Parameter For Risk Stratification Research Articles

68Ga-PSMA PET/CT for Primary Lymph Node and Distant Metastasis NM Staging of High-Risk Prostate Cancer.

With the largest high-risk prostate cancer (PCa) cohort to date undergoing 68Ga-prostate-specific membrane antigen (PSMA) PET/CT primary staging, we aimed to, first, characterize the metastatic spread of PCa in relation to tumor 68Ga-PSMA uptake and the D'Amico classification and, second, compare 68Ga-PSMA PET/CT findings with radical prostatectomy and pelvic lymph node dissection (PLND) histopathology findings. Methods: The study included 691 consecutive newly diagnosed, biopsy-proven, treatment-naïve, D'Amico high-risk PCa patients primary-staged by 68Ga-PSMA PET/CT. PSMA SUVmax and metastatic findings were compared with prostate-specific antigen level, International Society of Urological Pathology (ISUP) grade, and clinical stage as traditional risk stratification parameters. Moreover, 68Ga-PSMA PET/CT findings were compared with histology findings in radical prostatectomy patients undergoing PLND. Undetected lymph node metastases (LNMs) underwent immunohistochemical PSMA staining. Results: Advanced disease (N1/M1) was observed in 35.3% of patients (244/691) and was associated with increasing prostate-specific antigen level, ISUP grade, and clinical stage. LNMs (N1/M1a) were detected in 31.4% (217/691) and bone metastases (M1b) in 16.8% (116/691). Advanced disease frequencies in patients with ISUP grades 2 and 3 were 10.8% (11/102) and 37.1% (33/89), respectively. Risk of advanced disease for cT2a, cT2b, and cT2c tumors was almost equal (24.2%, 27.9%, and 22.4%, respectively). We observed a weak correlation between SUVmax and biopsy ISUP grade (ρ = 0.21; P < 0.001) and a modest correlation between SUVmax and postprostatectomy ISUP grade (ρ = 0.38; P < 0.001). Sensitivity, specificity, positive and negative predictive value, and accuracy for LNM detection on 68Ga-PSMA PET/CT in the PLND cohort were 30.6%, 96.5%, 68.8%, 84.5%, and 83.1%, respectively. Undetected LNMs either were micrometastases located in the lymph node border or were without PSMA expression. Conclusion: In this high-risk PCa cohort, we identified advanced disease in about one third at diagnosis. ISUP grade was the superior predictor for advanced disease at diagnosis. We found a significant difference in frequency of advanced disease between ISUP grades 2 and 3, as supports the Gleason score 7 subdivision. Interestingly, we observed no significant differences in risk of advanced disease when comparing the different cT2 stages. The undetected LNMs were either PSMA-negative or micrometastases.

Clinical Impact of CD25/CD123 Coexpression in Adult B-Cell Acute Lymphoblastic Leukemia Patients.

This study aimed to determine the clinical impact of CD25+/CD123+ coexpression in adult B-cell acute lymphoblastic leukemia (B-ALL) cases. One hundred and twenty newly diagnosed B-ALL patients (≤60 years old) were included in this study. CD123 and CD25 expression on leukemic blast cells were assessed using flow cytometry. CD25+/CD123+ coexpression was detected in 40/120 B-ALL patients (33.3%). All B-ALL patients showed CD25+/CD123+ coexpression had lower induction of remission response and shorter overall survival as compared to B-ALL cases lacking coexpression. In conclusion, CD25+/CD123+ positive coexpression is a reliable flow cytometry marker for prediction of the outcome of adult B-ALL patients and could be used as a novel parameter for risk stratification of adult B-ALL cases.

The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China

ObjectiveTo investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. MethodConfirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. Result75 patients were enrolled, with a mean age of 46.6 ± 14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). ConclusionThe common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate.

Cardiopulmonary Exercise Test in heart failure: A Sine qua non

A robust literature, over the last years, supports the indication of cardiopulmonary exercise testing (CPET) in patients with cardiovascular diseases. Understanding exercise physiology is a crucial component of the critical evaluation of exercise intolerance. Shortness of breath and exercise limitation is often treated with an improper focus, partly because the pathophysiology is not well understood in the frame of the diagnostic spectrum of each subspecialty. A vital field and research area have been cardiopulmonary exercise test in heart failure with preserved/reduced ejection fraction, evaluation of heart failure patients as candidates for LVAD-Implantation, as well as for LVAD-Explantation and ultimately for heart transplantation. All the CPET variables provide synergistic prognostic discrimination. However, Peak VO2 serves as the most critical parameter for risk stratification and prediction of survival rate.

Automated CT biomarkers for opportunistic prediction of future cardiovascular events and mortality in an asymptomatic screening population: a retrospective cohort study

Body CT scans are frequently performed for a wide variety of clinical indications, but potentially valuable biometric information typically goes unused. We investigated the prognostic ability of automated CT-based body composition biomarkers derived from previously-developed deep-learning and feature-based algorithms for predicting major cardiovascular events and overall survival in an adult screening cohort, compared with clinical parameters. Mature and fully-automated CT-based algorithms with pre-defined metrics for quantifying aortic calcification, muscle density, visceral/subcutaneous fat, liver fat, and bone mineral density (BMD) were applied to a generally-healthy asymptomatic outpatient cohort of 9223 adults (mean age, 57.1 years; 5152 women) undergoing abdominal CT for routine colorectal cancer screening. Longitudinal clinical follow-up (median, 8.8 years; IQR, 5.1-11.6 years) documented subsequent major cardiovascular events or death in 19.7% (n=1831). Predictive ability of CT-based biomarkers was compared against the Framingham Risk Score (FRS) and body mass index (BMI). Significant differences were observed for all five automated CT-based body composition measures according to adverse events (p<0.001). Univariate 5-year AUROC (with 95% CI) for automated CT-based aortic calcification, muscle density, visceral/subcutaneous fat ratio, liver density, and vertebral density for predicting death were 0.743(0.705-0.780)/0.721(0.683-0.759)/0.661(0.625-0.697)/0.619 (0.582-0.656)/0.646(0.603-0.688), respectively, compared with 0.499(0.454-0.544) for BMI and 0.688(0.650-0.727) for FRS (p<0.05 for aortic calcification vs. FRS and BMI); all trends were similar for 2-year and 10-year ROC analyses. Univariate hazard ratios (with 95% CIs) for highest-risk quartile versus others for these same CT measures were 4.53(3.82-5.37) /3.58(3.02-4.23)/2.28(1.92-2.71)/1.82(1.52-2.17)/2.73(2.31-3.23), compared with 1.36(1.13-1.64) and 2.82(2.36-3.37) for BMI and FRS, respectively. Similar significant trends were observed for cardiovascular events. Multivariate combinations of CT biomarkers further improved prediction over clinical parameters (p<0.05 for AUROCs). For example, by combining aortic calcification, muscle density, and liver density, the 2-year AUROC for predicting overall survival was 0.811 (0.761-0.860). Fully-automated quantitative tissue biomarkers derived from CT scans can outperform established clinical parameters for pre-symptomatic risk stratification for future serious adverse events, and add opportunistic value to CT scans performed for other indications.

Evaluation of Hepatocyte Growth Factor in Iraqi Patients with Acute Myeloid Leukemia: Its Correlation with Clinical Parameters and Response to Induction Therapy

BACKGROUND: Hepatocyte growth factor (HGF) is a proangiogenic factor that exerts different effects over stem cell survival growth, apoptosis, and adhesion. Its impact on leukemogenesis has been established by many studies.&#x0D; AIM: This study aimed to determine the effect of plasma HGF activity on acute myeloid leukemia (AML) patients at presentation and after remission.&#x0D; PATIENTS AND METHODS: This was a cross-sectional prospective study of 30 newly-diagnosed, adult, and AML patients. All patients received the 7+3 treatment protocol. Patients’ clinical data were taken at presentation, and patients were followed up for 6 months to evaluate the clinical status. Plasma HGF levels were estimated by ELISA based methods in the patients at two intervals first at diagnosis and the 2nd time after remission of disease. Plasma HGF levels were only measured once in twenty healthy control individuals.&#x0D; RESULTS: A statistically significant lowering in the median levels of HGF after remission induction therapy has been found when compared with those before treatment (p = 0.006) and in the group of patients who achieved complete remission in comparison with those before treatment (p = 0.005). Furthermore, a significant reduction was also demonstrated after treatment in patients presenting with extramedullary involvement (p = 0.003) and in the alive group (p = 0.001).&#x0D; CONCLUSION: Plasma HGF estimation can be a useful parameter in predicting treatment outcomes in patients with AML, and it can add potentially useful information to risk stratification parameters.

Which is the best PML risk stratification strategy in natalizumab-treated patients affected by multiple sclerosis?

BackgroundThe risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCPyV), is the main limitation to the use of natalizumab, highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Establishing the PML risk against expected benefits represents an obligatory requirement of MS treatment algorithm. In order to achieve this goal, the aims of this study were to establish if JCPyV-DNA detection and non-coding control region (NCCR) arrangements could play a role of biomarkers, supporting anti-JCPyV antibodies measurement, actually the only parameter for PML risk stratification. MethodsThirty RRMS patients in treatment with natalizumab were enrolled. Urine and blood samples were collected according to this calendar: baseline (T0), 4 (T1), 8 (T2), 12 (T3), 16 (T4), 20 months (T5) after beginning of natalizumab therapy. After JCPyV DNA extraction, a specific quantitative-PCR (Q-PCR) and arrangements’ analysis of NCCR and Viral Capsid Protein 1 (VP1) were carried out. ResultsQ-PCR detected JCPyV DNA in urine and blood from baseline (T0) to 20 natalizumab infusions (T5), although JC viral load in urine was significantly higher compared to viremia, at all selected time points. A contextual analysis of the anti-JCPyV-antibodies versus JCPyV-DNA detection revealed that viral DNA preceded the antibodies’ presence in the serum. During the first year of natalizumab treatment, sequences isolated from blood displayed an archetype JCPyV NCCR structure with the occurrence of point mutations, whereas after one year NCCR re-organizations were observed in plasma and PBMC with duplication of NF-1 binding site in box F, duplication of box C and partial or total deletion of box D. VP1 analysis showed the amino acid change mutation S269F in plasma and S267L in PBMC, involving the receptor-binding region of VP1. Phylogenetic analysis suggested a stability and a similarity across different isolates of the JCPyV VP1. ConclusionsWe highly recommend considering JCPyV-DNA detection and NCCR re-organizations as viral biomarkers in order to accurately identify JCPyV-infected patients with a specific humoral response not yet detectable and to identify NCCR arrangements correlated with the onset of neurovirulent variants.

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma

AbstractPediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma–related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD). Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention. ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001). ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.

Physiologic risk factors for early acute kidney injury in severely injured patients.

The evaluation of the predictive value of the neutrophil gelatinase-associated lipocalin (NGAL) for an early acute kidney injury (AKI) development in severely injured patients. Determination of the time-dependent roles of trauma-related physiologic markers of tissue hypoxia, systemic inflammation and rhabdomyolysis in AKI development. 81 adult patients were screened for the presence of AKI for eight consecutive days following the injury. Arterial levels of plasma NGAL, lactate, interleukin-6, procalcitonin, and myoglobin were investigated at 24 hours (T1), 48 hours (T2), and 96 hours (T3) after the injury. The incidence of AKI was 32.1 %. Patients with AKI were older, but no significant difference in injury severity was observed. NGAL levels were significantly higher in the AKI group at T1, T2, and T3 when compared to the non-AKI group. Lactate levels were significantly higher in the AKI group at T2 only, and IL-6 levels were significantly higher in the AKI group at T2 and T3. Procalcitonin and myoglobin levels were significantly higher in the AKI group at T1, T2, and T3, when compared to the non-AKI group. Positive correlations were found between plasma NGAL and all screened physiological factors at all defined time points. Development of AKI after blunt trauma is very complex and multifactorial. Activation of the systemic inflammatory response and rhabdomyolysis (high concentration of myoglobin) were strongly involved in AKI development. Blood NGAL levels after injury were significantly higher in patients, who developed posttraumatic AKI. Plasma NGAL, lactate, procalcitonin, interleukin-6, and myoglobin had potential to be useful parameters for risk stratification and prediction of AKI after trauma (Tab. 6, Ref. 40).

P93 The usefulness of dual cardiac autonomic nervous modulation assessment for prediction of mortality in patients with relatively preserved left ventricular ejection fraction

Abstract Background Recent guidelines have stated that reduced left ventricular ejection fraction (LVEF) is the gold standard marker for identifying patients at risk for cardiac mortality. Although reduced LVEF identifies patients at an increased risk of cardiac arrest, sudden cardiac deaths (SCDs) occur considerably more often in patients with relatively preserved LVEF. Current guidelines on SCDs risk stratification do not adequately cover this general population pool. Heart rate variability (HRV) and heart rate turbulence (HRT) are non-invasive electrocardiography (ECG)-based techniques capable of providing relevant information on the cardiac autonomic nervous modulation. Although a large body of evidence about autonomic nervous modulation markers has been reported, the usefulness of HRV and HRT parameters for risk stratification in such patients with relatively preserved LVEF has not yet been elucidated. Purpose This study aimed to evaluate HRV and HRT parameters for predicting cardiac mortality in patients with structural heart disease (SHD), including ischemic heart disease, dilated cardiomyopathy and valvular heart disease, who have mid-range left ventricular dysfunction (LVD). Methods We prospectively enrolled 229 patients (187 men, age 63 ± 13 years) with SHD who have mid-range LVD (LVEF &amp;gt; 40%). HRV and HRT parameters based on 24-hour ambulatory ECG recordings (Fukuda Denshi Co., Ltd., Tokyo, Japan) were evaluated as follows; SDNN, triangular index, high and low frequency HRV, turbulence onset and slope. The primary endpoint was all-cause mortality. Univariate and multivariate Cox regression analysis were used to assess the association between these cardiac autonomic nervous modulation and mortality. Results During a mean follow-up of 21 ± 11 months, all-cause mortality was seen in 11 (4.8%) patients. Univariate Cox regression analysis showed that reduced SDNN (&amp;lt;50ms), reduced triangular index (&amp;lt;20ms) and HRT category 2 were significantly associated with the primary endpoint (P &amp;lt; 0.05). When HRT category 2 combined with reduced SDNN, Multivariate Cox regression analysis revealed that this combination more strongly associates with the primary endpoint (hazard ratio =7.91, 95%CI, 1.82-34.2; P = 0.006). Conclusion Dual cardiac autonomic nervous modulation assessment which combined HRT and HRV could be a superior technique to predict mortality in patients with relatively preserved LVEF.

Myocardial electrical instability score: clinical and prognostic significance

Aim. To develop and test a risk-stratification model for patients with coronary artery disease (CAD) and non-ischemic pathologies based on a computer analysis of electrical instability ECG markers.Material and methods. In the period from 2011 to 2018, the study included 1014 patients with CAD and non-ischemic pathologies. Depending on ventricular arrhythmia status, the analyzed cohort was divided into 3 groups: 1) 644 patients without lifethreatening ventricular tachyarrhythmias (-VTA), mean age 51,7±16,1 years; 2) 280 patients with clinically significant ventricular arrhythmias (+csVA): ventricular extrasystoles (VES) &gt;1500/24 h, coupled VES &gt;50/24 h or unstable ventricular tachycardia (uVT), mean age 46,7±14,0 years; 3) 90 patients with life-threatening ventricular tachyarrhythmias (+VTA): persistent VT (pVT), successful cardiopulmonary resuscitation (CPR), appropriate discharges by implanted cardioverter defibrillator (CVD), sudden cardiac death (SCD), mean age 46,8±12,7 years.Using the Intekard 7.3 software, ECG markers of myocardial electrical instability were analyzed: T wave alternation, QT interval and dispersion, fragmented QRS, spatial QRS-T angle, turbulence onset and slope, and heart rate deceleration/acceleration.Results. Statistically significant differences were found between the values of T wave alternation, QT interval, fragmented QRS and QRS-T angle in groups 1 and 3 (-VTA) and (+VTA), p&lt;0,005.Personalized model was formed for predicting the risk of life-threatening VTA (primary endpoints: pVT, appropriate CVD discharges, CPR, SCD) in patients with CAD and non-ischemic pathologies (cardiomyopathy, channelopathy) in 5 years follow-up. Integral score of myocardial electrical instability is proposed as new quantitative parameter for risk stratification (sensitivity 75%, specificity 78%, accuracy 77%).Conclusion. The myocardial electrical instability score provides the individual assessment of the dynamic SCD risk. The Intekard 7.3 software is a simple, economic and accessible ECG tool for arrhythmia monitoring.

Risk Stratification of Bethesda III Category Thyroid Nodules

Background: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) carries a malignancy risk reaching up to 50%. Based on the reported malignancy rate in a given population, the clinical practice towards such a category varies. We hereby identify clinical parameters for risk stratification to aid in decision making for either surgical referral or a clinical follow-up. Our aim is to calculate the malignancy risk in Bethesda category III and to identify clinical parameters that guided both clinicians and patients at our institutions to reach a clinical decision. Methods: A retrospective review of patients with Bethesda category III thyroid nodules from the tertiary centers in the Emirate of Abu Dhabi during January 2011 through December 2015 was carried out. Malignancy risk in Bethesda category III nodules and repeat fine-needle aspiration (FNA) utility were calculated. Parameters guided referral to surgery were studied. Results: A total of 202 cases were included in the study. Of these, 101 cases underwent surgery initially following the first FNA, and 10 cases following repeat FNA. Histology confirmed malignancy in 41% of cases that went initially to surgery, and in 40% of cases that underwent a repeat FNA. Repeat FNA resulted in 17 (44.74%) cases being re-classified into benign category, 10 (26.3%) being AUS/FLUS category, six (15.7%) being both suspicious and malignant, and five (13.16%) being unsatisfactory. Repeating FNA resulted in a definitive diagnostic utility in 50% of the cases. Conclusions: The relatively high malignancy rate in our institutions, the suspicious radiographic features and the repeat FNA predictive value stratified Bethesda category III nodules for appropriate referrals to surgery. J Endocrinol Metab. 2019;9(6):180-185 doi: https://doi.org/10.14740/jem625

Admission Body Temperature in Critically Ill Patients as an Independent Risk Predictor for Overall Outcome

Introduction: Body temperature (BT) abnormalities are frequently observed in critically ill patients. We aimed to assess admission BT in a heterogeneous critically ill patient population admitted to an intensive care unit (ICU) as a prognostic parameter for intra-ICU and long-term mortality. Methods: A total of 6,514 medical patients (64 ± 15 years) admitted to a German ICU between 2004 and 2009 were included. A follow-up of patients was performed retrospectively. The association of admission BT with both intra-ICU and long-term mortality was investigated by logistic regression. Results: Patients with hypothermia (<36°C BT) were clinically worse and had more pronounced signs of multi-organ failure. Admission BT was associated with adverse overall outcome, with a 2-fold increase for hyperthermia (mortality 12%; odds ratio [OR] 1.80, 95% confidence interval [CI] 1.43–2.26; p < 0.001), and a 4-fold increase for the risk of hypothermia (mortality 24%; OR 4.05, 95% CI 3.38–4.85; p < 0.001) with respect to intra-ICU and long-term mortality. Moreover, hypothermia was even more harmful than hyperthermia, and both were strongly associated with intra-ICU mortality, especially in patients admitted with acute coronary syndrome (hypothermia: hazard ratio 6.12, 95% CI 4.12–9.11; p < 0.001; hyperthermia: OR 2.70, 95% CI 1.52–4.79; p< 0.001). Conclusion: Admission BT is an independent risk predictor for both overall intra-ICU and long-term mortality in critically ill patients admitted to an ICU. Therefore, BT at admission might not only serve as a parameter for individual risk stratification but can also influence individual therapeutic decision-making.

DISTRIBUTION OF PULSE WAVE VELOCITY IN CHILDREN AT A SCHOOL IN THE NORTH OF PORTUGAL AND ITS RELATIONSHIP WITH CENTRAL ADIPOSITY INDICES AND BLOOD PRESSURE

Objective:Pulse wave velocity is a measure of arterial stiffness and vascular aging and an important parameter for cardiovascular risk stratification. A previous study showed high prevalence rates of early vascular aging in an adult population from the North of Portugal. The aim of this study was to

Right ventricular systolic to diastolic duration ratio: A novel predictor of outcome in adult idiopathic pulmonary arterial hypertension

BackgroundThe systolic to diastolic (SD) duration ratio reflects global RV performance in pulmonary arterial hypertension (PAH) yet limited data exists on its application to adult non-congenital PAH. We measured SD ratios on echocardiogram in idiopathic PAH (IPAH) to establish its response to pulmonary vasodilator therapy and prognostic value at diagnosis and follow up. MethodsIncident patients with IPAH undergoing echocardiogram, haemodynamic and exercise assessments were identified within our centre between 2005 and 2018. SD ratios were adjusted for heart rate at diagnosis and follow up. ResultsIn 98 patients at diagnosis, the mean SD ratio was 1.03 ± 0.37 decreasing to 0.85 ± 0.25, p < 0.001 at follow-up echocardiogram performed at a median interval of 9.0 months. The SD ratio at diagnosis correlated weakly with RV basal diameter (r = 0.24, p = 0.04) and 6MWD (r = 0.23, p = 0.04). At follow up, the mean SD ratio was lower in those receiving combination vs monotherapy pulmonary vasodilator treatment (71 ± 25 vs 92 ± 22% baseline respectively, p < 0.001). After a median follow-up of 4.8 years, 3 patients were transplanted and 23 patients died. The SD ratio at diagnosis and follow up predicted an increased risk of death/transplantation (HR 2.41 (1.09–5.29), p = 0.03; HR 5.02 (1.27–19.77), p = 0.02 respectively), retaining its predictive value at diagnosis in bivariate models with 6MWD (HR 2.18 (1.06–4.08)), WHO Functional Class (HR 2.33 (1.04–5.21)) and TAPSE (HR 2.36 (1.07–5.19)), all p < 0.05. ConclusionsThe SD ratio carries prognostic value at diagnosis and follow up in IPAH. Its further evaluation alongside current PAH risk stratification parameters should be considered.

Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study

BackgroundCardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software. MethodsWe used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type. ResultsThe intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm3) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm3) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p < 0.0001 for correlation) for both epicardial and intra-thoracic fat. By Bland-Altman analysis for epicardial fat measurements, mean difference of intra-observer was 0.90 cm3 with 95% confidence intervals (0.22,1.7) and −1.8 cm3 for inter-observer, with 95% CI (−2.9, −0.69). Bland-Altman plots for intra-thoracic fat measurements were similarly impressive for both inter- and intra-observer reads. ConclusionsOur data showed that measuring epicardial and intra-thoracic fat volumes by CT using a semi-automated software has excellent intra-observer and inter-observer reliability. Cardiac fat volumes can be obtained easily and reproducibly from routine calcium scoring scans and may help in assessing cardiovascular risk. Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer.

Fast manual long-axis strain assessment provides optimized cardiovascular event prediction following myocardial infarction.

Cardiovascular magnetic resonance feature tracking (CMR-FT) global longitudinal strain (GLS) provides incremental prognostic value following acute myocardial infarction (AMI) but requires substantial post-processing. Alternatively, manual global long-axis strain (LAS) can be easily assessed from standard steady state free precession images. We aimed to define the prognostic value of LAS in a large multicentre study in patients following AMI. A total of 1235 patients with myocardial infarction [n = 795 with ST-elevation myocardial infarction (STEMI) and 440 with non-ST-elevation myocardial infarction (NSTEMI)] underwent cardiovascular magnetic resonance imaging after primary percutaneous coronary intervention in eight centres across Germany. Assessment of LAS was performed in a blinded core-laboratory measuring the systolic shortening between the epicardial apical border and the middle of a line connecting the origins of the mitral leaflets. Primary clinical endpoint was the occurrence of major adverse clinical events (MACE) including death, reinfarction, and congestive heart failure within 1 year after AMI. During 1-year follow-up, 76 patients suffered from MACE. Impaired LAS was associated with higher MACE occurrence both in STEMI (P < 0.001) and NSTEMI (P = 0.001) patients. Association of LAS remained significant (P = 0.017) after correction for univariate significant parameters for MACE prediction. C-statistics revealed incremental value of additional LAS assessment for optimized event prediction compared with left ventricular ejection fraction (MACE P = 0.044; mortality P = 0.013) and a combination of established clinical and imaging parameters (MACE P = 0.084; mortality P = 0.027), but not CMR-FT GLS (MACE P = 0.075; mortality P = 0.380). LAS provides software independent, widely available, easy and fast approximation of longitudinal left ventricular shortening early after reperfused AMI with incremental prognostic value beyond established risk stratification parameters. NCT00712101 and NCT01612312.

Cell-Free SHOX2 DNA Methylation in Blood as a Molecular Staging Parameter for Risk Stratification in Renal Cell Carcinoma Patients: A Prospective Observational Cohort Study.

Novel targeted treatments and immunotherapies have substantially changed therapeutic options for advanced and metastatic renal cell carcinomas (RCCs). However, accurate diagnostic tests for the identification of high-risk patients are urgently needed. Here, we analyzed SHOX2 mRNA expression in RCC tissues and SHOX2 gene body methylation quantitatively in circulating cell-free DNA (ccfDNA) and RCC tissues with regard to risk stratification. The clinical performance of SHOX2 methylation was tested retrospectively and prospectively in a training and testing cohort of RCC tissue samples (n = 760 in total). SHOX2 mRNA expression analysis was included in the training cohort. In matched blood plasma samples from the testing cohort (n = 100), we prospectively examined the capability of pretherapeutic quantitative SHOX2 ccfDNA methylation to assess disease stage and identify patients at high risk of death. SHOX2 gene body methylation was positively correlated with mRNA expression in RCC tissues (training cohort: Spearman ρ = 0.23, P < 0.001). SHOX2 methylation in tissue and plasma strongly correlated with an advanced disease stage (training cohort: ρ = 0.28, P < 0.001; testing cohort/tissue: ρ = 0.40, P < 0.001; testing cohort/plasma: ρ = 0.34, P = 0.001) and risk of death after initial partial or radical nephrectomy [training cohort: hazard ratio (HR) = 1.40 (95% CI, 1.24-1.57), P < 0.001; testing cohort/tissue: HR = 1.16 (95% CI, 1.07-1.27), P = 0.001; testing cohort/plasma: HR = 1.50 (95% CI, 1.29-1.74), P < 0.001]. Pretherapeutic SHOX2 ccfDNA methylation testing allows for the identification of RCC patients at high risk of death after nephrectomy. These patients might benefit from an adjuvant treatment or early initiation of a palliative treatment.

Research Progress in Formation and Application of Tp-Te Interval

Tp-Te interval refers to the duration from the peak to the end time points of T wave in electrocardiogram. Tp-Te interval is an electrocardiogram index reflecting mail-gnant ventricular arrhythmia, while Tp-Te interval mainly reflects ventricular transmural repolarization dispersion. The increase of ventricular transmural repolarization dispersion makes it easy to appear depolarization after repolarization, and forms functional conduction block between different regions, which leads to malignant arrhythmias. In this review we discuss how these markers have demonstrated to be effective to predict malignant arr- hythmias in medical conditions such as long and short QT syndromes, Brugada syndrome and so on. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients.