scholarly journals Semi-quantification of Myocardial Uptake of Bone-seeking Agents in Suspected Cardiac Amyloidosis

2021 ◽  
Author(s):  
Cristina Campi ◽  
Chiara Briani ◽  
Sara Gusella ◽  
Alessandro Spimpolo ◽  
Alessandro Salvalaggio ◽  
...  
Keyword(s):  
Scoring System ◽  
Cardiac Amyloidosis ◽  
Roc Curves ◽  
Myocardial Uptake ◽  
Male Population ◽  
Non Invasive ◽  
Pulmonary Uptake ◽  
Males And Females ◽  
Etiologic Diagnosis

Abstract Introduction:In recent years, bone scintigraphy has emerged as a key tool for non-invasive etiologic diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). The qualitative Perugini scoring system is currently the most widely-used method to evaluate myocardial uptake of bone-seeking agents. A semi-quantitative approach may, however, be more useful in clinical practice for both diagnosis and therapeutic follow-up. In this study we focused on a new semi-quantification method with the aim of improving the diagnostic accuracy of CA. Material and Methods:We retrospectively evaluated 8674 consecutive 99mTc-biphosphonate (HMDP or DPD) scintigraphies performed at the Nuclear Medicine Unit of the Azienda Ospedale-Università Padova between January 2012 and December 2016. The qualitative Perugini scoring system was compared with three recently proposed semi-quantitative indices (ratio of heart to thighs: RHT; ratio of lungs to thighs: RLT; ratio of femur to thighs: RFT) in 68 individuals presenting significant myocardial uptake (mean age 79 ± 7 years, range 62-100 years; female/male ratio 16/52). We took 349 consecutive bone scintigraphies qualitatively absent of any cardiac/pulmonary uptake as healthy controls (HC).Results:The RHT and RLT indices (for both males and females) were significantly higher in patients (visual Perugini scores from 1 to 3) than in HCs (p £0.0001). There were also statistically significant differences for RHT (in both sexes) in HCs vs patients with qualitative scores of 1 or >1 (with p ranging from £0.001 to £0.0001). Analysis of the ROC curves showed that RHT outperformed the other two indices (RLT and RFT) and was more sensitive and specific in both male and female groups. Furthermore, in the male population, RHT very accurately distinguished HCs and patients with scores of 1 (known to be less likely affected by ATTR) from patients with qualitative scores >1 (known to be more likely affected by ATTR) with an AUC of 99% (sensitivity: 95%; specificity: 97%).Conclusion:The proposed semi-quantitative RHT index can accurately distinguish between HCs and subjects with CA (Perugini scores from 1 to 3) in both females and males. Furthermore, RHT is able to predict with very high accuracy subjects in the male population more likely to be affected by ATTR (qualitative scores >1).

Imaging Techniques As An Aid In The Early Detection Of Cardiac Amyloidosis

2020 ◽  
Vol 26 ◽  
Author(s):  
M.F. Santarelli ◽  
M. Scipioni ◽  
D. Genovesi ◽  
A. Giorgetti ◽  
P. Marzullo ◽  
...  
Keyword(s):  
Early Detection ◽  
Early Diagnosis ◽  
Cardiac Amyloidosis ◽  
Imaging Techniques ◽  
Myocardial Biopsy ◽  
Immunoglobulin Light Chain ◽  
Transthyretin Amyloidosis ◽  
Non Invasive ◽  
Immunoglobulin Light Chain Amyloidosis

: The idea that performing a proper succession of imaging tests and techniques allows an accurate and early diagnosis of cardiac amyloidosis, avoiding the need to perform myocardial biopsy, is becoming increasingly popular. Furthermore, being imaging techniques non-invasive, it is possible to perform the follow-up of the pathology through repeated image acquisitions. In the present review, the various innovative imaging methodologies are presented, and it is discussed how they have been applied for early diagnosis of cardiac amyloidosis (CA), also to distinguish the two most frequent subtypes in CA: immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR); this allows to perform the therapy in a targeted and rapid manner.

Quantifying copy number variations in cell-free DNA for potential clinical utility from a large prostate cancer cohort.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5072-5072
Author(s):  
Ekkehard Schütz ◽  
Mohammad R Akbari ◽  
Julia Beck ◽  
Howard B. Urnovitz ◽  
William Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Copy Number Variations ◽  
Male Population ◽  
Cell Free Dna ◽  
Free Dna ◽  
Statistical Separation

5072 Background: Prostate cancer (PrCa) is the most frequent non-dermatological malignancy in the male population. Genomic instability resulting in copy number variation (CNV) is a hallmark of malignant transformation. CNV traces from tumors in cell-free DNA (cfDNA) of prostate cancer patients may be identified through massive parallel sequencing (MPS) of serum DNA. These CNV traces may be biomarkers of cancer with clinical applications for screening and follow-up. Methods: DNA was extracted from serum of 205 PrCa patients (Gleason 2 to10), 207 age matched male controls (HC), 10 men with benign hyperplasia (BPH) and 10 with prostatitis (PiS). DNA was amplified using random primers, tagged with a unique molecular identifier per sample, sequenced on a SOLiD system and aligned to the human genome (Build 37). Hits were counted in sliding 100kbp intervals and normalized. Using a random-resampling procedure, genomic regions showing copy number variations in cfDNA that distinguish PrCa from HC were selected. A model using 20 cfDNA regions was cross-validated and used as cfDNA biomarker. Receiver operator characteristics (ROC) curves were calculated for assessment of diagnostic performance by means of area under the curve (AUC). Results: To assess whether CNVs in cfDNA are indicative of PrCa, the number of regions with significant CNV deviation was counted in a first subset of 82 PrCa. Using only the number of regions as measure resulted in an AUC of 0.81 (0.7 – 0.9, p<0.001). Therefore, all samples were used to select regions (n=80) in random resampling (50/50). These regions were used to define a highly significant 20-regions model using five rounds of 10-fold cross-validation (AUC: 0.85±0.7; p< 10-7). This final model discriminated between PrCa and HC with an AUC of 0.92 (0.87 – 0.95) reaching a calculated accuracy of 83%. Both BPH and PiS could be distinguished from PrCa using the cfDNA CNV biomarker with a predicted accuracy of 90%. Conclusions: MPS revealed that only a limited number of chromosomal regions showing CNVs are necessary to achieve statistical separation between prostate cancer and controls. This technique may prove to be clinically useful for screening and follow up of men with prostate cancer.

Scoring System for the Diagnosis of COVID-19

2020 ◽  
Vol 13 (1) ◽  
pp. 413-414 ◽  
Author(s):  
Mohamed Farouk Allam
Keyword(s):  
Scoring System ◽  
Clinical Symptoms ◽  
False Negative ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Negative Results ◽  
False Negative Results ◽  
Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Amyloidosis ◽  
T1 Mapping ◽  
Group Versus ◽  
Control Group ◽  
Cardiac Amyloid ◽  
Attr Amyloidosis ◽  
Amyloid Load ◽  
The Impact

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

scholarly journals Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 660
Author(s):  
Csilla-Andrea Eötvös ◽  
Roxana-Daiana Lazar ◽  
Iulia-Georgiana Zehan ◽  
Erna-Brigitta Lévay-Hail ◽  
Giorgia Pastiu ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Amyloidosis ◽  
Ventricular Hypertrophy ◽  
Low Voltage ◽  
Disease Process ◽  
Left Ventricular ◽  
Clinical Suspicion ◽  
Immunoglobulin Light Chain ◽  
Different Types

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.

scholarly journals Taxonomic signatures of cause-specific mortality risk in human gut microbiome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aaro Salosensaari ◽  
Ville Laitinen ◽  
Aki S. Havulinna ◽  
Guillaume Meric ◽  
Susan Cheng ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Gut Microbiome ◽  
Human Gut ◽  
Cross Sectional ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Non Invasive ◽  
Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

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 Non-Invasive Dengue Diagnostics—The Use of Saliva and Urine for Different Stages of the Illness

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1345
Author(s):  
Mahathir Humaidi ◽  
Wei Ping Tien ◽  
Grace Yap ◽  
Choon Rong Chua ◽  
Lee Ching Ng
Keyword(s):  
Clinical Symptoms ◽  
Detection Algorithm ◽  
Acute Stage ◽  
Serum Samples ◽  
Non Invasive ◽  
Fever Onset ◽  
Dengue Transmission ◽  
Dengue Diagnostics ◽  
Potential Tool

Dengue diagnosis is largely dependent on clinical symptoms and routinely confirmed with laboratory detection of dengue virus in patient serum samples collected via phlebotomy. This presents a challenge to patients not amenable to venipuncture. Non-invasive methods of dengue diagnosis have the potential to enhance the current dengue detection algorithm. In this study, samples from dengue infected patients were collected between January 2012 until September 2012 and September 2013 until December 2013 in two different setups. Panel A samples (blood, urine, and saliva) were collected daily when the 39 patients were hospitalised and during their follow-up visits while Panel B samples (saliva) were collected from 23 patients during the acute stage of dengue. Using DENV PCR on Panel A, from day 2 to day 4 post fever onset, serum showed the best overall positivity followed by saliva and urine (100%/82.1%/67.9%). From day 5 until day 10 post fever onset, serum and urine had similar positivity (67.4%/61.2%), followed by saliva (51.3%). Beyond day 10 post fever onset, DENV was undetectable in sera, but urine and saliva showed 56.8% and 28.6% positivity, respectively. DENV in urine was detectable up until 32 days post fever. Panel B results showed overall sensitivity of 32.4%/36% (RNA/NS1) for DENV detection in saliva. Our results suggest that the urine-based detection method is useful especially for late dengue detection, where DENV is undetected in sera but still detectable in urine. This provides a potential tool for the physician to pick up new cases in an area where there is ongoing dengue transmission and subsequently prompt for intensified vector control activities.

scholarly journals Risk assessment in precapillary pulmonary hypertension: a comparative analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas Sonnweber ◽  
Eva-Maria Schneider ◽  
Manfred Nairz ◽  
Igor Theurl ◽  
Günter Weiss ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Prediction ◽  
Mortality Risk ◽  
Assessment Tool ◽  
Risk Models ◽  
Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

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