scholarly journals 501 Investigating the epidemiology of cardiac amyloidosis: design of the ‘cardiac amyloidosis registry’ (CARRY)

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Giuseppe Vergaro ◽  
Vincenzo Castiglione ◽  
Giulia Elena Mandoli ◽  
Alberto Aimo ◽  
Francesco Cappelli ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Large Scale ◽  
Amyloid Fibrils ◽  
Clinical Laboratory ◽  
High Sensitivity ◽  
Diagnostic Procedures ◽  
Final Diagnosis ◽  
Diagnostic Tools ◽  
Case Report Form ◽  
Prospective Multicentre Study

Abstract Aims Amyloidosis are a group of diseases characterized by the extracellular deposition of amyloid fibrils. The two most common forms of cardiac amyloidosis (CA) are caused by the accumulation of immunoglobulin light-chains (AL) or transthyretin (ATTR). While previously considered as a rare disease, increased awareness and recent advances in diagnostic tools have shown that prevalence of CA is likely underestimated. Nonetheless, large-scale population registries of CA, also focusing on the pathways leading to the final diagnosis, are still missing. Methods and results The Cardiac Amyloidosis RegistRY (CARRY) is an observational, prospective, multicentre study endorsed by the Italian Society of Cardiology (Sezione Regionale Tosco-Umbra), collecting data from in- and outpatients referred with the clinical suspicion of CA. Clinical, laboratory (including natriuretic peptides and high-sensitivity troponins), and echocardiographic data at enrollment will be collected. Detailed information about the diagnostic procedures up to the final diagnosis of either CA or mimicking conditions will be registered. Patients with a diagnosis of CA will be followed up, and the baseline assessment will be repeated at 1-year (Figure). Twenty centres in Tuscany and Umbria, including amyloidosis referral centres as well as second-level Hospitals, are contributing to the CARRY registry. A common, web-based, case report form is being used for data collection. Recruitment begun in July 2021 and will end in July 2022. The first interim analysis is planned in January 2022. Conclusions The CARRY registry is expected to give novel information on the epidemiology of CA, with a focus on the incidence and diagnostic pathways of CA in Tuscany and Umbria, setting the bases for a larger nationwide registry. Clarification of the epidemiology of CA through the data from the CARRY registry may prove useful in the next future for either clinicians and policy makers. FigureStudy flow chart of the CARRY registry.

Hyphenated Mass Spectrometry Techniques in the Diagnosis of Amyloidosis

2019 ◽  
Vol 26 (1) ◽  
pp. 104-120 ◽  
Author(s):  
Marta Spodzieja ◽  
Sylwia Rodziewicz-Motowidło ◽  
Aneta Szymanska
Keyword(s):  
Mass Spectrometry ◽  
Biological Samples ◽  
Large Scale ◽  
Amyloid Fibrils ◽  
High Sensitivity ◽  
Diagnostic Procedures ◽  
Comprehensive Information ◽  
Diagnostic Biopsy ◽  
Separation Of Proteins ◽  
Subcutaneous Adipose

Amyloidoses are a group of diseases caused by the extracellular deposition of proteins forming amyloid fibrils. The amyloidosis is classified according to the main protein or peptide that constitutes the amyloid fibrils. The most effective methods for the diagnosis of amyloidosis are based on mass spectrometry. Mass spectrometry enables confirmation of the identity of the protein precursor of amyloid fibrils in biological samples with very high sensitivity and specificity, which is crucial for proper amyloid typing. Due to the fact that biological samples are very complex, mass spectrometry is usually connected with techniques such as liquid chromatography or capillary electrophoresis, which enable the separation of proteins before MS analysis. Therefore mass spectrometry constitutes an important part of the so called “hyphenated techniques” combining, preferentially in-line, different analytical methods to provide comprehensive information about the studied problem. Hyphenated methods are very useful in the discovery of biomarkers in different types of amyloidosis. In systemic forms of amyloidosis, the analysis of aggregated proteins is usually performed based on the tissues obtained during a biopsy of an affected organ or a subcutaneous adipose tissue. In some cases, when the diagnostic biopsy is not possible due to the fact that amyloid fibrils are formed in organs like the brain (Alzheimer’s disease), the study of biomarkers presented in body fluids can be carried out. Currently, large-scale studies are performed to find and validate more effective biomarkers, which can be used in diagnostic procedures. We would like to present the methods connected with mass spectrometry which are used in the diagnosis of amyloidosis based on the analysis of proteins occurring in tissues, blood and cerebrospinal fluid.

scholarly journals From Clinical Clues to Final Diagnosis: The Return of Detective Work to Clinical Medicine in Cardiac Amyloidosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hani Sabbour ◽  
Khwaja Yousuf Hasan ◽  
Firas Al Badarin ◽  
Haluk Alibazoglu ◽  
Andrew L. Rivard ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Clinical Medicine ◽  
Imaging Techniques ◽  
Diagnostic Algorithm ◽  
Signs And Symptoms ◽  
Final Diagnosis ◽  
Diagnostic Tools ◽  
Case Examples ◽  
Non Invasive ◽  
High Index Of Suspicion

Cardiac amyloidosis is frequently misdiagnosed, denying patients the opportunity for timely and appropriate management of the disease. The purpose of this review and case studies is to raise awareness of the diagnostic “red flags” associated with cardiac amyloidosis and the currently available non-invasive strategies for diagnosis. The review focuses on the identification of one of the two main types of cardiac amyloidosis, transthyretin amyloid cardiomyopathy, and non-invasive tools to distinguish this from light-chain amyloidosis. A diagnostic algorithm centered around the use of non-invasive imaging and laboratory analysis is presented. The algorithm generates four differential diagnoses for patients presenting with signs and symptoms consistent with cardiac amyloidosis. Case examples are presented, representing the four potential outcomes of diagnosis using the algorithm. The review provides a guide on how to recognize the often-overlooked presentations of this disease in clinical practice. Non-invasive imaging techniques and diagnostic tools that do not require the involvement of a specialty center have allowed for the improved diagnosis of cardiac amyloidosis. Timely diagnosis of this life-threatening disease is essential for optimal management and it is imperative that clinicians have a high index of suspicion for patients presenting with “red flag” symptoms.

scholarly journals Evaluation of Four Automated High-Sensitivity C-Reactive Protein Methods: Implications for Clinical and Epidemiological Applications

2000 ◽  
Vol 46 (4) ◽  
pp. 461-468 ◽  
Author(s):  
William L Roberts ◽  
Rachel Sedrick ◽  
Linda Moulton ◽  
Anthony Spencer ◽  
Nader Rifai
Keyword(s):  
Large Scale ◽  
Clinical Laboratory ◽  
High Sensitivity ◽  
Reference Interval ◽  
Healthy Population ◽  
C Reactive Protein ◽  
Prognostic Information ◽  
Reactive Protein ◽  
Hs Crp ◽  
Apparently Healthy

Abstract Background: C-reactive protein (CRP) can provide prognostic information about the risk of developing atherosclerotic complications in apparently healthy patients. This new clinical application requires quantification of CRP concentrations below those traditionally measured in the clinical laboratory. Methods: The Dade Behring BN II, the Abbott IMx, the Diagnostic Products Corporation IMMULITE, and the Beckman Coulter IMMAGE are four automated analyzers with high-sensitivity CRP (hs-CRP) methods. We evaluated these assays for precision, linearity, and comparability with samples from 322 apparently healthy blood donors. Results: The imprecision (CV) of the BN II, IMx, IMMULITE, and IMMAGE methods was ≤7.6%, ≤12%, ≤9.8%, and ≤9.7% at 3.5 mg/L, respectively. The BN II, IMx, IMMULITE, and IMMAGE methods were linear down to ≤0.30, ≤0.32, ≤0.85, and 2.26 mg/L, respectively. CRP concentrations demarcating each quartile in a healthy population were method dependent. The IMx method gave results comparable to the BN II method for values in the reference interval. The IMMULITE method had a positive intercept compared with the BN II method. The IMMAGE method demonstrated more scatter and a positive intercept compared with the BN II method, which may reflect the fact that it is a less sensitive assay. Conclusions: The four hs-CRP methods exhibited differences in results for a healthy population. Additional standardization efforts are required to ensure that hs-CRP results can be related to large-scale epidemiologic studies.

Impact of COVID-19 on Nuclear Medicine in Germany, Austria and Switzerland: An International Survey in April 2020

2020 ◽  
Vol 59 (04) ◽  
pp. 294-299 ◽  
Author(s):  
Lutz S. Freudenberg ◽  
Ulf Dittmer ◽  
Ken Herrmann
Keyword(s):  
Nuclear Medicine ◽  
Health Systems ◽  
Personal Protective Equipment ◽  
Large Scale ◽  
Diagnostic Procedures ◽  
Protective Equipment ◽  
Current Crisis ◽  
Web Based ◽  
Public Versus Private ◽  
The Impact

Abstract Introduction Preparations of health systems to accommodate large number of severely ill COVID-19 patients in March/April 2020 has a significant impact on nuclear medicine departments. Materials and Methods A web-based questionnaire was designed to differentiate the impact of the pandemic on inpatient and outpatient nuclear medicine operations and on public versus private health systems, respectively. Questions were addressing the following issues: impact on nuclear medicine diagnostics and therapy, use of recommendations, personal protective equipment, and organizational adaptations. The survey was available for 6 days and closed on April 20, 2020. Results 113 complete responses were recorded. Nearly all participants (97 %) report a decline of nuclear medicine diagnostic procedures. The mean reduction in the last three weeks for PET/CT, scintigraphies of bone, myocardium, lung thyroid, sentinel lymph-node are –14.4 %, –47.2 %, –47.5 %, –40.7 %, –58.4 %, and –25.2 % respectively. Furthermore, 76 % of the participants report a reduction in therapies especially for benign thyroid disease (-41.8 %) and radiosynoviorthesis (–53.8 %) while tumor therapies remained mainly stable. 48 % of the participants report a shortage of personal protective equipment. Conclusions Nuclear medicine services are notably reduced 3 weeks after the SARS-CoV-2 pandemic reached Germany, Austria and Switzerland on a large scale. We must be aware that the current crisis will also have a significant economic impact on the healthcare system. As the survey cannot adapt to daily dynamic changes in priorities, it serves as a first snapshot requiring follow-up studies and comparisons with other countries and regions.

Analysis and design of suitable model structures for activated sludge tanks with circulating flow

1999 ◽  
Vol 39 (4) ◽  
pp. 55-60 ◽  
Author(s):  
J. Alex ◽  
R. Tschepetzki ◽  
U. Jumar ◽  
F. Obenaus ◽  
K.-H. Rosenwinkel
Keyword(s):  
Activated Sludge ◽  
Large Scale ◽  
Wastewater Treatment Plants ◽  
Treatment Plant ◽  
High Sensitivity ◽  
Suitable Model ◽  
Model Structure ◽  
Analysis And Design ◽  
Hydraulic Behaviour ◽  
Model Structures

Activated sludge models are widely used for planning and optimisation of wastewater treatment plants and on line applications are under development to support the operation of complex treatment plants. A proper model is crucial for all of these applications. The task of parameter calibration is focused in several papers and applications. An essential precondition for this task is an appropriately defined model structure, which is often given much less attention. Different model structures for a large scale treatment plant with circulation flow are discussed in this paper. A more systematic method to derive a suitable model structure is applied to this case. Results of a numerical hydraulic model are used for this purpose. The importance of these efforts are proven by a high sensitivity of the simulation results with respect to the selection of the model structure and the hydraulic conditions. Finally it is shown, that model calibration was possible only by adjusting to the hydraulic behaviour and without any changes of biological parameters.

scholarly journals Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 869
Author(s):  
Amedeo De Nicolò ◽  
Valeria Avataneo ◽  
Jessica Cusato ◽  
Alice Palermiti ◽  
Jacopo Mula ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Real Time Pcr ◽  
Large Scale ◽  
High Sensitivity ◽  
Analytical Validation ◽  
Pcr Assay ◽  
Serological Tests ◽  
Flow Test ◽  
Lateral Flow Test ◽  
Large Scale Screening

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kellisha Harley ◽  
Sarah Bissonnette ◽  
Rosanna Inzitari ◽  
Karen Schulz ◽  
Fred S. Apple ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Clinical Laboratory ◽  
Troponin T ◽  
High Sensitivity ◽  
Combined Effects ◽  
Over The Counter ◽  
Heparin Plasma ◽  
Abbott Architect ◽  
Roche Cobas

Abstract Objectives This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Methods Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer’s claims. Results All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer’s claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Conclusions Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0–3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10–2000 ng/mL (41–8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

scholarly journals Through thick and thin: Diagnosis of transthyretin cardiac amyloidosis through non-invasive multimodality imaging

2021 ◽  
pp. 201010582110061
Author(s):  
Raja Ezman Raja Shariff ◽  
Hafisyatul Aiza Zainal Abidin ◽  
Sazzli Kasim
Keyword(s):  
Cardiac Amyloidosis ◽  
Troponin T ◽  
Multimodality Imaging ◽  
High Sensitivity ◽  
Dark Blood ◽  
Non Invasive ◽  
Doppler Study ◽  
Alternative Means ◽  
High Sensitivity Troponin T

Cardiac amyloidosis is a severely underdiagnosed cause of heart failure with preserved ejection fraction. We report a case of highly probable transthyretin (ATTR) cardiac amyloidosis (ATTR-CA) diagnosed through the assistance of non-invasive multimodality imaging. An 81-year-old man presented with worsening dyspnoea, reduced effort tolerance and limb swelling. Examination and bedside investigations demonstrated congestive cardiac failure. On arrival, N-terminal-pro B-type natriuretic peptide was 2400 ng/L, and high-sensitivity troponin T was 78 mmol/L. Echocardiography showed severe left and right ventricular hypertrophy, and a Doppler study revealed diastolic dysfunction. Cardiac magnetic resonance imaging revealed on non-conventional dark blood sequence an abnormal inversion time for nulling myocardium suggestive of infiltrative disease, including amyloidosis. The patient was referred for nuclear-based studies involving technetium-99m pyrophosphate which demonstrated changes highly diagnostic of ATTR-CA. Early diagnosis of ATTR-CA remains paramount due to the increasing availability of disease-modifying therapies. Current guidelines recognise the role of multimodality imaging in confidently recognising the disease without the need for histological evidence in the appropriate context, providing an alternative means of diagnosis.

scholarly journals GASTON: Galactic Star Formation with NIKA2. Evidence for the mass growth of star-forming clumps

2021 ◽  
Author(s):  
A J Rigby ◽  
N Peretto ◽  
R Adam ◽  
P Ade ◽  
M Anderson ◽  
...  
Keyword(s):  
Star Formation ◽  
Large Scale ◽  
Galactic Plane ◽  
High Sensitivity ◽  
High Mass ◽  
Evolutionary Stage ◽  
Mass Star ◽  
Mass Growth ◽  
Star Forming ◽  
Compact Source

Abstract Determining the mechanism by which high-mass stars are formed is essential for our understanding of the energy budget and chemical evolution of galaxies. By using the New IRAM KIDs Array 2 (NIKA2) camera on the Institut de Radio Astronomie Millimétrique (IRAM) 30-m telescope, we have conducted high-sensitivity and large-scale mapping of a fraction of the Galactic plane in order to search for signatures of the transition between the high- and low-mass star-forming modes. Here, we present the first results from the Galactic Star Formation with NIKA2 (GASTON) project, a Large Programme at the IRAM 30-m telescope which is mapping ≈2 deg2 of the inner Galactic plane (GP), centred on ℓ = 23${_{.}^{\circ}}$9, b = 0${_{.}^{\circ}}$05, as well as targets in Taurus and Ophiuchus in 1.15 and 2.00 mm continuum wavebands. In this paper we present the first of the GASTON GP data taken, and present initial science results. We conduct an extraction of structures from the 1.15 mm maps using a dendrogram analysis and, by comparison to the compact source catalogues from Herschel survey data, we identify a population of 321 previously-undetected clumps. Approximately 80 per cent of these new clumps are 70 μm-quiet, and may be considered as starless candidates. We find that this new population of clumps are less massive and cooler, on average, than clumps that have already been identified. Further, by classifying the full sample of clumps based upon their infrared-bright fraction – an indicator of evolutionary stage – we find evidence for clump mass growth, supporting models of clump-fed high-mass star formation.

scholarly journals Adding stress biomarkers to high sensitivity troponin measurements increases precision and efficacy of rapid rule out protocols for NSTEMI

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Restan ◽  
O.T Steiro ◽  
H.L Tjora ◽  
J Langoergen ◽  
T Omland ◽  
...  
Keyword(s):  
Chest Pain ◽  
Acute Chest Pain ◽  
High Sensitivity ◽  
Final Diagnosis ◽  
Public Institution ◽  
P Value ◽  
Funding Source ◽  
University Hospitals ◽  
High Sensitivity Troponin ◽  
Rule Out

Abstract Background NSTEMI may be ruled out in patients presenting with acute chest pain based on low baseline high sensitivity troponin (cTn) at admission. This procedure is limited by a low expected frequency of ruled out non-cardiac chest pain (NCCP) patients. Purpose To investigate if stress-induced biomarkers (glucose or copeptin) combined with cTn can increase the rate of NCCP ruled out without an unacceptable increase in incorrectly ruled out NSTEMI. Method 971 patients with suspected NSTE-ACS were included. Final diagnosis was adjudicated by two independent cardiologists using clinical data including routine cTnT. Additionally, baseline cTnI, cTnI from Singulex Clarity System (cTnI(sgx)), copeptin and glucose were measured. Diagnostic performance to rule out NSTEMI was compared between the ESC rule out algorithms for cTnT and cTnI(Abbott), a local cTnI(sgx) algorithm and different combinations of cTn with copeptin or glucose Results Median age 61 years, 60% male. 13% had NSTEMI, 12% had UAP and 60% NCCP. Distribution of copeptin and glucose concentrations (NSTEMI and NCCP) is shown in figure 1. Copeptin and cTnT produces an algorithm with lower miss rate for NSTEMI, increased rule out rate for NCCP and significantly higher AUC (DeLong test, p value <0.001) compared to the ESC algorithm (Table 1). cTnI(sgx) and copeptin showed higher rule out for NCCP and higher AUC (p value <0.001), however an increased rule out rate for NSTEMIs. Combining cTnI(Abbott) and glucose gave a similar miss rate for NSTEMI as ESC, but increased rule out rate for NCCP and higher AUC (p value <0.001). Conclusion Combining cTnT or cTnI(sgx) with copeptin; or cTnI with glucose, improves diagnostic precision and efficacy of rule out protocols for NSTEMI in patients presenting with acute chest pain. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority; Haukeland and Stavanger University Hospitals

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