Serum fibrosis index-based risk score predicts hepatocellular carcinoma in untreated patients with chronic hepatitis B

Background/AimsSerum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients.MethodsFifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort.Results180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted.Conclusion: A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.     

A polygenic risk score for multiple myeloma risk prediction

There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p = 3.55 × 10⁻¹⁵ for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p = 1.62 × 10⁻¹³ for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.Subject terms: Cancer genomics, Cancer epidemiology     

Asthma score: predictive ability and risk factors

BACKGROUND: Definition of asthma as a continuous score is a promising tool for population studies that has not yet been fully evaluated. OBJECTIVE: We assessed (i) the predictive ability of an asthma score against the occurrence of different asthma-related outcomes and (ii) the risk factors identified when using an asthma score. METHODS: The European Community Respiratory Health Study II included subjects from the general population randomly studied during 1991-1993 who were followed up in the years 1998-2001, from 29 centres in 14 countries. A total of 8956 subjects were included. The asthma score consisted of a simple sum of the positive answers to five respiratory symptoms. RESULTS: Asthma score at baseline showed a linear relationship with incidence of asthma, the occurrence of asthma attacks, use of asthma medication and bronchial reactivity at the end of the follow-up. Asthma score at the end of follow-up was associated with known risk factors at baseline such as IgE to grass, rhinitis or body mass index, in addition to passive smoking in men [average score ratio (RR) = 1.30; 95% confidence interval (CI) 1.09-1.50] or changes in body mass index (RR = 1.27; 95% CI 1.05-1.27, per each kg/m(2)). CONCLUSION: The asthma score had good predictive ability against outcomes related with asthma and also good ability to detect risk factors. This encourages the use of the score as a measure of asthma in epidemiological studies on aetiology of asthma.     

Obesity phenotype and coronary heart disease risk as estimated by the Framingham risk score

There are conflicting data as to whether general or abdominal obesity is a better predictor of cardiovascular risk. This cross-sectional study involved 4,573 subjects aged 30 to 74 yr who participated in the Fourth Korea National Health and Nutrition Examination Survey conducted in 2008. Obesity phenotype was classified by means of body mass index (BMI) and waist circumference (WC), and participants were categorized into 4 groups. Individuals' 10-yr risk of coronary heart diseases (CHD) was determined from the Framingham risk score. Subjects with obese WC had a higher proportion of high risk for CHD compared to the normal WC group, irrespective of BMI level. Relative to subjects with normal BMI/normal WC, the adjusted odds ratios (ORs) of normal BMI/obese WC group (OR 2.93 [1.70, 5.04] and OR 3.10 [1.49, 6.46]) for CHD risk in male were higher than obese BMI/obese WC group (OR 1.91 [1.40, 2.61] and OR 1.70 [1.16, 2.47]), whereas the adjusted ORs of obese BMI/obese WC group (OR 1.94 [1.24, 3.04] and OR 3.92 [1.75, 8.78]) were higher than the others in female. Subjects with obese BMI/normal WC were not significantly associated with 10-yr CHD risk in men (P = 0.449 and P = 0.067) and women (P = 0.702 and P = 0.658). WC is associated with increased CHD risk regardless of the level of BMI. Men with normal BMI and obese WC tend to be associated with CHD risk than those with obese BMI and obese WC.     

Coronary age as a risk factor in the modified Framingham risk score

Background  

Clinical guidelines emphasize risk assessment as vital to patient selection for medical primary intervention. However, risk assessment methods are restricted in their ability to predict further coronary events. The most widely accepted tool in the United States is the Framingham risk score. In these equations age is a powerful risk factor. Although the extent of coronary atherosclerosis increases with age, there is large inter-individual variability in the rate of development and progression of this disease. This fact limits the utility of Framingham scoring when applied to individuals. Electron beam tomography (EBT), which measures coronary calcium, provides a non-invasive method for assessing coronary plaque burden, thus offering the possibility of providing a more accurate estimate of an individual's "arterial age" than from chronological age alone.     

GRACE score of myocardial infarction patients correlates with oxidative stress index,hsCRP and inflammation

BackgroundEtiopathogenesis of myocardial infarction (MI) is contributed by oxidative injury and inflammatory response. The interplay of these processes determines outcomes in MI patients. However, studies showing the relationship of oxidative stress and inflammatory cytokines with prognosis and severity of MI are lacking.ObjectiveThe present study was designed to assess the degree of oxidative stress and inflammation in correlation with GRACE (Global Registry of Acute Coronary Events) risk score in patients of MI.MethodsMI patients were segregated according to GRACE risk score and age. Blood samples of the patients were used for determination of level of total peroxide, Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), pro-inflammatory molecules such as high sensitive C-reactive protein (hsCRP), Tumor Necrosis Factor α (TNFα), interleukin 1 β (IL 1β), interleukin 6 (IL 6), anti-inflammatory cytokine interleukin 10 (IL 10), and TNFα/IL 10 cytokine ratio.ResultsWe found significant elevation in concentration of total peroxide, TAS and OSI in all MI patients than healthy volunteers, this elevation showed pronouncement with higher GRACE score (GS) and age. Alteration in pro-inflammatory and anti-inflammatory cytokines was seen in MI patients than control group, and this alteration displayed polarization with GS and age.ConclusionMI patients with higher GS and age have greater degree of OSI and inflammation, and these biochemical parameters were significantly correlated with GS and thus disease severity.     

MTHFR C677T polymorphism as a risk factor for vascular calcification in chronic hemodialysis patients

Polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T is one of the suggested risk factors for atherosclerosis. However, few studies have reported on the relationship between MTHFR C677T polymorphism and vascular calcification (VC) in chronic hemodialysis patients. We investigated the relationship between the MTHFR C677T polymorphism and VC in 152 chronic hemodialysis patients. Patients with a TT genotype exhibited significantly higher VC scores than patients expressing CC and CT (P = 0.002). The prevalence of peripheral vascular disease increased with the incidence of MTHFR C677T mutations for all patients, and the incidence of cerebrovascular accidents also increased with the presence of mutations for young patients (≤ 60 yr) (P < 0.05). Patients with CT and TT genotypes had adjusted odds ratios for VC of 1.39 and 1.58, respectively (P < 0.05). In summary, these data suggest that the MTHFR C677T polymorphism affects the degree of VC in chronic hemodialysis patients.     

Genetic risk score modifies the effect of APOE on risk and age onset of Alzheimer's disease

Single nucleotide polymorphism (SNP)-based genetic risk score (GRS) and APOE genotype are both important in risk prediction of Alzheimer's disease (AD); however, the interaction between GRS and APOE has not been extensively investigated. Our objective was to determine whether GRS modifies the APOE effect on AD risk and age at onset (AAO). The study included 774 AD cases and 767 controls of European descent. Population standardized GRS was calculated based on 17 previously implicated AD risk-associated SNPs. Association was analyzed using logistic regression, Cox proportional hazards model and Kaplan-Meier curve. We found that GRS was significantly associated with AD risk and the association was stronger among APOE ε4 carriers. Compared to ε4 non-carriers, the Odds Ratio (OR) for AD was 8.09 (95% Confidence Interval [CI]: 4.98-13.63) for ε4 carriers with high-GRS (≥1.5). In contrast, the OR was 2.55 (95% CI: 1.46-4.49) for ε4 carriers with low-GRS (<0.6). In conclusion, these results suggest SNP-based GRS may supplement APOE for better assessment of inherited risk and age of onset of AD.     

Positive rate and score discrepancies of myeloperoxidase staining at different temperatures

Myeloperoxidase (MPO) is a strong marker of acute myeloid leukemia. The aim of this study was to compare MPO staining at different temperatures. Four bone marrow aspirate smears of each case were incubated with MPO staining solution at 4 °C, 20 °C, 37 °C and 50 °C, respectively. 30 patients with score <150 at 50 °C were group A; 26 patients with score ≥150 at 50 °C were group B. The results showed that at 4 °C, MPO-positive blasts in two cases of group A were both 2%; at 50 °C, MPO-positive blasts in the two cases were 42% and 30%, respectively. At 4 °C, 20 °C, 37 °C and 50 °C, the mean positive rates of group A were 30.6%, 42.2%, 53.7% and 56.5%, respectively (P < 0.001); their mean scores were 52.2, 75.9, 99.5 and 105.3, respectively (P < 0.001); the mean positive rates of group B were 84.1%, 88.7%, 92.3% and 93.7%, respectively (P < 0.001); their mean scores were 199.5, 224.7, 243.5 and 244.5, respectively (P < 0.001). From this study we can conclude that most MPO staining is effective over a wide temperature range with the highest positive rate at 50 °C. MPO staining intensity at low temperature is much lower and may be false negative. Good MPO staining is achieved at 37 °C.     

Vascular function and cardiovascular risk factors in women with severe flushing

Cardiovascular disease is the leading cause of death in women of postmenopausal age worldwide. It is a relatively rare occurrence before the menopause and the increase in incidence coincides with the most common symptom associated with menopausal transition, hot flushing. Interest in cardiovascular disease post-menopause has largely focused on the effect of hormone therapy on risk of coronary events and stroke, with vasomotor symptoms considered merely a nuisance symptom, but recent work suggests that the presence of flushing may be a marker of underlying cardiovascular disease.     

Validation of the qSOFA score compared to the CRB-65 score for risk prediction in community-acquired pneumonia

ObjectiveThe qSOFA (quick sepsis-related organ failure assessment) score shows similarities to the CRB-65 pneumonia score, but its prognostic accuracy in patients with community-acquired pneumonia (CAP) has not been extensively evaluated. Our aim was to validate the qSOFA (-65) score in a large cohort of CAP patients.MethodsWe conducted a retrospective population-based cohort study including all CAP cases hospitalized between 1st January 2014 and 31st December 2018 from the German nationwide mandatory quality assurance programme. We excluded cases transferred from another hospital, with mechanical ventilation present on admission, and without documented respiratory rate. Predefined outcomes were hospital mortality and need for mechanical ventilation.ResultsAmong the 1,262,250 included cases, hospital mortality was 12.4% and the mechanical ventilation rate was 7.1%. All CRB and qSOFA criteria were associated with both outcomes, but the qSOFA had inferior sensitivity compared to the CRB-65 for mortality prediction. Including the age criterion ≥65 years, qSOFA-65 and CRB-65 performed similarly (AUC 0.69, 95%CI 0.69–0.69 versus 0.68, 95%CI 0.68–0.68). A qSOFA-65 of 0 was associated with fewer missed deaths (3328, 2.0%) compared to a CRB-65 of 0 (5480, 2.4%). The sensitivity of the suggested qSOFA cut-off of ≥2 for sepsis was low (mortality 25.8%, 95%CI 25.6–26.0%; mechanical ventilation 24.1%, 95%CI 23.8–24.4%). Results were similar when frail and palliative patients were excluded.ConclusionsThe qSOFA parameters show prognostic accuracy similar to the CRB parameters in CAP, but the sepsis cut-off of ≥2 lacked sensitivity. For sensitive mortality prediction, the age criterion ≥65 years should be added to the qSOFA.     

Genotype concordance and polygenic risk score estimation across consumer genetic testing data

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services—two single nucleotide polymorphism (SNP)-array based and one sequencing based. In an N-of-one setting, we found the three services genotyped predominantly distinct sets of sites. While there was a high concordance between overlapping sites of the two SNP-array services (99.6%), there was a lower concordance between these services and a low-pass whole-genome service (73.0%). The discrepancy between the three sets of data resulted in different APOE genotypes and genetic risk scores of Alzheimer's disease. Our results demonstrate genotype results across consumer genomics platforms may lead to different genetic risk estimates, highlighting the need for careful quality control and interpretation.     

Serum gamma-glutamyltransferase concentration correlates with Framingham risk score in Koreans

Gamma-glutamyltransferase (GGT) is a novel coronary artery disease (CAD) risk factor, but its use as an independent factor for CAD risk prediction remains unclear in Asian population. This study examined the association between serum GGT concentration and Framingham risk score (FRS) in the Korean population. This cross-sectional study was performed on 30,710 Koreans. Besides FRS, body mass index, fasting blood glucose, liver enzymes, lipid profile, uric acid and high sensitive C-reactive protein data were used. The study subjects were grouped into quartiles according to the levels of GGT. Analyses relating GGT to FRS ≥ 20% utilized multiple confounders adjusted logistic regression. Positive correlations were established between log-transformed GGT concentration and FRS (r = 0.38; P < 0.001). Increasing the quartile of serum GGT concentration was significantly associated with linear increasing trends in FRS (P-trend < 0.001). Compared to the lowest baseline GGT category, age-gender adjusted odd ratios for FRS ≥ 20% were significantly increased from the lowest to highest GGT quartiles; these results remained significantly after adjustments for multiple confounders. Increased GGT concentration is associated with the increase in FRS. Serum GGT may be helpful to predict the future risk of CAD.     

CRP and the risk of atherosclerotic events

A large body of literature supports the idea that inflammation plays a pivotal role in all phases of atherosclerosis, from the fatty streak lesion formation to the acute coronary event due to vulnerable plaque rupture. Indeed, vascular inflammation contributes to the pathogenesis of atherosclerosis, and later in the disease process, it is a major determinant for the acute coronary syndromes. There are various inflammatory markers that have been shown to predict cardiovascular events. These include high-sensitivity C-reactive protein (hs-CRP), a simple downstream marker of inflammation, recently emerged as a major cardiovascular risk factor. Elevated baseline concentrations of hs-CRP are associated with the risk of atherosclerotic events in general populations and show a predictive value even in terms of secondary prevention, both in patients with chronic stable angina and acute coronary syndromes. In recent year, a lot of concerns have emerged about the experimental models used to study the role of CRP in atherosclerosis; moreover, the results of trials evaluating the clinical association between this molecules and outcome are still controversial. In this paper, we attempt to review the pathophysiological evidences about the link between CRP and atherosclerosis and, most notably, about its utility as a marker and risk predictor in various clinical settings. The identification of specific triggers and mechanisms of underlying inflammation and a better understanding of each step involved in this complex process might lead to new ways to manage patients with atherosclerosis, both in terms of primary and secondary prevention, and CRP still appears to be a suitable candidate for this purpose.     

前列腺癌8号染色体改变与Gleason评分之间的相关性

目的探索前列腺癌8号染色体数目增加及c-myc基因和脂蛋白脂酶（LPL）基因状态和发生频率,分析8号染色体改变与前列腺癌Gleason评分之间的相关性及其在前列腺癌发生发展中的作用。方法采用ProVysion^TM三色探针组合,以荧光原位杂交（FISH）方法检测34例未经临床治疗的前列腺癌穿刺组织石蜡切片标本的8号染色体改变,其中包括Gleason评分5分者1例,6分者10例,7分者14例,8分者4例,9分者5例,并进行8号染色体各种异常之间及其与前列腺癌Gleason评分级别之间的关联性分析。结果8号染色体增加为17／34（50％）,c-myc基因拷贝数增加为21／34（61．8％）,LPL单体为15／34（44．1％）,c-myc基因扩增为23／34（67．6％）,LPL基因缺失为21／34（61．8％）,同时具有LPL基因缺失和c-myc基因扩增为16／34（47．1％）,至少有其中一种遗传学异常者为29／34（85．3％）。8号染色体增加与Gleason评分级别增高呈明显的正相关关系（P=0．0006）;c-myc基因拷贝数增加与Gleason评分级别增高呈正相关关系（P=0．0035）;LPL缺失与Gleason评分级别增高呈负相关关系（P=0．0383）;调整年龄后,除了上述三个变量与Gleason评分级别的相关关系仍然存在以外,c-myc基因扩增与Gleason评分级别增高也呈现正相关关系（P=0．0462）。结论8号染色体数目增加、c-myc基因拷贝数增加、c-myc基因扩增和LPL基因丢失都与Gleason评分级别有关,c-myc基因扩增同时伴有LPL基因缺失也是前列腺癌的遗传学特征之一,提示8号染色体异常可能与前列腺癌的发生和进展有关。