Marker For Risk Stratification Research Articles

Rediscovering CPET: the prognostic value of hemodynamic gain index in heart failure

Abstract Introduction Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Hemodynamic gain index (HGI) derived from CPET has been proposed as a new marker of risk stratification in general population cohorts. Purpose We aimed to evaluate the prognostic value of HGI in patients with HF. Methods We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. HGI was calculated based on heart rate (HR) and systolic blood pressure (SBP): HGI = [(HRpeak × SBPpeak) − (HRrest × SBPrest)] / (HRrest × SBPrest). Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), circulatory power (CP = pVO2 × peak SBP), and ventilatory power (VP = peak SBP/(VE/VCO2) slope). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality. Results A total of 212 patients (mean age 55.4±10.9, 76.9% male) were included. Most patients had dilated cardiomyopathy (43.9%) followed by ischaemic aetiology (38.7%), with a mean left ventricle ejection fraction of 29±13%. The most used exercise protocol was the modified Naughton (76.6%), followed by the original Naughton (18.7%), and Bruce (4.8%). Mean pVO2 was 16.7±5.9mL O2 kg–1 min–1 and median VE/VCO2 slope was 37.5 [32.7–44.3]. Mean VP was 3.46±1.31mmHg while median CP was 1927 [1427–2697]mmHg min/mL/kg. Mean HGI was 0.90±0.5 bpm/mmHg. Despite weak, there were significant positive correlations between HGI and mean pVO2 (rs=0.55, p<0.01), VP (r=0.60, p<0.01), and CP (rs=0.68, p<0.01), but negative correlation between HGI and VE/VCO2 slope (rs=−0.45, p<0.01). HGI was grouped by terciles: T1 (<0.59), T2 (0.59–1.02), and T3 (>1.02). After a median follow-up of 71 [49–81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). In the T1 group, the multivariable-adjusted odds ratio (OR) for the primary outcome was 3.73 (95% CI 1.97–7.06, p<0.01) compared to the T3. In the T2 group, the multivariable-adjusted OR for the primary outcome was 0.47 (95% CI 0.27–0.81, p<0.01) compared to T1. There were no significant differences between T2 and T3 groups. Kaplan-Meier estimates of primary outcome during follow-up according to HGI tercile are shown in Figure 1. Conclusion HGI is inversely associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification. Funding Acknowledgement Type of funding sources: None.

Sex differences in frequency of instrumental activities of daily living after cardiac rehabilitation and its impact on long-term mortality in patients with heart failure

Abstract Introduction While the major outcome of cardiac rehabilitation for heart failure (HF) is the improvement of exercise tolerance, prognosis, and quality of life, instrumental activities of daily living (IADL) has also been focused on as one of the its outcomes. IADL has been reported to be associated with all-cause mortality and quality of life in community-dwelling people and in patients with stable heart disease, but no report has examined the relationship between IADL after cardiac rehabilitation for HF and prognosis. In addition, it is assumed that sex differences may affect the frequency of performing each component of IADL, but there are no reports examining the association with prognosis by sex. Purpose The present study aimed to investigate the sex differences in frequency of IADL and its impact on outcomes. Methods We retrospectively studied 490 consecutive patients who were admitted due to acute decompensated HF and participated in outpatient cardiac rehabilitation after discharge. The study was performed in accordance with the tenets of the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of our institution. IADL frequency was assessed using the questionnaire-based Frenchay Activities Index (FAI). The primary endpoint was all-cause death and secondary endpoint was combined events (all-cause death and/or readmission due to HF). We performed the Kaplan–Meier and log-rank tests and multivariable Cox regression analysis to evaluate the prognostic predictive capability of the FAI. Results The study population had a median age of 69 (interquartile range [IQR]: 58–76) years, and 33.9% of patients were females. The median FAI score was 24 (IQR: 16–29) points. According to the Youden index based on the area under the curve calculated by the receiver operating characteristics curve, the cut-off values of FAI for all-cause death in all-over, females, and males were 23, 22, and 23 points, respectively. Over a median follow-up period of 4.8 years (IQR: 2.3–6.6 years), all-cause death and combined events were occurred in 95 (19.4%) and 213 (43.5%), respectively. After adjustment for several pre-existing prognostic factors, IADL assessed by the FAI was independently associated with all-cause mortality (hazard ratio [HR]: 0.961, 95% confidence interval [CI]:0.937–0.986) and combined events (HR: 0.968, 95% CI: 0.952–0.985), respectively. In addition, there was no interaction between sex in prognostic capability (P=0.664). Conclusion Lower IADL frequency assessed by FAI at the end of outpatient cardiac rehabilitation was shown to be associated with poorer prognosis in patients with HF, regardless of sex. The IADL level is generally higher in females than in males but seems to be a useful marker for risk stratification at the end of cardiac rehabilitation in both females and males. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid [JSPS KAKENHI Grant Number JP 19K19884]

Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients

Abstract Background The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. Purpose In the present study we aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients. Methods We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n=751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n=2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology (ESC) guidelines (clinical ESCrisk). Intima-media thickness (IMT) excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As endpoint of the study was defined the composite of CV death, acute myocardial infarction (MI) and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort. Results MaxWT >2.00mm and avg.maxWT >1.39mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (p<0.05 for net reclassification index, integrated discrimination index and Delta Harrell's C index). MaxWT <0.9mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort. Conclusion Integration of carotid ultrasonography in guidelines-defined risk stratification may identify very high risk patients in need for further residual risk reduction or at very low probability Funding Acknowledgement Type of funding sources: None.

Ventricular activation time as a marker for complex ventricular arrhythmias, sudden cardiac death and ICD implantation in hypertrophic cardiomyopathy

Abstract Background Identification of patients with hypertrophic cardiomyopathy (HCM) who are at high risk of sudden cardiac death (SCD) is essential, as life-threatening ventricular arrhythmias (VAs) can be effectively prevented with an implantable cardioverter defibrillator (ICD). Risk stratification using HCM Risk-SCD score is recommended in the 2014 ESC guidelines for the management of patients with HCM. However, the role of electrocardiogram (ECG) in risk stratification is less well established. Purpose We investigated the association between the ventricular activation time (VAT), an ECG marker of the duration of ventricular depolarization, with the HCM Risk-SCD score, the presence of complex VAs, the implantation of an ICD and ICD-therapy for VAs. Methods Patients with a history of HCM, documented by echocardiography, were studied. The 12-lead ECG and echocardiography were performed on the same day. On ECG, we evaluated the VAT in milliseconds, between the onset of the QRS complex to the peak of R wave on V5 or V6 precordial ECG leads. A careful personal and family history for unexplained syncope and SCD was obtained, respectively. The presence of non-sustained ventricular tachycardia (NSVT) and ICD therapy were assessed either with 48h ECG recording or ICD interrogation. HCM Risk-SCD score was calculated by the corresponding ESC online calculator. Statistical analysis was performed using the SPSS software. Results Thirty-three patients with HCM were included (mean age 51±12 years, 78.8% male). According to the HCM Risk-SCD score, HCM patients were divided into three groups: low-risk (<4, 45.5%), intermediate-risk (4 to <6, 24.2%) and high-risk (>6, 30.3%) for SCD. Approximately half of the HCM patients had episodes of NSVT (48.5%) and an ICD (48.5%). Ventricular activation time was significantly prolonged in high-risk group compared either with intermediate-risk (74±24.5 vs 48.7±16.4, p=0.006) or low-risk (74±24.5 vs 44.3±12.6, p<0.001). HCM patients with NSVT had a significantly prolonged VAT compared with those without NSVT (62.19±25.2 vs 47.06±15.3, p=0.022). Moreover, HCM patients with an ICD had a higher VAT than those without an ICD (62.1±25.2 vs 47±15.3, p=0.003). VAT was also significantly prolonged in the group with appropriate ICD therapy for VAs compared with that without ICD therapy (82.8±22.1 vs 52.2±16.4, p=0.007). Finally, there was a significant positive correlation between VAT and NSVT (r=0.352, p=0.044), history of syncope (r=0.604, p<0.001), HCM risk-SCD score (r=0.493, p=0.004), ICD implantation (r=0.508, p=0.003) and ICD therapy (r=0.648, p=0.007) for VAs while there was not a correlation with the family history of SCD. Conclusion Prolongation of VAT is associated with NSVT, HCM risk score for SCD, ICD implantation and ICD therapy for VAs in patients with HCM and it seems to be a novel, easy to measure, ECG marker for risk stratification. Funding Acknowledgement Type of funding sources: None.

ESTIMATED PULSE WAVE VELOCITY INDEPENDETLY PREDICTS SURVIVAL-TO-DISCHARGE IN PATIENTS REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION: A SINGLE-CENTRE RETROSPECTIVE COHORT STUDY

ESTIMATED PULSE WAVE VELOCITY INDEPENDETLY PREDICTS SURVIVAL-TO-DISCHARGE IN PATIENTS REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION: A SINGLE-CENTRE RETROSPECTIVE COHORT STUDY

Активное наблюдение при раке предстательной железы промежуточной группы риска.

Introduction. Prostate cancer (PСa) is one of the most common malignant diseases in men in the world. Radical prostatectomy remains the «gold standard» for treating this pathology. Good long-term oncological results Active follow-up of low-risk patients, as well as modification of the Gleason scale, suggested the possibility of using AS in carefully selected patients with intermediate-risk PCa. The introduction of molecular genetic markers into practice will allow a personalized choice of a treatment method. Purpose. Conduct a systematic review of the literature on the analysis of active surveillance in patients with PCa of an intermediate risk group, existing molecular genetic markers for additional risk stratification. Materials and methods. A systematic review of publications on active surveillance in prostate cancer, published in the PubMed, Cochrane, e-Library databases, was performed. Databases were searched using the following keywords: active surveillance, prostate cancer, intermediate risk, molecular genetic markers. Results. This review selected 39 articles, of which 24 are devoted to Active Surveillance, 15 molecular genetic markers of PCа aggressiveness. In the analysis of active surveillance, parameters such as the percentage of patients without active (radical) treatment, overall survival, tumor-specific survival, and metastasis-free survival were evaluated. Conclusions. Currently, AS in prostate cancer can be used for carefully selected group of patients at an intermediate risk group, the introduction of modern molecular genetic markers will allow more accurate determination of the amount of treatment without worsening long-term oncological results.

Neurological examination at 32-weeks postmenstrual age predicts 12-month cognitive outcomes in very preterm-born infants

BackgroundTo determine the diagnostic accuracy of Hammersmith Neonatal Neurological Examination (HNNE) at 30–32 weeks postmenstrual age (PMA, ‘Early’) and term equivalent age (TEA) in infants born <31 weeks PMA to predict cognitive outcomes at 12 months corrected age (CA).MethodsProspective cohort study of 119 infants (73 males; median 28.4 weeks gestational age at birth) who underwent Early and TEA HNNE. At 12 months CA, 104 participants completed Bayley Scales of Infant and Toddler Development, 3rd Edition, (Bayley-III). Optimum cut-off points for each HNNE subscale were determined to establish diagnostic accuracy for predicting adverse cognitive outcomes on the Bayley-III Cognitive Composite Scale (≤85).ResultsThe best diagnostic accuracy for HNNE total score at 30–32 weeks PMA predicting cognitive impairment occurred at cut-off ≤16.7 (sensitivity (Se) = 71%, specificity (Sp) = 51%). The Abnormal Signs subscale demonstrated the best balance of sensitivity/specificity combination (Se = 71%, Sp = 71%; cut-off ≤1.5). For HNNE at TEA, the total score at cut-off ≤24.5 had Se = 71% and Sp = 47% for predicting cognitive impairment. The Tone Patterns subscale demonstrated the strongest diagnostic accuracy at TEA (Se = 71%, Sp = 63%; cut-off ≤3).ConclusionsEarly and TEA HNNE demonstrated moderate diagnostic accuracy for cognitive outcomes at 12-months CA in infants born <31 weeks gestational age.Clinical Trial Registration: Australian New Zealand Clinical Trials Registry; Trial Registration Number: ACTRN12613000280707; web address of trial: http://www.ANZCTR.org.au/ACTRN12613000280707.aspx.ImpactEarly Hammersmith Neonatal Neurological Examination (HNNE) assessment at 30–32 weeks postmenstrual age has moderate diagnostic accuracy for cognitive outcomes at 12 months corrected age in infants born <31 weeks gestation.Early HNNE at 30–32 weeks has stronger predictive validity than HNNE at term equivalent age.Early HNNE may provide an early marker for risk-stratification to optimise the planning of post-discharge support and follow-up services for infants born preterm.

The Influence of SARS-CoV-2 Infection on Lipid Metabolism-The Potential Use of Lipid-Lowering Agents in COVID-19 Management.

Several studies have indicated lipid metabolism alterations during COVID-19 infection, specifically a decrease in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations and an increase in triglyceride (TG) levels during the infection. However, a decline in triglycerides can also be observed in critical cases. A direct correlation can be observed between a decrease in serum cholesterol, HDL-C, LDL-C and TGs, and the severity of the disease; these laboratory findings can serve as potential markers for patient outcomes. The transmission of coronavirus increases proportionally with rising levels of cholesterol in the cell membrane. This is due to the fact that cholesterol increases the number of viral entry spots and the concentration of angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral penetration. Studies have found that lower HDL-C levels correspond with a higher susceptibility to SARS-CoV-2 infection and infections in general, while higher HDL-C levels were related to a lower risk of developing them. However, extremely high HDL-C levels in serum increase the risk of infectious diseases and is associated with a higher risk of cardiovascular events. Low HDL-C levels are already accepted as a marker for risk stratification in critical illnesses, and higher HDL-C levels prior to the infection is associated with a lower risk of death in older patients. The correlation between LDL-C levels and disease severity is still unclear. However, TG levels were significantly higher in non-surviving severe patients compared to those that survived; therefore, elevated TG-C levels in COVID-19 patients may be considered an indicator of uncontrolled inflammation and an increased risk of death.

Identification of a Biomarker Combination for Survival Stratification in pStage II/III Gastric Cancer after Curative Resection.

Simple SummaryGastric cancer (GC) is the fifth most common cancer worldwide and the fourth most common cause of cancer-related deaths, with a high frequency of recurrence and metastasis, and a poor prognosis. This study presents a novel combination of four proteins (PDGFRB, INHBA, MMP11, and galectin-10) in GC tissues that have been identified as useful survival stratification markers in patients with pStage II/III GC after curative resection by quantitative polymerase chain reaction (qPCR), proteomic analysis, and immunohistochemistry (IHC).Background: We sought to identify an optimal combination of survival risk stratification markers in patients with pathological (p) stage II/III gastric cancer (GC) after curative resection. Methods: We measured the expression levels of 127 genes in pStage II/III GC tissues of two patient cohorts by quantitative polymerase chain reaction (qPCR) and the expression of 1756 proteins between two prognosis (good and poor) groups by proteomic analysis to identify candidate survival stratification markers. Further, immunohistochemistry (IHC) using tumor microarrays (TMAs) in another cohort of patients was performed to identify an optimal biomarker combination for survival stratification in GC patients. Results: secreted protein acidic and rich in cysteine (SPARC), erb-b2 receptor tyrosine kinase 2 (ERBB2), inhibin subunit beta A (INHBA), matrix metallopeptidase-11 (MMP11), tumor protein p53 (TP53), and platelet-derived growth factor receptor-beta (PDGFRB) were identified as candidate biomarkers from qPCR analysis, and SPARC and galectin-10 were obtained from the proteomic analysis. The combination of PDGFRB, INHBA, MMP11, and galectin-10 was identified as the optimal combination of survival risk stratification markers. Conclusions: A combination of four proteins in GC tissues may serve as useful survival risk stratification markers in patients with pStage II/III GC following curative resection. Our results may facilitate future multicenter prospective clinical trials.

Identification of recurrent variants implicated in disease in bicuspid aortic valve patients through whole-exome sequencing

Bicuspid aortic valve (BAV) is the most common congenital heart defect in human beings, with an estimated prevalence in the general population of between 0.5 and 2%. Moreover, BAV is the most common cause of aortic stenosis in the pediatric population. Patients with BAV may have no symptoms for life, and some of them may progress to aortic stenosis. Genetic factors increase the susceptibility and development of BAV. However, the pathogenesis and BAV are still unclear, and more genetic variants are still needed for elucidating the molecular mechanism and stratification of patients. The present study carried out screening of variants implicated in disease in BAV patients. The whole-exome sequencing (WES) was performed in 20 BAV patients and identified 40 different heterozygous missense mutations in 36 genes (MIB2, FAAH, S100A1, RGS16, MAP3K19, NEB, TTN, TNS1, CAND2, CCK, KALRN, ATP10D, SLIT3, ROS1, FABP7, NUP205, IL11RA, NPR2, COL5A1, CUBN, JMJD1C, ANXA7, TRIM8, LGR4, TPCN2, APOA5, GPR84, LRP1, NCOR2, AKAP11, ESRRB, NGB, AKAP13, WWOX, KCNJ12, ARHGEF1). The mutations in these genes were identified as recurrent variants implicated in disease by in silico prediction tool analysis. Nine genes (MIB2, S100A1, TTN, CCK, NUP205, LGR4, NCOR2, ESRRB, and WWOX) among the 36 genes were identified as variants implicated in disease via unanimous agreement of in silico prediction tool analysis and sequenced in an independent cohort of 137 BAV patients to validate the results of WES. BAV patients carrying these variants demonstrated reduced left ventricular ejection fractions (LVEF) (63.8 ± 7.5% vs. 58.4 ± 5.2%, P < 0.001) and larger calcification volume [(1129.3 ± 154) mm3 vs. (1261.8 ± 123) mm3, P < 0.001]. The variants in TTN, NUP205 and NCOR2 genes are significantly associated with reduced LVEF, and the variants in S100A1, LGR4, ESRRB, and WWOX genes are significantly associated with larger calcification volume. We identified a panel of recurrent variants implicated in disease in genes related to the pathogenesis of BAV. Our data speculate that these variants are promising markers for risk stratification of BAV patients with increased susceptibility to aortic stenosis.

Correlation between heart rate variability and polysomnography-derived scores of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is one of the most common sleep disorders and affects nearly a billion people worldwide. Furthermore, it is estimated that many patients with OSA are underdiagnosed, which contributes to the development of comorbidities, such as cardiac autonomic imbalance, leading to high cardiac risk. Heart rate variability (HRV) is a non-invasive, widely used approach to evaluating neural control of the heart. This study evaluates the relationship between HRV indices and the presence and severity of OSA. We hypothesize that HRV, especially the nonlinear methods, can serve as an easy-to-collect marker for OSA early risk stratification. Polysomnography (PSG) exams of 157 patients were classified into four groups: OSA-free (N = 26), OSA-mild (N = 39), OSA-moderate (N = 37), and OSA-severe (N = 55). The electrocardiogram was extracted from the PSG recordings, and a 15-min beat-by-beat series of RR intervals were generated every hour during the first 6h of sleep. Linear and nonlinear HRV approaches were employed to calculate 32 indices of HRV. Specifically, time- and frequency-domain, symbolic analysis, entropy measures, heart rate fragmentation, acceleration and deceleration capacities, asymmetry measures, and fractal analysis. Results with indices of sympathovagal balance provided support to reinforce previous knowledge that patients with OSA have sympathetic overactivity. Nonlinear indices showed that HRV dynamics of patients with OSA display a loss of physiologic complexity that could contribute to their higher risk of development of cardiovascular disease. Moreover, many HRV indices were found to be linked with clinical scores of PSG. Therefore, a complete set of HRV indices, especially the ones obtained by the nonlinear approaches, can bring valuable information about the presence and severity of OSA, suggesting that HRV can be helpful for in a quick diagnosis of OSA, and supporting early interventions that could potentially reduce the development of comorbidities.

Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas

PurposeAdenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs.MethodsTissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression.ResultsOut of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4+ T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4+ T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs.ConclusionIn our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4+ cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine.

Correlation of lipoprotein (a) levels and plaque morphology in very young acute coronary syndrome patients using optical coherence tomography

IntroductionLevels of lipoprotein (LP) (a) are useful marker for risk stratification of cardiovascular disease. This genetic biomarker is suggestive of patient predisposition to acute coronary event. The present study was to study correlation of LP(a) levels and plaque morphology in very young patients (<35 years) with acute coronary syndrome (ACS). MethodsA prospective, single-center, observational study consisting of very young patients with ACS and fit for optical coherence tomography (OCT) guided invasive coronary angiography was conducted at tertiary-care centre. LP(a) levels were compared between healthy controls and very young ACS patients. Correlation of LP(a) levels and plaque characteristics in very young ACS patients was done using OCT imaging. ResultsOut of enrolled 80 subjects, 40 were very young ACS and 40 were matched healthy controls. In very young patients, plaque rupture and erosion were mechanism of ACS in 67.5% and 32.5% patients, respectively. Mean levels of LP(a) were 28.10 ± 13.96 nmol/l in healthy controls and 47.19 ± 29.85 nmol/l in very young patients with ACS (p = 0.022). Among very young ACS patients, patients with LP(a) levels<75 nmol/l and ≥75 nmol/l had mean thin cap fibroatheroma thickness of 117.08 ± 52.542 μm and 95.00 ± 36.286 μm, respectively (p = 0.2355). ConclusionHigher levels of LP(a) were seen in younger patients with ACS compared with matched healthy individuals. Plaque rupture was the commonest mechanism of ACS in very young ACS patients. Patients with high LP(a) levels had lesser thickness of fibrous cap in OCT imaging compared with low levels of LP(a).

Plasma l-carnitine and risks of cardiovascular events and recurrent stroke after ischemic stroke: A nested case-control study

Background and aimsl-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study. Methods and resultsA total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57–0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58–0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21–0.57) and 0.36 (95% CI: 0.21–0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement. ConclusionsHigher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke. Trial registrationClinicaltrials.gov as NCT01840072. URL: https://www.clinicaltrials.gov.

Risk stratification and prognostic value of prothrombin time and activated partial thromboplastin time among COVID-19 patients.

BackgroundCOVID-19 is a viral disease caused by a new strain of corona virus. Currently, prognosis and risk stratification of COVID-19 patients is done by the disease’s clinical presentation. Therefore, identifying laboratory biomarkers for disease prognosis and risk stratification of COVID-19 patients is critical for prompt treatment. Therefore, the main objective of this study was to assess the risk stratification and prognostic value of basic coagulation parameters and factors associated with disease severity among COVID-19 patients at the Tibebe Ghion Specialized Hospital, COVID-19 treatment center, Northwest Ethiopia.MethodsA follow-up study was conducted among conveniently recruited COVID-19 patients attended from March to June 2021. Socio-demographic and clinical data were collected using a structured questionnaire and checklist, respectively. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were analyzed by the HUMACLOT DUE PLUS® machine. Descriptive statistics were used to summarize the socio-demographic and clinical characteristics of study participants. Kruskal Wallis tests were used to compare the difference between parametric and non-parametric continuous variables, respectively. The area under the receiver operating characteristic curve (AUC) was used to evaluate the value of PT and APTT in the risk stratification and disease prognosis of COVID-19 patients. Ordinal logistic regression was used to identify the factors associated with disease severity and prognosis. A P-value < 0.05 was defined as statistically significant for all results.ResultBaseline PT at a cut-off value ≥ 16.25 seconds differentiated severe COVID-19 patients from mild and moderate patients (AUC: 0.89, 95% CI: 0.83–0.95). PT also differentiated mild COVID-19 patients from moderate and severe patients at a cut-off value ≤ 15.35 seconds (AUC: 0.90, 95% CI: 0.84–0.96). Moreover, alcohol drinkers were a 3.52 times more likely chance of having severe disease than non-drinkers (95% CI: 1.41–8.81). A one-year increment in age also increased the odds of disease severity by 6% (95% CI: 3–9%). An increment of ≥ 0.65 seconds from the baseline PT predicted poor prognosis (AUC: 0.93, 0.87–0.99).Conclusions and recommendationsProlonged baseline PT was observed in severe COVID-19 patients. Prolonged baseline PT was also predicted to worsen prognosis. An increase from the baseline PT was associated with worsen prognosis. Therefore, PT can be used as a risk stratification and prognostic marker in COVID-19 patients.

Association of a genetic variant in the ATP-binding cassette sub-family B member 1 with risk of cervical cancer

BackgroundCervical cancer is one of the most prevalent cancers among women and is associated with high morbidity and mortality. Several factors are involved in the pathogenesis of cervical cancer including viral infections and/or genetic modifications that include single nucleotide polymorphisms (SNPs). MethodsWe aimed to investigate the association of genetic variants in ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs1128503) and Fc Gamma Receptor IIIa (FCGR3A) (rs396991) genes and susceptibility to cervical cancer in 263 individuals with or without this form of cancer. DNA samples were isolated and genotyped using a TaqMan based real-time (RT-) PCR method. ResultsThe rs1128503 was found to be associated with an increased risk of cervical cancer (recessive model: OR = 2.6, CI: 1.1–5.8, p = 0.02). whilst there was no association between the rs396991 and susceptibility to cervical cancer. ConclusionOur results showed that there is an association between the ABCB1 polymorphism and susceptibility for cervical cancer suggesting its potential as a risk stratification marker for cervical neoplasia.

Clinical and biological markers for risk-stratification of T1 high-grade non-muscle invasive bladder cancer.

To summarize the prognostic and predictive role of current clinical and biological markers in patients with T1 high-grade (T1HG) nonmuscle invasive bladder cancer (NMIBC). Classical clinico-pathologic markers such as age, tumor size, focality, and location as well as the presence of concomitant carcinoma in situ, lymphovascular invasion, and histological variants at the time of transurethral resection (TUR) should be used in the risk-stratification of T1HG to improve patients' selection for early aggressive treatment. pathological T1 substaging has shown to predict disease progression and response to intravesical therapy, and should therefore be reported in the pathological assessment to improve clinical decision-making. Urinary inducible cytokines measured at different time points during Bacillus Calmette-Guerin therapy may be used to predict response to treatment, while urinary mRNA-based biomarkers may be of value to select patients for repeated TUR (reTUR). The advent of genomic classification in NMIBC and that of immune markers may improve current risk-stratification tools and pave the way toward personalized treatment. The role of clinico-pathologic variables in the risk-stratification of T1HG NMIBC remains unaltered, despite insufficient. Urinary biomarkers and tissue-based immune markers hold the promise to revolutionize the paradigm of risk-stratification due to their potential role in predicting response to intravesical and systemic immunotherapy. However, to date, none of the investigated biomarkers is used in clinical practice to risk-stratify T1HG patients due to the lack of external and/or prospective validations.

Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases.

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

Stress hyperglycemia ratio and long-term mortality after acute myocardial infarction in patients with and without diabetes: A prospective, nationwide, and multicentre registry.

To assess the predictive value of stress hyperglycemia ratio (SHR) for long-term mortality after acute myocardial infarction (AMI) in patients with and without diabetes. We evaluated 6892 patients with AMI from the prospective, nationwide, multicentre China Acute Myocardial Infarction registry, of which 2820 had diabetes, and the remaining 4072 were nondiabetic patients. Patients were divided into high SHR and low SHR groups according to the optimal cutoff values of SHR to predict long-term mortality for diabetic and nondiabetic patients, respectively. The primary endpoint was all-cause mortality at 2years. The optimal cutoff values of SHR for predicting 2-year mortality were 1.20 and 1.08 for the diabetic and nondiabetic population, respectively. Overall, patients with high SHR were significantly associated with higher all-cause mortality compared with those with low SHR, in both diabetic patients (18.5% vs. 9.7%; hazard ratio [HR] 2.01, 95% confidence interval 1.63-2.49) and nondiabetic patients (12.0%vs. 6.4%; HR 1.95, 95%CI 1.57-2.41). After the potential confounders were adjusted, high SHR was significantly associated with higher risks of long-term mortality in both diabetic (adjusted HR 1.73, 95%CI 1.39-2.15) and nondiabetic (adjusted HR 1.63, 95%CI 1.30-2.03) patients. Moreover, adding SHR to the original model led to a slight albeit significant improvement in C-statistic, net reclassification, and integrated discrimination regardless of diabetic status. This study demonstrated a strong positive association between SHR and long-term mortality in patients with AMI with and without diabetes, suggesting that SHR should be considered a useful marker for risk stratification in these patients. ClinicalTrials.gov NCT01874691.

Concordance between Ki-67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint.

Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.