C, respectively). To which extent these conditions cause cold- or cryostress has rarely been investigated systematically. Using ATP content as an indicator of the physiological state of cells, we found that representatives of bacteria, fungi, algae, plant tissue, as well as plant and human cell lines exhibited similar responses during freezing and thawing. Compared to optimum growth conditions, the cellular ATP content of most model organisms decreased significantly upon treatment with cryoprotectant and cooling to up to -196°C. After thawing and a longer period of regeneration, the initial ATP content was restored or even exceeded the initial ATP levels. To assess the implications of cellular ATP concentration for the physiology of cryostress, cell viability was determined in parallel using independent approaches. A significantly positive correlation of ATP content and viability was detected only in the cryosensitive algae Chlamydomonas reinhardtii SAG 11-32b and Chlorella variabilis NC64A, and in plant cell lines of Solanum tuberosum. When comparing mesophilic with psychrophilic bacteria of the same genera, and cryosensitive with cryotolerant algae, ATP levels of actively growing cells were generally higher in the psychrophilic and cryotolerant representatives. During exposure to ultralow temperatures, however, psychrophilic and cryotolerant species showed a decline in ATP content similar to their mesophilic or cryosensitive counterparts. Nevertheless, psychrophilic and cryotolerant species attained better culturability after freezing. Cellular ATP concentrations and viability measurements thus monitor different features of live cells during their exposure to ultralow temperatures and cryostress.

MnSi nanostructures obtained from epitaxially grown thin films: magnetotransport and Hall effect.

We present a comparative study of the (magneto)transport properties, including Hall effect, of bulk, epitaxially grown thin film and nanostructured MnSi. In order to set our results in relation to published data we extensively characterize our materials, this way establishing a comparatively good sample quality. Our analysis reveals that in particular for thin film and nanostructured material, there are extrinsic and intrinsic contributions to the electronic transport properties, which by modeling the data we separate out. Finally, we discuss our Hall effect data of nanostructured MnSi under consideration of the extrinsic contributions and with respect to the question of the detection of a topological Hall effect in a skyrmionic lattice.

Nonmonotonic Classical Magnetoconductivity of a Two-Dimensional Electron Gas in a Disordered Array of Obstacles.

Magnetotransport measurements in combination with molecular dynamics simulations on two-dimensional disordered Lorentz gases in the classical regime are reported. In quantitative agreement between experiment and simulation, the magnetoconductivity displays a pronounced peak as a function of the perpendicular magnetic field B which cannot be explained by existing kinetic theories. This peak is linked to the onset of a directed motion of the electrons along the contour of the disordered obstacle matrix when the cyclotron radius becomes smaller than the size of the obstacles. This directed motion leads to transient superdiffusive motion and strong scaling corrections in the vicinity of the insulator-to-conductor transitions of the Lorentz gas.

Minimum Resistance Anisotropy of Epitaxial Graphene on SiC.

We report on electronic transport measurements in rotational square probe configuration in combination with scanning tunneling potentiometry of epitaxial graphene monolayers which were fabricated by polymer-assisted sublimation growth on SiC substrates. The absence of bilayer graphene on the ultralow step edges of below 0.75 nm scrutinized by atomic force microscopy and scanning tunneling microscopy result in a not yet observed resistance isotropy of graphene on 4H- and 6H-SiC(0001) substrates as low as 2%. We combine microscopic electronic properties with nanoscale transport experiments and thereby disentangle the underlying microscopic scattering mechanism to explain the remaining resistance anisotropy. Eventually, this can be entirely attributed to the resistance and the number of substrate steps which induce local scattering. Thereby, our data represent the ultimate limit for resistance isotropy of epitaxial graphene on SiC for the given miscut of the substrate.

Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis.

Objective: To test the performance of the 2015 ACR-EULAR gout classification criteria against presence of SF MSU crystals in a primary healthcare population. Methods: The criteria were applied to an existing dataset of consecutive patients with monoarthritis presenting to Dutch family physicians; all patients underwent microscopic SF analysis by design. The data had been prospectively collected to develop a diagnostic decision rule for gout in 2010. Diagnostic performance was assessed by calculating area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and constructing calibration plots for the full version of the criteria (including SF analysis results of all patients) and the clinical-only version (not including SF analysis results). Performance of both versions was compared with the 2010 diagnostic rule. Results: Of 381 patients enrolled into the study, 216 (57%) were MSU crystal-positive. The full and clinical-only versions of the criteria had satisfactory area under the receiver operating characteristic curve (0.96 and 0.87, respectively), high specificity (0.98 and 0.84), high PPV (0.98 and 0.84), but lower sensitivity (0.68 and 0.68) and NPV (0.70 and 0.67). Specificity and PPV of both versions were higher compared with 0.71 and 0.89 of the 2010 diagnostic decision rule. The decison rule had the highest sensitivity and NPV (0.99 and 0.97). Conclusion: This study presents the first external validation of the 2015 ACR-EULAR gout classification criteria in a primary healthcare setting. The criteria perform well in this setting in patients presenting with monoarthritis for the purpose of enrolling into gout clinical trials.

Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard.

OBJECTIVE: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. METHODS: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. RESULTS: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62]). CONCLUSION: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi.

Survey Definitions of Gout for Epidemiologic Studies: Comparison With Crystal Identification as the Gold Standard.

OBJECTIVE: To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies. METHODS: Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard. RESULTS: For all tested GUGC definitions, the simple definition of "self-report of gout or urate-lowering therapy use" had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%). CONCLUSION: A simple definition of "self-report of gout or urate-lowering therapy use" has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered.

Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises.

OBJECTIVE: To establish consensus for potential remission criteria to use in clinical trials of gout. METHODS: Experts (n = 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete-choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined. RESULTS: There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point scale), and patient global assessment (<2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission. CONCLUSION: These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.

Diagnostic Arthrocentesis for Suspicion of Gout Is Safe and Well Tolerated.

OBJECTIVE: To determine the frequency of adverse events of diagnostic arthrocentesis in patients with possible gout. METHODS: Consecutive patients underwent arthrocentesis and were evaluated at 6 weeks to determine adverse events. The 95% CI were obtained by bootstrapping. RESULTS: Arthrocentesis was performed in 910 patients, and 887 (97.5%) were evaluated for adverse events. Any adverse event was observed in 12 participants (1.4%, 95% CI 0.6-2.1). There was 1 case (0.1%, 95% CI 0-0.34) of septic arthritis. CONCLUSIONS: Diagnostic arthrocentesis is associated with a low frequency of adverse events. Septic arthritis rarely occurs.

Performance of classification criteria for gout in early and established disease.

OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p<0.001) and specificity was better in early disease (79.9% vs 52.5%, p<0.001). The overall best performing clinical criteria were the Rome criteria with sensitivity/specificity in early and established disease of 60.3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease. CONCLUSIONS: Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.

2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSION: The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists.

OBJECTIVE: To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. METHODS: We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. RESULTS: Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. CONCLUSION: This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease.

Low resting heart rates are associated with new-onset atrial fibrillation in patients with vascular disease: results of the ONTARGET/TRANSCEND studies.

BACKGROUND: Elevated systolic blood pressure (SBP) and high resting heart rate (HR) are associated with cardiovascular end-points. Although the association between atrial fibrillation (AF) and SBP is well established, the relation between AF and HR remains unclear. METHODS: In patients from the ONTARGET and TRANSCEND studies with high cardiovascular disease risk (n = 27 064), new-onset AF was evaluated in relation to mean SBP, visit-to-visit variation in SBP (SBP-CV; i.e. SD/mean × 100%), mean HR and visit-to-visit variation in HR (HR-CV). RESULTS: Low mean HR (P < 0.0001) and high SBP (P = 0.0021) were associated with incident AF. High SBP-CV (P = 0.031) and HR-CV (P < 0.0001) were also associated with incident AF. After adjustment for confounders, SBP and SBP-CV were no longer significantly associated with AF. The detrimental effect of low HR was particularly evident in subjects who were not receiving treatment with beta-blockers (P = 0.014 for interaction between beta-blocker use and mean HR). In addition to low HR, high HR-CV and high SBP had additive effects on incident AF. CONCLUSIONS: Low mean HR (<60 beats min(-1) ) is independently associated with incident AF, and low HR-CV and high SBP further increase the incidence of new-onset AF in patients at high risk of cardiovascular disease.

Study for Updated Gout Classification Criteria: Identification of Features to Classify Gout.

OBJECTIVE: To determine which clinical, laboratory, and imaging features most accurately distinguished gout from non-gout. METHODS: We performed a cross-sectional study of consecutive rheumatology clinic patients with ≥1 swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (two-thirds) and test sample (one-third). Univariate and multivariate association between clinical features and monosodium urate-defined gout was determined using logistic regression modeling. Shrinkage of regression weights was performed to prevent overfitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. RESULTS: In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n = 653), the following features were selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13), difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved (multivariate OR 2.30), location of currently tender joints in other foot/ankle (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6 mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49). The final model performed adequately in the test set, with no evidence of misfit, high discrimination, and predictive ability. MTP1 joint involvement was the most common joint pattern (39.4%) in gout cases. CONCLUSION: Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria.

Resting heart rate is associated with renal disease outcomes in patients with vascular disease: results of the ONTARGET and TRANSCEND studies.

BACKGROUND: Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). METHODS: We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. RESULTS: Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. CONCLUSION: Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.

Imaging modalities for the classification of gout: systematic literature review and meta-analysis.

BACKGROUND: Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. OBJECTIVE: To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. METHODS: We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.